bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allometry, sexual selection, and evolutionary lines of least resistance shaped the evolution of exaggerated sexual traits within the genus Tyrannus
Authors: Fasanelli MN , Milla Carmona P , Soto IM , Tuero DT 
Published: July 2021

AbstractVariational properties hold a fundamental role in shaping biological evolution, exerting control over the magnitude and direction of evolutionary change elicited by microevolutionary processes that sort variation, such as selection or drift. We studied the Tyrannus genus, as a model for examining the conditions and drivers that facilitate the repeated evolution of exaggerated, secondary sexual traits in the face of significant functional limitations. We study the role of allometry, sexual selection, and their interaction on the diversification of tail morphology in the genus, assessing whether and how they promoted or constrained phenotypic evolution. The exaggerated and functionally-constrained long feathers of deep-forked species, T. savana and T. forficatus, independently diverged from the rest of the genus following the same direction of main interspecific variation common to the entire cluster of species. However, at a macroevolutionary scale those axes summarising both sexual dimorphism and allometric variation of the deep-forked species were aligned with the between-species maximum variation axis of non deep-forked species. Thus, we are presenting evidence of amplified divergence via the co-option and reorientation of allometric shape variation involved in a sexual selection process that repeatedly drove morphology along a historically favoured direction of cladogenetic evolution.
Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines
Authors: Albalawi Omar M. , Alomran Maha I. , Alsagri Ghada M. , Althunian Turki A. , Alshammari Thamir M. 
Published: July 2021

AbstractBackgroundSince December 2020, three COVID-19 vaccines have been authorized in the United States (U.S.) and were proceeded by large immunization programs. The aim of this study was to characterize the U.S. post-marketing safety (PMS) profiles of these vaccines with an in-depth analysis of mortality data.MethodsThis was a retrospective database analysis study. Details of the U.S. PMS reports (15 December 2020 to 19 March 2021) of the three vaccines (Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S) were retrieved from the U.S. Vaccine Adverse Event Reporting System (VAERS). A descriptive analysis was conducted to characterize the reported adverse events (AEs). A comparative (Pfizer-BioNTech vs. Moderna) analysis of mortality was conducted. The mean count ratio of death between the two vaccines was estimated using a negative binomial regression model adjusting for the measured confounders.ResultsA total of 44,451 AE reports were retrieved (corresponding to 0.05% of the U.S. population who received at least one dose). The most commonly reported AEs were injection site reactions (30.4% of the reports), pain (reported in 26.7% of the reports), and headache (18.6% of the reports). Serious AEs were reported in only 14.6% of the reports with 4,108 hospitalizations. The total number of deaths was 1,919 with a mean count ratio of Moderna (n=997) vs. Pfizer-BioNTech (n=899) of 1.07 (95% confidence interval 0.86 to 1.33).ConclusionsThe vast majority of PMS AEs in the U.S. were non-serious, and the number of serious AEs is very low given the total number of vaccinated U.S. population.
Enhanced chemotaxis through spatially-regulated absolute concentration robustness
Authors: Biswas Debojyoti , Bhattacharya Sayak , Iglesias Pablo A. 
Published: July 2021

AbstractChemotaxis, the directional motility of cells in response to spatial gradients of chemical cues, is a fundamental process behind a wide range of biological events, including the innate immune response and cancer metastasis. Recent advances in cell biology have shown that the protrusions that enable amoeboid cells to move are driven by the stochastic threshold crossings of an underlying excitable system. As a cell encounters a chemoattractant gradient, the size of this threshold is regulated spatially so that the crossings are biased towards the front of the cell. For efficient directional migration, cells must limit undesirable lateral and rear-directed protrusions. The inclusion of a control mechanism to suppress these unwanted firings would enhance chemotactic efficiency. It is known that absolute concentration robustness (ACR) exerts tight control over the mean and variance of species concentration. Here, we demonstrate how the coupling of the ACR mechanism to the cellular signaling machinery reduces the likelihood of threshold crossings in the excitable system. Moreover, we show that using the cell’s innate gradient sensing apparatus to direct the action of ACR to the rear, suppresses the lateral movement of the cells and that this results in improved chemotactic performance.
CADD-SV – a framework to score the effects of structural variants in health and disease
Authors: Kleinert Philip , Kircher Martin 
Published: July 2021

AbstractWhile technological advances improved the identification of structural variants (SVs) in the human genome, their interpretation remains challenging. Several methods utilize individual mechanistic principles like the deletion of coding sequence or 3D genome architecture disruptions. However, a comprehensive tool using the broad spectrum of available annotations is missing. Here, we describe CADD-SV, a method to retrieve and integrate a wide set of annotations to predict the effects of SVs.Previously, supervised learning approaches were limited due to a small number and biased set of annotated pathogenic or benign SVs. We overcome this problem by using a surrogate training-objective, the Combined Annotation Dependent Depletion (CADD) of functional variants. We use human and chimpanzee derived SVs as proxy-neutral and contrast them with matched simulated variants as proxy-pathogenic, an approach that has proven powerful for SNVs.Our tool computes summary statistics over diverse variant annotations and uses random forest models to prioritize deleterious structural variants. The resulting CADD-SV scores correlate with known pathogenic and rare population variants. We further show that we can prioritize somatic cancer variants as well as non-coding variants known to affect gene expression. We provide a website and offline-scoring tool for easy application of CADD-SV (https://cadd-sv.bihealth.org/).
Power Calculator for Detecting Allelic Imbalance Using Hierarchical Bayesian Model
Authors: Sherbina Katrina , León-Novelo Luis G. , Nuzhdin Sergey V. , McIntyre Lauren M. , Marroni Fabio 
Published: July 2021

AbstractAllelic imbalance (AI) is the differential expression of the two alleles in a diploid. AI can vary between tissues, treatments, and environments. Statistical methods for testing in this area exist, with impacts of explosive type I error in the presence of bias well understood. However, for study design, the more important and understudied problem is the type II error and power. As the biological questions for this type of study explode, and the costs of the technology plummet, what is more important: reads or replicates? How small of an interaction can be detected while keeping the type I error at bay? Here we present a simulation study that demonstrates that the proper model can control type I error below 5% for most scenarios. We find that a minimum of 2400, 480, and 240 allele specific reads divided equally among 12, 5, and 3 replicates is needed to detect a 10%, 20%, and 30%, respectively, deviation from allelic balance in a condition with power >80%. A minimum of 960 and 240 allele specific reads is needed to detect a 20% or 30% difference in AI between conditions with comparable power but these reads need to be divided amongst 8 replicates. Higher numbers of replicates increase power more than adding coverage without affecting type I error. We provide a Python package that enables simulation of AI scenarios and enables individuals to estimate type I error and power in detecting AI and differences in AI between conditions tailored to their own specific study needs.
A novel non-antibiotic selectable marker GASA6 for plant transformation
Authors: Luo Yuewan , Gu Jiena , Wang Xiaojing , Zhang Shengchun 
Published: July 2021

AbstractSelectable markers help the transformed cell/tissue to survive in an otherwise lethal exposure of an antibiotic or herbicide. Unfortunately, almost all the traditional selectable markers are antibiotic and herbicide resistance genes, which are controversial on human health concerns and environmental impact. Novel plant-derived, non-antibiotic, and non-herbicide selectable markers are urgently needed in plant transformation. Our previous work showed that the seedlings of overexpression Arabidopsis lines of AtGASA6 survived on medium with a high concentration of sugar, which leads to the hypothesis that AtGASA6 could be a selectable marker on media with high or low sugar content. In this study, leaf explants of AtGASA6 overexpression tobacco lines regenerated shoots on sugar-free shooting medium while those of wild type could not. Moreover, the seeds of AtGASA6 overexpression tobacco lines germinated and grew into normal seedlings on sugar-free MS medium while those of WT could not. Attractively, no developmental defects were observed in AtGASA6 transgenic progenies. Using AtGASA6 as a selectable marker, overexpression tobacco lines of GAI, which restrains plant size, were created on sugar-free media. The GAI overexpression lines had a smaller plant size than that of control. Considering its plant-derived and non-antibiotic nature, GASA6 is promising to be used as a selectable marker in plant transformation.
Independent adoptions of a set of proteins found in the matrix of the mineralized shell-like eggcase of Argonaut octopuses
Authors: Setiamarga Davin H. E. , Hirota Kazuki , Ikai Risa , Imoto Seiji , Sato Noriyoshi , Ono Hiroki , Isowa Yukinobu , Yonemitsu Hiroshi , Sasaki Takenori , Yoshida Masa-aki 
Published: July 2021

AbstractThe Argonaut octopus, commonly called the paper nautilus, has a spiral-coiled shell-like eggcase. As the main characteristics, the eggcase has no internal septum, is composed entirely of calcite with chitosan being the main polycarbonate and is reportedly formed by organic materials secreted from the membranes of the arms. Meanwhile, the biomineralized external “true” shells of the Mollusks, which includes the Cephalopods, are secreted from the mantle tissue. Therefore, the histological origin of the two shells is completely different. The question of how the Argonauts, which phylogenetically diverged from the completely shell-less octopuses, could form a converging shell-like external structure has thus intrigued biologists for a long time. To answer this question, we performed a multi-omics analysis of the transcriptome and proteome of the two congeneric Argonaut species,Argonauta argoandA. hians. Our result indicates that the shell-like eggcase is not a homolog of the shell, even at the protein level, because the Argonauts apparently recruited a different set of protein repertoires to as eggcase matrix proteins (EcMPs). However, we also found the homologs of three shell matrix proteins (SMPs) of the Conchiferan Mollusks, Pif-like, SOD, and TRX, in the eggcase matrix. The proteins were also found in the only surviving shelled Cephalopods, the nautiloidNautilus pompilius. Phylogenetic analysis revealed that homologous genes of the Conchiferan SMPs and EcMPs were found in the draft genome of shell-less octopuses. Our result reported here thus suggests that the SMP-coding genes are conserved in both shelled and shell-less Cephalopods. Meanwhile, the Argonauts adopted some of the SMP-coding genes and other non-SMP-coding genes, to form a convergent, non-homologous biomineralized external structure, the eggcase, which is autapomorphic to the group.
Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs
Authors: Sun Yu H. , Wang Ruoqiao Huiyi , Du Khai , Zheng Jihong , Xie Li Huitong , Pereira Amanda A. , Zhang Chao , Ricci Emiliano P. , Li Xin Zhiguo 
Published: July 2021

ABSTRACTPIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. Previously, we showed that ribosomes guide the biogenesis of piRNAs from long non-coding RNAs (lncRNAs) after translating the short open reading frames (ORFs) near their 5’ cap. It remained unclear, however, how ribosomes proceed downstream of ORFs and how piRNA precursors distinguish from other RNAs. It is thus important to test whether a short ORF length is required for substrate recognition for ribosome guided-piRNA biogenesis. Here, we characterized a poorly understood class of piRNAs that originate from the 3’ untranslated regions (3’UTRs) of protein coding genes in mice and chickens. We demonstrate that their precursors are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3’UTRs after translation of upstream long ORFs. Similar to non-sense mediated decay (NMD), piRNA biogenesis degrades mRNA right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Interestingly, however, we found that NMD, along with other surveillance pathways for ribosome recycling are temporally sequestered during the pachytene stage to allow for robust piRNA production. Although 3’UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded transposable elements (TEs) and produce piRNAs that cleave TEs, suggesting that TE suppression, rather than the function of proteins, is the primary evolutionary force maintaining a subset of mRNAs as piRNA precursors. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved, general piRNA biogenesis mechanism that recognizes translating RNAs regardless of their ORF length in amniotes.
Bacterial type 1A topoisomerases maintain the stability of the genome by preventing and dealing with R-loop-and nucleotide excision repair-dependent topological stress
Authors: Brochu Julien , Vlachos-Breton Emilie , Drolet Marc 
Published: July 2021

ABSTRACTE. coli type 1A topoisomerases (topos), topo I (topA) and topo III (topB) have both relaxation and decatenation activities. B. subtilis and E. coli topA topB null cells can survive owing to DNA amplifications allowing overproduction of topo IV, the main cellular decatenase that can also relax supercoiling. We show that overproducing human topo IB, a relaxase but not a decatenase, can substitute for topo IV in allowing E. coli topA null but not topA topB null cells to survive. Deleting topB exacerbates phenotypes of topA null mutants including hypernegative supercoiling, R-loop formation, and RNase HI-sensitive replication, phenotypes that are not corrected by topo IV overproduction. These phenotypes lead to Ter DNA amplification causing a chromosome segregation defect that is corrected by topo IV overproduction. Furthermore, topA topB null mutants not overproducing topo IV acquire uvrB or uvrC mutations, revealing a nucleotide excision repair (NER)-dependent problem with replication fork progression. Thus, type IA topos maintain the stability of the genome by providing essential relaxase and decatenase activities to prevent and solve topological stress related to R-loops and NER. Moreover, excess R-loop formation is well tolerated in cells that have enough topoisomerase activity to support the subsequent replication-related topological stress.
Pili Expression inGeobacter sulfurreducensLacking the Putative Gene for the PilB Pilus Assembly Motor
Authors: Ueki Toshiyuki , Walker David J.F. , Nevin Kelly P. , Ward Joy E. , Woodard Trevor L. , Nonnenmann Stephen S. , Lovley Derek R. 
Published: July 2021

AbstractMultiple lines of evidence suggest that electrically conductive pili (e-pili) are an important conduit for long-range electron transport inGeobacter sulfurreducens, a common model microbe for the study of extracellular electron transport mechanisms. One strategy to study the function of e-pili has been to delete the gene for PilB, the pilus assembly motor protein, in order to prevent e-pili expression. However, we found that e-pili are still expressed after the gene for PilB is deleted. Conducting probe atomic force microscopy revealed filaments with the same diameter and similar current-voltage response as e-pili harvested from wild-typeG. sulfurreducensor when e-pili are heterologously expressed from theG. sulfurreducenspilin gene inE. coli. Immunogold labeling demonstrated that aG. sulfurreducensstrain expressing e-pili with a His-tag continued to express His-tag labelled e-pili when the PilB gene was deleted. Strains with the PilB gene deleted produced maximum current densities comparable to wild-type controls. These results demonstrate that deleting the gene for PilB is not an appropriate strategy for constructing strains ofG. sulfurreducenswithout e-pili, necessitating a reinterpretation of the results of previous studies that have employed this approach.ImportanceGeobacter sulfurreducensis a model microbe for the study of biogeochemically and technologically significant processes such as the reduction of Fe(III) oxides in soils and sediments; bioelectrochemical applications that produce electric current from waste organic matter or drive useful processes with the consumption of renewable electricity; direct interspecies electron transfer in anaerobic digestors and methanogenic soils and sediments; and metal corrosion. The phenotypes associated with gene deletions are an important strategy for determining the mechanisms for extracellular electron transfer inG. sulfurreducens. The results reported here demonstrate that a gene deletion previously thought to prevent the expression of electrically conductive pili inG. sulfurreducensdoes not have the intended result. Conductive pili continue to be expressed. This finding is important for interpreting the results of several previous studies on conductive pili function.
Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing
Authors: Wang Yiquan , Lei Ruipeng , Nourmohammad Armita , Wu Nicholas C. 
Published: July 2021

AbstractAs one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has emerged as an effective vaccine target recently, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply deep mutational scanning to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region can be predicted by charge states and pairwise epistasis. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a predictive model of influenza evolution.
Identification of RNA base pairs and complete assignment of nucleobase resonances by proton-detected solid-state NMR spectroscopy at 100 kHz MAS
Authors: Aguion Philipp Innig , Kirkpatrick John , Carlomagno Teresa , Marchanka Alexander 
Published: July 2021

AbstractKnowledge of RNA structure, either in isolation or in complex, is fundamental to understand the mechanism of cellular processes. Solid-state NMR (ssNMR) is applicable to high molecular-weight complexes and does not require crystallization; thus, it is well-suited to study RNA as part of large multicomponent assemblies. Recently, we solved the first structures of both RNA and an RNA–protein complex by ssNMR using conventional 13C- and 15N-detection. This approach is limited by the severe overlap of the RNA peaks together with the low sensitivity of multidimensional experiments. Here, we overcome the limitations in sensitivity and resolution by using 1H-detection at fast MAS rates. We develop experiments that allow the identification of complete nucleobase spin-systems together with their site-specific base pair pattern using sub-milligram quantities of one uniformly labelled RNA sample. These experiments provide rapid access to RNA secondary structure by ssNMR in protein–RNA complexes of any size.
The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes
Authors: Costello Shawn M. , Shoemaker Sophie R. , Hobbs Helen T. , Nguyen Annalee W. , Hsieh Ching-Lin , Maynard Jennifer A. , McLellan Jason S. , Pak John E. , Marqusee Susan 
Published: July 2021

AbstractCurrent COVID-19 vaccines and many clinical diagnostics are based on the structure and function of the SARS-CoV-2 spike ectodomain. Using hydrogen deuterium exchange mass spectrometry, we have uncovered that, in addition to the prefusion structure determined by cryo-EM, this protein adopts an alternative conformation that interconverts slowly with the canonical prefusion structure. This new conformation—an open trimer— contains easily accessible RBDs. It exposes the conserved trimer interface buried in the prefusion conformation, thus exposing potential epitopes for pan-coronavirus antibody and ligand recognition. The population of this state and kinetics of interconversion are modulated by temperature, receptor binding, antibody binding, and sequence variants observed in the natural population. Knowledge of the structure and populations of this conformation will help improve existing diagnostics, therapeutics, and vaccines.One Sentence SummaryAn alternative conformation of SARS-CoV-2 spike ectodomain modulated by temperature, binding, and sequence variants.
Evolution with private resources reverses some changes from long-term evolution with public resources
Authors: van Raay Katrina , Stolyar Sergey , Sevigny Jordana , Tirado Adamaris Muñiz , Draghi Jeremy A. , Lenski Richard E. , Marx Christopher J. , Kerr Benjamin , Zaman Luis 
Published: July 2021

AbstractA population under selection to improve one trait may evolve a sub-optimal state for another trait due to tradeoffs and other evolutionary constraints. How this evolution affects the capacity of a population to adapt when conditions change to favor the second trait is an open question. We investigated this question using isolates from a lineage spanning 60,000 generations of the Long-Term Evolution Experiment (LTEE) with Escherichia coli, where cells have access to a shared pool of resources, and have evolved increased competitive ability and a concomitant reduction in numerical yield. Using media-in oil emulsions we shifted the focus of selection to numerical yield, where cells grew in isolated patches with private resources. We found that the time spent evolving under shared resources did not affect the ability to re-evolve toward higher numerical yield. The evolution of numerical yield commonly occurred through mutations in the phosphoenolpyruvate phosphotransferase system. These mutants exhibit slower uptake of glucose, making them poorer competitors for public resources, and produce smaller cells that release less carbon as overflow metabolites. Our results demonstrate that mutations that were not part of adaptation under one selective regime may enable access to ancestral phenotypes when selection changes to favor evolutionary reversion.