bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles and mechanisms of leptomeningeal collaterals in human distal MCA territory ischemia
Authors: Zou Xiang , Mei Shuhao , Wu Zehan , Song Kun , Xu Yuhao , Hu Jie , Chen Liang , Mao Ying 
Published: May 2024

ABSTRACTBackgroundLeptomeningeal collaterals (LMCs) provided hemodynamic support and reperfusion during acute ischemic stroke (AIS). Although regulation details have been deeply acquired from animal models, human cortex may share limited hemodynamic patterns due to larger physical scale that needs further investigation.MethodsWe performed ‘sequential hierarchical blocking’ during awake craniotomy on fourteen human subjects to mimic AIS in middle cerebral artery (MCA) M4segment territory. Widefield microscope was applied to reveal microcirculation of LMCs. Relative flow rate (RFR) was measured to evaluate the impact of LMCs hierarchy on microcirculation maintenance. Single-cell sequencing and spatial transcriptomics were further performed to analyze the mechanism of different LMCs recruitment abilities.ResultsLMCs RFR decreased to 30.75% immediately (95% CI, 6.64 - 54.86%, P < 0.001), and about 80.25% RFR was finally recovered within 5 minutes (95% CI, 55.2 - 105.3%, P = 0.0034) during M4occlusion. For M5and pial branches occlusion, RFR decreased to 55.78% with no further recovery (95% CI, 22.50-89.05%, P = 0.014), and 4 in 11 subjects had no valid microcirculation. For subjects with better recruitment ability, the proportion of arteriole is much higher in leptomeninx (76 - 79% vs. 36 - 56%). There were more significant interaction pairs associated with key signaling pathways between arteriole and neuron/astrocyte (TGF-beta signaling pathway, ECM-receptor interaction)ConclusionsAbundant LMCs supported hemodynamic stability during AIS in human subjects. The proportion of arteriole is much higher in leptomeninx for subjects with better recruitment ability. The Active neuron/astrocyte - arteriole interaction may improve LMCs recruitment.GRAPH ABSTRACT
Innovating Urban Mosquito Control: Introducing Human-Controlled Breeding Sites as a Component of Integrated Mosquito Management (IMM)
Authors: Baigorria Guillermo A. , Romero Consuelo C. 
Published: May 2024

ABSTRACTThis study introduces a novel method for mosquito control tailored specifically for urban and suburban areas, addressing their unique challenges. The concept of Human-Controlled Breeding Sites (HCBS) is presented as an innovative approach to reducing mosquito populations by providing controlled oviposition sites within households. The paper is structured into three main components. The first details the meticulous development of the HCBS method, the second explores the intricate development of the HCBS device, crucial for effective implementation of the HCBS approach. Finally, the experiment validating the HCBS methodology is described, offering insights into its practical application and efficacy in mosquito population control. Our proposal emphasizes the importance of considering mosquito needs, behavior and preferences in designing effective mosquito control strategies. Gravid mosquitoes must find a suitable place for oviposition, and HCBS provides an easy-access controlled environment for them to do so within households. Contrary to the commonly current recommendation to destroy all possible locations where mosquitoes can lay their eggs, the HCBS methodology provides an opportunity for gravid mosquitoes to oviposit their eggs without being deterred by chemical odors or dead larvae or pupae. It involves waiting for a timespan before effectively collecting and destroying the individuals in one concerted effort with zero impact on the environment and at minimal cost. Successful deposition of eggs by gravid mosquitoes into HCBS devices, followed by their destruction within the designated timeframe, validates the system’s efficacy in disrupting the mosquito life cycle. Moreover, our findings demonstrate the significant influence of color selection on HCBS effectiveness, with green HCBS devices being the preferred choice, although not an indispensable condition for oviposition. These integrated components offer a comprehensive understanding of the HCBS approach, effectively bridging the gap between methodological development, device design, and practical application. The findings underscore HCBS as a valuable addition to mosquito control strategies, with potential applications in diverse environments. Further research is essential to delve into and model the long-term effectiveness of HCBS, aiming to optimize its design for maximum efficacy and scalability. This includes studying its performance over extended periods and refining the design parameters to enhance its functionality and widespread applicability including the use of disaster risk management systems.
Food insecurity is associated with poor hypertension management in the Eastern Caribbean
Authors: Oladele Carol R. , Khandpur Neha , Galusha Deron , Nair Sanya , Hassan Saria , Martinez-Brockman Josefa , Nunez-Smith Marcella , Perez-Escamilla Rafael 
Published: May 2024

ABSTRACTBackgroundLimited evidence exists on the association between food insecurity (FI) and blood pressure control in the Caribbean despite the high burden of both. The objective of this study is to examine the relationship between FI and hypertension prevalence, awareness, and control in the Eastern Caribbean.Methods and FindingsWe conducted a cross-sectional analysis of baseline data (2013-2018) from the Eastern Caribbean Health Outcomes Research Network Cohort Study (n=2961). Food insecurity was measured using the Latin American and Caribbean Food Security Scale (ELCSA) and classified as 0=no FI, 1-6 mild/moderate FI, and 7-9 severe FI. Hypertension was defined by the Seventh Report of the Joint National Committee on Prevention. Logistic regression modeling was conducted to examine the relationship between FI and hypertension prevalence, awareness, and control, adjusting for age, sex, educational attainment, site, and usual source of care. Prevalence of FI was 28 percent among participants and was higher in Puerto Rico and Trinidad and Tobago compared to other sites. Seventeen percent of the participants experienced low, 6 percent moderate, and 4 percent experienced severe FI. Aggregate model results showed no association between FI and hypertension outcomes. Sex-stratified results showed moderate (OR=2.65, CI=1.25-5.65) and severe FI (OR=3.69, CI=1.20-11.31) were positively associated with lack of control among women.Limitations of this study include the cross-sectional design, small sample size, and the average age of our cohort. Cross-sectional design precluded the ability to make inferences about temporality between FI and HTN prevalence and awareness. Small sample size precluded the ability to detect statistically significant differences despite strong odds ratios for model results like lack of control.ConclusionsFindings align with prior evidence of greater FI prevalence among women and negative health impact. Nutrition policies are needed to reduce the overall FI burden in the Caribbean and increase access to affordable, nutritious foods.
Diurnal butterfly diversity in a human-modified landscape of the subtropical montane forest of NW Argentina
Authors: Guanuco Andrea del V. , Ordano Mariano , Pereyra Laura C. , Barrionuevo María José , Gonzalez Baffa Trasci Noelia V. , Vaira Marcos 
Published: May 2024

AbstractThe change and intensification in land-use is currently among the main causes of species declines and local extinctions around the world, therefore, forecasting changes in species diversity concerning habitat conditions may be crucial for conservation strategies. We explored the diurnal lepidopteran diversity in a modified landscape of subtropical montane forests of Jujuy, NW Argentina. We considered that degradation of the natural forest habitat would likely impact on resources crucial for butterflies, consequently altering both species richness and composition within these forests. We assessed and compared alpha diversity through Hill diversity profiles and beta diversity through the beta-diversity partitioning method. Additionally, we employed a multivariate permutational analysis of variance, and rank-abundance curves of butterfly species at different habitat types. Our results suggest that land-use changes diminish the number of forest-dependent species and increase species more tolerant to modified habitats and open areas. While alpha diversity did not decrease as land use changed, beta diversity showed significant changes in the butterfly species composition with a worrying reduction of forest-related species in altered habitats. Species composition became increasingly dominated by open area butterfly species resulting in biota homogenization, with possible consequences for ecosystem functioning and services of these forests. Further research on the mechanisms underlying the effects of human-induced habitat changes on forest butterfly diversity could help clarify which mitigation efforts are most likely to be successful for the conservation of butterflies of the subtropical montane forests.
Processing of auditory feedback in perisylvian and insular cortex
Authors: Kurteff Garret Lynn , Field Alyssa M. , Asghar Saman , Tyler-Kabara Elizabeth C. , Clarke Dave , Weiner Howard L. , Anderson Anne E. , Watrous Andrew J. , Buchanan Robert J. , Modur Pradeep N. , Hamilton Liberty S. 
Published: May 2024

SummaryWhen we speak, we not only make movements with our mouth, lips, and tongue, but we also hear the sound of our own voice. Thus, speech production in the brain involves not only controlling the movements we make, but also auditory and sensory feedback. Auditory responses are typically suppressed during speech production compared to perception, but how this manifests across space and time is unclear. Here we recorded intracranial EEG in seventeen pediatric, adolescent, and adult patients with medication-resistant epilepsy who performed a reading/listening task to investigate how other auditory responses are modulated during speech production. We identified onset and sustained responses to speech in bilateral auditory cortex, with a selective suppression of onset responses during speech production. Onset responses provide a temporal landmark during speech perception that is redundant with forward prediction during speech production. Phonological feature tuning in these “onset suppression” electrodes remained stable between perception and production. Notably, the posterior insula responded at sentence onset for both perception and production, suggesting a role in multisensory integration during feedback control.
The complete genome of lettuce reveals centromere landscape and empowers breeding
Authors: Wang Ke , Jin Jingyun , Wang Jingxuan , Wang Xinrui , Sun Jie , Meng Dian , Wang Xiangfeng , Guo Li 
Published: May 2024

AbstractLettuce (Lactuca sativaL.) is a globally grown vegetable crop as the most popular salad ingredient. Lettuce breeding is crucial to enhancing yield, nutrition and disease resistance, but impeded by lacking a high-quality genome resource. In addition, the released genomes remain fragmented (with hundreds of gaps) and incomplete with omitting pivotal centromeres and telomeres. Here, we report a 2.59 Gb complete telomere-to-telomere (T2T) genome assembly for lettuce. T2T genome analysis revealed the unique genetic and epigenetic architectures of centromere repeats dominated by retrotransposons and satellites. The complete genome and annotation facilitate the identification of candidate disease resistance (NLR) genes induced during grey mold infection. The genomic resources, and biological insights into genetic and epigenetic landscape of centromeres not only advance lettuce research and breeding, but also propel the biology and evolution of centromeres across plant kingdom.
KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes
Authors: Xie Xiaowen , Zhang Olivia , Yeo Megan J.R. , Lee Ceejay , Harry Stefan A. , Paul Leena , Li Yiran , Payne N. Connor , Nam Eunju , Kwok Hui Si , Jiang Hanjie , Mao Haibin , Hadley Jennifer L. , Lin Hong , Batts Melissa , Gosavi Pallavi M. , D’Angiolella Vincenzo , Cole Philip A. , Mazitschek Ralph , Northcott Paul A. , Zheng Ning , Liau Brian B. 
Published: May 2024

AbstractCancer mutations can create neomorphic protein-protein interactions to drive aberrant function1. As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma (MB)2, the most common embryonal brain tumor in children, and pineoblastoma3. These mutations impart gain-of-function to KBTBD4 to induce aberrant degradation of the transcriptional corepressor CoREST4. However, their mechanism of action remains unresolved. Here, we elucidate the mechanistic basis by which KBTBD4 mutations promote CoREST degradation through engaging HDAC1/2, the direct neomorphic target of the substrate receptor. Using deep mutational scanning, we systematically map the mutational landscape of the KBTBD4 cancer hotspot, revealing distinct preferences by which insertions and substitutions can promote gain-of-function and the critical residues involved in the hotspot interaction. Cryo-electron microscopy (cryo-EM) analysis of two distinct KBTBD4 cancer mutants bound to LSD1-HDAC1-CoREST reveals that a KBTBD4 homodimer asymmetrically engages HDAC1 with two KELCH-repeat propeller domains. The interface between HDAC1 and one of the KBTBD4 propellers is stabilized by the MB mutations, which directly insert a bulky side chain into the active site pocket of HDAC1. Our structural and mutational analyses inform how this hotspot E3-neo-substrate interface can be chemically modulated. First, our results unveil a converging shape complementarity-based mechanism between gain-of-function E3 mutations and a molecular glue degrader, UM171. Second, we demonstrate that HDAC1/2 inhibitors can block the mutant KBTBD4-HDAC1 interface, the aberrant degradation of CoREST, and the growth of KBTBD4-mutant MB models. Altogether, our work reveals the structural and mechanistic basis of cancer mutation-driven neomorphic protein-protein interactions and pharmacological strategies to modulate their action for therapeutic applications.
Chromosomal domain formation by archaeal SMC, a roadblock protein, and DNA structure
Authors: Yamaura Kodai , Takemata Naomichi , Kariya Masashi , Ishino Sonoko , Yamauchi Masataka , Takada Shoji , Ishino Yoshizumi , Atomi Haruyuki 
Published: May 2024

SUMMARYStructural maintenance of chromosomes (SMC) complexes fold genomes by extruding DNA loops. In eukaryotes, loop-extruding SMC complexes form topologically associating domains (TADs) by being stalled by roadblock proteins. It remains unclear whether a similar mechanism of domain formation exists in prokaryotes. Using high-resolution chromosome conformation capture sequencing, we show that an archaeal homolog of the bacterial Smc-ScpAB complex organizes the genome ofThermococcus kodakarensisinto TAD-like domains. We also find that TrmBL2, a nucleoid- associated protein that forms a stiff nucleoprotein filament, stalls theT. kodakarensisSMC complex and establishes a boundary at the site-specific recombination sitedif. TrmBL2 stalls the SMC complex at tens of additional non-boundary loci with lower efficiency. Intriguingly, the stalling efficiency is correlated with structural properties of underlying DNA sequences. Our study illuminates not only a eukaryotic-like mechanism of domain formation in archaea, but also an unforeseen role of intrinsic DNA structure in large-scale genome organization.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vectorAnopheles gambiae
Authors: Tolosana Ignacio , Willis Katie , Burt Austin , Gribble Matthew , Nolan Tony , Crisanti Andrea , Bernardini Federica 
Published: May 2024

ABSTRACTGenetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings but hesitancy due to their invasive and persistent nature may delay their implementation. Here instead we describe a self-limiting strategy, designed to have geographically and/or temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. Males are unaffected. To our knowledge, our system represents the first engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to 8 times more efficient for population suppression than optimal versions of other self-limiting strategies.
CRISPR gene and transcriptome engineering (CRISPRgate) improves loss-of-function genetic screening approaches
Authors: Stadager Jannis , Bernardini Chiara , Hartmann Laura , May Henrik , Wiepcke Jessica , Kuban Monika , Najafova Zeynab , Johnsen Steven A. , Legewie Stefan , Traube Franziska R. , Jude Julian , Rathert Philipp 
Published: May 2024

AbstractThe CRISPR/Cas9 technology has revolutionized genotype-to-phenotype assignments through large-scale loss-of-function (LOF) screens. However, limitations like editing inefficiencies and unperturbed genes cause significant noise in data collection. To address this, we introduce CRISPR Gene and Transcriptome Engineering (CRISPRgate), which uses two specific sgRNAs to simultaneously repress and cleave the target gene within the same cell, increasing LOF efficiencies and reproducibility. CRISPRgate outperforms conventional CRISPRko, CRISPRi, or CRISPRoff systems in suppressing challenging targets and regulators of cell proliferation. Additionally, it efficiently suppresses modulators of EMT and impairs neuronal differentiation in a human iPSC model. In a multiplexed chromatin-focused phenotypic LOF screen, CRISPRgate exhibits improved depletion efficiency, reduced sgRNA performance variance, and accelerated gene depletion compared to individual CRISPRi or CRISPRko, ensuring consistency in phenotypic effects and identifying more significant gene hits. By combining CRISPRko and CRISPRi, CRISPRgate increases LOF rates without increasing genotoxic stress, facilitating library size reduction for advanced LOF screens.MotivationThe CRISPR technology (CRISPRko/CRISPRi) enables the specific depletion of target genes with fewer off-target effects, facilitating precise investigations of gene function. Despite its benefits, CRISPR applications have limitations. Residual active protein expression mediated by in-frame DNA repair or alternative splicing1–8as well as strong epigenetic regulation and difficulties in sgRNA design to the transcription start site (TSS)9–12hinder the full potential of loss-of-function studies using CRISPRko or CRISPRi. We aimed to achieve robust target gene reduction in order to improve the reproducibility of the CRISPR technology by integrating the widely used CRISPRko and CRISPRi approaches into a single application.
The hippocampus supports interpolation into new states during category abstraction
Authors: Schäfer Theo A.J. , Thalmann Mirko , Schulz Eric , Doeller Christian F. , Theves Stephanie 
Published: May 2024

AbstractThe hippocampus forms concepts by integrating multi-feature relations into a unified representation. A common yet unconfirmed assumption is that such cognitive maps afford interpolations to never-experienced states. We approach this question as a category-learning problem in which prototypes are omitted from training but guide category-based decisions in a subsequent feature-inference task. Consistent with behavior, missing inferred stimulus features were represented at prototypical values in neocortex. This cortical completion effect correlated with hippocampal responses, which in turn reflected the distance between imagined prototypes and experienced exemplars. This was paralleled by a learning-dependent grid-like representation of the underlying conceptual space in entorhinal cortex. Our results suggest that abstracted prototypes correspond to interpolated central states in a cognitive map that guide cortical pattern completion during category-based decisions.
Compositional Shifts and Co-occurrence Patterns of Topsoil Bacteria and Micro-Eukaryotes Across a Permafrost Thaw Gradient in Alpine Meadows of the Qilian Mountains, China
Authors: Wang Zhu , Liu Yang , Wang Fang 
Published: May 2024

AbstractSoil microorganisms play a pivotal role in the biogeochemical cycles of alpine meadow ecosystems, especially in the context of permafrost thaw. However, the mechanisms driving microbial community responses to environmental changes, such as variations in active layer thickness (ALT) of permafrost, remain poorly understood. This study utilized next-generation sequencing to explore the composition and co-occurrence patterns of soil microbial communities, focusing on bacteria and micro-eukaryotes along a permafrost thaw gradient. Results showed a decline in bacterial alpha diversity with increasing permafrost thaw, while micro-eukaryotic diversity exhibited an opposite trend. Although changes in microbial community composition were observed in permafrost and seasonally frozen soils, these shifts were not statistically significant. Bacterial communities exhibited greater differentiation between frozen and seasonally frozen soils, a pattern not mirrored in eukaryotic communities. LEfSe analysis revealed a higher number of potential biomarkers in bacterial communities compared to micro-eukaryotes. Bacterial co-occurrence networks were more complex, with more nodes, edges, and positive linkages than those of micro-eukaryotes. Key factors such as soil texture, ALT, and bulk density significantly influenced bacterial community structures, particularly affecting the relative abundances of the Acidobacteria, Proteobacteria, and Actinobacteria phyla. In contrast, fungal communities (e.g.,Nucletmycea,Rhizaria,Chloroplastida, andDiscoseagroups) were more affected by electrical conductivity, vegetation coverage, and ALT. This study highlights the distinct responses of soil bacteria and micro-eukaryotes to permafrost thaw, offering insights into microbial community stability under global climate change.ImportanceThis study sheds light on how permafrost thaw affects microbial life in the soil, with broader implications for understanding climate change impacts. As permafrost degrades, it alters the types and numbers of microbes in the soil. These microbes play essential roles in environmental processes, such as nutrient cycling and greenhouse gas emissions. By observing shifts from bacteria-dominated to fungi-dominated communities as permafrost thaws, the study highlights potential changes in these processes. Importantly, this research suggests that the stability of microbial networks decreases with permafrost degradation, potentially disrupting the delicate balance of these ecosystems. The findings not only deepen our understanding of microbial responses to changing climates but also support the development of strategies to monitor and potentially mitigate the effects of climate change on fragile high-altitude ecosystems.