bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA partitioning into stress granules is based on the summation of multiple interactions
Authors: Matheny Tyler , Van Treeck Briana , Huynh Thao Ngoc , Parker Roy 
Published: April 2020

SUMMARYStress granules (SGs) are stress-induced RNA-protein assemblies formed from a complex transcriptome of untranslating ribonucleoproteins (RNPs). Although RNAs can be either enriched or depleted from SGs, the rules that dictate RNA partitioning into SGs are unknown. We demonstrate that the SG-enrichedNORADRNA is sufficient to enrich a reporter RNA within SGs through the combined effects of multiple elements. Moreover, artificial tethering of G3BP1 or TIA1 can target mRNAs into SGs in a dose-dependent manner that suggests individual protein interactions have small effects on the SG partitioning of mRNPs, which is supported by the observation that the SG transcriptome is largely unchanged in cell lines lacking the abundant SG RNA-binding proteins G3BP1 and G3BP2. We suggest the targeting of RNPs into SGs is due to a summation of potential RNA-protein, protein-protein, and RNA-RNA interactions with no single interaction dominating RNP recruitment into SGs.
Predicting the Viability of Beta-Lactamase: How Folding and Binding Free Energies Correlate with Beta-Lactamase Fitness
Authors: Yang Jordan , Naik Nandita , Patel Jagdish Suresh , Wylie Christopher S. , Gu Wenze , Huang Jessie , Ytreberg Marty , Naik Mandar T. , Weinreich Daniel M. , Rubenstein Brenda M. 
Published: April 2020

AbstractOne of the long-standing holy grails of molecular evolution has been the ability to predict an organism’s fitness directly from its genotype. With such predictive abilities in hand, researchers would be able to more accurately forecast how organisms will evolve and how proteins with novel functions could be engineered, leading to revolutionary advances in medicine and biotechnology. In this work, we assemble the largest reported set of experimental TEM-1β-lactamase folding free energies and use this data in conjunction with previously acquired fitness data and computational free energy predictions to determine how much of the fitness ofβ-lactamase can be directly predicted by thermodynamic folding and binding free energies. We focus uponβ-lactamase because of its long history as a model enzyme and its central role in antibiotic resistance. Based upon a set of 21β-lactamase single and double mutants expressly designed to influence protein folding, we first demonstrate that modeling software such as FoldX and PyRosetta designed to compute folding free energies can meaningfully, although not perfectly, predict the experimental folding free energies of single mutants. Interestingly, while these techniques also yield sensible double mutant free energies, we show that they do so for the wrong physical reasons. We then go on to assess how well both experimental and computational folding free energies explain single mutant fitness. We find that folding free energies account for, at most, 24% of the variance inβ-lactamase fitness values according to linear models and, somewhat surprisingly, complementing folding free energies with computationally-predicted binding free energies of residues near the active site only increases the folding-only figure by a few percent. This strongly suggests that the majority ofβ-lactamase’s fitness is controlled by factors other than free energies. Overall, our results shed a bright light on to what extent the community is justified in using thermodynamic measures to infer protein fitness as well as how applicable modern computational techniques for predicting free energies will be to the large data sets of multiply-mutated proteins forthcoming.
TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Times-Series Data in Circadian Biology Research
Authors: Ness-Cohn Elan , Iwanaszko Marta , Kath William , Allada Ravi , Braun Rosemary 
Published: April 2020

AbstractThe circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms’ performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest; and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.
Determining the probability of hemiplasy in the presence of incomplete lineage sorting and introgression
Authors: Hibbins Mark S. , Gibson Matthew J.S. , Hahn Matthew W. 
Published: April 2020

AbstractThe incongruence of character states with phylogenetic relationships is often interpreted as evidence of convergent evolution. However, trait evolution along discordant gene trees can also generate these incongruences – a phenomenon known as hemiplasy. Classic phylogenetic comparative methods do not account for discordance, resulting in incorrect inferences about the number of times a trait has evolved, and therefore about convergence. Biological sources of discordance include incomplete lineage sorting (ILS) and introgression, but only ILS has received theoretical consideration in the context of hemiplasy. Here, we derive expectations for the probabilities of hemiplasy and homoplasy with ILS and introgression acting simultaneously. We find that introgression makes hemiplasy more likely than ILS alone, suggesting that methods that account for discordance only due to ILS will be conservative. We also present a method for making statistical inferences about the relative probabilities of hemiplasy and homoplasy in empirical datasets. Our method is implemented in the software packageHeIST(Hemiplasy Inference Simulation Tool), and estimates the most probable number of transitions among character states given a set of relationships with discordance.HeISTcan accommodate ILS and introgression simultaneously, and can be applied to phylogenies where the number of taxa makes finding an analytical solution impractical. We apply this tool to two empirical cases of apparent trait convergence in the presence of high levels of discordance, one of which involves introgression between the convergent lineages. In both cases we find that hemiplasy is likely to contribute to the observed trait incongruences.
In-field bioreactors demonstrate dynamic shifts in microbial communities in response to geochemical perturbations
Authors: Wilpiszeski Regina L. , Gionfriddo Caitlin M. , Wymore Ann M. , Moon Ji-Won , Lowe Kenneth A. , Podar Mircea , Rafie Sa’ad , Fields Matthew W. , Hazen Terry C. , Ge Xiaoxuan , Poole Farris , Adams Michael W.W. , Chakraborty Romy , Fan Yupeng , Nostrand Joy D. Van , Zhou Jizhong , Arkin Adam P. , Elias Dwayne A. 
Published: April 2020

AbstractSubsurface microbial communities mediate the transformation and fate of redox sensitive materials including organic matter, metals and radionuclides. Few studies have explored how changing geochemical conditions influence the composition of groundwater microbial communities over time. We temporally monitored alterations in abiotic forces on microbial community structure using 1L in-field bioreactors receiving background and contaminated groundwater at the Oak Ridge Reservation, TN. Planktonic and biofilm microbial communities were initialized with background water for 4 days to establish communities in triplicate control reactors and triplicate test reactors and then fed filtered water for 14 days. On day 18, three reactors were switched to receive filtered groundwater from a contaminated well, enriched in total dissolved solids relative to the background site, particularly chloride, nitrate, uranium, and sulfate. Biological and geochemical data were collected throughout the experiment, including planktonic and biofilm DNA for 16S rRNA amplicon sequencing, cell counts, total protein, anions, cations, trace metals, organic acids, bicarbonate, pH, Eh, DO, and conductivity. We observed significant shifts in both planktonic and biofilm microbial communities receiving contaminated water. This included a loss of rare taxa, especially amongst members of theBacteroidetes,Acidobacteria,Chloroflexi, andBetaproteobacteria, but enrichment in the Fe- and nitrate-reducingFerribacteriumand parasiticBdellovibrio. These shifted communities were more similar to the contaminated well community, suggesting that geochemical forces substantially influence microbial community diversity and structure. These influences can only be captured through such comprehensive temporal studies, which also enable more robust and accurate predictive models to be developed.
Role of gene length in control of human gene expression: chromosome-specific and tissue-specific effects
Authors: Brown Jay C. 
Published: April 2020

AbstractBackgroundThis study was carried out to pursue the observation that the level of gene expression is affected by gene length in the genomes of higher vertebrates. As transcription is a time-dependent process, it is expected that gene expression will be inversely related to gene length, and this is found to be the case. Here I describe the results of studies performed with the human genome to test whether the gene length/gene expression linkage is affected by two factors, the chromosome where the gene is located and the tissue where it is expressed.Experimental designStudies were carried out with a database of 2413 human genes that were divided into short, mid-length and long groups. Each of the 24 human chromosomes was then characterized according to the proportion of each gene length group present. A similar analysis was performed with 19 human tissues. The proportion of short, mid-length and long genes was noted for each tissue.ResultsBoth chromosome and tissue studies revealed new information about the role of gene length in control of gene expression. Chromosome studies led to the identification of two chromosome populations that differ in the level of short gene expression. Tissue studies support the conclusion that short, highly expressed genes are enriched in tissues that produce protein products that are exported from the host cell.
Structure of the bacterial cellulose ribbon and its assembly-guiding cytoskeleton by electron cryotomography
Authors: Nicolas William J. , Ghosal Debnath , Tocheva Elitza I. , Meyerowitz Elliot M. , Jensen Grant J. 
Published: April 2020

AbstractCellulose is a widespread component of bacterial biofilms, where its properties of exceptional water retention, high tensile strength and stiffness prevents dehydration and mechanical disruption of the biofilm. Bacteria in theGluconacetobactergenus secrete crystalline cellulose, with a structure very similar to that found in plant cell walls. How this higher-order structure is produced is poorly understood. We used cryo-electron tomography and focused ion beam milling of native bacterial biofilms to image cellulose-synthesizingG. hanseniiandG. xylinusbacteria in a frozen-hydrated, near-native state. We confirm previous results suggesting that cellulose crystallization occurs serially following its secretion along one side of the cell, leading to a cellulose ribbon that can reach several microns in length and combine with ribbons from other cells to form a robust biofilm matrix. We were able to take direct measurements in a near-native state of the cellulose sheets. Our results also reveal a novel cytoskeletal structure, that we name the cortical belt, adjacent to the inner membrane and underlying the sites where cellulose is seen emerging from the cell. We find that this structure is not present in other cellulose-synthesizing bacterial species,Agrobacterium tumefaciensandEscherichia coli1094, which do not produce organized cellulose ribbons. We therefore propose that the cortical belt holds the cellulose synthase complexes in a line, to form higher-order cellulose structures such as sheets and ribbons.
Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs
Authors: Shastri Aditi , Wheat Justin , Agrawal Sachee , Chaterjee Nirjhar , Pradhan Kith , Goldfinger Mendel , Kornblum Noah , Steidl Ulrich , Verma Amit , Shastri Jayanthi 
Published: April 2020

AbstractThe novel coronavirus SARS-CoV2 has been observed to cause a higher incidence and greater severity of disease in males, as seen in multiple cohorts across the globe. The reasons for gender disparity in disease severity is unclear and can be due to host factors. To determine whether males have delayed viral clearance after infection, we evaluated the time to clearance in symptomatic patients tested by serial oropharyngeal/nasopharyngeal swabs followed by RT-PCR at a reference lab in Mumbai, India. A total of 68 subjects with median age of 37 years (3-75 range) were examined and included 48 (71%) males and 20 (29%) females. We observed that females were able to achieve viral clearance significantly earlier than males, with a median difference of 2 days in achieving a negative PCR result (P value = 0.038). Furthermore, examination of 3 families with both male and female patients followed serially, demonstrated that female members of the same household cleared the SARS-CoV2 infection earlier in each family. To determine reasons for delayed clearance in males, we examined the expression patterns of the SARS-CoV2 receptor, Angiotensin-converting enzyme 2 (ACE2), in tissue specific repositories. We observed that the testes was one of the highest sites of ACE2 expression in 3 independent RNA expression databases (Human Protein Atlas, FAMTOM5 and GETx). ACE2 was also determined to be highly expressed in testicular cells at the protein levels. Interestingly, very little expression of ACE2 was seen in ovarian tissue. Taken together, these observations demonstrate for the first time that male subjects have delayed viral clearance of SARS-CoV2. High expression of ACE2 in testes raises the possibility that testicular viral reservoirs may play a role in viral persistence in males and should be further investigated.
Outcomes of the 2019 Novel Coronavirus in patients with or without a history of cancer - a multi-centre North London experience
Authors: Joharatnam-Hogan Nalinie , Hochhauser Daniel , Shiu Kai-Keen , Rush Hannah , Crolley Valerie , Butcher Emma , Sharma Anand , Muhammad Aun , Anwar Muhammad , Vasdev Nikhil , Kantser Ganna , Saha Aramita , Raja Fharat , Bridgewater John , Khan Khurum 
Published: April 2020

AbstractBackgroundFour months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer.MethodWe retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March-7th April 2020).ResultsA total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission.ConclusionOld age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.
Changes in Sound Localization Performance of Single-Sided Deaf Listeners after Visual Feedback Training in Azimuth
Authors: Zonooz Bahram , Opstal A. John Van 
Published: April 2020

AbstractChronic single-sided deaf (CSSD) listeners lack the availability of binaural difference cues to localize sounds in the horizontal plane. Hence, for directional hearing they have to rely on different types of monaural cues: loudness perceived in their hearing ear, which is affected in a systematic way by the acoustic head shadow, on spectral cues provided by the low-pass filtering characteristic of the head, and on high-frequency spectral-shape cues from the pinna of their hearing ear. Presumably, these cues are differentially weighted against prior assumptions on the properties of sound sources in the environment. The rules guiding this weighting process are not well understood. In this preliminary study, we trained three CSSD listeners to localize a fixed intensity, high-pass filtered sound source at ten locations in the horizontal plane with visual feedback. After training, we compared their localization performance to sounds with different intensities, presented in the two-dimensional frontal hemifield to their pre-training results. We show that the training had rapidly readjusted the contributions of monaural cues and internal priors, which resulted to be imposed by the multisensory information provided during the training. We compare the results with the strategies found for the acute monaural hearing condition of normal-hearing listeners, described in an earlier study [1].
Phylogenomic terraces: presence and implication in species tree estimation from gene trees
Authors: Farah Ishrat Tanzila , Islam Md Muktadirul , Zinat Kazi Tasnim , Rahman Atif Hasan , Bayzid Md Shamsuzzoha 
Published: April 2020

AbstractSpecies tree estimation from multi-locus dataset is extremely challenging, especially in the presence of gene tree heterogeneity across the genome due to incomplete lineage sorting (ILS).Summary methodshave been developed which estimate gene trees and then combine the gene trees to estimate a species tree by optimizing various optimization scores. In this study, we have formalized the concept of “phylogenomic terraces” in the species tree space, where multiple species trees with distinct topologies may have exactly the same optimization score (quartet score, extra lineage score, etc.) with respect to a collection of gene trees. We investigated the presence and implication of terraces in species tree estimation from multi-locus data by taking ILS into account. We analyzed two of the most popular ILS-aware optimization criteria:maximize quartet consistency(MQC) andminimize deep coalescence(MDC). Methods based on MQC are provably statistically consistent, whereas MDC is not a consistent criterion for species tree estimation. Our experiments, on a collection of dataset simulated under ILS, indicate that MDC-based methods may achieve competitive or identical quartet consistency score as MQC but could be significantly worse than MQC in terms of tree accuracy – demonstrating the presence and affect of phylogenomic terraces. This is the first known study that formalizes the concept of phylogenomic terraces in the context of species tree estimation from multi-locus data, and reports the presence and implications of terraces in species tree estimation under ILS.
Analytical models forβ-diversity and the power-law scaling ofβ-deviation
Authors: Xing Dingliang , He Fangliang 
Published: April 2020

ABSTRACTβ-diversity is a primary biodiversity pattern for inferring community assembly. A randomized null model that generates a standardizedβ-deviation has been widely used for this purpose. However, the null model has been much debated and its application is limited to abundance data.Here we derive analytical models forβ-diversity to address the debate, clarify the interpretation, and extend the application to occurrence data.The analytical analyses show unambiguously that the standardizedβ-deviation is a quantification of the effect size of non-random spatial distribution of species onβ-diversity for a given species abundance distribution. It robustly scales with sampling effort following a power law with exponent of 0.5. This scaling relationship offers a simple method for comparingβ-diversity of communities of different sizes.Assuming logseries distribution for the metacommunity species abundance distribution, our model allows for calculation of the standardizedβ-deviation using occurrence data plus a datum on the total abundance.Our theoretical model justifies and generalizes the use of theβnull model for inferring community assembly rules.