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This essay develops, within the terms of the recent New York Declaration, an account of the shared responsibility of states to refugees and of how the character of that responsibility effects the ways in which it can be fairly shared. However, it also moves beyond the question of the general obligations that states owe to refugees to consider ways in which refugee choices and refugee voice can be given appropriate standing with the global governance of refuge. It offers an argument for the normative significance of refugee’s reasons for choosing states of asylum and linked this to consideration of a refugee matching system and to refugee quota trading conceived as responsibility-trading, before turning to the issue of the inclusion of refugee voice in relation to the justification of the norms of refugee governance and in relation to the institutions and practices of refugee governance through which those norms are given practical expression.
The issue of statelessness poses problems for the statist (or nationalist) approach to the philosophy of immigration. Despite the fact that the statist approach claims to constrain the state’s right to exclude with human rights considerations, the arguments statists offer for the right of states to determine their own immigration policies would also justify citizenship rules that would render some children stateless. Insofar as rendering a child stateless is best characterized as a violation of human rights and insofar as some states have direct responsibility for causing such harm, the problem of non-refugee stateless children points to greater constraints than most statists accept on states’ right to determine their own rules for membership. While statists can ultimately account for the right not to be rendered stateless, recognizing these additional human rights constraints ultimately weakens the core of the statist position.
While global justice theorists heatedly discuss the responsibilities of the affluent and powerful, those states which can legitimately be seen as victims of global injustice have seldom, if ever, been considered as duty bearers to whom responsibilities can be attached. However, recognising agents whose options are constrained not only as victims, but also as duty bearers is necessary as a proof of respect for their agency and indispensable to mobilise the type of action required to alter global injustices. In this article, I explore what responsibilities state officials of dominated states have. I argue that they have the responsibility to resist domination in the name of the dominated states members. While under particular circumstances this responsibility gives rise to a duty to engage in acts of state civil disobedience, under other circumstances state officials of dominated states ought to resist domination in an internal, attitudinal way by recognising themselves as outcome responsible agents.
Fair Trade is under fire. Some critics argue, for instance, that there is no obligation to purchase Fair Trade certified products and that doing so may even be counter-productive. Others worry that well-justified conceptions of what makes trade fair can conflict. Yet others suggest that the common arguments for Fair Trade cannot justify purchasing Fair Trade certified goods, in particular. This paper starts by sketching one common argument for Fair Trade and defends it against this last line of criticism. In particular, it argues that we should purchase Fair Trade certified goods because doing so benefits the poor even though there are other ways to alleviate poverty. It then considers how other common arguments for Fair Trade fare in light of similar criticism and concludes that they may well succeed.
Political realists claim that international relations are in a state of anarchy, and therefore every state is allowed to disregard its moral duties towards other states and their inhabitants. Realists argue that complying with moral duties is simply too risky for a state’s national security. Political moralists convincingly show that realists exaggerate both the extent of international anarchy and the risks it poses to states who act morally. Yet moralists do not go far enough, since they do not question realism’s normative core: the claim that when national security is really at risk, states are allowed to disregard their moral duties. I contend that there is at least one moral duty that states should not disregard even if their inhabitants are at risk of death by military aggression: the duty to reduce extreme global poverty. The reason is that even granting that national security is about securing individuals’ right to life, global poverty relief is about that as well.
Chronic granulomatous disease (CGD) is a primary immunodeficiency, which is diagnosed in most patients between one and three years of age. Here we report on a boy who presented at birth with extensive skin lesions and lymphadenopathy which were caused by CGD. An analysis of the literature revealed 24 patients with CGD who became symptomatic during the first six weeks of life. Although pulmonary complications and skin lesions due to infection were the leading symptoms, clinical features were extremely heterogenous. As follow-up was not well specified in most patients, the long-term prognosis of children with very early onset of CGD remains unknown.
Aging is accompanied by unisensory decline. To compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to the predictive coding (PC) model, we form “templates” (internal models or “priors”) of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, which may however come at the cost of integrating irrelevant information. Both strategies can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 years, N = 25) and older (mean: 67 years, N = 28) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to beta-band activity. Transfer entropy analysis and dynamic causal modeling of pre-stimulus magnetoencephalography data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults leading to the illusory percept.
Background: Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma.
Methods: Eight pigs (Sus scrofa) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an in vitro ex vivo whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled E. coli, S. aureus or S. cerevisiae for phagocytosis assessment by flow cytometry.
Results: Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of E. coli-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of S. aureus significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of S. cerevisiae-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic E. coli-phagocytizing percentage did not change, while their capacity increased after 24–72 h. After a significant decrease in S. aureus-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in S. cerevisiae-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h.
Conclusion: Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.
The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.
The spread of the COVID-19 virus was met by a strict lockdown in many countries around the world, with the closure of all physical activity (PA) facilities and limitations on moving around freely. The aim of the present online survey was to assess the effect of lockdown on physical activity in Italy. Physical activity was assessed using the European Health Interview Survey questionnaire. A total of 1500 datasets were analyzed. Differences between conditions were tested with a chi2-based (χ2) test for categorical variables, and with the Student’s t-test for paired data. A fixed effects binary logistic regression analysis was conducted to identify relevant predictor variables to explain the compliance with World Health Organisation (WHO) recommendations. We found a substantial decline in all physical activity measures. Mean differences in walking and cycling metabolic equivalent of task minutes per week (METmin/week), respectively, were 344.4 (95% confidence interval (95% CI): 306.6–382.2; p < 0.001) and 148.5 (95% CI: 123.6–173.5; p < 0.001). Time spent in leisure time decreased from 160.8 to 112.6 min/week (mean difference 48.2; 95% CI: 40.4–56.0; p < 0.001). Compliance with WHO recommendations decreased from 34.9% to 24.6% (chi2 (1, 3000) = 38.306, p < 0.001, V = 0.11). Logistic regression showed a reduced chance (OR 0.640, 95% CI: 0.484–0.845; p = 0.001) to comply with WHO PA recommendations under lockdown conditions. Measures to promote physical activity should be intensified to limit detrimental health effects.
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.
Mitochondrial F1Fo-ATP-synthase dimers play a critical role in shaping and maintenance of mitochondrial ultrastructure. Previous studies have revealed that ablation of the F1Fo-ATP-synthase assembly factor PaATPE of the ascomycete Podospora anserina strongly affects cristae formation, increases hydrogen peroxide levels, impairs mitochondrial function and leads to premature cell death. In the present study, we investigated the underlying mechanistic basis. Compared to the wild type, we observed a slight increase in non-selective and a pronounced increase in mitophagy, the selective vacuolar degradation of mitochondria. This effect depends on the availability of functional cyclophilin D (PaCYPD), the regulator of the mitochondrial permeability transition pore (mPTP). Simultaneous deletion of PaAtpe and PaAtg1, encoding a key component of the autophagy machinery or of PaCypD, led to a reduction of mitophagy and a partial restoration of the wild-type specific lifespan. The same effect was observed in the PaAtpe deletion strain after inhibition of PaCYPD by its specific inhibitor, cyclosporin A. Overall, our data identify autophagy-dependent cell death (ADCD) as part of the cellular response to impaired F1Fo-ATP-synthase dimerization, and emphasize the crucial role of functional mitochondria in aging.
Background: In clinical practice range of motion (RoM) is usually assessed with low-cost devices such as a tape measure (TM) or a digital inclinometer (DI). However, the intra- and inter-rater reliability of typical RoM tests differ, which impairs the evaluation of therapy progress. More objective and reliable kinematic data can be obtained with the inertial motion capture system (IMC) by Xsens. The aim of this study was to obtain the intra- and inter-rater reliability of the TM, DI and IMC methods in five RoM tests: modified Thomas test (DI), shoulder test modified after Janda (DI), retroflexion of the trunk modified after Janda (DI), lateral inclination (TM) and fingertip-to-floor test (TM).
Methods: Two raters executed the RoM tests (TM or DI) in a randomized order on 22 healthy individuals while, simultaneously, the IMC data (Xsens MVN) was collected. After 15 warm-up repetitions, each rater recorded five measurements.
Findings: Intra-rater reliabilities were (almost) perfect for tests in all three devices (ICCs 0.886–0.996). Inter-rater reliability was substantial to (almost) perfect in the DI (ICCs 0.71–0.87) and the IMC methods (ICCs 0.61–0.993) and (almost) perfect in the TM methods (ICCs 0.923–0.961). The measurement error (ME) for the tests measured in degree (°) was 0.9–3.3° for the DI methods and 0.5–1.2° for the IMC approaches. In the tests measured in centimeters the ME was 0.5–1.3cm for the TM methods and 0.6–2.7cm for the IMC methods. Pearson correlations between the results of the DI or the TM respectively with the IMC results were significant in all tests except for the shoulder test on the right body side (r = 0.41–0.81).
Interpretation: Measurement repetitions of either one or multiple trained raters can be considered reliable in all three devices.
Three AKT serine/threonine kinase isoforms (AKT1/AKT2/AKT3) mediate proliferation, metabolism, differentiation and anti-apoptotic signals. AKT isoforms are activated down- stream of PI3-kinase and also by PI3-kinase independent mechanisms. Mutations in the lipid phosphatase PTEN and PI3-kinase that increase PIP3 levels increase AKT signaling in a large proportion of human cancers. AKT and other AGC kinases possess a regulatory mechanism that relies on a conserved hydrophobic motif (HM) C-terminal to the catalytic core. In AKT, the HM is contiguous to the serine 473 and two other newly discovered (serine 477 and tyrosine 479) regulatory phosphorylation sites. In AKT genes, this regulatory HM region is encoded in the final exon. We identified a splice variant of AKT2 (AKT2-13a), which contains an alternative final exon and lacks the HM regulatory site. We validated the presence of mRNA for this AKT2-13a splice variant in different tissues, and the presence of AKT2-13a protein in extracts from HEK293 cells. When overexpressed in HEK293 cells, AKT2-13a is phosphorylated at the activation loop and at the zipper/turn motif phosphoryla- tion sites but has reduced specific activity. Analysis of the human transcriptome correspond- ing to other AGC kinases revealed that all three AKT isoforms express alternative transcripts lacking the HM regulatory motif, which was not the case for SGK1-3, S6K1-2, and classical, novel and atypical PKC isoforms. The transcripts of splice variants of Akt1-3 excluding the HM regulatory region could lead to expression of deregulated forms of AKT.
Objectives: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.
Materials and methods: Patients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study.
Results: Two hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0–19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6–30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002).
Conclusions: MDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections.
Nomadic movements are often a consequence of unpredictable resource dynamics. However, how nomadic ungulates select dynamic resources is still understudied. Here we examined resource selection of nomadic Mongolian gazelles (Procapra gutturosa) in the Eastern Steppe of Mongolia. We used daily GPS locations of 33 gazelles tracked up to 3.5 years. We examined selection for forage during the growing season using the Normalized Difference Vegetation Index (NDVI). In winter we examined selection for snow cover which mediates access to forage and drinking water. We studied selection at the population level using resource selection functions (RSFs) as well as on the individual level using step-selection functions (SSFs) at varying spatio-temporal scales from 1 to 10 days. Results from the population and the individual level analyses differed. At the population level we found selection for higher than average NDVI during the growing season. This may indicate selection for areas with more forage cover within the arid steppe landscape. In winter, gazelles selected for intermediate snow cover, which may indicate preference for areas which offer some snow for hydration but not so much as to hinder movement. At the individual level, in both seasons and across scales, we were not able to detect selection in the majority of individuals, but selection was similar to that seen in the RSFs for those individuals showing selection. Difficulty in finding selection with SSFs may indicate that Mongolian gazelles are using a random search strategy to find forage in a landscape with large, homogeneous areas of vegetation. The combination of random searches and landscape characteristics could therefore obscure results at the fine scale of SSFs. The significant results on the broader scale used for the population level RSF highlight that, although individuals show uncoordinated movement trajectories, they ultimately select for similar vegetation and snow cover.
Our aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR- BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.
Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 ± 16.9 to 51.9 ± 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11–1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16–1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05–1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16–1.44/OR = 1.35, 95% CI: 1.23–1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 ± 18.7% pre-restrictions to 81.3 ± 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50–1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18–1.36), and young age (OR = 1.10, 95% CI: 1.03–1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.
Identification and regulation of tomato Serine/Arginine-rich proteins under high temperatures
(2021)
Alternative splicing is an important mechanism for the regulation of gene expression in eukaryotes during development, cell differentiation or stress response. Alterations in the splicing profiles of genes under high temperatures that cause heat stress (HS) can impact the maintenance of cellular homeostasis and thermotolerance. Consequently, information on factors involved in HS-sensitive alternative splicing is required to formulate the principles of HS response. Serine/arginine-rich (SR) proteins have a central role in alternative splicing. We aimed for the identification and characterization of SR-coding genes in tomato (Solanum lycopersicum), a plant extensively used in HS studies. We identified 17 canonical SR and two SR-like genes. Several SR-coding genes show differential expression and altered splicing profiles in different organs as well as in response to HS. The transcriptional induction of five SR and one SR-like genes is partially dependent on the master regulator of HS response, HS transcription factor HsfA1a. Cis-elements in the promoters of these SR genes were predicted, which can be putatively recognized by HS-induced transcription factors. Further, transiently expressed SRs show reduced or steady-state protein levels in response to HS. Thus, the levels of SRs under HS are regulated by changes in transcription, alternative splicing and protein stability. We propose that the accumulation or reduction of SRs under HS can impact temperature-sensitive alternative splicing.
The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multi-scale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review experimental strategies aimed at revealing quantitative and dynamic properties of T-cell development and how they have been implemented in mathematical modeling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next- generation multi-scale picture of T-cell development.
Background: International travel is a major driver of the introduction and spread of SARS- CoV-2. Aim: To investigate SARS-CoV-2 genetic diversity in the region of a major transport hub in Germany, we characterized the viral sequence diversity of the SARS-CoV-2 variants circulating in Frankfurt am Main, the city with the largest airport in Germany, from the end of October to the end of December 2020. Methods: In total, we recovered 136 SARS-CoV-2 genomes from nasopharyngeal swab samples. We isolated 104 isolates that were grown in cell culture and RNA from the recovered viruses and subjected them to full-genome sequence analysis. In addition, 32 nasopharyngeal swab samples were directly sequenced. Results and conclusion: We found 28 different lineages of SARS- CoV-2 circulating during the study period, including the variant of concern B.1.1.7 (∆69/70, N501Y). Six of the lineages had not previously been observed in Germany. We detected the spike protein (S) deletion ∆69/∆70 in 15% of all sequences, a four base pair (bp) deletion (in 2.9% of sequences) and a single bp deletion (in 0.7% of sequences) in ORF3a, leading to ORF3a truncations. In four sequences (2.9%), an amino acid deletion at position 210 in S was identified. In a single sample (0.7%), both a 9 bp deletion in ORF1ab and a 7 bp deletion in ORF7a were identified. One sequence in lineage B.1.1.70 had an N501Y substitution while lacking the ∆69/70 in S. The high diversity of sequences observed over two months in Frankfurt am Main highlights the persisting need for continuous SARS-CoV-2 surveillance using full-genome sequencing, particularly in cities with international airport connections.
Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.
There are longstanding calls for international organizations (IOs) to be more inclusive of the voices and interests of people whose lives they affect. There is nevertheless widespread disagreement among practitioners and political theorists over who ought to be included in IO decision-making and by what means. This paper focuses on the inclusion of IOs’ ‘intended beneficiaries,’ both in principle and practice. It argues that IOs’ intended beneficiaries have particularly strong normative claims for inclusion because IOs can affect their vital interests and their political agency. It then examines how these claims to inclusion might be feasibly addressed. The paper proposes a model of inclusion via representation and communication, or ‘mediated inclusion.’ An examination of existing practices in global governance reveals significant opportunities for the mediated inclusion of IOs’ intended beneficiaries, as well as pervasive obstacles. The paper concludes that the inclusion of intended beneficiaries by IOs is both appropriate and feasible.
Background: Mesenchymal stromal cells (MSCs), multipotent progenitors that can be isolated from a variety of different tissues, are becoming increasingly important as cell therapeutics targeting immunopathologies and tissue regeneration. Current protocols for MSC isolation from bone marrow (BM) rely on density gradient centrifugation (DGC), and the production of sufficient MSC doses is a critical factor for conducting clinical MSC trials. Previously, a Good Manufacturing Practice (GMP)–compatible non-woven fabric filter device system to isolate MSCs was developed to increase the MSC yield from the BM. The aim of our study was to compare high-resolution phenotypic and functional characteristics of BM-MSCs isolated with this device and with standard DGC technology.
Methods: Human BM samples from 5 donors were analyzed. Each sample was divided equally, processing by DGC, and with the filter device. Stem cell content was assessed by quantification of colony-forming units fibroblasts (CFU-F). Immunophenotype was analyzed by multicolor flow cytometry. In vitro trilineage differentiation potential, trophic factors, and IDO-1 production were assessed. Functionally, immunomodulatory potential, wound healing, and angiogenesis were assayed in vitro.
Results: The CFU-F yield was 15-fold higher in the MSC preparations isolated with the device compared to those isolated by DGC. Consequently, the MSC yield that could be manufactured at passage 3 per mL collected BM was more than 10 times higher in the device group compared to DGC (1.65 × 109 vs. 1.45 × 108). The immunomodulatory potential and IDO-1 production showed donor-to-donor variabilities without differences between fabric filter-isolated and DGC-isolated MSCs. The results from the wound closure assays, the tube formation assays, and the trilineage differentiation assays were similar between the groups with respect to the isolation method. Sixty-four MSC subpopulations could be quantified with CD140a+CD119+CD146+ as most common phenotype group, and CD140a+CD119+CD146+MSCA-1–CD106–CD271– and CD140a+CD119+CD146–MSCA-1–CD106–CD271– as most frequent MSC subpopulations. As trophic factors hepatocyte growth factor, epidermal growth factor, brain-derived neurotrophic factor, angiopoietin-1, and vascular endothelial growth factor A could be detected in both groups with considerable variability between donors, but independent of the respective MSC isolation technique.
Conclusion: The isolation of MSCs using a GMP-compatible fabric filter system device resulted in higher yield of CFU-F, producing substantially more MSCs with similar subpopulation composition and functional characteristics as MSCs isolated by DGC.
Reduced social functioning in depression has been explained by different factors. Reduced social connectedness and prosocial motivation may contribute to interpersonal difficulties, particularly in chronic depression. In the present study, we tested whether social connectedness and prosocial motivation are reduced in chronic depression. Forty-seven patients with persistent depression and 49 healthy controls matched for age and gender completed the Inclusion of the Other in the Self Scale (IOS), the Compassionate Love Scale (CLS), the Beck Depression Inventory-II, and the Childhood Trauma Questionnaire. A Multivariate analysis of variance (MANOVA) with IOS and CLS as dependent variables revealed a highly significant difference between both groups. The IOS and the CLS-subscale Close Others were lower in persistent depression, whereas there was no difference in the CLS-subscale Strangers/Humanity. IOS and CLS-Close Others showed significant negative correlations with depressive symptoms. Connectedness to family members as measured by the IOS was negatively correlated with childhood trauma in patients with chronic depression. The results indicate that compassion and perceived social connection are reduced in depressed patients toward close others, but not to others in general. Implications for the treatment of depression are discussed.
Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.
It is important to understand the processes behind how and why individuals emerge as leaders, so that the best and most capable individuals may occupy leadership positions. So far, most literature in this area has focused on individual characteristics, such as personality or cognitive ability. While interactions between individuals and context do get research attention, we still lack a comprehensive understanding of how the social context at work may help individuals to emerge as leaders. Such knowledge could make an important contribution toward getting the most capable, rather than the most dominant or narcissistic individuals, into leadership positions. In the present work, we contribute toward closing this gap by testing a mediation chain linking a leader's leader self-awareness to a follower's leadership emergence with two time-lagged studies (nstudy1 = 449, nstudy2 = 355). We found that the leader's leader self-awareness was positively related to (a) the follower's leadership emergence and (b) the follower's nomination for promotion and that both relationships were serially mediated by the follower's self-leadership and the follower's leader self-efficacy. We critically discuss our findings and provide ideas for future research.
Magnetic resonance imaging (MRI) is the gold standard imaging technique for diagnosis and monitoring of many neurological diseases. However, the application of conventional MRI in clinical routine is mainly limited to the visual detection of macroscopic tissue pathology since mixed tissue contrasts depending on hardware and protocol parameters hamper its application for the assessment of subtle or diffuse impairment of the structural tissue integrity. Multiparametric quantitative (q)MRI determines tissue parameters quantitatively, enabling the detection of microstructural processes related to tissue remodeling in aging and neurological diseases. In contrast to measuring tissue atrophy via structural imaging, multiparametric qMRI allows for investigating biologically distinct microstructural processes, which precede changes of the tissue volume. This facilitates a more comprehensive characterization of tissue alterations by revealing early impairment of the microstructural integrity and specific disease-related patterns. So far, qMRI techniques have been employed in a wide range of neurological diseases, including in particular conditions with inflammatory, cerebrovascular and neurodegenerative pathology. Numerous studies suggest that qMRI might add valuable information, including the detection of microstructural tissue damage in areas appearing normal on conventional MRI and unveiling the microstructural correlates of clinical manifestations. This review will give an overview of current qMRI techniques, the most relevant tissue parameters and potential applications in neurological diseases, such as early (differential) diagnosis, monitoring of disease progression, and evaluating effects of therapeutic interventions.
Reasoning may help solving problems and understanding personal experiences. Ruminative reasoning, however, is inconclusive, repetitive, and usually regards negative thoughts. We asked how reasoning as manifested in oral autobiographical narratives might differ when it is ruminative versus when it is adaptive by comparing two constructs from the fields of psychotherapy research and narrative research that are potentially beneficial: innovative moments (IMs) and autobiographical reasoning (AR). IMs captures statements in that elaborate on changes regarding an earlier personal previous problem of the narrator, and AR capture the connecting of past events with other parts of the narrator’s life or enduring aspects of the narrator. A total of N = 94 university students had been selected from 492 students to differ maximally on trait rumination and trait adaptive reflection, and were grouped as ruminators (N = 38), reflectors (N = 37), and a group with little ruminative and reflective tendencies (“unconcerned,” N = 19). Participants narrated three negative personal experiences (disappointing oneself, harming someone, and being rejected) and two self-related experiences of more mixed valence (turning point and lesson learnt). Reflectors used more IMs and more negative than positive autobiographical arguments (AAs), but not more overall AAs than ruminators. Group differences were not moderated by the valence of memories, and groups did not differ in the positive effect of narrating on mood. Trait depression/anxiety was predicted negatively by IMs and positively by AAs. Thus, IMs are typical for reflectors but not ruminators, whereas the construct of AR appears to capture reasoning processes irrespective of their ruminative versus adaptive uses.
This article outlines a new approach to answering the foundational question in democratic theory of how the boundaries of democratic political units should be delineated. Whereas democratic theorists have mostly focused on identifying the appropriate population-group – or demos – for democratic decisionmaking, it is argued here that we should also take account of considerations relating to the appropriate scope of a democratic unit’s institutionalized governance capabilities – or public power. These matter because democratically legitimate governance is produced not only through the decision-making agency of a demos, but also through the institutionally distinct sources of political agency that shape the governance capabilities of public power. To develop this argument, the article traces a new theoretical account of the normative and institutional sources of collective agency, political legitimacy, and democratic boundaries, and illustrates it through a democratic reconstruction of the classical body politic metaphor. It further shows how this theoretical account lends strong prescriptive support to pluralist institutional boundaries within democratic global governance.
The democratic boundary problem raises the question of who has democratic participation rights in a given polity and why. One possible solution to this problem is the all-affected principle (AAP), according to which a polity ought to enfranchise all persons whose interests are affected by the polity’s decisions in a morally significant way. While AAP offers a plausible principle of democratic enfranchisement, its supporters have so far not paid sufficient attention to economic participation rights. I argue that if one commits oneself to AAP, one must also commit oneself to the view that political participation rights are not necessarily the only, and not necessarily the best, way to protect morally weighty interests. I also argue that economic participation rights raise important worries about democratic accountability, which is why their exercise must be constrained by a number of moral duties.
The combined behaviours of individuals within insect societies determine the survival and development of the colony. For the western honey bee (Apis mellifera), individual behaviours include nest building, foraging, storing and ripening food, nursing the brood, temperature regulation, hygiene and defence. However, the various behaviours inside the colony, especially within the cells, are hidden from sight, and until recently, were primarily described through texts and line drawings, which lack the dynamics of moving images. In this study, we provide a comprehensive source of online video material that offers a view of honey bee behaviour within comb cells, thereby providing a new mode of observation for the scientific community and the general public. We analysed long-term video recordings from longitudinally truncated cells, which allowed us to see sideways into the cells in the middle of a colony. Our qualitative study provides insight into worker behaviours, including the use of wax scales and existing nest material to remodel combs, storing pollen and nectar in cells, brood care and thermoregulation, and hygienic practices, such as cannibalism, grooming and surface cleaning. We reveal unique processes that have not been previously published, such as the rare mouth-to-mouth feeding by nurses to larvae as well as thermoregulation within cells containing the developing brood. With our unique video method, we are able to bring the processes of a fully functioning social insect colony into classrooms and homes, facilitating ecological awareness in modern times. We provide new details and images that will help scientists test their hypotheses on social behaviours. In addition, we encourage the non-commercial use of our material to educate beekeepers, the media and the public and, in turn, call attention to the general decline of insect biomass and diversity.
This essay presents contributions by Jürgen Habermas and Paulo Freire for the constitution of critical-reflexive subjects and the implications in the teaching-research-extension processes in the field of Organizational Studies. We show that intersubjectivity and dialogicity are conditions for the understanding between subjects and it is precisely through these conditions that the subjects are constituted, in a process that is dialogical, pedagogical and political. Freire and Habermas offer elements to deconstruct dominant instrumental logic and provide the basis for the reconstruction of unprecedented-viable possibilities of ways of organizing and managing. Therefore, this article highlights the importance of Organizational Studies to broaden the focus of teaching-research-extension possibilities and directs them to a communicative and dialogic engagement, beyond the borders of universities. This reconstruction indicates that researchers participate in different public arenas, debate and build public problems, processes of resistance, visibility, and dramatization of problematic issues. Observing the contributions of Freire and Habermas, Organizational Studies as a field cannot be limited to developing a critique, from a distant point of view: it is necessary to co-participate, co-act, co-operate and co-construct with its public.
Introduction: Surgical practices constitute a common topic of complaint among medical students. The aim of this study is to analyze the type of surgical training that students receive in medical school and the impact of SARS-CoV-2 pandemic.
Methods: A survey based on the National Spanish Agency for the Quality of Evaluation and Accreditation (ANECA) guidelines was spread on social media between medical students and physicians waiting to start their residency. The time spent in surgical practices, the number of times that certain abilities were performed, and the desire of choosing a surgical specialty were analyzed.
Results: 1053 surveys were analyzed. Significant differences between the number of months that students rotate and the number of procedures performed as they gained seniority were found. A weak positive correlation between the number of months rotating and the number of procedures performed was found. The desire of choosing a surgical specialty was not associated with the time spent in surgical practice. SARS-CoV-2 pandemic has reduced the time spent in surgical practice and some of the surgical procedures performed.
Conclusion: The amount of surgical procedures performed by students is below the requirements of ANECA guidelines. A different level of dexterity between 6th year students’ group affected by SARS-CoV-2 pandemic and physicians’ group should not be expected because of the low number of procedures performed by both groups. Students’ role in the operating room and the need for different systems of skills learning should be reconsidered.
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
This article seeks to build a bridge between the empirical scholarship rooted in the traditional theory of political representation and constructivist theory on representation by focusing on the authorization of claims. It seeks to answer how claims can be authorized beyond elections - selecting three democratic innovations and tracing claims through the claim-making process. Different participatory democratic innovations are selected - providing various claims and taking place in different institutional contexts, i.e., (elected) members of the Council of Foreigners Frankfurt; individual citizens in participatory budgeting procedures in Münster; and citizen’s associations elected politicians in the referendum campaign in Hamburg. We first analyze the claims raised by the different claim-makers to identify their claimed constituency eligible to authorize claims. In the second step, we focus on the authorization by the claimed constituency and the relevant decision-making authority. The article finds that claim-making in democratic innovations is fractured and incomplete. Nevertheless, this is not the reason to dismiss democratic innovations as possible loci of representation; on the contrary, seen through the prism of claim-making, all representation – electoral and nonelectoral – is partial. Focusing on the authorization of claims in democratic innovations provides novel inferences about the potential and limits of democratic innovations for broadening democratic representation.
Radiotherapy is a frequently used treatment for prostate cancer. It does not only causes the intended damage to cancer cells, but also affects healthy surrounding tissue. As a result radiation-induced urethral strictures occur in 2.2% of prostate cancer patients. Management of urethral strictures is challenging due to the presence of poor vascularized tissue for reconstruction and the proximity of the sphincter, which can impair the functional outcome. This review provides a literature overview of risk factors, diagnostics and management of radiation-induced urethral strictures.
Many early taxonomic works on North American bees were published by Europeans using specimens collected in the New World, some with type locations so imprecise that uncertainty on the nomenclatural status remains to this day. Two examples come from Fabricius (1745–1808) who described Andrena virescens Fabricius, 1775 and Apis viridula Fabricius, 1793 from “America” and “Boreal America”, respectively. The former species of Agapostemon Guérin-Méneville, 1844 occurs across most of the United States and southern Canada, the latter presumed an endemic to Cuba. The type materials of these two taxa have never been compared to each other, though a morphology-based phylogenetic analysis placed both in distinct species groups. Here we synonymize Apis viridula under Ag. virescens, thereby making Ag. femoralis (Guérin-Méneville, 1844) available as the name for the Cuban species. A lectotype for Ag. femoralis (the type species for the genus Agapostemon) is hereby designated to stabilize this taxonomy. We also synonymize Ag. obscuratus Cresson, 1869 under Ag. femoralis, suggesting that it represents a dark colour polymorphism. As Ag. cubensis Roberts, 1972 is a junior secondary homonym of Ag. cubensis (Spinola, 1851), we offer Ag. robertsi as a replacement name for the former.
The Smicridea (Smicridea) fasciatella species group occurs from the southwestern USA, throughout Central America, the Greater Antilles islands, and most of South America, except for the Chilean subregion. It is characterized by the phallic apparatus being a simple tube with eversible internal sclerites at the apex. The fasciatella group is composed of 61 species, of which only 11 occur in Brazil, mainly in the Atlantic Forest biome in the southeastern region. In order to reduce the Linnean and Wallacean shortfalls for the Smicridea Brazilian fauna, we diagnose, describe, and illustrate males of six new species in the fasciatella group: Smicridea (Smicridea) blahniki Desiderio, Pes & Hamada sp. nov., S. (Smicridea) brevitruncata Desiderio, Pes & Hamada sp. nov., S. (Smicridea) caaguara Desiderio, Pes & Hamada sp. nov., S. (Smicridea) ipiranga Desiderio, Pes & Hamada sp. nov., S. (Smicridea) jeaneae Desiderio, Pes & Hamada sp. nov., and S. (Smicridea) polyacantha Desiderio, Pes &; Hamada sp. nov. Additionally, we provide distributional data for S. (Smicridea) albosignata Ulmer, 1907, S. (Smicridea) bivittata (Hagen, 1861), S. (Smicridea) erecta Flint, 1974, S. (Smicridea) obliqua Flint, 1974, S. (Smicridea) paranensis Flint, 1983, and S. (Smicridea) sattleri Denning & Sykora, 1968. The number of S. (Smicridea) species in Brazil increases from 21 to 27 and Smicridea is recorded from the states of Acre, Amapá, and Sergipe for the first time.
Most valvatiform genera of the gastropod family Hydrobiidae are narrow-range taxa. One exception is the genus Arganiella, which is comprised of three congeners: the type species A. pescei from the Apennine Peninsula, A. wolfi from the Iberian Peninsula and A. tabanensis from the Balkans. The genus assignment of the latter two species was based on morphological similarities with A. pescei in the shell, operculum, radula and genitalia. Given that the morphology of hydrobiids is sometimes susceptible to convergence, this study re-evaluates the taxonomic status of species of Arganiella by analysing mitochondrial (mtCOI) and nuclear (18S rRNA) sequences of topotypes or near topotypes to infer their phylogenetic position. Our phylogenetic analyses depicted Arganiella as a non-monophyletic group within Hydrobiidae, and sequence divergence among the three species ranged from 14.5 to 16.7% for mtCOI and 2.0 to 3.8% for 18S. We also re-examined the extent of morphological variation among species of Arganiella and found a few differences among them and other valvatiform genera. Consequently, we propose two new genera for A. wolfi and A. tabanensis. Our results conflict with the classification of valvatiform hydrobiid species solely based on traditional phenotypical methods and suggest further taxonomic evaluation within a molecular framework.
Selizitapia gen. nov. (Hemiptera: Fulgoromorpha: Flatidae) from tapia woodlands of Madagascar
(2021)
A new monotypic genus of flatid planthoppers (Hemiptera: Fulgoromorpha: Flatidae), Selizitapia gen. nov., is described for Selizitapia pennyi gen. et sp. nov. (type species) from the island of Madagascar. Habitus, male and female external and internal genital structures of the new species are illustrated and compared with similar taxa. Selizitapia pennyi gen. et sp. nov. is endemic to Madagascar where it is known to date only from one locality in the Central Plateau and is associated with tapia woodland formation.
This is the first part of a revision of the type specimens of the South American Sericini. Herein, we examine type specimens of Astaena described by Lawrence Webster Saylor (1913–1999). We provide diagnostic redescriptions, images of habitus, aedeagus, and labels of the type specimens of all 18 species described by him in the genus Astaena. We raise Sayloria Frey, 1973, a former subgenus of Symmela Erichson, 1835 that includes three species, to genus level. Our study results in the following new combinations and synonymy: Sayloria bicoloripes (Saylor, 1946) comb. nov. (= A. postnodata Frey, 1973 syn. nov.), S. abcora (Saylor, 1946) comb. nov. (= A. apolinarmaria Saylor, 1946 syn. nov.) and S. pottsi (Saylor, 1946) comb. nov.
Cell-free therapy using extracellular vesicles (EVs) from adipose-derived mesenchymal stromal/stem cells (ASCs) seems to be a safe and effective therapeutic option to support tissue and organ regeneration. The application of EVs requires particles with a maximum regenerative capability and hypoxic culture conditions as an in vitro preconditioning regimen has been shown to alter the molecular composition of released EVs. Nevertheless, the EV cargo after hypoxic preconditioning has not yet been comprehensively examined. The aim of the present study was the characterization of EVs from hypoxic preconditioned ASCs. We investigated the EV proteome and their effects on renal tubular epithelial cells in vitro. While no effect of hypoxia was observed on the number of released EVs and their protein content, the cargo of the proteins was altered. Proteomic analysis showed 41 increased or decreased proteins, 11 in a statistically significant manner. Furthermore, the uptake of EVs in epithelial cells and a positive effect on oxidative stress in vitro were observed. In conclusion, culture of ASCs under hypoxic conditions was demonstrated to be a promising in vitro preconditioning regimen, which alters the protein cargo and increases the anti-oxidative potential of EVs. These properties may provide new potential therapeutic options for regenerative medicine.
Nucleoredoxin (NXN) is a redox regulator of Disheveled and thereby of WNT signaling. Deficiency in mice leads to cranial dysmorphisms and defects of heart, brain, and bone, suggesting defects of cell fate determination. We used shRNA-mediated knockdown of NXN in SH-SY5Y neuroblastoma cells to study its impact on neuronal cells. We expected that shNXN cells would easily succumb to redox stress, but there were no differences in viability on stimulation with hydrogen peroxide. Instead, the proliferation of naïve shNXN cells was increased with a higher rate of mitotic cells in cell cycle analyses. In addition, basal respiratory rates were higher, whereas the relative change in oxygen consumption upon mitochondrial stressors was similar to control cells. shNXN cells had an increased expression of redox-sensitive heat shock proteins, Hsc70/HSPA8 and HSP90, and autophagy markers suggested an increase in autophagosome formation upon stimulation with bafilomycin and higher flux under low dose rapamycin. A high rate of self-renewal, autophagy, and upregulation of redox-sensitive chaperones appears to be an attractive anti-aging combination if it were to occur in neurons in vivo for which SH-SY5Y cells are a model.
Recent proposals suggest that timing in acquisition, i.e., the age at which a phenomenon is mastered by monolingual children, influences acquisition of the L2, interacting with age of onset of bilingualism and amount of L2 input. Here, we examine whether timing affects acquisition of the bilingual child’s heritage language, possibly modulating the effects of environmental and child-internal factors. The performance of 6- to 12-year-old Greek heritage children residing in Germany (age of onset of German: 0–4 years) was assessed across a range of nine syntactic structures via the Greek LITMUS (Language Impairment Testing in Multilingual Settings) Sentence Repetition Task. Based on previous studies on monolingual Greek, the structures were classified as “early” (main clauses (SVO), coordination, clitics, complement clauses, sentential negation, non-referential wh-questions) or as “late” (referential wh-questions, relatives, adverbial clauses). Current family use of Greek and formal instruction in Greek (environmental), chronological age, and age of onset of German (child-internal) were assessed via the Questionnaire for Parents of Bilingual Children (PABIQ); short-term memory (child-internal) was measured via forward digit recall. Children’s scores were generally higher for early than for late acquired structures. Performance on the three early structures with the highest scores was predicted by the amount of current family use of Greek. Performance on the three late structures was additionally predicted by forward digit recall, indicating that higher short-term memory capacity is beneficial for correctly reconstructing structurally complex sentences. We suggest that the understanding of heritage language development and the role of child-internal and environmental factors will benefit from a consideration of timing in the acquisition of the different structures.
This paper intends to provide some speculative remarks on how consistency and continuity in language use practices within and across contexts inform heritage language acquisition outcomes. We intend “consistency” as maintenance of similar patterns of home language use over the years. “Continuity” refers to the possibility for heritage language speakers to be exposed to formal education in the heritage language. By means of a questionnaire study, we analyze to what extent Italian heritage families in Germany are consistent in their use of the heritage language with their children. Furthermore, by analyzing the educational offer related to Italian as a heritage language across different areas in Germany, we reflect on children’s opportunities to experience continuity between home and school language practices. Finally, we interpret the results of previous studies on Italian heritage language acquisition through the lens of consistency and continuity of language experience. In particular, we show that under the appropriate language experience conditions (involving consistency and continuity), heritage speakers may be successful even in the acquisition of linguistic phenomena that have been shown to be acquired late in first language acquisition.
Based on recent perturbative and non-perturbative lattice calculations with almost quark flavors and the thermal contributions from photons, neutrinos, leptons, electroweak particles, and scalar Higgs bosons, various thermodynamic quantities, at vanishing net-baryon densities, such as pressure, energy density, bulk viscosity, relaxation time, and temperature have been calculated up to the TeV-scale, i.e., covering hadron, QGP, and electroweak (EW) phases in the early Universe. This remarkable progress motivated the present study to determine the possible influence of the bulk viscosity in the early Universe and to understand how this would vary from epoch to epoch. We have taken into consideration first- (Eckart) and second-order (Israel–Stewart) theories for the relativistic cosmic fluid and integrated viscous equations of state in Friedmann equations. Nonlinear nonhomogeneous differential equations are obtained as analytical solutions. For Israel–Stewart, the differential equations are very sophisticated to be solved. They are outlined here as road-maps for future studies. For Eckart theory, the only possible solution is the functionality, H(a(t)), where H(t) is the Hubble parameter and a(t) is the scale factor, but none of them so far could to be directly expressed in terms of either proper or cosmic time t. For Eckart-type viscous background, especially at finite cosmological constant, non-singular H(t) and a(t) are obtained, where H(t) diverges for QCD/EW and asymptotic EoS. For non-viscous background, the dependence of H(a(t)) is monotonic. The same conclusion can be drawn for an ideal EoS. We also conclude that the rate of decreasing H(a(t)) with increasing a(t) varies from epoch to epoch, at vanishing and finite cosmological constant. These results obviously help in improving our understanding of the nucleosynthesis and the cosmological large-scale structure.