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This article departs from the hypothesis that Alexander von Humboldt used ‘Big Data’ in order to bring new scientific evidence into the open. His method of measuring and combining temperature, humidity, altitude and magnetism in a geographical environment must be regarded as innovative, indeed, as the foundation of modern science. Although Humboldt lived in an analogue world and used the instruments of his time, his way of assembling information was not so different from what we are seeing in today's digitalised world. Information has no value unless it is shared. It does not say anything unless it is linked with other data. It cannot remain isolated but must be compared and interpreted. The generation of ʻBig Dataʼ was a pathway to Humboldt's concept of ʻKosmosʼ in much the same way as ʻBig Dataʼ today is the pathway to a virtual world. In this sense, Humboldt not only laid the foundation of modern science but anticipated the existence of a world where data and information are the source of everything when it comes to understanding the interconnectivity of the physical and the virtual world.
Background: To investigate patients’ perspectives on polypharmacy and the use of a digital decision support system to assist general practitioners (GPs) in performing medication reviews. Methods: Qualitative interviews with patients or informal caregivers recruited from participants in a cluster-randomized controlled clinical trial (cRCT). The interviews were transcribed verbatim and analyzed using thematic analysis. Results: We conducted 13 interviews and identified the following seven themes: the patients successfully integrated medication use in their everyday lives, used medication plans, had both good and bad personal experiences with their drugs, regarded their healthcare providers as the main source of medication-related information, discussed medication changes with their GPs, had trusting relationships with them, and viewed the use of digital decision support tools for medication reviews positively. No unwanted adverse effects were reported. Conclusions: Despite drug-related problems, patients appeared to cope well with their medications. They also trusted their GPs, despite acknowledging polypharmacy to be a complex field for them. The use of a digital support system was appreciated and linked to the hope that reasons for selecting specific medication regimens would become more comprehensible. Further research with a more diverse sampling might add more patient perspectives.
Downy mildews caused by obligate biotrophic oomycetes result in severe crop losses worldwide. Among these pathogens, Pseudoperonospora cubensis and P. humuli, two closely related oomycetes, adversely affect cucurbits and hop, respectively. Discordant hypotheses concerning their taxonomic relationships have been proposed based on host–pathogen interactions and specificity evidence and gene sequences of a few individuals, but population genetics evidence supporting these scenarios is missing. Furthermore, nuclear and mitochondrial regions of both pathogens have been analyzed using microsatellites and phylogenetically informative molecular markers, but extensive comparative population genetics research has not been done. Here, we genotyped 138 current and historical herbarium specimens of those two taxa using microsatellites (SSRs). Our goals were to assess genetic diversity and spatial distribution, to infer the evolutionary history of P. cubensis and P. humuli, and to visualize genome-scale organizational relationship between both pathogens. High genetic diversity, modest gene flow, and presence of population structure, particularly in P. cubensis, were observed. When tested for cross-amplification, 20 out of 27 P. cubensis-derived gSSRs cross-amplified DNA of P. humuli individuals, but few amplified DNA of downy mildew pathogens from related genera. Collectively, our analyses provided a definite argument for the hypothesis that both pathogens are distinct species, and suggested further speciation in the P. cubensis complex.
This study explores how ‘gatherings’ turn into ‘encounters’ in a virtual world (VW) context. Most communication technologies enable only focused encounters between distributed participants, but in VWs both gatherings and encounters can occur. We present close sequential analysis of moments when after a silent gathering, interaction among participants in a VW is gradually resumed, and also investigate the social actions in the verbal (re-)opening turns. Our findings show that like in face-to-face situations, also in VWs participants often use different types of embodied resources to achieve the transition, rather than rely on verbal means only. However, the transition process in VWs has distinctive characteristics compared to the one in face-to-face situations. We discuss how participants in a VW use virtually embodied pre-beginnings to display what we call encounter-readiness, instead of displaying lack of presence by avatar stillness. The data comprise 40 episodes of video-recorded team interactions in a VW.
The term structure of interest rates is crucial for the transmission of monetary policy to financial markets and the macroeconomy. Disentangling the impact of monetary policy on the components of interest rates, expected short rates, and term premia is essential to understanding this channel. To accomplish this, we provide a quantitative structural model with endogenous, time-varying term premia that are consistent with empirical findings. News about future policy, in contrast to unexpected policy shocks, has quantitatively significant effects on term premia along the entire term structure. This provides a plausible explanation for partly contradictory estimates in the empirical literature.
Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day intravitally up to wound closure. Wounds were stained for VEGF, CD31, TGF-β, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-β level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.
The stem-loop (SL1) is the 5'-terminal structural element within the single-stranded SARS-CoV-2 RNA genome. It is formed by nucleotides 7–33 and consists of two short helical segments interrupted by an asymmetric internal loop. This architecture is conserved among Betacoronaviruses. SL1 is present in genomic SARS-CoV-2 RNA as well as in all subgenomic mRNA species produced by the virus during replication, thus representing a ubiquitous cis-regulatory RNA with potential functions at all stages of the viral life cycle. We present here the 1H, 13C and 15N chemical shift assignment of the 29 nucleotides-RNA construct 5_SL1, which denotes the native 27mer SL1 stabilized by an additional terminal G-C base-pair.
The SARS-CoV-2 (SCoV-2) virus is the causative agent of the ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to the genus of Betacoronaviruses. The 5′- and 3′-genomic ends of the 30 kb SCoV-2 genome are potential antiviral drug targets. Major parts of these sequences are highly conserved among Betacoronaviruses and contain cis-acting RNA elements that affect RNA translation and replication. The 31 nucleotide (nt) long highly conserved stem-loop 5a (SL5a) is located within the 5′-untranslated region (5′-UTR) important for viral replication. SL5a features a U-rich asymmetric bulge and is capped with a 5′-UUUCGU-3′ hexaloop, which is also found in stem-loop 5b (SL5b). We herein report the extensive 1H, 13C and 15N resonance assignment of SL5a as basis for in-depth structural studies by solution NMR spectroscopy.
The SARS-CoV-2 virus is the cause of the respiratory disease COVID-19. As of today, therapeutic interventions in severe COVID-19 cases are still not available as no effective therapeutics have been developed so far. Despite the ongoing development of a number of effective vaccines, therapeutics to fight the disease once it has been contracted will still be required. Promising targets for the development of antiviral agents against SARS-CoV-2 can be found in the viral RNA genome. The 5′- and 3′-genomic ends of the 30 kb SCoV-2 genome are highly conserved among Betacoronaviruses and contain structured RNA elements involved in the translation and replication of the viral genome. The 40 nucleotides (nt) long highly conserved stem-loop 4 (5_SL4) is located within the 5′-untranslated region (5′-UTR) important for viral replication. 5_SL4 features an extended stem structure disrupted by several pyrimidine mismatches and is capped by a pentaloop. Here, we report extensive 1H, 13C, 15N and 31P resonance assignments of 5_SL4 as the basis for in-depth structural and ligand screening studies by solution NMR spectroscopy.
Introduction: The treatment of carious lesions is one of the most fundamental competencies in daily dental practice. However, many commercially available training models lack in reality regarding the simulation of pathologies such as carious lesions. 3D printed models could provide a more realistic simulation. This study provides an exemplary description of the fabrication of 3D printed dental models with carious lesions and assesses their educational value compared to commercially available models in conservative dentistry.
Materials and Methods: A single-stage, controlled cohort study was conducted within the context of a curricular course. A stereolithographic model was obtained from an intraoral scan and then printed using fused deposition modelling. These models were first piloted by experts and then implemented and compared against commercial models in a conservative dentistry course. Experts and students evaluated both models using a validated questionnaire. Additionally, a cost analysis for both models was carried out.
Results: Thirteen dentists and twenty-seven 5th year dental students participated in the study. The 3D printed models were rated significantly more realistic in many test areas. In particular, the different tactility and the distinction in colour was rated positively in the 3D printed models. At 28.29€ (compared to 112.36€), the 3D printed models were exceptionally cost-efficient.
Conclusions: 3D printed dental models present a more realistic and cost-efficient alternative to commercial models in the undergraduate training of conservative dentistry.
Popular media now often present 3D printing as a widely employed technology for the production of dental prostheses. This article aims to show, based on factual information, to what extent 3D printing can be used in dental laboratories and dental practices at present. It attempts to present a rational evaluation of todays´ applications of 3D printing technology in the context of dental restorations. In addition, the article discusses future perspectives and examines the ongoing viability of traditional dental laboratory services and manufacturing processes. It also shows which expertise is needed for the digital additive manufacturing of dental restorations.
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.
Purpose: Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study.
Methods: We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS.
Results: IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years).
Conclusion: This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas.
New World species of the histerid beetle genus Xestipyge Marseul (Coleoptera: Histeridae: Dendrophilinae: Paromalini) are reviewed, and X. skelleyi, new species, is described. A dichotomous key and illustrations are provided as identification means for the now five included species from the Western Hemisphere.
A world catalogue and bibliography of the family Cybocephalidae (Coleoptera) is presented. The catalogue contains 207 species within 16 genera. Each taxon is accompanied by a complete taxonomic history, including a full annotated synonymy with original references cited. The reversal of the recent synonymy of Cybocephalus brevis Grouvelle over Cybocephalus minimus Grouvelle is proposed. Cybocephalus aeneus Reiche is removed from synonymy with Cybocephalus micans Reitter and considered incertae sedis.
During early G1 phase, Rb is exclusively mono-phosphorylated by cyclin D:Cdk4/6, generating 14 different isoforms with specific binding patterns to E2Fs and other cellular protein targets. While mono-phosphorylated Rb is dispensable for early G1 phase progression, interfering with cyclin D:Cdk4/6 kinase activity prevents G1 phase progression, questioning the role of cyclin D:Cdk4/6 in Rb inactivation. To dissect the molecular functions of cyclin D:Cdk4/6 during cell cycle entry, we generated a single cell reporter for Cdk2 activation, RB inactivation and cell cycle entry by CRISPR/Cas9 tagging endogenous p27 with mCherry. Through single cell tracing of Cdk4i cells, we identified a time-sensitive early G1 phase specific Cdk4/6-dependent phosphorylation gradient that regulates cell cycle entry timing and resides between serum-sensing and cyclin E:Cdk2 activation. To reveal the substrate identity of the Cdk4/6 phosphorylation gradient, we performed whole proteomic and phospho-proteomic mass spectrometry, and identified 147 proteins and 82 phospho-peptides that significantly changed due to Cdk4 inhibition in early G1 phase. In summary, we identified novel (non-Rb) cyclin D:Cdk4/6 substrates that connects early G1 phase functions with cyclin E:Cdk2 activation and Rb inactivation by hyper-phosphorylation.
The discovery of clustered regularly interspaced short palindromic repeats and their associated proteins (Cas) has revolutionized the field of genome and epigenome editing. A number of new methods have been developed to precisely control the function and activity of Cas proteins, including fusion proteins and small-molecule modulators. Proteolysis-targeting chimeras (PROTACs) represent a new concept using the ubiquitin-proteasome system to degrade a protein of interest, highlighting the significance of chemically induced protein-E3 ligase interaction in drug discovery. Here, we engineered Cas proteins (Cas9, dCas9, Cas12, and Cas13) by inserting a Phe-Cys-Pro-Phe (FCPF) amino acid sequence (known as the π-clamp system) and demonstrate that the modified CasFCPF proteins can be (1) labeled in live cells by perfluoroaromatics carrying the fluorescein or (2) degraded by a perfluoroaromatics-functionalized PROTAC (PROTAC-FCPF). A proteome-wide analysis of PROTAC-FCPF-mediated Cas9FCPF protein degradation revealed a high target specificity, suggesting a wide range of applications of perfluoroaromatics-induced proximity in the regulation of stability, activity, and functionality of any FCPF-tagging protein.
Two subvalent, redox-active diborane(4) anions, [3]4− and [3]2−, carrying exceptionally high negative charge densities are reported: Reduction of 9-methoxy-9-borafluorene with Li granules without stirring leads to the crystallization of the B(sp3)−B(sp2) diborane(5) anion salt Li[5]. [5]− contains a 2,2′-biphenyldiyl-bridged B−B core, a chelating 2,2′-biphenyldiyl moiety, and a MeO substituent. Reduction of Li[5] with Na metal gives the Na+ salt of the tetraanion [3]4− in which two doubly reduced 9-borafluorenyl fragments are linked via a B−B single bond. Comproportionation of Li[5] and Na4[3] quantitatively furnishes the diborane(4) dianion salt Na2[3], the doubly boron-doped congener of 9,9′-bis(fluorenylidene). Under acid catalysis, Na2[3] undergoes a formal Stone–Wales rearrangement to yield a dibenzo[g,p]chrysene derivative with B=B core. Na2[3] shows boron-centered nucleophilicity toward n-butyl chloride. Na4[3] produces bright blue chemiluminescence when exposed to air.
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: Researchers who wish to study stress-related disorders need to use valid, reliable, and sensitive instruments and the Clinician-administered PTSD Scale (CAPS) con- stitutes the gold standard in the assessment of posttraumatic stress disorder (PTSD). While the CAPS corresponds with PTSD criteria according to the DSM-5, researchers face a challenge with the forthcoming ICD-11: ICD-11 introduces the new diagnosis Complex PTSD (CPTSD) that does not exist in DSM-5.
Objective: Researchers as well as clinicians will need to assess the incidence and prevalence of CPTSD and will want to evaluate treatment effects according to both criteria sets. However, using two clinician-rated interviews is often not feasible and a burden to patients, particularly in psychotherapy research.
Method & Results: We have therefore developed the Complex PTSD Item Set additional to the CAPS (COPISAC). This clinician rating is an easy-to-use and economic addition to the CAPS that permits assessing diagnosis and evaluating symptom severity of CPTSD. COPISAC consists of three items that assess disturbances in self-regulation including prompts for symptom description and frequency, and two additional items assessing impairment. Diagnostic status and severity ratings for CPTSD are possible. Items that account for the specific forms of trauma which the ICD-11 describes as precursors of CPTSD (e.g. torture, being enslaved) are further suggested as additions to the Life Events Checklist. Conclusion: With an introduction of COPISAC at this point, we aim at suggesting an easy transition into diagnosing CPTSD and evaluating its course over treatment.
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
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.
Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.
Commercialization of consumers’ personal data in the digital economy poses serious, both conceptual and practical, challenges to the traditional approach of European Union (EU) Consumer Law. This article argues that mass-spread, automated, algorithmic decision-making casts doubt on the foundational paradigm of EU consumer law: consent and autonomy. Moreover, it poses threats of discrimination and under- mining of consumer privacy. It is argued that the recent legislative reaction by the EU Commission, in the form of the ‘New Deal for Consumers’, was a step in the right direction, but fell short due to its continued reliance on consent, autonomy and failure to adequately protect consumers from indirect discrimination. It is posited that a focus on creating a contracting landscape where the consumer may be properly informed in material respects is required, which in turn necessitates blending the approaches of competition, consumer protection and data protection laws.
The genus Afronurus has several very common mayfly species in China and they are widely distributed in this country. Some of them are quite similar to each other in both imaginal and nymphal stages. However, these species have not been systematically compared and reviewed so far. In this study, six species are recognized. All nymphs of them share the following characters: gills V–VI with additional arrow-like accessory lobes, branched dentisetae, two rows of bristles and setae on hindtibiae and spotted abdominal terga. The males have divergent penes and clearly expressed titillators. The nymphs of the new species A. drepanophyllus sp. nov. have sickle-like gills I, spotted and striped body color, and males have unique genitalia. The nymphal stages of A. furcatus and A. hunanensis, which are associated and described for the first time, have similar body color to A. drepanophyllus sp. nov., but their pale dots on the head capsules and the shape of the hypopharynx are different. Keys to males and nymphs of the six species are provided.
Dual-task paradigms encompass a broad range of approaches to measure cognitive load in instructional settings. As a common characteristic, an additional task is implemented alongside a learning task to capture the individual’s unengaged cognitive capacities during the learning process. Measures to determine these capacities are, for instance, reaction times and interval errors on the additional task, while the performance on the learning task is to be maintained. Opposite to retrospectively applied subjective ratings, the continuous assessment within a dual-task paradigm allows to simultaneously monitor changes in the performance related to previously defined tasks. Following the Cognitive Load Theory, these changes in performance correspond to cognitive changes related to the establishment of permanently existing knowledge structures. Yet the current state of research indicates a clear lack of standardization of dual-task paradigms over study settings and task procedures. Typically, dual-task designs are adapted uniquely for each study, albeit with some similarities across different settings and task procedures. These similarities range from the type of modality to the frequency used for the additional task. This results in a lack of validity and comparability between studies due to arbitrarily chosen patterns of frequency without a sound scientific base, potentially confounding variables, or undecided adaptation potentials for future studies. In this paper, the lack of validity and comparability between dual-task settings will be presented, the current taxonomies compared and the future steps for a better standardization and implementation discussed.
Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.
We present a deterministic workflow for genotyping single and double transgenic individuals directly upon nascence that prevents overproduction and reduces wasted animals by two-thirds. In our vector concepts, transgenes are accompanied by two of four clearly distinguishable transformation markers that are embedded in interweaved, but incompatible Lox site pairs. Following Cre-mediated recombination, the genotypes of single and double transgenic individuals were successfully identified by specific marker combinations in 461 scorings.
Stationarity of the constituents of the body and of its functionalities is a basic requirement for life, being equivalent to survival in first place. Assuming that the resting state activity of the brain serves essential functionalities, stationarity entails that the dynamics of the brain needs to be regulated on a time-averaged basis. The combination of recurrent and driving external inputs must therefore lead to a non-trivial stationary neural activity, a condition which is fulfiled for afferent signals of varying strengths only close to criticality. In this view, the benefits of working in the vicinity of a second-order phase transition, such as signal enhancements, are not the underlying evolutionary drivers, but side effects of the requirement to keep the brain functional in first place. It is hence more appropriate to use the term 'self-regulated' in this context, instead of 'self-organized'.
Polo-like kinase 1 (PLK1) is a crucial regulator of cell cycle progression. It is established that the activation of PLK1 depends on the coordinated action of Aurora-A and Bora. Nevertheless, very little is known about the spatiotemporal regulation of PLK1 during G2, specifically, the mechanisms that keep cytoplasmic PLK1 inactive until shortly before mitosis onset. Here, we describe PLK1 dimerization as a new mechanism that controls PLK1 activation. During the early G2 phase, Bora supports transient PLK1 dimerization, thus fine-tuning the timely regulated activation of PLK1 and modulating its nuclear entry. At late G2, the phosphorylation of T210 by Aurora-A triggers dimer dissociation and generates active PLK1 monomers that support entry into mitosis. Interfering with this critical PLK1 dimer/monomer switch prevents the association of PLK1 with importins, limiting its nuclear shuttling, and causes nuclear PLK1 mislocalization during the G2-M transition. Our results suggest a novel conformational space for the design of a new generation of PLK1 inhibitors.
The upcoming commissioning of the superconducting (SC) continuous wave Helmholtz linear accelerators first of series cryomodule is going to demand precise alignment of the four internal SC cavities and two SC solenoids. For optimal results, a beam-based alignment method is used to reduce the misalignment of the whole cryomodule, as well as its individual components. A symmetric beam of low transverse emittance is required for this method, which is to be formed by a collimation system. It consists of two separate plates with milled slits, aligned in the horizontal and vertical direction. The collimation system and alignment measurements are proposed, investigated, and realized. The complete setup of this system and its integration into the existing environment at the GSI High Charge State Injector are presented, as well as the results of the recent reference measurements.
Amide proton transfer-chemical exchange saturation transfer (APT-CEST) imaging provides important information for the diagnosis and monitoring of tumors. For such analysis, complete coverage of the brain is advantageous, especially when registration is performed with other magnetic resonance (MR) modalities, such as MR spectroscopy (MRS). However, the acquisition of Z-spectra across several slices via multislice imaging may be time-consuming. Therefore, in this paper, we present a new approach for fast multislice imaging, allowing us to acquire 16 slices per frequency offset within 8 s. The proposed fast CEST-EPI sequence employs a presaturation module, which drives the magnetization into the steady-state equilibrium for the first frequency offset. A second module, consisting of a single CEST pulse (for maintaining the steady-state) followed by an EPI acquisition, passes through a loop to acquire multiple slices and adjacent frequency offsets. Thus, the whole Z-spectrum can be recorded much faster than the conventional saturation scheme, which employs a presaturation for each single frequency offset. The validation of the CEST sequence parameters was performed by using the conventional saturation scheme. Subsequently, the proposed and a modified version of the conventional CEST sequence were compared in vitro on a phantom with different T1 times and in vivo on a brain tumor patient. No significant differences between both sequences could be found in vitro. The in vivo data yielded almost identical MTRasym contrasts for the white and gray matter as well as for tumor tissue. Our results show that the proposed fast CEST-EPI sequence allows for rapid data acquisition and provides similar CEST contrasts as the modified conventional scheme while reducing the scanning time by approximately 50%.
The HADES experiment at GSI has recently provided data on the flow coefficients v1,..., v4 for protons in Au+Au reactions at Elab = 1.23 AGeV (or √sNN = 2.4 GeV). This data allows to estimate the shear viscosity over entropy density ratio, η/s at low energies via a coarse graining analysis of the UrQMD transport simulations of the flow harmonics in comparison to the experimental data. By this we can provide for the first time an estimate of η/s ≈ 0.65 ± 0.15 (or (8 ± 2)(4π)−1) at such low energies.
We derive a shape derivative formula for the family of principal Dirichlet eigenvalues λs(Ω) of the fractional Laplacian (−Δ)s associated with bounded open sets Ω⊂RN of class C1,1. This extends, with a help of a new approach, a result in Dalibard and Gérard-Varet (Calc. Var. 19(4):976–1013, 2013) which was restricted to the case s=12. As an application, we consider the maximization problem for λs(Ω) among annular-shaped domains of fixed volume of the type B∖B¯¯¯¯′, where B is a fixed ball and B′ is ball whose position is varied within B. We prove that λs(B∖B¯¯¯¯′) is maximal when the two balls are concentric. Our approach also allows to derive similar results for the fractional torsional rigidity. More generally, we will characterize one-sided shape derivatives for best constants of a family of subcritical fractional Sobolev embeddings.
The ambersnails (Succineidae), found nearly worldwide, are considered a very challenging group to classify and identify with even genus-level identifications requiring dissection. In this study, we use mitochondrial and nuclear DNA markers, shell morphometrics, and anatomical dissection to examine fresh material collected from the type localities of two nominal species in Oxyloma (Neoxyloma). We conclude from these evidence that Oxyloma salleanum (L. Pfeiffer, 1850) and Oxyloma effusum (L. Pfeiffer, 1853) are conspecific, and accordingly reduce O. effusum to the status of junior synonymy. We present a redescription of O. salleanum.
Model frameworks, based on Floquet theory, have been shown to produce effective tools for accurately predicting phase-noise response of single (free-running) oscillator systems. This method of approach, referred to herein as macro-modeling, has been discussed in several highly influential papers and now constitutes an established branch of modern circuit theory. The increased application of, for example, injection-locked oscillators and oscillator arrays in modern communication systems has subsequently exposed the demand for similar rigorous analysis tools aimed at coupled oscillating systems. This paper presents a novel solution in terms of a macro-model characterizing the phase-response of synchronized coupled oscillator circuits and systems perturbed by weak noise sources. The framework is generalized and hence applicable to all circuit configurations and coupling topologies generating a synchronized steady-state. It advances and replaces the phenomenological descriptions currently found in the published literature pertaining to this topic and, as such, represents a significant breakthrough w.r.t. coupled oscillator noise modeling. The proposed model is readily implemented numerically using standard routines.
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications – phosphorylation, ubiquitination, acetylation and oligomerisation – that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications – phosphorylation, ubiquitination, acetylation and oligomerisation – that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
The transcription factor vitamin D receptor (VDR) is the high affinity nuclear target of the biologically active form of vitamin D3 (1,25(OH)2D3). In order to identify pure genomic transcriptional effects of 1,25(OH)2D3, we used VDR cistrome, transcriptome and open chromatin data, obtained from the human monocytic cell line THP-1, for a novel hierarchical analysis applying three bioinformatics approaches. We predicted 75.6% of all early 1,25(OH)2D3-responding (2.5 or 4 h) and 57.4% of the late differentially expressed genes (24 h) to be primary VDR target genes. VDR knockout led to a complete loss of 1,25(OH)2D3–induced genome-wide gene regulation. Thus, there was no indication of any VDR-independent non-genomic actions of 1,25(OH)2D3 modulating its transcriptional response. Among the predicted primary VDR target genes, 47 were coding for transcription factors and thus may mediate secondary 1,25(OH)2D3 responses. CEBPA and ETS1 ChIP-seq data and RNA-seq following CEBPA knockdown were used to validate the predicted regulation of secondary vitamin D target genes by both transcription factors. In conclusion, a directional network containing 47 partly novel primary VDR target transcription factors describes secondary responses in a highly complex vitamin D signaling cascade. The central transcription factor VDR is indispensable for all transcriptome-wide effects of the nuclear hormone.
For genus g=2i≥4 and the length g−1 partition μ=(4,2,…,2,−2,…,−2) of 0, we compute the first coefficients of the class of D¯¯¯¯(μ) in PicQ(R¯¯¯¯g), where D(μ) is the divisor consisting of pairs [C,η]∈Rg with η≅OC(2x1+x2+⋯+xi−1−xi−⋯−x2i−1) for some points x1,…,x2i−1 on C. We further provide several enumerative results that will be used for this computation.
The ability to respond appropriately to employees' work-related well-being requires leaders to pay attention to their employees' well-being in the first place. We propose that leaders' stress mindset, that is, the belief that stress is enhancing versus debilitating, may bias their perception of employees' well-being. We further propose that this judgment then influences leaders' intention to engage in or refrain from health-oriented leadership behavior, to express higher performance expectations, or to promote their employees. We expect this process to be stronger if leaders strongly identify with their team, increasing their perceived similarity with their employees. In three experiments (N1 = 198, N2 = 292, N3 = 250), we tested the effect of participants' stress mindset on their intention to show certain leadership behaviors, mediated by their perception of employee well-being (emotional exhaustion, somatic symptoms, work engagement) and moderated by their team identification. Our findings largely support the association between stress mindset and the perception of well-being. The results for the proposed mediation and the moderating function of identification were mixed. Overall, the results emphasize the critical role of leaders' stress mindset and may, thus, improve health promotion in organizations by helping leaders to adequately recognize employees' well-being and respond appropriately.
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These elements seem to act as modification-rescue systems, also called toxin/antidote pairs. Here we show that the maternal-effect toxin/zygotic antidote pair sup-35/pha-1 is required for proper expression of apical junction (AJ) components in epithelia and that sup-35 toxicity increases when pathways that establish and maintain basal epithelial characteristics, die-1, elt-1, lin-26, and vab-10, are compromised. We demonstrate that pha-1(e2123) embryos, which lack the antidote, are defective in epidermal morphogenesis and frequently fail to elongate. Moreover, seam cells are frequently misshaped and mispositioned and cell bond tension is reduced in pha-1(e2123) embryos, suggesting altered tissue material properties in the epidermis. Several aspects of this phenotype can also be induced in wild-type embryos by exerting mechanical stress through uniaxial loading. Seam cell shape, tissue mechanics, and elongation can be restored in pha-1(e2123) embryos if expression of the AJ molecule DLG-1/Discs large is reduced. Thus, our experiments suggest that maternal-effect toxicity disrupts proper development of the epidermis which involves distinct transcriptional regulators and AJ components.
Background: Compound flaps offer the advantage of one stage defect reconstruction respecting all relevant tissues and early functional recovery by optimal vascularity of all components. Due to its specific vascular anatomy and the three-dimensional donor site, compound flaps with bone components may result in higher complication rates compared to soft tissue compound flaps. The meta-analysis summarizes the available evidence and evaluates whether bone components are a risk factor for periprocedural complications in upper extremity multidimensional defect reconstruction. Method: PubMed and Embase were searched for all publications addressing compound free flaps for upper extremity defect reconstruction with bone or soft tissue components published between January 1988 and May 2018. The methodological quality was assessed with the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies. Flap loss, thrombosis rate, early infection, hematoma, seroma, as well as donor site complications were extracted and analyzed. Results: Twelve out of 1157 potentially eligible studies (evidence-III) comprising 159 patients were finally included with publication bias for all summarized complication rates. Complication rates for flaps with/ without bone components were: total flap loss 5%, 95% CI = 3%–10% (6%/5%); partial flap loss 8%, 95% CI = 5%–15%, (9%/8%); arterial/venous thrombosis 7%, 95% CI = 4%–12%, (8%/5%)/14%, 95% CI = 9%–21% (16%/6%, P < .05) with higher risk for flaps with bone components; infection 6%, 95% CI = 3%–12% (6%/6%); hematoma 6%, 95% CI = 3%–11% (6%/5%); seroma 5%, 95% CI = 3%–10% (5%/5%); dehiscence 10%, 95% CI = 6%–17% (11%/9%). Conclusion: Compound flaps for upper extremity defect reconstruction including bone components have a higher venous thrombosis rate compared to compound soft-tissue flaps.
We consider a linear ill-posed equation in the Hilbert space setting. Multiple independent unbiased measurements of the right-hand side are available. A natural approach is to take the average of the measurements as an approximation of the right-hand side and to estimate the data error as the inverse of the square root of the number of measurements. We calculate the optimal convergence rate (as the number of measurements tends to infinity) under classical source conditions and introduce a modified discrepancy principle, which asymptotically attains this rate.
A morphological and molecular review of the genus Goniurosaurus, including an identification key
(2021)
The genus Goniurosaurus (tiger geckos) currently consists of 23 species distributed in China, Japan and Vietnam. Several species complexes and recent discoveries of cryptic species pose challenges to the species identification, which is crucial to effectively implement the recent listing of the species from China and Vietnam in CITES Appendix II and the species from Japan in CITES Appendix III. Based on the results of our field work in northern Vietnam and data compiled from literature, we herein provide a taxonomic review of the genus Goniurosaurus. Our phylogenetic analyses showed that all recorded populations of tiger geckos from Vietnam, which were found to be monophyletic with low intra-specific genetic divergences, are assigned to one of the four species: G. catbaensis, G. huuliensis, G. lichtenfelderi or G. luii. Both genetic and morphological analyses confirm that the species from China and Vietnam can be split into three major groups. Based on the newly collected data, we provide an extended morphological description of the Vietnamese species. In addition, we provide an identification key for all Goniurosaurus species from China, Japan and Vietnam in order to assist authorities in the enforcement of the recent CITES listing.
The calcareous substrate of spring-fed fens makes them unique islands of biodiversity, hosting endangered, vulnerable, and protected vascular plants. Hence, spring-fed fens ecosystems require special conservation attention because many of them are destroyed (e.g. drained, forested) and it is extremely difficult or even impossible to restore the unique hydrogeological and geochemical conditions enabling their function. The long-term perspective of paleoecological studies allows indication of former wetland ecosystem states and provides understanding of their development over millennia. To examine the late Holocene dynamics of a calcareous spring-fed fen (Raganu Mire) ecosystem on the Baltic Sea coast (Latvia) in relation to environmental changes, substrate and human activity, we have undertaken high-resolution analyses of plant macrofossils, pollen, mollusc, stable carbon (δ13C) and oxygen (δ18O) isotopes combined with radiocarbon dating (AMS) in three coring locations. Our study revealed that peat deposits began accumulating ca. 7000 cal. yr BP and calcareous deposits (tufa) from 1450 cal. yr BP, coinciding with regional hydrological changes. Several fire events occurred between 4000 and 1600 cal. yr BP, which appeared to have had a limited effect on local vegetation. The most significant changes in the forest and peatland ecosystems were at 3200 cal. yr BP associated with a dry climate stage and high fire activity, and then between 1400 and 500 cal. yr BP potentially associated with temperature changes during the Medieval Climate Anomaly (MCA) and Little Ice Age. Hydrological disturbances in the peatland catchment from 1400 cal. yr BP were most likely strengthened by human activity (deforestation) in this region. The relationship between the development of this peatland and changes in its catchment area, such as land cover changes or fluctuations in groundwater levels, suggest that protection and restoration of spring-fed fen ecosystems should also include the surrounding catchment. The presence of calcareous sediments, as well as appropriate temperature and local hydrological conditions appear to be the most crucial factors controlling Cladium marisus populations in our site - currently at the eastern limit of its distribution in Europe.
Aim: To evaluate preclinical education in Endodontology at Austrian, German and Swiss dental schools using an online survey. Methodology: An online survey divided into nine categories was sent using SurveyMonkey software to 37 dental schools, before the spread of the COVID-19 pandemic. The questionnaire included 50 questions to evaluate preclinical endodontic education, such as faculty-to-student ratios, topics taught and materials used, in preclinical phantom head courses. Seven and 14 days after the first e-mail contact, dental schools received a reminder e-mail. After four and six weeks, the dental schools were contacted by telephone and asked to participate in the online survey. The processing time was eight weeks in total. Results: The response rate was 89%. Preclinical endodontic education at the participating dental schools differs considerably. Theory classes ranged from 1 to 70 h (15 h mean), and practical classes ranged from 3 to 78 h (39 h mean). The faculty-to-student ratio varied between 1:4 and 1:38 (1:15 mean). Forty-five per cent of the dental schools had a specialist in endodontics teaching theory. Several dental microscopes were available for preclinical teaching purposes at 82% of the dental schools. The majority (82%) taught root canal preparation with rotary or reciprocating NiTi instruments. Overall, 85% of the dental schools taught lateral compaction, amongst other methods, for canal filling. Conclusion: A substantial divergence amongst the dental schools regarding the time dedicated to theory and practical instruction in Endodontology was reported. However, convergence in the use of root canal treatment techniques and materials was reported.
Research on Podospora anserina unraveled a network of molecular pathways affecting biological aging. In particular, a number of pathways active in the control of mitochondria were identified on different levels. A long-known key process active during aging of P. anserina is the age- related reorganization of the mitochondrial DNA (mtDNA). Mechanisms involved in the stabilization of the mtDNA lead to lifespan extension. Another critical issue is to balance mitochondrial levels of reactive oxygen species (ROS). This is important because ROS are essential signaling molecules, but at increased levels cause molecular damage. At a higher level of the network, mechanisms are active in the repair of damaged compounds. However, if damage passes critical limits, the corresponding pathways are overwhelmed and impaired molecules as well as those present in excess are degraded by specific enzymes or via different forms of autophagy. Subsequently, degraded units need to be replaced by novel functional ones. The corresponding processes are dependent on the availability of intact genetic information. Although a number of different pathways involved in the control of cellular homeostasis were uncovered in the past, certainly many more exist. In addition, the signaling pathways involved in the control and coordination of the underlying pathways are only initially understood. In some cases, like the induction of autophagy, ROS are active. Additionally, sensing and signaling the energetic status of the organism plays a key role. The precise mechanisms involved are elusive and remain to be elucidated.
A remarkable new apterous genus of Xanthopygina beetles is described here as Ikaros gen. nov. The new genus includes three new species, I. apteros gen. et sp. nov. from Colombia, I. paramo gen. et sp. nov. from Colombia and I. polygonos gen. et sp. nov. from Venezuela. Phylogenetic analyses using molecular and morphological data were performed to assess the phylogenetic position of Ikaros gen. nov. and whether the three new taxa formed a monophyletic group. All analyses, including those with aptery-associated characters removed, strongly supported the monophyly of Ikaros gen. nov. The genus could not be confidently resolved as a member of any of the existing genus-group lineages, likely due to a lack of morphological signal in the backbone of the tree. Further analyses, ideally with molecular data, are needed to determine the position of Ikaros gen. nov.
We describe a new species of Cyrtodactylus on the basis of two specimens collected from Ta Kou Nature Reserve, Binh Thuan Province, southern Vietnam. Cyrtodactylus chungi sp. nov. is distinguished from the remaining Indochinese bent-toed geckos by a combination of the following characters: relatively small body size (SVL up to 68.5 mm); a continuous neckband; 5 or 6 irregular transverse dorsal bands; 11 or 12 bands on original tail; keeled tubercles present on dorsum, posterior limbs and tail; 17 or 18 irregular dorsal tubercle rows; 30 or 31 ventral scale rows; ventrolateral skin folds indistinct; an angular series of seven precloacal pores in male and six pitted, enlarged precloacal scales in female, each series separated by a diastema of undifferentiated scales from 4–6 enlarged, poreless femoral scales; median subcaudals slightly enlarged; 17–20 subdigital lamellae under the fourth toe. Based on molecular analyses of the fragment of mitochondrial gene cytochrome c oxidase subunit I (COI), the new species is recovered as the sister taxon to Cyrtodactylus cattienensis s. str. with a genetic divergence of more than 9%. In phylogenetic analyses, the new species is recovered as a member of the Cyrtodactylus irregularis species group.
A new dipluran species, Plusiocampa (Plusiocampa) imereti Sendra & Barjadze sp. nov., from the deep zone in three caves in the Imereti region, Georgia, is described. This new troglobitic Plusiocampa is an addition to four others known Diplura from around the Black Sea region, two Dydimocampa and two Plusiocampa s. str. The present study also provides the first CO1 sequences for the Plusiocampinae taxa and the first molecular data for cave-dwelling Plusiocampa species. Although bootstrap values were low, the maximum-likelihood phylogenetic tree grouped Plusiocampa (P.) imereti Sendra & Barjadze sp. nov. with two Plusiocampa s. str. species from Eastern Europe. Morphologically, P. (P.) imereti Sendra & Barjadze sp. nov. is closely related to two cave-dwelling species: Plusiocampa (Plusiocampa) glabra Condé, 1984 and Plusiocampa (P.) chiosensis Sendra & Gasparo, 2020. The new species can be distinguished by the presence of lateral anterior macrosetae on metanotum, more uneven claws, and the presence of 2+2 lateral anterior macrosetae on middle urotergites. The five species currently known for the Black Sea region inhabit caves located at low altitude but with no influence from former glacial or permafrost processes.
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.
A new genus and five new species of the subfamily Florarctinae (Tardigrada, Arthrotardigrada)
(2021)
A new genus Higginsarctus gen. nov. in the subfamily Florarctinae Renaud-Mornant, 1982 (Arthrotardigrada) is established on the basis of the type species H. signeae gen. et sp. nov. described from carbonated sand habitats from Faroe Bank, North Atlantic Ocean. Three other Atlantic species H. laurae gen. et sp. nov., H. martini gen. et sp. nov. and H. shintai gen. et sp. nov. are described from Dentalium sand, Roscoff, France and finally H. lassei gen. et sp. nov. is described from the deep sea in the South Pacific Ocean off the coast of Chile. The recently described species Ligiarctus alatus Gomes-Júnior, E. Santos, da Rocha, P.J.P. Santos & Fontoura, 2018 is investigated and compared with the type species Ligiarctus eastwardi Renaud-Mornant, 1982. New and additional information to the original description of L. alatus is provided and this species is moved to Higginsarctus gen. nov. as H. alatus comb. nov.
Susamyia Ziegler & Gilasian gen. nov. and its type species Susamyia mira Ziegler & Gilasian gen. et sp. nov. are described from southwestern Karkheh National Park and southeastern Jazmourian Wetland of Iran. Drawings of terminalia and head of the male as well as images of habitus, head and egg are provided. Susamyia gen. nov. is incorporated into the identification key to the Palearctic tachinid genera of Tschorsnig & Richter (1998). The systematic position of Susamyia gen. nov. in the tribe Goniini (Exoristinae) is discussed in light of molecular analyses based on the ribosomal genes 16S, 18S and 28S, and the egg type of females. The morphology of the microtype eggs was studied and compared with that of other Goniini, but proved too unreliable to be included in the phylogenetic analysis. Susamyia gen. nov. is believed to be most closely related to the goniine genera Gymnophryxe Villeneuve, 1922, Palesisa Villeneuve, 1929 and Prosopodopsis Townsend, 1926.
A new genus, Cicatrisphaerion Lingafelter, Morris, Skillman, and Santos-Silva (Coleoptera: Cerambycidae), and three new species of the same authorship, C. wappesi from Quintana Roo, Mexico, C. rileyi from Chiapas, Mexico, and Eupogonius wappesi from Quintana Roo, Mexico, are described. New records and clarification on the distribution of Psyrassaforma janzeni Chemsak, 1991 and P. nitida Chemsak, 1991 are provided. Ameriphoderes amoena (Chemsak and Linsley, 1979) is redescribed based on four male specimens and a new country record from Guatemala is documented. New distributional records are provided for Estola flavobasalis Breuning, 1940 (including a new country record for Bolivia) and Estola vittulata Bates, 1874. A redescription and new distributional record are provided for Eupogonius flavovittatus Breuning, 1940 based on a female specimen.
Ysachron pilosus gen. et sp. nov. is described from the Caribbean region of Colombia, and an updated key to genera of South American Achrysonini is provided. Moreover, the geographical distribution of 45 species of Cerambycidae, belonging to the subfamilies Cerambycinae, Lamiinae and Prioninae, is expanded, including nine new country records for Colombia and a further locality in Colombia for nine species.
Obligate endoparasitic oomycetes are known to ubiquitously occur in marine and freshwater diatoms, but their diversity is still largely unexplored. Many of these parasitoids are members of the early-diverging oomycete lineages (Miracula, Diatomophthora), others are within the Leptomitales of the Saprolegniomycetes (Ectrogella, Lagenisma) and some have been described in the Peronosporomycetes (Aphanomycopsis, Lagenidium). Even though some species have been recently described and two new genera were introduced (Miracula and Diatomophthora), the phylogeny and taxonomy of most of these organisms remain unresolved. This is contrasted by the high number of sequences from unclassified species, as recently revealed from environmental sequencing, suggesting the presence of several undiscovered species. In this study, a new species of Miracula is reported from a marine centric diatom (Minidiscus sp.) isolated from Skagaströnd harbor in Northwest Iceland. The morphology and life cycle traits of this novel oomycete parasite are described herein, and its taxonomic placement within the genus Miracula is confirmed by molecular phylogeny. As it cannot be assigned to any previously described species, it is introduced as Miracula islandica in this study. The genus Miracula thus contains three described holocarpic species (M. helgolandica, M. islandica, M. moenusica) to which likely additional species will need to be added in the future, considering the presence of several lineages known only from environmental sequencing that clustered within the Miracula clade.
We describe and illustrate a new Neotropical predaceous midge, Parabezzia carlae Huerta, Spinelli and Grogan, new species (Diptera: Ceratopogonidae) from males collected by Malaise trap in La Union, Ayutla de los Libres, state of Guerrero, Mexico. We also report a second record of P. alexanderi Wirth from Veracruz, Mexico. A key to the known species in Mexico is included.
A new and readily available pentafluorothiophenyl-substituted N-methyl-piperidone curcuminoid 1a was prepared and investigated for its anti-proliferative, pro-apoptotic and cancer stem cell-differentiating activities against a panel of human tumor cell lines derived from various tumor entities. The compound 1a was highly anti-proliferative and reached IC50 values in the nanomolar concentration range. 1a was superior to the known anti-tumorally active curcuminoid EF24 (2) and its known N-ethyl-piperidone analog 1b in all tested tumor cell lines. Furthermore, 1a induced a noticeable increase of intracellular reactive oxygen species in HT-29 colon adenocarcinoma cells, which possibly leads to a distinct increase in sub-G1 cells, as assessed by cell cycle analysis. A considerable activation of the executioner-caspases 3 and 7 as well as nuclei fragmentation, cell rounding, and membrane protrusions suggest the triggering of an apoptotic mechanism. Yet another effect was the re-organization of the actin cytoskeleton shown by the formation of stress fibers and actin aggregation. 1a also caused cell death in the adherently cultured glioblastoma cell lines U251 and Mz54. We furthermore observed that 1a strongly suppressed the stem cell properties of glioma stem-like cell lines including one primary line, highlighting the potential therapeutic relevance of this new compound.
Modeling long-term neuronal dynamics may require running long-lasting simulations. Such simulations are computationally expensive, and therefore it is advantageous to use simplified models that sufficiently reproduce the real neuronal properties. Reducing the complexity of the neuronal dendritic tree is one option. Therefore, we have developed a new reduced-morphology model of the rat CA1 pyramidal cell which retains major dendritic branch classes. To validate our model with experimental data, we used HippoUnit, a recently established standardized test suite for CA1 pyramidal cell models. The HippoUnit allowed us to systematically evaluate the somatic and dendritic properties of the model and compare them to models publicly available in the ModelDB database. Our model reproduced (1) somatic spiking properties, (2) somatic depolarization block, (3) EPSP attenuation, (4) action potential backpropagation, and (5) synaptic integration at oblique dendrites of CA1 neurons. The overall performance of the model in these tests achieved higher biological accuracy compared to other tested models. We conclude that, due to its realistic biophysics and low morphological complexity, our model captures key physiological features of CA1 pyramidal neurons and shortens computational time, respectively. Thus, the validated reduced-morphology model can be used for computationally demanding simulations as a substitute for more complex models.
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.
Fractipes tayrona new species (Coleoptera: Chrysomelidae: Eumolpinae: Eumolpini) is described from a dry forest on the Caribbean coast of Colombia. This locality is very distant from the localities in southeast Brazil, where the other two known species of Fractipes Bechynĕ were described. Male and female genitalia are described for the first time in this genus, and F. tayrona is compared with holotype photographs of F. rhabdopteroides Bechynĕ and F. secundus Bechynĕ and Springlová de Bechynĕ.
A new species of the genus Mesopolobus Westwood, 1833, Mesopolobus robiniae Lakatos & László sp. nov., is described and illustrated from east-central Europe (Romania and Hungary). The species was reared from black locust (Robinia pseudoacacia) seedpod samples, where it most likely parasitizes the black locust’s seed predator Bruchophagus robiniae Zerova, 1970. Here we present the new species and report on its ecological relationships within the European seed predator community of black locust. We also give details regarding type material and type locality, a detailed description with images, a differential diagnosis of the new species, and a modification to the identification key published by Graham (1969), that distinguishes this new species from closely related species. In addition, we provide information on the distribution, biology and results of barcoding analysis. We also provide the DNA sequence data to complement the morphological taxonomy.
A new species of ant-mimicking spider of the subfamily Castianeirinae, Myrmecotypus rubrofemoratus Perger and Rubio, new species (Araneae: Corinnidae), is described from the Pre-Andean area of the Bolivian orocline. Adults of M. rubrofemoratus new species resemble the carpenter ant Camponotus femoratus Forel, 1907, which is considered one of the most aggressive ants in the world.
Scirtes goodrichi Springer and Waller, a new species of Scirtes Illiger, 1807 (Coleoptera: Scirtidae: Scirtinae) from Virginia and South Carolina, is described and illustrated. Six species are now recognized for Scirtes in America north of Mexico: S. orbiculatus (Fabricius), S. tibialis Guérin-Méneville, S. oblongus Guérin-Méneville, S. plagiatus Schaeffer and S. goliai Epler. A taxonomic key to the six species of Scirtes is provided.
A new spider genus (Araneae: Linyphiidae: Erigoninae) from a tropical montane cloud forest of Mexico
(2021)
A new genus and species of spider (Araneae, Linyphiidae, Erigoninae) from a tropical montane cloud forest of Mexico is described from both male and female specimens, Xim trenzado gen. et sp. nov. A phylogenetic parsimony analysis situates Xim gen. nov. as a distinct genus among the distal Erigoninae. Xim gen. nov. is sister to a clade including Ceratinopsis, Tutaibo and Sphecozone, but differs from those genera by having a high cymbium, large paracymbium, short straight embolus, male cheliceral stridulatory striae widely and evenly spaced, both sexes with a post-ocular lobe, male with two series of prolateral macrosetae on femur I, and the female by having strongly oblong, u-shaped spermathecae.
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.
A new montane species of Vaejovis C.L. Koch (Scorpiones: Vaejovidae) is described from the Sierra Madre Occidental of Durango, Mexico. Vaejovis baggins Azzinnari, Bryson, Graham, Solís-Rojas, and Sissom, new species,is similar to mexicanus group species in the mountain range, including V. montanus Graham and Bryson, V. sierrae Sissom, Graham, Donaldson, and Bryson, and V. mcwesti Sissom, Graham, Donaldson, and Bryson, but differs from these species based on aspects of body size, pedipalp carination, chelae granulation, morphometrics, and setal patterns on the metasoma. A molecular clock estimate indicates that the new species shared a common ancestor with V. mcwesti during the late Miocene or Pliocene.
In this article we use techniques from tropical and logarithmic geometry to construct a non-Archimedean analogue of Teichmüller space T¯g whose points are pairs consisting of a stable projective curve over a non-Archimedean field and a Teichmüller marking of the topological fundamental group of its Berkovich analytification. This construction is closely related to and inspired by the classical construction of a non-Archimedean Schottky space for Mumford curves by Gerritzen and Herrlich. We argue that the skeleton of non-Archimedean Teichmüller space is precisely the tropical Teichmüller space introduced by Chan–Melo–Viviani as a simplicial completion of Culler–Vogtmann Outer space. As a consequence, Outer space turns out to be a strong deformation retract of the locus of smooth Mumford curves in T¯g.
Background and Objectives: We tested if a novel combination of predictors could improve the accuracy of outcome prediction after transfemoral transcatheter aortic valve implantation (TAVI). Materials and Methods: This prospective study recruited 169 participants (49% female; median age 81 years). The primary endpoint was midterm mortality; secondary endpoints were acute Valve Academic Research Consortium (VARC)-3 complication rate and post-TAVI in-hospital length of stay (LoS). EuroSCORE II (ESII), comorbidities (e.g., coronary artery disease), eGFR (estimated glomerular filtration rate; based on cystatin C), hemoglobin, creatinine, N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) levels and patient-reported outcome measures (PROMs, namely EuroQol-5-Dimension-5-Levels, EQ5D5L; Kansas City Cardiomyopathy Questionnaire, KCCQ; clinical frailty scale, CFS) at baseline were tested as predictors. Regression (uni- and multi-variate Cox; linear; binary logistic) and receiver operating characteristic (ROC)-curve analysis were applied. Results: Within a median follow-up of 439 (318–585) days, 12 participants died (7.1%). Independent predictors of mortality using multivariate Cox regression were baseline eGFR (p = 0.001) and KCCQ (p = 0.037). Based on these predictors, a Linear Prediction Score (LPS1) was calculated. The LPS1-area under the curve (AUC)-value (0.761) was significantly higher than the ESII-AUC value (0.597; p = 0.035). Independent predictors for LoS > 6 days (the median LoS) were eGFR (p = 0.028), NTproBNP (p = 0.034), and EQ5D5L values (p = 0.002); a respective calculated LPS2 provided an AUC value of 0.677 (p < 0.001). Eighty participants (47.3%) experienced complications. Male sex predicted complications only in the univariate analysis. Conclusions: The combination of KCCQ and eGFR can better predict midterm mortality than ES II alone. Combining eGFR, NTproBNP, and EQ5D5L can reliably predict LoS after TAVI. This novel method improves personalized TAVI risk stratification and hence may help reduce post-TAVI risk.
Mechanotransduction is elicited in cells upon the perception of physical forces transmitted via the extracellular matrix in their surroundings and results in signaling events that impact cellular functions. This physiological process is a prerequisite for maintaining the integrity of diarthrodial joints, while excessive loading is a factor promoting the inflammatory mechanisms of joint destruction. Here, we describe a mechanotransduction pathway in synovial fibroblasts (SF) derived from the synovial membrane of inflamed joints. The functionality of this pathway is completely lost in the absence of the disintegrin metalloproteinase ADAM15 strongly upregulated in SF. The mechanosignaling events involve the Ca2+-dependent activation of c-Jun-N-terminal kinases, the subsequent downregulation of long noncoding RNA HOTAIR, and upregulation of the metabolic energy sensor sirtuin-1. This afferent loop of the pathway is facilitated by ADAM15 via promoting the cell membrane density of the constitutively cycling mechanosensitive transient receptor potential vanilloid 4 calcium channels. In addition, ADAM15 reinforces the Src-mediated activation of pannexin-1 channels required for the enhanced release of ATP, a mediator of purinergic inflammation, which is increasingly produced upon sirtuin-1 induction.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Governments have restricted public life during the COVID-19 pandemic, inter alia closing sports facilities and gyms. As regular exercise is essential for health, this study examined the effect of pandemic-related confinements on physical activity (PA) levels. A multinational survey was performed in 14 countries. Times spent in moderate-to-vigorous physical activity (MVPA) as well as in vigorous physical activity only (VPA) were assessed using the Nordic Physical Activity Questionnaire (short form). Data were obtained for leisure and occupational PA pre- and during restrictions. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). In total, n = 13,503 respondents (39 ± 15 years, 59% females) were surveyed. Compared to pre-restrictions, overall self-reported PA declined by 41% (MVPA) and 42.2% (VPA). Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 80.9% (95% CI: 80.3–81.7) to 62.5% (95% CI: 61.6–63.3). Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic.
Posterior fossa tumor surgery is challenging due to the proximity and exposure of cerebellar structures. A favorable operative approach is unknown. Following lesions to the dentato–rubro–olivary-pathway, a neurodegenerative disease called hypertrophic olivary degeneration (HOD) can occur. This study for the first time demonstrates that paravermal trans-cerebellar approaches are associated with a significantly higher likelihood of HOD on MRI when compared to other approaches. This finding can well be attributed to dentate nucleus (DN) injury. Furthermore, cerebellar mutism syndrome (CMS) was discussed in the literature to be correlated with HOD due to a functional overlap of pathways involved. We found no such correlation in this study, but HOD was shown to be a reliable indicator for surgical disruption of efferent cerebellar pathways involving the DN. Henceforth, neurosurgeons should consider more midline or lateral approaches in posterior fossa surgery to spare the DN whenever feasible, and focus on cerebellar functional anatomy in their preoperative planning.
Background: Plaque psoriasis is a common, chronic and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP).
Objectives: Pooled analysis of two different phase 3 clinical trails to compare superiority regarding efficacy, safety and quality of life (QoL) between CAL/BDP PAD-cream and CAL/BDP TS.
Methods: The data from two phase 3, multicentre, randomized, investigator-blind, active and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS) and cream vehicle, which were applied once daily for 8 weeks.
Results: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy end points after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%; P < 0.0001), the mean per cent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (P < 0.0001) and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (P = 0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream.
Conclusions: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favourable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel.
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.
Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.
Droughts are anticipated to intensify in many parts of the world due to climate change. However, the issue of drought definition, namely the diversity of drought indices, makes it difficult to compare drought assessments. This issue is widely known, but its relative importance has never been quantitatively evaluated in comparison to other sources of uncertainty. Here, encompassing three drought categories (meteorological, agricultural, and hydrological droughts) with four temporal scales of interest, we evaluated changes in the drought frequency using multi-model and multi-scenario simulations to identify areas where the definition issue could result in pronounced uncertainties and to what extent. We investigated the disagreement in the signs of changes between drought definitions and decomposed the variance into four main factors: drought definitions, greenhouse gas concentration scenarios, global climate models, and global water models, as well as their interactions. The results show that models were the primary sources of variance over 82% of the global land area. On the other hand, the drought definition was the dominant source of variance in the remaining 17%, especially in parts of northern high-latitudes. Our results highlight specific regions where differences in drought definitions result in a large spread among projections, including areas showing opposite signs of significant changes. At a global scale, 7% of the variance resulted independently from the definition issue, and that value increased to 44% when 1st and 2nd order interactions were considered. The quantitative results suggest that by clarifying hydrological processes or sectors of interest, one could avoid these uncertainties in drought assessments to obtain a clearer picture of future drought change.
Background: Lipedema is a chronic disorder of the adipose tissue that affects mainly women, characterised by symmetrical, excessive fatty tissue on the legs and pain. Standard conservative treatment is long-term comprehensive decongestive therapy (CDT) to alleviate lipedema-related pain and to improve psychosocial well-being, mobility and physical activity. Patients may benefit from surgical removal of abnormally propagated adipose tissue by liposuction. The LIPLEG trial evaluates the efficacy and safety of liposuction compared to standard CDT.
Methods/design: LIPLEG is a randomised controlled multicentre investigator-blinded trial. Women with lipedema (n=405) without previous liposuction will be allocated 2:1 to liposuction or CDT. The primary outcome of the trial is leg pain reduction by ≥2 points on a visual analogue scale ranging 0–10 at 12 months on CDT or post-completion of liposuction. Secondary outcomes include changes in leg pain severity, health-related quality of life, depression tendency, haematoma tendency, prevalence of oedema, modification physical therapy scope, body fat percentage, leg circumference and movement restriction.
The primary analysis bases on intention-to-treat. Success proportions are compared using the Mantel-Haenszel test stratified by lipedema stage at a 5% two-sided significance level. If this test is statistically significant, the equality of the response proportions in the separate strata is evaluated by Fisher’s exact test in a hierarchical test strategy.
Discussion: LIPLEG assesses whether surgical treatment of lipedema is safe and effective to reduce pain and other lipedema-related health issues. The findings of this trial have the potential to change the standard of care in lipedema.
Trial registration: ClinicalTrials.gov NCT04272827. Registered on February 14, 2020.
Trial status: Protocol version is 02_0, December 17, 2019
The unique Neotropical species of the alderfly genus Protosialis van der Weele, 1909, P. bifasciata (Hagen, 1861), is herein transferred to the newly described genus Caribesialis gen. nov. This new taxon is proposed to be sister to the clade Protosialis + Sialis Latreille, 1802, after a phylogenetic analysis that included male genital characters scored on a previous morphological matrix of the family. Also, Ilyobius nigrocephalus sp. nov., a remarkable new species from Ecuador, is described and its phylogenetic position is discussed. Furthermore, Ilyobius bimaculatus (Banks, 1920) from Bolivia, known solely from the female holotype, is redescribed. Based on the present study, the Neotropical fauna of Sialidae is proposed to be constituted by two genera, one insular (Cuba) and one continental (Mexico to Chile and Argentina).
A remark on the bank cases
(2021)
Since their formulation by Keith DeRose (1992), the so-called bank cases have played a major role in the discussion about whether knowledge depends on practical factors. According to the proponents of pragmatic encroachment, the proper conclusion to be drawn from the bank cases and similar examples is that knowledge of a proposition p does not supervene on one’s evidence for or against p. In my view, this conclusion is ill-founded. The reason is that the bank cases and similar examples suffer from an ambiguity concerning the known proposition — an ambiguity that has so far been overlooked. When this ambiguity is made explicit, it becomes clear that the conclusion does not follow.
A reply to my critics
(2021)
It is a real pleasure to reply to so many thoughtful and probing responses to my book. In what follows, I will focus on six key themes that emerge across the various pieces. Some of them call into question core commitments of my theory, and in those cases I will try to show what might be said in its defence. Quite a number of the critics, however, present what we might call expansionist arguments: though they endorse some of the arguments I make, that is – or pick up some of its key concepts – they seek to push them in new and interesting directions. I will suggest that many of those arguments look likely to be successful, though I will also express caution about one or two of them. I doubt, however, that I will be the final judge of their success. Early on in the book I express the hope that it might provide a set of conceptual tools capable of advancing discussions about resource justice more broadly, even for scholars who reject my own idiosyncratic approach. Having made that gambit, I cannot now claim to have a monopoly on the use of the tools in question. Witnessing the use that others have already made of them has been a refreshing and rewarding experience.
Grasstrees (Xanthorrhoea) are a group of monocotyledonous plants endemic to Australia, with a characteristic crown of long and narrow leaves. In the present study, the grasstree-associated weevils of the genus Paratranes Zimmerman, 1994 are reviewed and two species are recognised: P. monopticus (Pascoe, 1870) and P. zimmermani sp. nov. A lectotype for Tranes xanthorrhoeae Lea, 1898, which was recently synonymised with P. monopticus, is herein designated, and the validity of this synonymy is confirmed. Descriptions and diagnoses of the species are supplemented with photographs of their habitus and salient structures as well as a map of their distributions.
We provide keys, descriptions and illustrations for 16 species of Scoliidae Latreille, 1802 found in Hong Kong, of which nine are new records for the territory, one is new to China and one is new to science: Scolia pakshaoensis sp. nov. The status of one species (Megacampsomeris sp. 1) remains uncertain; it may represent an additional new species.
The Acanthocinini genus Alcathousiella Monné, 2005 (Coleoptera, Cerambycidae, Lamiinae) is revised with both the genus and the type species, Alcathousiella polyrhaphoides (White, 1855) redescribed. New country records for the species, greatly expanding its known distribution in South America, are also presented. Lastly, Alcathousiella giesberti sp. nov., from Nicaragua, Costa Rica and Panama is described and illustrated.
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.
Hamaticherus Dejean, 1821 (Coleoptera: Cerambycidae: Cerambycinae) is considered a junior synonym of Cerambyx Linnaeus, 1758. Hamaticherus sensu Audinet-Serville, 1834 is considered a posterior usage of Hamaticherus Dejean, 1821, and an unavailable name. Plocaederus is considered as a new genus, and not a replacement name, proposed by Dejean (1835) to allocate the species included in Hamaticherus sensu Audinet-Serville, 1834. Therefore, a new genus, Hamaederus Santos-Silva, Garcia and Botero,is herein proposed to include the species currently allocated in Plocaederus Dejean, 1835, creating 15 new combinations, and additionally, a new species from French Guiana, Hamaederus allofasciatus Santos-Silva, Garcia and Botero, is described. Furthermore, Plocaederus barauna Martins and Monné, 2002 and Plocaederus confusus Martins and Monné,2002 are proposed as new junior synonyms of Hamaederus yucatecus (Chemsak and Noguera, 1997), and Hamaticherus bellator Audinet-Serville, 1834 is transferred to Plocaederus Dejean,
1835, new combination. New geographical records are provided for Hamaederus fraterculus (Martins), H. glaberrimus (Martins), H. rusticus (Gounelle), and H. yucatecus (Chemsak and Noguera). Hamaederus fasciatus is formally excluded from the fauna of French Guiana. A key to American genera of Cerambycina (Cerambycini) is provided.
The Nearctic species of Nematodes Berthold (Coleoptera: Eucnemidae: Macraulacinae: Nemato-dini) are reviewed. Four species are redescribed. One new species, Nematodes rugosipennis Otto (Coleoptera: Eucnemidae) is described from Florida, Georgia, and Oklahoma, USA. A key to species modified from Muona (2000) is provided for all known species of Nematodes present in the Nearctic region.
This paper reviews the genera Xylothrips Lesne, 1901 and Calophagus Lesne, 1902, and their species, and proposes that Calophagus should be reinstated as a full genus from a subgenus of Xylothrips (contra Borowski & Węgrzynowicz 2019). The genera and their included species are diagnosed and redescribed, and a summary of information on the distribution and biology of all species is provided. The importance of characters of the antennal club and pronotum in separating the two genera is stressed. A key to the two genera and the two species of Xylothrips is provided.
The genus Onychelmis Hinton, 1941 was for a long time regarded as a small taxon with only three known species distributed in the Andes. A study of new material from Ecuador, using morphological and molecular data, has resulted in the discovery of five new species: Onychelmis lenkae sp. nov., O. lobata sp. nov., O. minor sp. nov., O. onorei sp. nov. and O. splendida sp. nov. We also revised the entire genus and redescribed the three known species, O. longicollis (Sharp, 1882), O. leleupi Delève, 1968 and O. whiteheadi Spangler & Santiago, 1991. Habitus photographs of adults are provided, together with line drawings of male and female genitalia, and schematic illustrations of the distribution of femoral tomentum for each species. DNA sequences for barcoding the COI mtDNA fragment were used to support species delimitation and to suggest possible relationships among species. The revision includes a key to adults of all species of Onychelmis and notes on the biogeography of the genus, with an updated distribution map.
We present an immersed boundary method for the solution of elliptic interface problems with discontinuous coefficients which provides a second-order approximation of the solution. The proposed method can be categorised as an extended or enriched finite element method. In contrast to other extended FEM approaches, the new shape functions get projected in order to satisfy the Kronecker-delta property with respect to the interface. The resulting combination of projection and restriction was already derived in Höllbacher and Wittum (TBA, 2019a) for application to particulate flows. The crucial benefits are the preservation of the symmetry and positive definiteness of the continuous bilinear operator. Besides, no additional stabilisation terms are necessary. Furthermore, since our enrichment can be interpreted as adaptive mesh refinement, the standard integration schemes can be applied on the cut elements. Finally, small cut elements do not impair the condition of the scheme and we propose a simple procedure to ensure good conditioning independent of the location of the interface. The stability and convergence of the solution will be proven and the numerical tests demonstrate optimal order of convergence.
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.
Taking blood via venipuncture is part of the necessary surveillance before and after liver transplantation. The spectrum of response from children and their parents is variable, ranging from a short and limited aversion to paralyzing phobia. The aim of this retrospective, cross-sectional study was to determine the level of anxiety amongst children during venipuncture, to compare the anxiety reported by children and parents, and to identify the factors affecting the children’s and parents’ anxiety in order to develop therapeutic strategies. In total, 147 children (aged 0–17 years, 78 female) and their parents completed questionnaires. Statistical analysis was performed using qualitative and quantitative methods. Results showed that the majority of children reported anxiety and pain during venipuncture. Younger children had more anxiety (self-reported or assessed by parents). Children and parental reports of anxiety were highly correlated. However, the child’s anxiety was often reported as higher by parents than by the children themselves. The child’s general anxiety as well as the parents’ perceived stress from surgical interventions (but not the number of surgical interventions) prompted parental report of child anxiety. For children, the main stressors that correlated with anxiety and pain were factors during the blood collection itself (e.g., feeling the puncture, seeing the syringe). Parental anxiety was mainly related to circumstances before the blood collection (e.g., approaching the clinic, sitting in the waiting room). The main stressors mentioned by parents were the child’s discomfort and their inability to calm the child. Results indicate that the children’s fear of factors during the blood collection, along with the parents’ perceived stress and helplessness as well as their anticipatory anxiety are important starting points for facilitating the drawing of blood from children before and after liver transplantation, thereby supporting a better disease course in the future.
In this survey paper, we present a multiscale post-processing method in exploration. Based on a physically relevant mollifier technique involving the elasto-oscillatory Cauchy–Navier equation, we mathematically describe the extractable information within 3D geological models obtained by migration as is commonly used for geophysical exploration purposes. More explicitly, the developed multiscale approach extracts and visualizes structural features inherently available in signature bands of certain geological formations such as aquifers, salt domes etc. by specifying suitable wavelet bands.
Promyelocytic leukemia nuclear bodies (PML NBs) are multi-protein assemblies representing distinct sub-nuclear structures. As phase-separated molecular condensates, PML NBs exhibit liquid droplet-like consistency. A key organizer of the assembly and dynamics of PML NBs is the ubiquitin-like SUMO modification system. SUMO is covalently attached to PML and other core components of PML NBs thereby exhibiting a glue-like function by providing multivalent interactions with proteins containing SUMO interacting motifs (SIMs). PML NBs serve as the catalytic center for nuclear SUMOylation and SUMO-SIM interactions are essential for protein assembly within these structures. Importantly, however, formation of SUMO chains on PML and other PML NB-associated proteins triggers ubiquitylation and proteasomal degradation which coincide with disruption of these nuclear condensates. To date, a plethora of nuclear activities such as transcriptional and post-transcriptional regulation of gene expression, apoptosis, senescence, cell cycle control, DNA damage response, and DNA replication have been associated with PML NBs. Not surprisingly, therefore, SUMO-dependent PML NB integrity has been implicated in regulating many physiological processes including tumor suppression, metabolism, drug-resistance, development, cellular stemness, and anti-pathogen immune response. The interplay between PML NBs and viral infection is multifaceted. As a part of the cellular antiviral defense strategy, PML NB components are crucial restriction factors for many viruses and a mutual positive correlation has been found to exist between PML NBs and the interferon response. Viruses, in turn, have developed counterstrategies for disarming PML NB associated immune defense measures. On the other end of the spectrum, certain viruses are known to usurp specific PML NB components for successful replication and disruption of these sub-nuclear foci has recently been linked to the stimulation rather than curtailment of antiviral gene repertoire. Importantly, the ability of invading virions to manipulate the host SUMO modification machinery is essential for this interplay between PML NB integrity and viruses. Moreover, compelling evidence is emerging in favor of bacterial pathogens to negotiate with the SUMO system thereby modulating PML NB-directed intrinsic and innate immunity. In the current context, we will present an updated account of the dynamic intricacies between cellular PML NBs as the nuclear SUMO modification hotspots and immune regulatory mechanisms in response to viral and bacterial pathogens.
The COVID-19 pandemic has triggered health-related anxiety in ways that undermine peoples’ mental and physical health. Contextual factors such as living in a high-risk area might further increase the risk of health deterioration. Based on the Social Identity Approach, we argue that social identities can not only be local that are characterized by social interactions, but also be global that are characterized by a symbolic sense of togetherness and that both of these can be a basis for health. In line with these ideas, we tested how identification with one’s family and with humankind relates to stress and physical symptoms while experiencing health-related anxiety and being exposed to contextual risk factors. We tested our assumptions in a representative sample (N = 974) two-wave survey study with a 4-week time lag. The results show that anxiety at Time 1 was positively related to stress and physical symptoms at Time 2. Feeling exposed to risk factors related to lower physical health, but was unrelated to stress. Family identification and identification with humankind were both negatively associated with subsequent stress and family identification was negatively associated with subsequent physical symptoms. These findings suggest that for social identities to be beneficial for mental health, they can be embodied as well as symbolic.