bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pangenome analysis of the soil-borne fungal phytopathogenRhizoctonia solaniand development of a comprehensive web resource: RsolaniDB
Authors: Kaushik A. , Roberts D.P. , Ramaprasad A. , Mfarrej S. , Nair Mridul , Lakshman D.K. , Pain A. 
Published: December 2020

AbstractRhizoctonia solaniis a collective group of genetically and pathologically diverse basidiomycetous fungus that damages economically important crops. Its isolates are classified into 13 Anastomosis Groups (AGs) and subgroups having distinctive morphology and host range. The genetic factors driving the unique features ofR. solanipathology are not well characterized due to the limited availability of its annotated genomes. Therefore, we performed genome sequencing, assembly, annotation and functional analysis of 12R. solaniisolates covering 7 AGs and selected subgroups (AG1-IA, AG1-IB, AG1-IC, AG2-2IIIB, AG3-PT (isolates Rhs 1AP and the hypovirulent Rhs1A1), AG3-TB, AG4-HG-I (isolates Rs23 and R118-11), AG5, AG6, and AG8), in which six genomes are reported for the first time, wherein we discovered unique and shared secretomes, CAZymes, and effectors across the AGs. Using a pangenome comparative analysis of 12R. solaniisolates and 15 other basidiomycetes, we also elucidated the molecular factors potentially involved in determining the AG-specific host preference, and the attributes distinguishing them from other Basidiomycetes. Finally, we present the largest repertoire ofR. solanigenomes and their annotated components as a comprehensive database, viz. RsolaniDB, with tools for large-scale data mining, functional enrichment and sequence analysis not available with other state-of-the-art platforms, to assist mycologists in formulating new hypotheses.
Prochlorococcusextracellular vesicles: Molecular composition and adsorption to diverse microbes
Authors: Biller Steven J. , Lundeen Rachel A. , Hmelo Laura R. , Becker Kevin W. , Arellano Aldo A. , Dooley Keven , Heal Katherine R. , Carlson Laura T. , Van Mooy Benjamin A. S. , Ingalls Anitra E. , Chisholm Sallie W. 
Published: December 2020

AbstractExtracellular vesicles are small (~50–200 nm diameter) membrane-bound structures released by cells from all domains of life. While vesicles are abundant in the oceans, our understanding of their functions, both for cells themselves and the emergent ecosystem, is in its infancy. To advance this understanding, we analyzed the lipid, protein, and metabolite content of vesicles produced by the marine cyanobacteriumProchlorococcus. We show thatProchlorococcusexports an enormous array of cellular compounds into the surrounding seawater within vesicles. Vesicles produced by two different strains contain some materials in common, but also display numerous strain-specific differences, reflecting functional complexity within natural vesicle populations.Prochlorococcusvesicles contain active enzymes, indicating that they can mediate extracellular biogeochemical reactions in the ocean. We demonstrate that vesicles fromProchlorococcusand other bacteria associate with diverse microbes including the most abundant marine bacterium,Pelagibacter. Our observations suggest that vesicles may play diverse functional roles in the oceans, including but not limited to mediating energy and nutrient transfers, catalyzing extracellular biochemical reactions, and mitigating toxicity of reactive oxygen species. These findings indicate that a portion of ‘dissolved’ compounds in the oceans are not truly dissolved, but are instead packaged within locally structured, particulate vesicles.
Quantifying shifts in natural selection on codon usage between protein regions: A population genetics approach
Authors: Cope Alexander L. , Gilchrist Michael A. 
Published: December 2020

AbstractBackgroundCodon usage bias (CUB), the non-uniform usage of synonymous codons, occurs across all domains of life. Adaptive CUB is hypothesized to result from selection for efficient ribosome elongation, accurate translation, mRNA secondary structure, and/or protein folding. Given the critical link between protein folding and protein function, numerous studies have analyzed the relationship between codon usage and protein structure. The results from these studies have often been contradictory, likely reflecting the differing methods used for measuring codon usage and the failure to appropriately control for confounding factors, such as differences in amino acid usage between protein structures and changes in the frequency of different structures with gene expression.ResultsHere we take an explicit population genetics approach to quantify codon-specific shifts in natural selection related to protein structure. As a result, our approach avoids the problem of needing to choose a specific metric of codon usage, naturally takes amino acid usage of a region into account, and explicitly takes variation in gene expression into account. Our results reveal a weak relationship between codon usage and protein structure, indicating that differences in selection between structures are subtle and/or intermittent. While the magnitude of differences in selection are slight, our results indicate the relationship between codon usage and protein structure is more complex than previously believed.ConclusionsWhile our results clearly indicate that selection on codon usage shifts between secondary structure, the overall impact of these shifts on codon usage are small. Nevertheless, our work demonstrates the statistical power and benefits of studying selective shifts on codon usage or other genomic features from an explicitly evolutionary approach. Limitations of this approach are discussed.
Body size affects immune cell proportions in birds and non-volant mammals, but not bats
Authors: Ruhs Emily Cornelius , Becker Daniel J. , Oakey Samantha J. , Ogunsina Ololade , Fenton M. Brock , Simmons Nancy B. , Martin Lynn B. , Downs Cynthia J. 
Published: December 2020

AbstractPowered flight has evolved several times in vertebrates and constrains morphology and physiology in ways that likely have shaped how organisms cope with infections. Some of these constraints likely have impacts on aspects of immunology, such that larger fliers might prioritize risk reduction and safety. Addressing how the evolution of flight may have driven relationships between body size and immunity could be particularly informative for understanding the propensity of some taxa to harbor many virulent and sometimes zoonotic pathogens without showing clinical disease. Here, we used a scaling framework to quantify scaling relationships between body mass and the proportions of two types of white blood cells--lymphocytes, and granulocytes (neutr-/heterophils)--across 60 bat species, 414 bird species, and 256 non-volant mammal species. By using phylogenetically-informed statistical models on field-collected data from wild Neotropical bats, data gleaned from other wild bats available in the literature, and data from captive non-volant mammals and birds, we show that lymphocyte and neutrophil proportions do not vary systematically with body mass among bats. In contrast, larger birds and non-volant mammals have disproportionately higher granulocyte proportions than expected for their body size. Future comparative studies of wild bats, birds, and non-volant mammals of similar body mass should aim to further differentiate evolutionary effects and other aspects of life history on immune defense.Summary statementPowered flight might constrain morphology such that certain immunological features are prioritized. We show that bats largely have similar cell proportions across body mass compared to strong allometric scaling relationships in birds and non-flying mammals.
Amphipathic Bax core dimer forms part of apoptotic pore wall in the mitochondrial membrane
Authors: Lv Fujiao , Qi Fei , Zhang Zhi , Wen Maorong , Piai Alessandro , Du Lingyu , Zhou LiuJuan , Yang Yaqing , Wu Bin , Liu Zhijun , del Rosario Juan , Chou James J. , Andrews David W. , Lin Jialing , OuYang Bo 
Published: December 2020

SummaryBax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. They may embed in the cytosolic leaflet of the lipid bilayer generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, they may comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determine a high-resolution structure of the Bax core region that forms a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.
Genetics of white color and iridophoroma in “Lemon Frost” leopard geckos
Authors: Guo Longhua , Bloom Joshua , Sykes Steve , Huang Elaine , Kashif Zain , Pham Elise , Ho Katarina , Alcaraz Ana , Xiao Xinshu Grace , Duarte-Vogel Sandra , Kruglyak Leonid 
Published: December 2020

AbstractThe squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko1,Eublepharis macularius,is a popular companion animal, and displays a variety of coloration patterns. We took advantage of a large breeding colony and used linkage analysis, synteny, and homozygosity mapping to investigate a spontaneous semi-dominant mutation, “Lemon Frost”, that produces white coloration and causes skin tumors (iridophoroma). We localized the mutation to a single locus which contains a strong candidate gene, SPINT12,3, a tumor suppressor implicated in human skin cutaneous melanoma (SKCM) and over-proliferation of epithelial cells in mice and zebrafish4–16. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.
Persistence of ambigrammatic narnaviruses requires translation of the reverse open reading frame
Authors: Retallack Hanna , Popova Katerina D. , Laurie Matthew T. , Sunshine Sara , DeRisi Joseph L. 
Published: December 2020

ABSTRACTNarnaviruses are RNA viruses detected in diverse fungi, plants, protists, arthropods and nematodes. Though initially described as simple single-gene non-segmented viruses encoding RNA-dependent RNA polymerase (RdRp), a subset of narnaviruses referred to as “ambigrammatic” harbor a unique genomic configuration consisting of overlapping open reading frames (ORFs) encoded on opposite strands. Phylogenetic analysis supports selection to maintain this unusual genome organization, but functional investigations are lacking. Here, we establish the mosquito-infecting Culex narnavirus 1 (CxNV1) as a model to investigate the functional role of overlapping ORFs in narnavirus replication. In CxNV1, a reverse ORF without homology to known proteins covers nearly the entire 3.2 kb segment encoding the RdRp. Additionally, two opposing and nearly completely overlapping novel ORFs are found on the second putative CxNV1 segment, the 0.8 kb “Robin” RNA. We developed a system to launch CxNV1 in a naïve mosquito cell line, then showed that functional RdRp is required for persistence of both segments, and an intact reverse ORF is required on the RdRp segment for persistence. Mass spectrometry of persistently CxNV1-infected cells provided evidence for translation of this reverse ORF. Finally, ribosome profiling yielded a striking pattern of footprints for all four CxNV1 RNA strands that was distinct from actively-translating ribosomes on host mRNA or co-infecting RNA viruses. Taken together, these data raise the possibility that the process of translation itself is important for persistence of ambigrammatic narnaviruses, potentially by protecting viral RNA with ribosomes, thus suggesting a heretofore undescribed viral tactic for replication and transmission.IMPORTANCEFundamental to our understanding of RNA viruses is a description of which strand(s) of RNA are transmitted as the viral genome, relative to which encode the viral proteins. Ambigrammatic narnaviruses break the mold. These viruses, found broadly in fungi, plants, and insects, have the unique feature of two overlapping genes encoded on opposite strands, comprising nearly the full length of the viral genome. Such extensive overlap is not seen in other RNA viruses, and comes at the cost of reduced evolutionary flexibility in the sequence. The present study is motivated by investigating the benefits which balance that cost. We show for the first time a functional requirement for the ambigrammatic genome configuration in Culex narnavirus 1, which suggests a model for how translation of both strands might benefit this virus. Our work highlights a new blueprint for viral persistence, distinct from strategies defined by canonical definitions of the coding strand.
Auto-segmentation of the parotid glands on MR images of head and neck cancer patients with deep learning strategies
Authors: Kieselmann Jennifer P. , Fuller Clifton D. , Gurney-Champion Oliver J. , Oelfke Uwe 
Published: December 2020

AbstractAdaptive online MRI-guided radiotherapy of head and neck cancer requires the reliable segmentation of the parotid glands as important organs at risk in clinically acceptable time frames. This can hardly be achieved by manual contouring. We therefore designed deep learning-based algorithms which automatically perform this task.Imaging data comprised two datasets: 27 patient MR images (T1-weighted and T2-weighted) and eight healthy volunteer MR images (T2-weighted), together with manually drawn contours by an expert. We used four different convolutional neural network (CNN) designs that each processed the data differently, varying the dimensionality of the input. We assessed the segmentation accuracy calculating the Dice similarity coefficient (DSC), Hausdorff distance (HD) and mean surface distance (MSD) between manual and auto-generated contours. We benchmarked the developed methods by comparing to the inter-observer variability and to atlas-based segmentation. Additionally, we assessed the generalisability, strengths and limitations of deep learning-based compared to atlas-based methods in the independent volunteer test dataset.With a mean DSC of 0.85± 0.11 and mean MSD of 1.82 ±1.94 mm, a 2D CNN could achieve an accuracy comparable to that of an atlas-based method (DSC: 0.85 ±0.05, MSD: 1.67 ±1.21 mm) and the inter-observer variability (DSC: 0.84 ±0.06, MSD: 1.50 ±0.77 mm) but considerably faster (<1s v.s. 45 min). Adding information (adjacent slices, fully 3D or multi-modality) did not further improve the accuracy. With additional preprocessing steps, the 2D CNN was able to generalise well for the fully independent volunteer dataset (DSC: 0.79 ±0.10, MSD: 1.72 ±0.96 mm)We demonstrated the enormous potential for the application of CNNs to segment the parotid glands for online MRI-guided radiotherapy. The short computation times render deep learning-based methods suitable for online treatment planning workflows.
COVID-19 PANDEMICS: HOW FAR ARE WE FROM HERD IMMUNITY?
Authors: Hernandez-Suarez Carlos , Murillo-Zamora Efren , Gómez Francisco Espinoza 
Published: December 2020

ABSTRACTObjectivesto estimate the current number of total infections in a region in order to measure the progress of the epidemic with the purpose of reopening activities and planning the deployment of vaccines.Study designWe recovered estimates of the basic reproductive number (R0) and the Infection Fatality Risk (IFR) as well as the number of confirmed cases and deaths in several countries.Methodsthis works presents an expression to estimate the number of remaining susceptible in a population using the observed number of SARS-CoV-2 related deaths and current estimates of R0and IFR.Resultsthe epidemic will infect most of the population causing 2.5 deaths per thousand inhabitants on average, and herd immunity will be achieved when the number of deaths per thousand inhabitants is close to two. This work introduces an expression to provide estimates of the number of remaining susceptible in a region using the reported number of deaths.Conclusionsany region with fewer than 2.5 deaths per thousand individuals will continue accumulating deaths until this average is achieved, and the infection rate will exceed the removal rate until the number of deaths is about two deaths per thousand, when herd immunity is reached. Waves may occur in any region where the number of deaths is below the herd immunity level.
Modelling population-wide screening of SARS-CoV-2 infection for containing COVID-19 pandemic in Okinawa, Japan
Authors: Shimizu Kazuki , Kuniya Toshikazu , Tokuda Yasuharu 
Published: December 2020

AbstractBackgroundTo break the chains of SARS-CoV-2 transmission and contain the coronavirus disease 2019 (COVID-19) pandemic, population-wide testing is practiced in various countries. However, scant research has addressed this topic in Japan.Materials and MethodsIn this modelling exercise, we extracted the number of daily reported cases of COVID-19 in Okinawa from October 1 to November 30, 2020 and explored possible scenarios for decreasing COVID-19 incidence by combining population-wide screening and/or social distancing policy.ResultsWe reveal that permanent lockdown can be replaced by mass testing that mobilizes sufficient target population at an adequate frequency. In addition, solely imposing a circuit breaker will not bring a favorable outcome in the long-term, and mass testing presents implications for minimizing a period of lockdown.DiscussionOur results highlight the importance of incentivizing citizens to join the frequent testing and ensure their appropriate isolation. To contain the COVID-19 pandemic, rigorous investment in public health is manifestly vital.
Free recall scaling laws and short-term memory effects in a latching attractor network
Authors: Boboeva Vezha , Pezzotta Alberto , Clopath Claudia 
Published: December 2020

AbstractDespite the complexity of human memory, paradigms like free recall have revealed robust qualitative and quantitative characteristics, such as power laws governing recall capacity. Although abstract random matrix models could explain such laws, the possibility of their implementation in large networks of interacting neurons has so far remained unexplored. We study an attractor network model of long-term memory endowed with firing rate adaptation and global inhibition. Under appropriate conditions, the transitioning behaviour of the network from memory to memory is constrained by limit cycles that prevent the network from recalling all memories, with scaling similar to what has been found in experiments. When the model is supplemented with a heteroassociative learning rule, complementing the standard autoassociative learning rule, as well as short-term synaptic facilitation, our model reproduces other key findings in the free recall literature, namely serial position effects, contiguity and forward asymmetry effects, as well as the semantic effects found to guide memory recall. The model is consistent with a broad series of manipulations aimed at gaining a better understanding of the variables that affect recall, such as the role of rehearsal, presentation rates and (continuous/end-of-list) distractor conditions. We predict that recall capacity may be increased with the addition of small amounts of noise, for example in the form of weak random stimuli during recall. Moreover, we predict that although the statistics of the encoded memories has a strong effect on the recall capacity, the power laws governing recall capacity may still be expected to hold.
Genome evolution in bacteria isolated from million-year-old subseafloor sediment
Authors: Orsi William D. , Magritsch Tobias , Vargas Sergio , Coskun Ömer K. , Vuillemin Aurele , Höhna Sebastian , Wörheide Gert , D’Hondt Steven , Shapiro B. Jesse , Carini Paul 
Published: December 2020

AbstractBeneath the seafloor, microbial life subsists in isolation from the surface world under persistent energy limitation. The nature and extent of genomic evolution in subseafloor microbes has been unknown. Here we show that the genomes ofThalassospirabacterial populations cultured from million-year-old subseafloor sediments evolve by point mutation, with a relatively low rate of homologous recombination and a high frequency of pseudogenes. Ratios of synonymous to non-synonymous mutation rates correlate with the accumulation of pseudogenes, consistent with a dominant role for genetic drift in the subseafloor strains, but not in type strains ofThalassospiraisolated from the surface world. Our findings demonstrate that the long term physical isolation of these bacteria, in the absence of recombination, has resulted in clonal populations that evolve consistent with ‘Mullers Ratchet’, whereby reduced access to novel genetic material from neighbors has resulted in fixation of new mutations that accumulate in genomes over millions of years.Significance statementThe nature and extent of genomic evolution in subseafloor microbial populations subsisting for millions of years below the seafloor is unknown. Subseafloor populations have ultra-slow metabolic rates that are hypothesized to restrict reproduction and, consequently, the spread of new traits. Our findings demonstrate that genomes of cultivated bacterial strains from the genusThalassospiraisolated from million-year-old abyssal sediment exhibit greatly reduced levels of homologous recombination, elevated numbers of pseudogenes, and genome-wide evidence of relaxed purifying selection. These substitutions and pseudogenes are fixed into the population, suggesting the genome evolution of these bacteria has been dominated by genetic drift, whereby under long-term physical isolation in small population sizes, and in the absence of homologous recombination, newly acquired mutations accumulate in the genomes of clonal populations over millions of years.