bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobility changes following COVID-19 stay-at-home policies varied by socioeconomic measures: An observational study in Ontario, Canada
Authors: Wang Siyi , Wang Linwei , Baral Stefan D , Moloney Gary , Johns Jaimie , Huber Carmen , Mistry Jaydeep , Khan Kamran , Rao Amrita , Janjua Naveed , Williamson Tyler , Katz Alan , Ma Huiting , Maheu-Giroux Mathieu , Kustra Rafal , Mishra Sharmistha
Published: January 2024

In Canada, lower income households and essential workers and were disproportionately at risk of SARS-CoV-2. Early in the pandemic, stay-at-home restriction policies were used to limit virus transmission. There remains an evidence gap in how changes in mobility, in response to the policies, varied across socioeconomic measures in Canada. The study objective was to describe the variability in mobility change to two restrictions, by neighborhood-level income and by proportion essential workers across five regions in Ontario, Canada. The first restriction was implemented on March 17, 2020 in all five regions; and the second restriction was implemented in November 23, 2020 in two of the regions. Using cell-phone mobility data aggregated to the census tract, we compared the average mobility (% of devices that travelled outside their “primary location”) three weeks before and after each restriction. We defined the adjusted mobility change via pre-restriction mobility subtracted from post-restriction, adjusted for 2019 levels. We used difference-in-differences analysis to quantify effect modification of the second restriction’s effect by socioeconomic measures. With the first restriction, crude mobility fell from 77.7% to 41.6% across the five regions. The adjusted mobility change to the first restriction was largest in the highest-income neighborhoods (-43.3% versus -38.4%) and in neighborhoods with the fewest essential workers (-44.5% versus -37.6%). The overall adjusted mobility change to the second restriction was small: -0.96% (95% confidence intervals, -1.53 to -0.38%). However, there was evidence of effect modification by socioeconomic measures (less pronounced decrease in lower-income neighborhoods and more essential workers). The findings suggest a temporal saturation effect of restrictions over subsequent waves, and a saturation effect by income and occupation, leading to prevention gaps across populations by socioeconomic measures. Findings highlight the need for tailored approaches at the intersections of income and occupation when addressing epidemics of novel and resurging respiratory pathogens.
A transversal overview of Intensive Care Units environmental microbiome and antimicrobial resistance profile in Brazil
Authors: de Bastiani Daniela Carolina , Silva Claudia Vallone , Christoff Ana Paula , Cruz Giuliano Netto Flores , Tavares Leonardo Daniel , de Araújo Luana Silva Rodrigues , Tomazini Bruno Martins , Arns Beatriz , Piastrelli Filipe Teixeira , Cavalcanti Alexandre Biasi , de Oliveira Luiz Felipe Valter , Pereira Adriano Jose ,   the IMPACTO MR investigators
Published: January 2024

Introduction

Infections acquired during healthcare setting stay pose significant public health threats. These infections are known as Healthcare-Associated Infections (HAI), mostly caused by pathogenic bacteria, which exhibit a wide range of antimicrobial resistance.

Objective

Characterize the microbiome and antimicrobial resistance genes present in high-touch Intensive Care Unit (ICU) surfaces, and to identify the potential contamination of the sanitizers/processes used to clean hospital surfaces.

Methods

In this national, multicenter, observational, and prospective cohort, bacterial profiles and antimicrobial resistance genes from 41 hospitals across 16 Brazilian states were evaluated. Using high-throughput 16S rRNA amplicon sequencing and real-time PCR, the bacterial abundance and resistance genes presence were analyzed in both ICU environments and cleaning products.

Results

We identified a wide diversity of microbial populations with a recurring presence of HAI-related bacteria among most of the hospitals. The median bacterial positivity rate in surface samples was high (88.24%), varying from 21.62% to 100% in different hospitals. Hospitals with the highest bacterial load in samples were also the ones with highest HAI-related abundances.Streptococcus spp,Corynebacterium spp,Staphylococcus spp,Bacillus spp,Acinetobacter spp,and bacteria from the Flavobacteriaceae family were the microorganisms most found across all hospitals. Despite each hospital particularities in bacterial composition, clustering profiles were found for surfaces and locations in the ICU. Antimicrobial resistance genesmecA,blaKPC-like,blaNDM-like, andblaOXA-23-likewere the most frequently detected in surface samples. A wide variety of sanitizers were collected, with 19 different active principles in-use, and 21% of the solutions collected showed viable bacterial growth with antimicrobial resistance genes detected.

Conclusion

This study demonstrated a diverse and spread pattern of bacteria and antimicrobial resistance genes covering a large part of the national territory in ICU surface samples and in sanitizers solutions. This data should contribute to the adoption of surveillance programs to improve HAI control strategies and demonstrate that large-scale epidemiology studies must be performed to further understand the implications of bacterial contamination in hospital surfaces and sanitizer solutions.
A Genetic Perspective on Diabetic Complications: A Mendelian Randomization Study on the Increased Risk of Cataracts in Type 1 Diabetes
Authors: Pei Dongliang , Wang Shuyan , Wang Yuan , Sun Chenmin
Published: January 2024

Background

The well-documented epidemiological link between type 1 diabetes and cataract is recognized. Yet, the question of a shared genetic foundation for these conditions, and the potential implication of a causal connection, is still an area of uncertainty.

Methods

We utilized a two-sample Mendelian randomization approach to extract and analyze four GWAS datasets from public databases, aiming to elucidate the causal relationship between Type 1 Diabetes and cataracts. Our study design incorporated multiple Mendelian randomization methods to assess the influence of Type 1 Diabetes genetic risk on the susceptibility to cataracts, and employed the MR-PRESSO global test for the evaluation of horizontal heterogeneity among the results.

Results

Mendelian Randomization analysis has indicated a statistically significant association between Type 1 Diabetes and an increased risk of cataract development. All applied Mendelian Randomization methods pointed to a positive causal estimate, suggesting that Type 1 Diabetes contributes to an elevated risk of cataracts.

Conclusion

This study supports the hypothesis of a causal relationship between Type 1 Diabetes and cataracts. Despite some heterogeneity, all outcomes are positively aligned, and leave-one-out analysis confirms the robustness of these findings. This research is significant for understanding the process of cataract prevention and treatment in patients with Type 1 Diabetes.
A UK survey of young people’s views on condom removal during sex
Authors: Ezzat Farida , Hart Graham , Barrett Geraldine
Published: January 2024

Introduction

Non-consensual condom removal (NCCR) refers to the act of removing a condom during sex without the other person’s permission. It poses physical and psychological risks to women’s health. Views and attitudes regarding this sexual practice are not well understood in the UK. This study aimed to explore young people’s views on the morality and criminality of NCCR and how their views are affected by negative health outcomes, relationship status, and socio-demographic characteristics.

Methods

A quantitative online survey of people aged 18-25 living in the UK was conducted. The survey consisted of two NCCR scenarios, varied by health outcome and relationship status, followed by questions about the morality and criminality of NCCR and respondents’ socio-demographic characteristics. Statistical analysis included Chi-square testing and logistic regression modelling.

Results

Most of the 1729 respondents considered NCCR to be a violation of consent to sex (97.4%-98.1%), to be wrong (99.3%-99.5%), and to be sexual assault (86.3%-89.2%). Respondents were more likely to support prison time for NCCR if the victim got pregnant (52.1%) (rather than depressed (41.6%)) or was part of a casual hook-up (53.9%) (as opposed to a long-term dating relationship (47.2%). Respondents who were female or non-heterosexual were more likely to view NCCR as sexual assault and support prison as a penalty for NCCR.

Conclusion

The majority of young UK adults in this survey considered condom removal during sex without the other person’s permission to be a violation of consent, morally wrong, and a form of sexual assault. Support for prison as a penalty was lower. These findings can inform future campaigns on consent in sexual relationships and legislation to provide support for women affected by NCCR.
Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression
Authors: Rivera Frederick Berro , Lumbang Grace Nooriza O. , Gaid Danielle Rose Magno , Cruz Linnaeus Louisse A. , Magalong John Vincent , Bantayan Nathan Ross B. , Lara-Breitinger Kyla M. , Gulati Martha , Bakris George
Published: January 2024

Background

The cardiovascular benefits provided by glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond weight reduction and glycemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP lowering effect by GLP1-RAs.

Methods

A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until December 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with mean difference (MD) in millimeters mercury (mmHg) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic and diastolic BP. Subgroup analyses and meta-regression were done to account for covariates.

Results

Compared to placebo, GLP-1RAs modestly reduced SBP (semaglutide: MD −3.40, [95% CI −4.22 to −2.59, p<0.001], liraglutide: MD −2.61, [95% CI −3.48 to −1.74, p<0.001], dulaglutide: MD −1.46, [95% CI −2.20 to −0.72, p<0.001] and exenatide: MD −3.36, [95% CI - 3.63 to −3.10, p<0.001]). This benefit consistently increased with longer treatment duration. Established people with type 2 diabetes experienced less SBP lowering with semaglutide. DBP reduction was only significant in the exenatide group (MD −0.94, [95% CI −1.78 to −0.1], p=0.03). Among semaglutide cohorts, mean change in hemoglobin A1c and mean change in body mass index were directly associated with SBP reduction.

Conclusion

Patients on GLP-1RA experienced modest SBP lowering compared to placebo. Only exenatide reduced DBP. Further studies are needed to clarify the mechanisms and the clinical benefit of GLP-1RA effects in BP reduction.
Brainwide hemodynamics predict neural rhythms across sleep and wakefulness in humans
Authors: Jacob Leandro P. L. , Bailes Sydney M. , Williams Stephanie D. , Stringer Carsen , Lewis Laura D.
Published: January 2024

The brain exhibits rich oscillatory dynamics that play critical roles in vigilance and cognition, such as the neural rhythms that define sleep. These rhythms continuously fluctuate, signaling major changes in vigilance, but the brainwide dynamics underlying these oscillations are unknown. Using simultaneous EEG and fast fMRI in humans drifting between sleep and wakefulness, we developed a machine learning approach to investigate which brainwide fMRI networks predict alpha (8-12 Hz) and delta (1-4 Hz) fluctuations. We predicted moment-to-moment EEG power variations from fMRI activity in held-out subjects, and found that information about alpha rhythms was highly separable in two networks linked to arousal and visual systems. Conversely, delta rhythms were diffusely represented on a large spatial scale across the cortex. These results identify the large-scale network patterns that underlie alpha and delta rhythms, and establish a novel framework for investigating multimodal, brainwide dynamics.
Giant polyketide synthase enzymes biosynthesize a giant marine polyether biotoxin
Authors: Fallon Timothy R. , Shende Vikram V. , Wierzbicki Igor H. , Auber Robert P. , Gonzalez David J. , Wisecaver Jennifer H. , Moore Bradley S.
Published: January 2024

Prymnesium parvumare harmful haptophyte algae that cause massive environmental fish-kills. Their polyketide polyether toxins, theprymnesins, are amongst the largest nonpolymeric compounds in nature, alongside structurally-related health-impacting “red-tide” polyether toxins whose biosynthetic origins have been an enigma for over 40 years. Here we report the ‘PKZILLAs’, massiveP. parvumpolyketide synthase (PKS) genes, whose existence and challenging genomic structure evaded prior detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 MDa with 140 and 99 enzyme domains, exceeding the largest known protein titin and all other known PKS systems. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon-backbone A-type prymnesins. This discovery establishes a model system for microalgal polyether biosynthesis and expands expectations of genetic and enzymatic size limits in biology.
The sense of agency from active causal inference
Authors: Chang Acer Yu-Chan , Oi Hiroki , Maeda Takaki , Wen Wen
Published: January 2024

This study investigates the active component of the sense of agency (SoA), positing that SoA is fundamentally an outcome of active causal inference regarding one’s own actions and their impact on the environment. Participants controlled visual objects via a computer mouse, with tasks designed to test their ability to judge control or detect controlled objects under varying noise conditions. Our findings reveal that participants formed high-level, low-dimensional action plans that were idiosyncratic across but consistent within individuals to infer their degree of control. Employing transformer-LSTM-based autoencoders, we captured these action plans and demonstrated that the geometrical and dynamical properties of these action plans could predict behavioural profiles in the tasks with remarkable accuracy. This suggests that participants’ sense of control is shaped by actively altering action plans, viewed as generating causal evidence through intervention. Further, participants proactively expanded the diversity of their action plans, facilitating the exploration of available action plan options while accumulating causal evidence for the inference process. Contrarily, patients with schizophrenia exhibited reduced action plan diversity, suggesting impaired active control inference and detection of self-relevant cues. These findings offer a more comprehensive understanding of the sense of agency, deeply rooted in the process of active causal inference.
MacAction: Realistic 3D macaque body animation based on multi-camera markerless motion capture
Authors: Martini Lucas M. , Bognár Anna , Vogels Rufin , Giese Martin A.
Published: January 2024

Social interaction is crucial for survival in primates. For the study of social vision in monkeys, highly controllable macaque face avatars have recently been developed, while body avatars with realistic motion do not yet exist. Addressing this gap, we developed a pipeline for three-dimensional motion tracking based on synchronized multi-view video recordings, achieving sufficient accuracy for life-like full-body animation. By exploiting data-driven pose estimation models, we track the complete time course of individual actions using a minimal set of hand-labeled keyframes. Our approach tracks single actions more accurately than existing pose estimation pipelines for behavioral tracking of non-human primates, requiring less data and fewer cameras. This efficiency is also confirmed for a state-of-the-art human benchmark dataset. A behavioral experiment with real macaque monkeys demonstrates that animals perceive the generated animations as similar to genuine videos, and establishes an uncanny valley effect for bodies in monkeys.
Localization of S1P1Receptor Signaling in the rat, mouse and human Central Nervous System
Authors: Martínez-Gardeazabal Jonatan , Pereira-Castelo Gorka , Moreno-Rodríguez Marta , Llorente-Ovejero Alberto , Fernández Manuel , Fernández-Vega Iván , Manuel Iván , Rodríguez-Puertas Rafael
Published: January 2024

Some specific lipid molecules present in the brain are signaling molecules at the intracellular compartments or behaving as neurotransmitters or neuromodulators of other systems, binding to specific G protein-coupled receptors (GPCR) for neurolipids. One of these receptors is the sphingosine 1-phosphate receptor subtype 1, coupled to Gαi/o-proteins and involved in cell proliferation, growth or neuroprotection. Thus, an interesting target for neurodegenerative diseases, such as Alzheimer’s. The present study compares the human cerebral distribution of the activity mediated by S1P1receptor with the that in the brain of rodent experimental models, rat and mice by functional autoradiography, measuring the [35S]GTPγS binding stimulated by the S1P1receptor selective agonist CYM-5442 to get the anatomy of the S1P1receptor activity.

The S1P1receptor-mediated activity is, together with that of the CB1cannabinoid receptor, one of the highest recorded for any GPCR in most of the grey matter areas of the brain, reaching up to 50%-500% over basal, depending on the agonist and brain area. The S1P1receptor signaling is very relevant in those areas that regulate learning and memory processes, such as the basal forebrain, but also in others involved in control of motor processes or nociception e.g. basal ganglia. The results also reveal that the rat would be a preferable experimental model to extrapolate for the S1P1receptor-mediated responses in human brain.
The Arabidopsis leucine rich repeat receptor-like kinase MIK2 interacts with RKS1 and participates to the control of quantitative disease resistance to the bacterial pathogenXanthomonas campestris
Authors: Delplace Florent , Huard-Chauveau Carine , Roux Fabrice , Roby Dominique
Published: January 2024

Molecular mechanisms underlying qualitative resistance have been intensively studied. In contrast, although quantitative disease resistance (QDR) is a common, durable and broad-spectrum form of immune responses in plants, only a few related functional analyses have been reported. In this context, the atypical kinase RKS1 is a major actor of QDR to the bacterial pathogenXanthomonas campestris(Xcc) and is positioned in a robust protein-protein decentralized network. Among the putative interactors of RKS1 found by yeast two hybrid screening, we identified the receptor like kinase MDIS1-Interacting Receptor-like Kinase 2 (MIK2). Here, by multiple and complementary strategies including protein-protein interaction tests, mutant analysis and network reconstruction, we report thatMIK2is a component ofRKS1mediated QDR toXcc. First, by co-localization experiment, co-immunoprecipitation (Co-IP) and Bimolecular Fluorescence Complementation (BiFC), we validated the physical interaction between RKS1 and MIK2 in the plasma membrane. Usingmik2mutants, we then showed thatMIK2is required for QDR at the same level asRKS1. Interestingly, a catalytic mutant of MIK2 was able to interact with RKS1 but unable to fully complement themik2-1mutant in response toXcc. Finally, we investigated a potential role of the MIK2-RKS1 complex as a scaffolding component for coordination of perception events, by constructing a RKS1-MIK2 centered protein-protein network. Eight mutants corresponding to seven RLKs of this network showed a strong and significant alteration in QDR toXcc. Our findings provide new insights into the molecular mechanisms underlying perception events involved in QDR toXcc.
Fluorescence hybridization chain reaction enables localization of multiple molecular classes combined with plant cell ultrastructure
Authors: Yu Yunqing , Huss David , Li Mao , Wickramanayake Janithri S. , Bélanger Sébastien , Klebanovych Anastasiya , Meyers Blake , Kellogg Elizabeth A. , Czymmek Kirk J.
Published: January 2024

Background

Recent developments in hybridization chain reaction (HCR) have enabled robust simultaneous localization of multiple mRNA transcripts using fluorescencein situhybridization (FISH). Once multiple split initiator oligonucleotide probes bind their target mRNA, HCR uses DNA base-pairing of fluorophore-labeled hairpin sets to self-assemble into large polymers, amplifying the fluorescence signal and reducing non-specific background. Few studies have applied HCR in plants, despite its demonstrated utility in whole mount animal tissues and cell culture. Our aim was to optimize this technique for sectioned plant tissues embedded with paraffin and methacrylate resins, and to test its utility in combination with immunolocalization and subsequent correlation with cell ultrastructure using scanning electron microscopy.

Results

Application of HCR to 10 µm paraffin sections of 17-day-oldSetaria viridis(green millet) inflorescences using confocal microscopy revealed that the transcripts of the transcription factorKNOTTED 1(KN1) were localized to developing floret meristem and vascular tissue whileSHATTERING 1(SH1) andMYB26transcripts were co-localized to the breakpoint below the floral structures (the abscission zone). We also used methacrylate de-embedment with 1.5 µm and 0.5 µm sections of 3-day-oldArabidopsis thalianaseedlings to show tissue specificCHLOROPHYLL BINDING FACTOR a/b(CAB1) mRNA highly expressed in photosynthetic tissues andELONGATION FACTOR 1 ALPHA(EF1α) highly expressed in meristematic tissues of the shoot apex. The housekeeping geneACTIN7(ACT7) mRNA was more uniformly distributed with reduced signals using lattice structured-illumination microscopy. HCR using 1.5 µm methacrylate sections was followed by backscattered imaging and scanning electron microscopy thus demonstrating the feasibility of correlating fluorescent localization with ultrastructure.

Conclusion

HCR was successfully adapted for use with both paraffin and methacrylate de-embedment on diverse plant tissues in two model organisms, allowing for concurrent cellular and subcellular localization of multiple mRNAs, antibodies and other affinity probe classes. The mild hybridization conditions used in HCR made it highly amenable to observe immunofluorescence in the same section. De-embedded semi-thin methacrylate sections with HCR were compatible with correlative electron microscopy approaches. Our protocol provides numerous practical tips for successful HCR and affinity probe labeling in electron microscopy-compatible, sectioned plant material.
Inferring drift, genetic differentiation, and admixture graphs from low-depth sequencing data
Authors: Rasmussen Malthe Sebro , Wiuf Carsten , Albrechtsen Anders
Published: January 2024

A number of popular methods for inferring the evolutionary relationship between populations require essentially two components: First, they require estimates off2-statistics, or some quantity that is a linear combination of these. Second, they require estimates of the variability of the statistic in question. Examples of methods in this class include qpGraph and TreeMix.

It is known, however, that these statistics are biased when based on genotype calls at low depth. Moreover, as we show, this leads to downstream inference of significantly distorted trees. To solve this problem, we demonstrate how to accurately and efficiently compute a broad class of statistics from low-depth whole-genome sequencing data, including estimates of their standard errors, by using the site frequency spectrum. In particular, we focus onf2and the sample covariance of allele frequencies to show how this method leads to accurate estimate of drift when fitting trees using qpGraph and TreeMix with low-depth data. However, the same considerations lead to uncertainty estimates for a variety of other statistics, including heterozygosity, kinship estimates (e.g. King), and quantities relating to genetic differentiation such asFstandDxy.
An analysis of natural variation inPinus pinasterthrough the lens of systems biology
Authors: Pascual Jesús , López-Hidalgo Cristina , Feito Isabel , Majada Juan , Meijón Mónica
Published: January 2024

Pinus pinasteris a main species in Mediterranean forests, being naturally distributed through the Mediterranean basin, covering regions with a variety of geoclimatic conditions. This distribution in different environments leads, by natural selection, to a natural variation within the species that manifests at phenotypic level in populations with different growth features and overall tree architectures. StudyingP. pinasternatural variation is necessary to understand the genetic heritage of the species and can provide valuable information for information-based decision-making regarding forest management and breeding programmes. In this paper, we analyzed the natural variation in needles and buds from three provenances from contrasting geoclimatic locations using a common garden approach and proteomics. The integration of the proteomics data with tree growth-related parameters, geoclimatic features at provenances original locations, and sample-matched metabolomics data previously generated provided novel knowledge on metabolism rearrangements related to secondary metabolism and associated to growth features and the adaptation to light and UV-B radiation intensities.
The transcription factor IRF-5 is essential for the metabolic rewiring of CD8 T cells during chronic infection
Authors: Mai Linh Thuy , Swaminathan Sharada , Nguyen Trieu Hai , Charpentier Tania , Loucif Hamza , Carmona-Pérez Liseth , Lamarre Alain , Heinonen Krista M. , Fritz Jörg H. , Stäger Simona
Published: January 2024

Numerous transcription factors are involved in promoting an intricate gene expression program that leads to CD8 T cell exhaustion. Here, we found that the transcription factor IRF-5 is involved in limiting functional exhaustion of CD8 T cells by regulating the cell cycle and contributing to sustaining the mitochondrial functions and oxidative phosphorylation during the chronic stage of LCMV Cl13 infection. CD8 T cells lacking IRF-5 display reduced survival capacity and show increased signs of functional exhaustion during the chronic stage of infection. IRF-5-deficiency also resulted in a severely defective lipid metabolism, in a faulty mitochondrial envelope, and in the reduced capacity to produce ATP. Additionally, we observed increased lipid peroxidation in CD8 T cells lacking IRF-5, when compared with WT cells. These findings identify IRF-5 as a pivotal regulator of the metabolic rewiring that occurs in CD8 T cells during the chronic stages of infection and highlight its role in protecting cells from cell death, possibly by lipid peroxidation.

IRF-5 is critical for regulating mitochondrial functions and oxidative phosphorylation in CD8 T cells during chronic stages of LCMV Cl13 infection.
Revealing brain network dynamics during the emotional state of suspense using topological data analysis
Authors: Olave Astrid A. , Perea Jose A. , Gómez Francisco
Published: January 2024

Abstract

Suspense is an affective state ubiquitous in human life, from art to quotidian events. However, little is known about the behavior of large-scale brain networks during suspenseful experiences. To address this question, we examined the continuous brain responses of participants watching a suspenseful movie, along with reported levels of suspense from an independent set of viewers. We employ sliding window analysis and Pearson correlation to measure functional connectivity states over time. Then, we use Mapper, a topological data analysis tool, to obtain a graphical representation that captures the dynamical transitions of the brain across states; this representation enables the anchoring of the topological characteristics of the combinatorial object with the measured suspense. Our analysis revealed changes in functional connectivity within and between the salience, fronto-parietal, and default networks associated with suspense. In particular, the functional connectivity between the salience and fronto-parietal networks increased with the level of suspense. In contrast, the connections of both networks with the default network decreased. Together, our findings reveal specific dynamical changes in functional connectivity at the network level associated with variation in suspense, and suggest topological data analysis as a potentially powerful tool for studying dynamic brain networks.
The actomyosin system is essential for the integrity of the endosomal system in bloodstream formTrypanosoma brucei
Authors: Link Fabian , Jung Sisco , Malzer Xenia , Zierhut Felix , Konle Antonia , Borges Alyssa , Batters Christopher , Weiland Monika , Pöllmann Mara , Nguyen An Binh , Kullmann Johannes , Veigel Claudia , Engstler Markus , Morriswood Brooke
Published: January 2024

The actin cytoskeleton is a ubiquitous feature of eukaryotic cells, yet its complexity varies across different taxa. In the parasitic protistTrypanosoma brucei, a rudimentary actomyosin system consisting of one actin gene and two myosin genes has been retained despite significant investment in the microtubule cytoskeleton. The functions of this highly simplified actomyosin system remain unclear, but appear to centre on the endomembrane system. Here, advanced light and electron microscopy imaging techniques together with biochemical and biophysical assays were used to explore the relationship between the actomyosin and endomembrane systems. The class I myosin (TbMyo1) had a large cytosolic pool and its ability to translocate actin filamentsin vitrowas shown here for the first time. TbMyo1 exhibited strong association with the endosomal system and was additionally found on glycosomes. At the endosomal membranes, TbMyo1 colocalised with markers for early and late endosomes (TbRab5A and TbRab7, respectively), but not with the marker associated with recycling endosomes (TbRab11). Actin and myosin were simultaneously visualised for the first time in trypanosomes using an anti-actin chromobody. Disruption of the actomyosin system using the actin-depolymerising drug latrunculin A resulted in a delocalisation of both the actin chromobody signal and an endosomal marker, and was accompanied by a specific loss of endosomal structure. This suggests that the actomyosin system is required for maintaining endosomal integrity inT. brucei.
Coordinate regulation of Activin and Bone Morphogenetic Protein signaling by a lysosomal trafficking switch
Authors: Hom Warren W. , Aykul Senem , Panagis Lampros , Patel Krunal , Brydges Susannah , Goebel Erich J. , Lydon Kaitlin N. , Lees-Shepard John B. , Hatsell Sarah J. , Idone Vincent , Economides Aris N.
Published: January 2024

BMP/TGFß family ligands act mainly as factors that differentially initiate Smad1/5/8 or Smad2/3 signaling via heterotetrameric complexes comprised of two type I and two type II receptors (IIR). ActA (ActA) stands out as it activates Smad2/3 signaling through type I receptor ACVR1B, whereas it generates non-signaling complexes (NSCs) with ACVR1. In fibrodysplasia ossificans progressiva (FOP), a genetic disorder caused by missense mutations in ACVR1 (ACVR1.FOP), ACVR1.FOP•ActA•IIR complexes activate Smad1/5 signaling, mimicking those formed with BMPs. As the NSCs that ActA forms with ACVR1 are stoichiometrically identical with signaling complexes formed with ACVR1.FOP, we explored how NSCs differ from their signaling counterparts. We show that ACVR1•ActA•IIR complexes rapidly traffic to lysosomes, where their constituent components are degraded, reducing the cell’s responsiveness to BMPs along with ActA’s availability. This property is specific to ActA as Activin B, AB, and AC do not form lysosomal trafficking complexes with ACVR1, but rather remain on the surface as NSCs. Lysosomal trafficking and degradation of ACVR1•ActA•IIR complexes is a novel regulatory mechanism of BMP/TGFß signaling whose physiological roles remain largely unexplored.
Putrescine acts as a signaling metabolite in the transition from nodulation to nitrogen fixation inRhizobium phaseoli
Authors: Hernandez-Benitez Ericka M. , Martínez-Romero Esperanza , Aguirre-Noyola José Luis , Ledezma-Tejeida Daniela
Published: January 2024

Growth of the common bean plantPhaseolus vulgarisis tightly linked to its symbiotic relationship with diverse rhizobial species, particularlyRhizobium phaseoli, an alphaproteobacteria that forms root nodules and provides high levels of nitrogen to the plant. Molecular cross-talk is known to happen via plant-derived metabolites, but only flavonoids have been identified as signals. Flavonoids are transported inside the bacteria, where they signal the NodD regulator to elicit nodulation. Although seven other regulators are known to be involved, our knowledge of the regulatory mechanisms underlying the nodulation, and nitrogen fixation processes is limited, and the signals recognized by regulators are mostly unknown. Here, we identified 75 transcription factors inR. phaseoligenome through sequence conservation fromEscherichia coli, and assembled a transcriptional regulatory network comprising 24 regulators, and 652 target genes. We identified the interactions relevant to nodulation via gene expression, and signaled out putrescine as a signaling metabolite. We propose a model where putrescine acts as a switch on the transition from nodulation to nitrogen fixation via the dual transcription factor PuuR, and its regulation of thenodIandnifU2genes.

Importance

This study provides new insights into the molecular cross-talk betweenPhaseolus vulgarisandRhizobium phaseoli, which is crucial for the development of alternative cropping strategies, including biopesticides and biofertilizers. In addition, we present the first transcriptional regulatory network systematically assembled forRhizobium phaseoli, which opens new avenues of research in the relationship between the transcriptional regulation and metabolism of these organisms.
A transcriptomic study of PF06830 root cap proteins
Authors: Raymond James A.
Published: January 2024

PF06830 is a family of about 2000 root cap proteins (RCPs) that are almost certainly involved in the major functions of the root cap, which include root growth and development, obtaining nutrients and sensing environmental variables. They appear to be expressed in the outer cell layers of the root tip where they are in intimate contact with the soil. Surprisingly, almost nothing is known about their individual functions, and they have received virtually no attention since their first description a quarter century ago. RCPs have easily identifiable characteristics and can be found in almost all plant species. The enormous expansion of plant transcriptomes in recent years provides an opportunity to better understand their functions, i.e., to see what biotic and abiotic variables affect their expressions. Here, the expressions of RCP genes in 49 root transcriptome studies (representing 14 species) obtained under different environmental conditions and at different development stages were investigated. (deleted sentence) In 19 of these studies, RCP expressions were found to be positively affected by environmental or developmental factors in specific cultivars of Arabidopsis, barley, rye, wheat, rice and cucumber. However, several negative effects were also found, often in different cultivars of the same species. These studies represent a first step in understanding the functions of RCPs that should help in the design of further studies. RCPs share some structural properties with, and may have overlapping functions with, other plant protein families, including small heat shock proteins, late embryogenesis abundant proteins and lectins. Their origins appear to predate the development of roots.
New antiviral defences are genetically embedded within prokaryotic immune systems
Authors: Payne Leighton J. , Hughes Tom C. D. , Fineran Peter C. , Jackson Simon A.
Published: January 2024

Bacteria and archaea typically have multiple defence systems that protect them against viral predation. Recently, many new defence systems have been discovered, yet the full scope of the prokaryotic pan-immune system remains to be determined. In this study, we observed that many multi-gene defence systems have additional genes nested or ‘embedded’ within them. Based on this observation, we present a new approach to predict new defence systems, where defence function of uncharacterised genes is inferred based on their genetic embedding in known defence systems. Applying this ‘guilt-by-embedding’ method, we identified and confirmed anti-phage function for seven defence systems and predicted 145 additional candidates. Our findings expand the known immune repertoire of prokaryotes, provide a wealth of new systems for future functional studies, and demonstrate a simple, efficient approach to identify new antiviral defences.
Spatiotemporal orchestration of Ca2+-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop
Authors: Qiao Lingxia , Getz Michael , Gross Ben , Tenner Brian , Zhang Jin , Rangamani Padmini
Published: January 2024

The nanoscale organization of enzymes associated with the dynamics of second messengers is critical for ensuring compartmentation and localization of signaling molecules in cells. Specifically, the spatiotemporal orchestration of cAMP and Ca2+oscillations is critical for many cellular functions. Previous experimental studies have shown that the formation of nanodomains of A-kinase anchoring protein 79/150 (AKAP150) and adenylyl cyclase 8 (AC8) on the surface of pancreatic MIN6 β cells modulates the phase of Ca2+-cAMP oscillations from out-of-phase to in-phase. In this work, we develop computational models of the Ca2+/cAMP pathway and AKAP/AC nanodomain formation that give rise to the two important predictions: instead of an arbitrary phase difference, the out-of-phase Ca2+/cAMP oscillation reaches Ca2+trough and cAMP peak simultaneously, which is defined as inversely out-of-phase; the in-phase and inversely out-of-phase oscillations associated with Ca2+-cAMP dynamics on and away from the nanodomains can be explained by an incoherent feedforward loop. Factors such as cellular surface-to-volume ratio, compartment size, and distance between nan-odomains do not affect the existence of in-phase or inversely out-of-phase Ca2+/cAMP oscillation, but cellular surface-to-volume ratio and compartment size can affect the time delay for the inversely out-of-phase Ca2+/cAMP oscillation while the distance between two nanodomains does not. Finally, we predict that both the Turing pattern-generated nanodomains and experimentally measured nan-odomains demonstrate the existence of in-phase and inversely out-of-phase Ca2+/cAMP oscillation when the AC8 is at a low level, consistent with the behavior of an incoherent feedforward loop. These findings unveil the key circuit motif that governs cAMP and Ca2+oscillations and advance our understanding of how nanodomains can lead to spatial compartmentation of second messengers.
Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis
Authors: Verma Rohit Kumar , Lokhande Kiran Bharat , Srivastava Prashant Kumar , Singh Ashutosh
Published: January 2024

Liver hepatocellular carcinoma (LIHC) is one of the most frequent types of malignant cancer in the globe. The identification of new biomarkers for the LIHC is critical. We used TCGA-LIHC gene expression datasets for this study. Several feature selection methods were used to find the top gene signatures that distinguish LIHC cancer from normal samples. Eleven machine learning algorithms were used on these selected characteristics, and model performance evaluation revealed that Naive Bayes Classifiers (AUC = 0.965) performs the best for a selection of 55 protein coding genes. Among 55 protein coding genes we found B4GALNT1 (Beta-1,4-N-acetyl-galactosaminyltransferase 1) which is differentially regulated in LIHC. With several evidence B4GALNT1 plays crucial role in tumorigenesis in many cancers, therefore we conducted systematic bioinformatics approach with mutational and structural analysis of B4GALNT1 in LIHC. Moreover, survival analysis, immune cell infiltration, most significant associated methylated CpG probe and access the accuracy of B4GALNT1 conducted to find the potential role of B4GALNT1. The results suggested that B4GALNT1 was significantly expressed in most cancers including LIHC. Finally, 16 missense mutations identified through cBioportal, Cosmic Database, and Human Variant Database, among which 6 mutations (P64Q, S131F, A311S, R340Q, D478H, and P507Q) found to be deleterious when analysed byin-silicoprediction algorithms such as SIFT, PolyPhen2, I Mutent2 and CADD in LIHC. Molecular Dynamics simulation analysis was performed to understand the atomic details of the structure and functional changes. Results from this study suggest the impact of these missense variants on the structure of the B4GALNT1 protein and its pathogenic relevance. Our study demonstrated that B4GALNT1 may be evaluated as a novel target for liver cancer therapy because it has been found to be overexpressed in Liver and correlates with a poor prognosis.
Low pre-infection levels of neutralizing antibody in breakthrough infections after bivalent BA.4-5 vaccine and practical application of dried blood spots
Authors: Kawasuji Hitoshi , Morinaga Yoshitomo , Tani Hideki , Yamada Hiroshi , Yoshida Yoshihiro , Ezaki Masayoshi , Koshiyama Yuki , Takegoshi Yusuke , Kaneda Makito , Murai Yushi , Kimoto Kou , Nagaoka Kentaro , Niimi Hideki , Yamamoto Yoshihiro
Published: January 2024

The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4-5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50% using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4-5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.
Information Bottlenecks in Forecasting COVID-19
Authors: Gamarnik David , Ma Muzhi
Published: January 2024

Reliable short term and long term forecasting of the number of COVID-19 incidences is a task of clear importance. Numerous attempts for such forecasting have been attempted historically since the onset of the pandemic. While many successful short-term forecasting models have been put forward, predictions for mid-range time intervals (few weeks) and long-range ones (few months to half a year) appeared to be largely inaccurate.

In this paper we investigate systematically the question as to what extend such predictions are even possible given the information available at the times when the predictions are made. We demonstrate that predictions on the daily basis is practically impossible beyond the horizon of 20+ days, and predictions on the weekly basis is similarly impossible beyond the horizon of roughly half a year. We arrive at this conclusion by computing information bottlenecks arising in the dynamics of the COVID-19 pandemic. Such bottlenecks stem from the “memoryless” property of the stochastic dynamical systems describing COVID-19 evolution, specifically from the so-called mixing rate of the system. The mixing rate is then used to gage the rate at which the information used at a time when predictions are made no longer impacts the actual outcomes of the pandemic.
CD83 Receptor Unveiled as a Therapeutic Target in Metastatic Breast Cancer through Single-Cell RNA-Seq
Authors: Sayad Saed , Hiatt Mark , Mustafa Hazem
Published: January 2024

Background

Metastatic breast cancer is an advanced stage of the disease in which cancer cells have spread to organs beyond the breast, posing a significant clinical challenge, necessitating the development of novel therapeutic approaches. Gaining a profound understanding of the intricacies of metastasis is essential for developing effective interventions. In this study, we investigated the CD83 gene and its receptor as a promising therapeutic target in metastatic breast cancer.

Method

We obtained single-cell transcriptomes (GSE75688) from the NIH portal website. These transcriptomes encompassed samples from eleven patients (BC01-BC11), which included two lymph node metastases (BC03LN, BC07LN). Our analysis focused on identifying genes with distinct expression patterns between metastatic and primary single cells.

Results

In the array of 22 tables (comprising two metastatic and eleven primary tables) featuring the top 800 differentially expressed genes in each, CD83 stood out as the sole significantly upregulated gene consistently shared across all eleven patients at the intersection. CD83 is a protein that plays a crucial role in the immune system, particularly in the context of antigen presentation, immune regulation and immune checkpoint, suggesting its potential involvement in breast cancer progression and metastasis. Based on these findings, we hypothesized that blocking the CD83 receptor on the cell membrane using an antibody could effectively inhibit cell growth in metastatic breast cancer.

Conclusion

We propose a novel therapeutic approach by targeting the CD83 receptor on the cell membrane to inhibit cell growth and metastasis in breast cancer. While these findings are promising, further research is needed to validate the efficacy and safety of CD83-targeted therapies. If successful, such treatments could offer improved options for patients with metastatic breast cancer, addressing a critical need for more effective interventions in advanced stages of the disease.
Cluster effect through the oligomerisation of bioactive disaccharide AMOR on pollen tube capacitation inTorenia fournieri
Authors: Mizukami Akane G , Kusano Shuhei , Hagihara Shinya , Higashiyama Tetsuya
Published: January 2024

ABSTRACRT

Arabinogalactan proteins (AGPs) are plant-specific glycoproteins involved in cellular mechanics and signal transduction. There has been major progress in understanding the structure, synthesis, and molecular functions of their carbohydrate chains; however, the mechanisms by which they function as signalling molecules remain unclear. Here, methyl-glucuronosyl arabinogalactan (AMOR; Me-GlcA-β(1,6)-Gal), a disaccharide structure at the end of AGP carbohydrate chains, was oligomerised via chemical synthesis. The biological activity of AMOR oligomers was enhanced via clustering of the carbohydrate chains. Furthermore, AMOR oligomers yielded a pollen tube morphology (i.e., callose plug formation) similar to that when cultured with native AMOR, suggesting it may be functionally similar to native AMOR.