bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrovirus-derivedRTL9plays an important role in innate antifungal immunity in the eutherian brain
Authors: Ishino Fumitoshi , Itoh Johbu , Irie Masahito , Matsuzawa Ayumi , Naruse Mie , Suzuki Toru , Hiraoka Yuichi , Kaneko-Ishino Tomoko 
Published: July 2023

AbstractRetrotransposon Gag-like (RTL) genes plays a variety of essential/important roles in the eutherian placenta and brain. It has recently been demonstrated thatRTL5andRTL6(akasushi-ichi retrotransposon homolog 8(SIRH8) andSIRH3) are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria by their removal of double-stranded RNA and lipopolysaccharide, respectively. Here we demonstrate thatRTL9(akaSIRH10) also plays an important role, degrading fungal zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Interestingly, inRtl9knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost, demonstrating that RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system,RTL9,RTL5andRTL6responding to fungi, viruses and bacteria, respectively.Author SummaryWe have recently demonstrated thatRTL5andRTL6are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria. In this report, we demonstrate thatRTL9is functional in innate antifungal immunity in the brain becauseRtl9KO mice lose zymosan degradation activity. Fungi are one of the most dangerous infectious pathogens, along with viruses, bacteria and protozoa. Phagocytic cells, such as microglia/macrophages, are essential for mounting a defense against fungal infection. As defects in these cells reduce host resistance to fungal infection,RTL9is an antifungal therapy target as a newly identified member of innate antifungal immunity in eutherians.
Spatially resolved transcriptomic profiling for glomerular and tubulointerstitial gene expression in C3 glomerulopathy
Authors: Koh Jung Hun , Kang Minji , Park Sehoon , Cho Jeong Min , Cho Semin , Kim Yaerim , Lee Soojin , Lee Hajeong , Joo Kwon-Wook , Kim Yon Su , Moon Kyung Chul , Kim Hyun Je , Kim Dong Ki 
Published: July 2023

AbstractIntroductionC3 glomerulopathy (C3G) is a rare but clinically significant glomerulopathy. However, little is known about its transcriptomic profile. We investigated the substructure-specific gene expression profile of C3G using the recently introduced spatial transcriptomics technology.MethodsWe performed spatial transcriptomic profiling using GeoMx Digital Spatial Profiler with formalin-fixed paraffin-embedded kidney biopsy specimens of three C3G cases and seven controls from donor kidney biopsy. Additionally, 41 samples of other glomerulonephritis, including focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease, were included as disease controls. Gene expression levels were compared by DESeq2 method to identify differentially expressed genes (DEGs). We performed gene ontology (GO) annotation through the ToppGene suite and mapped interactions among the DEGs using the STRING database.ResultsWe identified 229 and 157 highly expressed DEGs in the glomeruli of C3G compared to those of donor and disease controls, respectively, with consistently highest fold changes in POSTN, COL1A2, and IFI44L. Protease binding, structural molecule activity, and extracellular matrix structural constituent were among the top enriched GO terms in the glomeruli of C3G, with consistent features seen in the network analysis. In contrast, no significant GO enrichment was found among the 563 and 347 lowly expressed DEGs in the glomeruli of C3G compared to the controls. The tubulointerstitial transcriptomic profiles of C3G were similar to those of the controls.ConclusionIn the glomerulus of C3G, genes related to the extracellular matrix and interferon activity were the most upregulated. Significant disease-specific transcriptomic alterations in C3G provide potential insights into the pathophysiology.
BOston Neonatal Brain Injury Dataset for Hypoxic Ischemic Encephalopathy (BONBID-HIE): Part I. MRI and Manual Lesion Annotation
Authors: Bao Rina , Song Ya’nan , Bates Sara V. , Weiss Rebecca J. , Foster Anna N. , Cobos Camilo Jaimes , Sotardi Susan , Zhang Yue , Gollub Randy L. , Grant P. Ellen , Ou Yangming 
Published: July 2023

ABSTRACTHypoxic ischemic encephalopathy (HIE) is a brain injury that occurs in 1 ∼5/1000 term neonates. Accurate identification and segmentation of HIE-related lesions in neonatal brain magnetic resonance images (MRIs) is the first step toward predicting prognosis, identifying high-risk patients, and evaluating treatment effects. It will lead to a more accurate estimation of prognosis, a better understanding of neurological symptoms, and a timely prediction of response to therapy. We release the first public dataset containing neonatal brain diffusion MRI and expert annotation of lesions from 133 patients diagnosed with HIE. HIE-related lesions in brain MRI are often diffuse (i.e., multi-focal), and small (over half the patients in our data having lesions occupying <1% of brain volume). Segmentation for HIE MRI data is remarkably different from, and arguably more challenging than, other segmentation tasks such as brain tumors with focal and relatively large lesions. We hope that this dataset can help fuel the development of MRI lesion segmentation methods for HIE and small diffuse lesions in general.
A globally synthesised and flagged bee occurrence dataset and cleaning workflow
Authors: Dorey James B. , Fischer Erica E. , Chesshire Paige R. , Nava-Bolaños Angela , O’Reilly Robert L. , Bossert Silas , Collins Shannon M. , Lichtenberg Elinor M. , Tucker Erika M. , Smith-Pardo Allan , Falcon-Brindis Armando , Guevara Diego A. , Ribeiro Bruno , de Pedro Diego , Pickering John , Hung Keng-Lou James , Parys Katherine A. , McCabe Lindsie M. , Rogan Matthew S. , Minckley Robert L. , Velazco Santiago J.E. , Griswold Terry , Zarrillo Tracy A. , Jetz Walter , Sica Yanina V. , Orr Michael C. , Guzman Laura Melissa , Ascher John S. , Hughes Alice C. , Cobb Neil S. 
Published: July 2023

AbstractSpecies occurrence data are foundational for research, conservation, and science communication, but the limited availability and accessibility of reliable data represents a major obstacle, particularly for insects, which face mounting pressures. We presentBeeBDC, a newRpackage, and a global bee occurrence dataset to address this issue. We combined >18.3 million bee occurrence records from multiple public repositories (GBIF, SCAN, iDigBio, USGS, ALA) and smaller datasets, then standardised, flagged, deduplicated, and cleaned the data using the reproducibleBeeBDC R-workflow. Specifically, we harmonised species names (following established global taxonomy), country names, and collection dates and we added record-level flags for a series of potential quality issues. These data are provided in two formats, “cleaned” and “flagged-but-uncleaned”. TheBeeBDCpackage with online documentation provides end users the ability to modify filtering parameters to address their research questions. By publishing reproducibleRworkflows and globally cleaned datasets, we can increase the accessibility and reliability of downstream analyses. This workflow can be implemented for other taxa to support research and conservation.
Morphological variability may limit single-cell specificity to electric field stimulation
Authors: Trotter Daniel , Pariz Aref , Hutt Axel , Lefebvre Jérémie 
Published: July 2023

AbstractNon-invasive brain stimulation techniques are widely used for manipulating the behaviour of neuronal circuits and the excitability of the neurons therein. While the usage of these techniques is widely studied at the meso- and macroscopic scales, less is known about the specificity of such approaches at the level of individual cells. Here we use models based on the morphologies of real pyramidal and parvalbumin neurons from mouse primary visual cortex created by the Allen Institute for Brain Science to explore the variability and evoked response susceptibility of different morphologies to uniform electric fields. We devised a range of metrics quantifying various aspects of cellular morphology, ranging from whole cell attributes to net compartment length, branching, diameter to orientation. In supporting layer- and cell-type specific responses, none of these physical traits passed statistical significance tests. While electric fields can modulate somatic, dendritic and axonal compartments reliably and subtype-specific responses could be observed, the specificity of such stimuli was blurred by the variability in cellular morphology. These null results suggest that morphology alone may not account for the reported subtype specificity of brain stimulation paradigms, and question the extent to which such techniques may be used to probe and control neural circuitry.Author summaryOver the last several decades there has been increased interest in the efficacy of non-invasive brain stimulation, particularly in determining the limits of specificity of such techniques. Despite this growing area of research, much remains unknown about the interactions of non-invasive techniques with neurons at the single-cell level, notably the importance of morphology to these interactions. We make use of detailed single-neuron models and simulate them in a uniform electric field and demonstrate that the high variability in neuron morphologies may limit how specifically single neurons can be targeted non-invasively. We confirmed this for neuron morphology characteristics at macro- and meso- scales and at varied orientations. Our work suggests that previously reported subtype specificities in non-invasive frameworks are not accounted for by considering only morphological factors.
Unbiased phosphoproteomics analysis unveils modulation of insulin signaling by extramitotic CDK1 kinase activity in human myotubes
Authors: Han Bitnara , Li Ginny X. , Liew Wei Lin , Chan Edmund , Huang Shiqi , Khoo Chin Meng , Leow Melvin Khee-Shing , Lee Yung Seng , Zhao Tianyun , Wang Loo Chien , Sobota Radoslaw , Choi Hyungwon , Liu Mei Hui , Kim Kwang Pyo , Tai E Shyong 
Published: July 2023

SUMMARYSensitivity and plasticity of insulin signaling and glucose uptake in skeletal muscle depends on determinants such as genetic variation and obesity. We collected muscle biopsies and isolated myoblasts from a multi-ethnic cohort of lean South Asians (N=10), lean Chinese (N=10), and obese Chinese (N=10), and analysed the proteome and phosphoproteome dynamics in terminally differentiated myotubes after a low-dose insulin stimulation (10nM at 0, 5, 30 min). The myotubes initially responded with increased abundance and phosphorylation level changes along the PI3K/AKT/mTOR axis, decreased abundance of translation initiation factors, and increased phosphorylation levels on proteins involved in mRNA processing at 5 min. After the acute response, protein abundance returned to baseline at 30 min, while phosphorylation changes persisted in proteins including AKT, RPS6 and AS160 (TBC1D4). A joint kinase-substrate statistical analysis revealed that protein abundance changes of AKT, PAK1 and CDK1 showed concordant phosphorylation changes in their respective substrates upon insulin stimulation. We also observed increased phosphorylation of some substrates uniquely in each group, particularly the substrates of CDKs showing stronger changes in South Asians than in Chinese. Pharmacological inhibition and siRNA knockdown of CDK1, a non-myogenic kinase, in terminally differentiated myotubes reduced glucose uptake and desensitized several phosphorylation-mediated signaling on protein translation initiation factors, IRS1, and AS160. Our data suggest that basal extramitotic activity of CDK1 is required for PI3K/AKT/mTORC1 signaling cascade and glucose uptake in insulin-stimulated myotubes. The data also provide a rich resource for studying the role of other kinases in the mechanism of insulin resistance in human myotubes.
Intra-Articular Sprouting Of Nociceptors Accompanies Progressive Osteoarthritis: Comparative Evidence In Four Murine Models
Authors: Obeidat Alia M. , Ishihara Shingo , Li Jun , Lammlin Lindsey , Junginger Lucas , Maerz Tristan , Miller Richard J. , Miller Rachel E. , Malfait Anne-Marie 
Published: July 2023

ABSTRACTObjectiveKnee joints are densely innervated by nociceptors. Sprouting of nociceptors has been reported in late-stage osteoarthritis (OA), both in human knees and in rodent models. Here, we sought to describe progressive nociceptor remodeling in four mouse models of knee OA, capturing early and late-stage disease.MethodsSham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 NaV1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naïve male wildtype mice was evaluated at 6 and 24 months. Twenty-μm thick mid-joint cryosections were assessed qualitatively and quantitatively for NaV1.8+ and PGP9.5+ innervation. Cartilage damage (using a modified OARSI score), synovitis, and osteophytes were assessed blindly.ResultsProgressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in both the medial and the lateral compartment, accompanied with neuroplasticity in the synovium and the subchondral bone. All 4 models had an increased nerve signal in osteophytes.ConclusionAnatomical neuroplasticity of nociceptors was observed in association with joint damage in 4 distinct mouse models, suggesting that it is intrinsic to OA pathology.
FADS1/2-mediated lipid metabolic reprogramming drives ferroptosis sensitivity in triple-negative breast cancer
Authors: Lorito Nicla , Subbiani Angela , Smiriglia Alfredo , Bacci Marina , Bonechi Francesca , Tronci Laura , Corrado Alessia , Longo Dario Livio , Iozzo Marta , Ippolito Luigi , Comito Giuseppina , Giannoni Elisa , Meattini Icro , Avgustinova Alexandra , Chiarugi Paola , Bachi Angela , Morandi Andrea 
Published: July 2023

AbstractTriple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value.Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA).Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, lipid susceptible to peroxidation, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 renders those tumors ferroptosis-resistant. These findings were validatedin vitroandin vivoin mouse and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.One sentence summaryThe availability of intracellular PUFA depends on FADS1/2 desaturases, expressed at higher levels in aggressive triple-negative breast cancers highly susceptible to ferroptosis.
Differentiation of hypervirulent and classicalKlebsiella pneumoniaewith acquired drug resistance
Authors: Russo Thomas A. , Alvarado Cassandra L. , Davies Connor J. , Drayer Zachary J. , Carlino-MacDonald Ulrike , Hutson Alan , Luo Ting L. , Martin Melissa J. , Corey Brendan W. , Moser Kara A. , Rasheed J. Kamile , Halpin Alison L. , McGann Patrick T. , Lebreton Francois 
Published: July 2023

AbstractDistinguishing hypervirulent (hvKp) from classicalKlebsiella pneumoniae(cKp) strains is important for clinical care, surveillance, and research. Some combination ofiucA, iroB, peg-344, rmpA,andrmpA2are most commonly used, but it is unclear what combination of genotypic or phenotypic markers (e.g. siderophore concentration, mucoviscosity) most accurately predicts the hypervirulent phenotype. Further, acquisition of antimicrobial resistance may affect virulence and confound identification. Therefore, 49K. pneumoniaestrains that possessed some combination ofiucA, iroB, peg-344, rmpA,andrmpA2and had acquired resistance were assembled and categorized as hypervirulent hvKp (hvKp) (N=16) or cKp (N=33) via a murine infection model. Biomarker number, siderophore production, mucoviscosity, virulence plasmid’s Mash/Jaccard distances to the canonical pLVPK, and Kleborate virulence score were measured and evaluated to accurately differentiate these pathotypes. Both stepwise logistic regression and a CART model were used to determine which variable was most predictive of the strain cohorts. The biomarker count alone was the strongest predictor for both analyses. For logistic regression the area under the curve for biomarker count was 0.962 (P = 0.004). The CART model generated the classification rule that a biomarker count = 5 would classify the strain as hvKP, resulting in a sensitivity for predicting hvKP of 94% (15/16), a specificity of 94% (31/33), and an overall accuracy of 94% (46/49). Although a count of ≥ 4 was 100% (16/16) sensitive for predicting hvKP, the specificity and accuracy decreased to 76% (25/33) and 84% (41/49) respectively. These findings can be used to inform the identification of hvKp.ImportanceHypervirulentKlebsiella pneumoniae(hvKp) is a concerning pathogen that can cause life-threatening infections in otherwise healthy individuals. Importantly, although strains of hvKp have been acquiring antimicrobial resistance, the effect on virulence is unclear. Therefore, it is of critical importance to determine whether a given antimicrobial resistantK. pneumoniaeisolate is hypervirulent. This report determined which combination of genotypic and phenotypic markers could most accurately identify hvKp strains with acquired resistance. Both logistic regression and a machine-learning prediction model demonstrated that biomarker count alone was the strongest predictor. The presence of all 5 of the biomarkersiucA, iroB, peg-344, rmpA,andrmpA2was most accurate (94%); the presence of ≥ 4 of these biomarkers was most sensitive (100%). Accurately identifying hvKp is vital for surveillance and research, and the availability of biomarker data could alert the clinician that hvKp is a consideration, which in turn would assist in optimizing patient care.
Direction-Specific Effects of Artificial Skin-Stretch on Stiffness Perception and Grip Force Control
Authors: Farajian Mor , Leib Raz , Kossowsky Hanna , Nisky Ilana 
Published: July 2023

AbstractWhen interacting with an object, we use kinesthetic and tactile information to create our perception of the object’s properties and to prevent its slippage using grip force control. We previously showed that applying artificial skin-stretch together with, and in the same direction as, kinesthetic force increases the perceived stiffness. Here, we investigated the effect of the direction of the artificial stretch on stiffness perception and grip force control. We presented participants with kinesthetic force together with negative or positive artificial stretch, in the opposite or the same direction of the natural stretch due to the kinesthetic force, respectively. Our results showed that artificial skin-stretch in both directions augmented the perceived stiffness; however, the augmentation caused by the negative stretch was consistently lower than that caused by the positive stretch. Additionally, we proposed a computational model that predicts the perceptual effects based on the preferred directions of the stimulated mechanoreceptors. When examining the grip force, we found that participants applied higher grip forces during the interactions with positive skin-stretch in comparison to the negative skin-stretch, which is consistent with the perceptual results. These results may be useful in tactile technologies for wearable haptic devices, teleoperation, and robot-assisted surgery.
A Cardiac Transcriptional Enhancer is Repurposed During Regeneration to Activate an Anti-proliferative Program
Authors: Rao Anupama , Russell Andrew , Segura-Bermudez Jose , Franz Charles , Dockery Rejenae , Blatnik Anton , Panten Jacob , Zevallos Mateo , McNulty Carson , Pietrzak Maciej , Goldman Joseph Aaron 
Published: July 2023

AbstractZebrafish have a high capacity to regenerate their hearts. Several studies have surveyed transcriptional enhancers to understand how gene expression is controlled during heart regeneration. We have identifiedRENor therunx1enhancer that during regeneration regulates the expression of the nearbyrunx1gene. We show thatrunx1mRNA is reduced with deletion ofREN(ΔREN)and cardiomyocyte proliferation is enhanced in both ΔRENand Δrunx1mutants only during regeneration. Interestingly, in uninjured hearts, ΔRENmutants have reduced expression ofadamts1, a nearby gene that encodes a Collagen protease. This results in excess Collagen within cardiac valves of uninjured hearts. The ΔRENCollagen phenotype is rescued even by Δrunx1mutations, suggesting that in uninjured heartsRENregulatesadamts1independently ofrunx1. Taken together, this suggests thatRENis rewired fromadamts1in uninjured hearts to stimulaterunx1transcription during regeneration. Our data point to a previously unappreciated mechanism for gene regulation during zebrafish heart regeneration. We report that an enhancer is rewired from expression in a distal cardiac domain to activate a different gene in regenerating tissue.
Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A
Authors: Vasudevan Amruta , Ratnakaran Neena , Murthy Kausalya , Ahlawat Shikha , Koushika Sandhya P. 
Published: July 2023

AbstractAsymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branchesin vivoin wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point inC. elegansPLM neurons. The anterograde motor UNC-104/KIF1A regulates this vesicle behaviour at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM- 4/Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behaviour at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight towards the asynaptic end. This suggests that the neuron optimises UNC-104 levels on the cargo surface to maximise the fraction of vesicles entering the branch and minimise the fraction going to the asynaptic end.