bluuebunny/crossref_metadata_2025_split huggingface dataset:
Net-shaped DNA nanostructure designed for rapid/sensitive detection and potential inhibition of SARS-CoV-2 virus
Authors: Chauhan Neha , Xiong Yanyu , Ren Shaokang , Dwivedy Abhisek , Magazine Nicholas , Zhou Lifeng , Lin Xiaohe , Zhang Tianyi , Cunningham Brian T. , Yao Sherwood , Huang Weishan , Wang Xing 
Published: May 2022

ABSTRACTWe present a net-shaped DNA nanostructure (called “DNA Net” herein) design strategy for selective recognition and high-affinity capture of the intact SARS-CoV-2 virions through spatial pattern-matching and multivalent interactions between the aptamers (targeting wild type spike-RBD) positioned on the DNA Net and the trimeric spike glycoproteins displayed on the viral outer surface. Carrying a designer nanoswitch, the DNA Net-aptamers releases fluorescent signal upon virus binding that is easily read by a hand-held fluorimeter for a rapid (in 10 mins), simple (mix- and-read), sensitive (PCR equivalent), room temperature compatible, and inexpensive (∼ $1.26/test) COVID-19 test assay. The DNA Net-aptamers also impede authentic wild-type SARS-CoV-2 infection in cell culture with a near 1×103-fold enhancement of the monomeric aptamer. Furthermore, our DNA Net design principle and strategy can be customized to tackle other life-threatening and economically influential viruses like influenza and HIV, whose surfaces carry class-I viral envelope glycoproteins like the SARS-CoV-2 spikes in trimeric forms.
Modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550
Authors: Lee Yejin , Kim Hyeongju , Barker Douglas , Vijayvargia Ravi , Atwal Ranjit Singh , Specht Harrison , Keshishian Hasmik , Carr Steven A , Lee Ramee , Kwak Seung , Hyun Kyung-gi , Loupe Jacob , MacDonald Marcy E. , Song Ji-Joon , Seong Ihn Sik 
Published: May 2022

ABSTRACTHuntington’s disease (HD) is a neurodegerative disorder caused by an inherited unstable HTT CAG repeat that expands further, thereby eliciting a disease process that may be initiated by polyglutamine-expanded huntingtin or a short polyglutamine-product. Phosphorylation of selected candidate residues is reported to mediate polyglutamine-fragment degradation and toxicity. Here to support the discovery of phospho-sites involved in the life-cycle of (full-length) huntingtin, we employed mass spectrometry-based phosphoproteomics to systematically identify sites in purified huntingtin and in the endogenous protein, by proteomic and phospho-proteomic analyses of members of an HD neuronal progenitor cell panel. Our results bring total huntingtin phospho-sites to 95, with more located in the N-HEAT domain relative to numbers in the Bridge and C-HEAT domains. Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels. Taken together these findings highlight categories of phospho-sites that merit further study and provide a phospho-site kinase pair (pSer2550-PKA) with which to investigate the biological processes that regulate huntingtin degradation and thereby influence the steady state levels of huntingtin in HD cells.
A comprehensive analysis of Usutu virus (USUV) genomes revealed lineage-specific codon usage patterns and host adaptation
Authors: Zhou Jianglin , Xing Yaling , Zhou Zhe , Wang Shengqi 
Published: May 2022

ABSTRACTThe Usutu virus (USUV) is an emerging arbovirus virus maintained in the environment of Afro-Eurasia via a bird-mosquito-bird enzootic cycle and sporadically infected other vertebrates. Despite primarily asymptomatic or mild symptoms, humans infected by USUV can develop severe neurological diseases such as meningoencephalitis. However, no detailed study has yet been conducted to investigate its evolution from the perspective of codon usage patterns. Codon usage choice of viruses reflects the genetic variations that enable them to reconcile their viability and fitness towards the external environment and new hosts. This study performed a comprehensive evolution and codon usage analysis in USUVs. Our reconstructed phylogenetic tree confirmed the circulation viruses belonging to eight distinct lineages, reaffirmed by principal component analysis based on codon usage patterns. We also found a relatively small codon usage bias and that natural selection, mutation pressure, and evolutionary processes collectively shaped the codon usage of the USUV, with natural selection predominating over the others. Additionally, a complex interaction of codon usage between the USUV and its host was observed. This process could have enabled USUVs to adapt to various hosts and vectors, including humans. Therefore, the USUV may possess a potential risk of cross-species transmission and subsequent outbreaks. In this respect, further epidemiologic surveys, diversity monitoring, and pathogenetic research are warranted.
Controls of SAR11 subclade abundance, diversity, and growth in two Mid-Atlantic estuaries
Authors: Campbell Barbara J. , Lim Shen Jean , Kirchman David L. 
Published: May 2022

AbstractSAR11 is a dominant bacterial clade in marine oligotrophic ecosystems. SAR11 can also be dominant in estuarine systems, where they are not well-studied. We examined the effects of season, nutrient concentrations, and salinity in shaping SAR11 subclade abundance, diversity, function, and growth in two Mid-Atlantic estuaries, the Delaware and Chesapeake Bays. Using metagenome-assembled genomes, we identified twelve distinct genomospecies within the Ia, II, IIIa, and V subclades, which made up to 60% of the total bacterial community. The functional potential of all SAR11 genomospecies varied, especially in carbohydrate metabolism, transporters, and one-carbon metabolic pathways. Predicted growth rates, estimated by the Peak to Trough method, varied by season and genomospecies. SAR11 growth rates negatively correlated in the spring but positively correlated in the summer with chlorophyll a concentrations and bacterial production, as well as phosphate and ammonium concentrations. Genomospecies in Ia.1, IIIa.2, and IIIa.4 subclades had low growth rates, while genomospecies in Ia.3, Ia.5, Ia.6, II, and V subclades had higher and more variable growth rates that were positively correlated with phosphate concentrations and temperature. Growth rate variation between subclades was associated with carbohydrate metabolic gene repertoires, especially glycolysis and number of transporters. While total transcript to genome ratios generally mirrored growth rates, transcription of genes involved in phosphate and nitrogen transport were negatively associated with growth rates. These data suggest that SAR11 genomospecies abundance varies in these estuaries because of differences in growth rates and metabolic capacities in response to changes in environmental conditions.ImportanceThe SAR11 clade is one of the most abundant bacterial groups in marine systems, including many estuaries. From the Delaware Bay and Chesapeake Bay environmental metagenomes, we reconstructed nearly complete SAR11 metagenome-assembled genomes representing ten genomospecies in four subclades, of which at least one is novel. Growth rate estimates of genomospecies correlated with functional gene repertoires of carbohydrate transporter and metabolism. Different SAR11 genomospecies dominated among the seasons, depending on their growth rates, biological productivity, and nutrient concentrations. Our RNAseq approach facilitated an understanding of the environmental controls on the abundance of SAR11 genomospecies in their natural habitat. This study is the first to combine multiple measures of diversity, abundance, functional potential, growth rates and activity of this important group, demonstrating a direct link between SAR11 genomospecies abundance and growth in the context of its environment.
An attempt to find the correlations between body weight and the composition of gut microbiota in Zhejiang and Shanghai
Authors: Xia Yihan , Jin Ziying 
Published: May 2022

AbstractPrevious studies showed that the human gut microbiota was associated with metabolic diseases, but the interaction and mechanism between the gut microbiota and metabolic disease are still unclear. In this study, the gut microbiota of 58 persons living in Zhejiang and Shanghai area will be analyzed. Then, the potential contribution of the human gut microbiota to obesity/high Body Mass Index (BMI) will be explored. The gut microbiota was studied by high throughput sequencing analysis of bacterial 16S rRNA gene fragments, and the gut microbiota samples with different BMI were compared. Meanwhile, some gut microorganisms from faeces of a healthy individual were cultivated and isolated, and the classification was identified by 16S rRNA sequencing. The main microbes in human gut microbiota were assigned to the phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Moreover, four strains were isolated from an individual fecal sample, of which one species was assigned to Escherichia fergusonii and the other three strains were assigned to Weissella cibaria. These four species belong to both abundant and low-abundant species revealed by high throughput sequencing. It was found that individuals with different BMI have different gut microbiota; while the differences are not significant. Also, the Firmicutes/Bacteroidetes ratio increases with the decrease of BMI, which is corresponding to previous results. In the future, more cohort gut microbiota in Zhejiang and Shanghai area will be collected and recovered, and the gut microbiota database of Zhejiang and Shanghai area will be built up in order to provide the basis for future gut microbiota modulation in this area.
Molecular basis of C9orf72 poly-PR interference with the β-karyopherin family of nuclear transport receptors
Authors: Jafarinia Hamidreza , Van der Giessen Erik , Onck Patrick R. 
Published: May 2022

AbstractNucleocytoplasmic transport (NCT) is affected in several neurodegenerative diseases including C9orf72-ALS. It has recently been found that arginine-containing dipeptide repeat proteins (R-DPRs), translated from C9orf72 repeat expansions, directly bind to several importins. To gain insight into how this can affect nucleocytoplasmic transport, we use coarse-grained molecular dynamics simulations to study the molecular interaction of poly-PR, the most toxic DPR, with several Kapβs (importins and exportins). We show that poly-PR–Kapβ binding depends on the net charge per residue (NCPR) of the Kapβ, salt concentration of the solvent, and poly-PR length. Poly-PR makes contact with the inner surface of most importins, which strongly interferes with Kapβ binding to cargo-NLS, IBB, and RanGTP in a poly-PR length-dependent manner. Longer poly-PRs at higher concentrations are also able to make contact with the outer surface of importins that contain several binding sites to FG-Nups. We also show that poly-PR binds to exportins, especially at lower salt concentrations, interacting with several RanGTP and FG-Nup binding sites. Overall, our results suggest that poly-PR might cause length-dependent defects in cargo loading, cargo release, Kapβ transport and Ran gradient across the nuclear envelope.
Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes
Authors: Arianti Rini , Vinnai Boglárka Ágnes , Győry Ferenc , Guba Andrea , Csősz Éva , Kristóf Endre , Fésüs László 
Published: May 2022

AbstractBrown/beige adipocytes express uncoupling protein-1 (UCP1) that enables them to dissipate energy as heat. Systematic activation of this process can alleviate obesity. Human brown adipose tissues are interspersed in distinct anatomical regions including deep neck. We found that UCP1 enriched adipocytes differentiated from precursors of this depot highly expressed ThTr2 transporter of thiamine and consumed thiamine during thermogenic activation of these adipocytes by cAMP which mimics adrenergic stimulation. Inhibition of ThTr2 led to lower thiamine consumption with decreased proton leak respiration reflecting reduced uncoupling. In the absence of thiamine, cAMP-induced uncoupling was diminished but restored by thiamine addition reaching the highest levels at thiamine concentrations larger than present in human blood plasma. Thiamine is converted to thiamine pyrophosphate (TPP) in cells; the addition of TPP to permeabilized adipocytes increased uncoupling fueled by TPP-dependent pyruvate dehydrogenase. ThTr2 inhibition also hampered cAMP-dependent induction of UCP1, PGC1a, and other browning marker genes, and thermogenic induction of these genes was potentiated by thiamine in a concentration dependent manner. Our study reveals the importance of amply supplied thiamine during thermogenic activation in human adipocytes which provides TPP for TPP-dependent enzymes not fully saturated with this cofactor and by potentiating the induction of thermogenic genes.Abstract FigureHighlightsAbundant thiamine is required for efficient activation of UCP1 dependent thermogenesis in human deep neck derived adipocytesInhibition of thiamine transporters leads to decreased thermogenic responseIn stimulated adipocytes, thiamine supply provides extra thiamine pyrophosphate for increasing pyruvate dehydrogenase activity to generate sufficient fuel of UCP1 dependent respirationAdrenergic stimulation of thermogenic gene expression is potentiated by thiamine in a concentration dependent manner
The mechanism underlying redundant functions of the YTHDF proteins
Authors: Zou Zhongyu , Sepich-Poore Caraline , Zhou Xiaoming , Wei Jiangbo , He Chuan 
Published: May 2022

AbstractThe YTH N6-methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N6-methyladenosine (m6A) on RNA. Recently, a report proposed that all YTHDFs work redundantly to facilitate RNA decay, raising questions about the exact functions of individual YTHDFs, especially YTHDF1 and YTHDF2. We show that YTHDF1 and YTHDF2 differ in their low-complexity domains (LCDs) and exhibit different behaviors in condensate formation and subsequent physiological functions. Biologically, we also find that the global stabilization of RNA after depletion of all YTHDFs is driven by increased P-body formation and is not strictly m6A dependent.
Gene family expansion and functional diversification of chitinase and chitin synthase genes in Atlantic salmon (Salmo salar)
Authors: Holen Matilde Mengkrog , Kent Matthew Peter , Vaaje-Kolstad Gustav , Sandve Simen Rød 
Published: May 2022

ABSTRACTBackgroundChitin is one of the most abundant polysaccharides in nature, forming important structures in insects, crustaceans, and fungal cell walls. Vertebrates on the other hand are generally considered “non-chitinous” organisms, despite having highly conserved chitin metabolism associated genes. Recent work has revealed that the largest group of vertebrates, the teleosts, have the potential to both synthesize and degrade endogenous chitin. Yet little is still known about the genes and proteins responsible for these dynamic processes. Here we used comparative genomics, transcriptomics, and chromatin accessibility data to characterize the repertoire, evolution, and regulation of genes involved in chitin-metabolism in teleosts, with a particular focus on Atlantic salmon.ResultsReconstruction of gene family phylogenies provide evidence for an expansion of teleost and salmonid chitinase and chitin synthase genes after multiple whole-genome duplications. Analyses of multi-tissue gene expression data demonstrated a strong bias of gastrointestinal tract expression for chitin metabolism genes, but with different spatial and temporal tissue specificities. Finally, we integrated transcriptomes from a developmental time series of the gastrointestinal tract with chromatin accessibility data to identify putative transcription factors responsible for regulating chitin-metabolism gene expression (CDX1 and CDX2) as well as tissue-specific divergence in the regulation of gene duplicates (FOXJ2). These transcription factors are also potential regulators of multiple glycosyltransferases being co-expressed with the chitin remodeling genes.ConclusionThe findings presented here add support to the hypothesis that chitin metabolism genes in teleosts play a role in developing and maintaining a chitin-based barrier in the teleost gut and provide a basis for further investigations into the molecular basis of this barrier.
Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells
Authors: Fowler Joseph W. , Zhang Rong , Tao Bo , Boutagy Nabil E. , Sessa William C. 
Published: May 2022

AbstractThere is a growing appreciation that a tight relationship exists between cholesterol homeostasis and immunity in leukocytes, however, this relationship has not been deeply explored in the vascular endothelium. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors to activate and recruit circulating leukocytes to the site of injury and aberrant activation of ECs leads to inflammatory based diseases, such as multiple sclerosis and atherosclerosis. Here, we studied the role of cholesterol and its master regulator, SREBP2, in the EC responses to inflammatory stress. Treatment of ECs with pro-inflammatory cytokines upregulates SREBP2 cleavage and cholesterol biosynthetic gene expression within the late phase of the acute inflammatory response. Furthermore, SREBP2 activation was dependent on NF-κB DNA binding and canonical SCAP-SREBP2 processing. Mechanistically, inflammatory activation of SREBP was mediated by a reduction in accessible cholesterol, leading to heightened sterol sensing and downstream SREBP2 cleavage. Detailed analysis of NF-κB inducible genes that may impact sterol sensing resulted in the identification of a novel RELA-inducible target, STARD10, that mediates accessible cholesterol homeostasis in ECs. Thus, this study provides an in-depth characterization of the relationship between cholesterol homeostasis and the acute inflammatory response in EC.
PKD autoinhibition in trans regulates activation loop autophosphorylation in cis
Authors: Reinhardt Ronja , Hirzel Kai , Link Gisela , Eisler Stephan A. , Hägele Tanja , Parson Matthew A.H. , Burke John E. , Hausser Angelika , Leonard Thomas A. 
Published: May 2022

SummaryPhosphorylation is a ubiquitous mechanism by which signals are transduced in cells. Protein kinases, enzymes that catalyze the phospho-transfer reaction are, themselves, often regulated by phosphorylation. Paradoxically, however, a substantial fraction of the more than 500 human protein kinases are capable of catalyzing their own activation loop phosphorylation. Commonly, these kinases perform this autophosphorylation reaction in trans, whereby transient dimerization leads to the mutual phosphorylation of the activation loop of the opposing protomer. In this study, we demonstrate that Protein Kinase D (PKD) is regulated by the inverse mechanism of dimerization-mediated trans-autoinhibition, followed by activation loop autophosphorylation in cis. We show that PKD forms a stable face-to-face homodimer that is incapable of either auto- or substrate phosphorylation. Dissociation of this trans-autoinhibited dimer results in activation loop autophosphorylation, which occurs exclusively in cis. Phosphorylation serves to increase PKD activity and prevent trans-autoinhibition, thereby switching PKD on. Our findings not only reveal the mechanism of PKD regulation, but have profound implications for the regulation of many other eukaryotic kinases.
Structure of the lysosomal membrane fusion machinery
Authors: Shvarev Dmitry , Schoppe Jannis , König Caroline , Perz Angela , Füllbrunn Nadia , Kiontke Stephan , Langemeyer Lars , Januliene Dovile , Schnelle Kilian , Kümmel Daniel , Fröhlich Florian , Moeller Arne , Ungermann Christian 
Published: May 2022

AbstractLysosomes are of central importance in cellular recycling, nutrient signaling1,2and endocytosis, and are tightly connected to autophagy3and the invasion of pathogenic bacteria and viruses1,4. Lysosomal fusion events are fundamental to cell survival and require HOPS, a conserved heterohexameric tethering complex5,6. HOPS recognizes and binds small membrane-associated GTPases on lysosomes and organelles, and assembles membrane bound SNAREs for fusion7,8. Through tethering, HOPS brings membranes in close proximity to each other and significantly increases fusion efficacy by catalysing SNARE assembly. Consequently, different HOPS mutations are causative for severe diseases6. Despite its fundamental cellular duties, it remained speculative how HOPS fulfils its function as high-resolution structural data were unavailable. Here, we used cryo-electron microscopy to reveal the structure of HOPS. In the complex, two central subunits form the backbone and an assembly hub for the functional domains. Two GTPase binding units extend to opposing ends, while the SNARE binding module points to the side, resulting in a triangular shape of the complex. Unlike previously reported, HOPS is surprisingly rigid and extensive flexibility is confined to its extremities. We show that HOPS complex variants with mutations proximal to the backbone can still tether membranes but fail to efficiently promote fusion indicating, that the observed integrity of HOPS is essential to its function. In our model, the core of HOPS acts as a counter bearing between the flexible GTPase binding domains. This positions the SNARE binding module exactly between the GTPase anchored membranes to promote fusion. Our structural and functional analysis reveals the link between the spectacular architecture of HOPS and its mechanism that couples membrane tethering and SNARE assembly, to catalyse lysosomal fusion.