bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression ofaedes aegyptiby sterile insect technique on captiva island, florida, usa from 2020 to 2022
Authors: Morreale Rachel , Carvalho Danilo Oliveira , Stenhouse Steven , Bajonero Johanna , Pereira Rui , Hahn Daniel A , Lloyd Aaron , Hoel David F. 
Published: October 2024

ABSTRACTAedes aegypti, an aggressive nuisance biter and the primary vector for numerous arboviruses, such as chikungunya, dengue, and Zika, presents significant control challenges due to its ability to thrive in urban environments, escapes insecticide treatment by using cryptic resting and oviposition sites, and development of resistance to chemical mosquito control products being used routinely. To test a new approach in their integrative mosquito management toolbox. From 2020 to 2022, the Lee County Mosquito Control District (LCMCD) employed the Sterile Insect Technique (SIT) to test a new approach in its integrated mosquito management toolbox, targeting the population suppression ofAe. aegyption Captiva Island, Florida. Over 24.1 million sterile males were released across three phases, covering up to 142 hectares. The study demonstrated a population reduction of up to 79% in wild adults and a 59% decline in egg densities in the primary intervention area. While population control was successful, an influx of wild females from untreated zones posed ongoing challenges to complete suppression in areas close to non-intervention areas. This supported a need for an area-wide integrated pest management (AW-IPM) approach. These results underscore SIT’s potential as a critical tool in integrated mosquito management strategies and emphasize practical application.
Multi-timescale neural adaptation underlying long-term musculoskeletal reorganization
Authors: Philipp Roland , Hara Yuki , Uchida Naoki , Ohta Naohito , Oya Tomomichi , Funato Tetsuro , Seki Kazuhiko 
Published: October 2024

ABSTRACTThe central nervous system (CNS) can effectively control body movements despite environmental changes. While much is known about adaptation to external environmental changes, less is known about responses to internal bodily changes. This study investigates how the CNS adapts to long-term alterations in the musculoskeletal system using a tendon transfer model in non-human primates. We surgically relocated finger flexor and extensor muscles to examine how the CNS adapts its strategy for finger movement control by measuring muscle activities during grasping tasks. Two months post-surgery, the monkeys demonstrated significant recovery of grasping function despite the initial disruption. Our findings suggest a two-phase CNS adaptation process: an initial phase enabling function with the transferred muscles, followed by a later phase abolishing this enabled function and restoring a more efficient and “good enough” control strategy resembling the original. These results highlight a multi-phase CNS adaptation process with distinct time constants in response to sudden bodily changes, offering potential insights into understanding and treating movement disorders.SIGNIFICANCE STATEMENTThis study demonstrates the remarkable ability of the CNS to adapt motor control to long-term internal changes, even after significant alterations to the musculoskeletal system. These findings expand our understanding of CNS plasticity and offer promising insights for enhancing rehabilitation following injuries or surgeries that disrupt body mechanics. By unraveling the mechanisms behind this long-term adaptation, targeted rehabilitation strategies to optimize motor recovery in patients with stroke, spinal cord injury, or musculoskeletal disorders can be developed, ultimately improving patient outcomes and quality of life.
Using readmers and hapmers in assessing phase switching after read error correction of Oxford Nanopore Sequences
Authors: Elbers Jean P. , Horner David , Löwenstern Tamara , Laccone Franco 
Published: October 2024

AbstractMethods for sequence error correction can improve sequence accuracy; however, there can be unintended errors added during error correction. One such example is phase switching, whereby sequences derived from genomes containing more than one parental copy have contributions from more than one parental haplotype. Such switches are mistakes that can confound downstream analyses especiallyde novogenome assembly. While DNA sequences do not possess words such as linguistic languages, one can partition a DNA sequence into word-like objects called k-mers. K-mers include pieces of DNA sequence of k length that can describe various properties of DNA sequences. With regard to phase switching, there are k-mers present in one parental haplotype not found in other(s). These so-called hapmers can represent inaccuracies in that parental haplotype’s assembly but also correct, unique DNA variation. Here we investigated the effect of DNA sequence error correction on phase switching at the sequence/read level. Using several error-correction methods, we find all methods tested are similar to raw, presumably, phase-switch-free Oxford Nanopore Technologies (ONT) sequences in the percentage of readmers (k-mers from the ONT sequences) matching one parental haplotype’s hapmers. This work demonstrates an efficient method to assess if an error-correction method has introduced phase switching implemented in the Julia programming language.
Sex and seasonal variations in melatonin suppression, and alerting response to light
Authors: Fazlali Fatemeh , Lazar Rafael , Yahya Faady , Stefani Oliver , Spitschan Manuel , Cajochen Christian 
Published: October 2024

AbstractLight influences human physiology and behaviour by regulating circadian rhythms, melatonin secretion, and alertness. Previous research has reported sex differences in melatonin secretion and circadian rhythms, possibly related to women’s greater sensitivity to bright light. Other studies have suggested reduced photosensitivity and earlier circadian phases in summer than in winter in mid-latitude regions. This study explores the effects of sex, seasonality, and their combination on melatonin suppression and subjective sleepiness in response to moderate light exposure, considering prior light history and menstrual phases in females. We conducted a controlled, within-subject experiment with 48 healthy adults (18–35 years, 50% female) across different seasons. The study design included two 9-h laboratory sessions, with at least 5-day washout in between. Participants were exposed to dim and moderate light through a screen for 2 hours after their habitual bedtime. Female participants exhibited greater melatonin suppression (+4.69 %) but a lower alerting response (−6.00%) to moderate light compared to males. Both sexes demonstrated increased sensitivity to the NIF effects of light in winter, with stronger melatonin suppression (+18.05 %) and increased alertness (+7.60 %) compared to summer. While prior light history did not significantly impact melatonin suppression or alertness, it was associated with an earlier dim light melatonin onset (DLMO). Females during their luteal phase had earlier DLMO than those in their follicular phase. Our findings indicate an interaction between sex, seasonality, and light exposure in modulating melatonin suppression, emphasising the need for personalised light exposure recommendations according to individual biological and environmental contexts.
Development and Characterization of a 2D Porcine Colonic Organoid Model for Studying Intestinal Physiology and Barrier Function
Authors: Plenge Masina , Schnepel Nadine , Müsken Mathias , Rohde Judith , Goethe Ralph , Breves Gerhard , Mazzuoli-Weber Gemma , Benz Pascal 
Published: October 2024

AbstractThe porcine colon epithelium plays a crucial role in nutrient absorption, ion transport, and barrier function. However ethical concerns necessitate the development of alternatives to animal models for its study. The objective of this study was to develop and characterise a two-dimensional (2D)in vitromodel of porcine colonic organoids that closely mimics native colon tissue, thereby supporting in vitro research in gastrointestinal physiology, pathology, and pharmacology. Porcine colonic crypts were isolated and cultured in three-dimensional (3D) organoid systems, which were subsequently disaggregated to form 2D monolayers on transwell inserts. The integrity of the monolayers was evaluated through the measurement of transepithelial electrical resistance (TEER) and electron microscopy. The functional prerequisites of the model were evaluated through the measurement of the mRNA expression of key ion channels and transporters, using quantitative RT-PCR. Ussing chamber experiments were performed to verify physiological activity. The 2D monolayer displayed robust TEER values and retained structural characteristics, including microvilli and mucus-secreting goblet cells, comparable to those observed in native colon tissue. Gene expression analysis revealed no significant differences between the 2D organoid model and native tissue with regard to critical transporters. Ussing chamber experiments demonstrated physiological responses that were consistent with those observed in native colonic tissue. In conclusion, 2D porcine colonic organoid model can be recommended as an accurate representation of the physiological and functional attributes of the native colon epithelium. This model offers a valuable tool for investigating intestinal barrier properties, ion transport, and the pathophysiology of gastrointestinal diseases, while adhering to the 3R principles.
Combined Linkage Disequilibrium and Linkage Analysis (cLDLA): implementation of a powerful approach to identify the genetic basis of complex traits in a bioinformatics workflow
Authors: Upadhyay M. , Panchal A. , Medugorac I. 
Published: October 2024

AbstractIdentifying the relationship between the polymorphism segregating in a population and phenotypic differences of a trait observed between the individuals of a population is of major biological interest and represents the basis of forward genetics. Much of the traits of interest are influenced by several polymorphic genes and environmental conditions. Often the loci associated with such measurable traits are referred to as Quantitative trait loci. These loci are identified using several statistical approaches. One of them is combined linkage disequilibrium and linkage analysis (cLDLA). This approach, first proposed by Meuwissen and colleagues in 2002, is shown to be robust against population stratification/family structure and requires a relatively lower sample size compared to a genome-wide association study design. Previously, we have successfully used this approach in mapping several important traits in livestock such as identifying the genetic basis of polled condition in cattle and tail length in sheep. A cLDLA requires several complex computation processing and intermediary file conversion steps; for some of these steps no open-source tools are available. Therefore, running this analysis, manually, can prove challenging, tedious, or error-prone. We present, cldla, a bioinformatics workflow implemented in nextflow which takes the vcf file and phenotype file as inputs and implements all the downstream processing required for cLDLA. Additionally, it also has a separate workflow to estimate SNP-based heritability and features for interactive visualization of the results. The workflow is freely available at:https://github.com/Popgen48/cldla.
LIFERING, an E3 ligase, ubiquitinates the acyl-CoA dehydrogenase-like protein IBR3, and coordinates cell proliferation and death upon DNA damage
Authors: Kállai Brigitta M. , Németh Edit , Pettkó-Szandtner Aladár , Ahmad Zaki , Nagy Fruzsina , Bögre László , Magyar Zoltán , Mészáros Tamás , Horváth Beatrix M. 
Published: October 2024

ABSTRACTPlants rapidly respond to environmental changes to ensure an optimal balance between growth and survival with intact genome. Here, we show that a DNA damage response gene, which we namedLIFERING, is under the direct and independent regulation of ATM/ATR-SOG1 and RBR pathways. We demonstrate that LIFERING upon DNA damage plays an essential role in maintaining the balance between cell proliferation and cell death. Downstream of RBR, it is required to maintain proliferation, and in response to DNA damaging agents it initiates a cell death accompanied by rapid elongation and differentiation of the transit amplifying cells in the root meristem. LIFERING is a RING-between-RING E3 ligase; its ligase activity is dependent on the Cys392 residue located in the BRcat domain, responsible for the coordination of zinc ion binding. Using proximity labelling, we identified the acyl-CoA dehydrogenase-like protein IBR3, which is involved in the conversion of indole-3-butyric acid (IBA) to indole-3-acetic acid (IAA), as one of its targets. We provide evidence that IBR3 is ubiquitinated at several Lys residues in the presence of LIFERING. Our findings show that LIFERING rapidly responds to DNA damage and via ubiquitination of IBR3, is likely to be involved in the regulation of free-auxin level, indicating a link between DNA damage response and auxin regulation in the root.
Integrin alpha1 beta1 promotes interstitial fibrosis in a mouse model of polycystic kidney disease
Authors: Grenier C. , Lin I-H. , Peters DJM. , Pozzi A. , Lennon R. , Naylor RW. 
Published: October 2024

AbstractFibrosis is the cause of end-stage kidney failure in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). The molecular and cellular mechanisms involved in fibrosis are complex and anti-fibrotic therapies have so far failed to make an impact on patient welfare. Using unbiased proteomics analysis on thePkd1nl/nlmouse, we found that expression of the integrin α1 subunit is increased in this model of ADPKD. In human ADPKD tissue and two single cell RNA kidney disease datasets,ITGA1was also upregulated. To investigate the functional role of this integrin subunit in ADPKD, we generated aPkd1nl/nlItga1−/−mouse. We observed a significant reduction in kidney volume and kidney dysfunction in mice lacking the integrin α1 subunit. Kidneys fromPkd1nl/nlItga1−/−mice had smaller cysts and reduced interstitial expansion and tubular atrophy. Picrosirius red staining identified a restriction in collagen staining in the interstitium and the myofibroblast marker α smooth muscle actin was also downregulated. Myofibroblast cell proliferation was reduced inPkd1nl/nlItga1−/−mice and primary fibroblast cultures demonstrated an abrogated fibrogenic phenotype in integrin α1-depleted fibroblasts. These results highlight a previously unrecognised role for the integrin α1 subunit in kidney fibrosis.
Zika and Dengue Viruses Differentially Modulate Host mRNA Processing Factors Defining Its Virulence
Authors: Scholl Aaron , Gong Binsheng , Li Bingjie , Fatima Tahira , Tirrell Nikki , Karaiskos Spyros , Rios Maria , Xu Joshua , De Sandip 
Published: October 2024

AbstractRising global temperatures coupled with increasing international travel, and trade are contributing to spread of vectors such as ticks and mosquitoes, resulting in a surge of vector-borne flavivirus infection in human population. Furthermore, this increase in flavivirus infection pose threat to the safety of biologics such as cell and gene therapy products as human-derived materials are commonly used during manufacturing of these drug products. In this study, we conducted time-course transcriptomic and protein analyses to uncover the host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in the context of host defense mechanisms, as these two viruses have caused the most recent and significant flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA sequencing analysis revealed differential expression of various cellular factors, including RNA processing factors. Further investigation identified cell-type and time-dependent upregulation nonsense-mediated RNA decay (NMD), RNA degradation factors and nuclear pore complex (NPC) transcripts. Protein analysis showed that ZIKV, unlike DENV, degrades NMD factors in host cells, which along with mis-regulation of RNA degradation factors resulted in accumulation in host intronic transcripts as revealed by RNA-seq data. We also found that active nuclear transport is required for ZIKV replication, suggesting that therapeutic targeting of the NPC could potentially be effective in controlling ZIKV infection. Furthermore, from our findings we hypothesize that, ZIKV, but not DENV, drives early host cell cytopathy through targeted protein degradation. Current studies are underway to develop novel strategies to detect ZIKV, DENV and other flaviviruses in biologics based on transcriptomics and proteomics.TeaserExploring the molecular basis of flavivirus virulence in host cells.
The representational geometry for naturalistic textures in macaque V1 and V2
Authors: Pavuluri Abhimanyu , Kohn Adam 
Published: October 2024

AbstractOur understanding of visual cortical processing has relied primarily on studying the selectivity of individual neurons in different areas. A complementary approach is to study how the representational geometry of neuronal populations differs across areas. Though the geometry is derived from individual neuronal selectivity, it can reveal encoding strategies difficult to infer from single neuron responses. In addition, recent theoretical work has begun to relate distinct functional objectives to different representational geometries. To understand how the representational geometry changes across stages of processing, we measured neuronal population responses in primary visual cortex (V1) and area V2 of macaque monkeys to an ensemble of synthetic, naturalistic textures. Responses were lower dimensional in V2 than V1, and there was a better alignment of V2 population responses to different textures. The representational geometry in V2 afforded better discriminability between out-of-sample textures. We performed complementary analyses of standard convolutional network models, which did not replicate the representational geometry of cortex. We conclude that there is a shift in the representational geometry between V1 and V2, with the V2 representation exhibiting features of a low-dimensional, systematic encoding of different textures and of different instantiations of each texture. Our results suggest that comparisons of representational geometry can reveal important transformations that occur across successive stages of visual processing.
P23H rhodopsin aggregation in the ER causes synaptic protein imbalance in rod photoreceptors
Authors: Thompson Samantha L. , Crowder Sophie M. , Hekmatara Maryam , Sechrest Emily R. , Deng Wen-Tao , Robichaux Michael A. 
Published: October 2024

AbstractRod photoreceptor neurons in the retina detect scotopic light through the visual pigment rhodopsin (Rho) in their outer segments (OS). Efficient Rho trafficking to the OS through the inner rod compartments is critical for long-term rod health. Given the importance of protein trafficking to the OS, less is known about the trafficking of rod synaptic proteins. Furthermore, the subcellular impact of Rho mislocalization on rod synapses (i.e., “spherules”) has not been investigated. In this study we used super-resolution and electron microscopies, along with proteomics, to perform a subcellular analysis of Rho synaptic mislocalization in P23H-Rho-RFP mutant mice. We discovered that mutant P23H-Rho-RFP protein mislocalized in distinct ER aggregations within the spherule cytoplasm, which we confirmed with AAV overexpression. Additionally, we found synaptic protein abundance differences in P23H-Rho-RFP mice. By comparison, Rho mislocalized along the spherule plasma membrane in WT and rd10 mutant rods, in which there was no synaptic protein disruption. Throughout the study, we also identified a network of ER membranes within WT rod presynaptic spherules. Together, our findings indicate that photoreceptor synaptic proteins are sensitive to ER dysregulation.Summary StatementThis study examines the impact of rhodopsin mislocalization on rod photoreceptor synaptic structures and synaptic protein levels using P23H rhodopsin and other retinitis pigmentosa mouse models.
A Practical and Safe Model of Nitrogen Mustard Injury in Cornea
Authors: Sandoval-Castellanos Ana M. , Ke Yao , Dam Tiffany M. , Maverakis Emanual , Mannis Mark J. , Wang Xiao-Jing , Zhao Min 
Published: October 2024

AbstractPurposeSulfur mustard (SM) is an alkylating agent used in warfare and terrorism that inflicts devastating ocular injuries. Although the clinical symptoms are well described, the underlying mechanisms are not fully understood, hindering the development of effective treatments. One major roadblock is the lack of a suitable model due to the extremely hazardous nature of SM, which requires strict safety measures. As a safe and practical alternative, we report a novel model that uses mechlorethamine (nitrogen mustard) gel, an FDA-approved topical chemotherapeutic administered by patients at home. Here we demonstrate its suitability to induce mustard corneal injury in any laboratory.MethodsEx vivoporcine corneas were injured with mechlorethamine gel. Hematoxylin-eosin staining, and immunohistochemistry were performed to evaluate histopathology of SM-like corneal injuries: epithelium thickness and stromal separation, keratocyte and inflammatory cell counts, and expression of inflammation and fibrosis markers.ResultsThis model showed the characteristic histopathology and expression of cyclooxygenase-2 (inflammation) and fibronectin-1 (fibrosis), which were consistent with other well-established SM-like corneal injury models.ConclusionGiven its ease of implementation and safety, this mechlorethamine model could be used to study the full course of mustard corneal injuries. This model would greatly facilitate mustard injury research, shedding light on new knowledge that would increase our understanding of mustard ocular injuries while investigating novel therapeutics.Translational relevancethis model will allow safe evaluation of SM-like corneal injuries within 24 hours, facilitating the identification of early/new molecules that might help to develop novel treatments which could be readily translated into the clinic.
Nicotinamide Metabolism Reprogramming Drives Reversible Senescence of Glioblastoma Cells
Authors: Narayanan Ashwin , Saurty-Seerunghen Mirca S , Michieletto Jessica , Delaunay Virgile , Bruneel Arnaud , Dupré Thierry , Ottolenghi Chris , Pontoizeau Clément , Ciccone Lucrezia , De La Vara Andreas , Idbaih Ahmed , Turchi Laurent , Virolle Thierry , Chneiweiss Hervé , Junier Marie-Pierre , El-Habr Elias A. 
Published: October 2024

AbstractRecent studies show that metabolites, beyond their metabolic roles, can induce significant changes in cell behavior. Herein, we investigate the non-canonical role of nicotinamide (vitamin B3) on glioblastoma (GB) cell behavior. Nicotinamide induced senescence in GB cells, characterized by reduced proliferation, chromatin reorganization, increased DNA damage, enhanced beta-galactosidase activity, and decreased Lamin B1 expression. Nicotinamide-induced senescence was accompanied by an unexpected reprogramming of its metabolism, marked by simultaneous downregulated transcription of NNMT (nicotinamide N-methyltransferase) and NAMPT (nicotinamide phosphoribosyl-transferase). Nicotinamide effects on GB cells were mediated by decreased levels of SOX2. Consistently, analyses of patients’ single cell transcriptome datasets showed that GB cells with low NNMT and NAMPT expression levels were enriched in gene modules related to senescence. Remarkably, senescent GB cells retained tumor-forming abilityin vivo, albeit to a lesser extent compared to control cells. Further experiments at the single-cell level and transcriptomic analyses demonstrated that nicotinamide-induced senescence in GB cells is fully reversible. Overall, our findings identify a novel reversible senescent state in GB tumors and highlight the non-canonical role of NAM as a key driver of cancer cell plasticity.