bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Genome Assembly and Annotation of Northern Wild Rice,Zizania palustrisL., Supports a Whole Genome Duplication in theZizaniaGenus
Authors: Haas Matthew , Kono Thomas , Macchietto Marissa , Millas Reneth , McGilp Lillian , Shao Mingqin , Duquette Jacques , Hirsch Candice N. , Kimball Jennifer 
Published: March 2021

ABSTRACTNorthern Wild Rice (NWR;Zizania palustrisL.) is an aquatic grass native to North America that is notable for its nutritious grain. This is an important species with ecological, cultural, and agricultural significance, specifically in the Great Lakes region of the United States. Using long- and short-range sequencing, Hi-C scaffolding, and RNA-seq data from eight tissues, we generated an annotated whole genomede novoassembly of NWR. The assembly is 1.29 Gb, highly repetitive (∼76.0%), and contains 46,421 putative protein-coding genes. The expansion of retrotransposons within the genome and a whole genome duplication prior to theZizania-Oryzaspeciation event have both led to an increase in genome size of NWR in comparison withO. sativaandZ. latifolia. Both events depict a genome rapidly undergoing change over a short evolutionary time. Comparative analyses revealed conservation of large syntenic blocks withOryza sativaL., which were used to identify putative seed shattering genes. Estimates of divergence times revealed theZizaniagenus diverged fromOryza∼26-30 million years ago (MYA), while NWR andZizania latifoliadiverged from one another ∼6-8 MYA. Comparative genomics confirmed evidence of a whole genome duplication in theZizaniagenus and provided support that the event was prior to the NWR-Z. latifoliaspeciation event. This high-quality genome assembly and annotation provides a valuable resource for comparative genomics in the Oryzeae tribe and provides an important resource for future conservation and breeding efforts of NWR.
Environmental, structural and taxonomic diversity factors drive aboveground carbon stocks in a semi-deciduous tropical rainforest strata in Cameroon
Authors: Zekeng Jules Christian , van der Sande Masha T. , Fobane Jean Louis , Sebego Reuben , Mphinyane Wanda N. , Ebanga Paul André , Mbolo Marguerite Marie Abada 
Published: March 2021

AbstractTropical forests play an important role in biodiversity conservation and ecosystem functioning. Few studies have teased apart the independent effects of biotic and abiotic factors on aboveground carbon across tree size groups and the whole tree community level in a tropical semi-deciduous rainforest. This study aims to analyze the relative and independent effects of abiotic (topography, soil fertility/texture and disturbance) and biotic factors on carbon stocks across tree size groups, as well as at the whole tree community in semi-deciduous plots, including logged plots.We used data from 30 1-ha plots and 22,064 trees distributed in a semi-deciduous tropical rainforest of Cameroon. For each plot, we quantified disturbance, topography and eleven soil conditions. Besides, we quantified three taxonomic richness and diversity Gini index. We used structural equation models to test the hypothesis that all drivers have independent, positive effects on aboveground carbon stocks across tree-sized groups and the whole tree community.The logging disturbance decreased aboveground carbon stocks for the whole tree community and trees size groups across our site except for large trees. Topographical factors (i.e., slope and elevation) increased aboveground carbon (AGC) of the whole tree community and the large trees. In contrast, soil nitrogen (Nsoil) and clay proportion increased AGC of the small stems and understorey trees groups. This study found that biotics factors have some indirect and direct effects on AGC. Taxonomic diversity through niche complementarity had a positive relationship with aboveground carbon stocks across the trees size groups and the whole tree community, while diversity Gini index had strongest relationships with aboveground carbon stocks.The significant effects of structural diversity on aboveground carbon stocks of the whole tree community, large trees, and understory trees highlight the importance of maintaining a layered structure and tall trees in the forest.
Comparison of domain adaptation techniques for white matter hyperintensity segmentation in brain MR images
Authors: Sundaresan Vaanathi , Zamboni Giovanna , Dinsdale Nicola K. , Rothwell Peter M. , Griffanti Ludovica , Jenkinson Mark 
Published: March 2021

AbstractRobust automated segmentation of white matter hyperintensities (WMHs) in different datasets (domains) is highly challenging due to differences in acquisition (scanner, sequence), population (WMH amount and location) and limited availability of manual segmentations to train supervised algorithms. In this work we explore various domain adaptation techniques such as transfer learning and domain adversarial learning methods, including domain adversarial neural networks and domain unlearning, to improve the generalisability of our recently proposed triplanar ensemble network, which is our baseline model. We evaluated the domain adaptation techniques on source and target domains consisting of 5 different datasets with variations in intensity profile, lesion characteristics and acquired using different scanners. For transfer learning, we also studied various training options such as minimal number of unfrozen layers and subjects required for finetuning in the target domain. On comparing the performance of different techniques on the target dataset, unsupervised domain adversarial training of neural network gave the best performance, making the technique promising for robust WMH segmentation.
A metal ion orients mRNA to ensure accurate 2’-Oribosyl methylation of the first nucleotide of the SARS-CoV-2 genome
Authors: Viswanathan Thiruselvam , Misra Anurag , Chan Siu-Hong , Qi Shan , Dai Nan , Arya Shailee , Martinez-Sobrido Luis , Gupta Yogesh K. 
Published: March 2021

AbstractThe SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2’-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2’-Omethylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in the host cell. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2’-Omethylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain.
Primed to Die: An Investigation of the Genetic Mechanisms Underlying Noise-Induced Hearing Loss and Cochlear Damage in Homozygous Foxo3-knockout Mice
Authors: Beaulac Holly J. , Gilels Felicia , Zhang Jingyuan , Jeoung Sarah , White Patricia M. 
Published: March 2021

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following a mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type,Foxo3heterozygous (Foxo3+/KO), andFoxo3knock-out (Foxo3KO/KO) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and -independent apoptosis. Lower immunoreactivity of the calcium buffer oncomodulin inFoxo3KO/KOOHCs correlated with cell loss beginning 4 hours post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposedFoxo3KO/KOmice that may contribute to OHC noise susceptibility. Glycerophosphodiester Phosphodiesterase Domain Containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise exposedFoxo3KO/KOmice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.
Large-scale design and refinement of stable proteins using sequence-only models
Authors: Singer Jedediah M. , Novotney Scott , Strickland Devin , Haddox Hugh K. , Leiby Nicholas , Rocklin Gabriel J. , Chow Cameron M. , Roy Anindya , Bera Asim K. , Motta Francis C. , Cao Longxing , Strauch Eva-Maria , Chidyausiku Tamuka M. , Ford Alex , Ho Ethan , Mackenzie Craig O. , Eramian Hamed , DiMaio Frank , Grigoryan Gevorg , Vaughn Matthew , Stewart Lance J. , Baker David , Klavins Eric 
Published: March 2021

AbstractEngineered proteins generally must possess a stable structure in order to achieve their designed function. Stable designs, however, are astronomically rare within the space of all possible amino acid sequences. As a consequence, many designs must be tested computationally and experimentally in order to find stable ones, which is expensive in terms of time and resources. Here we report a neural network model that predicts protein stability based only on sequences of amino acids, and demonstrate its performance by evaluating the stability of almost 200,000 novel proteins. These include a wide range of sequence perturbations, providing a baseline for future work in the field. We also report a second neural network model that is able to generate novel stable proteins. Finally, we show that the predictive model can be used to substantially increase the stability of both expert-designed and model-generated proteins.
Platelet transcriptome yields progressive markers in chronic myeloproliferative neoplasms and identifies putative targets of therapy
Authors: Shen Zhu , Du Wenfei , Perkins Cecelia , Fechter Lenn , Natu Vanita , Maecker Holden , Rowley Jesse , Gotlib Jason , Zehnder James , Krishnan Anandi 
Published: March 2021

AbstractPredicting disease progression remains a particularly challenging endeavor in chronic degenerative disorders and cancer, thus limiting early detection, risk stratification, and preventive interventions. Here, profiling the spectrum of chronic myeloproliferative neoplasms (MPNs) as a model, we identify the blood platelet transcriptome as a proxy for highly sensitive progression biomarkers that also enables prediction of advanced disease via machine learning algorithms. Using RNA sequencing (RNA-seq), we derive disease-relevant gene expression in purified platelets from 120 peripheral blood samples constituting two time-separated cohorts of patients diagnosed with one of three MPN subtypes at sample acquisition – essential thrombocythemia, ET (n=24), polycythemia vera, PV (n=33), and primary or post ET/PV secondary myelofibrosis, MF (n=42), and healthy donors (n=21). The MPN platelet transcriptome reveals an incremental molecular reprogramming that is independent of patient driver mutation status or therapy and discriminates each clinical phenotype. Leveraging this dataset that shows a characteristic progressive expression gradient across MPN, we develop a machine learning model (Lasso-penalized regression) and predict advanced subtype MF at high accuracy and under two conditions of external validation: i) temporal: our two Stanford cohorts, AUC-ROC of 0.96; and ii) geographical: independently published data of an additional n=25 MF and n=46 healthy donors, AUC-ROC of 0.97). Lasso-derived signatures offer a robust core set of < 5 MPN transcriptome markers that are progressive in expression. Mechanistic insights from our data highlight impaired protein homeostasis as a prominent driver of MPN evolution, with persistent integrated stress response. We also identify JAK inhibitor-specific signatures and other interferon, proliferation, and proteostasis-associated markers as putative targets for MPN-directed therapy. Our platelet transcriptome snapshot of chronic MPNs demonstrates a proof of principle for disease risk stratification and progression beyond genetic data alone, with potential utility in other progressive disorders.HighlightsLeveraging two independent and mutually validating MPN patient cohorts, we identify progressive transcriptomic markers that also enable externally validated prediction in MPNs.Our platelet RNA-Seq data identifies impaired protein homeostasis as prominent in MPN progression and offers putative targets of therapy.VISUAL ABSTRACT
Synaptotagmin rings as high sensitivity regulators of synaptic vesicle docking and fusion
Authors: Zhu Jie , McDargh Zachary A. , Li Feng , Krishnakumar Shyam , Rothman James E. , O’Shaughnessy Ben 
Published: March 2021

AbstractSynchronous release at neuronal synapses is accomplished by a machinery that senses calcium influx and fuses the synaptic vesicle and plasma membranes to release neurotransmitters. Previous studies suggested the calcium sensor Synaptotagmin (Syt) is a facilitator of vesicle docking and both a facilitator and inhibitor of fusion. On phospholipid monolayers, the Syt C2AB domain spontaneously oligomerized into rings that are disassembled by Ca2+, suggesting Syt rings may clamp fusion as membrane-separating “washers” until Ca2+-mediated disassembly triggers fusion and release (Wang et al., 2014). Here we combined mathematical modeling with experiment to measure mechanical properties of Syt rings and to test this mechanism. Consistent with experiment, the model quantitatively recapitulates observed Syt ring-induced dome and volcano shapes on phospholipid monolayers, and predicts rings are stabilized by anionic phospholipid bilayers or bulk solution with ATP. The selected ring conformation is highly sensitive to membrane composition and bulk ATP levels, a property that may regulate vesicle docking and fusion in ATP-rich synaptic terminals. We find the Syt molecules hosted by a synaptic vesicle oligomerize into a halo, unbound from the vesicle, but in proximity to sufficiently PIP2-rich plasma membrane (PM) domains the PM-bound trans Syt ring conformation is preferred. Thus, the Syt halo serves as landing gear for spatially directed docking at PIP2-rich sites that define the active zones of exocytotic release, positioning the Syt ring to clamp fusion and await calcium. Our results suggest the Syt ring is both a Ca2+-sensitive fusion clamp and a high-fidelity sensor for directed docking.SignificanceSynchronous neurotransmitter release relies on directed docking of synaptic vesicles at active zones in axon terminals, where calcium influx activates membrane fusion and release. In vitro, the calcium sensor Synaptotagmin oligomerizes into rings disassembled by calcium. Here, experiment and modeling suggest the Synaptotagmin molecules hosted by an undocked vesicle oligomerize into a tethered, unbound halo in ATP-rich synaptic terminals. The halo directs vesicle docking to PIP2-rich plasma membrane domains in active zones, where the trans-bound ring conformation is favored, interposed between the membranes to clamp fusion until calcium triggers ring disassembly and neurotransmitter release. The mechanism exploits the extreme sensitivity of Synaptotagmin ring binding preferences to solution and membrane composition, with ~15 -fold-enhanced sensitivity for rings of ~15 molecules.
Intriguing effects of selection intensity on the evolution of prosocial behaviors
Authors: McAvoy Alex , Rao Andrew , Hauert Christoph 
Published: March 2021

AbstractIn many models of evolving populations, genetic drift has an outsized role relative to natural selection, or vice versa. While there are many scenarios in which one of these two assumptions is reasonable, intermediate balances between these forces are also biologically relevant. In this study, we consider some natural axioms for modeling intermediate selection intensities, and we explore how to quantify the long-term evolutionary dynamics of such a process. To illustrate the sensitivity of evolutionary dynamics to drift and selection, we show that there can be a “sweet spot” for the balance of these two forces, with sufficient noise for rare mutants to become established and sufficient selection to spread. This balance allows prosocial traits to evolve in evolutionary models that were previously thought to be unconducive to the emergence and spread of altruistic behaviors. Furthermore, the effects of selection intensity on long-run evolutionary outcomes in these settings, such as when there is global competition for reproduction, can be highly non-monotonic. Although intermediate selection intensities (neither weak nor strong) are notoriously difficult to study analytically, they are often biologically relevant; and the results we report suggest that they can elicit novel and rich dynamics in the evolution of prosocial behaviors.Author summaryTheoretical models of populations have been useful for assessing when and how traits spread, in large part because they are simple. Rather than being used to reproduce empirical data, these idealized models involve relatively few parameters and are utilized to gain a qualitative understanding of what promotes or suppresses a trait. For prosocial traits, which entail a cost to self to help another, one thing that mathematical models often suggest is that competition to reproduce must be localized, meaning an individual must be fitter than just a small subset of the population in order to produce an offspring. We show here that this finding is not robust. Such traits can indeed proliferate when there is global competition for reproduction, which we demonstrate by increasing the degree to which fitness affects birth rates. Since this kind of “stronger selection” has also been observed empirically, we discuss how it is incorporated into theoretical models more broadly.
Good host - bad host: molecular and evolutionary basis for survival, its failure, and virulence factors of the zoonotic nematodeAnisakis pegreffii
Authors: Trumbić Željka , Hrabar Jerko , Palevich Nikola , Carbone Vincenzo , Mladineo Ivona 
Published: March 2021

AbstractParasitism is a highly successful life strategy and a driving force in genetic diversity that has evolved many times over. Consequently, parasitic organisms have adopted a rich display of traits associated with survival that guarantees an effective “communication” with the host immunity and a balance with surrounding microbiome. However, gain/loss of hosts along the evolutionary axis represents a complex scenario that as contemporary onlookers, we can observe only after a long time displacement. The zoonotic and monophyletic Anisakidae diverged from its terrestrial sister group Ascarididae 150-250 Ma, although a split from their common ancestral host, a terrestrial amniote, seemingly happened already in Early Carboniferous (360.47 Ma). Faced with the sea-level rise during the Permian-Triassic extinction (215 Ma), anisakids acquired a semiaquatic tetrapod host, and as a result of lateral host-switches in Cenozoic, colonised marine mammals, co-evolving with their “new hosts”. Although contemporary anisakids have lost the ability to propagate in terrestrial hosts, they can survive for a limited time in humans. To scrutinize anisakid versatility to infect evolutionary-distant host, we performed transcriptomic profiling of larvae infecting the accidental host (rat) and compared it to that of larvae infecting an evolutionary-familiar, paratenic host (fish). Identified differences and the modeling of handful of shared transcripts, provides the first insights into evolution of larval nematode virulence, warranting further investigation of shared transcript as potential drug therapy targets. Our findings have also revealed some key intrinsic cues that direct larval fate during infection.
Changes and composition of microbial community during aerobic composting of household food waste
Authors: Jin Zhihua , Lu Tong , Feng Wenjun , Jin Qinchao , Wu Zhige , Yang Yu 
Published: March 2021

ABSTRACTIn order to explore the effect of added bacteria on microbial community and determine the dominant bacteria in the aerobic composting process of household food waste (HFW), two groups of HFW composting experiments were conducted for 30 days. The final degradation rates of the two groups were 69.95% (group A, natural composting) and 73.52% (Group C, composting with added bacteria), respectively. 16S rRNA high-throughput sequencing was used to analyze the changes of microbial community in the composting process. As the result displays, at the classification of phylum level, the relatively abundant bacteria of two groups wereFirmicutes, ProteobacteriaandCyanobacteria. At the classification of genus level,Pediococcusis the dominant bacteria of group A, which performed better in maintaining the microbial community stable in the later stage of composting, whileWeissellaaccounted for a relatively large proportion of group C and behaved well in promoting the final degradation rate of composting. The proportion ofOchrobactrumin the early stage of group C is considerable and it is closely related to the removal of odour during composting. The relative abundance of added bacteria was always in a rather low level, suggested that the way they affect the composting process is to change the proportion of dominant bacteria in different stage of composting. This experiment provides an important reference for improving the microbial degradation efficiency of HFW.IMPORTANCEIn recent years, food waste has gradually become a global problem, the annual waste of food is as high as 1.3 billion tons. FW, especially HFW, as a high content of organic matter waste, has a pretty good recycling value. So how to deal with and recycle it efficiently, quickly and conveniently becomes more and more important. Among many treatment and recovery methods, microbial treatment (including anaerobic digestion and aerobic composting) has gradually become a research hotspot due to its advantages of low pollution and low energy consumption, and microorganisms play a crucial role in these process.In this study we use 16S rRNA high-throughput sequencing method to explore aerobic composting of HFW. The purpose of this study is to find out the dominant bacteria which can improve the degradation efficiency, remove the odor and prolong the treatment cycle, and then provide further theoretical reference for future HFW related research.