bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-nucleus RNA sequencing atlas of the postnatal retina of the sharkScyliorhinus canicula
Authors: Vidal-Vázquez Nicolás , Hernández-Núñez Ismael , Carballo-Pacoret Pablo , Salisbury Sarah , Villamayor Paula R. , Hervas-Sotomayor Francisca , Yuan Xuefei , Lamanna Francesco , Schneider Céline , Schmidt Julia , Mazan Sylvie , Kaessmann Henrik , Adrio Fátima , Robledo Diego , Barreiro-Iglesias Antón , Candal Eva 
Published: April 2024

AbstractThe retina, whose basic cellular structure is highly conserved across vertebrates, constitutes an accessible system for studying the central nervous system. In recent years, single-cell RNA-sequencing studies have uncovered cellular diversity in the retina of a variety of species, providing new insights on retinal evolution and development. However, similar data in cartilaginous fishes, the sister group to all other extant jawed vertebrates, are still lacking. Here, we present a single-nucleus RNA-sequencing atlas of the postnatal retina of the catsharkScyliorhinus canicula, consisting of the expression profiles for 17,438 individual cells from three female, juvenile catshark specimens. Unsupervised clustering revealed 22 distinct cell types comprising all major retinal cell classes, as well as retinal progenitor cells (whose presence reflects the persistence of proliferative activity in postnatal stages in sharks) and oligodendrocytes. Thus, our dataset serves as a foundation for further studies on the development and function of the catshark retina. Moreover, integration of our atlas with data from other species will allow for a better understanding of vertebrate retinal evolution.
Precision and Accuracy of Single-Cell/Nuclei RNA Sequencing Data
Authors: Dai Rujia , Zhang Ming , Chu Tianyao , Kopp Richard , Zhang Chunling , Liu Kefu , Wang Yue , Wang Xusheng , Chen Chao , Liu Chunyu 
Published: April 2024

AbstractSingle-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue is the quality of sc/snRNA-Seq data that would impact the reliability of downstream analyses. Here we evaluated the precision and accuracy in 18 sc/snRNA-Seq datasets. The precision was assessed on data from human brain studies with a total of 3,483,905 cells from 297 individuals, by utilizing technical replicates. The accuracy was evaluated with sample-matched scRNA-Seq and pooled-cell RNA-Seq data of cultured mononuclear phagocytes from four species. The results revealed low precision and accuracy at the single-cell level across all evaluated data. Cell number and RNA quality were highlighted as two key factors determining the expression precision, accuracy, and reproducibility of differential expression analysis in sc/snRNA-Seq. This study underscores the necessity of sequencing enough high-quality cells per cell type per individual, preferably in the hundreds, to mitigate noise in expression quantification.
Cell wall digestibility outperforms ear in maintaining digestibility even under severe combined water and heat stress
Authors: Main Oscar , López-Malvar Ana , Meunier Florence , Guillaume Sophie , Jacquemot Marie-Pierre , Lopez-Marnet Paul-Louis , Barotin Charlène , Marmagne Anne , Cézard Laurent , Fargier Sébastien , Rey Sébastien , Larsonneau Pierre , Reymond Matthieu , Mangel Nathalie , Uijttewaal Anthony , Coursol Sylvie , Méchin Valérie 
Published: April 2024

AbstractForage maize is a central pillar of dairy cow feeding in France, directly influencing milk production. Drought significantly affects both its yield and digestibility, which are essential for registration purposes. Research on inbred lines revealed droughts notable effect on dry matter and cell wall digestibilities, directly impacting forage quality. Nevertheless, further investigation is warranted due to increasing frequency of drought. To delve deeper, we grew a range of modern forage maize hybrids for two years under four different field water-monitored modalities, representing a total of eight environmental conditions. The resulting dataset allowed us to perform a multiscale analysis, integrating agroclimatic, agronomic, biochemical and histological traits. By establishing a comprehensive heat and water stress index, we classified the environmental conditions. We demonstrated that under severe stress, ear production decreases significantly, but dry matter digestibility can be maintained through increased cell wall digestibility. This boost in cell wall digestibility was due to a reduction inp-hydroxycinnamic acid content, while lignin content remained relatively stable between environments. The significance of lignin distribution increased with the severity of the stress, reaching an extreme threshold where biochemical parameters solely account for digestibility variations.
TAM receptors control actomyosin dynamics in osteoclasts via RHOA-COFILIN-MYOSIN II signaling
Authors: Engelmann Janik , Zarrer Jennifer , Schmerder Max , Mess Christian , Ragipoglu Deniz , Riecken Kristoffer , Burstyn-Cohen Tal , Alberto Emily J. , Ghosh Sourav , Rothlin Carla , Pantel Klaus , Bokemeyer Carsten , Hesse Eric , Taipaleenmäki Hanna , Loges Sonja , Ben-Batalla Isabel 
Published: April 2024

AbstractThe TAM family of receptor tyrosine kinases were recently identified to regulate bone homeostasis by controlling osteoblasts and bone formation. Despite extensive knowledge of TAM receptor function in the mononuclear phagocyte system, the role of TAM receptors in osteoclasts remains largely unknown. Here, we identify a physiological regulatory system including MERTK and TYRO3 in osteoclasts controlling RHOA-ROCK-COFILIN/Myosin II signaling, thereby antagonistically regulating osteoclast-mediated bone remodeling to maintain bone homeostasis. Myeloid-specificlysozyme M-mediated deletion ofMertkled to increased bone mass in mice. In early stages of RANKL-induced osteoclast differentiation MERTK promotes amoeboid migration mode in osteoclast precursor cells by inducing RHOA-COFILIN-MLC2 pathway leading to increased osteoclast formation. In contrast, TYRO3 inhibits RHOA-ROCK signaling in osteoclast precursor cells thereby inhibiting these processes. Furthermore, we unraveled an inhibitory role of MERTK as well as TYRO3 in osteoclast differentiation and function. In line with this, mice withcathepsin K-mediated deletion ofMertkandTyro3exhibited an osteoporotic bone phenotype. We found that osteoclast precursor cell morphology dictates its fusion capacity and identified MERTK as a negative regulator of osteoclast fusion. In multinucleated cells, deletion ofMertkinhibits actin ring formation by mediating central actomyosin contraction and inactivation of COFILIN. In contrast, spatially well-ordered RHOA activation at adhesion structures, induced by loss ofTyro3,improves osteoclast biomechanotransduction to ameliorate podosome belt formation and enhance osteoclast function. By using a syngeneic breast cancer bone metastasis osteolysis models we identified TYRO3 as a bone protective receptor for osteolytic bone diseases, whereas MERTK represents a pharmacologic accessible target to inhibit osteoclast formation because its stimulatory effects of osteoclast precursors prevail the inhibitory effects on mature osteoclasts. Next to the recently uncovered role of MERTK as a target for osteoanabolic therapy MERTK may represent a one-drug two-target treatment strategy to increase osteoblast function and reduce osteoclast formation for treatments of bone diseases.
In VitroAnti-cancer potential of Aloe emodin against Oral Squamous Cell Carcinoma
Authors: T Jesse Joel , Suluvoy Jagadish Kumar , Kolla Harish babu 
Published: April 2024

AbstractOral squamous cell carcinoma is caused due to smoking, chewing of tobacco, high exposure of UV radiation and infectious agents such as human papilloma virus (HPV). Epigenetic dysregulation and uncontrolled cell growth are main factors that drives towards tumor development. Risk factors such as smoking, tobacco and viral agent’s up regulates its activity and leads to the cancer. Although chemotherapy, surgery and radiation were preferred for treating cancer but patients, feel extreme psychological stress and depression. Natural products are been investigated for their numerous diseases and in that they can be treated against cancer without side effects. Aloe emodin is one such natural molecule available, which possess various pharmacological activities for human beneficial. In this current study, we investigated the anti-cancer activity of aloe emodinin vitro. The KB 3-1 cell line were treated with different concentrations of Aloe emodin and its anti-cancer potential was determined through DNA fragmentation and cell viability assays.
Confinement in fibrous environments positions and orients mitotic spindles
Authors: Sarkar Apurba , Jana Aniket , Agashe Atharva , Wang Ji , Kapania Rakesh , Gov Nir S. , DeLuca Jennifer G. , Paul Raja , Nain Amrinder S. 
Published: April 2024

AbstractAccurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Adherent mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and, consequently, titling of the metaphase plate (MP). To understand the positioning and orientation of mitotic spindles under confinement by fibers (ECM-confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels. Rounded mitotic bodies are anchored in place by actin retraction fibers (RFs) originating from adhesion clusters on the ECM-mimicking fibers. We discover the extent of ECM-confinement patterns RFs in 3D: triangular and band-like at low and high confinement, respectively. A stochastic Monte-Carlo simulation of the centrosome (CS), chromosome (CH), membrane interactions, and 3D arrangement of RFs on the mitotic body recovers MP tilting trends observed experimentally. Our mechanistic analysis reveals that the 3D shape of RFs is the primary driver of the MP rotation. Under high ECM-confinement, the fibers can mechanically pinch the cortex, causing the MP to have localized deformations at contact sites with fibers. Interestingly, high ECM-confinement leads to low and high MP tilts, which mechanistically depend upon the extent of cortical deformation, RF patterning, and MP position. We identify that cortical deformation and RFs work in tandem to limit MP tilt, while asymmetric positioning of MP leads to high tilts. Overall, we provide fundamental insights into how mitosis may proceed in fibrous ECM-confining microenvironments in vivo.
CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility
Authors: Wu Bingbing , Long Chenghong , Yang Yuzhuo , Zhang Zhe , Ma Shuang , Ma Yanjie , Wei Huafang , Li Jinghe , Jiang Hui , Li Wei , Liu Chao 
Published: April 2024

AbstractThe structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility. Further analysis revealed that CCDC113 could bind to CFAP57 and CFAP91, and function as an adaptor protein for the connection of radial spokes, nexin-dynein regulatory complex (N-DRC) and doublet microtubules (DMTs) in the sperm axoneme. Moreover, CCDC113 was identified as a structural component of HTCA, collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Together, our studies reveal that CCDC113 serve as a critical hub for sperm axoneme and HTCA stabilization, providing insights into the potential pathogenesis of infertility associated with humanCCDC113mutations.
Toll-like receptor 3orchestrates a conserved mechanism of heart regeneration
Authors: Fiegl Manuel , Roehrs Bernhard , Hau Dominik , Mair Sophia , Niederwanger Philipp , Regele Dominik , Merotto Lorenzo , Toechterle Sonja , Engler Clemens , Graber Michael , Kirchmair Elke , Niedrist Veronika , Muller Lynn , Poelzl Leo , Hirsch Jakob , Naegele Felix , Happacher Isidor , Oberegger Simon , Bonaros Nikolaos , Grimm Michael , Tancevski Ivan , Finotello Francesca , Meyer Dirk , Holfeld Johannes , Gollmann-Tepekoeylue Can 
Published: April 2024

AbstractThe human’s heart responds to tissue damage with persistent fibrotic scarring. Unlike humans, zebrafish can repair cardiac injury and re-grow heart tissue throughout life. Recently,Toll-like receptor 3(Tlr3) was identified as an important mediator of cardiac regeneration in neonatal mice. However, no functional analysis oftlr3knock-out mutant zebrafish in respect to cardiac regeneration has yet been performed.We hypothesize that TLR3 signalling plays a central, conserved role in driving cardiac regeneration upon injury. Therefore, we focused ontlr3mediated cardiac regeneration in zebrafish, ultimately discovering an evolutionary conserved mechanism of heart repair. Using histological, behavioural, and RNA-Sequencing analysis, we uncovered a conserved mechanism oftlr3mediated cardiac repair after myocardial injury.Upon myocardial cryoinjury subjection, survival is decreased intlr3-/-fish as compared to wildtype controls.Tlr3-/-zebrafish fail to recruit immune cells to the injured ventricle, resulting in impaired DNA repair and transcriptional reprogramming of cardiomyocytes.Mechanistically, we uncover an evolutionary conserved mechanism oftlr3activation in fibroblasts promoting monocyte migration towards an injured ventricular area. Our data revealtlr3as a novel therapeutic target to promote cardiac regeneration.Every experiment including human participants has been approved by the ethics committee of the Medical University of Innsbruck (Ref. Nr.: 1262/2023). All experiments including the use of laboratory animals have been approved by the federal ministry of education, science, and research of Austria (Ref. Nr.: 2020-0.345.504).
Cortico-Spinal Intermittent Theta Burst Stimulation Propelling Sensorimotor Function Recovery in Complete Spinal Cord Injury: Randomized Control Trial Protocol
Authors: Patel Deeksha , Banerjee Rohit , Farooque Kamran , Gupta Deepak , Garg Bhavuk , Kumar Nand , Kocchar KP , Jain Suman 
Published: April 2024

AbstractBackgroundIntermittent theta burst stimulation (iTBS) is a non-invasive stimulation technique to induce neuronal and synaptic plasticity. The induced cortical plasticity is imperative in the recovery of motor and sensory functions. Spinal cord injury (SCI) causes damage to neurons and results in sensorimotor dysfunction. The effect of iTBS on recovery of motor and sensory dysfunction in complete SCI (cSCI) is still elusive.AIMThis study aims to assess the effect of iTBS on cortico-spinal tract integrity, plasticity, and regaining of motor and sensory function in cSCI patients. The rationale behind using an iTBS protocol is to modify and augment the communication between spared neurons of the cortico-spinal tract and strengthen the synaptic transmission, which will improve motor function in underlying muscles.MethodA total of 48 patients will be recruited and randomly divided into placebo and real stimulation groups. iTBS along with a rehabilitation program will be administered to the placebo and real stimulation groups. Follow-up will be done at 1 month, 2 months, and 3 months after the intervention.ResultThe outcome of the study will be defined by electrophysiological parameters elicited by single and paired-pulse stimulation, ASIA score, pain, activities of daily life, quality of life, anxiety, depression, and biomarkers related to SCI. The results of this study will uncover the effectiveness of iTBS stimulation on (i) recovery of motor and sensory function in cSCI (ii) excitability of cortico-spinal tract (iii) neurological recovery and modulation of pain (iv) cortical reorganization after injury.ConclusionIntermittent theta-burst stimulation (iTBS) in conjunction with an individualized rehabilitation program may serve as an integrated strategy to rejuvenate locomotor abilities and improve the overall quality of life for people with complete spinal cord injuries (SCI).Key PointsiTBS is a novel neurostimulation technique aimed to restore sensorimotor function after a complete SCIThe primary objective of the trial is to evaluate the efficacy of iTBS in promoting sensorimotor function recoveryAssessment of the potential impact of iTBS on SCI rehabilitationUnderstand the underlying mechanism of excitatory-inhibitory circuits associated with SCIUnlock the importance of neuronal plasticity in regaining mobility
CSF complement proteins are elevated in prodromal to moderate AD patients and are not altered by the anti-tau antibody semorinemab
Authors: Sandoval Cosme , Lee Julie , Toth Balazs , Nagaraj Rajini , Schauer Stephen , Hoffman Jennifer , Kollmorgen Gwendlyn , Monteiro Cecilia , Teng Edmond , Hanson Jesse E , Yeh Felix L , Gutierrez Johnny , Biever Anne 
Published: April 2024

ABSTRACTINTRODUCTIONGrowing evidence suggests a role for neuroinflammation in Alzheimer’s Disease (AD) pathogenesis. We investigated the complement system, a component of innate immunity, in AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti-tau antibody semorinemab.METHODSImmunoassays were applied to measure intact (inactive) and cleaved (active) CSF complement proteins C4, Factor B and C3 in AD patients and a separate cognitively normal (CN) cohort.RESULTSAll measured CSF complement proteins were increased in AD vs CN subjects, with cleaved C4 (C4a) displaying the most robust increase. Finally, semorinemab did not have a significant pharmacodynamic effect on CSF complement proteins.DISCUSSIONElevated levels of CSF intact/cleaved C4 and C3 are indicative of classical complement pathway activation in AD. Despite showing a reduction in CSF soluble tau species, semorinemab did not impact complement protein levels or activity. Further studies are needed to determine the value of complement proteins as neuroinflammation biomarkers in AD.
PTSD, Comorbidities, Gender, and Increased Risk of Cardiovascular Disease in a Large Military Cohort
Authors: Krantz David S. , Gabbay Frances H. , Belleau Elizabeth A. , Aliaga Pablo A. , Wynn Gary H. , Stein Murray B. , Ursano Robert J. , Naifeh James A. 
Published: April 2024

ABSTRACTImportancePosttraumatic stress disorder (PTSD) is a prevalent mental health problem that increases risk of cardiovascular disease (CVD). It is not known whether gender or comorbidities modify associations between PTSD and CVD.ObjectiveTo assess risk of hypertension and atherosclerotic CVD (ASCVD) associated with PTSD in a predominantly young military population, and determine if gender or PTSD comorbidities modify these associations.Design, setting, and participantsUsing administrative medical records, this longitudinal, retrospective cohort study assessed relationships of PTSD, gender, comorbidities (metabolic risk factors [MRF], behavioral risk factors [BRF], depression, and sleep disorders) to subsequent hypertension and ASCVD among 863,993 active-duty U.S. Army enlisted soldiers (86.2% male; 93.7% <age 40). Using discrete-time survival analysis, person-months with an initial hypertension diagnosis (n=49,656) were compared to an equal-probability control sample. Separate analyses compared person-months with ASCVD (n=2,427) to an equal-probability control sample.Main outcomes and measuresICD-9-CM diagnoses of hypertension, ASCVD (coronary artery disease, myocardial infarction, stroke, heart failure), PTSD, MRF (Type 2 diabetes, obesity), BRF (tobacco/alcohol use disorders), depression, and sleep disorders.ResultsPTSD was associated with subsequent hypertension (OR=3.0 [95% CI=2.9-3.1]), and ASCVD (OR=2.7 [95% CI=2.2-3.3]). These associations remained significant but were attenuated after adjusting for comorbidities and sociodemographic/service-related variables (Hypertension: OR=1.9 [95% CI=1.8-2.0]; ASCVD: OR=1.4 [95% CI=1.2-1.8]). For hypertension, gender and each comorbidity were significant explanatory variables in multivariable models, and there were significant PTSD interactions with gender, MRF, depression, and sleep disorders. Stratifying separately by gender and presence of each comorbidity, PTSD-hypertension associations were stronger among men, those without MRF, without depression, and without sleep disorders. Standardized risk estimates indicated that predicted hypertension rates for those with vs. without PTSD were higher for men, and for those with vs. without MRF, depression, and sleep disorders. For ASCVD, comorbidities, but not gender, were independent predictors, and associations between PTSD and ASCVD were not modified by gender or comorbidities.Conclusions and relevancePTSD and comorbidities are independent risk factors for hypertension and ASVD in younger individuals, and gender and comorbid conditions modify PTSD relationships with hypertension. These findings suggest that CVD preventive interventions address PTSD and medical and behavioral comorbidities.
Characterization ofMedusavirusencoded histones reveals nucleosome-like structures and a unique linker histone
Authors: Toner Chelsea Marie , Hoitsma Nicole Marie , Luger Karolin 
Published: April 2024

ABSTRACTThe organization of DNA into nucleosomes is a ubiquitous and ancestral feature that was once thought to be exclusive to the eukaryotic domain of life. Intriguingly, several representatives of the Nucleocytoplasmic Large DNA Viruses (NCLDV) encode histone-like proteins that in Melbournevirus were shown to form nucleosome-like particles.Medusavirus medusae(MM), a distantly related giant virus, encodes all four core histone proteins and, unique amongst most giant viruses, a putative acidic protein with two domains resembling linker histone H1. Here we report the structure of nucleosomes assembled with Medusavirus histones and highlight similarities and differences with eukaryotic and Melbournevirus nucleosomes. Our structure provides insight into how variations in histone tail and loop lengths are accommodated within the context of the nucleosome. We show that Medusavirus histones assemble into tri-nucleosome arrays, and that the putative linker histone H1 does not function in chromatin compaction. These findings expand our understanding of viral histones and suggest that Medusavirus histones represent a snapshot in the evolutionary timeline of nucleosome architecture.ONE SENTENCE SUMMARYThe fourMedusavirus medusaecore histones form nucleosome-like structures that combine features of eukaryotic and other viral nucleosomes.