bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells
Authors: Li Haiyan , Harvey Devon H. , Dai Jiannong , Swingle Steven P. , Compton Anthony M , Sugali Chenna Kesavulu , Dhamodaran Kamesh , Yao Jing , Lin Tsai-Yu , Sulchek Todd , Kim Taeyoon , Ethier C. Ross , Mao Weiming 
Published: August 2024

AbstractPurposeCross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells.MethodsGTM3L cells were fluorescently sorted for viral copy number analysis. CLAN incidence was increased by (i) differential sorting of cells by adhesion, (ii) cell deswelling, and (iii) cell selection based on cell stiffness. GTM3L cells were also cultured on glass or soft hydrogel to determine substrate stiffness effects on CLAN incidence. Computational models were constructed to mimic and study the biomechanical properties of CLANs.ResultsAll GTM3L cells had an average of 1 viral copy per cell. LifeAct-GFP expression level did not affect CLAN incidence rate, but CLAN rate was increased from ∼0.28% to ∼50% by a combination of adhesion selection, cell deswelling, and cell stiffness-based sorting. Further, GTM3L cells formed more CLANs on a stiff vs. a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus.ConclusionsIt is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the effect of CLANs on TM biomechanics and mechanobiology as well as the etiology of CLAN formation in the TM.
A low-cost virtual reality stroke rehabilitation system: development and initial feasibility assessment
Authors: Fisk Aidan , Fox Summer , Floyd Jenna , Blustein Daniel 
Published: August 2024

AbstractStroke is a leading cause of disability worldwide. Following a stroke, high doses of intensive motor rehabilitation provide maximal benefit. Barriers to realizing recommended levels of rehabilitation therapy include cost, physical access, and clinical resource availability. Virtual Reality (VR) offers a potential solution to overcome these challenges and enable home-based, self-directed therapy. Here we present a low-cost system utilizing the off-the-shelf Meta Quest 2 headset running custom software to deliver immersive rehabilitation exercises. The system employs movement amplification to partially reduce motor deficits and enable more engaging task completion. It leverages recent advances in VR technology, including inside-out hand tracking, voice recognition, and an AI-driven virtual coach, to create a more accessible environment for users with no prior VR experience. We present the development of the virtual rehabilitation implementation and an initial feasibility assessment to determine if motor amplification increases the visually induced motion sickness experienced by the user. We find that motor amplification does not result in additional reported motion sickness suggesting that low-cost VR systems may serve as a feasible option to increase individualized and guided post-stroke motor rehabilitation.
Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production
Authors: Borges Kleiton S. , Little Donald W. , de Almeida Magalhães Taciani , Ribeiro Claudio , Dumontet Typhanie , Lapensee Chris , Basham Kaitlin J. , Seth Aishwarya , Azova Svetlana , Guagliardo Nick A. , Barrett Paula Q. , Berber Mesut , O’Connell Amy E. , Turcu Adina F. , Lerario Antonio Marcondes , Mohan Dipika R. , Rainey William , Carlone Diana L. , Hirschhorn Joel N. , Salic Adrian , Breault David T. , Hammer Gary D. 
Published: August 2024

AbstractThe steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant inWNT2Band an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production. We further show that in both mice and humans, WNT2B is expressed in the mesenchymal capsule surrounding the adrenal cortex, in close proximity to the zG. Global loss ofWnt2bin the mouse results in a dysmorphic and hypocellular zG, with impaired aldosterone production. Similarly, humans harboringWNT2Bloss-of-function mutations develop a novel form of Familial Hyperreninemic Hypoaldosteronism, designated here as Type 4. Additionally, we demonstrate that WNT2B signals by activating the non-canonical Wnt/planar cell polarity pathway. Our findings identify WNT2B as a key regulator of zG function and aldosterone production with important clinical implications.HighlightsWNT2Bvariant is associated with increased risk for primary aldosteronismWnt2bknock-out mice show defects in adrenal morphologyWnt2bknock-out mice have hyperreninemic hypoaldosteronismWNT2B activates non-canonical Wnt/planar cell polarity signalingWNT2B deficiency causes a new form of familial hyperreninemic hypoaldosteronism
Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination
Authors: Vanderlip Casey R. , Taylor Lisa , Kim Soyun , Harris Alyssa L. , Tuteja Nandita , Meza Novelle , Escalante Yuritza Y. , McMillan Liv , Yassa Michael A. , Adams Jenna N. 
Published: August 2024

AbstractCerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer’s disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits. In this context, we tested whether specific domains of mnemonic discrimination, a neural computation essential for episodic memory, exhibit specific deficits related to early Aβ deposition. We tested 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (Aβ-PET), and a control group of 35 young adults, on a suite of mnemonic discrimination tasks taxing object, spatial, and temporal domains. We hypothesized that Aβ pathology would be selectively associated with temporal discrimination performance due to Aβ’s propensity to accumulate in the basal frontotemporal cortex, which supports temporal processing. Consistent with this hypothesis, we found a dissociation in which generalized age-related deficits were found for object and spatial mnemonic discrimination, while Aβ-PET levels were selectively associated with deficits in temporal mnemonic discrimination. Further, we found that higher Aβ-PET levels in medial orbitofrontal and inferior temporal cortex, regions supporting temporal processing, were associated with greater temporal mnemonic discrimination deficits, pointing to the selective vulnerability of circuits related to temporal processing early in AD progression. These results suggest that Aβ accumulation within basal frontotemporal regions may disrupt temporal mnemonic discrimination in preclinical AD, and may serve as a sensitive behavioral biomarker of emerging AD progression.
Lamellar Schwann cells in the Pacinian corpuscle potentiate vibration perception
Authors: Chen Yuh-Tarng , de Thomas Wagner Dominica , Loutit Alastair J. , Nourizonoz Ali , Croisier-Coeytaux Mary-Claude , Blanc Jérôme , Knott Graham , Lee Kuo-Sheng , Huber Daniel 
Published: August 2024

SummaryPacinian corpuscles are among the most sensitive mechanoreceptors found in vertebrates and they are tuned to vibrations in the highest perceptible frequency range (100-2000Hz). One of their anatomical hallmarks is the onion-like cell layers surrounding the central axon. The innermost layers consist of ∼60 densely packed lamellar Schwann cells (LSCs), whose function remains largely unknown. Using high-resolution 3D electron microscopy we found that LSCs in Pacinian corpuscles of the mouse hindlimb do not form concentric rings, but complex, multilayered and intertwining assemblies that are connected via an estimated 5805.1 desmosomes and 4142.5 gap-junctions. LSCs make multiple converging contacts with the afferent axon and its protrusions with desmosomes. Using optogenetic manipulations of LSCs we demonstrate that their activation does not only drive reliable time-locked spiking in the axon, but that their inactivation significantly elevates the thresholds in-situ and increases perceptual thresholds behaviorally. Together these findings provide evidence that LSCs are a key element of somatosensory processing, actively potentiating mechanosensitivity in Pacinian corpuscles.HighlightsHigh-resolution electron microscopy reveals details of the Pacinian corpuscleLamellar Schwann cells form claw-like structures with converging axonal contactsSchwann-cell modulation bidirectionally affects neural coding of Pacinian afferentInactivation of lamellar Schwann-cells increases perceptual thresholds
SPACE: Spatially variable gene clustering adjusting for cell type effect for improved spatial domain detection
Authors: Das Adhikari Sikta , Steele Nina G. , Theisen Brian , Wang Jianrong , Cui Yuehua 
Published: August 2024

AbstractRecent advances in spatial transcriptomics have significantly deepened our understanding of biology. A primary focus has been identifying spatially variable genes (SVGs) which are crucial for downstream tasks like spatial domain detection. Traditional methods often use all or a set number of top SVGs for this purpose. However, in diverse datasets with many SVGs, this approach may not ensure accurate results. Instead, grouping SVGs by expression patterns and using all SVG groups in downstream analysis can improve accuracy. Furthermore, classifying SVGs in this manner is akin to identifying cell type marker genes, offering valuable biological insights. The challenge lies in accurately categorizing SVGs into relevant clusters, aggravated by the absence of prior knowledge regarding the number and spectrum of spatial gene patterns. Addressing this challenge, we propose SPACE, SPatially variable gene clustering Adjusting for Cell type Effect, a framework that classifies SVGs based on their spatial patterns by adjusting for confounding effects caused by shared cell types, to improve spatial domain detection. This method does not require prior knowledge of gene cluster numbers, spatial patterns, or cell type information. Our comprehensive simulations and real data analyses demonstrate that SPACE is an efficient and promising tool for spatial transcriptomics analysis.Key PointsSPACE eliminates the need for prior knowledge about the number of gene clusters, known cell types, or the quantity of SVGs to identify clusters for downstream analysis.SPACE offers a method to effectively leverage SVGs for low-dimensional embedding within each cluster to improve the accuracy of spatial domain detection.The efficiency and utility of the SPACE algorithm have been validated across multiple datasets and simulations, demonstrating its effectiveness in producing meaningful and interpretable results.
Natural History, Phenotype Spectrum and Clinical Outcomes of Desmin (DES)-Associated Cardiomyopathy
Authors: Asatryan Babken , Rieder Marina , Murray Brittney , Muller Steven A. , Tichnell Crystal , Gasperetti Alessio , Carrick Richard T. , Joseph Emily , Leung Doris G. , te Riele Anneline S.J.M. , Zimmerman Stefan L. , Calkins Hugh , James Cynthia A. , Barth Andreas S. 
Published: August 2024

ABSTRACTBackgroundPathogenic/likely pathogenic (P/LP) desmin (DES) variants cause heterogeneous cardiomyopathy and/or skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACE), including cardiac conduction disease (CCD), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, LVAD/cardiac transplant, HF-related death), in patients with P/LPDESvariants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization.ObjectivesWe aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with P/LPDESvariants through a systematic review and individual patient data meta-analysis using published reports.MethodsWe searched Medline (PubMed) and Embase for studies that evaluated cardiac phenotypes in patients with P/LPDESvariants. Cardiomyopathy diagnosis or occurrence of MACE were considered evidence of cardiac involvement/penetrance. Lifetime event-free survival from CCD, sustained VA, HF events, and composite MACE was assessed.ResultsOut of 4,212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% male, 52.2% probands, median age: 31 years [22.0; 42.8] at first evaluation, median follow-up: 3 years [0; 11.0]). Overall, 124 (53.9%) patients were diagnosed with cardiomyopathy, predominantly dilated cardiomyopathy (14.8%), followed by restrictive cardiomyopathy (13.5%), whereas other forms were less common: arrhythmogenic cardiomyopathy (7.0%), hypertrophic cardiomyopathy (6.1%), arrhythmogenic right ventricular cardiomyopathy (5.2%), and other forms (7.4%). Overall, 132 (57.4%) patients developed MACE, with 96 [41.7%] having CCD, 36 [15.7%] sustained VA, and 43 [18.7%] HF events. Familial penetrance of cardiac disease was 63.6% among relatives with P/LPDESvariants. Male sex was associated with increased risk of sustained VA (HR 2.28, p=0.02) and HF events (HR 2.45, p=0.008).ConclusionsDEScardiomyopathy exhibits heterogeneous phenotypes and distinct natural history, characterized by high familial penetrance and substantial MACE burden. Male patients face higher risk of sustained VA events.
New insights into the structure of cellulose in plant cell walls
Authors: Cresswell Rosalie , Deralia Parveen Kumar , Yoshimi Yoshihisa , Brown Steven P. , Dupree Ray , Dupree Paul 
Published: August 2024

AbstractThe structure of native plant cellulose, despite its abundance and utility in industry, remains elusive. The cellulose structure of several species was studied using 2D solid-state Nuclear Magnetic Resonance (NMR) of13C labelled plants. Six major glucose environments were resolved which are common to the cellulose of poplar wood, spruce wood and grasses. The cellulose structure was maintained in isolated holo-cellulose nanofibrils, allowing more detailed characterisation. There are just two glucose environments within the fibril core which have the same NMR13C chemical shifts as tunicate cellulose Iβ. The third major glucose site with a carbon 4 shift near 89 ppm, previously assigned to the fibril interior, is one of four surface glucose environments. These advances allowed us to obtain a more accurate measure of the interior to surface ratio for poplar wood fibrils of 0.5, consistent with an 18 chain microfibril structure having 6 core and 12 surface chains.
msiFlow: Automated Workflows for Reproducible and Scalable Multimodal Mass Spectrometry Imaging and Immunofluorescence Microscopy Data Processing and Analysis
Authors: Spangenberg Philippa , Bessler Sebastian , Widera Lars , Bottek Jenny , Richter Mathis , Thiebes Stephanie , Siemes Devon , Krauß Sascha D. , Migas Lukasz G. , Kasarla Siva Swapna , Phapale Prasad , Kleesiek Jens , Führer Dagmar , Moeller Lars C. , Heuer Heike , Van de Plas Raf , Gunzer Matthias , Soehnlein Oliver , Soltwisch Jens , Shevchuk Olga , Dreisewerd Klaus , Engel Daniel R. 
Published: August 2024

AbstractMultimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and immunofluorescence microscopy holds great potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing open-source software solutions for analysis of MALDI MSI data are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries across interdisciplinary research fields. Here we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from import and pre-processing of raw MALDI MSI data to visual analysis output, as well as registration, along with state-of-the-art and newly developed algorithms, into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in the emerging field of multimodal imaging to uncover context-dependent cellular regulations in disease states.
Sodium Chloride Promotes the Growth of Bacterial Soil Isolate and Antimicrobial Activity of Polymixin B
Authors: Singh Diwakar Kumar 
Published: August 2024

AbstractThe decomposition of organic matter in the soil, soil salinity, and soil acidity are influenced by soil microbiology, which also controls the recycling and processing of nutrients in the soil. These factors affect soil fertility and ecological stability. This manuscript is focused on the isolation of seven gram-negative bacteria found in the agricultural soil of The Neotia University campus, West Bengal, India. These isolates have been found to be mesophilic based on their study of their growth profiles, which revealed that under the same incubation conditions, the isolates displayed rising development patterns between 24 and 120 hours. The presence of sodium and potassium chloride modulates the growth and development of bacterial strains (DNI1, DNI2, DNI3, DNI4, DNI5, DNI6, and DNI7) during laboratory set up. The sodium and potassium chloride composition of culture media that effectively regulates the development of bacterial isolates has been determined using the combinational method of salt treatment. The ideal physical factor required for the growth and development of microorganisms has been demonstrated by the pH and temperature titration during this study. The powerful antibiotics known as polymyxin B, which are nonribosomal lipopeptides produced byPaenibacillus polymyxa, are especially effective against Gram-negative bacteria. Because multidrug-resistant Gram-negative bacteria have few other choices for treating infections, the use of polymyxins in clinical settings has increased despite their toxicity in the past. This study offers an update on the most current findings about the bioactivity of soil isolates and their significant relationships to temperature, pH, salt, and polymixin B sensitivity. The toxicity impact may be reduced by enhancing polymixin B’s antibacterial activity with salt treatment in clinical research.
A LINK BETWEEN AGING AND PERSISTENCE
Authors: Proenca A. M. , Rang C. U. , Chao L. 
Published: August 2024

ABSRACTDespite the various strategies that microorganisms have evolved to resist antibiotic treatments, most chronic infections are caused by subpopulations of susceptible bacteria in a transient state of dormancy. This phenotype, known as bacterial persistence, arises due to a natural and ubiquitous heterogeneity of growth states in bacterial populations. Nonetheless, the unifying mechanism of persistence remains unknown, with several pathways being able to trigger the phenotype. Here, we show that asymmetric damage partitioning, a form of cellular aging, produces the underlying phenotypic heterogeneity upon which persistence is triggered. Using single-cell microscopy and microfluidic devices, we demonstrate that deterministic asymmetry in exponential phase populations leads to a state of growth stability, which prevents the spontaneous formation of persisters. However, as populations approach stationary phase, aging bacteria — those inheriting more damage upon division — exhibit a sharper growth rate decline, increased probability of growth arrest, and higher persistence rates. These results indicate that persistence triggers are biased by bacterial asymmetry, thus acting upon the deterministic heterogeneity produced by cellular aging. This work suggests unifying mechanisms for persistence and offers new perspectives on the treatment of recalcitrant infections.IMPORTANCEWhenever bacterial cultures are treated with antibiotics, a fraction of the population survives despite exhibiting no active resistance mechanisms. These “persisters” are cells in a state of slow growth or dormancy, already present in the population prior to antibiotic exposure. Although various stressors or mutations increase persistence rates, a unifying persistence mechanism has not been established. Here, we show that cellular aging can represent such a mechanism. Bacteria age through the inheritance of intracellular damage, which occurs even in unstressed populations. As populations approach stationary phase, agingEscherichia colihave a steeper decline in elongation rates and earlier division arrest compared to younger cells. Upon antibiotic treatment, aging bacteria have higher persistence rates. These results show that stationary phase, a well-established persistence trigger, operates on the phenotypic heterogeneity produced by cellular aging. Because aging is a deterministic and ubiquitous process, it could represent a fundamental mechanism for the formation of persisters.
A Unified Atlas of T cell Glycophysiology
Authors: Izzati Fauzia N. , Choksi Hani , Giuliana Paolo , Abd-Rabbo Diala , Elsaesser Heidi , Blundell Aled , Affe Vanessa , Kannen Vinicius , Jame-Chenarboo Zeinab , Schmidt Edward , Kuypers Meggie , Avila David B. , Chiu Eric S. Y. , Badmaev Dzhangar , Cui Haissi , Matthews Jason , Mallevaey Thierry , Macauley Matthew S. , Brooks David G. , Edgar Landon J. 
Published: August 2024

SUMMARYGlycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that existin vivo. Here, we couple single-cell analysis technologies with soluble lectins and chemical probes to interrogate glycosylation patterns on major T cell populations across multiple mouse and human tissues. Our analysis focused on terminal glycan epitopes with immunomodulatory functions, including sialoglycan ligands for Siglecs. We demonstrate that glycosylation patterns are diverse across the resting murine T cell repertoire and dynamically remodelled in response to antigen-specific stimulation. Surprisingly, we find that human T cell populations do not share the same glycoprofiles or glycan remodelling dynamics as their murine counterparts. We show that these differences can be explained by divergent regulation of glycan biosynthesis pathways between the species. These results highlight fundamental glycophysiological differences between mouse and human T cells and reveal features that are critical to consider for glycan-targeted therapies.