bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Histories and Study Duration matter less than Prior Knowledge of Vital Rates to Inverse Integral Projection Models
Authors: Bernard Connor D. , Bonsall Michael B. , Salguero-Gómez Roberto
Published: April 2024

Ecology has been surprisingly slow to address the uncertainty and bias that results from using short-term time series to draw long-term inference. To improve our understanding of assumptions around the temporal structure of vital rates (e.g., survival, reproduction), we need tools that are feasible and capture longer-term, state-structured population dynamics.

Here, we use inverse modelling of a set of integral projection models (IPMs) to show how demographic rates can be accurately reconstructed from state-structure fluctuations in a population time-series. We use a particle-filtering optimisation algorithm to fit vital rates from time-series of varying length, parameter combinations, priors, and life histories.

We show how key life history traits such as generation time have little effect on the ability of our approach to accurately identify vital rates using state structure over time. Further, contrary to our expectations, the duration of our time-series data has relatively modest impact on the estimation of vital rates compared to the critical role of prior knowledge on vital rates.

ur framework to estimate IPM vital rates highlights the potential of inverse models to extend time-series for demographic models, but also demonstrates that long-term time-series are not a perfect surrogate for detailed demographic inference. We discuss the need for more work exploring the conditions when inverse modelling is an adequate tool based on species traits.
Diet and Size-at-Birth Affect Larval Rockfish Condition and Survival
Authors: Walsh Kamran A. , Thompson Andrew R. , Kwan Garfield T. , Semmens Brice X. , Fennie H. William , Swalethorp Rasmus
Published: April 2024

Feeding success and maternal effects on larval size have long been hypothesized as important contributors to interannual recruitment variability in marine fishes. This study examined the feeding ecology and influences of diet and size-at-birth on length and growth of larval rockfishes (Sebastesspp.). Prey carbon biomass and selection were calculated from gut contents, size-at-birth was estimated using otolith core size, and recent growth was derived from outer otolith increment widths. Biomass contributions of preferred prey and otolith data were integrated into Bayesian hierarchical models predicting length and growth. Larvae primarily fed on and selected for copepod nauplii and Calanoid copepodites, modulating feeding with ontogeny and in response to prey availability. Based on carbon weight, the relative contribution of Calanoid copepodites to the diet was more strongly and positively correlated with length and growth than that of nauplii. Younger larvae experienced faster growth in association with Calanoid copepodite consumption than older larvae. Positive effects of core radius suggest that initial larval size, believed to be mediated by maternal provisioning, increases the likelihood of survival, larger size and faster growth. These findings ultimately provide evidence that selective feeding and size-at-birth mediate rockfish survival in early life stages.
Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations
Authors: Dabi Amjad , Schrider Daniel
Published: April 2024

Simulations are an essential tool in all areas of population genetic research, used in tasks such as the validation of theoretical analysis and the study of complex evolutionary models. Forward-in-time simulations are especially flexible, allowing for various types of natural selection, complex genetic architectures, and non-Wright-Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations and genomes. A popular method to alleviate this burden is to scale down the population size by some scaling factor while scaling up the mutation rate, selection coefficients, and recombination rate by the same factor. However, this rescaling approach may in some cases bias simulation results. To investigate the manner and degree to which rescaling impacts simulation outcomes, we carried out simulations with different demographic histories and distributions of fitness effects using several values of the rescaling factor,Q, and compared the deviation of key outcomes (fixation times, allele frequencies, linkage disequilibrium, and the fraction of mutations that fix during the simulation) between the scaled and unscaled simulations. Our results indicate that scaling introduces substantial biases to each of these measured outcomes, even at small values ofQ. Moreover, the nature of these effects depends on the evolutionary model and scaling factor being examined. While increasing the scaling factor tends to increase the observed biases, this relationship is not always straightforward, thus it may be difficult to know the impact of scaling on simulation outcomes a priori. However, it appears that for most models, only a small number of replicates was needed to accurately quantify the bias produced by rescaling for a givenQ. In summary, while rescaling forward-in-time simulations may be necessary in many cases, researchers should be aware of the rescaling procedure's impact on simulation outcomes and consider investigating its magnitude in smaller scale simulations of the desired model(s) before selecting an appropriate value ofQ.
Exploring new nanopore sensors from the aerolysin family
Authors: Cirauqui Nuria , Bada Juarez Juan F. , Meireles Fernando Augusto T. P. , Barry Julian , Bokori-Brown Monika , Marcaida Maria J. , Cao Chan , Dal Peraro Matteo
Published: April 2024

Aerolysin-like proteins are a family of β-pore-forming toxins which are widely present in all kingdoms of life. Recently, this family of proteins is gaining attention because of their biotechnological application as nanopore sensors for sensing and sequencing of biomolecules. Here, we explore the possibilities of using the knowledge of the sequence and structure of proteins to screen and explore new potential nanopore candidates. However, in spite of the conserved structural fold, the sequence identity in this family is very low. This complicates their sequence alignment, hindering the understanding of their pore structure and properties, therefore limiting further biotechnological applications. In an attempt to further understand the properties of aerolysin-like pores, we analyzed the pore structure of three family members,Clostridium perfringensepsilon toxin (ETX),Laetiporus sulphureuslectin (LSL) andBacillus thuringiensisparasporin-2, comparing it to aerolysin. Their structure and sensing capabilities for ssDNA were first assessed byin silicomethods. Moreover, ETX was characterized experimentally in planar lipid membranes for the detection of biomolecules. We found that ETX can form three distinct pore conformations, each presenting a specific open pore current, and only one of them being able to translocate ssDNA. When the ssDNA translocate through ETX, the depth of current blockage is higher compared to aerolysin which indicates a higher sensitivity for molecular sensing. Our findings open a new venue for improving and diversifying nanopore capabilities for molecular sensing.
Gossamer: Scaling Image Processing and Reconstruction to Whole Brains
Authors: Marrett Karl , Moradi Keivan , Park Chris Sin , Yan Ming , Choi Chris , Zhu Muye , Akram Masood , Nanda Sumit , Xue Qing , Mun Hyun-Seung , Gutierrez Adriana E. , Rudd Mitchell , Zingg Brian , Magat Gabrielle , Wijaya Kathleen , Dong Hongwei , Yang X. William , Cong Jason
Published: April 2024

Neuronal reconstruction–a process that transforms image volumes into 3D geometries and skeletons of cells– bottlenecks the study of brain function, connectomics and pathology. Domain scientists needexactandcompletesegmentations to study subtle topological differences. Existing methods are diskbound, dense-access, coupled, single-threaded, algorithmically unscalable and require manual cropping of small windows and proofreading of skeletons due to low topological accuracy. Designing a data-intensive parallel solution suited to a neurons’ shape, topology and far-ranging connectivity is particularly challenging due to I/O and load-balance, yet by abstracting these vision tasks into strategically ordered specializations of search, we progressively lower memory by 4 orders of magnitude. This enables 1 mouse brain to be fully processed in-memory on a single server, at 67× the scale with 870× less memory while having 78% higher automated yield than APP2, the previous state of the art in performant reconstruction.
Research Transparency in 59 Disciplines of Clinical Medicine: A Meta-Research Study
Authors: Sofi-Mahmudi Ahmad , Raittio Eero , Uribe Sergio E. , Khademioore Sahar , Zeraatkar Dena , Mbuagbaw Lawrence , Bouter Lex M. , Robinson Karen A.
Published: April 2024

Background

Transparency in health research is crucial as it allows for the scrutiny and replication of findings, fosters confidence in scientific outcomes, and ultimately contributes to the advancement of knowledge and the betterment of society.

Aim

We aimed to assess five transparency practices in scientific publications (data availability, code availability, protocol registration, conflicts of interest (COI) and funding disclosures) from open-access articles published in medical journals.

Methods

We searched and exported all open-access articles from Science Citation Index Expanded (SCIE)-indexed journals through the Europe PubMed Central database published until March 16, 2024. Basic journal- and article-related information was retrieved from the database. We then assessed five transparency practices in the articles using thertransparentpackage in R.

Results

The analysis included 2,002,955 open-access articles from SCIE-indexed medical journals (open-access percentage=59.0%). Of these, 87.5% (95% CI: 87.4%-87.5%) disclosed COI and 80.1% (95% CI: 80.0%-80.1%) disclosed funding. Protocol registration was declared in 6.6% (95% CI: 6.6%-6.6%), data sharing in 7.6% (95% CI: 7.6%-7.6%), and code sharing in 1.4% (95% CI: 1.4%-1.4%) of the articles. More than 76.0% declared at least two transparency practices, while all five practices were declared in less than 0.02%. The data showed an increasing trend in all transparency practices since the late 2000s. Articles published in journals with higher impact factors and articles receiving more citations had increased odds of COI and funding disclosures, as well as data and code sharing. There were notable differences in transparency practices across the disciplines.

Conclusion

While most articles had COI and funding disclosures, adherence to other transparency practices was grossly insufficient. To increase protocol registration, data, and code sharing, much stronger incentives and mandates are needed from all stakeholders.
GENDER NORMS AND ATTITUDE TOWARDS ABORTION AMONG VERY YOUNG ADOLESCENTS IN KENYA AND NIGERIA
Authors: Alabi Matthew Ayodele , Bello Bamidele M. , Maina Beatrice W.
Published: April 2024

Introduction

Unsafe abortion is a major cause of death in sub-Saharan African countries with very young adolescents (VYAs) at increased risk due to their high vulnerability to unprotected sex and unplanned pregnancies. Abortion beliefs and attitudes are considered to be partly rooted in traditional views on gender and religious influences. This study is informed by the limited data on gender norm perception and its association with abortion among VYAs despite the increasing prevalence of unsafe abortion reported among this group.

Materials

Data for this study was collected as part of a longitudinal survey on the gendered socialization and sexual and reproductive health of very young, in-school adolescents aged 10-14 years in Kenya and Nigeria. The study obtained quantitative data from 1,912 VYAs using a structured questionnaire. The results presented in this paper are from the quantitative baseline data collected in Kenya and Nigeria

Result

The study found significant regional differentials in attitudes toward abortion and gender norm perception of the VYAs from the two regions. VYAs from Nigeria were more likely to endorse abortion practices relative to their counterparts from Kenya. Factors associated with endorsement of abortion practice were gender norms about Sexual Double Standards (SDS) and Normative Heterosexual Relation (NHR) in Nigeria and knowledge of where to get a condom, NHR, and Normative Romantic Relationship (NRR) in Kenya.

Conclusion

Intervention efforts seeking to promote positive gender norms and attitudes towards SRH must begin with the VYAs and must consider regional variations and address knowledge and access to SRH commodities.

What is already known on this topic

previous studies have explored attitudes towards gender norms and abortion among young people and adults, with little known among very young adolescents aged 10-14 years.

What this study adds

the study contributed to the limited research on gender norms and attitudes towards abortion among very young adolescents.

How this study might affect research, practice, and policy

The outcome of this suggests the need to consider regional variations when developing interventions and policies addressing gender norms and attitudes towards abortion in Africa.
Evidence of aberrant anti-Epstein-Barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue
Authors: Mouat Isobel C. , Zhu Judy , Aslan Alperen , McColl Barry W. , Allan Stuart M. , Smith Craig J. , Buckwalter Marion S. , McCulloch Laura
Published: April 2024

BACKGROUND

Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.

AIMS

We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.

METHODS

In a chronic ischemic stroke cohort (>6 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F <40) and low fatigue (FACIT-F >41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data.

RESULTS

We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar between the groups, we observed an altered antibody response against EBV antigens in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (VCA; 2.244 ± 0.926 vs 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to EBV (3.23 × 105± 4.44 × 104high fatigue versus 4.60 × 105± 9.28 × 104low fatigue; P= 0.288).

CONCLUSIONS

These findings indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke and warrants further investigation.
AncestryPainter2.0: Visualizing ancestry composition and admixture history graph
Authors: Chen Shuanghui , Lei Chang , Zhao Xiaohan , Pan Yuwen , Lu Dongsheng , Xu Shuhua
Published: April 2024

To effectively depict the results of population genetics studies, it is essential to present ancestry composition and genetic distance. The growing amount of genomic data prompted us to designAncestryPainter1.0, a Perl program to display the ancestry composition of numerous individuals using a rounded graph. Motivated by the requests of users in practical applications, we updatedAncestryPainterto version 2.0 by coding in an R package and improving the layout, providing more options and compatible statistical functions for graphing. In particular,AncestryPainter2.0 implements a method admixture history graph (AHG) to infer the admixture sequence of multiple ancestry populations, and allows for multiple pie charts at the center of the graph to display the ancestry composition of more than one target population. We also introduced an additional graphing module to visualize genetic distance through radial bars of varying lengths surrounding a core. Visualization functionsper sehave been enhanced in this update as well. Furthermore,AncestryPainter2.0 includes two statistical modules to 1) merge ancestry proportion matrices and 2) infer admixture sequences through correlation analyses.AncestryPainter2.0 is publicly available athttps://github.com/Shuhua-Group/AncestryPainterV2andhttps://pog.fudan.edu.cn/#/Software.
Inhibitory Plasticity Enhances Sequence Storage Capacity and Retrieval Robustness
Authors: Gong Ziyi , Brunel Nicolas
Published: April 2024

The generation of motor behaviors and the performance of complex cognitive tasks rely on sequential activity in specific brain structures. The mechanisms of learning and retrieval of these temporal patterns of activity are still poorly understood. Emerging evidence has high-lighted the importance of inhibition to learning and memory. However, the specific functions of inhibitory plasticity in the learning and retrieval of sequential activity have been studied very little, apart from its role in maintaining excitation-inhibition (E-I) balance. Using simulations and dynamical mean-field theory of balanced E-I networks, we found that sequences can be stored and retrieved using plasticity in both E-to-I and I-to-E pathways, in the absence of recurrent excitatory plasticity. Networks with both E-to-I and I-to-E plasticity are shown to exhibit higher optimal capacity than models in which plasticity is restricted to recurrent excitation. We further show that inhibitory plasticity enhances robustness to external noise and initial cue perturbation. Thus, our work suggests new computational roles for inhibitory plasticity in improving capacity and robustness of sequence learning.
Selective modification of ascending spinal outputs in acute and neuropathic pain states
Authors: Yarmolinsky David A. , Zeng Xiangsunze , MacKinnon-Booth Natalie , Greene Caitlin , Kim Chloe , Woolf Clifford J.
Published: April 2024

Pain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain and alters pain perception. We utilized chronic calcium imaging of spinal dorsal horn neurons to determine how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy conditions, we identify stable, narrowly tuned outputs selective for cooling or warming, and a neuronal ensemble activated by intense/noxious thermal and mechanical stimuli. Induction of an acute peripheral sensitization with capsaicin selectively and transiently retunes nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury-induced neuropathic pain results in a persistent suppression of innocuous spinal outputs coupled with activation of a normally silent population of high-threshold neurons. These results demonstrate the differential modulation of specific spinal outputs to the brain during nociceptive and neuropathic pain states.
A prion-like protein regulates the 2-dimensional to 3-dimensional growth transition in the mossPhyscomitrium patens
Authors: Weeks Zoe , Chaturvedi Gargi , Day Emily , Kelly Steven , Moody Laura A.
Published: April 2024

The colonization of the land by plants coincided with the evolution of 3-dimensional (3D) growth; the acquisition of apical cells with the capacity to rotate the plane of cell division. The mossPhyscomitrium patenshas recently been developed as a model to dissect the genetic basis of 3D growth, an invariable and unifying feature of all land plants. The cytokinin-unresponsivePpnog1-Rmutant incorrectly orients division planes in developing buds and thus fails to make the transition to 3D growth. To reveal the genetic interactors of thePpNOG1gene, which encodes a protein with a C-terminal UBA domain, we performed a screen and identified thesuppressor of nog1a(snog1a) mutant. We have mapped the causative mutation to a gene that encodes a prion-like protein related to FLOE2/3 and demonstrated that the mutant phenotypes observed in both anog1disruptant mutant (nog1dis) andsnog1acan be attributed to changes in cytokinin perception. We present a revised model for 3D growth and suggest that the 2D-to-3D growth transition is regulated, at least in part, by liquid-liquid phase separation (LLPS).

SUMMARY STATEMENT

The transition to 3D growth is negatively regulated by a prion-like protein that both alters cytokinin signaling and has been implicated in liquid-liquid phase separation (LLPS).
CONCERTED PLANT GROWTH AND DEFENSE THROUGH TARGETED PHYTOHORMONE CROSSTALK MODIFICATION
Authors: Johnston Grace A. , Berry Hannah M. , Kojima Mikiko , Sakakibara Hitoshi , Argueso Cristiana T.
Published: April 2024

Plant immunity activation often results in suppression of plant growth, particularly in the case of constitutive immune activation. We discovered that signaling of the phytohormone cytokinin (CK), known to regulate plant growth through the control of cell division and shoot apical meristem (SAM) activity, can be suppressed by negative crosstalk with the defense phytohormones jasmonic acid (JA), and most evidently, salicylic acid (SA). We show that changing the negative crosstalk of SA on CK signaling in autoimmunity mutants by targeted increase of endogenous CK levels results in plants resistant to pathogens from diverse lifestyles, and relieves suppression of reproductive growth. Moreover, such changes in crosstalk result in a novel reproductive growth phenotype, suggesting a role for defense phytohormones in the SAM, likely through regulation of nitrogen response and cellular redox status. Our data suggest that targeted phytohormone crosstalk engineering can be used to achieve increased reproductive growth and pathogen resistance.

SIGNIFICANCE STATEMENT

Plants constantly integrate environmental stimuli with developmental programs to optimize their growth and fitness. Excessive activation of the plant immune system often leads to decreased plant growth, a process known as the growth-defense tradeoff. Here, we adapted phytohormone levels in Arabidopsis reproductive tissues of autoimmunity mutants to change phytohormonal crosstalk and diminish the growth tradeoff, resulting in increased broad resistance to pathogens and decreased growth suppression. Similar approaches to phytohormone crosstalk engineering could be used in different contexts to achieve outcomes of higher plant stress resilience and yield.
Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis
Authors: Kocot Joanna , Kosa Peter , Ashida Shinji , Pirjanian Nicolette , Goldbach-Mansky Raphaela , Peterson Karin , Fossati Valentina , Holland Steven M. , Bielekova Bibiana
Published: April 2024

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Clemastine fumarate, the over-the-counter antihistamine and muscarinic receptor blocker, has remyelinating potential in MS. A clemastine arm was added to an ongoing platform clinical trial TRAP-MS (NCT03109288) to identify a cerebrospinal fluid (CSF) remyelination signature and to collect safety data on clemastine in patients progressing independently of relapse activity (PIRA). The clemastine arm was stopped per protocol-defined criteria when 3/9 patients triggered individual safety stopping criteria (χ2p=0.00015 compared to remaining TRAP-MS treatments). Clemastine treated patients had significantly higher treatment-induced disability progression slopes compared to remaining TRAP-MS participants (p=0.0075). Quantification of ∼7000 proteins in CSF samples collected before and after clemastine treatment showed significant increase in purinergic/ATP signaling and pyroptosis cell death. Mechanistic studies showed that clemastine with sub-lytic doses of extracellular ATP activates inflammasome and induces pyroptotic cell death in macrophages. Clemastine with ATP also caused pyroptosis of induced pluripotent stem cell-derived human oligodendrocytes. Antagonist of the purinergic channel P2RX7 that is strongly expressed in oligodendrocytes and myeloid cells, blocked these toxic effects of clemastine. Finally, re-analyses of published snRNAseq studies revealed increased P2RX7 expression and pyroptosis transcriptional signature in microglia and oligodendrocytes in MS brain, especially in chronic active lesions. CSF proteomic pyroptosis score was increased in untreated MS patients, was higher in patients with progressive than relapsing-remitting disease and correlated significantly with rates of MS progression. Thus, pyroptosis is likely first well-characterized mechanism of CNS injury underlying PIRA even outside of clemastine toxicity.

One Sentence Summary

Clemastine enhanced disability accumulation in patients progressing by non-lesional MS activity by potentiating intrathecal P2RX7 signaling and pyroptosis.
vcfgl: A flexible genotype likelihood simulator for VCF/BCF files
Authors: Altinkaya Isin , Nielsen Rasmus , Korneliussen Thorfinn Sand
Published: April 2024

Motivation

Accurate quantification of genotype uncertainty is pivotal in ensuring the reliability of genetic inferences drawn from NGS data. Genotype uncertainty is typically modeled using Genotype Likelihoods (GLs), which can help propagate measures of statistical uncertainty in base calls to downstream analyses. However, the effects of errors and biases in the estimation of GLs, introduced by biases in the original base call quality scores or the discretization of quality scores, as well as the choice of the GL model, remain under-explored.

Results

We present vcfgl, a versatile tool for simulating genotype likelihoods associated with simulated read data. It offers a framework for researchers to simulate and investigate the uncertainties and biases associated with the quantification of uncertainty, thereby facilitating a deeper understanding of their impacts on downstream analytical methods. Through simulations, we demonstrate the utility of vcfgl in benchmarking GL-based methods. The program can calculate GLs using various widely used genotype likelihood models and can simulate the errors in quality scores using a Beta distribution. It is compatible with modern simulators such as msprime and SLiM, and can output data in pileup, VCF/BCF and gVCF file formats. The vcfgl program is freely available as an efficient and user-friendly software written in C/C++.

Availability

vcfgl is freely available athttps://github.com/isinaltinkaya/vcfgl.

Contact

isin.altinkaya@sund.ku.dk

Supplementary information

Supplementary information is available online.
Quantitative RNA spatial profiling using single-molecule RNA FISH on plant tissue cryosections
Authors: Zhang Xue , Fonseca Alejandro , Kutashev Konstantin , Sicard Adrien , Duncan Susan , Rosa Stefanie
Published: April 2024

Single-molecule fluorescencein situhybridization (smFISH) has emerged as a powerful tool to study gene expression dynamics with unparalleled precision and spatial resolution in a variety of biological systems. Recent advancements have expanded its application to encompass plant studies, yet a demand persists for a simple and robust smFISH method adapted to plant tissue sections. Here, we present an optimized smFISH protocol (cryo-smFISH) for visualizing and quantifying single mRNA molecules in plant tissue cryosections. This method exhibits remarkable sensitivity, capable of detecting low-expression transcripts, including long non-coding RNAs. Integrating a deep learning-based algorithm in our image analysis pipeline, our method enables us to assign RNA abundance precisely in nuclear and cytoplasmic compartments. Compatibility with Immunofluorescence also allows RNA and endogenous proteins to be visualized and quantified simultaneously. Finally, this study presents for the first time the use of smFISH for single-cell RNA sequencing (scRNA-seq) validation in plants. By extending the smFISH method to plant cryosections, an even broader community of plant scientists will be able to exploit the multiple potentials of quantitative transcript analysis at cellular and subcellular resolutions.
Interplay between the Xer recombination system and the dissemination of antibioresistance inAcinetobacter baumannii
Authors: Corentin Blanchais , Carine Pages , Campos Manuel , Boubekeur Kenza , Rachel Contarin , Orlando Mathias , Patricia Siguier , Maria-Halima Laaberki , François Cornet , Xavier Charpentier , Philippe Rousseau
Published: April 2024

Antibiotic-resistant infections pose a pressing challenge in clinical settings. Plasmids are widely recognized for hastening the emergence of resistance by facilitating horizontal gene transfer of antibiotic resistance genes among bacteria. We explore this inquiry inAcinetobacter baumannii, a globally emerging nosocomial pathogen responsible for a wide array of infections with worrying accumulation of resistances, notably involving plasmids. In this specie, plasmids of the Rep_3 family harbor adaptive genes within variable regions edged by potential site-specific recombination sites recognized by the XerCD recombinase. We first show that the Xer system ofAcinetobacter baumanniifunctions as described inEscherichia coli, resolving chromosome dimers at thedifsite as well as recombining plasmid-borne sites. The multiple Xer recombination sites found in Rep_3 plasmids do not, however, allow excising plasmid fragments. They rather recombine to co-integrate plasmids, which may then further evolve to exchange genes. Co-integrates represent a significative part of the plasmid population and their formation is controlled by the sequence of the recombination sites determining their compatibility between the recombining sites. We conclude that plasmids frequently exchange genes inAcinetobacter baumanniiusing Xer recombination, allowing a high level yet controlled plasticity involved in the acquisition and combination of resistance genes.
Serotype and distribution of adhesion genes inStreptococcus mutansclinical isolates
Authors: Donnet Laura , Claisse Olivier , Samot Johan
Published: April 2024

The delicate balance of the oral cavity is disrupted by hygiene and diet changes, leading to caries. The virulence ofStreptococcus mutans, a key caries pathogen, is partly explained by its rhamnose-glucose polysaccharide (RGP) and its sucrose-dependent and -independent adhesion mechanisms. This study investigates the diversity ofS. mutansthrough analysis of its RGP and the distribution of sucrose-independent adhesion proteins (SpaP, WapA, Cnm, Cbm) in Parkinson’s disease patients.

In the PARKIDENT clinical trial, strains were isolated from saliva samples of Parkinson’s patients before and after oral hygiene procedures. Strains were preanalyzed by multiplex PCR for serotype and collagen-binding proteins, followed by high-throughput sequencing and bioinformatics analysis using RAST® and BLAST®. Phylogenetic analyses and protein modeling were also conducted.

Of 40 patients in the Parkident clinical trial, only 24 hadStreptococcus mutansstrains isolable from salivary swabs. Serotyping revealed that over 80% of the 44 strains isolated were serotype c, in line with prevalence data in the literature. Furthermore, only SpaP types A and B were identified in the strains. The low variability observed for the WapA protein underlines its functional importance. Finally, thecbmgene was not found in any strain, and only 5 strains possessed thecnmgene, all of them serotype c.

The study of these 44Streptococcus mutansstrains showed characteristics similar to other populations. Serotype c predominates, with minimal peptide variability in adhesion proteins (SpaP, WapA). Collagen-binding proteins Cnm and Cbm are rare or absent. Further research is essential for detailed strain distribution in Parkinson’s-affected and general French populations due toS. mutans’growing role in extra-oral pathologies.
African Swine Fever Virus Protein B263R Inhibits Autophagy by Promoting Proteasomal Degradation of Beclin1
Authors: Ding Shuxiang , Wang Xingbo , Deng Tingjuan , Xu Kang , Dong Weiren , Yan Yan , Zhou Jiyong , Hu Boli
Published: April 2024

African swine fever (ASF) is a highly contagious viral disease that affects both domestic and wild pigs, leading to substantial economic losses in the swine industry. However,the precise role of ASFV-encoded viral protein in viral replication and disease has remained elusive. In our study, we elucidated that B263R inhibited autophagy by interacting with Beclin1. Mechanistically, the binding of B263R to Beclin1 promotes its degradation through the mediation of K48-linked ubiquitination at site K31. Notably, the knockdown of Beclin1 mitigated the effect of B263R on reducing the levels of LC3-II, thus further affirming the pivotal role of Beclin1 in B263R-mediated autophagy inhibition. The proliferation of recombinant adenovirus inherently expressing B263R significantly decreased, underscoring the inherent role of B263R-mediated autophagy in virus replication. These findings shed light on the molecular mechanisms employed by ASFV to evade host cell autophagic defenses and offered potential targets for therapeutic interventions against ASFV infection.

IMPORTANCE

Understanding the mechanisms underlying the evasion of host cellular defenses by the African swine fever virus (ASFV) is of pivotal significance owing to its profound impact on the global swine industry. The precise functional roles of ASFV proteins in virus replication and disease remain incompletely characterized. In this study, it is demonstrated that a specific ASFV protein, B263R, acts to inhibit autophagy by interacting with Beclin1, thereby facilitating its degradation. The elucidation of this molecular pathway not only advances our comprehension of ASFV pathogenesis but also furnishes potential targets for therapeutic interventions against ASFV infection. By unraveling the intricate interplay between ASFV and host cell autophagy, this scholarly endeavor contributes invaluable insights to the development of strategies aimed at mitigating the spread of ASFV and minimizing its adverse repercussions on the swine industry.
Unique cortical and subcortical activation patterns for different conspecific calls in marmosets
Authors: Jafari Azadeh , Dureux Audrey , Zanini Alessandro , Menon Ravi S. , Gilbert Kyle M. , Everling Stefan
Published: April 2024

The common marmoset (Callithrix jacchus) is known for its highly vocal nature, displaying a diverse range of different calls. Functional imaging in marmosets has shown that the processing of conspecific calls activates a brain network that includes fronto-temporal cortical and subcortical areas. It is currently unknown whether different call types activate the same or different networks. Here we show unique activation patterns for different calls. Nine adult marmosets were exposed to four common vocalizations (phee, chatter, trill, and twitter), and their brain responses were recorded using event-related fMRI at 9.4T. We found robust activations in the auditory cortices, encompassing core, belt, and parabelt regions, and in subcortical areas like the inferior colliculus, medial geniculate nucleus, and amygdala in response to these conspecific calls. Different neural activation patterns were observed among the vocalizations, suggesting vocalization-specific neural processing. Phee and twitter calls, often used over long distances, activated similar neural circuits, whereas trill and chatter, associated with closer social interactions, demonstrated a closer resemblance in their activation patterns. Our findings also indicate the involvement of the cerebellum and medial prefrontal cortex (mPFC) in distinguishing particular vocalizations from others.

Significance Statement

This study investigates the neural processing of vocal communications in the common marmoset (Callithrix jacchus), a species with a diverse vocal repertoire. Utilizing event-related fMRI at 9.4T, we demonstrate that different marmoset calls (phee, chatter, trill, and twitter) elicit distinct activation patterns in the brain, challenging the notion of a uniform neural network for all vocalizations. Each call type distinctly engages various regions within the auditory cortices and subcortical areas, reflecting the complexity and context-specific nature of primate communication. These findings offer insights into the evolutionary mechanisms of primate vocal perception and provide a foundation for understanding the origins of human speech and language processing.
Histone H3 Orchestrates the Ubiquitination of Nucleosomal H2A by BRCA1/BARD1-UbcH5c Complex
Authors: Goldman Alexandra R. , Shah Tejas , Torabifard Hedieh
Published: April 2024

The Breast Cancer Associated Protein 1 (BRCA1) is a human tumor suppressor protein that commonly functions as ubiquitin ligase enzyme (E3) in the ubiquitination of the C-terminal H2A. BRCA1 enhances ubiquitin ligase activity by forming a heterodimeric complex with the BRCA1 Associated Ring Domain Protein (BARD1). The BRCA1/BARD1 complex works in concert with the ubiquitin-conjugating enzyme (UbcH5c or E2) to ubiquitinate one of the five lysines of the H2A C-terminal, ultimately promoting the repair of double-stranded DNA breaks. The mutations in the BRCA1-UbcH5c portion of the E3-E2 complex have been linked to breast and ovarian cancer. However, the mechanism of BRCA1/BARD1-UbcH5c complex ubiquitination at H2A is poorly understood, and the ubiquitination of exact lysine is debated. In this study, we sought to expand on the current research on H2A ubiquitination by using all-atom molecular dynamics simulations to model the BRCA1/BARD1-UbcH5c complex with the human ubiquitin protein (Ub). The Ub protein covalently bonds to the active site of E2, resulting in diminished flexibility of the E3-E2 complex with respect to the nucleosome core particle. The results of this study suggest a possible contribution of H3 in determining the preferred orientation of E2-Ub with respect to the H2A C-terminal lysines.
Features of the DNAEscherichia coliRecN interaction revealed by fluorescence microscopy and single-molecule methods
Authors: Roshektaeva Viktoria D. , Alekseev Aleksandr A. , Vedyaykin Alexey D. , Vinnik Viktor A. , Baitin Dmitrii M. , Bakhlanova Irina V. , Pobegalov Georgii E. , Khodorkovskii Mikhail A. , Morozova Natalia E.
Published: April 2024

The SOS response is a condition that occurs in bacterial cells after DNA damage. In this state, the bacterium is able to recover the integrity of its genome. Due to the increased level of mutagenesis in cells during the repair of DNA double-strand breaks, the SOS response is also an important mechanism for bacterial adaptation to the antibiotics. One of the key proteins of the SOS response is the SMC-like protein RecN, which helps the RecA recombinase to find a homologous DNA template for repair. In this work, the localization of the recombinant RecN protein in livingEscherichia colicells was revealed using fluorescence microscopy. It has been shown that the RecN, outside the SOS response, is predominantly localized at the poles of the cell, and in dividing cells, also localized at the center. Usingin vitromethods including fluorescence microscopy and optical tweezers, we show that RecN predominantly binds single-stranded DNA in an ATP-dependent manner. RecN has both intrinsic and single-stranded DNA-stimulated ATPase activity. The results of this work may be useful for better understanding of the SOS response mechanism and homologous recombination process.
Computational studies of the order-disorder transition in block copolymer topological blends
Authors: Kumar Rahul , Goodson Amy D. , Alli Haroon , Chamness Clayton , Miserocchi Isabella L. , Ashbaugh Henry S. , Albert Julie N. L.
Published: April 2024

Block copolymer (BCP) nanolithography provides an economical way to pattern nanoscale features for the semiconductor industry. Molecular cyclization can reduce feature sizes, but like linear BCPs, cyclic BCP nanostructure size is limited by the order-disorder transition (ODT). Although the ODTs of pure linear and cyclic BCPs have been studied extensively, there is little information on binary blends of these BCPs. Here, we use dissipative particle dynamic simulations to study the impact of size mismatch and molecular architecture of component BCPs on the ODT for various blends. We see that the blend ODT always occurs at higher segregation strength than one would predict from linear interpolation between pure-component ODTs. The deviation from this simple prediction is greater for blends with greater size mismatch between components. We find clustering of like components (i.e., linear BCPs with linear BCPs and cyclic BCPs with cyclic BCPs) in the disordered phase, and the characteristic lengths of the component clusters correlate with molecular size. Because the ordered state consists of uniformly spaced lamellae, which requires interdigitation of linear and cyclic components of the blend, resolution of the size mismatch between clusters seen in the disordered state can be thought of as a barrier to ordering.

Published by the American Physical Society
2024
Measuring magnetic hysteresis curves with polarized soft X-ray resonant reflectivity
Authors: Fan Raymond , Kiranjot  , Aboljadayel Razan O. M. , Alsaeed Kalel , Bencok Peter , Burn David M. , Hindmarch Aidan T. , Steadman Paul
Published: April 2024

Calculations and measurements of polarization-dependent soft X-ray scattering intensity are presented during a magnetic hysteresis cycle. It is confirmed that the dependence of the intensity on the magnetic moment can be linear, quadratic or a combination of both, depending on the polarization of the incident X-ray beam and the direction of the magnetic moment. With a linearly polarized beam, the scattered intensity will have a purely quadratic dependence on the magnetic moment when the magnetic moment is parallel to the scattering plane. However, with the magnetic moment perpendicular to the scattering plane, there is also a linear component. This means that, when measuring the hysteresis with linear polarization during a hysteresis cycle, the intensity will be an even function of the applied field when the change in the magnetic moment (and field) is confined within the scattering plane but becomes more complicated when the magnetic moment is out of the scattering plane. Furthermore, with circular polarization, the dependence of the scattered intensity on the moment is a combination of linear and quadratic. With the moment parallel to the scattering plane, the linear component changes with the helicity of the incident beam. Surprisingly, in stark contrast to absorption studies, even when the magnetic moment is perpendicular to the scattering plane there is still a dependence on the moment with a linear component. This linear component is completely independent of the helicity of the beam, meaning that the hysteresis loops will not be inverted with helicity.
RCSB Protein Data Bank: supporting research and education worldwide through explorations of experimentally determined and computationally predicted atomic level 3D biostructures
Authors: Burley Stephen K. , Piehl Dennis W. , Vallat Brinda , Zardecki Christine
Published: April 2024

The Protein Data Bank (PDB) was established as the first open-access digital data resource in biology and medicine in 1971 with seven X-ray crystal structures of proteins. Today, the PDB houses >210 000 experimentally determined, atomic level, 3D structures of proteins and nucleic acids as well as their complexes with one another and small molecules (e.g. approved drugs, enzyme cofactors). These data provide insights into fundamental biology, biomedicine, bioenergy and biotechnology. They proved particularly important for understanding the SARS-CoV-2 global pandemic. The US-funded Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and other members of the Worldwide Protein Data Bank (wwPDB) partnership jointly manage the PDB archive and support >60 000 `data depositors' (structural biologists) around the world. wwPDB ensures the quality and integrity of the data in the ever-expanding PDB archive and supports global open access without limitations on data usage. The RCSB PDB research-focused web portal at https://www.rcsb.org/ (RCSB.org) supports millions of users worldwide, representing a broad range of expertise and interests. In addition to retrieving 3D structure data, PDB `data consumers' access comparative data and external annotations, such as information about disease-causing point mutations and genetic variations. RCSB.org also provides access to >1 000 000 computed structure models (CSMs) generated using artificial intelligence/machine-learning methods. To avoid doubt, the provenance and reliability of experimentally determined PDB structures and CSMs are identified. Related training materials are available to support users in their RCSB.org explorations.
Job-hopping executives and corporate social responsibility
Authors: Fang Jiali , Tian Yining , Hu Yuanyuan
Published: April 2024

Purpose

The purpose of this study is to examine the relationship between the corporate social responsibility (CSR) performance of job-hopping executives at their former and subsequent firms.

Design/methodology/approach

We conduct regression analyses using a sample of firms listed on the Shanghai and Shenzhen Stock Exchanges from 2010 to 2020 to examine whether CSR performance is similar from one firm to the next as executives switch jobs.

Findings

We find a positive relationship between the CSR performance of former and subsequent firms under job-hopping executives. This relationship is the strongest in the year of the job switch; it weakens in the second year and eventually disappears in the third year. In addition, we show that this relationship benefits different CSR stakeholder groups and is contingent on executive and subsequent firm attributes and job-hopping characteristics. Furthermore, we demonstrate that firms that hire a new chief executive officer from a firm with a strong track record in CSR, the new firm experiences a significant surge in CSR performance compared with firms that do not experience such a shock.

Practical implications

This study has implications for executive hiring decisions.

Originality/value

This study extends the understanding of CSR determinants through the lens of inter-organisational ties associated with job-hopping executives.