bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of brain pericytes requires expression of the transcription factornkx3.1in intermediate precursors
Authors: Ahuja Suchit , Adjekukor Cynthia , Li Qing , Kocha Katrinka M. , Rosin Nicole , Labit Elodie , Sinha Sarthak , Narang Ankita , Long Quan , Biernaskie Jeff , Huang Peng , Childs Sarah J. 
Published: June 2023

AbstractBrain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factornkx3.1develop into brain pericytes. We identify the gene signature of these precursors, and show that annkx3.1, foxf2a, andcxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, bothnkx3.1andcxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.
MEBRAINS 1.0: a new population-based macaque atlas
Authors: Balan Puiu F , Zhu Qi , Li Xiaolian , Niu Meiqi , Rapan Lucija , Funck Thomas , Bakker Rembrandt , Palomero-Gallagher Nicola , Vanduffel Wim 
Published: June 2023

ABSTRACTDue to their fundamental relevance, the number of anatomical macaque brain templates is constantly growing. Novel templates aim to alleviate limitations of previously published atlases and offer the foundation to integrate multiscale multimodal data. Typical limitations of existing templates include their reliance on one subject, their unimodality (usually only T1 or histological images), or lack of anatomical details. The MEBRAINS template overcomes these limitations by using a combination of T1 and T2 images, from the same 10 animals (Macaca mulatta), which are averaged by the multi-brain toolbox for diffeomorphic registration and segmentation. The resulting volumetric T1 and T2 templates are supplemented with high quality white and gray matter surfaces built with FreeSurfer. Human-curated segmentations of pial surface, white/gray matter interface and major subcortical nuclei were used to analyse the relative quality of the MEBRAINS template. Recently published 3D maps of the macaque inferior parietal lobe and (pre)motor cortex were warped to the MEBRAINS surface template, thus populating it with a parcellation scheme based on cyto- and receptor architectonic analyses. Finally, 9 CT scans of the same monkeys were registered to the T1 modality and co-registered to the template. Through its main features (multi-subject, multi-modal, volume-and-surface, traditional and deep learning-based segmentations), MEBRAINS aims to improve integration of multi-modal multi-scale macaque data and is quantitatively equal or better compared to currently widely used macaque templates. The template is integrated in the EBRAINS and Scalable Brain Atlas web-based infrastructures, each of which comes with its own suite of spatial registration tools.
Improved detection and phylogenetic analysis of plant proteins containing LysM domains
Authors: Dallachiesa Dardo , Aguilar O. Mario , Lozano Mauricio J 
Published: June 2023

ABSTRACTPlants perceive N-acetyl-d-glucosamine-containing oligosaccharides that play a role in the interaction with bacteria and fungi, both pathogenic and symbiotic, through cell-surface receptors that belong to the Receptor-Like Kinase (RLK) or Receptor-Like Protein (RLP) families. Structurally characterised proteins from these families have been shown to contain a tight bundle of three LysM domains in their extracellular domain. However, the identification of LysM domains of RLK/Ps using sequence based methods has led to some ambiguity, as some proteins have been annotated with one or only two LysM domains. This missing annotation was likely produced by the failure of the LysM hidden Markov model (HMM) from the PFAM database to correctly identify some LysM domains in proteins of plant origin. In this work, we provide improved HMMs for LysM domain detection in plants, that were built from the structural alignment of manually curated LysM domain structures from PDB and AlphaFold. Furthermore, we evaluated different sets of ligand-specific HMMs that were able to correctly classify a limited set of fully characterised RLK/Ps by their ligand specificity. In contrast, the phylogenetic analysis of the extracellular region of RLK/Ps, or of their individual LysM domains, was unable to discriminate these proteins by their ligand specificity. The HMMs reported here will allow a more sensitive detection of plant proteins containing LysM domains and help improve their characterisation.
Impact of random 50-base sequences inserted into an intron on splicing inSaccharomyces cerevisiae
Authors: Perchlik Molly , Sasse Alexander , Mostafavi Sara , Fields Stanley , Cuperus Josh T. 
Published: June 2023

ABSTRACTIntron splicing is a key regulatory step in gene expression in eukaryotes. Three sequence elements required for splicing – 5’ and 3’ splice sites and a branch point – are especially well- characterized inSaccharomyces cerevisiae, but our understanding of additional intron features that impact splicing in this organism is incomplete, due largely to its small number of introns. To overcome this limitation, we constructed a library inS. cerevisiaeof random 50-nucleotide elements (N50) individually inserted into the intron of a reporter gene and quantified canonical splicing and the use of cryptic splice sites by sequencing analysis. More than 70% of approximately 140,000 N50 elements reduced splicing by at least 20% compared to the intron control. N50 features, including higher GC content, presence of GU repeats and stronger predicted secondary structure of its pre-mRNA, correlated with reduced splicing efficiency. A likely basis for the reduced splicing of such a large proportion of variants is the formation of RNA structures that pair N50 bases – such as the GU repeats – with other bases specifically within the reporter pre-mRNA analyzed. However, neither convolutional neural network nor linear models were able to explain more than a small fraction of the variance in splicing efficiency across the library, suggesting that complex non-linear interactions in RNA structures are not accurately captured by RNA structure prediction methods given the limited number of variants. Our results imply that the specific context of a pre-mRNA may determine the bases allowable in an intron to prevent secondary structures that reduce splicing.
Assessment of Nutrient Composition and utilization of some popular wild Edible fruits of Kumaun Himalayan Region as Anti-oxidant agents
Authors: Pandey Neelaxi , Ghosh Puja , Muhasina K. M , Bisht Satpal Singh , Jha Abhishek 
Published: June 2023

AbstractFood and Nutrition security is the main problem faced by developing and underdeveloped countries. Proper utilization of wild edible plants for nutrition security is a great choice for reducing the wastage of these powerful foods. The present investigation has been made to understand the nutritional and phytochemical parameter of selected underutilized fruits such asDiospyros kaki, Pyrus pashia, Ficus semicordata, Diploknema butyracea, Pyracantha crenulata, andRubus niveus. The proximate analyses showed thatDiospyros kakiis most promising fruit with 44.86± 0.4 mg/g carbohydrate, 9.29±0.80 mg/g protein, 81.31±0.4, 7% moisture and 1.1±0.11% little amount of ash content. Micronutrient iron was quantify highest inPyracantha crenulata(3.52±0.24mg/100g) and zinc inRubus niveus(8.13±0.05 mg/100g). Phytochemical screening was recorded in the ethanolic and aqueous extract, in which Phenolic and flavonoid content were highest in ethanolic extract ofRubus niveus;64.05±0.13mg GAE/gm, 108.83±2.93mg QE/ g extract respectively and tannin content was highest in case ofDiospyros kaki(79.94±0.40mg TAE/100g of extract). The free radical scavenging activity of fruits have been analyzed by DPPH, H2O2and NO assay; it was observed that the ethanolic extract ofRubus niveusfruit is most promising with an IC50value 16.97μg/ml. In contrast, aqueous extract scored IC50value 28.86μg/ml. The lowest IC50value was found in aqueous extract ofDiospyros kakii.e., 81.9 μg/ml in DPPH assay. The potential usage of these plants will help the people of these regions to combat nutrient deficiency diseases. Further development of research may help us to come out with powerful functional foods using these fruits.Graphical Abstract
A widespread proteinaceous sulfur storage compartment in bacteria
Authors: Benisch Robert , Andreas Michael P. , Giessen Tobias W. 
Published: June 2023

AbstractIntracellular compartmentalization is essential for all cells and enables the regulation and optimization of metabolism1. One of the main functions of subcellular compartments is the storage of nutrients2–4. As bacteria do generally not possess membrane-bound organelles, they often have to rely on functionally analogous protein-based compartments2,5–7. Encapsulin nanocompartments are one of the most prevalent protein-based compartmentalization strategies found in prokaryotes5,8. Here we show that desulfurase encapsulins represent a novel sulfur storage compartment in bacteria able to sequester large amounts of crystalline elemental sulfur. We determined the 1.78 Å cryo-EM structure of a 24 nm desulfurase-loaded encapsulin highlighting the molecular details of the protein shell and desulfurase encapsulation. We found that elemental sulfur crystals can be formed inside encapsulin shells in a desulfurase-dependent manner with L-cysteine acting as the sulfur donor. Intracellular sulfur accumulation can be influenced by the concentration and type of sulfur source in growth media. The selectively permeable protein shell allows the long-term intracellular storage of redox-labile elemental sulfur by excluding cellular reducing agents from its interior. We found that encapsulation substantially improves desulfurase activity and stability while also preventing substrate inhibition. These findings represent the first example of a dedicated and widespread storage system for the essential element sulfur in bacteria and provide the basis for understanding how this novel protein-based storage compartment is integrated within bacterial metabolism.
Multiprotein Assemblies, Phosphorylation and Dephosphorylation in Neuronal Cytoskeleton
Authors: Kurochkina Natalya , Sapio Matthew R. , Iadarola Michael J. , Hall Bradford E , Kulkarni Ashok B. 
Published: June 2023

ABSTRACTFilament systems are comprised of fibrous and globular cytoskeletal proteins and are key elements regulating cell shape, rigidity, and dynamics. The cellular localization and assembly of neurofilaments depend on phosphorylation by kinases. The involvement of the BRCA1 (Breast cancer associated protein 1)/BARD1 (BRCA1-associated RING domain 1) pathways in Alzheimer disease (AD) is suggested by colocalization studies. In particular, BRCA1 accumulation within neurofibrillary tangles and colocalization with tau aggregates in the cytoplasm of AD patients implicates the involvement of mutant forms of BRCA1/BARD1 proteins in disease pathogenesis. The purpose of this study is to show that the location of mutations in the translated BARD1, specifically within ankyrin repeats, has strong correlation with the Cdk5 motifs for phosphorylation.Mapping of the mutation sites on the protein’s three-dimensional structure and estimation of the backbone dihedral angles show transitions between the canonical helical and extended conformations of the tetrapeptide sequence of ankyrin repeats.Clustering of mutations in BARD1 ankyrin repeats near the N-termini of the helices with T/SXXH motifs provides a basis for conformational transitions that might be necessary to ensure the compatibility of the substrate with active site geometry and accessibility of the substrate to the kinase.Ankyrin repeats are interaction sites for phosphorylation-dependent dynamic assembly of proteins including those involved in transcription regulation and signaling, and present potential targets for the design of new drugs.
Structural insights into a single semi-clathrate hydrate formed in a confined environment of porous protein crystal
Authors: Maity Basudev , Tian Jiaxin , Furuta Tadaomi , Abe Satoshi , Ueno Takafumi 
Published: June 2023

AbstractWater behavior on protein surfaces influences protein structure and function. Antifreeze Proteins (AFPs) have been intensively studied in context of biological cytotechnology. AFPs inhibit growth of ice microcrystals by forming unique water-cluster networks which are influenced by protein surface morphology and hydrophobicity. Such unique water-cluster networks have been identified as semi-clathrate structures in crystals and are believed to be stabilized by intermolecular interactions within the confined environment. However, there is little atomic-level information about the process of formation of semi-clathrates and the structural units of water-clathrate networks. We identified a single semi-clathrate formed on the pore surface of ferritin crystal which has a structure similar to that of a natural AFP. Comparison of ferritin mutants and determination of temperature-dependent structures revealed that semi-clathrate water molecules on an ⍺-helix undergo structural alterations with increasing temperature. Lowering the temperature regenerates the semi-clathrate structure. Water molecules hydrogen-bonded to main chain carbonyl groups are stably immobilized at room temperature and serve as starting points for clathrate formation. These findings provide a mechanistic understanding of water networks in AFPs and guidelines for designing new cryomaterials.
Membrane contact sites regulate vacuolar fission via sphingolipid metabolism
Authors: Hanaoka Kazuki , Nishikawa Kensuke , Ikeda Atsuko , Schlarmann Philipp , Yamashita Sayumi , Nakaji Aya , Fujii Sotaro , Funato Kouichi 
Published: June 2023

AbstractMembrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar fission/fusion processes are coupled with modifications in the membrane lipid composition. However, it has been still unclear whether MCS-mediated lipid metabolism controls the vacuolar morphology. Here we report that deletion of tricalbins (Tcb1, Tcb2, Tcb3), tethering proteins at endoplasmic reticulum (ER)-plasma membrane (PM) and ER-Golgi contact sites, alters fusion/fission dynamics and causes vacuolar fragmentation in the yeastSaccharomyces cerevisiae. In addition, we show that the sphingolipid precursor phytosphingosine accumulates in tricalbin-deleted cells, triggering the vacuolar division. Detachment of the nucleus vacuole junction (NVJ), an important contact site between the vacuole and the perinuclear ER, restored vacuolar morphology in both cells subjected to high exogenous phytosphingosine and Tcb3-deleted cells, supporting that phytosphingosine transport across the NVJ induces vacuole division. Thus, our results suggest that vacuolar morphology is maintained by MCSs through the metabolism of sphingolipids.
Cardiomyocytes Deficiency of SENP1 Promotes Myocardial Fibrosis via Paracrine Action
Authors: Liu Zhihao , Bian Xiyun , Li Lan , Liu Li , Feng Chao , Wang Ying , Ni Jingyu , Li Sheng , Lu Dading , Li Yanxia , Ma Chuanrui , Yu Tian , Xiao Xiaolin , Xue Na , Wang Yuxiang , Zhang Chunyan , Ma Xiaofang , Gao Xiumei , Fan Xiaohui , Liu Xiaozhi , Fan Guanwei 
Published: June 2023

AbstractBackgroundSENP1 (Sentrin-specific protease 1) is involved in heart disease by regulating intracellular SUMOylation. However, the role of cell type-specific SENP1 in the setting of myocardial infarction (MI) remains to be defined. We determined whether cardiomyocyte-specific SENP1 regulates maladaptive remodeling in the ischemic heart.MethodsWe generated cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Adult mouse cardiomyocytes and fibroblasts were separated to observe the paracrine effects of cardiomyocytes. DIA proteomic assay and bioinformatic analysis were performed to detect differential proteins in primary cardiomyocytes. Single-cell sequencing data were analyzed to identify key cardiomyocyte cluster regulated by SENP1 after MI. Mass spectrometry was performed to search for key effector proteins regulated by SENP1.ResultsSENP1 expression reduced in post-infarction mice and patients with heart failure. Cardiomyocyte-specific SENP1 deficiency (genetic or adeno-associated virus (AAV)-mediated) triggered a myocardial fibrotic response and progressive cardiac dysfunction. MI exacerbated the poor ventricular remodeling response mediated by SENP1 deletion, SENP1 overexpression improved cardiac function and reduced fibrosis. Further, we found that increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased Fn expression and secretion in cardiomyocytes, promoted fibroblast activation in response to myocardial injury. Mechanistically, SENP promoted deSUMOylation of the HSP90ab1 (heat shock protein 90 alpha, class B, member 1) Lys72 and ubiquitin-dependent degradation, which reduced HSP90ab1-mediated phosphorylation of STAT3 (signal transducer and activator of transcription 3) and transcriptional activation of Fn, and then reduced fibroblast activation in the indirect coculture model. On the other hand, AAV-mediated mutation of the HSP90ab1 Lys72 ameliorated adverse ventricular remodeling and dysfunction post-MI.ConclusionsSENP1 is essential for repressing STAT3-mediated Fn transcription by regulating deSUMOylation of HSP90ab1. Blockade of HSP90ab1 SUMOylation at the Lys72 site is a novel therapy effective in reversing adverse ventricular remodeling post-MI.Abstract Figure
Small-field visual projection neurons detect translational optic flow and support walking control
Authors: Isaacson Mathew D. , Eliason Jessica L. M. , Nern Aljoscha , Rogers Edward M. , Lott Gus K. , Tabachnik Tanya , Rowell William J. , Edwards Austin W. , Korff Wyatt L. , Rubin Gerald M. , Branson Kristin , Reiser Michael B. 
Published: June 2023

SUMMARYAnimals rely on visual motion for navigating the world, and research in flies has clarified how neural circuits extract information from moving visual scenes. However, the major pathways connecting these patterns of optic flow to behavior remain poorly understood. Using a high-throughput quantitative assay of visually guided behaviors and genetic neuronal silencing, we discovered a region inDrosophila’s protocerebrum critical for visual motion following. We used neuronal silencing, calcium imaging, and optogenetics to identify a single cell type, LPC1, that innervates this region, detects translational optic flow, and plays a key role in regulating forward walking. Moreover, the population of LPC1s can estimate the travelling direction, such as when gaze direction diverges from body heading. By linking specific cell types and their visual computations to specific behaviors, our findings establish a foundation for understanding how the nervous system uses vision to guide navigation.
Identification of a new human polyomavirus in distinct populations and tissues
Authors: Torres Carolina , Correa Rita M. , Picconi María A. , Buck Christopher B. , Mbayed Viviana A. 
Published: June 2023

ABSTRACTObjectivesThis work aimed to characterize a novel human polyomavirus (HPyV) with cutaneous tropism.MethodsSwabs of healthy skin (forehead) of 75 immunocompetent individuals from Argentina were screened for HPyV through sequence amplification techniques. Publicly available metagenomic datasets were also analyzed.ResultsA previously unknown polyomavirus sequence was detected in two skin swab samples. A nearly identical sequence was detected in public datasets representing metagenomic surveys of human skin and feces. Further analyses showed that the new polyomavirus diverges from its nearest relative, human polyomavirus 6 (HPyV6), by 17.3-17.7% (in nucleotides for the large T antigen), which meets criteria for a new species designation in the genusDeltapolyomavirus.The screening also revealed more distant HPyV6 relatives in macaque genital and chimpanzee fecal datasets. Since polyomaviruses are generally thought to cospeciate with mammalian hosts, the high degree of similarity to HPyV6 suggests the new polyomavirus species is human-tropic.ConclusionsA novel polyomavirus was identified and characterized from samples of distinct populations and tissues. We suggest the common name human polyomavirus 16 (HPyV16).
Hippocampal Codes for Real-World Human Navigation
Authors: Graves Kathryn N. , Letrou Ariadne , Gray Tyler E. , Quraishi Imran H. , Turk-Browne Nicholas B. 
Published: June 2023

AbstractAs animals move through the world, the hippocampus represents their location, direction, and speed. Parallel studies in humans have been mostly limited to virtual navigation because of physical constraints of suitable neural recording technologies. However, there are known differences between real-world and virtual navigation, leaving open the question of how the hippocampus supports real-world navigation in humans. Here we report evidence from ambulatory patients with chronic brain implants that the location, direction, and speed of humans walking along a linear track are represented in local field potentials from the hippocampus. We further show in a subset of patients who were tested twice after long delays that these representations can be reliable over time. These findings provide the first demonstration of multiple, stable neural codes for real-world navigation in the human hippocampus.