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Drawing on the role of teachers for peer ecologies, we investigated whether students favored ethnically homogenous over ethnically diverse relationships, depending on classroom diversity and perceived teacher care. We specifically studied students’ intra- and interethnic relationships in classrooms with different ethnic compositions, accounting for homogeneous subgroups forming on the basis of ethnicity and gender diversity (i.e., ethnic-demographic faultlines). Based on multilevel social network analyses of dyadic networks between 1299 early adolescents in 70 German fourth grade classrooms, the results indicated strong ethnic homophily, particularly driven by German students who favored ethnically homogenous dyads over mixed dyads. As anticipated, the results showed that there was more in-group bias if perceived teacher care was low rather than high. Moreover, stronger faultlines were associated with stronger in-group bias; however, this relation was moderated by teacher care: If students perceived high teacher care, they showed a higher preference for mixed-ethnic dyads, even in classrooms with strong faultlines. These findings highlight the central role of teachers as agents of positive diversity management and the need to consider contextual classroom factors other than ethnic diversity when investigating intergroup relations in schools.
Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
(2021)
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.
Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.
Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.
Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Systemic lupus erythematosus (SLE) is a severe autoimmune disease of unknown etiology. The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are stress-inducible cell surface molecules. MICA and MICB label malfunctioning cells for their recognition by cytotoxic lymphocytes such as natural killer (NK) cells. Alterations in this recognition have been found in SLE. MICA/MICB can be shed from the cell surface, subsequently acting either as a soluble decoy receptor (sMICA/sMICB) or in CD4+ T-cell expansion. Conversely, NK cells are frequently defective in SLE and lower NK cell numbers have been reported in patients with active SLE. However, these cells are also thought to exert regulatory functions and to prevent autoimmunity. We therefore investigated whether, and how, plasma membrane and soluble MICA/B are modulated in SLE and whether they influence NK cell activity, in order to better understand how MICA/B may participate in disease development. We report significantly elevated concentrations of circulating sMICA/B in SLE patients compared with healthy individuals or a control patient group. In SLE patients, sMICA concentrations were significantly higher in patients positive for anti-SSB and anti-RNP autoantibodies. In order to study the mechanism and the potential source of sMICA, we analyzed circulating sMICA concentration in Behcet patients before and after interferon (IFN)-α therapy: no modulation was observed, suggesting that IFN-α is not intrinsically crucial for sMICA release in vivo. We also show that monocytes and neutrophils stimulated in vitro with cytokines or extracellular chromatin up-regulate plasma membrane MICA expression, without releasing sMICA. Importantly, in peripheral blood mononuclear cells from healthy individuals stimulated in vitro by cell-free chromatin, NK cells up-regulate CD69 and CD107 in a monocyte-dependent manner and at least partly via MICA-NKG2D interaction, whereas NK cells were exhausted in SLE patients. In conclusion, sMICA concentrations are elevated in SLE patients, whereas plasma membrane MICA is up-regulated in response to some lupus stimuli and triggers NK cell activation. Those results suggest the requirement for a tight control in vivo and highlight the complex role of the MICA/sMICA system in SLE.
In this paper, we investigate the question of whether and how perspective taking at the linguistic level interacts with perspective taking at the level of co-speech gestures. In an experimental rating study, we compared test items clearly expressing the perspective of an individual participating in the event described by the sentence with test items which clearly express the speaker’s or narrator’s perspective. Each test item was videotaped in two different versions: In one version, the speaker performed a co-speech gesture in which she enacted the event described by the sentence from a participant’s point of view (i.e. with a character viewpoint gesture). In the other version, she performed a co-speech gesture depicting the event described by the sentence as if it was observed from a distance (i.e. with an observer viewpoint gesture). Both versions of each test item were shown to participants who then had to decide which of the two versions they find more natural. Based on the experimental results we argue that there is no general need for perspective taking on the linguistic level to be aligned with perspective taking on the gestural level. Rather, there is clear preference for the more informative gesture.
Aqueous solutions of a nonionic surfactant (either Tween20 or BrijL23) and an anionic surfactant (sodium dodecyl sulfate, SDS) are investigated, using small-angle neutron scattering (SANS). SANS spectra are analysed by using a core-shell model to describe the form factor of self-assembled surfactant micelles; the intermicellar interactions are modelled by using a hard-sphere Percus–Yevick (HS-PY) or a rescaled mean spherical approximation (RMSA) structure factor. Choosing these specific nonionic surfactants allows for comparison of the effect of branched (Tween20) and linear (BrijL23) surfactant headgroups, both constituted of poly-ethylene oxide (PEO) groups. The nonionic–anionic surfactant mixtures are studied at various concentrations up to highly concentrated samples (ϕ ≲ 0.45) and various mixing ratios, from pure nonionic to pure anionic surfactant solutions. The scattering data reveal the formation of mixed micelles already at concentrations below the critical micelle concentration of SDS. At higher volume fractions, excluded volume effects dominate the intermicellar structuring, even for charged micelles. In consequence, at high volume fractions, the intermicellar structuring is the same for charged and uncharged micelles. At all mixing ratios, almost spherical mixed micelles form. This offers the opportunity to create a system of colloidal particles with a variable surface charge. This excludes only roughly equimolar mixing ratios (X≈ 0.4–0.6) at which the micelles significantly increase in size and ellipticity due to specific sulfate–EO interactions.
Mild acquired factor XIII deficiency and clinical relevance at the ICU - a retrospective analysis
(2021)
Acquired FXIII deficiency is a relevant complication in the perioperative setting; however, we still have little evidence about the incidence and management of this rarely isolated coagulopathy. This study aims to help find the right value for the substitution of patients with an acquired mild FXIII deficiency. In this retrospective single-center cohort study, we enrolled critically ill patients with mild acquired FXIII deficiency (>5% and ≤70%) and compared clinical and laboratory parameters, as well as pro-coagulatory treatments. The results of the present analysis of 104 patients support the clinical relevance of FXIII activity out of the normal range. Patients with lower FXIII levels, beginning at <60%, had lower minimum and maximum hemoglobin values, corresponding to the finding that patients with a minimum FXIII activity of <50% needed significantly more packed red blood cells. FXIII activity correlated significantly with general coagulation markers such as prothrombin time, activated partial thromboplastin time, and fibrinogen. Nevertheless, comparing the groups with a cut-off of 50%, the amount of fresh frozen plasma, thrombocytes, PPSB, AT-III, and fibrinogen given did not differ. These results indicate that a mild FXIII deficiency occurring at any point of intensive care unit stay is also probably relevant for the total need of packed red blood cells, independent of pro-coagulatory management. In alignment with the ESAIC guidelines, the measurement of FXIII in critically ill patients with the risk of bleeding and early management, with the substitution of FXIII at levels <50%-60%, could be suggested.
Background: Various studies have been made about the most effective and safest type of treatment for vertebral compression fractures (VCFs). Long-term results are needed for qualitative evaluation.
Purpose: The purpose of the study is to evaluate the effectiveness of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) procedures for VCFs.
Materials and Methods: Forty-nine patients who received either PVP or PKP between 2002 and 2015 returned a specially developed questionnaire and were included in a cross-sectional outcome analysis. The questionnaire assessed pain development by use of a visual analog scale (VAS). Imaging data (CT scans) were retrospectively analyzed for identification of cement leakage.
Results: Patients’ VAS scores significantly decreased after treatment (7.0 ± 3.4 => 3.7 ± 3.4), (p < 0.001). The average pain reduction in patients treated with PVP was −3.3 ± 3.8 (p < 0.001) (median −3.5) and −4.0 ± 3.9 (p < 0.001) (median −4.5) in patients treated with PKP. Fifteen Patients (41.7%) receiving PVP and four patients (30.7%) receiving PKP experienced recurrence of pain. Cement leakage occurred in 10 patients (22.73%). Patients with cement leakage showed comparable VAS scores after treatment (6.8 ± 3.5 => 1.4 ± 1.6), (p = 0.008). Thirty-nine patients reported an increase in mobility (79.6%) and 41 patients an improvement in quality of life (83.7%).
Conclusion: Pain reduction by means of PVP or PKP in patients with VCFs was discernible over the period of observation. Percutaneous vertebroplasty and PKP contribute to the desired treatment results. However, the level of low pain may not remain constant.
Evidence of hydrothermal activity is reported for the Mesozoic pre- and syn-rift successions of the western Adriatic palaeomargin of the Alpine Tethys, preserved in the Western Southalpine Domain (NW Italy). The products of hydrothermal processes are represented by vein and breccia cements, as well as dolomitization and silicification of the host rocks. In the eastern part of the study area, interpreted as part of the necking zone of the continental margin, Middle Triassic dolostones and Lower Jurassic sediments are crossed by veins and hydrofracturing breccias cemented by saddle dolomite. The precipitation of dolomite cements occurred within the stratigraphic succession close to the sediment–water interface. Despite the shallow burial depth, fluid inclusion microthermometry and clumped isotopes show that hydrothermal fluids were relatively hot (80–150°C). In the western part of the study area, interpreted as part of the hyperextended distal zone, a polyphase history of host-rock fracturing is recorded, with at least two generations of veins cemented by calcite, dolomite and quartz. Vein opening and cementation occurred at shallow burial depth around the time of deposition of the syn-rift clastic succession. Fluid inclusion microthermometry on both quartz and dolomite cements indicates a fluid temperature of 90–130°C, again pointing to hydrothermal fluids. Both in Fenera-Sostegno and Montalto Dora areas, O, C and Sr isotope values, coupled with fluid inclusion and clumped isotope data, indicate that hydrothermal fluids derived from seawater interacted with crustal rocks during hydrothermal circulation. Stratigraphic and petrographic evidence, and U–Pb dating of dolomitized clasts within syn-rift sediments, document that hydrothermal fluids circulated through sediments from the latest Triassic to the Toarcian, corresponding to the entire syn-rift evolution of the western portion of the Adriatic palaeomargin. The documented hydrothermal processes are temporally correlated with regional-scale thermal events that took place in the same time interval at deeper crustal levels.
The physical processes behind the production of light nuclei in heavy ion collisions are unclear. The successful theoretical description of experimental yields by thermal models conflicts with the very small binding energies of the observed states, being fragile in such a hot and dense environment. Other available ideas are delayed production via coalescence, or a cooling of the system after the chemical freeze-out according to a Saha equation, or a ‘quench’ instead of a thermal freeze-out. A recently derived prescription of an (interacting) Hagedorn gas is applied to consolidate the above pictures. The tabulation of decay rates of Hagedorn states into light nuclei allows to calculate yields usually inaccessible due to very poor Monte Carlo statistics. Decay yields of stable hadrons and light nuclei are calculated. While the scale-free decays of Hagedorn states alone are not compatible with the experimental data, a thermalized hadron and Hagedorn state gas is able to describe the experimental data. Applying a cooling of the system according to a Saha-equation with conservation of nucleon and anti-nucleon numbers leads to (nearly) temperature independent yields, thus a production of the light nuclei at temperatures much lower than the chemical freeze-out temperature is compatible with experimental data and with the statistical hadronization model.
The plaque reduction neutralization test (PRNT) is a preferred method for the detection of functional, SARS-CoV-2 specific neutralizing antibodies from serum samples. Alternatively, surrogate enzyme-linked immunosorbent assays (ELISAs) using ACE2 as the target structure for the detection of neutralization-competent antibodies have been developed. They are capable of high throughput, have a short turnaround time, and can be performed under standard laboratory safety conditions. However, there are very limited data on their clinical performance and how they compare to the PRNT. We evaluated three surrogate immunoassays (GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (GenScript Biotech, Piscataway Township, NJ, USA), the TECO® SARS-CoV-2 Neutralization Antibody Assay (TECOmedical AG, Sissach, Switzerland), and the Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA (Leinco Technologies, Fenton, MO, USA)) and one automated quantitative SARS-CoV-2 Spike protein-based IgG antibody assay (Abbott GmbH, Wiesbaden, Germany) by testing 78 clinical samples, including several follow-up samples of six BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) vaccinated individuals. Using the PRNT as a reference method, the overall sensitivity of the examined assays ranged from 93.8 to 100% and specificity ranged from 73.9 to 91.3%. Weighted kappa demonstrated a substantial to almost perfect agreement. The findings of our study allow these assays to be considered when a PRNT is not available. However, the latter still should be the preferred choice. For optimal clinical performance, the cut-off value of the TECO assay should be individually adapted.
In ‘Justice and Natural Resources,’ Chris Armstrong offers a rich and sophisticated egalitarian theory of resource justice, according to which the benefits and burdens flowing from natural (and non-natural) resources are ideally distributed with a view to equalize people’s access to wellbeing, unless there are compelling reasons that justify departures from that egalitarian default. Armstrong discusses two such reasons: special claims from ‘improvement’ and ‘attachment.’ In this paper, I critically assess the account he gives of these potential constraints on global equality. I argue that his recognition of them has implications that Armstrong does not anticipate, and which challenge some important theses in his book. First, special claims from improvement will justify larger departures from the egalitarian default than Armstrong believes. Second, a consistent application of Armstrong’s life planfoundation for special claims from attachment implies that nation-states may move closer to justify ‘permanent sovereignty’ over the resources within their territories than what his analysis suggests.
In this paper, we discuss Armstrong’s account of attachment-based claims to natural resources, the kind of rights that follow from attachment-based claims, and the limits we should impose on such claims. We hope to clarify how and why attachment matters in the discourse on resource rights by presenting three challenges to Armstrong’s theory. First, we question the normative basis for certain attachment claims, by trying to distinguish more clearly between different kinds of attachment and other kinds of claims. Second, we highlight the need to supplement Armstrong’s account with a theory of how to weigh different attachment claims so as to establish the normative standing that different kinds of attachment claims should have. Third, we propose that sustainability must be a necessary requirement for making attachment claims to natural resources legitimate. Based on these three challenges and the solutions we propose, we argue that attachment claims are on the one hand narrower than Armstrong suggests, while on the other hand they can justify more far-reaching rights to control than Armstrong initially considers, because of the particular weight that certain attachment claims have.
Introduction
(2021)
Predator-induced plasticity in life-history and antipredator traits during the larval period has been extensively studied in organisms with complex life-histories. However, it is unclear whether different levels of predation could induce warning signals in aposematic organisms. Here, we investigated whether predator-simulated handling affects warning coloration and life-history traits in the aposematic wood tiger moth larva, Arctia plantaginis. As juveniles, a larger orange patch on an otherwise black body signifies a more efficient warning signal against predators but this comes at the costs of conspicuousness and thermoregulation. Given this, one would expect that an increase in predation risk would induce flexible expression of the orange patch. Prior research in this system points to plastic effects being important as a response to environmental changes for life history traits, but we had yet to assess whether this was the case for predation risk, a key driver of this species evolution. Using a full-sib rearing design, in which individuals were reared in the presence and absence of a non-lethal simulated bird attack, we evaluated flexible responses of warning signal size (number of orange segments), growth, molting events, and development time in wood tiger moths. All measured traits except development time showed a significant response to predation. Larvae from the predation treatment developed a more melanized warning signal (smaller orange patch), reached a smaller body size, and molted more often. Our results suggest plasticity is indeed important in aposematic organisms, but in this case may be complicated by the trade-off between costly pigmentation and other life-history traits.
In the model of randomly perturbed graphs we consider the union of a deterministic graph G with minimum degree αn and the binomial random graph G(n, p). This model was introduced by Bohman, Frieze, and Martin and for Hamilton cycles their result bridges the gap between Dirac’s theorem and the results by Pósa and Korshunov on the threshold in G(n, p). In this note we extend this result in G ∪G(n, p) to sparser graphs with α = o(1). More precisely, for any ε > 0 and α: N ↦→ (0, 1) we show that a.a.s. G ∪ G(n, β/n) is Hamiltonian, where β = −(6 + ε) log(α). If α > 0 is a fixed constant this gives the aforementioned result by Bohman, Frieze, and Martin and if α = O(1/n) the random part G(n, p) is sufficient for a Hamilton cycle. We also discuss embeddings of bounded degree trees and other spanning structures in this model, which lead to interesting questions on almost spanning embeddings into G(n, p).
Introduction: Obesity is classified as a global epidemic and judged to be the greatest public health threat in Western countries. The tremendously increasing prevalence rates in children lead to morbidity and mortality in adults. In many countries, prevalence has doubled since the 1980s. Other countries show a continuous increase or stagnate at a very high level. Given these regional differences, this study aims to draw a global world map of childhood obesity research, including regional epidemiological characteristics, to comprehensively assess research influences and needs. Methods: In addition to established bibliometric parameters, this study uses epidemiological data to interpret metadata on childhood obesity research from the Web of Science in combination with state-of-the-art visualization methods, such as density equalizing map projections. Results: It was not until the 1990s that belated recognition of the dangerous effects of childhood obesity led to an increase in the number of publications worldwide. In addition, our findings show that countries’ study output does not correlate with epidemiologic rates of childhood obesity. In contrast, the primary driver of the research efforts on childhood obesity appears to be largely driven government funding structures. Discussion/Conclusion: The geographical differences in the epidemiological background of childhood obesity complicate the implementation of transnational research projects and cross-border prevention programs. Effective realization requires a sound scientific basis, which is facilitated by globally valid approaches. Hence, there is a need for information exchange between researchers, policy makers, and private initiatives worldwide.
History films personalize, dramatize and emotionalize historical events and characters. They revive the past by exemplifying it in the present, engage ongoing discourses of history and as a result have proven to be the most influential medium in conveying history to large audiences. History films are regarded as an attractive, motivating and efficient (supplementary) teaching and learning medium in history as well as in foreign language classes. As part of the course "Historical Survey of Germany" (BA German-programme at University Putra Malaysia) history film projects on important periods and events in German history were conducted. The article introduces a film project on World War II and describes the pedagogical approach which aims to develop three core competencies of historical understanding – Content Knowledge, Historical Empathy/Perspective Recognition and Narrative Analysis. It discusses selected general findings provided as qualitative data in group and individual assignments. While the responses to questions related to Content Knowledge and Narrative Analysis show that students achieved higher competency levels, the participants showed shortcomings in the rational examination of historical characters, their perspectives and motivations for their actions. Time, practice and guidance can be identified as key factors in developing historical literacy competencies further.
We review the effective field theory associated with the superfluid phonons that we use for the study of transport properties in the core of superfluid neutrons stars in their low temperature regime. We then discuss the shear and bulk viscosities together with the thermal conductivity coming from the collisions of superfluid phonons in neutron stars. With regard to shear, bulk, and thermal transport coefficients, the phonon collisional processes are obtained in terms of the equation of state and the superfluid gap. We compare the shear coefficient due to the interaction among superfluid phonons with other dominant processes in neutron stars, such as electron collisions. We also analyze the possible consequences for the r-mode instability in neutron stars. As for the bulk viscosities, we determine that phonon collisions contribute decisively to the bulk viscosities inside neutron stars. For the thermal conductivity resulting from phonon collisions, we find that it is temperature independent well below the transition temperature. We also obtain that the thermal conductivity due to superfluid phonons dominates over the one resulting from electron-muon interactions once phonons are in the hydrodynamic regime. As the phonons couple to the Z electroweak gauge boson, we estimate the associated neutrino emissivity. We also briefly comment on how the superfluid phonon interactions are modified in the presence of a gravitational field or in a moving background.
Objectives: Inadequate oral hygiene still leads to many serious diseases all over the world. Therefore, this study aimed to analyze scientific research in the field of oral health in order to be able to comprehend their relevant subject areas, research connections, or developments. Methods: This study aimed to assess the global publication output on oral hygiene to create a world map that provides background information on key players, trends, and incentives of research. For this purpose, established bibliometric parameters were combined with state-of-the-art visualization techniques. Results: This study shows the actual key players of research on oral hygiene in high-income economies with only marginal participation from lower economies. This still corresponds to the current burden situations, but they are more and more shifting to the disadvantage of the low-income countries. There is a clear North–South and West–East gradient, with the USA and the Western European nations being the most publishing nations on oral hygiene. As an emerging country, Brazil plays a role in the research. Conclusions: The scientific power players were concentrated in high-income countries. However, the changing epidemiological situation requires a different scientific approach to oral hygiene. This requires an expansion of the international network to meet the demands of future global oral health burdens, which are mainly related to oral hygiene.
This article provides a comparative overview of phonological and phonetic differences of Mukrī Kurdish varieties and their geographical distribution. Based on the examined data, four distinct varieties can be distinguished. In each variety area, different phonological patterns are analyzed according to age, gender, and social groups in order to establish cross-regional and cross-generational developments in relation to specific phonological distributions and shifts. The variety regions which are examined in the present article include West Mukrī (representing an archaic form of Mukrī), Central Mukrī (representing a linguistically peripheral dialect), East Mukrī (representing mixed archaic and peripheral dialect features), and South Mukrī (sharing features of both Mukrī and Ardałānī). The study concludes that variation in the Mukrīyān region depends on phonological developments, which in turn are due to geographical and sociological factors. Moreover, contact-induced change and internal language development are also established as triggering factors distinguishing regional variants.
The thermal fit to preliminary HADES data of Au+Au collisions at sNN=2.4 GeV shows two degenerate solutions at T≈50 MeV and T≈70 MeV. The analysis of the same particle yields in a transport simulation of the UrQMD model yields the same features, i.e. two distinct temperatures for the chemical freeze-out. While both solutions yield the same number of hadrons after resonance decays, the feeddown contribution is very different for both cases. This highlights that two systems with different chemical composition can yield the same multiplicities after resonance decays. The nature of these two minima is further investigated by studying the time-dependent particle yields and extracted thermodynamic properties of the UrQMD model. It is confirmed, that the evolution of the high temperature solution resembles cooling and expansion of a hot and dense fireball. The low temperature solution displays an unphysical evolution: heating and compression of matter with a decrease of entropy. These results imply that the thermal model analysis of systems produced in low energy nuclear collisions is ambiguous but can be interpreted by taking also the time evolution and resonance contributions into account.
Few empirical studies have explored psychological attitudes toward out-of-home mobility in old age. We aimed to validate an instrument to assess mobility-related behavioral flexibility and routines in the context of everyday mobility and successful aging. Data were gathered from face-to-face interviews and travel diaries of 211 community-dwelling older adults (aged 65–92) in Germany. Analysis revealed sufficient reliability and confirmed the factorial and convergent validity of the instrument. Mobility-related behavioral flexibility predicted the number of daily trips, particularly by mobility-impaired participants, and was strongly linked to autonomy and to psychological well-being. However, a preference for routines predicted neither out-of-home mobility nor further outcomes. The results demonstrate the importance of mobility-related flexibility in maintaining an active and independent life in old age.
In this paper, we present an experimental and theoretical study of excitation processes for the heaviest stable helium-like ion, that is, He-like uranium occurring in relativistic collisions with hydrogen and argon targets. In particular, we concentrate on angular distributions of the characteristic Kα radiation following the K → L excitation of He-like uranium. We pay special attention to the magnetic sub-level population of the excited 1s2lj states, which is directly related to the angular distribution of the characteristic Kα radiation. We show that the experimental data can be well described by calculations taking into account the excitation by the target nucleus as well as by the target electrons. Moreover, we demonstrate for the first time an important influence of the electron-impact excitation process on the angular distributions of the Kα radiation produced by excitation of He-like uranium in collisions with different targets.
Similar to chloroplast loci, mitochondrial markers are frequently used for genotyping, phylogenetic studies, and population genetics, as they are easily amplified due to their multiple copies per cell. In a recent study, it was revealed that the chloroplast offers little variation for this purpose in central European populations of beech. Thus, it was the aim of this study to elucidate, if mitochondrial sequences might offer an alternative, or whether they are similarly conserved in central Europe. For this purpose, a circular mitochondrial genome sequence from the more than 300-year-old beech reference individual Bhaga from the German National Park Kellerwald-Edersee was assembled using long and short reads and compared to an individual from the Jamy Nature Reserve in Poland and a recently published mitochondrial genome from eastern Germany. The mitochondrial genome of Bhaga was 504,730 bp, while the mitochondrial genomes of the other two individuals were 15 bases shorter, due to seven indel locations, with four having more bases in Bhaga and three locations having one base less in Bhaga. In addition, 19 SNP locations were found, none of which were inside genes. In these SNP locations, 17 bases were different in Bhaga, as compared to the other two genomes, while 2 SNP locations had the same base in Bhaga and the Polish individual. While these figures are slightly higher than for the chloroplast genome, the comparison confirms the low degree of genetic divergence in organelle DNA of beech in central Europe, suggesting the colonisation from a common gene pool after the Weichsel Glaciation. The mitochondrial genome might have limited use for population studies in central Europe, but once mitochondrial genomes from glacial refugia become available, it might be suitable to pinpoint the origin of migration for the re-colonising beech population.
(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06–1.10), cardiovascular disease (OR 1.64, CI 1.06–2.55), pulmonary disease (OR 1.87, CI 1.16–3.03), baseline Statin treatment (0.54, CI 0.33–0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92–0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01–1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94–0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62–0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05–1.18), kidney failure (OR 1.68, CI 1.05–2.70), congestive heart failure (OR 2.62, CI 1.11–6.21), severe liver failure (OR 4.93, CI 1.94–12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14–2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.
11,12-Dihydrodibenzo[c,g]-1,2-diazocines have been established as a viable alternative to azobenzene for photoswitching, in particular, as they show an inverted switching behavior: the ground state is the Z isomer. In this paper, we present an improved method to obtain dibenzodiazocine and its derivatives from the respective 2-nitrotoluenes in two reaction steps, each proceeding in minutes. This fast access to a variety of derivatives permitted the study of substitution effects on the synthesis and on the photochemical properties. With biochemical applications in mind, methanol was chosen as a protic solvent system for the photochemical investigations. In contrast to the azobenzene system, none of the tested substitution patterns resulted in more efficient switching or in significantly prolonged half-lives, showing that the system is dominated by the ring strain.
Acinetobacter baumannii is an important nosocomial pathogen that requires thoughtful consideration in the antibiotic prescription strategy due to its multidrug resistant phenotype. Tetracycline antibiotics have recently been re-administered as part of the combination antimicrobial regimens to treat infections caused by A. baumannii. We show that the TetA(G) efflux pump of A. baumannii AYE confers resistance to a variety of tetracyclines including the clinically important antibiotics doxycycline and minocycline, but not to tigecycline. Expression of tetA(G) gene is regulated by the TetR repressor of A. baumannii AYE (AbTetR). Thermal shift binding experiments revealed that AbTetR preferentially binds tetracyclines which carry a O-5H moiety in ring B, whereas tetracyclines with a 7-dimethylamino moiety in ring D are less well-recognized by AbTetR. Confoundingly, tigecycline binds to AbTetR even though it is not transported by TetA(G) efflux pump. Structural analysis of the minocycline-bound AbTetR-Gln116Ala variant suggested that the non-conserved Arg135 interacts with the ring D of minocycline by cation-π interaction, while the invariant Arg104 engages in H-bonding with the O-11H of minocycline. Interestingly, the Arg135Ala variant exhibited a binding preference for tetracyclines with an unmodified ring D. In contrast, the Arg104Ala variant preferred to bind tetracyclines which carry a O-6H moiety in ring C except for tigecycline. We propose that Arg104 and Arg135, which are embedded at the entrance of the AbTetR binding pocket, play important roles in the recognition of tetracyclines, and act as a barrier to prevent the release of tetracycline from its binding pocket upon AbTetR activation. The binding data and crystal structures obtained in this study might provide further insight for the development of new tetracycline antibiotics to evade the specific efflux resistance mechanism deployed by A. baumannii.
Membrane-suspended nanopores in microchip arrays for stochastic transport recording and sensing
(2021)
The transport of nutrients, xenobiotics, and signaling molecules across biological membranes is essential for life. As gatekeepers of cells, membrane proteins and nanopores are key targets in pharmaceutical research and industry. Multiple techniques help in elucidating, utilizing, or mimicking the function of biological membrane-embedded nanodevices. In particular, the use of DNA origami to construct simple nanopores based on the predictable folding of nucleotides provides a promising direction for innovative sensing and sequencing approaches. Knowledge of translocation characteristics is crucial to link structural design with function. Here, we summarize recent developments and compare features of membrane-embedded nanopores with solid-state analogues. We also describe how their translocation properties are characterized by microchip systems. The recently developed silicon chips, comprising solid-state nanopores of 80 nm connecting femtoliter cavities in combination with vesicle spreading and formation of nanopore-suspended membranes, will pave the way to characterize translocation properties of nanopores and membrane proteins in high-throughput and at single-transporter resolution.
Scanning Hall probe microscopy is attractive for minimally invasive characterization of magnetic thin films and nanostructures by measurement of the emanating magnetic stray field. Established sensor probes operating at room temperature employ highly miniaturized spin-valve elements or semimetals, such as Bi. As the sensor layer structures are fabricated by patterning of planar thin films, their adaption to custom-made sensor probe geometries is highly challenging or impossible. Here we show how nanogranular ferromagnetic Hall devices fabricated by the direct-write method of focused electron beam induced deposition (FEBID) can be tailor-made for any given probe geometry. Furthermore, we demonstrate how the magnetic stray field sensitivity can be optimized in situ directly after direct-write nanofabrication of the sensor element. First proof-of-principle results on the use of this novel scanning Hall sensor are shown.
Biodiversity information is contained in countless digitized and unprocessed scholarly texts. Although automated extraction of these data has been gaining momentum for years, there are still innumerable text sources that are poorly accessible and require a more advanced range of methods to extract relevant information. To improve the access to semantic biodiversity information, we have launched the BIOfid project (www.biofid.de) and have developed a portal to access the semantics of German language biodiversity texts, mainly from the 19th and 20th century. However, to make such a portal work, a couple of methods had to be developed or adapted first. In particular, text-technological information extraction methods were needed, which extract the required information from the texts. Such methods draw on machine learning techniques, which in turn are trained by learning data. To this end, among others, we gathered the BIOfid text corpus, which is a cooperatively built resource, developed by biologists, text technologists, and linguists. A special feature of BIOfid is its multiple annotation approach, which takes into account both general and biology-specific classifications, and by this means goes beyond previous, typically taxon- or ontology-driven proper name detection. We describe the design decisions and the genuine Annotation Hub Framework underlying the BIOfid annotations and present agreement results. The tools used to create the annotations are introduced, and the use of the data in the semantic portal is described. Finally, some general lessons, in particular with multiple annotation projects, are drawn.
Growing amounts of genomic data and more efficient assembly tools advance organelle genomics at an unprecedented scale. Genomic resources are increasingly used for phylogenetic analyses of many plant species, but are less frequently used to investigate within-species variability and phylogeography. In this study, we investigated genetic diversity of Fagus sylvatica, an important broadleaved tree species of European forests, based on complete chloroplast genomes of 18 individuals sampled widely across the species distribution. Our results confirm the hypothesis of a low cpDNA diversity in European beech. The chloroplast genome size was remarkably stable (158,428 ± 37 bp). The polymorphic markers, 12 microsatellites (SSR), four SNPs and one indel, were found only in the single copy regions, while inverted repeat regions were monomorphic both in terms of length and sequence, suggesting highly efficient suppression of mutation. The within-individual analysis of polymorphisms showed >9k of markers which were proportionally present in gene and non-gene areas. However, an investigation of the frequency of alternate alleles revealed that the source of this diversity originated likely from nuclear-encoded plastome remnants (NUPTs). Phylogeographic and Mantel correlation analysis based on the complete chloroplast genomes exhibited clustering of individuals according to geographic distance in the first distance class, suggesting that the novel markers and in particular the cpSSRs could provide a more detailed picture of beech population structure in Central Europe.
Chloroplasts are difficult to assemble because of the presence of large inverted repeats. At the same time, correct assemblies are important, as chloroplast loci are frequently used for biogeography and population genetics studies. In an attempt to elucidate the orientation of the single-copy regions and to find suitable loci for chloroplast single nucleotide polymorphism (SNP)-based studies, circular chloroplast sequences for the ultra-centenary reference individual of European Beech (Fagus sylvatica), Bhaga, and an additional Polish individual (named Jamy) was obtained based on hybrid assemblies. The chloroplast genome of Bhaga was 158,458 bp, and that of Jamy was 158,462 bp long. Using long-read mapping on the configuration inferred in this study and the one suggested in a previous study, we found an inverted orientation of the small single-copy region. The chloroplast genome of Bhaga and of the individual from Poland both have only two mismatches as well as three and two indels as compared to the previously published genome, respectively. The low divergence suggests low seed dispersal but high pollen dispersal. However, once chloroplast genomes become available from Pleistocene refugia, where a high degree of variation has been reported, they might prove useful for tracing the migration history of Fagus sylvatica in the Holocene.
Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
Background: Transition metals play a crucial role in brain metabolism: since they exist in different oxidation states they are involved in ROS generation, but they are also co-factors of enzymes in cellular energy metabolism or oxidative defense. Methods: Paired serum and cerebrospinal fluid (CSF) samples were analyzed for iron, zinc, copper and manganese as well as for speciation using SEC-ICP-DRC-MS. Brain extracts from Mn-exposed rats were additionally analyzed with SEC-ICP-DRC-MS. Results: The concentration patterns of transition metal size fractions were correlated between serum and CSF: Total element concentrations were significantly lower in CSF. Fe-ferritin was decreased in CSF whereas a LMW Fe fraction was relatively increased. The 400–600 kDa Zn fraction and the Cu-ceruloplasmin fraction were decreased in CSF, by contrast the 40–80 kDa fraction, containing Cu- and Zn-albumin, relatively increased. For manganese, the α-2-macroglobulin fraction showed significantly lower concentration in CSF, whereas the citrate Mn fraction was enriched. Results from the rat brain extracts supported the findings from human paired serum and CSF samples. Conclusions: Transition metals are strictly controlled at neural barriers (NB) of neurologic healthy patients. High molecular weight species are down-concentrated along NB, however, the Mn-citrate fraction seems to be less controlled, which may be problematic under environmental load.
This article explores the liturgical functions of cross-shaped staurothekes, reliquaries of the True Cross, in twelfth-century Sicily. These luxurious objects were once at the centre of the devotion of the growing Christian communities on an island undergoing dramatic social changes. This contribution examines the figuration of these crosses and the messages they conveyed to their audiences, focusing on documented processions as displays of public piety. To this end, the contents of two liturgical manuscripts from Palermo, evidence in contemporary pictorial arts and coinage, and the urban layout of the Norman capital will shed light on the reception of the symbol of the cross in the cosmopolitan, yet increasingly intolerant Sicilian kingdom.
GAMESTOP, A COMPANY THAT WAS PRESUMED DEAD DUE TO SHRINKING PROFITS OFITS BRICK-AND-MORTAR BUSINESS MODEL, HIT THE HEADLINES BECAUSE OF ASHORT SQUEEZE OF ITS STOCK PRICE. THE POPULAR OPINION REPORTED BY MAIN-STREAM MEDIA SUGGESTED THAT THE GAMESTOP FRENZY WAS EXCLUSIVE TO YOUNGAND INEXPERIENCED INVESTORS GATHERING ON THE SOCIAL MEDIA PLATFORMREDDIT. IN CONTRAST, OUR RESULTS INDICATE THAT ALSO MORE EXPERIENCEDRETAIL INVESTORS IN GERMANY PARTICIPATED.
Iberia has one of the richest bee faunas in the world, and the genus Andrena is no exception with around 200 species known from the Peninsula. The fauna of Andrena was largely revised in the 1970s, but since then, it has received little attention. Molecular investigation of the taxonomically challenging subgenus Taeniandrena has revealed that the situation is more complicated than previously thought with several cryptic and overlooked species. From the species allied to Andrena (T. ) gelriae van der Vecht, 1927, Andrena (T. ) gredana Warncke, 1975 stat. nov. from Spain and Portugal is raised to species status, and Andrena (T. ) levante Wood & Praz sp. nov. from southeastern Spain is newly described. Furthermore, Andrena (T. ) benoisti Wood & Praz sp. nov. is described, having previously been referred to as Andrena (T. ) wilkella beaumonti Benoist, 1961. Andrena (T. ) beaumonti stat. rev. is itself distinct and restricted to the High Atlas Mountains of Morocco. Outside of the subgenus Taeniandrena, Andrena (Euandrena) fortipunctata Wood sp. nov. and Andrena (Charitandrena) hattorfiana nigricauda Wood subsp. nov. are described from Spain, and Andrena (Notandrena) juliana Wood sp. nov. is described from Spain and Portugal. The male of Andrena (Lepidandrena) baetica Wood, 2020 is also described. Andrena (Euandrena) impressa Warncke, 1967 stat. nov. is raised to species status, displaying a West Mediterranean distribution. Finally, a further two species of Andrena are newly recorded for Spain, Andrena laurivora Warncke, 1974 and Andrena confinis Stoeckhert, 1930. Altogether, these findings reinforce the fact that our understanding of the taxonomy and distribution of Andrena in southern Europe remains incomplete.
A new species of abyssal Neanthes Kinberg, 1865, N. goodayi sp. nov., is described from the Clarion-Clipperton Zone in the central Pacific Ocean, a region targeted for seabed mineral exploration for polymetallic nodules. It is a relatively large animal found living inside polymetallic nodules and in xenophyophores (giant Foraminifera) growing on nodules, highlighting the importance of the mineral resource itself as a distinct microhabitat. Neanthes goodayi sp. nov. can be distinguished from its congeners primarily by its distinctive, enlarged anterior pair of eyes in addition to characters of the head, pharynx and parapodia. Widespread, abundant, and easily recognisable, N. goodayi sp. nov. is also considered to be a suitable candidate as a potential indicator taxon for future monitoring of the impacts of seabed mining.
We describe one new tribe, two new genera and three new species of the subfamily Cypridopsinae Kaufmann, 1900 from Brazilian floodplains. Brasilodopsis gen. nov. belongs in the nominal tribe Cypridopsini, and both new species in this new genus were found in both sexual and asexual populations. Brasilodopsis baiabonita gen. et sp. nov. has a wide distribution and was found in three of the four major Brazilian floodplains. Brasilodopsis amazonica gen. et sp. nov. was recorded only from the Amazon floodplain. Brasilodopsis baiabonita gen. et sp. nov. has a subtriangular shape in lateral view, whereas Brasilodopsis amazonica gen. et sp. nov. is more elongated and has more rounded dorsal margins in both valves, as well as more pronounced external valve ornamentation, consisting of rimmed pores in shallow pits. Paranadopsis reducta gen. et sp. nov. was found in asexual populations in the Upper Paraná River floodplain only and differs from other Cypridopsinae in the more elongated carapace, an A1 with strongly reduced chaetotaxy (hence the specific name) and the total absence of caudal rami in females. Because of these strong reductions in valve and limb morphology, Paranadopsini trib. nov. is created within the Cypridopsinae for this intriguing new genus and species.
We describe a new species of riparian lizard from the foothills and submontane forest of El Sira Communal Reserve, Departamento de Huánuco, Peru, at elevations from 540 to 760 m. We name the new species Potamites hydroimperator sp. nov. because it is the only lizard living in streams in this isolated mountain. The new species is distinguishable from other congeners (except P. ecpleopus) by having longitudinal rows of keeled scales on dorsum, and males with 5–8 lateral ocelli on each flank. Potamites hydroimperator sp. nov. differs from P. ecpleopus by being smaller, having dorsal scales on forelimbs smooth or slightly keeled, subconical tubercles on forelimbs weakly present or absent, and four to five superciliar scales. We comment on variation in the pattern of keeling of dorsal scales among Amazonian lowland, Andean foothills and montane species of Potamites, and the potential relevance of this scalation pattern for taxonomic and biogeographic studies. The new species increases our knowledge of the diverse and endemic herpetofauna of El Sira, and of diversity within the genus Potamites. Despite El Sira’s status as natural protected area, gold mining activities are destroying the streams where we found P. hydroimperator sp. nov., threatening their populations.
In the Pacific Ocean, the taxonomy of the family Zosimeidae Seifried, 2003 is poorly understood and to date only five species of the genus Zosime Boeck, 1873 are known. During oceanographic cruises exploring the species diversity of harpacticoids, two undescribed zosimeid copepods were sampled from shallow Korean waters and the deep northwestern Pacific. A detailed morphological examination has led us to propose two new genera, Heterozosime gen. nov. for the Korean zosimeid H. tenuis gen. et sp. nov. and Acritozosime gen. nov. for the deep-sea zosimeid A. spinesco gen. et sp. nov. Both new genera exhibit a distinctive feature in that the first thoracic leg has a two-segmented exopod, in contrast to the three-segmented exopod of this leg in all known zosimeid genera. Furthermore, Acritozosime gen. nov. can also be discriminated from other genera by the two-segmented endopod in second to fourth thoracic legs and the reduced setal armatures of the second exopodal segment of antenna, the first endopodal segment of first to third thoracic legs and the third exopodal segment in second to fourth thoracic legs. A comparison of the fundamental structures of appendages suggests that A. spinesco gen. et sp. nov. experienced a unique evolutionary history within the Zosimeidae.
Marine isopods, despite being a very diverse group, have been little studied in the Mexican South Pacific. After a revision of 171 specimens collected from Guerrero and Oaxaca, six new species, belonging to five genera, were discovered: Amakusanthura guerrerensis sp. nov., Cortezura caeca sp. nov., Mesanthura antenniformis sp. nov., M. estacahuitensis sp. nov., Skuphonura oaxaquensis sp. nov., and Tinggianthura mexicana sp. nov. In this work, the genera Amakusanthura Nunomura, 1977 and Tinggianthura Chew, Abdul-Rahim & Haji Ross, 2014, are recorded for the first time in the Tropical Eastern Pacific. Also, the distribution range of the genus Skuphonura Barnard, 1925 is increased from the west coast of South America to the southern Mexican Pacific, this being the first record of this genus in the Mexican Pacific. This study doubles the number of species recorded of Anthuridae from the Mexican Pacific, of six to 12 species.
Simulium (Trichodagmia) Enderlein, 1934 has an unstable classification system. The broader concept of the subgenus includes five species-groups resulting from an extensive history of synonymisations, often outside of a phylogenetic framework. This concept also ignores relationship hypotheses with the Afrotropical subgenera S. (Anasolen) Enderlein, 1930, S. (Freemanellum) Crosskey, 1969, S. (Xenosimulium) Crosskey, 1969, and the Oviedoi species-group, with several Neotropical species of S. (Trichodagmia). We performed a morphological phylogenetic analysis to test the monophyly of S. (Trichodagmia), its species-groups, and their relationship with the above-mentioned subgenera and Oviedoi species-group. We analysed a data matrix with 69 terminal taxa and 62 characters under parsimony implied weights, with a range of concavities (k1–100), finding three categories of k. Our analysis concludes that S. (Trichodagmia) is not monophyletic, since Oviedoi and the Afrotropical subgenera group with its species-groups Tarsatum and Orbitale. Therefore, we propose a new classification for S. (Trichodagmia) by restricting it to the Orbitale species-group, revalidating S. (Hearlea) Vargas et al., 1946, S. (Hemicnetha) Enderlein, 1934, S. (Obuchovia) Rubtsov, 1947 and S. (Shewellomyia) Peterson, 1975, synonymysing S. (Xenosimulium) with S. (Anasolen), and erecting a new subgenus, S. (Disculter) subgen. nov. for Oviedoi. The geographical distribution of the groups involved is discussed.
In the framework of an ongoing extensive phylogenetic evaluation of the Ceratonotus group (Copepoda, Harpacticoida, Cletodidae), Poropsyllus menzelae gen. et sp. nov. from the sublittoral of south-western Cyprus (eastern Mediterranean Sea) and Paratouphapleura aaroni gen. et sp. nov. from the western Weddell Sea (Antarctica) are described. Both new species fit the autapomorphies of the Ceratonotus group but cannot be assigned to any of the genera so far known. Instead, each new species presents a set of derived characters that justify their placement in new genera, Poropsyllus gen. nov. and Paratouphapleura gen. nov., respectively. Furthermore, a comparison of the species placed in Ceratonotus Sars revealed that because of exclusive morphological deviations, Ceratonotus concavus Conroy-Dalton, C. steiningeri George, C. tauroides George, and C. vareschii George should be excluded from Ceratonotus and transferred to a new monophylum, Tauroceratus gen. nov. Likewise, Polyascophorus monoceratus George, Wandeness & Santos is characterized by several apomorphies that justify its transfer from Polyascophorus to a new taxon, Pseudopolyascophorus gen. nov. The Ceratonotus group is therefore increased to 31 species assigned to 13 genera. The systematic modifications conducted and resulting phylogenetic consequences are discussed in detail.
A new alpheid shrimp, Aretopsis sandybrucei sp. nov., is described on the basis of three specimens collected from three deep-water banks in the Chesterfield Plateau of the Coral Sea, between New Caledonia and Queensland, Australia, at a depth range of 280–550 m. The new species is the first known deep-water species of the genus Aretopsis De Man, 1910, with its two congeners, A. amabilis De Man, 1910 and A. manazuruensis Suzuki, 1971, being confined to the lower intertidal and shallow subtidal areas, to a maximum depth of 50 m. Based on morphological grounds, A. sandybrucei sp. nov. can be easily separated from A. amabilis and A. manazuruensis by the generally much stouter third to fifth pereiopods, with their dactyli each bearing a very small secondary unguis on the flexor margin, in comparison to a much stronger one in the other two species. Aretopsis sandybrucei sp. nov. also differs from A. amabilis and A. manazuruensis by the less contrasting colour pattern, including the more translucent, dull yellowish chelae and tail fan. An association of A. sandybrucei sp. nov. with a deep-water hermit crab appears to be highly likely due to the presence of several large hermit crabs (Paguridae) in at least one of the three dredge/bottom trawl hauls, which was also containing a paratype of the new species. The taxonomic status of A. amabilis and A. manazuruensis is discussed.
Four new Colombian species of the spider genus Medionops Sánchez-Ruiz & Brescovit, 2017 are described and illustrated: M. carolinae sp. nov. (male and female) from Boyacá department, M. cauca sp. nov. (male) from Cauca department, M. luiscarlosi sp. nov. (male and female) from Caldas department and M. santarosa sp. nov. (male) from Risaralda department. Additionally, the distribution of the type species of M. blades Sánchez-Ruiz & Brescovit, 2017, previously known only from Bogotá, Cundinamarca department, is extended to several localities in the Boyacá department. An updated identification key for all Medionops species is provided.
A new species of echinoderid kinorhynchs, Echinoderes xiphophorus sp. nov. collected from oxidized brown silt at the deepest depression in the Sea of Japan, North-West Pacific, is described and illustrated using light and electron microscopy. This new representative of the most speciose kinorhynch genus is characterized by the unique set of spines and tubes and can easily be distinguished from most of its congeners. The second trunk segment bears three pairs of tubes in subdorsal, midlateral and ventrolateral position in both sexes; one pair of tubes on trunk segment 5 in lateroventral position and on trunk segment 8 in sublateral position; aciculate lateroventral spines on trunk segments 6–9; aciculate middorsal spines on trunk segments 4, 6, 8. This species is well recognized by very long tergal extensions of the posteriormost segment, some of the longest within the family Echinoderidae. Males of Echinoderes xiphophorus sp. nov. are well distinguished from all the congeners by extremely long sword-like appendages dorsally to three pairs of penile spines. The species constitutes the first deep-sea representative of the Echinoderidae in the Sea of Japan and the deepest representative of the Kinorhyncha in this sea.
I propose a redefinition of the sexstrigatus group of Lasioglossum (Hemihalictus) Cockerell, 1897, including a phylogenetic analysis. This group is characterised by a combination of the following 12 characteristics: male antenna short, not attaining to metasoma, male labrum with distal process and well-developed basal elevation, male head with genal process as variation, female mesepisternum reticulate-punctate on lower area, mesepisternum without tubercle in both sexes, female metasomal terga with distinct fimbriae on posterior margin, male S8 with well-developed median process, gonobase ventral arm of male genitalia connected with each other at upper ends, gonocoxite of male genitalia smooth, gonostylus of male genitalia small and simple, bud-like, and the ventral retrorse lobe of male genitalia not attaining to gonobase. The Japanese species of the sexstrigatus group are revised. Thirteen species in total are recognised, including three new species: Lasioglossum (Hemihalictus) ikudomei sp. nov., L. (H.) spectrum sp. nov., and L. (H.) subsimplicior sp. nov. Lasioglossum (Hemihalictus) perplexans (Cockerell, 1925) is synonymised under L. (H.) kiautschouense (Strand, 1910). A key to the Japanese species is provided. Bionomical data, such as flight and flower records or habitat, are reported for some species. The distributions of all species are mapped. DNA sequences including a part of the barcode region are given for L. (H.) kiautschouense, L. (H.) ohei Hirashima & Sakagami, 1966, L. (H.) speculinum (Cockerell, 1925), L. (H. ) spectrum sp. nov., L. (H. ) subsimplicior sp. nov., and L. (H. ) taeniolellum (Vachal, 1903)
The genus Salvadora has not been subjected to a modern phylogenetic analysis. Described in 1853, its taxonomic history is complex and confusing. In this study, we evaluate the monophyly of the genus and present the first phylogenetic hypothesis based on an analysis of 66 qualitative and quantitative morphological characters of over 1000 specimens representing all described taxa across their entire distribution. Morphological characters were processed in Fast Morphology for subsequent phylogenetic analysis in PAUP under the maximum parsimony criterion. We obtained a single tree in which Salvadora appears as a monophyletic group with two clearly defined geographic species groups: a southern mexicana group and a northern grahamiae group. Based on our phylogenetic hypothesis, we evaluate the taxonomic status of all described taxa. Additionally, we include a diagnosis for all species, distribution maps, and an illustrated dichotomous taxonomic key of the genus.
The genus Oplognathus MacLeay, 1819 is revised based on type material of two of the three described species and scattered additional material from several collections around the world. The diagnostic characters of the genus are confirmed, distinguishing it from other Brazilian Areodina mainly by: quadrangular clypeus with trilobate apex in males, rounded in females, extending beyond labrum in both sexes; mandibles with three distinct teeth; maxillae with six teeth; antenna with 10 antennomeres; 10 elytral striae; mesoventral process present; and asymmetrical parameres. The genus and all three species are redescribed, and the female of Oplognathus bahianus Ohaus, 1912 is described for the first time. We consider Oplognathus helmenreichi var. maculicollis Ohaus, 1914 an unavailable infrasubspecific taxon that is conspecific with Oplognathus helmenreichi Ohaus, 1905; its distribution is updated, and the different spelling of the specific epithet is discussed. A neotype is designated for Oplognathus kirbii MacLeay, 1819 since the holotype is currently considered lost. Additionally, an identification key and a distribution map are included.
The Cerrado domain is the most diverse savannah biome in the world and a biodiversity hotspot for conservation. Only a few areas of the domain remain well preserved, among them the Jalapão region in Tocantins State, currently is considered the best preserved area of the Brazilian Cerrado. Listed in a recent Angiosperm checklist for the region, there were two species of Polygala series Trichospermae, which were recognized as new by the first author. Polygala bringelii sp. nov., endemic to the Jalapão region, is diagnosed by its obclavate seeds without a ring of trichomes at their base, keel with the crest shorter than the cuculus, and the internal sepals (wings) longer than the capsule. Polygala tocantinensis sp. nov., endemic to Tocantins state, is distinguished by its internal sepals (wings) with two glands near to the rounded apex, and a ring of convergent trichomes at the base of the seeds. The two species are morphologically closest with Polygala trichosperma of sect. Timutua, series Trichospermae, but differs in its corolla and seeds shape and pubescence. An identification key, photographic plates, photos of floral parts under magnification, preliminary conservation assessments, and ecological comments of both species are also provided.
The genus Trypheridium Brancucci, 1985 is endemic to the Hindu Kush Himalayan Region, and is currently known from a single species, T. nuristanicum (Wittmer, 1956). Here, the genus is reviewed, T. nuristanicum nom. emend. is re-described and T. kashmiricum sp. nov. is described from Kashmir Himalayan Region of India. Descriptions, diagnoses, high quality images, distribution maps and identification keys are presented. The morphology and distribution of Trypheridium are discussed and compared with those of the closely related genus Trypherus LeConte, 1851.
For each of the 534 species of the millipede order Chordeumatida known from Europe, available information on taxonomy, distribution and habitat is summarized, and the distribution in 50 × 50 km UTM/MGRS squares is shown on a map. Comparisons between Chordeumatida and the equally-sized order Julida are made with respect to distribution patterns and history of exploration.
This is a first inventory of Isopoda Anthuroidea from near-shore marine sites in Sulawesi. The material was collected from reefs, sea-grass beds and mangroves of the Minahasa Peninsula in North Sulawesi. Specimens were washed out from benthos samples collected in shallow water. The new species Hyssura reptans sp. nov., Kupellonura indonesica sp. nov., Kupellonura macaroni sp. nov., Pendanthura bangkaensis sp. nov., Expanathura marcoi sp. nov., and Colanthura gerungi sp. nov. are described. We discovered that in Colanthura the mandible is fused to the cephalothorax, a unique feature among isopods. Expanathura collaris (Kensley, 1979) is described from Bangka Island and several differences between other Indo-Pacific populations are discussed.
Drepanoistodus basiovalis (Sergeeva, 1963) is a common conodont species in Middle Ordovician strata of Baltica. For many years it has been widely accepted that the species encompasses a wide range of morphological plasticity. Hence, several different morphotypes that significantly deviate from the holotype have nonetheless been included in the broad species concept. In this study, we performed a detailed taxonomical study on 112 predominantly well-preserved specimens (geniculate elements) from the St. Petersburg region of Russia; 37 of these were selected for morphometric analyses together with 21 well-illustrated specimens from the published literature. The results demonstrate that, among the morphotypes that share some characteristics with D. basiovalis sensu lato, at least five species can be readily distinguished. Hence, three new species – Drepanoistodus iommii sp. nov., D. svendi sp. nov. and D. viirae sp. nov. – are here added to the previously known D. basiovalis and D. contractus (Lindström, 1955). In addition, some specimens were left under open nomenclature and assigned to Drepanoistodus aff. basiovalis and D. cf. suberectus (Branson & Mehl, 1933). In order to objectively compare the Drepanoistodus taxa and test the validity of the new species, we performed a Principal Component Analysis combined with non-parametric (PERMANOVA) tests based on 21 morphological characters.
A new Brazilian leafhopper genus of the subfamily Neocoelidiinae is proposed: Takiyaella gen. nov. based on T. sexguttata (Chiamolera & Cavichioli, 2003) gen. et comb. nov. and five new species: T. anomala gen. et sp. nov., T. coelhomarquesae gen. et sp. nov., and T. daniela gen. et sp. nov. from the state of Rio de Janeiro; T. cavichiolii gen. et sp. nov. from the state of Paraná, and T. mejdalanii gen. et sp. nov. from the state of Minas Gerais. A distribution map and identification key to Takiyaella species are provided.
Numerous pseudoplasmodia containing myxospores belonging to the genus Cystodiscus were found in the gallbladder of Elachistocleis cesarii from Mato Grosso State, Brazil. Herein, we describe Cystodiscus elachistocleis sp. nov., using morphological and small subunit ribosomal DNA sequences. The mature myxospores were ellipsoid to ovoid, measuring in average 10.6 (9.8–11.2) μm in length and 6.2 (5.6–6.6) μm in width. Polar capsules were pyriform and equal in size measuring in average 3.6 (2.8–4.3) μm in length and 2.6 (2.2–3.1) μm in width. Polar filaments had 2–4 coils. The myxospores had 3–5 transverse ridges. The phylogenetic analysis showed Cystodiscus elachistocleis sp. nov. as a sister species of Cystodiscus cf. immersus 1, in a subclade formed by species that parasitize the amphibians gallbladder. This is the first species of Cystodiscus described parasitizing a species of Elachistocleis and the third species of Cystodiscus described in Brazil.
A new genus with a new species of soft-winged flower beetle, Pectotibialis paghmanensis Tshernyshev gen. et sp. nov. are described from Afghanistan. The new genus can be distinguished from the congeners of the tribe Apalochrini by the dark pectination in the apices of tibiae in both sexes, and the anterior tibiae which are hollowed at distal half, flattened and rounded femora, bituberculate basal parts of head and pronotum, two lamellate metathoracic appendages, tarsal comb above second tarsomere of anterior legs, and serrate antennae in the male. Based on the metathoracic appendages and comb in anterior legs would attribute this new species to the new genus Dromanthomorphus Pic, 1921, but all the other above-mentioned characters define its independent status and the designation of a new genus; Pectotibialis Tshernyshev gen. nov. The external appearance, special male characters and genitalia of the type species of the new genus are illustrated, and a distribution map is provided. A key to the Apalochrus-section of the tribe Apalochrini is provided.
The present study focuses on shrimps belonging to the genus Lysmata Risso, 1816, collected from Madagascar during the Atimo Vatae expedition carried out in 2010. Lysmata malagasy sp. nov. is a new species belonging to the clade named “long accessory ramous” or “cosmopolitan” in previous phylogenetic studies. The new species can be distinguished from the only two other representatives of this group in the Indo-west Pacific, L. ternatensis De Man, 1902, and L. trisetacea (Heller, 1861), by the accessory ramus of the lateral antennular flagellum consisting of four elongated articles. Lysmata lipkei Okuno & Fiedler, 2010 is reported here from Madagascar with a remarkable extension of its known range after its original description from Japan. This species has also been reported from Singapore and, as alien species, from Brazil. Lastly, L. kuekenthali De Man, 1902 known from numerous localities in the Indo-West Pacific biogeographic area, is reported for the first time from Madagascar. Results of the present morphological and molecular analyses suggest that L. hochi Baeza & Anker, 2008 from the Caribbean Sea is a synonym of the Indo-West Pacific L. kuekenthali, and thus the latter species is alien in the western Atlantic.
The dung beetles belonging to the genus Deltochilum Eschscholtz, 1822 are widely distributed in the Neotropical region. This genus is divided into eight subgenera, of these, the subgenus Deltohyboma Lane, 1946 is the most diverse, with an estimated 212 species. The most recent revision of Deltohyboma divided the subgenus into 19 species group. Here, taxonomy of the gilli species group is revised. Four new species (D. jocelynae sp. nov., D. nonstriatum sp. nov., D. quasistriatum sp. nov. and D. tenuistriatum sp. nov.) are described, making a total of five species within the species group. Keys for species identification and habitus as well as male genitalia morphology are illustrated.
A new genus of freshwater mussels (Bivalvia: Unionidae) is described from the Mekong River Basin as Namkongnaia gen. nov. The validity of the new genus is supported by its unique conchological characteristics, namely the lack of hinge dentition and elongated shells, together with its evolutionary distinctiveness as estimated by multi-locus phylogenetic analyses (mitochondrial COI and 16S, and nuclear 28S genes). The new genus includes two lineages with deep divergence, shown by 5.10% uncorrected COI p-distance. One lineage is a type species described herein as Namkongnaia inkhavilayi gen. et sp. nov. The other is a recognized species under the name ‘Pilsbryoconcha lemeslei (Morelet, 1875)’. Molecular phylogenetic analysis further shows that the new genus belongs to the tribe Pseudodontini, and evolutionarily is closely related to the genus Monodontina Conrad, 1853. However, its conchology is similar to the genus Pilsbryoconcha Simpson, 1900. Time-calibrated phylogeny suggests that the main radiation events of the tribe Pseudodontini occurred during the Late Cretaceous to the Eocene, with the divergence between the new genus and Monodontina placed in the Miocene. The discovery of new freshwater mussel taxa in this study highlights the importance of the Mekong River Basin as one of the world’s biodiversity hotspots for freshwater fauna.
Coelogynoporidae (Platyhelminthes) includes comparatively large and slender Proseriata, usually occurring in shallow benthic environments. Coelogynopora Steinböck, 1924 is the most frequently reported genus and the one with the highest species diversity. Notwithstanding that, the genus has never been reported from the Southern Hemisphere. A recent analysis of sediment from the Magellan Strait shores (Chile) resulted in the discovery of a new species of Coelogynopora, the first representative of the genus to be found in austral waters. The new species is defined by the following combination of characters: sclerotised copulatory system consisting of a slender, ventrally curved stylet with a broad base and three pairs of symmetrically arranged spines, the proximal ends of which are fused laterally to the base of the stylet; distal ends of the three pairs of spines hooked, with apophyses at progressively longer distances from the tip; accessory spines and solar organ absent. Based on the morphological characters, the new species appears to be more related to species from the Pacific Ocean than to those from the Atlantic Ocean. The present work suggests a vast biogeographic disjunction in the genus Coelogynopora, which may be described as a bipolar or amphitropical pattern of distribution.
Misconceptions about scientific concepts often prevail even if learners are confronted with conflicting evidence. This study tested the facilitative role of surprise in children’s revision of misconceptions regarding water displacement in a sample of German children (N = 94, aged 6–9 years, 46% female). Surprise was measured via the pupil dilation response. It was induced by letting children generate predictions before presenting them with outcomes that conflicted with their misconception. Compared to a control condition, generating predictions boosted children’s surprise and led to a greater revision of misconceptions (d = 0.56). Surprise further predicted successful belief revision during the learning phase. These results suggest that surprise increases the salience of a cognitive conflict, thereby facilitating the revision of misconceptions.
Fluorescently labeled nanoparticles are widely used for evaluating their distribution in the biological environment. However, dye leakage can lead to misinterpretations of the nanoparticles’ biodistribution. To better understand the interactions of dyes and nanoparticles and their biological environment, we explored PLGA nanoparticles labeled with four widely used dyes encapsulated (coumarin 6, rhodamine 123, DiI) or bound covalently to the polymer (Cy5.5.). The DiI label was stable in both aqueous and lipophilic environments, whereas the quick release of coumarin 6 was observed in model media containing albumin (42%) or liposomes (62%), which could be explained by the different affinity of these dyes to the polymer and lipophilic structures and which we also confirmed by computational modeling (log PDPPC/PLGA: DiI—2.3, Cou6—0.7). The importance of these factors was demonstrated by in vivo neuroimaging (ICON) of the rat retina using double-labeled Cy5.5/Cou6-nanoparticles: encapsulated Cou6 quickly leaked into the tissue, whereas the stably bound Cy.5.5 label remained associated with the vessels. This observation is a good example of the possible misinterpretation of imaging results because the coumarin 6 distribution creates the impression that nanoparticles effectively crossed the blood–retina barrier, whereas in fact no signal from the core material was found beyond the blood vessels.
Simple Summary: Cancer immunotherapy mainly targets immune system components, such as immune-suppressive networks generated by cancer cells in the tumor microenvironment (TME). Programmed cell death ligand 1, which is a secretory immune-suppressive factor, is released by tumor-associated macrophages (TAMs). The TME also disrupts production of tumor-specific T cells and generates immunosuppressive leukocytes, regulatory T cells, and myeloid-derived suppressor cells. Immune checkpoint inhibitors are effective in various cancers but only in a subset of patients. Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are dysregulated in cancer through transcriptional, post-transcriptional, and epigenetic changes and have significant roles in cancer initiation and progression, which depends on deregulation of lncRNA expression. TAM function can be influenced by lncRNAs in various ways. However, our understanding of lncRNA dysregulation and function in cancer remains in the early stage.
Abstract: Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as “junk” in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis. In this review, we aimed to describe the complex roles and functions of lncRNAs in macrophages and their influence on lung cancer development and progression through the TME.
Inhibition of fatty acid synthesis (FAS) stimulates tumor cell death and reduces angiogenesis. When SH-SY5Y cells or primary neurons are exposed to hypoxia only, inhibition of FAS yields significantly enhanced cell injury. The pathophysiology of stroke, however, is not only restricted to hypoxia but also includes reoxygenation injury. Hence, an oxygen-glucose-deprivation (OGD) model with subsequent reoxygenation in both SH-SY5Y cells and primary neurons as well as a murine stroke model were used herein in order to study the role of FAS inhibition and its underlying mechanisms. SH-SY5Y cells and cortical neurons exposed to 10 h of OGD and 24 h of reoxygenation displayed prominent cell death when treated with the Acetyl-CoA carboxylase inhibitor TOFA or the fatty acid synthase inhibitor cerulenin. Such FAS inhibition reduced the reduction potential of these cells, as indicated by increased NADH2+/NAD+ ratios under both in vitro and in vivo stroke conditions. As observed in the OGD model, FAS inhibition also resulted in increased cell death in the stroke model. Stroke mice treated with cerulenin did not only display increased brain injury but also showed reduced neurological recovery during the observation period of 4 weeks. Interestingly, cerulenin treatment enhanced endothelial cell leakage, reduced transcellular electrical resistance (TER) of the endothelium and contributed to poststroke blood-brain barrier (BBB) breakdown. The latter was a consequence of the activated NF-κB pathway, stimulating MMP-9 and ABCB1 transporter activity on the luminal side of the endothelium. In conclusion, FAS inhibition aggravated poststroke brain injury as consequence of BBB breakdown and NF-κB-dependent inflammation.
Positive psychological coaching (PPC) has emerged as a popular “paradigm” for practitioners interested in the professional development of people. A recent review consolidated the literature on PPC and produced a 5-phase positive psychological coaching model aimed at facilitating professional growth. However, little is known about practically operationalizing each phase of the coaching process (i.e., how to facilitate each phase and which underlying tools and techniques could be employed to do so). As such, the purpose of this systematic review was to address this limitation by (a) determining which coaching tools and techniques are proposed within the coaching literature and (b) classifying the identified tools and techniques into the respective phases of PPC model. The investigation used a two-step approach by conducting a systematic literature review (to identify various PPC tools/techniques) followed by an iterative heuristic classification process (to assign these PPC tools/techniques to a known PPC model). The systematic literature review resulted in 24 peer-reviewed publications on positive psychological coaching, providing 117 different coaching tools that could be condensed into 18 overarching coaching techniques. The iterative classification process showed that most techniques and tools are useful in at least two phases. Interestingly, experts still vary in opinion on the timing and application of these specific techniques and tools within the positive psychological coaching process. This study provides researchers and practitioners with practical guidelines to facilitate a positive psychological coaching process.
The COVID-19 lockdown has significantly disrupted the higher education environment within the Netherlands and led to changes in available study-related resources and study demands of students. These changes in study resources and study demands, the uncertainty and confusion about educational activities, the developing fear and anxiety about the disease, and the implementation of the COVID-19 lockdown measures may have a significant impact on the mental health of students. As such, this study aimed to investigate the trajectory patterns, rate of change, and longitudinal associations between study resources–demands and mental health of 141 university students from the Netherlands before and during the COVID-19 lockdown. The present study employed a longitudinal design and a piecewise latent growth modeling strategy to investigate the changes in study resources and mental health over a 3 month period. The results showed that moderate levels of student resources significantly decreased before, followed by a substantial rate of increase during, lockdown. In contrast, study demands and mental health were reported to be moderate and stable throughout the study. Finally, the growth trajectories of study resources–demands and mental health were only associated before the lockdown procedures were implemented. Despite growing concerns relating to the negative psychological impact of COVID-19 on students, our study shows that the mental health during the initial COVID-19 lockdown remained relatively unchanged.
Background: Gan–Dou–Fu–Mu decoction (GDFMD) improves liver fibrosis in experimental and clinical studies including those on toxic mouse model of Wilson disease (Model). However, the mechanisms underlying the effect of GDFMD have not been characterized. Herein, we deciphered the potential therapeutic targets of GDFMD using transcriptome analysis.
Methods: We constructed a tx-j Wilson disease (WD) mouse model, and assessed the effect of GDFMD on the liver of model mice by hematoxylin and eosin, Masson, and immunohistochemical staining. Subsequently, we identified differentially expressed genes (DEGs) that were upregulated in the Model (Model vs. control) and those that were downregulated upon GDFMD treatment (compared to the Model) using RNA-sequencing (RNA-Seq). Biological functions and signaling pathways in which the DEGs were involved were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. A protein–protein interaction (PPI) network was constructed using the STRING database, and the modules were identified using MCODE plugin with the Cytoscape software. Several genes identified in the RNA-Seq analysis were validated by real-time quantitative PCR. Results: Total of 2124 DEGs were screened through the Model vs. control and Model vs. GDFMD comparisons, and dozens of GO and KEGG pathway terms modulated by GDFMD were identified. Dozens of pathways involved in metabolism (including metabolic processes for organic acids, carboxylic acids, monocarboxylic acids, lipids, fatty acids, cellular lipids, steroids, alcohols, eicosanoids, long-chain fatty acids), immune and inflammatory response (such as complement and coagulation cascades, cytokine–cytokine receptor interaction, inflammatory mediator regulation of TRP channels, antigen processing and presentation, T-cell receptor signaling pathway), liver fibrosis (such as ECM-receptor interactions), and cell death (PI3K-Akt signaling pathway, apoptosis, TGF-beta signaling pathway, etc.) were identified as potential targets of GDFMD in the Model. Some hub genes and four modules were identified in the PPI network. The results of real-time quantitative PCR analysis were consistent with those of RNA-Seq analysis. Conclusions: We performed gene expression profiling of GDFMD-treated WD model mice using RNA-Seq analysis and found the genes, pathways, and processes effected by the treatment. Our study provides a theoretical basis to prevent liver fibrosis resulting from WD using GDFMD.
Background: Both selective mutism (SM) and social anxiety disorder (SAD) are severe pediatric anxiety disorders with the common trait of behavioral inhibition (BI). The underlying pathophysiology of these disorders remains poorly understood, however converging evidence suggests that alterations in several peripheral molecular pathways might be involved. In a pilot study, we investigated alterations in plasma molecular markers (dipeptidyl peptidase-4 [DPPIV], interleukin-6 [IL-6], tumor necrosis factor-β [TNF-β] and neuropeptide-Y [NPY]) in children with SM, SAD, and healthy controls, as well as the correlation of these markers to symptom severity. Methods: We included 51 children and adolescents (aged 5–18 years; n = 29 girls): n = 20 children in the SM-, n = 16 in the SAD- and n = 15 in the control-group (CG). Peripheral blood samples were analyzed for DPPIV, IL-6, TNF-β, and NPY concentrations. Diverse psychometric measures were used for BI, anxiety, and mutism symptoms. Results: Lower DPPIV-levels were correlated with more anxiety symptoms. However, we could not find a difference in any molecular marker between the patients with SAD and SM in comparison to the CG. Conclusion: DPPIV is proposed as relevant marker for child and adolescent anxiety. Investigating the pathophysiology of SM and SAD focusing on state and trait variables as anxiety or BI might help better understanding the underlying mechanisms of these disorders. Further studies with especially larger cohorts are needed to validate the current pilot-findings.
In sports and clinical settings, roller massage (RM) interventions are used to acutely increase range of motion (ROM); however, the underlying mechanisms are unclear. Apart from changes in soft tissue properties (i.e., reduced passive stiffness), neurophysiological alterations such as decreased spinal excitability have been described. However, to date, no study has investigated both jointly. The purpose of this trial was to examine RM’s effects on neurophysiological markers and passive tissue properties of the plantar flexors in the treated (ROLL) and non-treated (NO- ROLL) leg. Fifteen healthy individuals (23 ± 3 years, eight females) performed three unilateral 60-s bouts of calf RM. This procedure was repeated four times on separate days to allow independent assessments of the following outcomes without reciprocal interactions: dorsiflexion ROM, passive torque during passive dorsiflexion, shear elastic modulus of the medial gastrocnemius muscle, and spinal excitability. Following RM, dorsiflexion ROM increased in both ROLL (+19.7%) and NO-ROLL (+13.9%). Similarly, also passive torque at dorsiflexion ROM increased in ROLL (+15.0%) and NO-ROLL (+15.2%). However, there were no significant changes in shear elastic modulus and spinal excitability (p > 0.05). Moreover, significant correlations were observed between the changes in DF ROM and passive torque at DF ROM in both ROLL and NO-ROLL. Changes in ROM after RM appear to be the result of sensory changes (e.g., passive torque at DF ROM), affecting both rolled and non-rolled body regions. Thus, therapists and exercise professionals may consider applying remote treatments if local loading is contraindicated.
The abyssal seafloor is a mosaic of highly diverse habitats that represent the least known marine ecosystems on Earth. Some regions enriched in natural resources, such as polymetallic nodules in the Clarion-Clipperton Zone (CCZ), attract much interest because of their huge commercial potential. Since nodule mining will be destructive, baseline data are necessary to measure its impact on benthic communities. Hence, we conducted an environmental DNA and RNA metabarcoding survey of CCZ biodiversity targeting microbial and meiofaunal eukaryotes that are the least known component of the deep-sea benthos. We analyzed two 18S rRNA gene regions targeting eukaryotes with a focus on Foraminifera (37F) and metazoans (V1V2), sequenced from 310 surface-sediment samples from the CCZ and other abyssal regions. Our results confirm huge unknown deep-sea biodiversity. Over 60% of benthic foraminiferal and almost a third of eukaryotic operational taxonomic units (OTUs) could not be assigned to a known taxon. Benthic Foraminifera are more common in CCZ samples than metazoans and dominated by clades that are only known from environmental surveys. The most striking results are the uniqueness of CCZ areas, both datasets being characterized by a high number of OTUs exclusive to the CCZ, as well as greater beta diversity compared to other abyssal regions. The alpha diversity in the CCZ is high and correlated with water depth and terrain complexity. Topography was important at a local scale, with communities at CCZ stations located in depressions more diverse and heterogeneous than those located on slopes. This could result from eDNA accumulation, justifying the interim use of eRNA for more accurate biomonitoring surveys. Our descriptions not only support previous findings and consolidate our general understanding of deep-sea ecosystems, but also provide a data resource inviting further taxon-specific and large-scale modeling studies. We foresee that metabarcoding will be useful for deep-sea biomonitoring efforts to consider the diversity of small taxa, but it must be validated based on ground truthing data or experimental studies.
Simple Summary: Mutations in RAS-family genes frequently cause different types of human cancers. Inhibitors of the MEK (mitogen-activated protein kinase) and ERK (extracellular signal-regulated kinase) protein kinases that function downstream of RAS proteins have shown some clinical benefits when used for the treatment of these cancers, but drug resistance frequently emerges. Here we show that combined treatment with MEK and ERK inhibitors blocks the emergence of resistance to either drug alone. However, if cancer cells have already developed resistance to MEK inhibitors or to ERK inhibitors, the combined therapy is frequently ineffective. These findings imply that these inhibitors should be used together for cancer therapy. We also show that drug resistance involves complex patterns of rewiring of cellular kinase signaling networks that do not overlap between each different cancer cell line. Nonetheless, we show that MAP4K4 is required for efficient cell proliferation in several different MEK/ERK inhibitor resistant cancer cell lines, uncovering a potential new therapeutic target.
Abstract: Oncogenic mutations in RAS family genes arise frequently in metastatic human cancers. Here we developed new mouse and cellular models of oncogenic HrasG12V-driven undifferentiated pleomorphic sarcoma metastasis and of KrasG12D-driven pancreatic ductal adenocarcinoma metastasis. Through analyses of these cells and of human oncogenic KRAS-, NRAS- and BRAF-driven cancer cell lines we identified that resistance to single MEK inhibitor and ERK inhibitor treatments arise rapidly but combination therapy completely blocks the emergence of resistance. The prior evolution of resistance to either single agent frequently leads to resistance to dual treatment. Dual MEK inhibitor plus ERK inhibitor therapy shows anti-tumor efficacy in an HrasG12V-driven autochthonous sarcoma model but features of drug resistance in vivo were also evident. Array-based kinome activity profiling revealed an absence of common patterns of signaling rewiring in single or double MEK and ERK inhibitor resistant cells, showing that the development of resistance to downstream signaling inhibition in oncogenic RAS-driven tumors represents a heterogeneous process. Nonetheless, in some single and double MEK and ERK inhibitor resistant cell lines we identified newly acquired drug sensitivities. These may represent additional therapeutic targets in oncogenic RAS-driven tumors and provide general proof-of-principle that therapeutic vulnerabilities of drug resistant cells can be identified.
Simple Summary: Infections are an important cause of morbidity and mortality in childhood cancer treatment. The aim of our retrospective study was to assess the infectious burden in pediatric sarcoma patients during neoadjuvant chemotherapy administered according to the EWING 2008, CWS SoTiSaR and EURAMOS clinical trial or registry. Our analyses indicate a substantial infectious morbidity in this group of patients, with 58.8% experiencing at least one episode of febrile neutropenia (FN) and 20.6% at least one microbiologically documented infection (MDI). We also identified parameters that impact on the occurrence of FN and MDIs, including treatment protocol, patient age, and mucositis. These findings may contribute to a better risk stratification for prevention and management of FN and infections as well as for maintaining quality of life, cost control, and optimum outcomes of anticancer treatment.
Abstract: The purpose of this retrospective, single-center cohort study was to assess the infectious burden in pediatric sarcoma patients during neoadjuvant chemotherapy. The review included all patients with a new diagnosis of Ewing sarcoma, osteosarcoma or soft tissue sarcoma between September 2009 and December 2018 who were enrolled in the EWING 2008, CWS SoTiSaR and EURAMOS clinical trial or registry. Primary endpoints were the occurrence of febrile neutropenia (FN) and microbiologically documented infection (MDI). Parameters with a potential impact on FN and MDI were also analyzed. A total of 170 sarcoma patients (median age: 13 years, range: 0–21; 96 m/74 f) received 948 chemotherapy courses (median: 6; range: 2–8). Of these patients, 58.8% had ≥1 FN episode and 20.6% ≥ 1 MDI. FN occurred in 272/948 courses (28.7%) with fever of unknown origin (FUO) in 231 courses and 45 MDI and 19 clinically documented infections (CDI) occurring in a total of 57 courses. Patients enrolled in EWING 2008 had significantly more FN (p < 0.001), infections (p = 0.02) and MDI (p = 0.035). No infection-related deaths were observed. Younger age, tumor type and localization, and higher median and maximum mucositis grades were significantly associated with higher numbers of FN (p < 0.001), and younger age (p = 0.024) and higher median mucositis grade (p = 0.017) with MDI. The study shows substantial infectious morbidity in sarcoma patients during neoadjuvant chemotherapy treatment and opportunities to improve prevention and management.
Bartonellae are facultative intracellular alpha-proteobacteria often transmitted by arthropods. Ixodes ricinus is the most important vector for arthropod-borne pathogens in Europe. However, its vector competence for Bartonella spp. is still unclear. This study aimed to experimentally compare its vector competence for three Bartonella species: B. henselae, B. grahamii, and B. schoenbuchensis. A total of 1333 ticks (1021 nymphs and 312 adults) were separated into four groups, one for each pathogen and a negative control group. Ticks were fed artificially with bovine blood spiked with the respective Bartonella species. DNA was extracted from selected ticks to verify Bartonella-infection by PCR. DNA of Bartonella spp. was detected in 34% of nymphs and females after feeding. The best engorgement results were obtained by ticks fed with B. henselae-spiked blood (65.3%) and B. schoenbuchensis (61.6%). Significantly more nymphs fed on infected blood (37.3%) molted into adults compared to the control group (11.4%). Bartonella DNA was found in 22% of eggs laid by previously infected females and in 8.6% of adults molted from infected nymphs. The transovarial and transstadial transmission of bartonellae suggest that I. ricinus could be a potential vector for three bacteria.
Working memory capacity (WMC) and fluid intelligence (Gf) are highly correlated, but what accounts for this relationship remains elusive. Process-overlap theory (POT) proposes that the positive manifold is mainly caused by the overlap of domain-general executive processes which are involved in a battery of mental tests. Thus, executive processes are proposed to explain the relationship between WMC and Gf. The current study aims to (1) achieve a relatively purified representation of the core executive processes including shifting and inhibition by a novel approach combining experimental manipulations and fixed-links modeling, and (2) to explore whether these executive processes account for the overlap between WMC and Gf. To these ends, we reanalyzed data of 215 university students who completed measures of WMC, Gf, and executive processes. Results showed that the model with a common factor, as well as shifting and inhibition factors, provided the best fit to the data of the executive function (EF) task. These components explained around 88% of the variance shared by WMC and Gf. However, it was the common EF factor, rather than inhibition and shifting, that played a major part in explaining the common variance. These results do not support POT as underlying the relationship between WMC and Gf.
The sketch map tool facilitates the assessment of OpenStreetMap data for participatory mapping
(2021)
A worldwide increase in the number of people and areas affected by disasters has led to more and more approaches that focus on the integration of local knowledge into disaster risk reduction processes. The research at hand shows a method for formalizing this local knowledge via sketch maps in the context of flooding. The Sketch Map Tool enables not only the visualization of this local knowledge and analyses of OpenStreetMap data quality but also the communication of the results of these analyses in an understandable way. Since the tool will be open-source and several analyses are made automatically, the tool also offers a method for local governments in areas where historic data or financial means for flood mitigation are limited. Example analyses for two cities in Brazil show the functionalities of the tool and allow the evaluation of its applicability. Results depict that the fitness-for-purpose analysis of the OpenStreetMap data reveals promising results to identify whether the sketch map approach can be used in a certain area or if citizens might have problems with marking their flood experiences. In this way, an intrinsic quality analysis is incorporated into a participatory mapping approach. Additionally, different paper formats offered for printing enable not only individual mapping but also group mapping. Future work will focus on advancing the automation of all steps of the tool to allow members of local governments without specific technical knowledge to apply the Sketch Map Tool for their own study areas.
Simple Summary: Tooth roots are increasingly applied for bone reconstruction before implant placement. Growth factors stored in the dentin are assumed to enhance bone regeneration, however, the evidence is low. To this aim, collagen membranes were coated with dentin lysates obtained from extracted porcine teeth or remain untreated. The collagen membranes were tested for their capacity to stimulate bone formation in rat calvarial bone defects. After four weeks of healing, micro-computed tomography and histological analyses revealed that dentin lysates coating had no significant impact on the rather strong bone regeneration reaching a nearly complete defect closure even in untreated defects. It can thus be concluded that dentin lysates do not hinder bone regeneration. Conclusions concerning a possible stimulation of bone regeneration by dentin lysates should not be drawn.
Abstract: Autogenous tooth roots are increasingly applied as a grafting material in alveolar bone augmentation. Since tooth roots undergo creeping substitution similar to bone grafts, it can be hypothesized that osteoclasts release the growth factors stored in the dentin thereby influencing bone formation. To test this hypothesis, collagen membranes were either soaked in acid dentin lysates (ADL) from extracted porcine teeth or serum–free medium followed by lyophilization. Thereafter, these membranes covered standardized 5-mm-diameter critical-size defects in calvarial bone on rats. After four weeks of healing, micro-computed tomography and histological analyses using undecalcified thin ground sections were performed. Micro-computed tomography of the inner 4.5 mm calvaria defects revealed a median bone defect coverage of 91% (CI: 87–95) in the ADL group and 94% (CI: 65–100) in the control group, without significant differences between the groups (intergroup p > 0.05). Furthermore, bone volume (BV) was similar between ADL group (5.7 mm3, CI: 3.4–7.1) and control group (5.7 mm3, CI: 2.9–9.7). Histomorphometry of the defect area confirmed these findings with bone area values amounting to 2.1 mm2 (CI: 1.2–2.6) in the ADL group and 2.0 mm2 (CI: 1.1–3.0) in the control group. Together, these data suggest that acid dentin lysate lyophilized onto collagen membranes failed to modulate the robust bone formation when placed onto calvarial defects.
The strengths use scale: psychometric properties, longitudinal invariance and criterion validity
(2021)
Strengths use is an essential personal resource to consider when designing higher-educational programs and interventions. Strengths use is associated with positive outcomes for both the student (e.g., study engagement) and the university (e.g., academic throughput/performance). The Strengths Use Scale (SUS) has become a popular psychometric instrument to measure strengths use in educational settings, yet its use has been subjected to limited psychometric scrutiny outside of the U.S. Further, its longitudinal stability has not yet been established. Given the wide use of this instrument, the goals of this study were to investigate (a) longitudinal factorial validity and the internal consistency of the scale, (b) its equivalence over time, and (c) criterion validity through its relationship with study engagement over time. Data were gathered at two-time points, 3 months apart, from a sample of students in the Netherlands (n = 360). Longitudinal confirmatory factor analyses showed support for a two-factor model for overall strengths use, comprised of Affinity for Strengths and Strengths Use Behaviors. The SUS demonstrated high levels of internal consistency at both the lower- and upper bound limits at both time points. Further, strict longitudinal measurement invariance was established, which confirmed the instrument's temporal stability. Finally, criterion validity was established through relating strengths use to study engagement at different time stamps. These findings support the use of the SUS in practice to measure strengths use and to track the effectiveness of strengths use interventions within the higher education sector.
Radon adsorption in charcoal
(2021)
Radon is pervasive in our environment and the second leading cause of lung cancer induction after smoking. Therefore, the measurement of radon activity concentrations in homes is important. The use of charcoal is an easy and cost-efficient method for this purpose, as radon can bind to charcoal via Van der Waals interaction. Admittedly, there are potential influencing factors during exposure that can distort the results and need to be investigated. Consequently, charcoal was exposed in a radon chamber at different parameters. Afterward, the activity of the radon decay products 214Pb and 214Bi was measured and extrapolated to the initial radon activity in the sample. After an exposure of 1 h, around 94% of the maximum value was attained and used as a limit for the subsequent exposure time. Charcoal was exposed at differing humidity ranging from 5 to 94%, but no influence on radon adsorption could be detected. If the samples were not sealed after exposure, radon desorbed with an effective half-life of around 31 h. There is also a strong dependence of radon uptake on the chemical structure of the recipient material, which is interesting for biological materials or diffusion barriers as this determines accumulation and transport.
We show that throughout the satisfiable phase the normalized number of satisfying assignments of a random 2-SAT formula converges in probability to an expression predicted by the cavity method from statistical physics. The proof is based on showing that the Belief Propagation algorithm renders the correct marginal probability that a variable is set to “true” under a uniformly random satisfying assignment.
Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.
Coagulation factor XIII (FXIII) is a protransglutaminase which plays an important role in clot stabilization and composition by cross-linking the α- and γ-chains of fibrin and increasing the resistance of the clot to mechanical and proteolytic challenges. In this study, we selected six DNA aptamers specific for activated FXIII (FXIIIa) and investigated the functional characterization of FXIIIa after aptamer binding. One of these aptamers, named FA12, efficiently captures FXIIIa even in the presence of zymogenic FXIII subunits. Furthermore, this aptamer inhibits the incorporation of FXIII and α2-antiplasmin (α2AP) into fibrin(ogen) with IC50-values of 38 nM and 17 nM, respectively. In addition to FA12, also another aptamer, FA2, demonstrated significant effects in plasma-based thromboelastometry (rotational thromboelastometry analysis, ROTEM)-analysis where spiking of the aptamers into plasma decreased clot stiffness and elasticity (p < 0.0001). The structure–function correlations determined by combining modeling/docking strategies with quantitative in vitro assays revealed spatial overlap of the FA12 binding site with the binding sites of two FXIII substrates, fibrinogen and α2AP, while FA2 binding sites only overlap those of fibrinogen. Taken together, these features especially render the aptamer FA12 as an interesting candidate molecule for the development of FXIIIa-targeting therapeutic strategies and diagnostic assays.
Presolar grains and their isotopic compositions provide valuable constraints to AGB star nucleosynthesis. However, there is a sample of O- and Al-rich dust, known as group 2 oxide grains, whose origin is difficult to address. On the one hand, the 17O/16O isotopic ratios shown by those grains are similar to the ones observed in low-mass red giant stars. On the other hand, their large 18O depletion and 26Al enrichment are challenging to account for. Two different classes of AGB stars have been proposed as progenitors of this kind of stellar dust: intermediate mass AGBs with hot bottom burning, or low mass AGBs where deep mixing is at play. Our models of low-mass AGB stars with a bottom-up deep mixing are shown to be likely progenitors of group 2 grains, reproducing together the 17O/16O, 18O/16O and 26Al/27Al values found in those grains and being less sensitive to nuclear physics inputs than our intermediate-mass models with hot bottom burning.
Background: One of the lesser recognized complications of diabetes mellitus are musculoskeletal (MSK) complications of the upper and lower extremity. No prevalence studies have been conducted in general practice. Thus, the aim of this study was to investigate the prevalence of upper extremity MSK disorders in patients with type 2 diabetes (T2DM) in the Netherlands. Methods: We conducted a cross-sectional study with two different approaches, namely a representative Dutch primary care medical database study and a questionnaire study among patients with T2DM. Results: In the database study, 2669 patients with T2DM and 2669 non-diabetes patients were included. MSK disorders were observed in 16.3% of patients with T2DM compared to 11.2% of non-diabetes patients (p < 0.001, OR 1.53, 95% CI 1.31, 1.80). In the questionnaire study, 200 patients with T2DM were included who reported a lifetime prevalence of painful upper extremity body sites for at least four weeks of 67.3%. Conclusion: We found that upper extremity MSK disorders have a high prevalence in Dutch patients with T2DM presenting in general practice. The prevalence ranges from 16% based on GP registered disorders and complaints to 67% based on self-reported diagnosis and pain. Early detection and treatment of these disorders may play a role in preventing the development of chronic MSK disorders.
Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Crystal structures of two representatives of the new chemotype in complex with Aurora A showed the ligand orientation in the ATP binding pocket and provided the basis for rational structural modifications. Congeners with attached sulfamide substituents retained Aurora A inhibitory activity. In vitro screening of two members of the new kinase inhibitor family against the cancer cell line panel of the National Cancer Institute (NCI) showed antiproliferative activity in the single-digit micromolar concentration range in the majority of the cell lines.
Centris xanthomelaena Moure & Castro, 2001 is a relict species, endemic to northeastern Brazil and broadly recorded within the semiarid region of Caatinga xerophilous open vegetation. It was originally included in the subgenus Paracentris Cameron, 1903 but posteriorly interpreted as remotely related to it or to the subgenus Centris s. str. Fabricius, 1804. In this paper it is proposed to recognize this species as the single member of the monotypic Relicthemisia, a new subgenus which belongs to the ‘Centris group’, one of the main internal lineages of the genus. The proposition of this new subgenus is based on both, morphological and molecular data which indicate its long history as a distinct lineage. Distribution records, floral hosts as well as photographs of both sexes of C. xanthomelaena are also provided.
Predicting the cumulative medical load of COVID-19 outbreaks after the peak in daily fatalities
(2021)
The distinct ways the COVID-19 pandemic has been unfolding in different countries and regions suggest that local societal and governmental structures play an important role not only for the baseline infection rate, but also for short and long-term reactions to the outbreak. We propose to investigate the question of how societies as a whole, and governments in particular, modulate the dynamics of a novel epidemic using a generalization of the SIR model, the reactive SIR (short-term and long-term reaction) model. We posit that containment measures are equivalent to a feedback between the status of the outbreak and the reproduction factor. Short-term reaction to an outbreak corresponds in this framework to the reaction of governments and individuals to daily cases and fatalities. The reaction to the cumulative number of cases or deaths, and not to daily numbers, is captured in contrast by long-term reaction. We present the exact phase space solution of the controlled SIR model and use it to quantify containment policies for a large number of countries in terms of short and long-term control parameters. We find increased contributions of long-term control for countries and regions in which the outbreak was suppressed substantially together with a strong correlation between the strength of societal and governmental policies and the time needed to contain COVID-19 outbreaks. Furthermore, for numerous countries and regions we identified a predictive relation between the number of fatalities within a fixed period before and after the peak of daily fatality counts, which allows to gauge the cumulative medical load of COVID-19 outbreaks that should be expected after the peak. These results suggest that the proposed model is applicable not only for understanding the outbreak dynamics, but also for predicting future cases and fatalities once the effectiveness of outbreak suppression policies is established with sufficient certainty. Finally, we provide a web app (https://itp.uni-frankfurt.de/covid-19/) with tools for visualising the phase space representation of real-world COVID-19 data and for exporting the preprocessed data for further analysis.
KCNQ1 encodes the voltage-gated potassium (Kv) channel KCNQ1, also known as KvLQT1 or Kv7.1. Together with its ß-subunit KCNE1, also denoted as minK, this channel generates the slowly activating cardiac delayed rectifier current IKs, which is a key regulator of the heart rate dependent adaptation of the cardiac action potential duration (APD). Loss-of-function mutations in KCNQ1 cause congenital long QT1 (LQT1) syndrome, characterized by a delayed cardiac repolarization and a prolonged QT interval in the surface electrocardiogram. Autosomal dominant loss-of-function mutations in KCNQ1 result in long QT syndrome, called Romano–Ward Syndrome (RWS), while autosomal recessive mutations lead to Jervell and Lange-Nielsen syndrome (JLNS), associated with deafness. Here, we identified a homozygous KCNQ1 mutation, c.1892_1893insC (p.P631fs*20), in a patient with an isolated LQT syndrome (LQTS) without hearing loss. Nevertheless, the inheritance trait is autosomal recessive, with heterozygous family members being asymptomatic. The results of the electrophysiological characterization of the mutant, using voltage-clamp recordings in Xenopus laevis oocytes, are in agreement with an autosomal recessive disorder, since the IKs reduction was only observed in homomeric mutants, but not in heteromeric IKs channel complexes containing wild-type channel subunits. We found that KCNE1 rescues the KCNQ1 loss-of-function in mutant IKs channel complexes when they contain wild-type KCNQ1 subunits, as found in the heterozygous state. Action potential modellings confirmed that the recessive c.1892_1893insC LQT1 mutation only affects the APD of homozygous mutation carriers. Thus, our study provides the molecular mechanism for an atypical autosomal recessive LQT trait that lacks hearing impairment.
The genus Levizonus Attems, 1898 is rediagnosed and shown to contain eight species from Russia (Far East), North Korea, Japan and North-East China. One species is described here as new to science: Levizonus nakhodka sp. nov. A new formal synonym is proposed: Levizonus circularis Takakuwa, 1942 = Levizonus variabilis Lokschina & Golovatch, 1977 syn. nov., the valid name being the former. Levizonus circularis Takakuwa, 1942 is recorded for the fauna of China for the first time. All currently known species of Levizonus are included in a key, mapped and discussed.
Two new species of Sonerila Roxb. (Melastomataceae), S. erectifolia Phonep., Soulad. & Tagane sp. nov. from southern Laos, and S. souvannii Phonep. & Soulad. sp. nov. from central Laos, are described and illustrated. Comparisons with morphologically similar species are presented, along with ecological information and preliminary conservation status. A key to the species of Sonerila in Laos is also provided.
Recurrent cortical networks provide reservoirs of states that are thought to play a crucial role for sequential information processing in the brain. However, classical reservoir computing requires manual adjustments of global network parameters, particularly of the spectral radius of the recurrent synaptic weight matrix. It is hence not clear if the spectral radius is accessible to biological neural networks. Using random matrix theory, we show that the spectral radius is related to local properties of the neuronal dynamics whenever the overall dynamical state is only weakly correlated. This result allows us to introduce two local homeostatic synaptic scaling mechanisms, termed flow control and variance control, that implicitly drive the spectral radius toward the desired value. For both mechanisms the spectral radius is autonomously adapted while the network receives and processes inputs under working conditions. We demonstrate the effectiveness of the two adaptation mechanisms under different external input protocols. Moreover, we evaluated the network performance after adaptation by training the network to perform a time-delayed XOR operation on binary sequences. As our main result, we found that flow control reliably regulates the spectral radius for different types of input statistics. Precise tuning is however negatively affected when interneural correlations are substantial. Furthermore, we found a consistent task performance over a wide range of input strengths/variances. Variance control did however not yield the desired spectral radii with the same precision, being less consistent across different input strengths. Given the effectiveness and remarkably simple mathematical form of flow control, we conclude that self-consistent local control of the spectral radius via an implicit adaptation scheme is an interesting and biological plausible alternative to conventional methods using set point homeostatic feedback controls of neural firing.
Recent proposals suggest that timing in acquisition, i.e., the age at which a phenomenon is mastered by monolingual children, influences acquisition of the L2, interacting with age of onset of bilingualism and amount of L2 input. Here, we examine whether timing affects acquisition of the bilingual child’s heritage language, possibly modulating the effects of environmental and child-internal factors. The performance of 6- to 12-year-old Greek heritage children residing in Germany (age of onset of German: 0–4 years) was assessed across a range of nine syntactic structures via the Greek LITMUS (Language Impairment Testing in Multilingual Settings) Sentence Repetition Task. Based on previous studies on monolingual Greek, the structures were classified as “early” (main clauses (SVO), coordination, clitics, complement clauses, sentential negation, non-referential wh-questions) or as “late” (referential wh-questions, relatives, adverbial clauses). Current family use of Greek and formal instruction in Greek (environmental), chronological age, and age of onset of German (child-internal) were assessed via the Questionnaire for Parents of Bilingual Children (PABIQ); short-term memory (child-internal) was measured via forward digit recall. Children’s scores were generally higher for early than for late acquired structures. Performance on the three early structures with the highest scores was predicted by the amount of current family use of Greek. Performance on the three late structures was additionally predicted by forward digit recall, indicating that higher short-term memory capacity is beneficial for correctly reconstructing structurally complex sentences. We suggest that the understanding of heritage language development and the role of child-internal and environmental factors will benefit from a consideration of timing in the acquisition of the different structures.
Specifying accurate informative prior distributions is a question of carefully selecting studies that comprise the body of comparable background knowledge. Psychological research, however, consists of studies that are being conducted under different circumstances, with different samples and varying instruments. Thus, results of previous studies are heterogeneous, and not all available results can and should contribute equally to an informative prior distribution. This implies a necessary weighting of background information based on the similarity of the previous studies to the focal study at hand. Current approaches to account for heterogeneity by weighting informative prior distributions, such as the power prior and the meta-analytic predictive prior are either not easily accessible or incomplete. To complicate matters further, in the context of Bayesian multiple regression models there are no methods available for quantifying the similarity of a given body of background knowledge to the focal study at hand. Consequently, the purpose of this study is threefold. We first present a novel method to combine the aforementioned sources of heterogeneity in the similarity measure ω. This method is based on a combination of a propensity-score approach to assess the similarity of samples with random- and mixed-effects meta-analytic models to quantify the heterogeneity in outcomes and study characteristics. Second, we show how to use the similarity measure ω as a weight for informative prior distributions for the substantial parameters (regression coefficients) in Bayesian multiple regression models. Third, we investigate the performance and the behavior of the similarity-weighted informative prior distribution in a comprehensive simulation study, where it is compared to the normalized power prior and the meta-analytic predictive prior. The similarity measure ω and the similarity-weighted informative prior distribution as the primary results of this study provide applied researchers with means to specify accurate informative prior distributions.
Sprouting of surviving axons is one of the major reorganization mechanisms of the injured brain contributing to a partial restoration of function. Of note, sprouting is maturation as well as age-dependent and strong in juvenile brains, moderate in adult and weak in aged brains. We have established a model system of complex organotypic tissue cultures to study sprouting in the dentate gyrus following entorhinal denervation. Entorhinal denervation performed after 2 weeks postnatally resulted in a robust, rapid, and very extensive sprouting response of commissural/associational fibers, which could be visualized using calretinin as an axonal marker. In the present study, we analyzed the effect of maturation on this form of sprouting and compared cultures denervated at 2 weeks postnatally with cultures denervated at 4 weeks postnatally. Calretinin immunofluorescence labeling as well as time-lapse imaging of virally-labeled (AAV2- hSyn1-GFP) commissural axons was employed to study the sprouting response in aged cultures. Compared to the young cultures commissural/associational sprouting was attenuated and showed a pattern similar to the one following entorhinal denervation in adult animals in vivo. We conclude that a maturation-dependent attenuation of sprouting occurs also in vitro, which now offers the chance to study, understand and influence maturation-dependent differences in brain repair in these culture preparations.
The estimation of the minimum time since death is one of the main applications of forensic entomology. This can be done by calculating the age of the immature stage of necrophagous flies developing on the corpse, which is confined to approximately 2–4 weeks, depending on temperature and species of the first colonizing wave of flies. Adding the age of the adult flies developed on the dead body could extend this time frame up to several weeks when the body is in a building or closed premise. However, the techniques for accurately estimating the age of adult flies are still in their beginning stages or not sufficiently validated. Here we review the current state of the art of analysing the aging of flies by evaluating the ovarian development, the amount of pteridine in the eyes, the degree of wing damage, the modification of their cuticular hydrocarbon patterns, and the increasing number of growth layers in the cuticula. New approaches, including the use of age specific molecular profiles based on the levels of gene and protein expression and the application of near infrared spectroscopy, are introduced, and the forensic relevance of these methods is discussed.
Background: We conducted a comprehensive medication review at the patients’ home, using data from electronic patient records, and with input from relevant specialists, general practitioners and pharmacists formulated and implemented recommendations to optimize medication use in patients aged 60+ years with polypharmacy. We evaluated the effect of this medication review on quality of life (QoL) and medication use. Methods: Cluster randomized controlled trial (stepped wedge), randomly assigning general practices to one of three consecutive steps. Patients received usual care until the intervention was implemented. Primary outcome was QoL (SF-36 and EQ-5D); secondary outcomes were medication changes, medication adherence and (instrumental) activities of daily living (ADL, iADL) which were measured at baseline, and around 6- and 12-months post intervention. Results: Twenty-four general practices included 360 women and 410 men with an average age of 75 years (SD 7.5). A positive effect on SF-36 mental health (estimated mean was stable in the intervention, but decreased in the control condition with −6.1, p = 0.009,) was found with a reduced number of medications at follow-up compared to the control condition. No significant effects were found on other QoL subscales, ADL, iADL or medication adherence. Conclusion: The medication review prevented decrease of mental health (SF36), with no significant effects on other outcome measures, apart from a reduction in the number of prescribed medications.