bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjunctival Chalasis Should Not be Overlooked: Investigation Into Postoperative Ocular Surface Changes in Involutional Blepharoptosis
Authors: Uemura Kazuhisa , Hiroki Iwanishi , Saika Shizuya , Suzuki Takuya , Asamura Shinichi 
Published: April 2024

Background:
Involutional blepharoptosis is common among elderly people. The tightening of eyelids postptosis surgery could potentially increase friction between the eyelid and the ocular surface, but this hypothesis has not yet been substantiated by research. The authors explored the relationship between involutional blepharoptosis surgery and friction-related diseases, namely conjunctivochalasis, lid wiper epitheliopathy, and superior limbic keratoconjunctivitis.

Methods:
We conducted a prospective study involving 31 patients who underwent levator advancement for involutional blepharoptosis. Both preoperatively and 6 weeks postoperatively, the authors assessed a range of outcome measures, including margin reflex distance-1, 2, tear film break-up time, superficial punctate keratopathy, inferior conjunctivochalasis, upper lid wiper epitheliopathy, and superior limbic keratoconjunctivitis

Results:
Conjunctivochalasis was detected in 18 eyes preoperatively and 20 eyes postoperatively. Lid wiper epitheliopathy was detected in 2 eyes preoperatively and in no eyes postoperatively. Superior limbic keratoconjunctivitis was detected in 2 eyes preoperatively and 1 eye postoperatively. From preoperative to postoperative assessments, conjunctivochalasis worsened in 11 eyes (17.2%), and there were no eyes with worsening lid wiper epitheliopathy or superior limbic keratoconjunctivitis. There was a significant worsening of superficial punctate keratopathy in the group with exacerbated conjunctivochalasis compared with the unchanged group (0.72 vs. 0.12, P=0.0222). The superficial petechial keratopathy in the 6 cases in which there was worsening of both conjunctivochalasis and superficial petechial keratopathy were all located inferiorly in the cornea.

Conclusions:
Conjunctivochalasis can worsen following ptosis surgery, potentially leading to an increase in inferior superficial punctate keratopathy. When performing involutional blepharoptosis surgery, surgeons should be mindful of the potential implications of friction-related diseases, particularly conjunctivochalasis.
Age-related changes of Peak width Skeletonized Mean Diffusivity (PSMD) across the adult life span: a multi-cohort study
Authors: Beaudet Grégory , Tsuchida Ami , Petit Laurent , Tzourio Christophe , Caspers Svenja , Schreiber Jan , Pausova Zdenka , Patel Yash , Paus Tomas , Schmidt Reinhold , Pirpamer Lukas , Sachdev Perminder S. , Brodathy Henry , Kochan Nicole , Trollor Julian , Wen Wei , Armstrong Nicola J. , Deary Ian J. , Bastin Mark E. , Wardlaw Joanna M. , Maniega Susana Munõz , Witte A. Veronica , Villringer Arno , Duering Marco , Debette Stéphanie , Mazoyer Bernard 
Published: April 2024

AbstractParameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and meta-analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing DTI metrics. For each individual MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40 and 50, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70’s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60’s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.
Daily glycome and transcriptome profiling reveals polysaccharide structures and glycosyltransferases critical for cotton fiber growth
Authors: Swaminathan Sivakumar , Grover Corrinne E. , Mugisha Alither S. , Sichterman Lauren E. , Lee Youngwoo , Yang Pengcheng , Mallery Eileen L. , Jareczek Josef J , Leach Alexis G , Xie Jun , Wendel Jonathan F. , Szymanski Daniel B. , Zabotina Olga A. 
Published: April 2024

AbstractCotton fiber length and strength are key determinants of its quality. Dynamic changes in the pectin, xyloglucan, xylan, and cellulose polysaccharide epitopes content during fiber growth contribute to complex remodeling of fiber cell wall (CW) and quality. Detailed knowledge about polysaccharide compositional and structural alteration in the fiber during fiber elongation and strengthening is vastly limited. Here, large-scale glycome profiling coupled with fiber phenotype and transcriptome profiling was conducted on fiber collected daily covering the most critical fiber developmental window. High temporal resolution profiling allowed us to identify specific polysaccharide epitopes associated with distinct fiber phenotypes that might contribute to fiber quality. This study revealed the critical role of highly branched RG-I pectin epitopes such as, β-1,4-linked-galactans, β-1,6-linked-galactans, and arabinogalactans, in addition to earlier reported homogalacturonans and xyloglucans in the formation of cotton-fiber-middle-lamella and contributing to fiber plasticity and elongation. We also propose the essential role of heteroxylans (Xyl-MeGlcA and Xyl-3Ar), as a guiding factor for secondary CW cellulose-microfibril arrangement, thus contributing to fiber strength. Correlation analysis of glycome and transcriptome data identified several key putative glycosyltransferases involved in synthesizing the critical polysaccharide epitopes. Novel details discovered here provide a foundation to identify molecular factors that dictate important fiber traits.
Leg stiffness adjustment during hopping by dynamic interaction between the muscle and tendon of the triceps surae
Authors: Kuriyama Kazuki , Takeshita Daisuke 
Published: April 2024

AbstractThe biomechanics underlying bouncing exercises are characterized by the spring-like behavior of the human leg. However, the mechanism underlying the mechanistic contribution of muscle dynamics to the adjustment of leg stiffness is unclear. This study aimed to elucidate the mechanisms governing the changes in leg stiffness during hopping at different frequencies by examining the dynamics of the muscle–tendon complex (MTC) of the medial gastrocnemius muscle (MG). We hypothesized that an increase in muscle stiffness would augment leg stiffness, thereby enabling hopping at higher frequencies. Kinematic and kinetic data were obtained using a motion capture system and force plates. Simultaneously, ultrasound images of the MG were acquired to quantify the muscle fascicle length and pennation angle. The results showed that the stiffness of the MTC increased with hop frequency and exhibited a strong correlation with the leg stiffness. In addition, with increasing frequency, the fascicle contractions shifted from isometric to concentric. To explain these results, an MTC model comprising a contractile component (CC) and series elastic component (SEC) was constructed. We observed a negative CC stiffness, which increased the MTC stiffness. Although this result appears to diverge from our initial hypothesis, the effect of negative CC stiffness on MTC stiffness can be understood, from the perspective of two springs in series, as an extension of the very high stiffness effect. This quantitative understanding of the dynamic interaction between the muscle and tendon offers a unified framework for interpreting various results of previous studies on fascicle dynamics during hopping.
Pisum sativumapplies sanctions to less effective strains at the nodule level, but not within mixed nodules
Authors: Underwood Thomas J. , Jorrin Beatriz , Turnbull Lindsay A. , Poole Philip S. 
Published: April 2024

SummaryLegumes sanction root nodules containing rhizobial strains with low nitrogen fixation rates (less effective fixers). Pea (Pisum sativum) nodules contain both undifferentiated bacteria and terminally differentiated nitrogen-fixing bacteroids. It is critical to understand how sanctions act on both bacteria and bacteroids and how they differ. In addition, less effective strains could potentially evade sanctioning by entering the same nodule as an effective strain i.e., piggybacking.P. sativumwas co-inoculated with pairwise combinations of three strains of rhizobia with different effectiveness, to test whether ineffective strains can evade sanctions in this way.We assessed the effect of sanctions on nodule populations of bacteria and bacteroids using flow cytometry and the effects on nodule ultra-structure using confocal microscopy.We show that sanctioning lowered the bacteroid population and caused a reduction in the size of bacteria. Sanctions also precipitated an early change in nodule cell morphology. In nodules containing two strains that differed in their nitrogen-fixation ability, both were sanctioned equally. Thus, peas sanction whole nodules based on their nitrogen output, but do not sanction at the cellular level.Our results demonstrate that whole-nodule conditional sanctioning in peas provides long-term stability to the symbiosis by effectively reducing the fitness of ineffective strains.
A comparison of lipid diffusive dynamics in monolayers and bilayers in the context of interleaflet coupling
Authors: Mandal Titas , Brandt Nadine , Tempra Carmelo , Javanainen Matti , Fábián Balázs , Chiantia Salvatore 
Published: April 2024

AbstractCellular membranes are composed of lipids typically organized in a double-leaflet structure. Interactions between these two leaflets – often referred to as interleaflet coupling – play a crucial role in various cellular processes. Despite extensive study, the mechanisms governing such interactions remain incompletely understood. Here, we investigate the effects of interleaflet coupling from a specific point of view, i.e. by comparing diffusive dynamics in bilayers and monolayers, focusing on potential lipid-specific interactions between opposing leaflets. Through quantitative fluorescence microscopy techniques, we characterize lipid diffusion and mean molecular area in monolayers and bilayers composed of different lipids. Our results suggest that the observed decrease in bilayer lipid diffusion compared to monolayers depends on lipid identity. Furthermore, our analysis suggests that lipid acyl chain structure and spatial configuration at the bilayer may strongly influence interleaflet interactions and dynamics in bilayers. These findings provide insights into the role of lipid structure in mediating interleaflet coupling and underscore the need for further experimental investigations to elucidate the underlying mechanisms.
Mimicking opioid analgesia in cortical pain circuits
Authors: James Justin G. , McCall Nora M. , Hsu Alex I. , Oswell Corinna S. , Salimando Gregory J. , Mahmood Malaika , Wooldridge Lisa M. , Wachira Meghan , Jo Adrienne , Sandoval Ortega Raquel Adaia , Wojick Jessica A. , Beattie Katherine , Farinas Sofia A. , Chehimi Samar N. , Rodrigues Amrith , Ejoh Lindsay L. , Kimmey Blake A. , Lo Emily , Azouz Ghalia , Vasquez Jose J. , Banghart Matthew R. , Creasy Kate Townsend , Beier Kevin T. , Ramakrishnan Charu , Crist Richard C. , Reiner Benjamin C. , Deisseroth Karl , Yttri Eric A. , Corder Gregory 
Published: April 2024

AbstractThe anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice—LUPE (Light aUtomated Pain Evaluator). LUPE removes human bias in behavior quantification and accelerated analysis from weeks to hours, which we leveraged to discover that morphine altered attentional and motivational pain behaviors akin to affective analgesia in humans. Through activity-dependent genetics and single-nuclei RNA sequencing, we identified specific ensembles of nociceptive cingulate neuron-types expressing mu-opioid receptors. Tuning receptor expression in these cells bidirectionally modulated morphine analgesia. Moreover, we employed a synthetic opioid receptor promoter-driven approach for cell-type specific optical and chemical genetic viral therapies to mimic morphine’s pain-relieving effects in the cingulate, without reinforcement. This approach offers a novel strategy for precision pain management by targeting a key nociceptive cortical circuit with on-demand, non-addictive, and effective analgesia.Abstract Figure
Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions
Authors: Wang Yan , Kim Bokyung , Gong Shuaishuai , Park Joohyun , Zhu Meina , Wong Evelyn M. , Park Audrey Y. , Chernoff Jonathan , Guo Fuzheng 
Published: April 2024

AbstractAppropriate proliferation and repopulation of oligodendrocyte progenitor cells (OPCs) determine successful (re)myelination in homeostatic and demyelinating brains. Activating mutations in p21-activated kinase 1 (PAK1) cause intellectual disability, neurodevelopmental abnormality, and white matter anomaly in children. It remains unclear if and how PAK1 regulates oligodendroglial development. Here, we report that PAK1 controls proliferation and regeneration of OPCs. Unlike differentiating oligodendrocytes, OPCs display high PAK1 activity which maintains them in a proliferative state by modulating PDGFRa-mediated mitogenic signaling. PAK1-deficient or kinase-inhibited OPCs reduce their proliferation capacity and population expansion. Mice carrying OPC-specific PAK1 deletion or kinase inhibition are populated with fewer OPCs in the homeostatic and demyelinated CNS than control mice. Together, our findings suggest that kinase-activating PAK1 mutations stall OPCs in a progenitor state, impacting timely oligodendroglial differentiation in the CNS of affected children and that PAK1 is a potential molecular target for replenishing OPCs in demyelinating lesions.
Can seminal fluid proteins be honest signals of sperm availability?
Authors: Michalak Piotr , Duneau David , Ferdy Jean-Baptiste 
Published: April 2024

AbstractSeminal fluid proteins (Sfps) are produced by males, yet they have significant effects on female physiology and behaviour. Sfps are often viewed as a mechanism for males to manipulate female reproductive behaviours, but despite many studies identifying their varied effects and their molecular underpinnings, the ways males and females use Sfps remain unclear. In the most studied case ofDrosophila melanogasterparticular peptides within the seminal fluid have been identified to guide female reproduction: sex peptide (SP, Acp70A) is known to induce changes in egg production, oviposition and remating and is attached to sperm and continuously supplied for days after mating, while ovulation inducing peptide, ovulin (Acp26Aa), is a free peptide with only short term effects after mating. Using a biologically informed model we show how these peptides can synchronize sperm and egg release, hence reducing the number of unfertilized eggs a female lays. We further show that the exhaustion of SP might be the key signal of this synchronization. Finally, we demonstrate that sexual conflict over the regulation of female reproductive physiology by Sfps should be limited, with the primary conflict probably centring around the regulation of remating behaviour.
Identifying key amino acid types that distinguish paralogous proteins using Shapley value based feature subset selection
Authors: Machingal Pranav , Busi Rakesh , Hemachandra Nandyala , Balaji Petety V. 
Published: April 2024

AbstractWe view a protein as the composite of the standard 20 amino acids, ignoring their order in the protein sequence. With this view, we try to identify the important amino acid types that distinguish pairs of paralogous proteins, thereby playing a role in their functional difference. Using only the amino acid composition (AAC) as features and a linear classifier, we find that many pairs of paralogous protein families can be classified accurately. Next, we use an existing Shapley value-based feature subset selection algorithm, SVEA, to identify the important amino acid types that distinguish a pair of paralogous proteins. The SVEA algorithm assigns a score, Shapley value, to each feature, amino acid type, based on its contribution to the classifier’s training error. We identify the important distinguishing amino acid types as those whose Shapley value exceeds a data-driven threshold. We refer to these as the amino acid feature subset (AFS). We find that many paralog pairs can still be accurately classified using only theAFScomposition. We partitionAFSbased on the classifier weights to infer class-wise amino acid importance. We verify whether the identifiedAFSamino acids indeed play a role in the functional difference of the paralog pairs using various methods - multiple sequence alignment, 3D structure analysis, and supporting evidence from biology literature. We also discuss some consistencies observed in the Shapley value based ranking and theAFSwhen comparing theAFSof two different but related paralog pairs. We demonstrate the results for 15 pairs of paralogous proteins.
Notch dimerization provides robustness against environmental insults and is required for vascular integrity
Authors: Preusse Kristina , Cochran Kim , Dai Quanhui , Kopan Raphael 
Published: April 2024

ABSTRACTThe Notch intracellular domain (NICD) regulates gene expression during development and homeostasis in a transcription factor complex that binds DNA either as monomer, or cooperatively as dimers. Mice expressingNotchdimerization-deficient (NDD) alleles of Notch1 and Notch2 have defects in multiple tissues that are sensitized to environmental insults. Here, we report that cardiac phenotypes and DSS (Dextran Sodium Sulfate) sensitivity in NDD mice can be ameliorated by housing mice under hypo-allergenic conditions (food/bedding). However, compound heterozygote NDD mice (N1RA/–; N2RA/–) in hypo-allergenic conditions subsequently develop severe hydrocephalus and hemorrhages. Further analysis revealed multiple vascular phenotypes in NDD mice including leakage, malformations of brain vasculature, and vasodilation in kidneys, leading to demise around P21. This mouse model is thus a hypomorphic allele useful to analyze vascular phenotypes and gene-environment interactions. The possibility of a non-canonical Notch signal regulating barrier formation in the gut, skin, and blood systems is discussed.
Loop Catalog: a comprehensive HiChIP database of human and mouse samples
Authors: Reyna Joaquin , Fetter Kyra , Ignacio Romeo , Ali Marandi Cemil Can , Rao Nikhil , Jiang Zichen , Figueroa Daniela Salgado , Bhattacharyya Sourya , Ay Ferhat 
Published: April 2024

ABSTRACTHiChIP enables cost-effective and high-resolution profiling of regulatory and structural loops. To leverage the increasing number of publicly available HiChIP datasets from diverse cell lines and primary cells, we developed the Loop Catalog (https://loopcatalog.lji.org), a web-based database featuring HiChIP loop calls for 1319 samples across 133 studies and 44 high-resolution Hi-C loop calls. We demonstrate its utility in interpreting fine-mapped GWAS variants (SNP-to-gene linking), in identifying enriched sequence motifs and motif pairs at loop anchors, and in network-level analysis of loops connecting regulatory elements (community detection). Our comprehensive catalog, spanning over 4M unique 5kb loops, along with the accompanying analysis modalities constitutes an important resource for studies in gene regulation and genome organization.
Genetic Deletion of Calcium-independent Phospholipase A2γ Protects Mice from Diabetic Nephropathy
Authors: Cybulsky Andrey V. , Papillon Joan , Guillemette Julie , Navarro-Betancourt José R. , Elimam Hanan , Fantus I. George 
Published: April 2024

AbstractCalcium-independent phospholipase A2γ (iPLA2γ) is localized in glomerular epithelial cells (GECs)/podocytes at the mitochondria and endoplasmic reticulum, and can mediate release of arachidonic acid and prostanoids. Global knockout (KO) of iPLA2γ in mice did not cause albuminuria, but resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes. In acute glomerulonephritis, deletion of iPLA2γ exacerbated albuminuria and podocyte injury. This study addresses the role of iPLA2γ in diabetic nephropathy. Hyperglycemia was induced in male mice with streptozotocin (STZ). STZ induced progressive albuminuria in control mice (over 21 weeks), while albuminuria did not increase in iPLA2γ KO mice, remaining comparable to untreated groups. Despite similar exposure to STZ, the STZ-treated iPLA2γ KO mice developed a lower level of hyperglycemia compared to STZ-treated control. However, there was no significant correlation between the degree of hyperglycemia and albuminuria, and even iPLA2γ KO mice with greatest hyperglycemia did not develop significant albuminuria. Mortality at 21 weeks was greatest in diabetic control mice. Sclerotic glomeruli and enlarged glomerular capillary loops were increased significantly in diabetic control compared to diabetic iPLA2γ KO mice. Glomerular matrix was expanded in diabetic mice, with control exceeding iPLA2γ KO. Glomerular autophagy (increased LC3-II and decreased p62) was enhanced in diabetic iPLA2γ KO mice compared to control. Treatment of cultured GECs with H2O2resulted in increased cell death in control GECs compared to iPLA2γ KO, and the increase was slightly greater in medium with high glucose compared to low glucose. H2O2-induced cell death was not affected by inhibition of prostanoid production with indomethacin. In conclusion, mice with global deletion of iPLA2γ are protected from developing chronic glomerular injury in diabetic nephropathy. This is associated with increased glomerular autophagy.