bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel risk variant block across introns 36–45 of CACNA1C for schizophrenia: a cohort-wise replication and cerebral region-wide validation study
Authors: Guo Xiaoyun , Wang Shibin , Lin Xiandong , Wang Zuxing , Dou Yikai , Cao Yuping , Zhang Yong , Luo Xinqun , Kang Longli , Yu Ting , Wang Zhiren , Tan Yunlong , Gao Shenshen , Zheng Hangxiao , Zhao Fen , Wang Huifen , Wang Kesheng , Xie Fan , Chen Wenzhong , Luo Xinguang 
Published: September 2023

Objectives
Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions.

Methods
We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (n = 348), gray matter volumes (GMVs) of five subcortical structures (n = 34 431), and surface areas and thickness of 34 cortical regions (n = 36 936) were also examined.

Results
A novel 17-variant block across introns 36–45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 × 10−4 ≤ P ≤ 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 × 10−3 ≤ P ≤ 0.050), GMVs of subcortical structures (0.016 ≤ P ≤ 0.048), cortical surface areas (0.010 ≤ P ≤ 0.050), and thickness (0.004 ≤ P ≤ 0.050) in multiple brain regions.

Conclusion
We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.
Socio-economic predictors of Inuit hunting choices and their implications for climate change adaptation
Authors: Hillemann Friederike , Beheim Bret A. , Ready Elspeth 
Published: September 2023

In the Arctic, seasonal variation in the accessibility of the land, sea ice and open waters influences which resources can be harvested safely and efficiently. Climate stressors are also increasingly affecting access to subsistence resources. Within Inuit communities, people differ in their involvement with subsistence activities, but little is known about how engagement in the cash economy (time and money available) and other socio-economic factors shape the food production choices of Inuit harvesters, and their ability to adapt to rapid ecological change. We analyse 281 foraging trips involving 23 Inuit harvesters from Kangiqsujuaq, Nunavik, Canada using a Bayesian approach modelling both patch choice and within-patch success. Gender and income predict Inuit harvest strategies: while men, especially men from low-income households, often visit patches with a relatively low success probability, women and high-income hunters generally have a higher propensity to choose low-risk patches. Inland hunting, marine hunting and fishing differ in the required equipment and effort, and hunters may have to shift their subsistence activities if certain patches become less profitable or less safe owing to high costs of transportation or climate change (e.g. navigate larger areas inland instead of targeting seals on the sea ice). Our finding that household income predicts patch choice suggests that the capacity to maintain access to country foods depends on engagement with the cash economy.
This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Small-scale farmer responses to the double exposure of climate change and market integration
Authors: Kramer K. L. , Hackman J. V. 
Published: September 2023

Anthropologists have long studied how small-scale societies manage climate variation. Here, we investigate how Yucatec Maya subsistence farmers respond to climate stress, and the ways in which market integration may enhance or disturb response stategies. Using information on harvest returns, climate perceptions, household economics and helping networks, modelling results show that as farmers rely more on market inputs (e.g. seed, tractors, fertilizer) for a successful yield, the reasons given for a bad harvest shift from climate variables to access to quality inputs. We also find that social and economic diversification is key to mediating a household's experience of climate and market shocks. The Maya are astute stewards of climate knowledge, and have effective social and economic means to mitigate potential fluctuations in food availability. In the transition from a subsistence to a market integrated economy, these traditional strategies become strained. Reliance on market inputs forges a more rigid food production system that conflicts with the diversity and flexibility on which traditional strategies depend to manage climate variation. Moving forward, the best policies would be those that facilitate maintaining an equal footing in both a subsistence maize economy, while incorporating new market opportunities.
This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Modeling the impact of genotype, age, sex, and continuous navigation on pathway integration performance
Authors: Pink Dorothea , Ilkel Ekin , Chandreswaran Varnan , Moser Dirk , Getzmann Stephan , Patrick Gajewski , Axmacher Nikolai , Zhang Hui 
Published: September 2023

AbstractThe Path Integration (PI) task stands as a fundamental activity within spatial navigation, encompassing a multifaceted underlying process that requires extensive computation of both translational and directional information during navigation. This task is postulated to engage the entorhinal cortex (EC), a critical brain region. Although rodent studies have firmly linked the EC with the PI task, such a correlation has yet to be definitively established in humans. Individuals harboring high-risk genes associated with Alzheimer’s disease (AD) present a unique opportunity to explore PI task performance in humans because EC is the first targeted region during the pathological development of AD. Furthermore, the execution of the PI task is also susceptible to the influences of age and gender. In order to methodically probe the influences of various factors on PI performance, we conducted a PI task in a cohort characterized by high-risk AD-associated genes in a virtual island environment with surrounding landmarks. Our findings unveiled intricate interactions between these risk genes, age, and gender in shaping PI performance, an influence primarily mediated through distance and angle estimation. This study provides an illuminating perspective on the investigation into the functional role of the entorhinal cortex within the context of the PI task.
Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study
Authors: Zoabi Dana , Abado Elinor , Shamay-Tsoory Simone , Peled-Avron Leehe 
Published: September 2023

AbstractSocial touch is essential for reducing stress, improving mood and fostering a sense of social connectedness. Stimuli related to social touch are generally perceived as positive. Nevertheless, the social restrictions imposed by the COVID-19 pandemic may have changed the way human beings perceive and react to social touch. Indeed, the social distancing imposed by the pandemic may have had long term effects on human perceptions of social touch. In the current study, we examined how perceptions of interpersonal touch in social interactions were affected by the COVID-19 pandemic. Specifically, we compared behavioral and neural responses to observed social touch between two groups: pre- and post-COVID-19. Participants in both groups rated the pleasantness of photos of social touch between humans, nonsocial touch between inanimate objects or non-touch photos of either two humans or inanimate objects. We hypothesized that social touch in the post-COVID-19 group would induce hypervigilance due to the risk of infection. In line with our predictions, we found behavioral changes in perceptions of social touch among participants in this group, who rated photos with touch as less pleasant than did participants in the pre-COVID-19 group. Participants in the post-COVID-19 group also rated photos with humans as less pleasant than did participants in the pre-COVID-19 group. Additionally, EEG analysis revealed neural changes in the ERP components associated with hypervigilance: P1 and LPP. Contrary to pre-COVID-19 measures showing more positive P1 amplitudes for touch than for non-touch photos, after COVID-19 no differences in P1 amplitudes were found between touch and non-touch photos. Furthermore, after COVID-19 the P1 amplitudes for human and inanimate photos in the touch condition were similar, a pattern that did not emerge prior to COVID-19. These findings suggest that COVID-19 had a surprising impact on human perceptions of social touch, such that observing nonsocial touch evoked more positive emotions than observing human touch. Further, these findings may reflect shifts in attention or changes in the salience of touch-related information due to the altered circumstances brought about by the pandemic. Overall, our results indicate that COVID-19 has modified human perceptions of social touch, providing evidence that the pandemic has affected individuals’ perceptual and evaluative processes and highlighting the importance of considering social and environmental factors in understanding subjective experiences.
Exploring associations between the teat apex metagenome andStaphylococcus aureusintramammary infection risk in primiparous cows under organic directives
Authors: Dean C. J. , Peña-Mosca F. , Ray T. , Wehri T. J. , Sharpe K. , Antunes A.M. , Doster E. , Fernandes L. , Calles V. F. , Bauman C. , Godden S. , Heins B. , Pinedo P. , Machado V. S. , Caixeta L. S. , Noyes N. R. 
Published: September 2023

ABSTRACTThe primary objective of this study was to identify associations between teat apex microbiome andStaphylococcus aureusintramammary infection (IMI) risk in primiparous cows during the first 5 weeks after calving. We performed a case-control study using shotgun metagenomics of the teat apex and culture-based milk data collected longitudinally from 710 primiparous cows on 5 organic dairy farms. We observed a strong association betweenS. aureusDNA in the metagenomic teat apex data prior to parturition and the odds ofS. aureusIMI after parturition (OR = 38.9, 95% CI: 14.84-102.21). Differential abundance analysis confirmed this association, with cases having a 23.8 higher log fold change (LFC) in abundance ofS. aureusin their samples compared to controls. Of the most prevalent microorganisms in controls, those associated with a lower risk of post-calvingS. aureusIMI includedMicrobacteriumphage Min 1 (OR = 0.37, 95% CI: 0.25-0.53),Corynebacterium efficiens(OR = 0.53, 95% CI: 0.30-0.94),Kocuria polaris(OR = 0.54, 95% CI: 0.35-0.82),Micrococcus terreus(OR = 0.64, 95% CI: 0.44-0.93) andDietzia alimentaria(OR = 0.45, 95% CI: 0.26-0.75). Microcin B17 was the most prevalent antibacterial peptide on the teat apex of cases and controls (99.7% in both groups). The predicted abundance of Microcin B17 was also higher in cases compared to controls (LFC 0.26). Cow and farm random effects often explained a large proportion of the observed variability in the teat apex microbiome, suggesting that our results need to be interpreted within the context of the random effects.IMPORTANCEIntramammary infections (IMI) caused byStaphylococcus aureusremain an important problem for the organic dairy industry. The microbiome on the external skin of the teat apex may play a role in mitigatingS. aureusIMI risk, in particular the production of antimicrobial peptides (AMPs) by commensal microbes. However, current studies of the teat apex microbiome utilize a 16S approach, which precludes detection of genomics features such as AMPs. Therefore, further research using a shotgun metagenomic approach is needed to understand what role pre-partum teat apex microbiome dynamics play in IMI risk.
An analysis of the onset and clinical characteristics in cystic lymphatic malformations
Authors: Hashizume Naoki , Fujino Akihiro , Takahashi Masataka , Furugane Ryoya , Kobayashi Tamotsu , Mori Teizaburo , Watanabe Eiichiro , Kano Motohiro , Yoneda Akihiro , Kanamori Yutaka 
Published: September 2023

ABSTRACTBackgroundThis study aimed to investigate and compare the applied treatments and the prognosis between patients with congenital and acquired onset cystic lymphatic malformation (cLM).MethodsThis study was a retrospective cohort study in a single hospital. Patients with cLM treated at our institution were included in this study, and divided into those diagnosed in utero or at birth (CO) and those diagnosed later after birth (AO) with the acquired emerged lesion. Age, site, and size of the lesion, histological subtype, invasiveness grade of the treatment, and the treatment outcomes were compared.ResultsIn total, 147 patients were included. The CO group (n = 85) received more invasive treatment, with the distribution of treatment grades differing significantly from the AO group (n = 62,p= 0.005). cLMs were mainly located on the neck (n = 53, 36.1%), followed by the head and face (n = 31, 21.1%), axilla (n = 7, 4.8%), chest wall (n = 18, 12.2%), mediastinum (n = 5, 3.4%), abdominal wall (n = 4, 2.7%), retroperitoneum (n = 4, 2.7%), hip (n = 5, 3.4%), arm and hand (n = 8, 5.4%), and leg and foot (n = 12, 8.2%). No significant between-group difference was found in terms of the distribution of the main lesions (p= 0.45).Macrocystic LM was more frequent in the AO group, with a significantly different subtype ratio (p= 0.02). The frequency of lower-grade treatment was significantly higher in the macrocystic LM subtype in the AO group (p< 0.001), and this group had a significantly higher treatment completion rate (p= 0.004). During the treatment course, improvement was seen in 72.9% and 71.0% of patients in the CO group and the AO group, respectively, indicating no significant difference (p=0.79).ConclusionscLMs that newly appeared after birth tended to be macrocystic and had better outcomes with less-invasive treatment than congenital-onset cLMs. The timing of cLM onset could be a key prognostic factor.
The transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis to cytoplasmic decay
Authors: Kelbert M. , Jordán-Pla A. , de-Miguel-Jiménez L. , García-Martínez J. , Selitrennik M. , Guterman A. , Henig N , Granneman S. , Pérez-Ortín J.E. , Chávez S. , Choder M. 
Published: September 2023

AbstractTo function effectively as an integrated system, the transcriptional and post-transcriptional machineries must communicate through mechanisms that are still poorly understood. Here we focus on Sfp1, known to regulate transcription of proliferation-related genes. We show that Sfp1 can regulate transcription either by binding to promoters, like most known transcription activators, or by binding to the transcribed regions (gene bodies), probably via RNA polymerase II (Pol II). We further studied the first mode of Sfp1 activity and found that, following promoter binding, Sfp1 binds to gene bodies and affects Pol II configuration, manifested by dissociation or conformational change of its Rpb4 subunit and increased backtracking. Surprisingly, Sfp1 binds to a subset of mRNAs co-transcriptionally and stabilizes them. The interaction between Sfp1 and its client mRNAs is controlled by their respective promoters and coincides with Sfp1’s dissociation from chromatin. . Intriguingly, Sfp1 dissociation from the chromatin correlates with the extent of the backtracked Pol II. We propose that, following promoter recruitment, Sfp1 accompanies Pol II and regulates backtracking. The backtracked Pol II is more compatible with Sfp1’s relocation to the nascent transcripts, whereupon Sfp1 accompanies these mRNAs to the cytoplasm and regulates their stability. Thus, Sfp1’s co-transcriptional binding imprints the mRNA fate, serving as a paradigm for the cross-talk between the synthesis and decay of specific mRNAs. The interplay between Sfp1’s two modes of transcription regulation remains to be examined.
Increasing the Throughput and Reproducibility of Activity-Based Proteome Profiling Studies with Hyperplexing and Intelligent Data Acquisition
Authors: Budayeva Hanna G. , Ma Taylur P. , Wang Shuai , Choi Meena , Rose Christopher M. 
Published: September 2023

AbstractIntelligent data acquisition (IDA) strategies, such as real-time database search (RTS), have improved the depth of proteome coverage for experiments that utilize isobaric labels and gas phase purification techniques (i.e., SPS-MS3). While most applications of IDA have been focused on the analysis of protein abundance, these approaches have recently been applied to activity-based proteome profiling (ABPP) studies aimed at characterization of protein site engagement by small molecules. In this work, we extend IDA capabilities offered by vendor software through a program called InSeqAPI. First, we demonstrate robust performance of InSeqAPI in the analysis of biotinylated cysteine peptides from ABPP experiments. Then, we describe PairQuant, a method within InSeqAPI designed for the hyperplexing approach that utilizes protein-level isotopic labeling and peptide-level TMT labeling. PairQuant allows for TMT analysis of 36 conditions in a single sample and achieves ∼98% coverage of both peptide pair partners in a hyperplexed experiment as well as a 40% improvement in the number of quantified cysteine sites compared to non-RTS acquisition. We applied this method in ABPP study of ligandable cysteine sites in the nucleus leading to an identification of additional druggable sites on protein-and DNA-interaction domains of transcription regulators and on nuclear ubiquitin ligases.
A Functional Exodermal Suberin is Key for Plant Nutrition and Growth in Potato
Authors: Company-Arumí Dolors , Montells Carlota , Iglesias Mònica , Marguí Eva , Verdaguer Dolors , Vogel-Mikus Katarina , Kelemen Mitja , Figueras Mercè , Anticó Enriqueta , Serra Olga 
Published: September 2023

ABSTRACTAngiosperm roots, except in Arabidopsis, have both endodermis and exodermis, which regulate radial water and solute movement through lignin and suberin deposition. While endodermal suberin in Arabidopsis acts as a barrier to water and solute uptake and backflow, its implications in other angiosperms with both layers and the role of exodermal suberin remain unclear. We examined potato roots (Solanum tuberosum) and found that exodermis lacks the typical Casparian strip but forms an outer lignin cap, and quickly suberizes near the root tip. In contrast, a few endodermal cells, with Casparian strip, start suberizing much later. The continuous early exodermal suberization covering the root underlines its potential role in mineral nutrient radial movement. To demonstrate it, we used plants downregulating the suberin biosynthetic geneCYP86A33, which had the root suberin reduced in a 61%. Phenotypic analyses of the suberin-deficient mutant showed altered mineral nutrient concentration, slightly reduced water content and compromised growth. Micro-PIXE analyses identified the distribution of elements within the roots and highlighted anatomical compartments defined by apoplastic barriers. These findings advance our understanding of nutrient radial transport, demonstrate exodermal suberin as a bidirectional and selective barrier to element movement, and underscore its importance in nutrient homeostasis and plant growth.
High-Throughput Short Sequence Typing Schemes forPseudomonas aeruginosaandStenotrophomonas maltophiliapure culture and environmental DNA
Authors: Bourdin Thibault , Benoit Marie-Ève , Bédard Emilie , Prévost Michèle , Quach Caroline , Déziel Eric , Constant Philippe 
Published: September 2023

AbstractMolecular typing techniques are employed to determine the genetic similarities between bacterial isolates. These methods primarily utilize specific genetic markers or analyze the complete genome sequence of pure bacterial cultures. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been explored in depth. This work reports on the development and validation of two High-Throughput Short Sequence Typing (HiSST) schemes targeting the opportunistic pathogensPseudomonas aeruginosaandStenotrophomonas maltophilia, along with a modified SM2I medium for specific isolation ofS. maltophilia. Our HiSST schemes are based on four discriminative loci for each species and demonstrate high discrimination power, comparable to pairwise whole genomes comparison. Moreover, each scheme includes species-specific PCR primers, enabling precise differentiation from closely related taxa without the need for upstream culture-dependent methods. For example, the primers designed to target thebvgSlocus allow to distinguishP. aeruginosafrom the very closely relatedPseudomonas paraeruginosasp. nov. The selected loci included in the schemes forP. aeruginosa(pheT,btuB,sdaA,bvgS) and forS. maltophilia(yvoA,glnG,ribA,tycC), are within the range of 271 to 330 base pairs adapted to massive parallel amplicon sequencing technology. A R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analysis for efficient and accurate genotyping ofP. aeruginosaandS. maltophilia. The performance of both schemes was demonstrated throughin-silicovalidations, assessments against reference culture collections, and a case study involving environmental samples.
Leishmania infantum-exploited Nrf2 transcription factor as a virulence process to escape macrophage-driven ferroptosis-like leishmanicidal process
Authors: Blot Clément , Coulson Kimberley , Salon Marie , Tertrais Margot , Planès Rémi , Santoni Karin , Authier Hélène , Jacquemin Godefroy , Rahabi Mouna , Parny Mélissa , Letron Isabelle Raymond , Meunier Etienne , Lefèvre Lise , Coste Agnès 
Published: September 2023

AbstractMacrophages are the main effector cells duringLeishmaniainfection. They contribute to the detection and elimination ofLeishmania spp.and may also promote parasite resilience. Here, we report that the activation of the transcription factor Nrf2 in macrophages plays a pivotal role in the progression ofLeishmania infantuminfection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of NOX2/ROS axis in the early Nrf2 activation and subsequently of PGE2/EP2r signalling in the sustainment of Nrf2 activation uponL. infantuminfection. Moreover, we establish macrophage-driven ferroptosis-like process as a cell death program ofL. infantumand the protective effect of Nrf2 in macrophages againstL. infantumdeath. Altogether, these results identify Nrf2 as a critical factor for the susceptibility ofLeishmania infantuminfection, highlighting Nrf2 as a promising pharmacological target for the development of new therapeutic approaches for the treatment of visceral leishmaniasis.