bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Dextran Sodium Sulfate-Induced Ulcerative Colitis
Authors: Li Mingyue , Guo Weina , Dong Yalan , Wang Wenzhu , Tian Chunxia , Zhang Zili , Yu Ting , Zhou Haifeng , Gui Yang , Xue Kaming , Li Junyi , Jiang Feng , Sarapultsev Alexey , Luo Shanshan , Fan Heng , Hu Desheng
Published: September 2021

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.
A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy
Authors: Mannuthodikayil Jamsad , Sinha Suman , Singh Sameer , Biswas Anamika , Ali Irshad , Mashurabad Purna Chandra , Tabassum Wahida , Vydyam Pratap , Bhattacharyya Mrinal Kanti , Mandal Kalyaneswar
Published: September 2021

Inhibition of tight junction formation between two malaria parasite proteins, apical membrane antigen 1 and rhoptry neck protein 2, crucial for red blood cell invasion, prevents the disease progression. In this work, we have utilized a unique approach to design a chimeric peptide, prepared by fusion of the best features of two peptide inhibitors, that has displayed parasite growth inhibition, in-vitro, with nanomolar IC50, which is hundredfold better than any of its parent peptides. Further, to gain structural insights, we computationally modeled the hybrid peptide on its receptor.
Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and drug resistance
Authors: Rai Maruti Nandan , Parsania Chirag , Rai Rikky , Shirgaonkar Niranjan , Tan Kaeling , Wong Koon Ho
Published: September 2021

Candida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophage with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects azole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabrata’s survival in macrophages and drug tolerance.
Influenza A virus undergoes compartmentalized replication in vivo dominated by stochastic bottlenecks
Authors: Amato Katherine A. , Haddock Luis A. , Braun Katarina M. , Meliopoulos Victoria , Livingston Brandi , Honce Rebekah , Schaack Grace A. , Boehm Emma , Higgins Christina A. , Barry Gabrielle L. , Koelle Katia , Schultz-Cherry Stacey , Friedrich Thomas C. , Mehle Andrew
Published: September 2021

Transmission of influenza A viruses (IAV) between hosts is subject to numerous physical and biological barriers that impose genetic bottlenecks, constraining viral diversity and adaptation. The presence of bottlenecks within individual hosts and their potential impacts on evolutionary pathways taken during infection and subsequent transmission are poorly understood. To address this knowledge gap, we created highly diverse IAV libraries bearing molecular barcodes on two independent gene segments, enabling high-resolution tracking and quantification of unique virus lineages within hosts. Here we show that IAV infection in lungs is characterized by multiple within-host bottlenecks that result in “islands” of infection in lung lobes, each with genetically distinct populations. We performed site-specific inoculation of barcoded IAV in the upper respiratory tract of ferrets and tracked viral diversity as infection spread to the trachea and lungs. We observed compartmentalized replication of discrete barcoded populations within the lobes of the lung. Bottlenecks stochastically sampled individual viruses from the upper respiratory tract or the trachea that became the dominant genotype in a particular lobe. These populations are shaped strongly by founder effects, with no evidence for positive selection. The segregated sites of replication highlight the jackpot-style events that contribute to within-host influenza virus evolution and may account for low rates of intrahost adaptation.
Long-term experimental evolution decouples size and production costs in Escherichia coli
Authors: Marshall Dustin J. , Malerba Martino , Lines Thomas , Sezmis Aysha L. , Hasan Chowdhury M. , Lenski Richard E. , McDonald Michael J.
Published: September 2021

Body size covaries with population dynamics across life’s domains. Theory holds that metabolism imposes fundamental constraints on the coevolution of size and demography. However, studies of interspecific patterns are confounded by other factors that covary with size and demography, and experimental tests of the causal links remain elusive. Here we leverage a 60,000-generation experiment in which Escherichia coli populations evolved larger cells to examine intraspecific metabolic scaling and correlations with demographic parameters. Metabolic theory successfully predicted the relations among size, metabolism, and maximum population density, with strong support for Damuth’s law of energy equivalence in this experiment. In contrast, populations of larger cells grew faster than those of smaller cells, contradicting the fundamental assumption that costs of production should increase proportionately with size. The finding that the costs of production are substantially decoupled from size requires re-examining the evolutionary drivers and ecological consequences of biological size more generally.