bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of residue-level filtering, and the Top2018 best-parts dataset of high-quality protein residues
Authors: Williams Christopher J. , Richardson David C. , Richardson Jane S. 
Published: October 2021

AbstractWe have curated a high-quality, “best parts” reference dataset of about 3 million protein residues in about 15,000 PDB-format coordinate files, each containing only residues with good electron density support for a physically acceptable model conformation. The resulting pre-filtered data typically contains the entire core of each chain, in quite long continuous fragments. Each reference file is a single protein chain, and the total set of files were selected for low redundancy, high resolution, good MolProbity score, and other chain-level criteria. Then each residue was critically tested for adequate local map quality to firmly support its conformation, which must also be free of serious clashes or covalent-geometry outliers. The resulting Top2018 pre-filtered datasets have been released on the Zenodo online web service and is freely available for all uses under a Creative Commons license. Currently, one dataset is residue-filtered on mainchain plus Cβ atoms, and a second dataset is full-residue filtered; each is available at 4 different sequence-identity levels. Here, we illustrate both statistics and examples that show the beneficial consequences of residue-level filtering. That process is necessary because even the best of structures contain a few highly disordered local regions with poor density and low-confidence conformations that should not be included in reference data. Therefore the open distribution of these very large, pre-filtered reference datasets constitutes a notable advance for structural bioinformatics and the fields that depend upon it.The Top2018 dataset provides the first representative sample of 3D protein structure for which excellence of experimental data constrains the detailed local conformation to be correct for essentially all 3 million residues included. Earlier generations of residue-filtered datasets were central in developing MolProbity validation used worldwide, and now Zenodo has enabled anyone to use out latest version as a sound basis for structural bioinformatics, protein design, prediction, improving biomedically important structures, or other applications.
Neural networks implicated in autobiographical memory training
Authors: Cȋrneci Dragoş , Onu Mihaela , Papasteri Claudiu C. , Georgescu Dana , Poalelungi Catalina , Sofonea Alexandra , Puşcaşu Nicoleta , Tanase Dumitru , Rădeanu Teofila , Toader Maria-Yaelle , Dogaru Andreea L. , Podină Ioana R. , Berceanu Alexandru I. , Carcea Ioana 
Published: October 2021

AbstractTraining of autobiographical memory has been proposed as intervention to improve cognitive functions. The neural substrates for such improvements are poorly understood. Several brain networks have been previously linked to autobiographical recollections, including the default mode network (DMN) and the sensorimotor network. Here we tested the hypothesis that different neural networks support distinct aspects of memory improvement in response to training on a group of 59 subjects. We found that memory training increases DMN connectivity, and this associates with improved recollection of cue-specific memories. On the contrary, training decreased connectivity in the sensorimotor network, a decrease that correlated with improved ability for voluntary recall. Moreover, only decreased sensorimotor connectivity associated with training-induced decrease in the TNFα immunological factor, which has been previously linked to improved cognitive performance. We identified functional and biochemical factors that associate with distinct memory processes improved by autobiographical training. Pathways which connect autobiographical memory to both high level cognition and somatic physiology are discussed.
A Minimum Perturbation Theory of Deep Perceptual Learning
Authors: Shan Haozhe , Sompolinsky Haim 
Published: October 2021

AbstractPerceptual learning (PL) involves long-lasting improvement in perceptual tasks following extensive training and is accompanied by modified neuronal responses in sensory cortical areas in the brain. Understanding the dynamics of PL and the resultant synaptic changes is important for causally connecting PL to the observed neural plasticity. This is theoretically challenging because learning-related changes are distributed across many stages of the sensory hierarchy. In this work, we modeled the sensory hierarchy as a deep nonlinear neural network and studied PL of fine discrimination, a common and well-studied paradigm of PL. Using tools from statistical physics, we developed a mean-field theory of the network in the limit of large number of neurons and large number of examples. Our theory suggests that, in this “thermodynamic” limit, the input-output function of the network can be exactly mapped to that of a deep linear network, allowing us to characterize the space of solutions for the task. Surprisingly, we found that modifications of synaptic weights in lower levels of the hierarchy are both sufficient and necessary for PL. To address the degeneracy of the space of solutions, we postulate that PL dynamics are constrained by a normative “minimum perturbation” (MP) principle, which favors weight matrices with minimal changes relative to their pre-learning values. Interestingly, MP plasticity induces changes to weights and neural representations in all layers of the network, except for the readout weight vector. In addition, such plasticity can be learned simply through slow learning. We further elucidate the properties of MP changes and compare them against experimental findings. Overall, our statistical mechanics theory of PL provides mechanistic and normative understanding of several important empirical findings of PL.
Improved Ultrasound Localization Microscopy based on Microbubble Uncoupling via Transmit Excitation (MUTE)
Authors: Kim Jihun , Lowerison Mathew R. , Sekaran Nathiya Chandra , Kou Zhengchang , Dong Zhijie , Oelze Michael L. , Llano Daniel A. , Song Pengfei 
Published: October 2021

AbstractUltrasound localization microscopy (ULM) demonstrates great potential for visualization of tissue microvasculature at depth with high spatial resolution. The success of ULM heavily depends on the robust localization of isolated microbubbles (MBs), which can be challenging in vivo especially within larger vessels where MBs can overlap and cluster close together. While MB dilution alleviates the issue of MB overlap to a certain extent, it drastically increases the data acquisition time needed for MBs to populate the microvasculature, which is already on the order of several minutes using recommended MB concentrations. Inspired by optical super-resolution imaging based on stimulated emission depletion (STED), here we propose a novel ULM imaging sequence based on microbubble uncoupling via transmit excitation (MUTE). MUTE “silences” MB signals by creating acoustic nulls to facilitate MB separation, which leads to robust localization of MBs especially under high concentrations. The efficiency of localization accomplished via the proposed technique was first evaluated in simulation studies with conventional ULM as a benchmark. Then an in vivo study based on the chorioallantoic membrane (CAM) of chicken embryos showed that MUTE could reduce the data acquisition time by half thanks to the enhanced MB separation and localization. Finally, the performance of MUTE was validated in an in vivo mouse brain study. These results demonstrate the high MB localization efficacy of MUTE-ULM, which contributes to a reduced data acquisition time and improved temporal resolution for ULM.
Intergenerational transport of double-stranded RNA inC. eleganscan limit heritable epigenetic changes
Authors: Shugarts Nathan , Sathya Aishwarya , Yi Andrew L. , Chan Winnie M. , Marré Julia A. , Jose Antony M. 
Published: October 2021

ABSTRACTRNAs in circulation carry sequence-specific regulatory information between cells in plant, animal, and host-pathogen systems. Such RNA can cross generational boundaries, as evidenced by somatic double-stranded RNA (dsRNA) in the nematodeC. eleganssilencing genes of matching sequence in progeny. Here we dissect the intergenerational path taken by dsRNA from parental circulation and discover that cytosolic import through the dsRNA importer SID-1 in the parental germline and/or developing progeny varies with developmental time and dsRNA substrates. Loss of SID-1 enhances initiation of heritable RNA silencing within the germline and causes changes in the expression of thesid-1-dependentgenesdg-1that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear germ granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop suggests how retrotransposons could persist by hosting genes that regulate their own silencing.
De novoSNP calling reveals the candidate genes regulating days to flowering through interspecies GWAS ofAmaranthusgenus
Authors: Lin Ya-Ping , Wu Tien-Hor , Chan Yan-Kuang , van Zonneveld Maarten , Schafleitner Roland 
Published: October 2021

AbstractAmaranths serve as pseudo cereals and also as traditional leafy vegetables worldwide. In addition to high vigor and richness in nutrients, drought and salinity tolerance of amaranth makes it a promising vegetable to acclimatize to the effects of global climate change. The World Vegetable Center genebank conserves about 1,000 amaranth accessions and various agronomic properties of these accessions were recorded during seed regeneration over decades. In this study, we verified the taxonomic annotation of the germplasm based on a 15K SNP set. Besides, in the assumption that the yield components of grain amaranths are different from those of leaf amaranths, we observed that grain amaranths presented larger inflorescences and earlier flowering than leaf amaranths. Dual-purpose amaranth showed larger leaves than leaf amaranths and later flowering than grain amaranths, which seemed reasonable because farmers can harvest more leaves during the prolonged vegetable stage, which also provides recovery time to enrich grain production. Considering frequent interspecies hybridization among grain amaranth complex, we proposed an interspecies GWAS for days to flowering, identifying aAGL20/SOC1homolog. Meanwhile, another GWAS using onlyA. tricoloraccessions revealed six candidate genes homologous tolba1,bri1,sgs1andfca. These homologous genes were involved in the regulation of flowering time in Arabidopsis. This study revealed the usefulness of genotypes for species demarcation in the genusAmaranthusand the potential of interspecies GWAS to detect QTLs across different species, opening up the possibility of targeted introduction of specific genetic variants into differentAmaranthusspecies.
Cryo-sensitive aggregation triggers NLRP3 inflammasome assembly in cryopyrin-associated periodic syndrome
Authors: Karasawa Tadayoshi , Komada Takanori , Yamada Naoya , Aizawa Emi , Mizushina Yoshiko , Watanabe Sachiko , Baatarjav Chintogtokh , Matsumura Takayoshi , Takahashi Masafumi 
Published: October 2021

AbstractCryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by mutations of NLRP3, which was originally identified as cryopyrin. Familial cold autoinflammatory syndrome (FCAS), the mildest form of CAPS, is characterized by cold-induced inflammation induced by the overproduction of IL-1β. However, the molecular mechanism of how mutated NLRP3 causes inflammasome activation in CAPS remains unclear. Here, we found that CAPS-associated NLRP3 mutants form cryo-sensitive aggregates that function as a scaffold for inflammasome activation. Cold exposure promoted inflammasome assembly and subsequent IL-1β release triggered by mutated NLRP3. While K+ efflux was dispensable, Ca2+ was indispensable for mutated NLRP3-mediated inflammasome assembly. Notably, Ca2+ influx was induced during mutated NLRP3-mediated inflammasome assembly. Furthermore, caspase-1 inhibition prevented Ca2+ influx and inflammasome assembly induced by the mutated NLRP3, suggesting a feed-forward Ca2+ influx loop triggered by mutated NLRP3. Thus, the mutated NLRP3 forms cryo-sensitive aggregates to promote inflammasome assembly distinct from canonical NLRP3 inflammasome activation.
quickBAM: a parallelized BAM file access API for high throughput sequence analysis informatics
Authors: Pitman T. Anders , Huang Xiaomeng , Marth Gabor T. , Qiao Yi 
Published: October 2021

ABSTRACTMotivationIn time-critical clinical settings, such as precision medicine, genomic data needs to be processed as fast as possible to arrive at data-informed treatment decisions in a timely fashion. While sequencing throughput has dramatically increased over the past decade, bioinformatics analysis throughput has not, and consequently has now turned into the primary bottleneck. Modern computational hardware are capable of much higher performance than current genomic informatics algorithms can typically utilize, therefore presenting opportunities for significant improvement of performance. Accessing the raw sequencing data from BAM files, for example, is a necessary and time-consuming step in nearly all sequence analysis tools, however existing programming libraries for BAM access do not take full advantage of the parallel input/output capabilities of storage devices.ResultsIn an effort to stimulate the development of a new generation of faster sequence analysis tools, We developed quickBAM, a software library to accelerate sequencing data access by exploiting the parallelism in commodity storage hardware currently widely available. We demonstrate that analysis software ported to quickBAM consistently outperforms their current versions, in some cases finishing an analysis in under 4 minutes while the original version took 1.5 hours, using the same storage solution.Availability and ImplementationOpen source and freely available athttps://gitlab.com/yiq/quickbam/, we envision that quickBAM will enable a new generation of high performance informatics tools, either directly boosting their performance if they are currently dataaccess bottlenecked, or allow data-access to keep up with further optimizations in algorithms and compute techniques.Contactyi.qiao@genetics.utah.edu.
SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury
Authors: Zhou Biao , Zhou Runhong , Chan Jasper Fuk-Woo , Zeng Jianwei , Zhang Qi , Yuan Shuofeng , Liu Li , Robinot Rémy , Shan Sisi , Ge Jiwan , Kwong Hugo Yat-Hei , Zhou Dongyan , Xu Haoran , Chan Chris Chung-Sing , Poon Vincent Kwok-Man , Chu Hin , Yue Ming , Kwan Ka-Yi , Chan Chun-Yin , Liu Na , Chan Chris Chun-Yiu , Chik Kenn Ka-Heng , Du Zhenglong , Au Ka-Kit , Huang Haode , Man Hiu-On , Cao Jianli , Li Cun , Wang Ziyi , Zhou Jie , Song Youqiang , Yeung Man-Lung , To Kelvin Kai-Wang , Ho David D. , Chakrabarti Lisa A. , Wang Xinquan , Zhang Linqi , Yuen Kwok-Yung , Chen Zhiwei 
Published: October 2021

ABSTRACTRobust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.
The Evolution of Larger Size in High Altitude Drosophila melanogaster has a Polymorphic Genetic Architecture
Authors: Sprengelmeyer Quentin D. , Lack Justin B. , Braun Dylan T. , Monette Matthew J. , Pool John E. 
Published: October 2021

AbstractImportant uncertainties persist regarding the genetic architecture of adaptive trait evolution in natural populations, including the number of genetic variants involved, whether they are drawn from standing genetic variation, and whether directional selection drives them to complete fixation. Here, we take advantage of a unique natural population of Drosophila melanogaster from the Ethiopian highlands, which has evolved larger body size than any other known population of this species. We apply a bulk segregant quantitative trait locus (QTL) mapping approach to four unique crosses between highland Ethiopian and lowland Zambian populations for both thorax length and wing length. Results indicated a persistently variable genetic basis for these evolved traits (with largely distinct sets of QTLs for each cross), and at least a moderately polygenic architecture with relatively strong effects present. We complemented these mapping experiments with population genetic analyses of QTL regions and gene ontology enrichment analysis, generating strong hypotheses for specific genes and functional processes that may have contributed to these adaptive trait changes.Finally, we find that the genetic architectures our QTL mapping results for size traits mirror those from similar experiments on other recently-evolved traits in this species. Collectively, these studies suggest a recurring pattern of polygenic adaptation in this species, in which causative variants do not approach fixation and moderately strong effect loci are present.
Ligands with poly-fluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities
Authors: Anisuzzaman Sharif , Geraskin Ivan M , Ilgu Muslum , Bendickson Lee , Kraus George A , Nilsen-Hamilton Marit 
Published: October 2021

ABSTRACTThe interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand the means by which nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI (3,5-difluoro-4-hydroxybenzylidene imidazolinone) that reach out from the Spinach2 ligand binding pocket. Studies of the interaction of these compounds with the aptamers revealed that poly-fluorophenyl-modified ligands initiate a slow change in aptamer affinity that takes an extended time (half-life of ~40 min) to achieve. The change in affinity appears to involve an initial disruption of the entrance to the ligand binding pocket followed by a gradual lockdown for which the most likely driving force is an interaction of the gateway adenine with a nearby 2’OH group. These results suggest that poly-fluorophenyl modifications might increase the ability of small molecule drugs to disrupt local structure and promote RNA remodeling.
The Effect of Headgear Use on Concussion Injury Rates in High School Lacrosse
Authors: Herman Daniel C. , Caswell Shane V. , Kelshaw Patricia M. , Vincent Heather K. , Lincoln Andrew E. 
Published: October 2021

AbstractObjectivesThe use of headgear is a controversial issue in girls’ lacrosse. We compared concussion rates among high school lacrosse players wearing versus not wearing lacrosse headgear.MethodsStudy participants included a sample of convenience of high schools with girls’ lacrosse from across the United States. Certified athletic trainers reported athlete exposure and injury data via the National Athletic Treatment, Injury and Outcomes Network during the 2019 through 2021 seasons. The Headgear cohort was inclusive of high schools from the state of Florida, which mandate the use of ASTM standard F3137 headgear, while the Non-Headgear cohort was inclusive of the remaining states, none of which have headgear mandates. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were calculated. IRRs with corresponding CIs that excluded 1.00 were deemed statistically significant.Results141 concussions (Headgear: 25; Non-Headgear: 116) and 357,225 Athlete Exposures (AE) were reported (Headgear: 91,074AE; Non-Headgear: 266,151AE) across all games and practices. Overall, the concussion injury rate per 1000AE was significantly higher in the Non-Headgear cohort (0.44) than the Headgear Cohort (0.27) (IRR=1.59, 95% CI:1.03 - 2.45). The IRR was significantly higher for the Non-Headgear cohort during games (1.74, 95% CI: 1.00, 3.02) but not for practices (1.42, 95% CI: 0.71, 2.83).ConclusionsThese findings indicate that concussion rates among high school girls’ lacrosse players not wearing headgear were 59% higher than those wearing headgear. These data support the use of protective headgear to reduce the risk of concussion among high school female lacrosse athletes.SummaryWhat are the new findingsThe use of lacrosse headgear meeting the ASTM F3137 standard was associated with a lower risk of experiencing a concussion injury among high school girls’ lacrosse players.How might these findings impact clinical practice in the future?Lacrosse headgear may be warranted for use for concussion risk mitigation among high school girls’ lacrosse players.Lacrosse headgear may be considered for concussion risk mitigation at other levels of play such as the youth or collegiate levels; further study is warranted.