bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes
Authors: Lycke Roy , Kim Robin , Zolotavin Pavlo , Montes Jon , Sun Yingchu , Koszeghy Aron , Altun Esra , Noble Brian , Yin Rongkang , He Fei , Totah Nelson , Xie Chong , Luan Lan 
Published: February 2023

SummaryIntracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation is often compromised by the adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-Nanoelectronic Threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models.In vivotwo-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2 μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over eight months at markedly low charge injection of 0.25 nC/phase. Quantified histological analysis show that chronic ICMS by StimNETs induce no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially-selective neuromodulation at low currents which lessen risks of tissue damage or exacerbation of off-target side-effects.
New insights on the genetics of hair whorls from twins and the Southern hemisphere
Authors: Willems Marjolaine , Hennocq Quentin , Cortés Santander Juan José , Khonsari Roman Hossein 
Published: February 2023

AbstractThe mechanisms determining the rotation direction and position of hair whorls are unknown. Here we report observations on twins suggesting that the morphological parameters of whorls have genetic bases, and provide comparative data on whorls from children born in the Northern and Southern hemispheres, indicating that whorl formation also depends on environmental factors. Our results underline the importance of unusual morphological phenomena for providing general information on normal developmental processes, and plead for large-scale epidemiological assessments to support our surprizing initial findings.
Comparison between Canine and Porcine Models of Chronic Deep Venous Thrombosis
Authors: Wang Chuang , Tang Tao , Ye Sheng-Lin , Jiang Xu-Dong , Xiang Guang-Yuan , Xiao Lun , Wang Lu-Lu , Xu Tian-Ze , Song Bin , Hu Nan , Du Xiao-Long , Li Xiao-Qiang 
Published: February 2023

AbstractVenous thromboembolism(VTE) refers to deep venous thrombosis(DVT) and pulmonary embolism(PE), which is a worldwide problem and has very high morbidity and mortality. The research of venous thrombosis involves pathogenesis, pathophysiology, and therapeutic attempt. Alternative experimental animal models have changed dramatically over the past 20 years, from small murine models to large ones. Larger animal models offer more options and are more consistent with human physiology. This article aims to induce chronic deep venous thrombosis in the left iliac vein in canine and porcine models and compare these two models. We think that feasible large animal models can better translate the results of therapeutic research into clinical application.
Utilizing Pre-trained Network Medicine Models for Generating Biomarkers, Targets, Re-purposing Drugs, and Personalized Therapeutic Regimes: COVID-19 Applications
Authors: Xiong Jianghui 
Published: February 2023

AbstractIn this paper, we present a novel pre-trained network medicine model called Selective Remodeling of Protein Networks by Chemicals (SEMO). We divide the global human protein-protein interaction (PPI) network into smaller sub-networks, and quantify the potential effects of chemicals by statistically comparing their target and non-target gene sets. By combining 9607 PPI gene sets with 2658 chemicals, we created a pre-trained pool of SEMOs, which we then used to identify SEMOs related to Covid-19 severity using DNA methylation profiling data from two clinical cohorts. The nutraceutical-derived SEMO features provided an effective model for predicting Covid-19 severity, with an AUC score of 81% in the training data and 80% in the independent validation data. Our findings suggest that Vitamin D3, Lipoic Acid, Citrulline, and Niacin, along with their associated protein networks, particularly STAT1, MMP2, CD8A, and CXCL8 as hub nodes,could be used to effectively predict Covid-19 severity. Furthermore, the severity-associated SEMOs were found to be significantly correlated with CD4+ and monocyte cell proportions. These insights can be used to generate personalized nutraceutical regimes by ranking the relative severity risk associated with each SEMO. Thus, our pre-trained SEMO model can serve as a fundamental knowledge map when coupled with DNA methylation measurements, allowing us to simultaneously generate biomarkers, targets, re-purposing drugs, and nutraceutical interventions.
Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) inC. elegansembryos
Authors: Nkoula Sylvia Nkombo , Velez-Aguilera Griselda , Ossareh-Nazari Batool , Hove Lucie Van , Ayuso Cristina , Legros Véronique , Chevreux Guillaume , Thomas Laura , Seydoux Géraldine , Askjaer Peter , Pintard Lionel 
Published: February 2023

AbstractThe nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In theC. eleganszygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words)One-Sentence SummaryPLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in theC. eleganszygote.
Visual experience shapes functional connectivity between occipital and non-visual networks
Authors: Tian Mengyu , Xiao Xiang , Hu Huiqing , Cusack Rhodri , Bedny Marina 
Published: February 2023

AbstractComparisons across adults with different sensory histories (blind vs. sighted) have uncovered effects of experience on human brain function. In people born blind visual cortices are responsive to non-visual tasks and show altered functional connectivity at rest. Since almost all research has been done with adults, little is known about the developmental origins of this plasticity. Are infant visual cortices initially functionally like those of sighted adults and blindness causes reorganization? Alternatively, do infants start like blind adults, with vision required to set up the sighted pattern? To distinguish between these possibilities, we compare resting state functional connectivity across blind (n= 30) and blindfolded sighted (n= 50) adults to a large cohort of sighted infants (Developing Human Connectome Project,n= 475). Remarkably, we find that infant secondary visual cortices functionally resemble those of blind more than sighted adults, consistent with the idea that visual experience is required to set up long-range functional connectivity. Primary visual cortices show a mixture of instructive effects of vision and reorganizing effects of blindness. Specifically, in sighted adults, visual cortices show stronger functional coupling with nonvisual sensory-motor networks (i.e., auditory, somatosensory/motor) than with higher-cognitive prefrontal cortices (PFC). In blind adults, visual cortices show stronger coupling with PFC. In infants, connectivity of secondary visual cortices is stronger with PFC, while V1 shows equal sensory-motor/PFC connectivity. In contrast, lateralization of occipital-to-frontal connectivity resembles the sighted adults at birth and is reorganized by blindness, possibly due to recruitment of occipital networks for lateralized cognitive functions, such as language.
Myomatrix arrays for high-definition muscle recording
Authors: Chung Bryce , Zia Muneeb , Thomas Kyle A. , Michaels Jonathan A. , Jacob Amanda , Pack Andrea , Williams Matthew J. , Nagapudi Kailash , Teng Lay Heng , Arrambide Eduardo , Ouellette Logan , Oey Nicole , Gibbs Rhuna , Anschutz Philip , Lu Jiaao , Wu Yu , Kashefi Mehrdad , Oya Tomomichi , Kersten Rhonda , Mosberger Alice C. , O’Connell Sean , Wang Runming , Marques Hugo , Mendes Ana Rita , Lenschow Constanze , Kondakath Gayathri , Kim Jeong Jun , Olson William , Quinn Kiara N. , Perkins Pierce , Gatto Graziana , Thanawalla Ayesha , Coltman Susan , Kim Taegyo , Smith Trevor , Binder-Markey Ben , Zaback Martin , Thompson Christopher K. , Giszter Simon , Person Abigail , Goulding Martyn , Azim Eiman , Thakor Nitish , O’Connor Daniel , Trimmer Barry , Lima Susana Q. , Carey Megan R. , Pandarinath Chethan , Costa Rui M. , Pruszynski J. Andrew , Bakir Muhannad , Sober Samuel J. 
Published: February 2023

AbstractNeurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system’s actual motor output – the activation of muscle fibers by motor neurons – typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices (“Myomatrix arrays”) that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a “motor unit”, during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system’s motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.
Drug metabolic activity as a selection factor for pluripotent stem cell-derived hepatic progenitor cells
Authors: Akiyama Saeko , Saku Noriaki , Miyata Shoko , Ite Kenta , Nonaka Hidenori , Toyoda Masashi , Kamiya Akihide , Kiyono Tohru , Kimura Tohru , Kasahara Mureo , Umezawa Akihiro 
Published: February 2023

ABSTRACTAs a metabolic organ, the liver plays a variety of roles, including detoxification. It has been difficult to obtain stable supplies of hepatocytes for transplantation and for accurate hepatotoxicity determination in drug discovery research. Human pluripotent stem cells, capable of unlimited self-renewal, may be a promising source of hepatocytes. In order to develop a stable supply of embryonic stem cell (ESC)-derived hepatocytes, we have purified human ESC-derived hepatic progenitor cells with exposure to cytocidal puromycin by using their ability to metabolize drugs. Hepatic progenitor cells stably proliferated at least 2^20-fold over 120 days, maintaining hepatic progenitor cell-like properties. High drug-metabolizing hepatic progenitor cells can be matured into liver cells by suppressing hepatic proliferative signals. The method we developed enables the isolation and proliferation of functional hepatic progenitors from human ESCs, thereby providing a stable supply of high-quality cell resources at high efficiency. Cells produced by this method may facilitate cell therapy for hepatic diseases and reliable drug discovery research.
Short- and long-term effects of continuous compost amendment on soil microbiome community
Authors: Kraut-Cohen Judith , Zolti Avihai , Rotbart Nativ , Bar-Tal Asher , Laor Yael , Medina Shlomit , Shawahna Raneen , Saadi Ibrahim , Raviv Michael , Green Stefan J , Yermiyahu Uri , Minz Dror 
Published: February 2023

AbstractOrganic amendment, and especially the use of composts, is a well-accepted sustainable agricultural practice. Compost increases soil carbon and microbial biomass, changes enzymatic activity, and enriches soil carbon and nitrogen stocks. However, relatively little is known about the immediate and long-term temporal dynamics of agricultural soil microbial communities following repeated compost applications. Our study was conducted at two field sites: Newe Ya’ar (NY, Mediterranean climate) and Gilat (G, semi-arid climate), both managed organically over 4 years under either conventional fertilization (0, zero compost) or three levels of compost amendment (20, 40 and 60 m3/ha or 2, 4, 6 L/m2). Microbial community dynamics in the soils was examined by high-and low-time-resolution analyses. Annual community composition in compost-amended soils was significantly affected by compost amendment levels in G (first, second and third years) and in NY (third year). Repeated sampling at high resolution (9–10 times over 1 year) showed that at both sites, compost application initially induced a strong shift in microbial communities, lasting for up to 1 month, followed by a milder response. Compost application significantly elevated alpha diversity at both sites, but differed in the compost–dose correlation effect. We demonstrate higher abundance of taxa putatively involved in organic decomposition and characterized compost-related indicator taxa and a compost-derived core microbiome at both sites. Overall, this study describes temporal changes in the ecology of soil microbiomes in response to compost vs. conventional fertilization.HighlightsDose-dependent changes in soil microbiome structure by manure compost applicationDynamic short-and long-term changes in soil microbiomes by compost amendmentClimate, soil properties and management influence compost-amendment effectsImmediate and temporal cumulative effects of compost on soil α and β diversity
Nanoparticles of bioactive natural collagen for wound healing: Experimental approach
Authors: Shalaby Manal , Ghareeb Ahmed .Z , Khedr Shaimaa M. , Mostafa Haitham M. , Saeed Hesham , Hamouda Dalia 
Published: February 2023

AbstractIntroductionBoth developing and developed nations have made the creation of innovative wound-healing nanomaterials based on natural extracts a top research goal. The objective of this research was to create a gel containing collagen nanoparticles and evaluate its therapeutic potential for skin lesions.MethodsCollagen nanoparticles from fish scales were produced for the first time using desolvation techniques. Using Fourier transform infrared spectroscopy (FTIR), the structure of the isolated collagen and its similarities to collagen type 1 were identified. The surface morphology of the isolated collagen and its reformulation into nanoparticles were examined using transmission and scanning electron microscopy. Human skin fibroblast cells were employed to examine the cytotoxicity of the nanomaterials, and an experimental model was used to evaluate the wound healing capability.ResultsCollagen nanoparticles formulation was confirmed using FTIR, SEM and TEM analysis. Cytotoxicity studies demomstrated that the manufactured nanoparticles have minor toxicity at high concentrations on human skin fibroblast. Histological investigation proved that the fabricated fish scale collagen nanoparticles promoted the healing process in comparison to the saline group.ConclusionThe fabricated product is a highly influential wound healing product that can be applicable for commercial use. The nanoscale size of collagen nanoparticles, make them interesting candidates for biological applications.Key Summary PointsThe goal of this research was to create natural, effective wound remedies that could lower health-care costs while also providing pain relief and, ultimately, effective scar repair.Collagen nanoparticles can be synthesized from fish scale utilizing various nanotechnology-based approaches to stimulate skin cell proliferation and promote wound healing.Collagen nanoparticles have a rough surface, have a negative potential, and can be used for drug delivery and wound healing.Histological and macroscopical analysis showed that the synthesized nanoparticles promoted faster wound healing.
RelB represses miR-193a-5p expression to promote the phenotypic transformation of vascular smooth muscle cells in aortic aneurysm
Authors: Liu Yisi , Tian Xiaoxiang , Liu Dan , Zhang Xiaolin , Yan Chenghui , Han Yaling 
Published: February 2023

AbstractAortic aneurysm (AA) is a potentially fatal disease with the possibility of rupture, causing high mortality rates with no effective drugs for the treatment of AA. The mechanism of AA, as well as its therapeutic potential to inhibit aneurysm expansion, has been minimally explored. Small non-coding RNA (miRNAs and miRs) is emerging as a new fundamental regulator of gene expression. This study aimed to explore the role and mechanism of miR-193a-5p in abdominal aortic aneurysms (AAA). In AAA vascular tissue and Angiotensin II (Ang II)-treated vascular smooth muscle cells (VSMCs), the expression of miR-193a-5 was determined using real-time quantitative PCR (RT-qPCR). Western blotting was used to detect the effects of miR-193a-5p on PCNA, CCND1, CCNE1, and CXCR4. To detect the effect of miR-193a-5p on the proliferation and migration of VSMCs, CCK-8, and EdU immunostaining, flow cytometry, wound healing, and Transwell Chamber analysis were performed. In vitro results suggest that overexpression of miR-193a-5p inhibited the proliferation and migration of VSMCs, and its inhibition aggravated their proliferation and migration. In VSMCs, miR-193a-5p mediated proliferation by regulating CCNE1 and CCND1 genes and migration by regulating CXCR4. Further, in the Ang II-induced abdominal aorta of mice, the expression of miR-193a-5p was reduced and significantly downregulated in the serum of patients with aortic aneurysm (AA). In vitro studies confirmed that Ang II-induced downregulation of miR-193a-5p in VSMCs by upregulation of the expression of the transcriptional repressor RelB in the promoter region. This study may provide new intervention targets for the prevention and treatment of AA.
Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis inMycobacterium ulceransinfection
Authors: Hsieh Louise Tzung-Harn , Hall Belinda S. , Newcombe Jane , Mendum Tom A. , Santana-Varela Sonia , Umrania Yagnesh , Deery Michael J. , Shi Wei Q. , Diaz-Delgado Josué , Salguero Francisco J. , Simmonds Rachel E 
Published: February 2023

AbstractThe drivers of tissue necrosis inMycobacterium ulceransinfection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action of the diffusible exotoxin, mycolactone. However, its role in the clinically-evident vascular component of disease aetiology remains poorly explained. We have now dissected mycolactone’s effects on primary vascular endothelial cellsin vitroandin vivo. We show that mycolactone-induced changes in endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven by rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis, combined with a reduction in the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disruptedin vivo. Remarkably, exogenous addition of laminin-511 reduced endothelial cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone. Hence supplementing mycolactone-depleted extracellular matrix may be a future therapeutic avenue, to improve wound healing rates.
Flame (v2.0): advanced integration and interpretation of functional enrichment results from multiple sources
Authors: Karatzas Evangelos , Baltoumas Fotis A. , Aplakidou Eleni , Kontou Panagiota I. , Stathopoulos Panos , Stefanis Leonidas , Bagos Pantelis G. , Pavlopoulos Georgios A. 
Published: February 2023

AbstractFunctional enrichment is the process of identifying implicated functional terms from a given input list of genes or proteins. In this article, we present Flame (v2.0), a web tool which offers a combinatorial approach through merging and visualizing results from widely-used functional enrichment applications while also allowing various flexible input options. In this version, Flame utilizes the aGOtool, g:Profiler, WebGestalt and Enrichr pipelines and presents their outputs separately or in combination following a visual analytics approach. For intuitive representations and easier interpretation, it uses interactive plots such as parameterizable networks, heatmaps, barcharts and scatter plots. Users can also:(i)handle multiple protein/gene lists and analyze union and intersection sets simultaneously through interactive UpSet plots,(ii)automatically extract genes and proteins from free text through text-mining and Named Entity Recognition (NER) techniques,(iii)upload single nucleotide polymorphisms (SNPs) and extract their relative genes or(iv)analyze multiple lists of differentially-expressed proteins/genes after selecting them interactively from a parameterizable volcano plot. Compared to the previous version of 197 supported organisms, Flame (v2.0) currently allows enrichment for 14,436 organisms.
Differential labelling of human sub-cellular compartments with fluorescent dye esters and expansion microscopy
Authors: Sheard Thomas M. D. , Shakespeare Tayla , Seehra Rajpinder S. , Spencer Michael E , Suen Kin M. , Jayasinghe Izzy 
Published: February 2023

AbstractAmine-reactive esters of aromatic fluorescent dyes are emerging as imaging probes for nondescript staining of cellular and tissue architectures. We characterised the differential staining patterns of 14 fluorescent dye ester species with varying physical and spectral properties in the broadly studied human cell line – HeLa. When combined with expansion microscopy (ExM), these stains reveal nanoscale features such as the nuclear proteome, membrane-bound compartments and vesicles. Among N-Hydroxysuccinimide (NHS) esters, we observe differential compartment specificity and weighting of labelling density which correlates with the hydrophobicity of the dye ester. We also observe changes in both staining density and compartment specificity for a given dye ester depending on the presence of a second dye ester species and on the timepoint of application in the ExM protocol. Our findings confirm these dye esters as a useful addition to the repertoire of biomedical stains of the cellular proteome, either on their own, or as counterstains to immunofluorescence.