bluuebunny/crossref_metadata_2025_split huggingface dataset:
CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity
Authors: Zhang Linlin , Sheng Chunxiang , Zhou Feiye , Zhu Kecheng , Wang Shushu , Liu Qianqian , Yuan Miaomiao , Xu Zhaoqian , Liu Yun , Lu Jieli , Liu Jianmin , Zhou Libin , Wang Xiao 
Published: May 2021

AbstractLoss of β cell identity and functional immaturity are thought to be involved in β cell failure in type 2 diabetes. CREB-binding protein (CBP) and its paralogue p300 act as multifunctional transcriptional co-activators and histone acetyltransferases (HAT) with extensive biological functions. However, whether the regulatory role of CBP/p300 in islet β cell function depends on the HAT activity remains uncertain. In this current study, A-485, a selective inhibitor of CBP/p300 HAT activity, greatly impaired glucose-stimulated insulin secretion from rat islets in vitro and in vivo. RNA-sequencing analysis showed a comprehensive downregulation of β cell and α cell identity genes in A-485-treated islets, without upregulation of dedifferentiation markers and derepression of disallowed genes. A-485 treatment decreased the expressions of genes involved in glucose sensing, not in glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. In the islets of prediabetic db/db mice, CBP/p300 displayed a significant decrease with key genes for β cell function. The deacetylation of histone H3K27 as well as the transcription factors Hnf1α and Foxo1 was involved in CBP/p300 HAT inactivation-repressed expressions of β cell identity and functional genes. These findings highlight the dominant role of CBP/p300 HAT in the maintenance of β cell identity by governing transcription network.
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
Authors: Dixit Updesh , Bhutoria Savita , Wu Xuhong , Qiu Liming , Spira Menachem , Mathew Sheeba , Harris Richard , Adams Lucas J. , Cahill Sean , Pathak Rajiv , Rajesh Kumar P. , Nguyen Minh , Acharya Seetharama A. , Brenowitz Michael , Almo Steven C. , Zou Xiaoqin , Steven Alasdair C. , Cowburn David , Girvin Mark , Kalpana Ganjam V. 
Published: May 2021

AbstractINI1/SMARCB1 binds to HIV-1 integrase (IN) through its Rpt1 domain and exhibits multifaceted role in HIV-1 replication. Determining the NMR structure of INI1-Rpt1 and modeling its interaction with the IN-C-terminal domain (IN-CTD) reveal that INI1-Rpt1/IN-CTD interface residues overlap with those required for IN/RNA interaction. Mutational analyses validate our model and indicate that the same IN residues are involved in both INI1 and RNA binding. INI1-Rpt1 and TAR RNA compete with each other for IN binding with similar IC50 values. INI1-interaction-defective IN mutant viruses are impaired for incorporation of INI1 into virions and for particle morphogenesis. Computational modeling of IN-CTD/TAR complex indicates that the TAR interface phosphates overlap with negatively charged surface residues of INI1-Rpt1 in three-dimensional space, suggesting that INI1-Rpt1 domain structurally mimics TAR. This possible mimicry between INI1-Rpt1 and TAR explains the mechanism by which INI1/SMARCB1 influences HIV-1 late events and suggests additional strategies to inhibit HIV-1 replication.
Estimating COVID-19 mortality in Italy early in the COVID-19 pandemic
Authors: Modi Chirag , Böhm Vanessa , Ferraro Simone , Stein George , Seljak Uroš 
Published: May 2021

AbstractEstimating rates of COVID-19 infection and associated mortality is challenging due to uncertainties in case ascertainment. We perform a counterfactual time series analysis on overall mortality data from towns in Italy, comparing the population mortality in 2020 with previous years, to estimate mortality from COVID-19. We find that the number of COVID-19 deaths in Italy in 2020 until September 9 was 59,000–62,000, compared to the official number of 36,000. The proportion of the population that died was 0.29% in the most affected region, Lombardia, and 0.57% in the most affected province, Bergamo. Combining reported test positive rates from Italy with estimates of infection fatality rates from the Diamond Princess cruise ship, we estimate the infection rate as 29% (95% confidence interval 15–52%) in Lombardy, and 72% (95% confidence interval 36–100%) in Bergamo.
Extensive introgression and mosaic genomes of Mediterranean endemic lizards
Authors: Yang Weizhao , Feiner Nathalie , Pinho Catarina , While Geoffrey M. , Kaliontzopoulou Antigoni , Harris D. James , Salvi Daniele , Uller Tobias 
Published: May 2021

AbstractThe Mediterranean basin is a hotspot of biodiversity, fuelled by climatic oscillation and geological change over the past 20 million years. Wall lizards of the genusPodarcisare among the most abundant, diverse, and conspicuous Mediterranean fauna. Here, we unravel the remarkably entangled evolutionary history of wall lizards by sequencing genomes of 34 major lineages covering 26 species. We demonstrate an early (>11 MYA) separation into two clades centred on the Iberian and Balkan Peninsulas, and two clades of Mediterranean island endemics. Diversification within these clades was pronounced between 6.5–4.0 MYA, a period spanning the Messinian Salinity Crisis, during which the Mediterranean Sea nearly dried up before rapidly refilling. However, genetic exchange between lineages has been a pervasive feature throughout the entire history of wall lizards. This has resulted in a highly reticulated pattern of evolution across the group, characterised by mosaic genomes with major contributions from two or more parental taxa. These hybrid lineages gave rise to several of the extant species that are endemic to Mediterranean islands. The mosaic genomes of island endemics may have promoted their extraordinary adaptability and striking diversity in body size, shape and colouration, which have puzzled biologists for centuries.
Colossal topological Hall effect at the transition between isolated and lattice-phase interfacial skyrmions
Authors: Raju M. , Petrović A. P. , Yagil A. , Denisov K. S. , Duong N. K. , Göbel B. , Şaşıoğlu E. , Auslaender O. M. , Mertig I. , Rozhansky I. V. , Panagopoulos C. 
Published: May 2021

AbstractThe topological Hall effect is used extensively to study chiral spin textures in various materials. However, the factors controlling its magnitude in technologically-relevant thin films remain uncertain. Using variable-temperature magnetotransport and real-space magnetic imaging in a series of Ir/Fe/Co/Pt heterostructures, here we report that the chiral spin fluctuations at the phase boundary between isolated skyrmions and a disordered skyrmion lattice result in a power-law enhancement of the topological Hall resistivity by up to three orders of magnitude. Our work reveals the dominant role of skyrmion stability and configuration in determining the magnitude of the topological Hall effect.
Landscape of allele-specific transcription factor binding in the human genome
Authors: Abramov Sergey , Boytsov Alexandr , Bykova Daria , Penzar Dmitry D. , Yevshin Ivan , Kolmykov Semyon K. , Fridman Marina V. , Favorov Alexander V. , Vorontsov Ilya E. , Baulin Eugene , Kolpakov Fedor , Makeev Vsevolod J. , Kulakovskiy Ivan V. 
Published: May 2021

AbstractSequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.
Spectroscopy of a tunable moiré system with a correlated and topological flat band
Authors: Liu Xiaomeng , Chiu Cheng-Li , Lee Jong Yeon , Farahi Gelareh , Watanabe Kenji , Taniguchi Takashi , Vishwanath Ashvin , Yazdani Ali 
Published: May 2021

AbstractMoiré superlattices created by the twisted stacking of two-dimensional crystals can host electronic bands with flat energy dispersion in which enhanced interactions promote correlated electron states. The twisted double bilayer graphene (TDBG), where two Bernal bilayer graphene are stacked with a twist angle, is such a moiré system with tunable flat bands. Here, we use gate-tuned scanning tunneling spectroscopy to directly demonstrate the tunability of the band structure of TDBG with an electric field and to show spectroscopic signatures of electronic correlations and topology for its flat band. Our spectroscopic experiments are in agreement with a continuum model of TDBG band structure and reveal signatures of a correlated insulator gap at partial filling of its isolated flat band. The topological properties of this flat band are probed with the application of a magnetic field, which leads to valley polarization and the splitting of Chern bands with a large effective g-factor.
A stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration
Authors: Mitoyan Louciné , Chevrier Véronique , Hernandez-Vargas Hector , Ollivier Alexane , Homayed Zeinab , Pannequin Julie , Poizat Flora , De Biasi-Cador Cécile , Charafe-Jauffret Emmanuelle , Ginestier Christophe , Guasch Géraldine 
Published: May 2021

AbstractAt numerous locations of the body, transition zones are localized at the crossroad between two types of epithelium and are frequently associated with neoplasia involving both type of tissues. These transition zones contain cells expressing markers of adult stem cells that can be the target of early transformation. The mere fact that transition zone cells can merge different architecture with separate functions implies for a unique plasticity that these cells must display in steady state. However, their roles during tissue regeneration in normal and injured state remain unknown. Here, by using in vivo lineage tracing, single-cell transcriptomics, computational modeling and a three-dimensional organoid culture system of transition zone cells, we identify a population of Krt17+ basal cells with multipotent properties at the squamo-columnar anorectal junction that maintain a squamous epithelium during normal homeostasis and can participate in the repair of a glandular epithelium following tissue injury.
Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling
Authors: Kim Young-Mee , Krantz Sarah , Jambusaria Ankit , Toth Peter T. , Moon Hyung-Geun , Gunarathna Isuru , Park Gye Young , Rehman Jalees 
Published: May 2021

AbstractEndothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as β-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell–cell adherens junctions and by binding to the transcriptional activator β-catenin.
Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease
Authors: Chen Chun , McDonald David , Blain Alasdair , Sachdeva Ashwin , Bone Laura , Smith Anna L. M. , Warren Charlotte , Pickett Sarah J. , Hudson Gavin , Filby Andrew , Vincent Amy E. , Turnbull Doug M. , Reeve Amy K. 
Published: May 2021

AbstractHere we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.
Eye movements in patients in early psychosis with and without a history of cannabis use
Authors: Sami Musa Basseer , Annibale Luciano , O’Neill Aisling , Collier Tracy , Onyejiaka Chidimma , Eranti Savitha , Das Debasis , Kelbrick Marlene , McGuire Philip , Williams Steve C. R. , Rana Anas , Ettinger Ulrich , Bhattacharyya Sagnik 
Published: May 2021

AbstractIt is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p < 0.001), patient effect (χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76–0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.
Superior haplotypes towards development of low glycemic index rice with preferred grain and cooking quality
Authors: Selvaraj Ramchander , Singh Arun Kumar , Singh Vikas Kumar , Abbai Ragavendran , Habde Sonali Vijay , Singh Uma Maheshwar , Kumar Arvind 
Published: May 2021

AbstractIncreasing trends in the occurrence of diabetes underline the need to develop low glycemic index (GI) rice with preferred grain quality. In the current study, a diverse set of 3 K sub-panel of rice consisting of 150 accessions was evaluated for resistant starch and predicted glycemic index, including nine other quality traits under transplanted situation. Significant variations were noticed among the accessions for the traits evaluated. Trait associations had shown that amylose content possess significant positive and negative association with resistant starch and predicted glycemic index. Genome-wide association studies with 500 K SNPs based on MLM model resulted in a total of 41 marker-trait associations (MTAs), which were further confirmed and validated with mrMLM multi-locus model. We have also determined the allelic effect of identified MTAs for 11 targeted traits and found favorable SNPs for 8 traits. A total of 11 genes were selected for haplo-pheno analysis to identify the superior haplotypes for the target traits where haplotypes ranges from 2 (Os10g0469000-GC) to 15 (Os06g18720-AC). Superior haplotypes for RS and PGI, the candidate gene Os06g11100 (H4-3.28% for high RS) and Os08g12590 (H13-62.52 as intermediate PGI). The identified superior donors possessing superior haplotype combinations may be utilized in Haplotype-based breeding to developing next-generation tailor-made high quality healthier rice varieties suiting consumer preference and market demand.
Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
Authors: Fujita Yu , Kano Kuniyuki , Kishino Shigenobu , Nagao Toshihiro , Shen Xuefeng , Sato Chiharu , Hatakeyama Hatsune , Ota Yume , Niibori Sho , Nomura Ayako , Kikuchi Kota , Yasuno Wataru , Takatori Sho , Kikuchi Kazunori , Sano Yoshitake , Tomita Taisuke , Suzuki Toshiharu , Aoki Junken , Zou Kun , Natori Shunji , Komano Hiroto 
Published: May 2021

AbstractConjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.
Computer-aided autism diagnosis based on visual attention models using eye tracking
Authors: Oliveira Jessica S. , Franco Felipe O. , Revers Mirian C. , Silva Andréia F. , Portolese Joana , Brentani Helena , Machado-Lima Ariane , Nunes Fátima L. S. 
Published: May 2021

AbstractAn advantage of using eye tracking for diagnosis is that it is non-invasive and can be performed in individuals with different functional levels and ages. Computer/aided diagnosis using eye tracking data is commonly based on eye fixation points in some regions of interest (ROI) in an image. However, besides the need for every ROI demarcation in each image or video frame used in the experiment, the diversity of visual features contained in each ROI may compromise the characterization of visual attention in each group (case or control) and consequent diagnosis accuracy. Although some approaches use eye tracking signals for aiding diagnosis, it is still a challenge to identify frames of interest when videos are used as stimuli and to select relevant characteristics extracted from the videos. This is mainly observed in applications for autism spectrum disorder (ASD) diagnosis. To address these issues, the present paper proposes: (1) a computational method, integrating concepts of Visual Attention Model, Image Processing and Artificial Intelligence techniques for learning a model for each group (case and control) using eye tracking data, and (2) a supervised classifier that, using the learned models, performs the diagnosis. Although this approach is not disorder-specific, it was tested in the context of ASD diagnosis, obtaining an average of precision, recall and specificity of 90%, 69% and 93%, respectively.
Great tits who remember more accurately have difficulty forgetting, but variation is not driven by environmental harshness
Authors: Hermer Ethan , Murphy Ben , Chaine Alexis S. , Morand-Ferron Julie 
Published: May 2021

AbstractThe causes of individual variation in memory are poorly understood in wild animals. Harsh environments with sparse or rapidly changing food resources are hypothesized to favour more accurate spatial memory to allow animals to return to previously visited patches when current patches are depleted. A potential cost of more accurate spatial memory is proactive interference, where accurate memories block the formation of new memories. This relationship between spatial memory, proactive interference, and harsh environments has only been studied in scatter-hoarding animals. We compare spatial memory accuracy and proactive interference performance of non-scatter hoarding great tits (Parus major) from high and low elevations where harshness increases with elevation. In contrast to studies of scatter-hoarders, we did not find a significant difference between high and low elevation birds in their spatial memory accuracy or proactive interference performance. Using a variance partitioning approach, we report the first among-individual trade-off between spatial memory and proactive interference, uncovering variation in memory at the individual level where selection may act. Although we have no evidence of harsh habitats affecting spatial memory, our results suggest that if elevation produced differences in spatial memory between elevations, we could see concurrent changes in how quickly birds can forget.