bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humoral and cellular immune memory to four COVID-19 vaccines
Authors: Zhang Zeli , Mateus Jose , Coelho Camila H. , Dan Jennifer M. , Moderbacher Carolyn Rydyznski , Gálvez Rosa Isela , Cortes Fernanda H. , Grifoni Alba , Tarke Alison , Chang James , Escarrega E. Alexandar , Kim Christina , Goodwin Benjamin , Bloom Nathaniel I. , Frazier April , Weiskopf Daniela , Sette Alessandro , Crotty Shane 
Published: March 2022

SUMMARYMultiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike—specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.
The motivational determinants of human action, their neural bases and functional impact in adolescents with OCD
Authors: Perkes Iain E. , Morris Richard W. , Griffiths Kristi R. , Quail Stephanie , Waters Felicity , O’Brien Margo , Hazell Philip L. , Balleine Bernard W. 
Published: March 2022

AbstractBackgroundEstablishing the motivational influences on human action is essential for understanding choice and decision-making in health and disease. Here we used tests of value-based decision-making, manipulating both predicted and experienced reward values to assess the motivational control of goal-directed action in adolescents and the functional impact of OCD.MethodsAfter instrumental training on a two action-two outcome probabilistic task, participants underwent Pavlovian conditioning using stimuli predicting either the instrumental outcomes, a third outcome or nothing. We then assessed fMRI during choice tests in which we varied predicted value, using specific and general Pavlovian-instrumental transfer (PIT), and experienced value, using outcome devaluation.ResultsBoth predicted and experienced values influenced the performance of goal-directed actions in healthy adolescent participants, mediated by distinct orbitofrontal (OFC)-striatal circuits involving the lateral-OFC and medial-OFC respectively. To establish their functional significance, we tested a matched cohort of adolescents with obsessive-compulsive disorder (OCD). We found that choice between actions in OCD was insensitive to changes in both predicted and experienced values and that these impairments corresponded to hypoactivity activity in the lateral OFC and hyperactivity in medial OFC during specific PIT and hypoactivity in anterior prefrontal cortex, caudate nucleus and their connectivity in the devaluation test.DiscussionWe found, therefore, that predicted and experienced values exerted a potent influence on the performance of goal-directed actions in adolescents via distinct orbitofrontal- and prefrontal-striatal circuits. The influence of these motivational processes was severely blunted in OCD resulting in dysregulated action control associated with the intrusion of competing actions.
WITHDRAWN: Retinal Microvasculature Alteration in Patients with Rheumatoid Arthritis
Authors: Lee Hsuan-Yi 
Published: March 2022

Withdrawal StatementThe authors have withdrawn this manuscript because they have identified areas that require significant modification to ensure the accuracy and reliability of our findings. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Unified Predictive Model for Endometriosis: Merging Clinical, Self-reporting and Genetic Information
Authors: Blass Ido , Sahar Tali , Shraibman Adi , Ofer Dan , Rappoport Nadav , Linial Michal 
Published: March 2022

AbstractEndometriosis is a condition characterized by implants of endometrial tissues into extrauterine sites, mostly within the pelvic peritoneum. The prevalence of endometriosis is under-diagnosed, and estimated to account for 5–10% of all women of reproductive age. The goal of this study is to develop a model for endometriosis based on the UK-biobank (UKBB). We partitioned the data into those diagnosed with endometriosis (5,924; ICD-10: N80) and a control group (142,576). We included over 1000 variables from UKBB covering personal information about female health, lifestyle, self-reported data, genetic variants, and medical history prior to endometriosis diagnosis. We applied machine learning algorithms to train an endometriosis prediction model. The optimal prediction was achieved with the gradient boosting algorithms of CatBoost for the data-combined model, with an area under the ROC curve (roc-AUC) of 0.78. We discovered that, prior to being diagnosed with endometriosis, women had significantly more ICD-10 diagnoses than the average unaffected woman. Informative features, ranked by SHAP values included irritable bowel syndrome (IBS) and the length of the menstrual cycle. We conclude that the rich population-based retrospective data from the UKBB is valuable for developing predictive models despite the limitations of missing data and noisy medical input. The informative features of the model may improve clinical utility for endometriosis diagnosis.
Targeting phenotypic plasticity prevents metastasis and the development of chemotherapy-resistant disease
Authors: San Juan Beatriz P , Hediyeh-Zadeh Soroor , Rangel Laura , Milioli Heloisa H , Rodriguez Vanina , Bunkum Abigail , Kohane Felix V , Purcell Carley A , Bhuva Dharmesh D , Kurumlian Anie , Castillo Lesley , Lim Elgene , Gill Anthony J , Ganju Vinod , Dear Rachel , O’Toole Sandra , Vargas A. Cristina , Hickey Theresa E , Goldstein Leonard D , Lock John G , Davis Melissa J , Chaffer Christine L 
Published: March 2022

ABSTRACTCancer cells invoke phenotypic plasticity programs to drive disease progression and evade chemotherapeutic insults, yet until now there have been no validated clinical therapies targeting this process. Here, we identify a phenotypic plasticity signature associated with poor survival in basal/triple-negative breast cancer, in which androgen signalling is prominent. We establish that anti-androgen therapies block cancer stem cell function and prevent chemotherapy-induced emergence of new cancer stem cells. In particular, the anti-androgen agent seviteronel synergizes with chemotherapy to improve chemotherapeutic inhibition of primary and metastatic tumour growth and prevent the emergence of chemotherapy-resistant disease. We validate cytoplasmic AR expression as a clinical phenotypic plasticity biomarker that predicts poor survival and poor response to chemotherapy, and positive response to seviteronel plus chemotherapy. This new targeted combination therapy validates modulating phenotypic plasticity as an effective strategy to prevent and treat chemotherapy-resistant cancers with transformative clinical potential.STATEMENT OF SIGNIFICANCEThere are currently no curative therapies for patients with chemotherapy-resistant cancer. We demonstrate that modulating phenotypic plasticity prevents the emergence of chemotherapy-resistant disease in triple-negative breast cancer. This represents the first known validated clinical therapy leveraging phenotypic plasticity. Moreover, we identify a highly effective anti-androgen drug and a biomarker to select and treat patients best-suited to this new therapy. A clinical trial is underway (NCT04947189).SUMMARY SENTENCEBlocking phenotypic plasticity is an effective targeted therapeutic strategy to treat cance
Traumatic Experience and Self-Control in Old Age
Authors: Choung Youngjoo , Pak Tae-Young 
Published: March 2022

AbstractThe behavioral economics literature suggests that exposure to traumatic events shifts preference features like risk aversion and time preference. Drawing on this literature, this study explored the relationship between early life exposure to traumatic events and self-control at older ages. The data were obtained from the Health and Retirement Study, which offers retrospective data on trauma exposure and a measure of self-control. The results showed that the experience of serious physical attacks or assaults was associated with a 3.1% reduction in self-control, above and beyond the influence of demographic characteristics and childhood socioeconomic disadvantages. The mean number of years elapsed since the physical attack was about 30, conditional on exposure, indicating that traumatic experiences early in life exert a lasting influence on self-control. Our findings were consistent with evidence that experiences of natural disasters and armed conflicts increased impatience among survivors.JEL classification codeD12, D14, D91
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
Authors: Modabbernia Amirhossein , Vidal-Pineiro Didac , Agartz Ingrid , Andreassen Ole A , Ayesa-Arriola Rosa , Bertolino Alessandro , Boomsma Dorret I , Bourque Josiane , Breier Alan , Brodaty Henry , Brouwer Rachel M , Buitelaar Jan K , Canales-Rodríguez Erick J , Caseras Xavier , Conrod Patricia J , Crespo-Facorro Benedicto , Crivello Fabrice , Crone Eveline A , de Zubicaray Greig I , Dickie Erin W , Dima Danai , Frenzel Stefan , Fisher Simon E , Franke Barbara , Glahn David C , Grabe Hans-Jörgen , Grotegerd Dominik , Gruber Oliver , Guerrero-Pedraza Amalia , Gur Raquel E , Gur Ruben C , Hartman Catharina A , Hoekstra Pieter J , Hulshoff Pol Hilleke E , Jahanshad Neda , Jernigan Terry L , Jiang Jiyang , Kalnin Andrew J , Kochan Nicole A , Mazoyer Bernard , McDonald Brenna C , McMahon Katie L , Nyberg Lars , Oosterlaan Jaap , Pomarol-Clotet Edith , Radua Joaquim , Sachdev Perminder S , Satterthwaite Theodore D , Salvador Raymond , Sarro Salvador , Saykin Andrew J , Schumann Gunter , Smoller Jordan W , Sommer Iris E , Espeseth Thomas , Thomopoulos Sophia I , Trollor Julian N , van ‘t Ent Dennis , Voineskos Aristotle , Wang Yang , Weber Bernd , Westlye Lars T , Whalley Heather C , Williams Steven CR , Wittfeld Katharina , Wright Margaret J , Thompson Paul M , Paus Thomas , Frangou Sophia 
Published: March 2022

AbstractMechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific marker gene expression levels. We found differences amidst early-life (<20 years), mid-life (20-60 years), and late-life (>60 years) in the patterns of association between inter-regional profiles of cortical thickness and expression profiles of marker genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated that each of the three life-stages was associated with different biological processes and cellular components: synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights into age-related cortical thinning during typical development and aging.
Polypyrimidine Tract-Binding Protein 1 (PTBP1) regulates CD4 T cell Activation independent of its role in proliferation
Authors: Narayanan Bitha , De Maio Diego Prado , LaPorta James , Voskoboynik Yekaterina , Matus-Nicodemos Rodrigo , Summers Sean , Ganapathi Usha , Valentin-Acevedo Anibal , Covey Lori R. 
Published: March 2022

ABSTRACTOur previous work found that the RNA binding protein polypyrimidine tract-binding protein (PTBP1) is critical for regulating multiple events in T cell activation including changes in proliferation, and expression of activation markers and cytokines. These changes corresponded to the regulation of the ERK1/2 and NF-κB pathways as well as through changes in steady-state RNA levels. Because proliferation is critical for driving T cell activation, it was unclear whether PTBP1 was required for optimal activationper seor whether changes were secondary to a requirement for initiating/sustaining proliferation. To address this question, the human T cell lymphoma cell line, Jurkat, which recapitulates many of the molecular events of TCR-induced activation, was used to understand how PTBP1 impacts early events in T cell activation with ongoing proliferation. Using two phenotypically distinct Jurkat subclones (D1.1 and B2.7), we first profiled global RNA expression patterns using RNAseq analysis and found marked differences between the two cell lines with the D1.1 line giving a more antigen-experienced phenotype. Reducing PTBP1 by shPTB expression, to 60% WT levels resulted in no significant decrease in proliferation in the two subclones. However, we observed that PTBP1 was required for both optimal expression of activation markers, CD25, CD38, CD69, and CD40L, and signaling through the ERK1/2, P38 and AKT pathways. Importantly, limiting PTBP1 had different effects on the activation signals for each cell line suggesting that the differentiation state of the cell is a critical factor in understanding the role of PTBP1 in T cell activation. This was further reinforced by our finding that PTBP1 regulated distinct groups of genes specific for each line. Together, our findings suggest that PTBP1 regulates specific T cell activation responses independent of its role in proliferation and that the initial phenotype of the T cell plays an essential role in the dependency of the cell on PTBP1 for driving these changes.
Leveraging shared ancestral variation to detect local introgression
Authors: Fang Lesly Lopez , Vecchyo Diego Ortega-Del , McTavish Emily Jane , Huerta-Sanchez Emilia 
Published: March 2022

AbstractIntrogression is a common evolutionary phenomenon that results in shared genetic material across non-sister taxa. Existing statistical methods such as Patterson’s D statistic can detect introgression by measuring an excess of shared derived alleles between populations. The D statistic is effective to detect genome-wide patterns of introgression but can give spurious inferences of introgression when applied to local regions. We propose a new statistic, D+, that leverages both shared ancestral and derived alleles to infer local introgressed regions. Incorporating both shared derived and ancestral alleles increases the number of informative sites per region, improving our ability to identify local introgression. We use a coalescent framework to derive the expected value of this statistic as a function of different demographic parameters under an instantaneous admixture model and use coalescent simulations to compute the power and precision of D+. While the power of D and D+ is comparable, D+ has better precision than D. We apply D+ to empirical data from the 1000 Genome Project and Heliconius butterflies to infer local targets of introgression in humans and in butterflies.
Identification of a Novel Osteogenetic Oligodeoxynucleotide (osteoDN) that Promotes Osteoblast Differentiation in a TLR9-Independent Manner
Authors: Nihashi Yuma , Miyoshi Mana , Umezawa Koji , Shimosato Takeshi , Takaya Tomohide 
Published: March 2022

AbstractRecent studies have revealed that oligodeoxynucleotides (ODNs) designed from genome sequences have the potential to regulate cell fate. Currently, ODNs that conduct cell differentiation are nanomolecular drug candidates for regenerative medicine. Herein, we demonstrate that iSN40, an 18-base ODN derived from theLacticaseibacillus rhamnosusGG genome, promoted the differentiation and calcification of osteoblasts that play a central role during bone formation. In the murine osteoblast cell line MC3T3-E1, iSN40 enhanced alkaline phosphatase activity at the early stage of differentiation and facilitated calcium deposition at the late stage by inducing the expression of osteogenic genes such as Msx2, osterix, collagen type 1α, osteopontin, and osteocalcin. Intriguingly, the CpG motif within iSN40 was not required for its osteogenetic activity, indicating that iSN40 functions in a TLR9-independent manner. These data suggest that iSN40, serving as an osteogenetic ODN (osteoDN), as a drug seed that target osteoblasts for bone regeneration.
Basal and stress-induced expression changes consistent with water loss reduction explain desiccation tolerance of natural Drosophila melanogaster populations
Authors: Horváth Vivien , Guirao-Rico Sara , Salces-Ortiz Judit , Rech Gabriel E. , Green Llewellyn , Aprea Eugenio , Rodeghiero Mirco , Anfora Gianfranco , González Josefa 
Published: March 2022

ABSTRACTBackgroundClimate change is one of the main factors shaping the distribution and biodiversity of organisms, among others by greatly altering water availability, thus exposing species and ecosystems to harsh desiccation conditions. Insects are especially threatened by these challenging dry environments, because of their small size and thus large surface area to volume ratio. Integrating transcriptomics and physiology is key to advancing our knowledge on how species cope with desiccation stress, and these studies are still best accomplished in model organisms.ResultsHere, we characterized the natural variation of European D. melanogaster populations across climate zones and found that strains from arid regions were similar or more tolerant to desiccation compared with strains from temperate regions. Tolerant and sensitive strains differed not only in their transcriptomic response to stress but also in their basal expression levels. We further showed that gene expression changes in tolerant strains correlated with their physiological response to desiccation stress and with their cuticular hydrocarbon composition. Transposable elements, which are known to influence stress response across organisms, were not found to be enriched nearby differentially expressed genes. Finally, we identified several tRNA-derived small RNA fragments that differentially targeted genes in response to desiccation stress.ConclusionsOur results showed that by integrating transcriptomics with physiological trait analysis we can pinpoint the genetic basis of the differences in tolerance to desiccation stress found in natural D. melanogaster populations. Moreover, we showed that, beyond starvation and aging, tRNA-derived small RNA fragments (tRFs) appear to be relevant post-transcriptional gene regulators in response to desiccation stress.
Solvent-induced allosteric transition of the Hepatitis C virus human cellular receptor CD81 large extracellular loop
Authors: Risueño C. , Charro D. , Abrescia N. G. A. , Coluzza I. 
Published: March 2022

AbstractCD81 is a tetraspanin receptor that clusters into microdomains to mediate cell signalling processes. CD81 is also one of the four primary cellular receptors of the Hepatitis C virus (HCV). Previous structural studies on the α-helical CD81 large-extracellular-loop domain (CD81LEL) have shown that it can adopt different conformations (from closed to open), likely depending on the environmental conditions. This conformational plasticity has been implicated in the endosomal fusion of HCV upon entry. However, the precise mechanism governing the CD81LEL plasticity has remained elusive so far.Here, by combining molecular dynamics simulations and circular dichroism experiments on wt-CD81LEL and two mutants at different endosomal pH conditions, pH 5.5 and pH 4.6, we show that the modulation of the solvation shell governs the plasticity of CD81LEL. The primarily implicated residues are D139 and E188, respectively, located near a loop preceded by a helix. At acidic conditions, their interaction with water is reduced, causing a re-ordering of the water molecules, and thus triggering the dynamics of CD81LEL. However, mutations E188Q and D139N retain the solvation shell and restrict the conformational space that the head subdomain can explore.We propose that residues E188 and D139 control the solvent-induced allosteric transition of the CD81LEL domain. This mechanism might play a role in other cellular receptors that function along the endosomal pathway.Popular SummaryUnderstanding the cellular mechanisms that are exploited by viruses to infect their host is key for the development of therapeutics. Here, in the context of Hepatitis C Virus infection we report the mechanism that governs the plasticity of the extra-cellular domain of tetraspanin CD81, one of the major cellular receptors of this virus. The mechanism proposed here is a novel form of solvent-induced allosteric transition in proteins mediated by two antenna residues located in the head subdomain of CD81. We propose that it could serve as a pH sensing strategy to time the endosomal pathway and trigger a signal at the right time for HCV fusion.
Implicit Versus Explicit Timing – Separate or Shared Mechanisms?
Authors: Herbst Sophie K , Obleser Jonas , van Wassenhove Virginie 
Published: March 2022

AbstractTime implicitly shapes cognition, but time is also explicitly represented, for instance in the form of durations. Parsimoniously, the brain could use the same mechanisms for implicit and explicit timing. Yet, the evidence has been equivocal, revealing both joint versus separate signatures of timing. Here, we directly compared implicit and explicit timing using magnetoencephalography, whose temporal resolution allows investigating the different stages of the timing processes. Implicit temporal predictability was induced in an auditory paradigm by a manipulation of the foreperiod. Participants received two consecutive task instructions: discriminate pitch (indirect measure of implicit timing) or duration (direct measure of explicit timing). The results show that the human brain efficiently extracts implicit temporal statistics of sensory environments, to enhance the behavioral and neural responses to auditory stimuli, but that those temporal predictions did not improve explicit timing. In both tasks, attentional orienting in time during predictive foreperiods was indexed by an increase in alpha power over visual and parietal areas. Furthermore, pre-target induced beta power in sensorimotor and parietal areas increased during implicit compared to explicit timing, in line with the suggested role for beta oscillations in temporal prediction. Interestingly, no distinct neural dynamics emerged when participants explicitly paid attention to time, compared to implicit timing. Our work thus indicates that implicit timing shapes the behavioral and sensory response in an automatic way, and is reflected in oscillatory neural dynamics, while the translation of implicit temporal statistics to explicit durations remains somewhat inconclusive, possibly due to the more abstract nature of this task.