bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural asymmetry during memory encoding and its association with markers of preclinical Alzheimer’s Disease
Authors: Li Jinghang , Mountz Elizabeth J. , Mizuno Akiko , Shah Ashti M , Weinstein Andrea , Cohen Ann D. , Klunk William E. , Snitz Beth E. , Aizenstein Howard J. , Karim Helmet T. 
Published: June 2021

ABSTRACTBackgroundAlzheimer’s Disease (AD) is the most common form of dementia and is characterized by cognitive dysfunction that impacts daily functioning. Beta-amyloid (Aβ) is a cytotoxic protein that deposits in the brain many years prior to the onset of cognitive dysfunction. The preclinical period is a stage of AD in which significant pathology is present without clinical symptoms. Aβ has been shown to deposit asymmetrically early in the AD trajectory, which has shown to have functional consequences (e.g., asymmetric hypometabolism). We aimed to investigate whether markers of AD and cognitive function were correlated with neural activation asymmetry during memory encoding tasks.MethodsWe recruited participants who were cognitively normal to undergo functional magnetic resonance imaging (fMRI), positron emission tomography (PET) imaging, and cognitive testing. We conducted analyses to identify regions of significant activation during a well-established face-name pair memory encoding task, and to identify regions of significant asymmetry. We then computed hemispheric asymmetry (negative/positive values indicate left/right asymmetry, respectively) and absolute asymmetry (greater values indicate greater asymmetry in either hemisphere) and investigated their associations with age, sex, education, global cerebral amyloid, global cerebral metabolism, memory encoding task performance, white matter hyperintensities, and multiple domains of cognitive function.ResultsWe identified expected regions of significant activation, including the hippocampus, and identified four regions with significant left-hemisphere asymmetry: superior medial frontal gyrus, middle frontal gyrus, supplemental motor area, and medial orbitofrontal gyrus, and two regions with significant right hemisphere asymmetry: putamen and ventral posterolateral nucleus of the thalamus. We found that greater left-hemisphere asymmetry in the middle frontal gyrus was correlated with greater global cerebral glucose metabolism. We also found that better performance in memory, learning, and executive attention was associated with greater absolute symmetry in the thalamus, while better visuospatial performance was associated with greater putamen absolute symmetry.DiscussionFunctional asymmetry is correlated with functional markers (e.g., glucose metabolism) in older cognitively normal adults and may reflect metabolic and cognitive changes. Longitudinal studies may help us better understand these associations and the causal impact of neural activation asymmetry.
Affinity tag coating enables reliable detection of antigen-specific B cells in ImmunoSpot assays
Authors: Köppert Sebastian , Wolf Carla , Becza Noémi , Sautto Giuseppe A. , Franke Fridolin , Kürten Stefanie , Ross Ted M. , Lehmann Paul V. , Kirchenbaum Greg A. 
Published: June 2021

ABSTRACTAssessment of humoral immunity to SARS-CoV-2 and other infectious agents is typically restricted to detecting antigen-specific antibody in the serum. Rarely does immune monitoring entail assessment of the memory B cell compartment itself, although it is these cells that engage in secondary antibody responses capable of mediating immune protection when pre-existing antibodies fail to prevent re-infection. There are few techniques that are capable of detecting rare antigen-specific B cells while also providing information regarding their precursory frequency, class/subclass usage and functional affinity. In theory, the ELISPOT/FluoroSpot (collectively ImmunoSpot) assay platform is ideally-suited for antigen-specific B cell assessments since it provides this information at single-cell resolution for individual antibody-secreting cells (ASC). Here, we tested the hypothesis that antigen coating efficiency could be universally improved across a diverse set of viral antigens if the standard direct (non-specific, low affinity) antigen absorption to the membrane was substituted by high affinity capture. Specifically, we report an enhancement in assay sensitivity and a reduction in required protein concentrations through the capture of recombinant proteins via their encoded hexahistidine (6XHis) affinity tag. Affinity tag antigen coating enabled detection of SARS-CoV-2 Spike receptor binding domain (RBD)-reactive ASC, and also significantly improved assay performance using additional control antigens. Collectively, establishment of a universal antigen coating approach streamlines characterization of the memory B cell compartment after SARS-CoV-2 infection or COVID-19 vaccinations, and facilitates high-throughput immune monitoring efforts of large donor cohorts in general.
EPIDEMIOLOGY OF MAXILLOFACIAL INJURIES IN “HERATSI” NO 1 UNIVERSITY HOSPITAL IN YEREVAN, ARMENIA: A RETROSPECTIVE STUDY
Authors: Aleksanyan Lusine V. , Poghosyan Anna Yu. , Misakyan Martin S. , Minasyan Armen M. , Bablumyan Aren Yu. , Tadevosyan Artashes E. , Muradyan Armen A. 
Published: June 2021

ABSTRACTObjectiveThe aim of this study was to perform a retrospective analysis of the prevalence, etiologies, and types of maxillofacial injuries (MFI) and sites of maxillofacial fractures (MFF) and their management in the Department of ENT and Maxillofacial Surgery of <<Heratsi>> No. 1 University Hospital in Yerevan, Armenia.Material and methodsA retrospective cross-sectional study was conducted. Data including age, sex, date of referral, mode of injury, etiology, radiology records and treatment methods were extracted. Study outcomes were measured using percentages, means, standard deviations and tests of proportions. P <.05 was considered significant.ResultsA total of 204 patients had a mean age of 36.26 ±1.08 years (156 males and 48 females), and a total of 259 MFIs were recorded between 2017 and 2020. Interpersonal violence was found to be the most common etiology of MFFs in this study (42.1%), followed by road traffic accidents (RTAs) (27.9%) and falls (18.6%). The nasal bone was the most common injury site (47.5%), followed by the mandible (31.4%) and zygomatic complex (11.7%). The most common fracture site was the mandibular angle (37.9%), followed by the symphysis/parasymphysis (28.1%) and body (12.6%). The majority of MFFs were treated by open reduction and internal fixation.ConclusionInterpersonal violence, followed by RTAs and falls, was the most common cause of MFIs. The nasal bone was the most common injury site, followed by the mandible and zygomatic complex. Social education with the objective of reducing aggression and interpersonal conflict should be improved, and appropriate RTA prevention strategies should be strengthened and implemented.KEY MESSAGESWhat is already known on this subjectTraumatic injuries continue to be important causes of morbidity and mortality in both developed and developing countries.The incidence rates, etiologies, types, and injuries associated with MFFs vary among different countries.RTAs are the most frequent cause of MFIs in developing countries, and in contrast, the most frequent cause of MFFs in developed countries is IV or assaultWhat this study addsInterpersonal violence was found to be the most common etiology of MFF in this study, followed by RTAs and falls.Patients aged 21-30 years were likely to have sustained nasal bone fractures and mandible fractures in equal proportions.The nasal bones were found to be the most common injury site, followed by the mandible and zygomatic complex.
Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers
Authors: Scurr Martin J. , Zelek Wioleta M. , Lippiatt George , Somerville Michelle , Burnell Stephanie E. A. , Capitani Lorenzo , Davies Kate , Lawton Helen , Tozer Thomas , Rees Tara , Roberts Kerry , Evans Mererid , Jackson Amanda , Young Charlotte , Fairclough Lucy , Wills Mark , Westwell Andrew D. , Morgan B. Paul , Gallimore Awen , Godkin Andrew 
Published: June 2021

AbstractAccurate assessment of SARS-CoV-2 immunity in the population is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature of the immune response that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 156 healthy donors and 67 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were harvested and analysed for TH1-type effector cytokines (IFN-γ and IL-2). Amongst healthy donors, highly significant differential IFN-γ+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst vaccinated or previously infected COVID-19-positive individuals in comparison to unknown/naïve individuals (P < 0.0001). IL-2 production from T cells in response to SARS-CoV-2 derived antigens was a highly predictive diagnostic assay (P < 0.0001; 96.0% sensitivity, 93.9% specificity); measurement of IFN-γ+ SARS-CoV-2 specific T cell responses was equally effective at identifying asymptomatic (antibody and T cell positive) participants. A single dose of COVID-19 vaccine induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 28/29 (96.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P = 0.0003). Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing.
Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment
Authors: Maes Margaret E , Wögenstein Gabriele M , Colombo Gloria , Casado-Polanco Raquel , Siegert Sandra 
Published: June 2021

AbstractAdeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette.Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.
The REF6-dependent H3K27 demethylation establishes transcriptional competence to promote germination in Arabidopsis
Authors: Pan Jie , Zhang Huairen , Zhan Zhenping , Zhao Ting , Jiang Danhua 
Published: June 2021

AbstractSeed germination is a critical developmental switch from a dormant state to active growth, which involves extensive changes in metabolism, gene expression and cellular identity. However, our understanding of epigenetic and transcriptional reprogramming during this process is limited. The histone H3 lysine 27 trimethylation (H3K27me3) plays a key role in regulating gene repression and cell fate specification. Here, we profile H3K27me3 dynamics and dissect the function of H3K27 demethylation during germination. Our temporal genome-wide profiling of H3K27me3 and transcription reveal delayed H3K27me3 reprogramming compared with transcriptomic changes during germination, with H3K27me3 changes mainly occurring when the embryo is entering into vegetative development. REF6-mediated H3K27 demethylation promotes germination but does not significantly contribute to H3K27me3 dynamics during germination, but rather stably establishes an H3K27me3-depleted state permissive to transcription. By analyzing REF6 genomic binding, we show that it is absent from mature embryo chromatin and gradually establishes occupancy during the course of germination to counteract increased PRC2 activity. Our study provides key insights into the dynamics of gene expression and H3K27me3 during seed germination and suggests the function of H3K27me3 in facilitating cell fate switch. Furthermore, we reveal the importance of H3K27 demethylation-established transcriptional competence in germination and likely other developmental processes.
The Hidden Side of Diversity: Effects of Imperfect Detection on Multiple Dimensions of Biodiversity
Authors: Richter Aline , Nakamura Gabriel , Iserhard Cristiano Agra , da Silva Duarte Leandro 
Published: June 2021

AbstractStudies on ecological communities often address patterns of species distribution and abundance, but few consider uncertainty in counts of both species and individuals when computing diversity measures.We evaluated the extent to which imperfect detection may influence patterns of taxonomic, functional, and phylogenetic diversity in ecological communities.We estimated the true abundance of fruit-feeding butterflies sampled in canopy and understory strata in a subtropical forest. We compared the diversity values calculated by observed and estimated abundance data through the hidden diversity framework. This framework evaluates the deviation of observed diversity when compared with diversities derived from estimated true abundances, and if such deviation represents a bias or a noise in the observed diversity pattern.The hidden diversity values differed between strata for all diversity measures, except for functional richness. The taxonomic measure was the only one where we observed an inversion of the most diverse stratum when imperfect detection was included. Regarding phylogenetic and functional measures, the strata showed distinct responses to imperfect detection, despite the tendency to overestimate observed diversity. While the understory showed noise for the phylogenetic measure, since the observed pattern was maintained, the canopy had biased diversity for the functional metric. This bias occurred since no significant differences were found between strata for observed diversity, but rather for estimated diversity, with the canopy being more clustered.We demonstrate that ignore imperfect detection may lead to unrealistic estimates of diversity and hence, to erroneous interpretations of patterns and processes that structure biological communities. For fruit-feeding butterflies, according to their phylogenetic position or functional traits, the undetected individuals triggered different responses in the relationship of the diversity measures to the environmental factor. This highlights the importance to evaluate and include the uncertainty in species detectability before calculating biodiversity measures to describe communities.
Resource and seasonality drive interspecific variability in a Dynamic Energy Budget model
Authors: Mariño Joany , Dufour Suzanne C. , Hurford Amy , Récapet Charlotte 
Published: June 2021

ABSTRACTAnimals show a vast array of phenotypic traits in time and space. These variation patterns have traditionally been described as ecogeographical rules; for example, the tendency of size and clutch size to increase with latitude (Bergman’s and Lack’s rules, respectively). Despite considerable research into these patterns, the processes behind trait variation remain controversial. Here, we show how food variability, which determines individual energy input and allocation trade-offs, can drive interspecific trait variation. Using a dynamic energy budget (DEB) model, we simulated different food environments as well as interspecific variability in the parameters for energy assimilation, mobilization, and allocation to soma. We found that interspecific variability is greater when the resource is non-limiting in both constant and seasonal environments. Our findings further show that individuals can reach larger biomass and greater reproductive output in a seasonal environment than in a constant environment of equal average resource due to the peaks of food surplus. Our results agree with the classical patterns of interspecific trait variation and provide a mechanistic understanding that supports recent hypotheses which explain them: the resource and the eNPP (net primary production during the growing season) rules. Due to the current alterations to ecosystems and communities, disentangling trait variation is increasingly important to understand and predict biodiversity dynamics under environmental change.
Gene regulatory networks underlying human microglia maturation
Authors: Han Claudia Z. , Li Rick Z. , Hansen Emily , Bennett Hunter R. , Poirion Olivier , Buchanan Justin , Challacombe Jean F. , Fixsen Bethany R. , Trescott Samantha , Schlachetzki Johannes C.M. , Preissl Sebastian , Wang Allen , O’Connor Carolyn , Warden Anna S. , Shriram Shreya , Kim Roy , Nguyen Celina T. , Schafer Danielle M. , Ramirez Gabriela , Anavim Samuel A. , Johnson Avalon , Sajti Eniko , Gupta Mihir , Levy Michael L. , Ben-Haim Sharona , Gonda David D. , Laurent Louise , Glass Christopher K. , Coufal Nicole G. 
Published: June 2021

AbstractThe fetal period is a critical time for brain development, characterized by neurogenesis, neural migration, and synaptogenesis1-3. Microglia, the tissue resident macrophages of the brain, are observed as early as the fourth week of gestation4 and are thought to engage in a variety of processes essential for brain development and homeostasis5-11. Conversely, microglia phenotypes are highly regulated by the brain environment12-14. Mechanisms by which human brain development influences the maturation of microglia and microglia potential contribution to neurodevelopmental disorders remain poorly understood. Here, we performed transcriptomic analysis of human fetal and postnatal microglia and corresponding cortical tissue to define age-specific brain environmental factors that may drive microglia phenotypes. Comparative analysis of open chromatin profiles using bulk and single-cell methods in conjunction with a new computational approach that integrates epigenomic and single-cell RNA-seq data allowed decoding of cellular heterogeneity with inference of subtype- and development stage-specific transcriptional regulators. Interrogation of in vivo and in vitro iPSC-derived microglia models provides evidence for roles of putative instructive signals and downstream gene regulatory networks which establish human-specific fetal and postnatal microglia gene expression programs and potentially contribute to neurodevelopmental disorders.
Drivers of Transcriptional Variance in Human Intestinal Epithelial Organoids
Authors: Criss Zachary K. , Bhasin Nobel , Di Rienzi Sara C. , Rajan Anubama , Deans-Fielder Kali , Swaminathan Ganesh , Kamyabi Nabiollah , Zeng Xi-Lei , Chakravarti Deepavali , Estrella Clarissa , Yu Xiaomin , Patil Ketki , Fleet James C. , Verzi Michael P. , Christakos Sylvia , Helmrath Michael A. , Arimura Sumimasa , DePinho Ronald A. , Britton Robert , Maresso Anthony , Grande-Allen Jane , Blutt Sarah E. , Crawford Sue E. , Estes Mary K. , Ramani Sasirekha , Shroyer Noah F. 
Published: June 2021

AbstractBackground & AimsHuman intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity.MethodsRNA-sequencing datasets from 251 experiments performed on 35 human enteroid and colonoid lines from 28 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and Gene Set Enrichment Analysis (GSEA) was used to identify differentially expressed genes and enriched of pathways.ResultsPERMANOVA, Pearson correlations, and dendrogram analysis of all data indicated three tiers of influence of culture methods on transcriptomic variation: substrate (collagen vs. Matrigel) and format (3D, transwell, and monolayer) had the largest effect (7,271-1,305 differentially expressed genes-DEGs); segment of origin (duodenum, jejunum, ileum, colon) and differentiation status had a moderate effect (5,977-420 DEGs), and patient heterogeneity and specific experimental manipulations (e.g., pathogen infection) had the smallest effect. GSEA identified hundreds of pathways that varied between culture methods, such as IL1 cytokine signaling enriched in transwell vs. monolayer cultures, and cholesterol biosynthesis genes enriched in Matrigel vs. collagen cultures.ConclusionsSurprisingly large differences in organoid transcriptome were driven by variations in culture methods such as format and substrate, whereas experimental manipulations such as infection had modest effects. These results show that common variations in culture conditions can have large effects on intestinal organoids and should be accounted for when designing experiments and comparing results between laboratories. Our data constitute the largest RNA-seq dataset interrogating human intestinal organoids.
Single-Cell Transcriptional Profiling of the Adult Corticospinal Tract Reveals Forelimb and Hindlimb Molecular Specialization
Authors: Golan Noa , Kauer Sierra , Ehrlich Daniel B , Ravindra Neal , van Dijk David , Cafferty William BJ 
Published: June 2021

AbstractThe corticospinal tract (CST) is refractory to repair after CNS trauma, resulting in chronic debilitating functional motor deficits after spinal cord injury. While novel pro-axon growth activators have stimulated plasticity and regeneration of corticospinal neurons (CSNs) after injury, robust functional recovery remains elusive. These repair strategies are sub-optimal in part due to underexplored molecular heterogeneity within the developing and adult CST. In this study, we combine retrograde CST tracing with single-cell RNA sequencing to build a comprehensive atlas of CSN subtypes. By comparing CSNs to non-spinally projecting neurons in layer Vb, we identify pan-CSN markers including Wnt7b. By leveraging retrograde tracing, we are able to compare forelimb and hindlimb projecting CSNs, identifying subtype-specific markers, including Cacng7 and Slc16a2 respectively. These markers are expressed in embryonic and neonatal CSNs and can be used to study early postnatal patterning of the CST. Our results provide molecular insight into the differences between anatomically distinct CSN subtypes and provide a resource for future screening and exploitation of these subtypes to repair the damaged CST after injury and disease.