bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inka2, a novel Pak4 inhibitor, regulates actin dynamics in neuronal development
Authors: Yamada Seiya , Mizukoshi Tomoya , Tokunaga Akinori , Sakakibara Shin-ichi 
Published: March 2022

AbstractThe actin filament is a fundamental part of the cytoskeleton defining cell morphology and regulating various physiological processes, including filopodia formation and dendritic spinogenesis of neurons. Serine/threonine-protein kinase Pak4, an essential effector, links Rho GTPases to control actin polymerization. Previously, we identified the Inka2 gene, a novel mammalian protein exhibiting sequence similarity to Inka1, which serves as a possible inhibitor for Pak4. Although Inka2 is dominantly expressed in the nervous system and involved in focal-adhesion dynamics, its molecular role remains unclear. Here, we found that Inka2-iBox directly binds to Pak4 catalytic domain to suppress actin polymerization. Inka2 promoted actin depolymerization and inhibited the formation of cellular protrusion caused by Pak4 activation. We further generated the conditional knockout mice of the Inka2 gene. The beta-galactosidase reporter indicated the preferential Inka2 expression in the dorsal forebrain neurons. Cortical pyramidal neurons of Inka2-/- mice exhibited decreased density and aberrant morphology of dendritic spines with marked activation/phosphorylation of downstream molecules of Pak4 signal cascade, including LIMK and cofilin. These results uncovered the unexpected function of endogenous Pak4 inhibitor in neurons. Unlike Inka1, Inka2 is a critical mediator for actin reorganization required for dendritic spine development.
Coverage-preserving sparsification of overlap graphs for long-read assembly
Authors: Jain Chirag 
Published: March 2022

AbstractRead-overlap-based graph data structures play a central role in computing de novo genome assembly using long reads. Many assembly tools use the string graph model [Myers, Bioinformatics 2005] to sparsify overlap graphs. Graph sparsification improves accuracy by removing spurious and redundant connections. However, a graph model must be coverage-preserving, i.e., it must ensure that each chromosome can be spelled as a walk in the graph, given sufficient sequencing coverage. This property becomes even more important for diploid genomes, polyploid genomes and metagenomes where there is a risk of losing haplotype-specific information.We develop a novel theoretical framework under which the coverage-preserving properties of a graph model can be analysed. We first prove that de Bruijn graph and overlap graph models are guaranteed to be coverage-preserving. We also show that the standard string graph model lacks this guarantee. The latter result is consistent with the observation made in [Hui et al. ISIT’16] that removal of contained reads during string graph construction can lead to coverage gaps. To remedy this, we propose practical heuristics that are well-supported by our theoretical results to sparsify overlap graphs. In our experiments conducted by using simulated long reads from HG002 human diploid genome, we find that 50 coverage gaps are introduced on average by ignoring contained reads from nanopore datasets. We tested the proposed heuristics for deciding which contained reads should be retained to avoid the coverage gaps. The proposed method retains a small fraction of contained reads (1 – 2%) and closes majority of the coverage gaps.
A single amino acid transporter controls the uptake of priming-inducing beta-amino acids and the associated trade-off between induced resistance and plant growth
Authors: Tao Chia-Nan , Buswell Will , Zhang Peijun , Walker Heather , Johnson Irene , Schwarzenbacher Roland , Ton Jurriaan 
Published: March 2022

ABSTRACTSelected beta-amino acids, such as beta-aminobutyric acid (BABA) and R-beta-homoserine (RBH), can prime plants for resistance against broad-spectrum diseases. Here, we describe a genome-wide screen of fully annotated Arabidopsis T-DNA insertion lines for impaired in RBH-induced immunity (iri) against the downy mildew pathogenHyaloperonospora arabidopsidis, yielding 104 lines that were partially affected and 4 lines that were completely impaired in RBH-induced resistance. Theiri1-1mutant phenotype could be confirmed by an independent T-DNA insertion in the same gene, encoding the high-affinity amino acid transporter LHT1. Using uptake experiments withIRI1/LHT1-expressing yeast cells and mass spectrometry-based quantification of RBH and BABA in leaves of mutant and over-expression lines ofIRI1/LHT1, we demonstrate that IRI1/LHT1 acts as the main transporter for cellular uptake and systemic distribution of RBH and BABA. Subsequent characterisation of mutant and over-expression lines ofIRI1/LHT1for induced resistance and growth responses revealed that the level ofIRI1/LHT1expression determines the trade-off between induced resistance and plant growth by RBH and BABA.
Glial control of sphingolipid levels sculpts diurnal remodeling of circadian circuits
Authors: Vaughen John P. , Theisen Emma , Rivas-Sema Irma Magaly , Berger Andrew B. , Kalakuntla Prateek , Anreiter Ina , Mazurak Vera C. , Rodriguez Tamy Portillo , Mast Joshua D , Hartl Tom , Perlstein Ethan O. , Reimer Richard J. , Clandinin M. Thomas , Clandinin Thomas R. 
Published: March 2022

SummaryStructural plasticity in the brain often necessitates dramatic remodeling of neuronal processes and attendant reorganization of the cytoskeleton and membranes. While cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce Glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. While the vast majority of membrane lipids are stable across the day, a specific subset, highly enriched in sphingolipids, cycles daily in a gba1b-dependant fashion. In parallel, circadian clock neurons remodel their neurites, growing and shrinking across the day to shape circadian behavior. Remarkably, this neuronal remodeling relies on a cycle of temporally offset sphingolipid biosynthesis and catabolism. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior.
Whole-brain comparison of rodent and human brains using spatial transcriptomics
Authors: Beauchamp Antoine , Yee Yohan , Darwin Ben , Raznahan Armin , Mars Rogier B. , Lerch Jason P. 
Published: March 2022

AbstractThe ever-increasing use of mouse models in preclinical neuroscience research calls for an improvement in the methods used to translate findings between mouse and human brains. Using openly accessible brain-wide transcriptomic data sets, we evaluated the similarity of mouse and human brain regions on the basis of homologous gene expression. Our results suggest that mouse-human homologous genes capture broad patterns of neuroanatomical organization, but that the resolution of cross-species correspondences can be improved using a novel supervised machine learning approach. Using this method, we demonstrate that sensorimotor subdivisions of the neocortex exhibit greater similarity between species, compared with supramodal sub-divisions, and that mouse isocortical regions separate into sensorimotor and supramodal clusters based on their similarity to human cortical regions. We also find that mouse and human striatal regions are strongly conserved, with the mouse caudoputamen exhibiting an equal degree of similarity to both the human caudate and putamen.
DISTINCTIVE FEATURES OF THE RESPIRATORY SYNCYTIAL VIRUS PRIMING LOOP COMPARED TO OTHER NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES
Authors: Cressey Tessa N. , Shareef Afzaal M. , Kleiner Victoria A. , Noton Sarah L. , Byrne Patrick O. , McLellan Jason S. , Muhlberger Elke , Fearns Rachel 
Published: March 2022

AbstractDe novo initiation by viral RNA-dependent RNA polymerases often requires a polymerase priming residue, located within a priming loop, to stabilize the initiating NTPs. Polymerase structures from three different non-segmented negative strand RNA virus (nsNSV) families revealed putative priming loops in different conformations, and an aromatic priming residue has been identified in the rhabdovirus polymerase. In a previous study of the respiratory syncytial virus (RSV) polymerase, we found that Tyr1276, the L protein aromatic amino acid residue that most closely aligns with the rhabdovirus priming residue, is not required for RNA synthesis but two nearby residues, Pro1261 and Trp1262, were required. In this study, we examined the roles of Pro1261 and Trp1262 in RNA synthesis initiation. Biochemical studies showed that substitution of Pro1261 inhibited RNA synthesis initiation without inhibiting back-priming, indicating a defect in initiation. Biochemical and minigenome experiments showed that the initiation defect incurred by a P1261A substitution could be rescued by factors that would be expected to increase the stability of the initiation complex, specifically increased NTP concentration, manganese, and a more efficient promoter sequence. These findings indicate that Pro1261 of the RSV L protein plays a role in initiation, most likely in stabilizing the initiation complex. However, we found that substitution of the corresponding proline residue in a filovirus polymerase had no effect on RNA synthesis initiation or elongation. These results indicate that despite similarities between the nsNSV polymerases, there are differences in the features required for RNA synthesis initiation.Author SummaryRSV has a significant impact on human health. It is the major cause of respiratory disease in infants and exerts a significant toll on the elderly and immunocompromised. RSV is a member of the Mononegavirales, the non-segmented, negative strand RNA viruses (nsNSVs). Like other viruses in this order, RSV encodes an RNA dependent RNA polymerase, which is responsible for transcribing and replicating the viral genome. Due to its essential role during the viral replication cycle, the polymerase is a promising candidate target for antiviral inhibitors and so a greater understanding of the mechanistic basis of its activities could aid antiviral drug development. In this study, we identified an amino acid residue within the RSV polymerase that appears to stabilize the RNA synthesis initiation complex and showed that it plays a role in both transcription and RNA replication. However, the corresponding residue in a different nsNSV polymerase does not appear to play a similar role. This work reveals a key feature of the RSV polymerase but identifies differences with the polymerases of other related viruses.
Post-transcriptional regulation by copper with a new upstream Open Reading Frame
Authors: Roy Gauthier , Antoine Rudy , Schwartz Annie , Slupek Stéphanie , Rivera-Millot Alex , Boudvillain Marc , Jacob-Dubuisson Françoise 
Published: March 2022

AbstractCopper is essential to most living beings but also toxic. Bacteria have thus developed homeostatic mechanisms to tightly control its intracellular concentration. The 3-gene operon bp2923-bfrG-bp2921 is down-regulated by copper and notably encodes a TonB-dependent transporter in Bordetella pertussis. We show that the protein encoded by bp2923, which is a member of the DUF2946 family, represents a new type of upstream Open Reading Frame (uORF) involved in post-transcriptional regulation of the downstream genes. In the absence of copper, the entire operon is transcribed and translated. Perception of copper by the nascent bp2923-coded protein via its conserved CXXC motif triggers Rho-dependent transcription termination between the first and second genes by relieving translation arrest on a conserved C-terminal RAPP motif. Homologues of bp2923 are widespread in bacterial genomes, where they head operons predicted to participate in copper homeostasis. This work has unveiled an original mode of genetic regulation by a transition metal and identified a regulatory function for a member of an uncharacterized family of bacterial proteins that we have named CruR, for copper-responsive upstream regulator.
The coordination between penicillin-binding protein 1a (PBP1a) and the hydrolytic peptidase DacB determines the integrity of bacterial cell poles
Authors: Zhang Huan , Venkatesan Srutha , Ng Emily , Nan Beiyan 
Published: March 2022

AbstractPeptidoglycan (PG) defines cell shape and protects bacteria against osmotic stress. The growth and integrity of PG require coordinated actions between synthases that insert new PG strands and hydrolases that generate openings to allow the insertion. However, the mechanisms of their coordination remain elusive. Here we show that moenomycin that inhibits a family of PG synthases known as Class-A penicillin-binding proteins (aPBPs), triggers cell lysis despite aPBPs being non-essential for cell integrity. We demonstrate that inhibited PBP1a2, an aPBP, accelerates the degradation of cell poles by DacB, a hydrolytic PG peptidase, in the bacterium Myxococcus xanthus. Moenomycin reduces the mobility of DacB molecules through PBP1a2, potentially promoting the binding between DacB and PG. Conversely, DacB also regulates the distribution and dynamics of aPBPs. These findings reveal the lethal action of moenomycin and suggest that disrupting the coordination between PG synthases and hydrolases could be more lethal than eliminating individual enzymes.
Female reproductive fluid composition differs based on mating system in Peromyscus mice
Authors: Hook Kristin A. , Liu Catherine , Joyner Katherine A. , Duncan Gregg A. , Fisher Heidi S. 
Published: March 2022

ABSTRACTPost-copulatory sexual selection is theorized to favor female traits that allow them to control sperm use and fertilization, leading to the prediction that female reproductive traits that influence sperm migration should differ between polyandrous and monogamous species. Here we exploit natural variation in the female mating strategies of closely related Peromyscus mice to compare female traits that influence sperm motility – the viscosity, pH, and calcium concentration of fluids in the reproductive tract – between polyandrous and monogamous species. We find that the viscosity and pH, but not calcium concentration, of fluids collected from both the uterus and the oviduct significantly differ between species based on mating system. Our results demonstrate the existence of a viscosity gradient within the female reproductive tract that increases in monogamous species but decreases in polyandrous species. Both species have a more alkaline environment in the uterus than oviduct, but only in the polyandrous species did we observe a decrease in calcium in the distal end of the tract. These results suggest that fluid viscosity and pH in the female reproductive tracts of these mice may be influenced by post-copulatory sexual selection and provide a promising potential mechanism for female sperm control given their importance in modulating sperm behavior.
Breakthrough Covid-19 cases despite tixagevimab and cilgavimab (Evusheld™) prophylaxis in kidney transplant recipients
Authors: Benotmane Ilies , Velay Aurélie , Vargas Gabriela Gautier , Olagne Jérôme , Fafi-Kremer Samira , Thaunat Olivier , Caillard Sophie 
Published: March 2022

AbstractWhile the combination of casirivimab-imdevimab (Ronapreve™ Roche Regeneron) has been shown to confer satisfactory protection against the delta variant kidney transplant recipients (KTRs) with COVID-19, it has limited neutralizing activity against the current variants of concern (Omicron BA.1, BA.1.1 and BA.2). In contrast, cilgavimab-tixagevimab combination (Evusheld™, Astra Zeneca) retains a partial neutralizing activity against omicron in vitro. We examined whether preexposure prophylaxis with Evusheld™ can effectively protect kidney transplant recipients (KTRs) against the Omicron variant.Of the 416 KTRs who received intramuscular prophylactic injections of Evusheld™ (150 mg tixagevimab and 150 mg cilgavimab), 39 (9.4%) developed COVID-19. With the exception of one patient, all KTRs were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients, respectively. Two KTRs died of COVID-19-related acute respiratory distress syndrome. SARS-CoV-2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n=1). Viral neutralizing activity of the serum against BA.1 variant was negative in the 12 tested patients, suggesting that this prophylaxis strategy provides insufficient protection against this variant of concern.Preexposure prophylaxis with Evusheld™ does not adequately protect KTRs against Omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.
Reproductive skew, fighting costs and winner–loser effects in social dominance evolution
Authors: Leimar Olof , Bshary Redouan 
Published: March 2022

Abstract

Social hierarchies are often found in group‐living animals and can be formed through pairwise aggressive interactions. The dominance rank can influence reproductive success (RS) with a skew towards high‐ranking individuals.

Using game theory, we investigate how the opportunity for differently ranked individuals to achieve RS influences the costs of hierarchy formation and the strength of winner and loser effects.

In our model, individuals adjust their aggressive and submissive behaviour towards others through reinforcement learning. The learning is based on rewards and penalties, which depend on relative fighting ability. From individual‐based simulations, we determine evolutionary equilibria of traits such as learning rates. We examine situations that differ in the extent of monopolisation of contested RS by dominants and in the proportion of total RS that is contested.

The model implements two kinds of fighting costs: a decrease in effective fighting ability from damage (loss of condition) and a risk of mortality that increases with the total accumulated damage. Either of these costs can limit the amount of fighting.

We find that individuals form stable dominance hierarchies, with a positive correlation between dominance position and fighting ability. The accumulated costs differ between dominance positions, with the highest costs paid by low or intermediately ranked individuals. Costs tend to be higher in high‐skew situations.

We identify a ‘stay‐in, opt‐out’ syndrome, comprising a range from weaker (stay‐in) to stronger (opt‐out) winner–loser effects. We interpret the opt‐out phenotype to be favoured by selection on lower ranked individuals to opt out of contests over social dominance, because it is more pronounced when more of the total RS is uncontested.

We discuss our results in relation to field and experimental observations and argue that there is a need for empirical investigation of the behaviour and reproductive success of lower ranked individuals.
Abundant and persistent sulfur‐oxidizing microbial populations are responsive to hypoxia in the Chesapeake Bay
Authors: Arora‐Williams Keith , Holder Christopher , Secor Maeve , Ellis Hugh , Xia Meng , Gnanadesikan Anand , Preheim Sarah P. 
Published: March 2022

SummaryThe number, size and severity of aquatic low‐oxygen dead zones are increasing worldwide. Microbial processes in low‐oxygen environments have important ecosystem‐level consequences, such as denitrification, greenhouse gas production and acidification. To identify key microbial processes occurring in low‐oxygen bottom waters of the Chesapeake Bay, we sequenced both 16S rRNA genes and shotgun metagenomic libraries to determine the identity, functional potential and spatiotemporal distribution of microbial populations in the water column. Unsupervised clustering algorithms grouped samples into three clusters using water chemistry or microbial communities, with extensive overlap of cluster composition between methods. Clusters were strongly differentiated by temperature, salinity and oxygen. Sulfur‐oxidizing microorganisms were found to be enriched in the low‐oxygen bottom water and predictive of hypoxic conditions. Metagenome‐assembled genomes demonstrate that some of these sulfur‐oxidizing populations are capable of partial denitrification and transcriptionally active in a prior study. These results suggest that microorganisms capable of oxidizing reduced sulfur compounds are a previously unidentified microbial indicator of low oxygen in the Chesapeake Bay and reveal ties between the sulfur, nitrogen and oxygen cycles that could be important to capture when predicting the ecosystem response to remediation efforts or climate change.
Beyond the pest: Life history, ecology and ethnoentomology of the giant wood moth (Endoxyla cinereus)
Authors: Thurman Jessa H. 
Published: March 2022

AbstractThe giant wood moth,Endoxyla cinereus(Tepper, 1890) (Cossidae: Zeuzerinae), is the heaviest known moth in the world and a traditional food resource to Indigenous Australians, but it is primarily understood as a pest. Research on its pest status has highlighted the different interactions this moth has with plants and animals, suggesting that it plays an important role in Australian ecosystems. Here, I review the literature onEndoxyla cinereusto compile and illustrate its life history and species‐specific ecological interactions for the first time. This life history is then applied to interpret the ecological role that this species plays in shaping forest communities, serving as a key food resource to other animals and creating habitat in the form of tree hollows. Based on this, the giant wood moth is an ecosystem engineer. The human impact of this species is then reviewed including indigenous use ofE. cinereusand otherEndoxylaspp., and the forestry pest status of these moths. Consideration of the moth's long, cryptic life history reveals the scientific knowledge possessed by Indigenous Australians on harvesting wood moth larvae, while future studies on earlier life stages and pest, identity may aid the development of sustainable pest management. Finally, the taxonomic status ofEndoxyla cinereusis briefly discussed, as previous research suggests the presence of either cryptic or misidentified species. Future research on the giant wood moth may aid both natural and cultural conservation programmes and provide novel solutions for managing the species as a pest. This review provides a framework for studying the giant wood moth and documenting the life history of other wood moths.