julilili42/papers huggingface dataset:
Faculty Opinions recommendation of IL-10–producing Tfh cells accumulate with age and link inflammation with age-related immune suppression
2020-08-05

Aging results in profound immune dysfunction, resulting in the decline of vaccine responsiveness previously attributed to irreversible defects in the immune system. In addition to increased interleukin-6 (IL-6), we found aged mice exhibit increased systemic IL-10 that requires forkhead box P3-negative (FoxP3-), but not FoxP3+, CD4+T cells. Most IL-10-producing cells manifested a T follicular helper (Tfh) phenotype and required the Tfh cytokines IL-6 and IL-21 for their accrual, so we refer to them as Tfh10 cells. IL-21 was also required to maintain normal serum levels of IL-6 and IL-10. Notably, antigen-specific Tfh10 cells arose after immunization of aged mice, and neutralization of IL-10 receptor signaling significantly restored Tfh-dependent antibody responses, whereas depletion of FoxP3+ regulatory and follicular regulatory cells did not. Thus, these data demonstrate that immune suppression with age is reversible and implicate Tfh10 cells as an intriguing link between "inflammaging" and impaired immune responses with age.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). PMID: 32832688
Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults
2020-08-06

Abstract Background Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts. Methods Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8–11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders. Results CMV-seropositivity was seen in 47%–79% of 10 122 white community-dwelling adults aged 59–93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97–1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83–1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04–1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99–1.29). The lack of increased mortality risk was confirmed in subanalyses. Conclusions CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.
Optical coherence tomography‐based determination of ischaemia onset – the temporal dynamics of retinal thickness increase in acute central retinal artery occlusion
2020-08-06

Abstract Purpose Acute central retinal artery occlusion (CRAO) induces ischaemic retinal oedema. The purpose of this study was to define sensitivity and specificity of optical coherence tomography (OCT) based retinal thickness analysis in determining ischaemia onset in CRAO. Methods The relative retinal thickness increase (RRTI) in comparison with the fellow eye was analysed retrospectively in OCT scans of 66 patients diagnosed with CRAO between January 2010 and December 2019 within 48 hr of ischaemia onset. The natural course of RRTI and the sensitivity and specificity of OCT‐based determination of ischaemia onset in identifying CRAO within 4.5 hr using the RRTI were evaluated. Results Relative retinal thickness increase (RRTI) in acute CRAO follows a hyperbolic curve with a steep incline within the early phase after which it reaches a plateau. Optical coherence tomography (OCT)‐based retinal thickness analysis in CRAO allows to differentiate patients with ischaemia onset within the past 4.5 hr or thereafter with a sensitivity of 100% and a specificity of 94.3%. Conclusion Relative retinal thickness increase (RRTI) allows to identify CRAO patients that are eligible for a potentially beneficial reperfusion therapy within a therapeutic window of 4.5 hr with a high accuracy. Especially in patients with unknown ischaemia onset, this diagnostic tool could be of major importance in the future clinical management.
Brain circuits signaling the absence of emotion in body language
2020-08-06

Significance How do we infer absence of emotion? As opposed to the brain mechanisms for recognizing emotions, this issue has remained underinvestigated. Present findings bond communication between the amygdala and insula with the ability to infer the absence of emotion in body language. Previously, both the amygdala and insula have been associated with emotion perception. The outcome of this study extends the conceptualization of these brain regions and their interplay to the processing of social signals without emotional content. This may have wide-ranging implications for better understanding neuropsychiatric conditions characterized by misinterpretation of neutral for emotional signals, such as depression or schizophrenia. The findings call for interdisciplinary research on how the brain infers the lack of emotional valence in social signals.
Automated Production of Human Induced Pluripotent Stem Cell-Derived Cortical and Dopaminergic Neurons with Integrated Live-Cell Monitoring
2020-08-06

Manual culture and differentiation protocols for human induced pluripotent stem cells (hiPSC) are difficult to standardize, show high variability and are prone to spontaneous differentiation into unwanted cell types. The methods are labor-intensive and are not easily amenable to large-scale experiments. To overcome these limitations, we developed an automated cell culture system coupled to a high-throughput imaging system and implemented protocols for maintaining multiple hiPSC lines in parallel and neuronal differentiation. We describe the automation of a short-term differentiation protocol using Neurogenin-2 (NGN2) over-expression to produce hiPSC-derived cortical neurons within 6‒8 days, and the implementation of a long-term differentiation protocol to generate hiPSC-derived midbrain dopaminergic (mDA) neurons within 65 days. Also, we applied the NGN2 approach to a small molecule-derived neural precursor cells (smNPC) transduced with GFP lentivirus and established a live-cell automated neurite outgrowth assay. We present an automated system with protocols suitable for routine hiPSC culture and differentiation into cortical and dopaminergic neurons. Our platform is suitable for long term hands-free culture and high-content/high-throughput hiPSC-based compound, RNAi and CRISPR/Cas9 screenings to identify novel disease mechanisms and drug targets.
Transcriptional Control of Quality Differences in the Lipid-Based Cuticle Barrier in Drosophila suzukii and Drosophila melanogaster
2020-08-06

Cuticle barrier efficiency in insects depends largely on cuticular lipids. To learn about the evolution of cuticle barrier function, we compared the basic properties of the cuticle inward and outward barrier function in adults of the fruit flies <i>Drosophila suzukii</i> and <i>Drosophila melanogaster</i> that live on fruits sharing a similar habitat. At low air humidity, <i>D. suzukii</i> flies desiccate faster than <i>D. melanogaster</i> flies. We observed a general trend indicating that in this respect males are less robust than females in both species. Xenobiotics penetration occurs at lower temperatures in <i>D. suzukii</i> than in <i>D. melanogaster</i>. Likewise, <i>D. suzukii</i> flies are more susceptible to contact insecticides than <i>D. melanogaster</i> flies. Thus, both the inward and outward barriers of <i>D. suzukii</i> are less efficient. Consistently, <i>D. suzukii</i> flies have less cuticular hydrocarbons (CHC) that participate as key components of the cuticle barrier. Especially, the relative amounts of branched and desaturated CHCs, known to enhance desiccation resistance, show reduced levels in <i>D. suzukii</i>. Moreover, the expression of <i>snustorr</i> (<i>snu</i>) that encodes an ABC transporter involved in barrier construction and CHC externalization, is strongly suppressed in <i>D. suzukii</i>. Hence, species-specific genetic programs regulate the quality of the lipid-based cuticle barrier in these two Drosophilae. Together, we conclude that the weaker inward and outward barriers of <i>D. suzukii</i> may be partly explained by differences in CHC composition and by a reduced Snu-dependent transport rate of CHCs to the surface. In turn, this suggests that <i>snu</i> is an ecologically adjustable and therefore relevant gene in cuticle barrier efficiency.
Compositional uncertainty in deep Gaussian processes.
2020-08-06

Gaussian processes (GPs) are nonparametric priors over functions. Fitting a GP implies computing a posterior distribution of functions consistent with the observed data. Similarly, deep Gaussian processes (DGPs) should allow us to compute a posterior distribution of compositions of multiple functions giving rise to the observations. However, exact Bayesian inference is intractable for DGPs, motivating the use of various approximations. We show that the application of simplifying mean-field assumptions across the hierarchy leads to the layers of a DGP collapsing to near-deterministic transformations. We argue that such an inference scheme is suboptimal, not taking advantage of the potential of the model to discover the compositional structure in the data. To address this issue, we examine alternative variational inference schemes allowing for dependencies across different layers and discuss their advantages and limitations.
Body Boundary Work: Praxeological Thoughts on Personal Corporality
2020-08-06

Abstract In everyday life, we usually go by the one - body - one - person rule : one person has one body (and vice versa). This social belief builds on two assumptions: bodies are individual units and they (and ‘their’ person) are the same in different situations. This is also the conceptual resource for social theories that build on the notion of individuals. In this article, we turn it into a sociological topic. We develop a vocabulary for reconstructing bodily one-ness and bodily sameness as practically achieved social order, as body boundary work : what belongs to a body is a matter of local practices that define its situational contours, limits and margins. Practices of identification and personification draw on social memories and enact bodies as trans-situational entities. Persons and bodies, we argue, evolve in co-individuation. Personal corporality, then, can be conceptualized as a body of work that encompasses these practical efforts of boundary-making.
Songbirds can learn flexible contextual control over syllable sequencing
2020-08-06

Abstract The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment by-moment control over vocalizations. Here, we demonstrate that Bengalese finches ( Lonchura striata domestica) , which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.
Google Trends Data and COVID-19 in Europe: correlations and model enhancement are European wide
2020-08-06

The current COVID-19 pandemic offers a unique opportunity to examine the utility of Internet search data in disease modelling across multiple countries. Google Trends data (GTD) indicating the volume of Internet searching on 'Coronavirus' were obtained for a range of European countries along with corresponding incident case numbers. Significant positive correlations between GTD with incident case numbers occurred across European countries, with the strongest correlations being obtained using contemporaneous data for most countries. GTD was then integrated into a lag distributed model; this improved model quality for both the increasing and decreasing epidemic phases.
Identifying Levers Related to Student Performance on High-Stakes Science Exams: Examining School, Teaching, Teacher, and Professional Development Characteristics
2020-08-06

Background: Many students enter into postsecondary education without the college readiness skills that allow them to face the demands of postsecondary education. Increasingly, policymakers and educational researchers are responding to calls for reforming secondary education to provide more opportunity for all students to receive high quality education and to become career and college ready. Purpose: This study attempts to identify levers to increase student performance in secondary education. In particular, it examines relationships of school, teaching, teacher, and teacher professional development characteristics with student scores on high-stakes Advanced Placement (AP) examinations in the sciences.Setting: This study is situated in the context of the large-scale, top-down, nationwide AP curriculum and examination reform in the sciences (Biology, Chemistry, Physics) in the United States. This is an unprecedented opportunity to analyze changing educational landscapes in the United States with large-scale national student-, teacher-, school-, and district-level data sets across multiple science disciplines and different stages of the curriculum reform implementation connected to a standardized and high-stakes student outcome measure.Population: This study analyzes nationwide data samples of the AP Biology, AP Chemistry, and AP Physics population during the first, second, and third year of the curriculum reform implementation. Across disciplines and years, the analytical samples include a total of 113,603 students and 6,046 teachers. Research design: This empirical quantitative study uses data from web-based surveys sent to all AP science teachers. Additionally, College Board provided student- and school-level data for all students taking AP examinations. Data preparation methods included exploratory and confirmatory factor analysis. Associations towards student achievement were analyzed through multi-level ordered logistic regression analysis separately by science discipline and year of the curriculum reform implementation. Afterwards, the results were aggregated through a meta-analysis. Findings: Student performance is not pre-determined by students’ background, leaving roughly 60% of the AP score variance potentially malleable for teacher and school-level factors. In particular, teachers’ perceived administrative support, self-efficacy, teaching experience, and elements of classroom instruction were related to student performance. Notably, teachers’ professional development participation has a small, mixed impact on student achievement. Conclusion: The identified levers for improving student achievement provide a strong rationale for the continued efforts of policy makers to improve school environments and to support science teachers to ultimately both increase student learning and help all students graduate prepared for college and ready for their future careers.
Reprogramming of stromal fibroblasts by chemotherapy-induced secretion of IFNβ1 drives re-growth of breast cancer cells after treatment
2020-08-06

Abstract Chemotherapy is still the standard of care for a large number of aggressive tumours including breast cancer. In breast cancer, chemotherapeutic regimens are administered in intervaled cycles of the maximum tolerated dose, allowing cancer cells to re-grow or adapt during the resting periods between cycles. However, how stromal fibroblasts impact the fate of cancer cells after chemotherapy treatment remains poorly understood. We show that cancer cells utilize paracrine signalling with stromal fibroblasts to drive their recovery after treatment withdrawal. Secretion of IFNβ1 by cancer cells after treatment with high doses of chemotherapy instigates the acquisition of an anti-viral state in stromal fibroblasts associated with the expression of several interferon stimulated genes (ISGs), including numerous pro-inflammatory cytokines. This crosstalk is an important driver of the expansion of breast cancer cells after chemotherapy and blocking of IFNβ1 in tumour cells abrogated their increased recovery potential. Analysis of human breast carcinomas supports the proposed role of IFNβ1 since its expression is inversely correlated with recurrence free survival (RFS). Moreover, expression of the interferon signature identified in stromal fibroblasts is equally associated with higher recurrence rates and a worse outcome in breast cancer patients. Our study unravels a novel paracrine communication between cancer cells and fibroblasts that ultimately results in the escape of malignant cells to treatment. Targeting of this axis could potentially improve the outcome of breast cancer patients to chemotherapy treatment.
Citrin Deficiency Mimicking Mitochondrial Depletion Syndrome
2020-08-06

Abstract Background Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. Results We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69+1_70-1)_(212+1_231-1)del in SLC25A13 . The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born one year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. Conclusion As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.
Discovery and Evaluation of Enantiopure 9H-pyrimido[4,5-b]indoles as Nanomolar GSK-3β Inhibitors with Improved Metabolic Stability
2020-08-06

Dataset related to publication Andreev et al.: "<em>Discovery and Evaluation of Enantiopure 9H-pyrimido[4,5-b]indoles as Nanomolar GSK-3β Inhibitors with Improved Metabolic Stability" Int. J. Mol. Sci.</em> <strong>2020</strong>, <em>21</em>(21), 7823 https://doi.org/10.3390/ijms21217823 Containing: a) Raw-trajectory files of 1 microsecond Desmond simulations of <strong>(<em>R</em>)-2 and (<em>R</em>)-28 </strong>(-out-cms and trj) b) QM Conformer &amp; Tautomer predictor tool derived conformations of compounds <strong>(<em>S</em>)-2; (<em>R</em>)-2 and (<em>R</em>)-28; </strong>(.mae) (10 lowest energy conformations in each file)
Identification and characterization of novel splice variants of human farnesoid X receptor
2020-08-06

Dataset related to publication: Mustonen E-K, Lee SML, Nieß H, Schwab M, Pantsar T, Burk O: "Identification and characterization of novel splice variants of human farnesoid X receptor". <em>Archives of Biochemistry and Biophysics</em> https://doi.org/10.1016/j.abb.2021.108893 Including: I. Full-length raw-trajectories of the 1 microsecond Desmond simulations (-out.cms, trj)
Absolute Numerosity Discrimination as a Case Study in Comparative Vertebrate Intelligence
2020-08-07

The question of whether some non-human animal species are more intelligent than others is a reoccurring theme in comparative psychology. To convincingly address this question, exact comparability of behavioral methodology and data across species is required. The current article explores one of the rare cases in which three vertebrate species (humans, macaques, and crows) experienced identical experimental conditions during the investigation of a core cognitive capability - the abstract categorization of absolute numerical quantity. We found that not every vertebrate species studied in numerical cognition were able to flexibly discriminate absolute numerosity, which suggests qualitative differences in numerical intelligence are present between vertebrates. Additionally, systematic differences in numerosity judgment accuracy exist among those species that could master abstract and flexible judgments of absolute numerosity, thus arguing for quantitative differences between vertebrates. These results demonstrate that Macphail's Null Hypotheses - which suggests that all non-human vertebrates are qualitatively and quantitatively of equal intelligence - is untenable.
Singlet Heterofission in Tetracene–Pentacene Thin‐Film Blends
2020-08-07

Abstract Heterofission is a photophysical process of fundamental and applied interest whereby an excited singlet state is converted into two triplets on chemically distinct chromophores. The potential of this process lies in the tuning of both the optical band gap and the splitting between singlet and triplet energies. Herein, we report the time‐domain observation of heterofission in mixed thin films of the prototypical singlet fission chromophores pentacene and tetracene using excitation wavelengths above and below the tetracene band gap. We found a time constant of 26 ps for endothermic heterofission of a singlet exciton on pentacene in blends with low pentacene fractions, which was outcompeted by pentacene homofission for increasing pentacene concentrations. Direct excitation of tetracene lead to fast energy transfer to pentacene and subsequent singlet fission, which prevented homo‐ or heterofission of a singlet exciton on tetracene.
The integral spliceosomal component CWC15 is required for development in Arabidopsis
2020-08-07

Abstract Efficient mRNA splicing is a prerequisite for protein biosynthesis and the eukaryotic splicing machinery is evolutionarily conserved among species of various phyla. At its catalytic core resides the activated splicing complex Bact consisting of the three small nuclear ribonucleoprotein complexes (snRNPs) U2, U5 and U6 and the so-called NineTeen complex (NTC) which is important for spliceosomal activation. CWC15 is an integral part of the NTC in humans and it is associated with the NTC in other species. Here we show the ubiquitous expression and developmental importance of the Arabidopsis ortholog of yeast CWC15 . CWC15 associates with core components of the Arabidopsis NTC and its loss leads to inefficient splicing. Consistent with the central role of CWC15 in RNA splicing, cwc15 mutants are embryo lethal and additionally display strong defects in the female haploid phase. Interestingly, the haploid male gametophyte or pollen in Arabidopsis, on the other hand, can cope without functional CWC15 , suggesting that developing pollen might be more tolerant to CWC15-mediated defects in splicing than either embryo or female gametophyte.