bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin-1 and Galectin-3 Expression in Lesional Skin of Patients With Systemic Sclerosis—Association With Disease Severity
Authors: Mora Gabriela Fernanda , Zubieta Mariana Rodríguez 
Published: June 2020

Galectin-1 (Gal-1) and galectin-3 (Gal-3) are carbohydrate-binding proteins involved in normal processes, autoimmunity, and cancer. Increased serum Gal-3 levels in scleroderma were associated with active disease, vasculopathy, and mortality.

Objectives
The aim of this study was to evaluate Gal-1 and Gal-3 expression in the lesional skin of patients with scleroderma regarding disease severity and organ involvement.

Methods
A cross-sectional study was conducted on patients diagnosed as systemic sclerosis (SSc), after informed consent. Clinical and serological profiles were reviewed from medical records. Lesional skin biopsies were taken by losange incision from patients. Samples were analyzed by immunohistochemistry and compared with normal skin of a healthy patient. Parametric statistical analysis was done with Student t test and Pearson coefficient. Significance was established as p ≤ 0.05 with a 95% confidence interval.

Results
Biopsies of 10 patients and a healthy control (9 female, 1 male) were analyzed. The mean age was 54.5 years (18–74 years). Four of 10 patients had diffuse, 4 had limited scleroderma, 1 had overlap syndrome, and 1 had sclerodermiform graft-versus-host disease. The mean fibroblasts count per field was 13.2 in scleroderma versus 7.2 in normal skin. The mean expression of Gal-1 in scleroderma fibroblasts was 13% (0%–56%) and 47.5% for Gal-3 (6.5%–95.5%); in normal skin, the mean expression was 91% (90%–95%) for Gal-1 and 97% (89%–100%) for Gal-3. A higher Gal-3 expression in scleroderma (within its lower expression compared with normal skin) was associated with pulmonary artery hypertension (p = 0.004) and to a higher modified Rodnan's skin score (p = 0.0003). In a similar manner, anti–centromere antibodies were associated with a higher Gal-1 expression in SSc skin fibroblasts (p = 0.04).

Conclusions
Gal-1 and Gal-3 had a lower expression in scleroderma lesional skin compared with a normal control. We found a significant correlation between a higher Gal-3 expression (within the lower ones compared with normal skin) in fibroblasts from SSc patients and severe disease (pulmonary hypertension and a higher modified Rodnan's skin score) compared with patients with lower expression of this protein. Similarly, the presence of anti–centromere antibodies was associated with a higher expression of Gal-1 within this group of patients.
Flavobacterium alkalisoli sp. nov., isolated from rhizosphere soil of Suaeda salsa
Authors: Xu Lian , Wang Hai-Tao , Zhang Jin-Xin , Zhang Hui , Wang Shuai , Sun Ji-Quan 
Published: June 2020

A Gram-negative, strictly aerobic, gliding motility, none-spore forming, yellow, rods bacterial strain, designated XS-5T, was isolated from rhizosphere soil of Suaeda salsa, in Tumd Right Banner, Inner Mongolia, PR China. A phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree both showed that strain XS-5T clustered with

Flavobacterium beibuense

F44-8T (shared 97.2 % of 16S rRNA gene similarity) and

Flavobacterium rakeshii

FCS-5T (97.6 %), and shared <96.0 % of 16S rRNA gene similarities with all other type strains. Strain XS-5T contained MK-6 as the major respiratory quinone. Its major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified lipid; and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0, iso-C15 : 0 3-OH, Summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1
ω7c), and Summed feature 9 (iso-C17 : 1
ω9c and/or C16 : 0 10-methyl). The genome consisted of a 3 985 855 bp circular chromosome, with a G+C content of 37.9 mol%, predicting 3616 coding sequences genes, 45 tRNA genes and three rRNA operons. The average nucleotide identity, amino acid identity and digital DNA–DNA hybridization values of strain XS-5T to

F. beibuense

F44-8T and

F. rakeshii

FCS-5T were 79.2 and 79.2 %, 81.7 and 81.6 %, 22.3 and 22.2 %, respectively. The results of phylogenetic, physiological and biochemical tests allowed the discrimination of strain XS-5T from its phylogenetic relatives. Flavobacterium alkalisoli sp. nov. is therefore proposed with strain XS-5T (=CGMCC 1.17077T=KCTC 72459T) as the type strain.
An exploration of the SARS-CoV-2 spike receptor binding domain (RBD) – a complex palette of evolutionary and structural features
Authors: Sanyal Dwipanjan , Chowdhury Sourav , Uversky Vladimir N. , Chattopadhyay Krishnananda 
Published: June 2020

AbstractSARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.
The Sequenced Genomes of Non-Flowering Land Plants Reveal the (R)Evolutionary History of Peptide Signaling
Authors: Furumizu Chihiro , Krabberød Anders K. , Hammerstad Marta , Alling Renate M. , Wildhagen Mari , Sawa Shinichiro , Aalen Reidunn B. 
Published: June 2020

AbstractAn understanding of land plant evolution is a prerequisite for in-depth knowledge of plant biology. Here we extract and explore information hidden in the increasing number of sequenced plant genomes, from bryophytes to angiosperms, to elucidate a specific biological question – how peptide signaling evolved. To conquer land and cope with changing environmental conditions, plants have gone through transformations that must have required a revolution in cell-to-cell communication. We discuss peptides mediating endogenous and exogenous changes by interaction with receptors activating intracellular molecular signaling. Signaling peptides were discovered in angiosperms and operate in tissues and organs like flowers, seeds, vasculature, and 3D meristems that are not universally conserved across land plants. Nevertheless, orthologues of angiosperm peptides and receptors have been identified in non-flowering plants. These discoveries provoke questions regarding the co-evolution of ligands and their receptors, and whetherde novointeractions in peptide signaling pathways may have contributed to generate novel traits in land plants. The answers to such questions will have profound implications for the understanding of evolution of cell-to-cell communication and the wealth of diversified terrestrial plants. Under this perspective we have generated, analyzed and reviewed phylogenetic, genomic, structural, and functional data to elucidate the evolution of peptide signaling.
Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer’s disease
Authors: Yang Hongtian Stanley , Onos Kristen D. , Choi Kwangbom , Keezer Kelly J. , Skelly Daniel A. , Carter Gregory W. , Howell Gareth R. 
Published: June 2020

AbstractMicroglia are now considered drivers of Alzheimer’s disease (AD) pathology. However, single-cell RNA-sequencing (scRNA-seq) of microglia in mice, a key preclinical model organsim, have shown mixed results regarding translatability to human studies. To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains WSB/EiJ, CAST/EiJ and PWK/PhJ carryingAPP/PS1was performed and demonstrated that genetic diversity significantly altered features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis. There was significant variation in abundance of microglial subpopulations, including numbers of disease-associated microglia and interferon-responding microglia across the strains. Further, for each subpopulation, significant gene expression differences were observed between strains, and relative to B6 that included nineteen genes previously associated with human AD includingApoe, Trem2, Bin1andSorl1. This resource will be critical in the development of appropriately targeted therapeutics for AD and a range of other neurological diseases.
Intestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomy
Authors: Bozadjieva Kramer Nadejda , Shin Jae Hoon , Shao Yikai , Gutierrez-Aguilar Ruth , Li Ziru , Heppner Kristy M. , Chiang Samuel , Vargo Sara G. , Granger Katrina , Sandoval Darleen A. , MacDougald Ormond A , Seeley Randy J. 
Published: June 2020

AbstractBariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive, but provide the most effective long-term metabolic improvements in obese and Type 2 diabetic patients. These powerful effects of manipulating the gastrointestinal tract point to an important role of gastrointestinal signals in regulating both energy balance and metabolism. To that end, we have used mouse models of VSG to identify key gut signals that mediate these beneficial effects. Preliminary data from our rodent model of VSG led us to hypothesize a potential role for the hormone Fibroblast-Growth Factor15/19 (mouse/human ortholog) which pharmacologically can regulate many aspects of energy homeostasis and glucose handling. FGF15 is expressed in ileal enterocytes of the small intestine and is released postprandially. Like many other gut hormones, postprandial plasma levels in humans and ileal FGF15 expression in mice increase after VSG. We generated intestinal-specific FGF15 knock out (VilCreERT2; Fgf15f/f) mice and controls, which were maintained on 60% high-fat diet. Interestingly, ablation of intestinal FGF15 in adult mice results in little change to body weight or glucose regulation when challenged with a high-fat diet. Unlike what we had predicted, intestinal-specific FGF15 knock out mice lost more weight after VSG and this was a result of increased lean tissue loss compared to control mice. Further, the loss of bone mineral density observed after VSG in control mice was increased in intestinal-specific FGF15 knock out mice. Finally the effect of VSG to reduce hepatic cholesterol was also absent in intestinal-specific FGF15 knock out mice. These data point to an important role for intestinal FGF15 to protect the organism from deleterious effects of rapid weight loss that occurs after VSG.
Resuscitation of the microbial seed bank alters plant-soil interactions
Authors: Kuo Venus , Lehmkuhl Brent K. , Lennon Jay T. 
Published: June 2020

ABSTRACTWhile microorganisms are recognized for driving belowground processes that influence the productivity and fitness of plant populations, the vast majority of bacteria and fungi in soil belong to a seed bank consisting of dormant individuals. Still, plant performance may be affected by microbial dormancy through its effects on the activity, abundance, and diversity of soil microorganisms. To test how microbial seed banks influence plant-soil interactions, we purified recombinant resuscitation promoting factor (Rpf), a bacterial protein that terminates dormancy. Then, in a factorially designed experiment, we applied the Rpf to soil containing field mustard (Brassica rapa), an agronomically important plant species. Plant biomass was ~33 % lower in the Rpf treatment compared to plants grown with an unmanipulated microbial seed bank. In addition, Rpf reduced soil respiration, decreased bacterial abundance, and increased fungal abundance. These effects of Rpf on plant performance were accompanied by shifts in bacterial community composition, which may have diluted mutualists or resuscitated pathogens. Our findings suggest that changes in microbial seed banks may influence the magnitude and direction of plant-soil feedbacks in ways that affect above- and below-ground biodiversity and function.
Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid
Authors: Dandage Rohan , Berger Caroline M. , Gagnon-Arsenault Isabelle , Moon Kyung-Mee , Stacey Richard Greg , Foster Leonard J. , Landry Christian R. 
Published: June 2020

AbstractHybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species,Saccharomyces cerevisiaeandSaccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for prefoldin complex. We also identify instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.
Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α
Authors: Mann Shivani N. , Hadad Niran , Nelson-Holte Molly , Rothman Alicia R. , Sathiaseelan Roshini , Ali-Mondal Samim , Agbaga Martin-Paul , Unnikrishnan Archana , Subramaniam Malayannan , Hawse John , Huffman Derek M. , Freeman Willard M. , Stout Michael B. 
Published: June 2020

ABSTRACTMetabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 acts primarily through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.
CASTLE: Cell Adhesion with Supervised Training and Learning Environment
Authors: Gilbert S G , Krautter F , Cooper D , Chimen M , Iqbal A J , Spill F 
Published: June 2020

AbstractDifferent types of microscopy are used to uncover signatures of cell adhesion and mechanics. Automating the identification and analysis often involve sacrificial routines of cell manipulation such asin vitrostaining. Phase-contrast microscopy (PCM) is rarely used in automation due to the difficulties with poor quality images. However, it is the least intrusive method to provide insights into the dynamics of cells, where other types of microscopy are too destructive to monitor. In this study, we propose an efficient workflow to automate cell counting and morphology in PCM images. We introduce Cell Adhesion with Supervised Training and Learning Environment (CASTLE), available as a series of additional plugins to ImageJ. CASTLE combines effective techniques for phase-contrast image processing with statistical analysis and machine learning algorithms to interpret the results. The proposed workflow was validated by comparing the results to a manual count and manual segmentation of cells in images investigating different adherent cell types, including monocytes, neutrophils and platelets. In addition, the effect of different molecules on cell adhesion was characterised using CASTLE. For example, we demonstate that Galectin-9 leads to differences in adhesion of leukocytes. CASTLE also provides information using machine learning techniques, namely principal component analysis andk-means clustering, to distinguish morphology currently inaccessible with manual methods. All scripts and documentation is open-source and available at the corresponding GitLab project.
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes
Authors: Jungreis Irwin , Sealfon Rachel , Kellis Manolis 
Published: June 2020

SummaryDespite its overwhelming clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. Here, we use comparative genomics to provide a high-confidence protein-coding gene set, characterize protein-level and nucleotide-level evolutionary constraint, and prioritize functional mutations from the ongoing COVID-19 pandemic. We select 44 complete Sarbecovirus genomes at evolutionary distances ideally-suited for protein-coding and non-coding element identification, create whole-genome alignments, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for all named genes and for 3a, 6, 7a, 7b, 8, 9b, and also ORF3c, a novel alternate-frame gene. By contrast, ORF10, and overlapping-ORFs 9c, 3b, and 3d lack protein-coding signatures or convincing experimental evidence and are not protein-coding. Furthermore, we show no other protein-coding genes remain to be discovered. Cross-strain and within-strain evolutionary pressures largely agree at the gene, amino-acid, and nucleotide levels, with some notable exceptions, including fewer-than-expected mutations in nsp3 and Spike subunit S1, and more-than-expected mutations in Nucleocapsid. The latter also shows a cluster of amino-acid-changing variants in otherwise-conserved residues in a predicted B-cell epitope, which may indicate positive selection for immune avoidance. Several Spike-protein mutations, including D614G, which has been associated with increased transmission, disrupt otherwise-perfectly-conserved amino acids, and could be novel adaptations to human hosts. The resulting high-confidence gene set and evolutionary-history annotations provide valuable resources and insights on COVID-19 biology, mutations, and evolution.
Single cell profiling of total RNA using Smart-seq-total
Authors: Isakova Alina , Neff Norma , Quake Stephen R. 
Published: June 2020

ABSTRACTThe ability to interrogate total RNA content of single cells would enable better mapping of the transcriptional logic behind emerging cell types and states. However, current RNA-seq methods are unable to simultaneously monitor both short and long, poly(A)+ and poly(A)-transcripts at the single-cell level, and thus deliver only a partial snapshot of the cellular RNAome. Here, we describe Smart-seq-total, a method capable of assaying a broad spectrum of coding and non-coding RNA from a single cell. Built upon the template-switch mechanism, Smart-seq-total bears the key feature of its predecessor, Smart-seq2, namely, the ability to capture full-length transcripts with high yield and quality. It also outperforms current poly(A)–independent total RNA-seq protocols by capturing transcripts of a broad size range, thus, allowing us to simultaneously analyze protein-coding, long non-coding, microRNA and other non-coding RNA transcripts from single cells. We used Smart-seq-total to analyze the total RNAome of human primary fibroblasts, HEK293T and MCF7 cells as well as that of induced murine embryonic stem cells differentiated into embryoid bodies. We show that simultaneous measurement of non-coding RNA and mRNA from the same cell enables elucidation of new roles of non-coding RNA throughout essential processes such as cell cycle or lineage commitment. Moreover, we show that cell types can be distinguished based on the abundance of non-coding transcripts alone.
Structural ordering of thePlasmodium bergheicircumsporozoite protein repeats by inhibitory antibody 3D11
Authors: Kucharska Iga , Thai Elaine , Srivastava Ananya , Rubinstein John , Pomès Régis , Julien Jean-Philippe 
Published: June 2020

ABSTRACTPlasmodiumsporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 – the leading malaria vaccine againstP. falciparum(Pf) – has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of otherPlasmodiumspecies via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding toP. bergheiCSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats ofPlasmodiumsporozoites.
The derlin Dfm1 promotes retrotranslocation of folded protein domains from the endoplasmic reticulum
Authors: Fonseca Daniel , Carvalho Pedro 
Published: June 2020

AbstractEndoplasmic reticulum (ER) proteins are degraded by proteasomes in the cytosol through ER-associated degradation (ERAD). This process involves retrotranslocation of substrates across the ER membrane, their ubiquitination and subsequent membrane extraction by the Cdc48/Npl4/Ufd1 ATPase complex prior delivery to proteasomes for degradation. Recently a mechanism for the retrotranslocation of misfolded substrates by the Hrd1 ubiquitin ligase complex was described. However, how substrates with folded luminal domains are retrotranslocated remains unknown. Here, we identify Dfm1 as an essential membrane component for the retrotranslocation of proteins with folded luminal domains. Both Dfm1 intramembrane rhomboid-like and the cytosolic Cdc48-binding domains are essential for substrate retrotranslocation. Substrate processing by Dfm1 and Cdc48 complex requires the ubiquitin shuttle factors Rad23/Dsk2 and the multi-ubiquitination enzyme Ufd2. Our findings suggest a pathway in which a series of ubiquitin modifying factors recruit Dfm1 to resolve a stalled retrotranslocation intermediate due to the presence of a folded luminal domain.