bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malaria vector diversity, transmission, and insecticide resistance, in island communities along the Volta Lake in southern Ghana
Authors: Ebuako Abena Ahema , Owusu-Asenso Christopher Mfum , Mohammed Abdul Rahim , Sraku Isaac Kwame , Akuamoah-Boateng Yaw , Appiah-Kwarteng Cornelia , Forson Akua Obeng , Ayeh-Kumi Patrick Ferdinand , Afrane Yaw A. 
Published: January 2025

AbstractIsland communities along the Volta Lake in southern Ghana present unique challenges for malaria control, characterized by high transmission rates, limited vector control measures, and isolated ecosystems. This study assessed the malaria vector diversity, seasonal abundance, transmission, and insecticide resistance status of malaria vectors in these communities to inform effective control strategies. Mosquitoes were collected from three island communities (Tuanikope, Allorkpem, and Pediatorkope) using human landing catches, light traps, and prokopack aspirators during the dry and rainy seasons. Morphological and molecular techniques were used to identify mosquito species, determine blood meal sources, and detect insecticide resistance mutations. Sporozoite infections and entomological inoculation rates (EIRs) were also quantified. A total of 25,079 mosquitoes from four genera were collected; Culicine = 88.19%, Anopheline = 8.89%. Mansonia = 2.24%. The Anophelines predominantly comprisedAnopheles gambiaes.l. 1,911/2,230 (85.70%), followed byAn.pharoensis236/2,230 (10.58%) andAn. rufipes83/2,230 (3.72%). Indoor biting and resting densities were high across sites and seasons, with sporozoite-positive mosquitoes more frequently found indoors. Blood meal analysis revealed a strong anthropophilic feeding pattern (HBI = 80%). Annual EIRs ranged from 37.40 (ib/m/y) to 100.08 (ib/m/y). Low frequencies of insecticide resistance mutations (Vgsc-1014F, Vgsc-1014S, ACE-1, and Vgsc-1575Y) were observed. The study indicates high indoor biting and resting densities ofAnophelesmosquitoes. High sporozoite rate along with low resistance mutation frequencies observed, emphasize the urgent need for continuous resistance monitoring and the implementation of targeted vector control strategies in these hard-to-reach island communities.
Characterization of BvlzGluc, a Novel Antifungal β-Glucanase fromBacillus velezensis, with Potential Agricultural and Industrial Applications
Authors: Vela-Corcia D. , Colino-Palomino A.M. , de Vicente A. , Pérez García A. , Romero D. 
Published: January 2025

Abstractβ-glucanases play a critical role in degrading β-glucans, which are essential components of fungal cell walls that maintain fungal structure and physiology. This study characterizes BvlzGluc, a novel β-glucanase produced byBacillus velezensisCECT 8237, which has potent antifungal properties. BvlzGluc specifically targets the β-glucan layer ofBotrytis cinerea, causing significant structural malformations, impaired fungal development, and reduced virulence. These effects weaken the fungal cell wall, increasing its susceptibility to environmental stress and reducing its capacity to infect host plants. Notably, BvlzGluc is a noncanonical β-glucanase belonging to glycoside hydrolase family 16 (GH16) but presents unique structural features that distinguish it from typical members of this family, suggesting potential reclassification. Its physicochemical stability and simple structural design increase its suitability for scalable production, positioning it as a promising candidate for agricultural and industrial applications requiring efficient β-glucan degradation. This work builds on previous studies of microbial antifungal mechanisms, providing new insights into bacterial‒fungal interactions and reinforcing the potential of bacterial enzymes in sustainable pathogen management and advancing biotechnological innovations.
Cell-APP: A generalizable method for microscopic cell annotation, segmentation, and classification
Authors: Virdi Anish , Joglekar Ajit P. 
Published: January 2025

AbstractHigh throughput fluorescence microscopy is an essential tool in systems biological studies of eukaryotic cells. Its power can be fully realized when all cells in a field of view and the entire time series can be accurately localized and quantified. These tasks can be mapped to the common paradigm in computer vision: instance segmentation. Recently, supervised deep learning-based methods have become state-of-the-art for cellular instance segmentation. However, these methods require large amounts of high-quality training data. This requirement challenges our ability to train increasingly performant object detectors due to the limited availability of annotated training data, which is typically assembled via laborious hand annotation. Here, we present a generalizable method for generating large instance segmentation training datasets for tissue-culture cells in transmitted light microscopy images. We use datasets created by this method to train vision transformer (ViT) based Mask-RCNNs (Region-based Convolutional Neural Networks) that produce instance segmentations wherein cells are classified as “m-phase” (dividing) or “interphase” (non-dividing). While training these models, we also address the dataset class imbalance between m-phase and interphase cell annotations, which arises for biological reasons, using probabilistically weighted loss functions and partisan training data collection methods. We demonstrate the validity of these approaches by producing highly accurate object detectors that can serve as general tools for the segmentation and classification of morphologically diverse cells. Since the methodology depends only on generic cellular features, we hypothesize that it can be further generalized to most adherent tissue culture cell lines.
Genetic Determinants of pOXA-48 Plasmid Maintenance and Propagation inEscherichia coli
Authors: Baffert Yannick , Fraikin Nathan , Makhloufi Yasmine , Baltenneck Julie , Val Marie-Eve , Dedieu-Berne Annick , Degosserie Jonathan , Iorga Bogdan I. , Bogaerts Pierre , Gueguen Erwan , Lesterlin Christian , Bigot Sarah 
Published: January 2025

AbstractConjugative plasmids are the main drivers of antibiotic resistance dissemination contributing to the emergence and extensive spread of multidrug resistance clinical bacterial pathogens. pOXA-48 plasmids, belonging to the IncL group, have emerged as the primary vehicle for carbapenem resistance inEnterobacteriaceae. Despite the problematic prevalence of pOXA-48, most research has focused on epidemiology and genomics, leaving gaps in our understanding of the mechanisms behind its propagation. In this study, we used a transposon sequencing approach to identify genetic elements critical for plasmid stability, replication, and conjugative transfer. Our results identified a novel type I toxin-antitoxin system, new essential maintenance factors, and components of the type IV secretion system and regulatory elements crucial for conjugation. This study advances our understanding of pOXA-48 biology, providing key insights into the genetic factors underlying its successful maintenance and spread in bacterial populations.
Homeostatic bidirectional plasticity in Upbound and Downbound micromodules of the olivocerebellar system
Authors: Fernández Santoro Elías M. , Landsmeer Lennart P.L. , Hamdioui Said , Strydis Christos , De Zeeuw Chris I. , Badura Aleksandra , Negrello Mario 
Published: January 2025

AbstractOlivocerebellar learning is highly adaptable, unfolding over minutes to weeks depending on the task. However, the stabilizing mechanisms of the synaptic dynamics necessary for ongoing learning remain unclear. We constructed a model to examine plasticity dynamics under stochastic input and investigate the impact of inferior olive (IO) reverberations on Purkinje cell (PCs) activity and synaptic plasticity. We explored Upbound and Downbound cerebellar micromodules, which are organized loops of IO neurons, cerebellar nuclei neurons and microzones of PCs characterized by their unique molecular profiles and different levels of baseline firing. Our findings show synaptic weight convergence followed by stability of synaptic weights. In line with their relatively low and high intrinsic firing, we observed that Upbound and Downbound PCs have a propensity for potentiation and depression, respectively, with both PC types reaching stability at differential levels of overall strength of their parallel-fiber (PF) inputs. The oscillations and coupling of IO neurons participating in the Upbound and Downbound modules determine at which frequency band PFs can be stabilized optimally. Our results indicate that specific frequency components drive IO resonance and synchronicity, which, in turn, regulate temporal patterning across Upbound and Downbound zones, orchestrating their plasticity dynamics.Author SummaryThe olivocerebellar system is a part of the brain that facilitates learning and controlling movements. To coordinate movements it integrates sensorimotor information with motor command signals. The resulting behaviour needs to be continuously adjusted during motor learning. The leading hypothesis is that changes in strength of the synaptic connections between neurons underlie the learning process. The challenge is to elucidate the factors that determine the exact timing and precision of the learned movements. To answer this question we developed a computational model of the two main types of modules of the olivocerebellar system that can control different types of movements in a bidirectional fashion. We found that the rhythm and coupling of the olivary neurons play an important role in controlling and stabilizing plasticity in the cerebellar cortex of both types of modules, together shaping learning-dependent timing of motor behaviour.
Hypothalamic Vasopressin Neurons Enable Maternal Thermoregulatory Behaviors
Authors: Adahman Zahra , Ooyama Rumi , Gashi Dinore B. , Medik Zeyneb Z. , Hollosi Hannah K. , Sahoo Biswaranjan , Akowuah Nana D. , Riceberg Justin S. , Carcea Ioana 
Published: January 2025

ABSTRACTNewborns of many mammalian species are partial poikilotherms and require adult thermoregulatory care for survival. In mice, pup survival in cold and cool ambient temperature depends on the ability of adult caregivers to huddle pups and bring them into a high-quality nest. It is therefore essential that adult mice adjust parental care as a function of changes in ambient temperature. Here, we investigated how mouse maternal care adapts to a range of temperatures, from cold to warm. We show that changes in ambient temperature affect several individual and co-parenting maternal behaviors in both dams and virgin female mice, and modulate activity of vasopressin neurons. Furthermore, we establish that the effects of ambient temperature on both maternal care and the activity of vasopressin neurons depend in part on thermosensation, specifically on the TRPM8 sensor. Using trans-synaptic anterograde tracing and whole-brain activity mapping, we find that vasopressin neurons from the paraventricular hypothalamic nucleus connect synaptically with temperature-responsive brain structures implicated in maternal care. We then show that optogenetic activation of vasopressin projections to the central amygdala, a structure activated by cold ambient temperature, recapitulates the effects of cold on co-parenting behaviors. Our data provide a biological mechanism for maternal thermoregulatory behavior in mice with translational relevance to the reported association between ecosystem temperature fluctuations and variations in human child neglect cases.
Maturation of Hippocampus-Medial Prefrontal Cortex Projections Defines a Pathway-Specific Sensitive Period for Cognitive Flexibility
Authors: Cruz-Sanchez Arely , Abdusalom Anusha , Chasiotis Helen , Gugustea Radu , Mumtaz Unza , Hasantash Maryam , Anacker Christoph , Arruda-Carvalho Maithe 
Published: January 2025

SummaryThe septotemporal axis of the hippocampus separates it into domains with unique molecular, cellular, downstream connectivity and behavioral profiles, and yet very little is known about the ontogenesis of these highly specialized subcircuits. Here, we used viral tracing, optogenetic-assisted patch clamping, chemogenetics and behavior in mice to examine changes in domain-defined hippocampus efferent projections from postnatal day (P)10 to P60. We found distinct anatomical and synaptic developmental signatures in ventral and intermediate CA1 downstream connectivity, with unique contributions to the prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC). Inhibition of the ventral CA1 (vCA1)-mPFC pathway during juvenility led to a deficit in adult cognitive flexibility exclusively in females, establishing a sex- and pathway-specific sensitive period preceding the stabilization of vCA1-mPFC synaptic transmission. Our data elucidate domain- and target-defined postnatal maturation of hippocampus efferents, identifying a sex-specific sensitive period with crucial implications for early life influences on adult cognition.
Complex Water Networks Visualized through 2.2-2.3 Å Cryogenic Electron Microscopy of RNA
Authors: Kretsch Rachael C. , Li Shanshan , Pintilie Grigore , Palo Michael Z. , Case David A. , Das Rhiju , Zhang Kaiming , Chiu Wah 
Published: January 2025

AbstractThe stability and function of biomolecules are directly influenced by their myriad interactions with water. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, theTetrahymenaribozyme, determined at 2.2 and 2.3 Å resolutions. By employing segmentation-guided water and ion modeling (SWIM), an approach combining resolvability and chemical parameters, we automatically modeled and cross-validated water molecules and Mg2+ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions. Unexpectedly, in regions where SWIM does not model ordered water, we observed highly similar densities in both cryo-EM maps. In many of these regions, the cryo-EM densities superimpose with complex water networks predicted by molecular dynamics (MD), supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate modeling. Our study demonstrates an approach to unveil both rigid and flexible waters that surround biomolecules through cryo-EM map densities, statistical and chemical metrics, and MD simulations.
Microbial cross-feeding is stabilized when a dependent mutant is segregated from its independent ancestor
Authors: Schakel Olivia F. , Fritts Ryan K. , Zmuda Anthony J. , Setayeshgar Sima , McKinlay James B. 
Published: January 2025

AbstractMicrobial gene loss is hypothesized to be beneficial when gene function is costly, and the gene product can be replaced via cross-feeding from a neighbor. However, cross-fed metabolites are often only available at low concentrations, limiting the growth rates of gene-loss mutants that are dependent on those metabolites. Here we define conditions that support a loss of function mutant in a three-member bacterial community of: (i) N2-utilizingRhodopseudomonas palustrisas an NH4+-excreting producer, (ii) N2-utilizingVibrio natriegensas the ancestor, and (iii) aV. natriegensN2-utilizaton mutant that is dependent on the producer for NH4+. Using experimental and simulated cocultures, we found that the ancestor outcompeted the mutant due to low NH4+availability under uniform conditions where bothV. natriegensstrains have equal access to nutrients. However, spatial structuring that separated the mutant from the ancestor, while maintaining access to NH4+from the producer, allowed the mutant to avoid extinction. Counter to predictions, mutant enrichment under spatially structured conditions did not require a growth rate advantage from gene loss and the mutant coexisted with its ancestor. Thus, cross-feeding can originate from loss-of-function mutations that are otherwise detrimental, provided that the mutant can segregate from a competitive ancestor.Graphical abstract
Combined ADAMTS10 and ADAMTS17 inactivation exacerbates bone shortening and compromises extracellular matrix formation
Authors: Taye Nandaraj , Karoulias Stylianos Z. , Balic Zerina , Wang Lauren W. , Willard Belinda B. , Martin Daniel , Richard Daniel , Okamoto Alexander S. , Capellini Terence D. , Apte Suneel S. , Hubmacher Dirk 
Published: January 2025

AbstractWeill-Marchesani syndrome (WMS) is characterized by severe short stature, short hands and feet (brachydactyly), joint contractures, tight skin, and heart valve, eye, and skin anomalies. Whereas recessive WMS is caused by mutations inADAMTS10,ADAMTS17, orLTBP2, dominant WMS is caused by mutations inFBN1(encoding fibrillin-1). Since bone growth is driven by chondrocyte proliferation and hypertrophy in the growth plates, the genetics of WMS suggests that the affected ECM proteins act within the same pathway to regulate chondrocyte and growth plate function. Here, we investigated the role of the secreted ADAMTS proteases ADAMTS10 and ADAMTS17 in growth plate function and ECM formation. We generatedAdamts10;Adamts17double knockout (DKO) mice, which showed significant postnatal lethality compared to singleAdamts10orAdamts17KO mice. Importantly, we observed severe bone shortening DKO mice, which correlated with a narrower hypertrophic zone in their growth plates. ADAMTS17 substrates identified by N-terminomics and yeast two-hybrid screening identified the ECM proteins fibronectin and collagen VI (COL6). However, validation experiments did not reveal direct proteolysis of either fibronectin or COL6 by ADAMTS17. We then investigated ECM formation in primary ADAMTS10- and ADAMTS17-deficient skin fibroblasts and observed compromised fibronectin deposition concomitant with aberrant intracellular accumulation of fibrillin-1. These findings support a role for ADAMTS17 in ECM protein secretion and assembly. Collectively, our data suggest that ADAMTS10 and ADAMTS17 regulate bone growth by regulating chondrocyte hypertrophy or hypertrophic chondrocyte turnover. Mechanistically, ADAMTS17 appears to be a critical regulator of ECM protein secretion or pericellular matrix assembly, whereas ADAMTS10 likely modulates ECM formation at later stages, possibly regulating the spatio-temporal deposition of fibrillin isoforms.
Frontal midline theta power accounts for inter-individual differences in motor learning ability
Authors: Fukuda Yuya , Uehara Kazumasa 
Published: January 2025

AbstractRecent neurophysiological studies have demonstrated that frontal midline theta (FMT) activity plays a significant role in motor learning. One of the key challenges in motor learning is to understand the interindividual variability in learning proficiency rates, yet the underlying neural mechanisms remain unclear. To address this open question, this study recorded electroencephalogram activity during a visuomotor tracking task to investigate whether modulation of FMT power and the consistency of theta phase during motor preparation could explain individual differences in learning proficiency. We found a significant positive correlation between increased FMT power during motor preparation and learning proficiency rates. Specifically, individuals with greater FMT power exhibited faster learning rates. In contrast to this, no significant correlation was observed between the consistency of theta phase during motor preparation and learning proficiency. Together, these findings highlight that the FMT power, rather than phase synchrony, is closely associated with motor learning efficiency. This study provides a novel perspective for understanding the causes of individual differences in motor learning and further corroborates the previous evidence showing FMT power contributes to motor learning processes.
Loss of Fanconi anemia proteins causes a reliance on lysosomal exocytosis
Authors: Fu Becky Xu Hua , Xu Albert , Li Hua , Johnson Daniel E. , Grandis Jennifer R. , Gilbert Luke A. 
Published: January 2025

AbstractMutations in the FA pathway lead to a rare genetic disease that increases risk of bone marrow failure, acute myeloid leukemia, and solid tumors. FA patients have a 500 to 800-fold increase in head and neck squamous cell carcinoma compared to the general population and the treatment for these malignancies are ineffective and limited due to the deficiency in DNA damage repair. Using unbiased CRISPR-interference screening, we found the loss of FA function renders cells dependent on key exocytosis genes such as SNAP23. Further investigation revealed that loss of FA pathway function induced deficiencies in lysosomal health, dysregulation of autophagy and increased lysosomal exocytosis. The compromised cellular state caused by the loss of FA genes is accompanied with decreased lysosome abundance and increased lysosomal membrane permeabilization in cells. We found these signaturesin vitroacross multiple cell types and cell lines and in clinically relevant FA patient cancers. Our findings are the first to connect the FA pathway to lysosomal exocytosis and thus expands our understanding of FA as a disease and of induced dependencies in FA mutant cancers.
Designing a hybrid organization structure based on competences: the importance of the organizational structure
Authors: Bagni Gustavo , Marçola Josadak Astorino , Escrivão Filho Edmundo , Nagano Marcelo Seido , Philippsen Luiz 
Published: January 2025

PurposeThe purpose of this study is to propose a comprehensive model of a hybrid organizational structure through action research, aiming to fill a gap in the literature on organizational structure implementation. The focus is on designing a model that integrates structural elements (centralization and specialization) and a non-structural element (competence), emphasizing operational efficiency and innovation capacity. The study was conducted in the production scheduling and control department (PSC) of a manufacturing company, with quantitative results demonstrating the feasibility of the proposed model.Design/methodology/approachThe study employs an action research approach to develop a hybrid organizational structure model in three phases comprising ten steps. It focuses on integrating structured elements like centralization and specialization, alongside a non-structural component, competence. The research was conducted within the PSC of a manufacturing firm. This methodological framework facilitates the systematic design and implementation of the organizational structure model, allowing for a comprehensive analysis of its impact on performance indicators.FindingsThe quantitative results of the action research revealed a 3% increase in Overall Equipment Efficiency (OEE) and a 4% improvement in On Time/In Full (OTIF) performance metrics. These findings demonstrate the effectiveness and feasibility of the hybrid organizational structure model implemented in the PSC. The structured elements (centralization and specialization) combined with the non-structural element (competence) contributed to enhancing operational efficiency and meeting production goals, underscoring the significance of aligning organizational structure with strategic objectives for improved performance in dynamic competitive environments.Originality/valueThis study contributes to the literature by addressing the gap in research on implementing organizational structures. It offers a novel approach through action research, proposing a comprehensive model of a hybrid organizational structure. By integrating structured elements (centralization and specialization) with a non-structural element (competence), the model enhances operational efficiency and innovation capacity. The quantitative findings demonstrate the model’s effectiveness in improving performance metrics, emphasizing its value in guiding organizational design processes. This research underscores the importance of aligning organizational structures with strategic objectives to foster competitiveness and adaptability in dynamic business environments.