bluuebunny/crossref_metadata_2025_split huggingface dataset:
epitope1D: Accurate Taxonomy-Aware B-Cell Linear Epitope Prediction
Authors: da Silva Bruna Moreira , Ascher David B. , Pires Douglas E. V. 
Published: October 2022

ABSTRACTThe ability to identify B-cell epitopes is an essential step in vaccine design, immunodiagnostic tests, and antibody production. Several computational approaches have been proposed to identify, from an antigen protein, which residues are likely to be part of an epitope, but have limited performance on relatively homogeneous data sets and lack interpretability, limiting biological insights that could be derived. To address these limitations, we have developed epitope1D, an explainable machine learning method capable of accurately identifying linear B-cell epitopes, leveraging two new descriptors: a graph-based signature representation of protein sequences, based on our well established CSM (Cutoff Scanning Matrix) algorithm and Organism Ontology information. Our model achieved Area Under the ROC curve of up to 0.935 on cross-validation and blind tests, demonstrating robust performance and outperforming state-of-the-art tools. epitope1D has been made available as a user-friendly web server interface and API athttp://biosig.lab.uq.edu.au/epitope1d.
Masked Minimizers: Unifying sequence sketching methods
Authors: Hoang Minh , Marçais Guillaume , Kingsford Carl 
Published: October 2022

AbstractMinimizers and syncmers are sequence sketching methods that extract representative substrings from a long sequence. We show that both these sampling rules are different instantiations of a new unifying concept we call masked minimizers, which applies a sub-sampling binary mask on a minimizer sketch. This unification leads to the first formal procedure to meaningfully compare minimizers, syncmers and other comparable masked minimizers. We further demonstrate that existing sequence sketching metrics, such as density (which measures the sketch sparseness) and conservation (which measures the likelihood of the sketch being preserved under random mutations), should not be independently measured when evaluating masked minimizers. We propose a new metric that reflects the trade-off between these quantities called the generalized sketch score, or GSS. Finally, we introduce a sequence-specific and gradient-based learning objective that efficiently optimizes masked minimizer schemes with respect to the proposed GSS metric. We show that our method finds sketches with better overall density and conservation compared to existing expected and sequence-specific approaches, enabling more efficient and robust genomic analyses in the many settings where minimizers and syncmers are used.
Expected Distractor Context Biases the Attentional Template for Target Shapes
Authors: Lerebourg Maëlle , Lange Floris P. de , Peelen Marius V. 
Published: October 2022

AbstractVisual search is supported by an internal representation of the target, the attentional template. However, which features are diagnostic of target presence critically depends on the distractors. Accordingly, previous research showed that consistent distractor context shapes the attentional template for simple targets, with the template emphasizing diagnostic dimensions (e.g., colour or orientation) in blocks of trials. Here, we investigated how distractor expectations bias attentional templates for complex shapes, and tested whether such biases reflect inter-trial priming or can be instantiated flexibly. Participants searched for novel shapes (cued by name) in two probabilistic distractor contexts: either the target’s orientation or rectilinearity was unique (80% validity). Across four experiments, performance was better when the distractor context was expected, indicating that target features in the expected diagnostic dimension were emphasized. Attentional templates were biased by distractor expectations when distractor context was blocked, also for participants reporting no awareness of the manipulation. Interestingly, attentional templates were also biased when distractor context was cued on a trial-by-trial basis, but only when the two contexts were consistently presented at distinct spatial locations. These results show that attentional templates can flexibly and adaptively incorporate expectations about target-distractor relations when looking for the same object in different contexts.Public significance statementWhen searching for an object (e.g., a green ball), the visual features that distinguish it from distractor objects depend on the features of these distractors (e.g., when searching among plants, its green colour is not useful to find the target). Here, we asked participants to search for novel shapes in contexts where different dimensions of the shapes were unique. We show that people learn which features are diagnostic in these distractor contexts and flexibly use expectations about the features that are diagnostic of the target to efficiently guide search.
Menopause, Brain Anatomy, Cognition and Alzheimer’s Disease
Authors: Costantino Manuela , Pigeau Grace , Parent Olivier , Ziolkowski Justine , Devenyi Gabriel A. , Gervais Nicole J. , Mallar Chakravarty M. 
Published: October 2022

AbstractThe menopause transition has been repeatedly associated with decreased cognitive performance and increased incidence of Alzheimer’s Disease (AD), particularly when it is induced surgically1,2or takes place at a younger age3,4. However, there are very few studies that use neuroimaging techniques to examine the effects of these variables in aggregate and in a large sample. Here, we use data from thousands of participants from the UK Biobank to assess the relationship between menopausal status, menopause type (surgical or natural), and age at menopause with cognition, AD, and neuroanatomical measures derived from magnetic resonance imaging. We find that for brain and cognitive measures, menopausal status, menopause type and age at surgical menopause do not impact the brain; but that there is a positive correlation between anatomy, cognition and age at non-surgical menopause. These results do not align with previous reports in the literature with smaller samples. However, we confirm that both early and surgical menopause are associated with a higher risk of developing AD, indicating that early and abrupt ovarian hormone deprivation might contribute to the development of the disorder.
Mora: abundance aware metagenomic read re-assignment for disentangling similar strains
Authors: Zheng Andrew , Shaw Jim , Yu Yun William 
Published: October 2022

AbstractBackgroundTaxonomic classification of reads obtained by metagenomic sequencing is often a first step for understanding a microbial community, but correctly assigning sequencing reads to the strain or sub-species level has remained a challenging computational problem.ResultsWe introduce Mora, a MetagenOmic read Re-Assignment algorithm capable of assigning short and long metagenomic reads with high precision, even at the strain level. Mora is able to accurately re-assign reads by first estimating abundances through an expectation-maximization algorithm and then utilizing abundance information to re-assign query reads. The key idea behind Mora is to maximize read re-assignment qualitieswhile simultaneouslyminimizing the difference from estimated abundance levels, allowing Mora to avoid over assigning reads to the same genomes. On simulated diverse reads, this allows Mora to achieve F1 scores comparable to other algorithms while having less runtime. However, Mora significantly outshines other algorithms on very similar reads. We show that the high penalty of over assigning reads to a common reference genome allows Mora to accurately infer correct strains for real data in the form of short E. coli reads and long Covid-19 reads.ConclusionsMora is a fast and accurate read re-assignment algorithm that is modularized, allowing it to be incorporated into general metagenomics and genomics workflows. It is freely available athttps://github.com/AfZheng126/MORA.
NEMETEX: a Python software for the visualisation of the network of metabolic exchanges
Authors: Palamin Michela , Frisinghelli Alice , Offer Elisabetta , Zampieri Guido , Basile Arianna , Campanaro Stefano 
Published: October 2022

SummaryMotivationMicroorganisms have a pivotal role in ecology and human health and form complex networks where different species can interact and exchange a range of different compounds. Flux balance analysis can offer an insight into the production and the absorption of these metabolic compounds, but frequently results are difficult to visualise and interpret. Additionally, a clear understanding of the roles of microbial species in the community requires the integration of different information sources, including relative abundance, taxonomy and compounds exchange rate.ResultsTo fill-in this gap the command-line tool NEMETEX (NEtwork for METabolic Exchanges) was developed to provide a graphical representation of the metabolites exchanged, joined with interactive visualisation of numerical data. This approach can undoubtedly represent an easy way to investigate high-throughput results obtained from metagenomics and flux balance analysis, providing a more direct interpretation of the data.Availability and implementationThis program, accessory utilities, and their documentation are freely available athttps://github.com/palakela/NEMETEX
Neural Representation of The Self
Authors: Levorsen Marie , Aoki Ryuta , Matsumoto Kenji , Sedikides Constantine , Izuma Keise 
Published: October 2022

AbstractKnowledge about one’s personality, the self-concept, shapes human experience. Social cognitive neuroscience has made strides addressing the question of where and how the self is represented in the brain. The answer, however, remains elusive. We conducted two functional magnetic resonance imaging experiments (with the second being preregistered) employing a self-reference task with a broad range of attributes and carrying out a searchlight representational similarity analysis. The importance of attributes to self-identity was represented in the medial prefrontal cortex (mPFC), whereas mPFC activation was unrelated both to self-descriptiveness of attributes (Experiments 1-2) and importance of attributes to a friend’s self-identity (Experiment 2). Our research provides a comprehensive answer to the abovementioned question: The self-concept is conceptualized in terms of self-importance and represented in the mPFC.
Novel Master Regulators of Microglial Phagocytosis and Repurposed FDA-approved Drug for Treatment of Alzheimer Disease
Authors: Zhu Kuixi , He Qianying , Tsai Sheng-Feng , Mudalige Dinusha Maheepala , Henrion Marc Y.R. , Zaidi Syed S.A. , Branden Lau , Tang Andrew , Cadiz Mika P. , Hodos-Nkhereanye Rachel , Moein Sara , Alamprese Melissa L. , Bennett David A. , De Jager Philip L. , Frye John D. , Ertekin-Taner Nilu□fer , Kuo Yu-Min , Ronaldson Patrick T. , Chang Rui 
Published: October 2022

SummaryMicroglia, the innate immune cells of the brain, are essential determinants of late-onset Alzheimer’s Disease (LOAD) neuropathology. Here, we developed an integrative computational systems biology approach to construct causal network models of genetic regulatory programs for microglia in Alzheimer’s Disease (AD). This model enabled us to identify novel key driver (KDs) genes for microglial functions that can be targeted for AD pharmacotherapy. We prioritizedFCER1G, HCK, LAPTM5, ITGB2, SLC1A2, PAPLN, GSAP, NTRK2, andCIRBPas KDs of microglial phagocytosis promoting neuroprotection and/or neural repair.In vitro, shRNA knockdown of each KD significantly reduced microglial phagocytosis. We repurposed riluzole, an FDA-approved ALS drug that upregulatesSLC1A2activity, and discovered that it stimulated phagocytosis of Aβ1-42 in human primary microglia and decreased hippocampal amyloid plaque burden/phosphorylated tau levels in the brain of aged 3xTg-AD mice. Taken together, these data emphasize the utlility of our integrative approach for repurposing drugs for AD therapy.
Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing and alters beta cell identity in mice
Authors: Chen Yi-Chun , Taylor Austin J. , Fulcher James M. , Swensen Adam C. , Dai Xiao-Qing , Komba Mitsuhiro , Wrightson Kenzie L.C. , Fok Kenny , Patterson Annette E. , Klein-Geltink Ramon I. , MacDonald Patrick E. , Qian Wei-Jun , Verchere C. Bruce 
Published: October 2022

AbstractCarboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers ofCPEmutations have elevated plasma proinsulin and develop severe obesity and hyperglycemia. We aimed to determine whether loss ofCpein pancreatic beta cells disrupts proinsulin processing and accelerates development of diabetes and obesity in mice. Pancreatic beta cell-specific Cpe knockout mice (βCpeKO;Cpefl/flxIns1Cre/+) lack mature insulin granules and have elevated proinsulin in plasma; however, glucose-and KCl-stimulated insulin secretion in βCpeKO islets remained intact. High fat diet-fed βCpeKO mice showed comparable weight gain and glucose tolerance compared toWtlittermates. Notably, beta-cell area was increased in chow-fed βCpeKO mice and beta-cell replication was elevated in βCpeKO islets. Transcriptomic analysis of βCpeKO beta cells revealed elevated glycolysis andHif1α-target gene expression. Upon high glucose challenge, beta cells from βCpeKO mice showed reduced mitochondrial membrane potential, increased reactive oxygen species, reducedMafA, and elevatedAldh1a3transcript levels. Following multiple low-dose streptozotocin treatment, βCpeKO mice had accelerated hyperglycemia with reduced beta-cell insulin and Glut2 expression. These findings suggest thatCpeand proper proinsulin processing are critical in maintaining beta cell function during the development of diabetes.
Specific and non-uniform brain states during cold perception in mice
Authors: Koorliyil Haritha , Sitt Jacobo , Rivals Isabelle , Liu Yushan , Cazzanelli Silvia , Bertolo Adrien , Dizeux Alexandre , Deffieux Thomas , Tanter Mickael , Pezet Sophie 
Published: October 2022

ABSTRACTThe quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamo-cortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of awake and freely-moving mice using Functional Ultrasound imaging during plantar exposure to constant and varying temperatures. Our study, a synchronous large field investigation of mice brains reveals for the first time the brain states and the specific dynamic interplay between key regions involved in thermal processing. Our study reveals: i) a dichotomy in the response of the somato-motor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. ii) We infer that cingulate areas may be involved in the affective responses to temperature changes. iii) Colder temperatures (ramped down) reinforces the disconnection between the somato-motor-cingulate and hypothalamus networks. iv) Finally, we also confirm the existence in the mouse brain of a dynamic brain mode characterized by low cognitive strength, described previously only in non-human primates and humans. The present study points towards the existence of a common hub between somato-motor and cingulate regions, whereas hypothalamus functions are related to a secondary network.
The GPI-anchored Ly6 protein Belly roll regulatesDrosophila melanogasterescape behaviors by modulating the excitability of nociceptive peptidergic interneurons
Authors: Li Kai , Tsukasa Yuma , Kurio Misato , Maeta Kaho , Tsumadori Akimitsu , Baba Shumpei , Nishimura Risa , Murakami Akira , Onodera Koun , Morimoto Takako , Uemura Tadashi , Usui Tadao 
Published: October 2022

SummaryAppropriate modulation of escape behaviors in response to potentially damaging stimuli is essential for survival. Although nociceptive circuitry has been studied, it is poorly understood how genetic contexts affect the relevant escape responses. Using an unbiased genome-wide association analysis, we identified a Ly6/α-neurotoxin family protein, Belly roll (Bero), which negatively regulatesDrosophilanociceptive escape behavior. We show that Bero is expressed in abdominal leucokinin-producing neurons (ABLK neurons) andberoknockdown in ABLK neurons resulted in enhanced escape behavior. Furthermore, we demonstrated that ABLK neurons responded to the activation of nociceptors and initiated the behavior. Notably,beroknockdown reduced the persistent neuronal activity and increased the evoked nociceptive responses in ABLK neurons. Our findings reveal that Bero modulates an escape response by regulating distinct neuronal activities in ABLK neurons.
Characterizing Eastern spruce budworm’s large-scale dispersal events through flight behavior and stable isotope analyses
Authors: Dargent F. , Candau J.N. , Studens K. , Perrault K.H. , Reich M.S. , Bataille C.P. 
Published: October 2022

AbstractEastern spruce budworm moth (Choristoneura fumiferana(Clem.)) mass outbreaks have widespread economic and ecological consequences. A key explanation for the large-scale spread and synchronization of these outbreaks is the long-distance dispersal (up to 450km) of moths from hotspots (high-density populations) to lower-density areas. These events have proved difficult to monitor because dispersal flights occur only a few times a year, have no consistent routes, and commonly used tracking methods (e.g., population genetics, mark-recapture, radio telemetry) are inadequate for this system. Distinguishing between local and immigrant individuals is a crucial step in identifying the physical and ecological drivers of moth dispersal. Here we test whether isotopes of hydrogen (i.e., delta notation:δ2H) and strontium (i.e., strontium isotope ratios:87Sr/86Sr), known to independently vary in space in a predictable manner, can be used to distinguish between local and immigrant adult spruce budworm moths. We used an automated pheromone trap system to collect individuals at six different sites in eastern Canada within and outside the current outbreak area of budworm moths. We first use moth flight behaviour and time of capture, currently the best available tool, to determine putative local vs. immigrant status, and then evaluate whether individual87Sr/86Sr andδ2H differ between putative classes. At all sites, we detect immigrant individuals that differ significantly from putative locals. Saliently, sites where putative locals were sampled before the occurrence of potential immigration events (~10 days) showed the strongest differences between immigrant individuals and the locals87Sr/86Sr andδ2H values. Sites where the collection of putative locals was close in time (hours) or following an immigration event had a less-clear distinction between putative immigrants and locals, and showed signs of mixing between these two groups. We speculate that recent immigration could have led to the misclassification of immigrants as putative locals.87Sr/86Sr andδ2H data generally support the adequacy of current approaches using capture-time to detect immigration events, and provide enhanced resolution to distinguish between local and immigrant individuals. We discuss the broader implication of adding isotopes to the toolkit to monitor spruce budworm dispersal and suggest next steps in implementing these tools.
PHF1 compartmentalizes PRC2 at target loci via phase separation
Authors: Lu Genzhe , Li Pilong 
Published: October 2022

AbstractPolycomb repressive complex 2 (PRC2) is central to polycomb repression as it trimethylates lysine 27 on histone H3 (H3K27me3). How PRC2 is recruited to its targets to deposit H3K27me3 remains an open question. Polycomb-like (PCL) proteins, a group of conserved PRC2 accessory proteins, direct PRC2 to its targets. In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated condensates at H3K27me3 loci that recruit PRC2. Combining cellular observation and biochemical reconstitution, we show that the N-terminal domains of PHF1 cooperatively mediate target recognition, the chromo-like domain recruits PRC2, and the intrinsically disordered region (IDR) drives phase separation. Moreover, we reveal that the condensates compartmentalize PRC2, DNA, and nucleosome arrays by phase separation. Luciferase reporter assays confirm that PHF1 phase separation promotes transcription repression, further supporting a role of the condensates in polycomb repression. Based on our findings, we propose that these condensates create favorable microenvironments at the target loci for PRC2 to function.
Comparison of DNA targeting CRISPR editors in human cells
Authors: Huang Hongxin , Lv Weiqi , Li Jinhe , Huang Guanjie , Tan Zhihong , Hu Yongfei , Ma Shufeng , Zhang Xin , Huang Linxuan , Lin Ying 
Published: October 2022

AbstractProfiling and comparing the performance of current widely used DNA targeting CRISPR systems provide the basic information for the gene-editing toolkit and can be a useful resource for this field. Herein we made a parallel comparison between the recently reported miniature Cas12f1 and the widely used Cas12a and Cas9 nucleases in mammalian cells. The results revealed that as a CRISPRa activator, Un1Cas12f1 could induce gene expression with a comparable level to these of Cas12a and Cas9, while as a cleaving editor, Cas12f1 exhibited similar properties to Cas12a, like high specificity and dominantly induced deletions over insertions, but with less activity. In contrast, wild-type SpCas9 showed the highest activity, lowest specificity, and induced balanced deletions over insertions. Thus, Cas12f1 is recommended for gene-activation-based applications, Cas12a is for therapy applications, and wild-type Cas9 is forin vitroand animal investigations. The comparison provided the editing properties of current widely used DNA-targeting CRISPR systems for the gene-editing field.