Diffusion of intrinsically disordered proteins within viscoelastic membraneless droplets

In living cells, intrinsically disordered proteins (IDPs), such as FUS and DDX4, undergo phase separation, forming biomolecular condensates. Using molecular dynamics simulations, we investigate their behavior in their respective homogenous droplets. We find that the proteins exhibit transient subdiffusion due to the viscoelastic nature and confinement effects in the droplets. The conformation and the instantaneous diffusivity of the proteins significantly vary between the interior and the interface of the droplet, resulting in non-Gaussianity in the displacement distributions. This study highlights key aspects of IDP behavior in biomolecular condensates

World Health Organization critical priority Escherichia coli clone ST648 in magnificent frigatebird (Fregata magnificens) of an uninhabited insular environment

Antimicrobial resistance is an ancient natural phenomenon increasingly pressured by anthropogenic activities. Escherichia coli has been used as markers of environmental contamination and human-related activity. Seabirds may be bioindicators of clinically relevant bacterial pathogens and their antimicrobial resistance genes, including extended-spectrum-beta-lactamase (ESBL) and/or plasmid-encoded AmpC (pAmpC), in anthropized and remote areas. We evaluated cloacal swabs of 20 wild magnificent frigatebirds (Fregata magnificens) of the Alcatrazes Archipelago, the biggest breeding colony of magnificent frigatebirds in the southern Atlantic and a natural protected area with no history of human occupation, located in the anthropized southeastern Brazilian coast. We characterized a highly virulent multidrug-resistant ST648 (O153:H9) pandemic clone, harboring bla, bla, qnrB, tetB, sul1, sul2, aadA1, aac(3)-VIa and mdfA, and virulence genes characteristic of avian pathogenic (APEC) (hlyF, iroN, iss, iutA, and ompT) and other extraintestinal E. coli (ExPEC) (chuA, kpsMII, and papC). To our knowledge, this is the first report of ST648 E. coli co-producing ESBL and pAmpC in wild birds inhabiting insular environments. We suggest this potentially zoonotic and pathogenic lineage was likely acquired through indirect anthropogenic contamination of the marine environment, ingestion of contaminated seafood, or by intra and/or interspecific contact. Our findings reinforce the role of wild birds as anthropization sentinels in insular environments and the importance of wildlife surveillance studies on pathogens of critical priority classified by the World Health Organization

Use of Lichen and Moss in Assessment of Forest Contamination with Heavy Metals in Praded and Glacensis Euroregions (Poland and Czech Republic)

The concentrations of selected metals—Cr, Ni, Cu, Zn, Cd, and Pb—were determined in the samples of Hypogymnia physodes lichen and Pleurozium schreberi moss collected in Polish and Czech Euroregions Praded and Glacensis. More specifically, the samples were collected in Bory Stobrawskie, Bory Niemodlińskie, and Kotlina Kłodzka (Poland) and in Jeseniki (Czech Republic). The concentration of metals in the samples was measured using the atomic absorption spectrometry (flame AAS technique and electrothermal atomization AAS technique). The results were used to calculate the comparison factor (CF) that quantifies the difference in concentration of a given bioavailable analyte × accumulated in lichens and mosses: CF = 2 (cx,lichen − cx,moss) (cx,lichen + cx,moss)−1. The values of CF greater than 0.62 indicate the most probable location of heavy metals deposited in the considered area. In this work, the method was used to show a significant contribution of urban emissions to the deposition of heavy metals in the area of Bory Stobrawskie and in the vicinity of Kłodzko City

WHO Critical Priority Escherichia coli as One Health Challenge for a Post-Pandemic Scenario: Genomic Surveillance and Analysis of Current Trends in Brazil.

The dissemination of carbapenem-resistant and third generation cephalosporin-resistant pathogens is a critical issue that is no longer restricted to hospital settings. The rapid spread of critical priority pathogens in Brazil is notably worrying, considering its continental dimension, the diversity of international trade, livestock production, and human travel. We conducted a nationwide genomic investigation under a One Health perspective that included Escherichia coli strains isolated from humans and nonhuman sources, over 45 years (1974-2019). One hundred sixty-seven genomes were analyzed extracting clinically relevant information (i.e., resistome, virulome, mobilome, sequence types [STs], and phylogenomic). The endemic status of extended-spectrum β-lactamase (ESBL)-positive strains carrying a wide diversity of variants, and the growing number of colistin-resistant isolates carrying -type genes was associated with the successful expansion of international ST10, ST38, ST115, ST131, ST354, ST410, ST648, ST517, and ST711 clones; phylogenetically related and shared between human and nonhuman hosts, and polluted aquatic environments. Otherwise, carbapenem-resistant ST48, ST90, ST155, ST167, ST224, ST349, ST457, ST648, ST707, ST744, ST774, and ST2509 clones from human host harbored and genes. A broad resistome to other clinically relevant antibiotics, hazardous heavy metals, disinfectants, and pesticides was further predicted. Wide virulome associated with invasion/adherence, exotoxin and siderophore production was related to phylogroup B2. The convergence of wide resistome and virulome has contributed to the persistence and rapid spread of international high-risk clones of critical priority E. coli at the human-animal-environmental interface, which must be considered a One Health challenge for a post-pandemic scenario. A One Health approach for antimicrobial resistance must integrate whole-genome sequencing surveillance data of critical priority pathogens from human, animal and environmental sources to track hot spots and routes of transmission and developing effective prevention and control strategies. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we present genomic data of WHO critical priority carbapenemase-resistant, ESBL-producing, and/or colistin-resistant Escherichia coli strains isolated from humans and nonhuman sources in Brazil, a country with continental proportions and high levels of antimicrobial resistance. The present study provided evidence of epidemiological and clinical interest, highlighting that the convergence of wide virulome and resistome has contributed to the persistence and rapid spread of international high-risk clones of E. coli at the human-animal-environmental interface, which must be considered a One Health threat that requires coordinated actions to reduce its incidence in humans and nonhuman hosts

Systematic target function annotation of human transcription factors

Abstract Background Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs. Result We compiled a human gene regulatory network for 384 TFs covering the 146,096 TF–target gene (TF–TG) relationships, extracted from over 850 ChIP-seq experiments as well as the literature. By integrating this network of TF–TF and TF–TG relationships with 3715 functional concepts from six sources of gene function annotations, we obtained over 9000 confident functional annotations for 279 TFs. We observe extensive connectivity between TFs and Mendelian diseases, GWAS phenotypes, and pharmacogenetic pathways. Further, we show that TFs link apparently unrelated functions, even when the two functions do not share common genes. Finally, we analyze the pleiotropic functions of TFs and suggest that the increased number of upstream regulators contributes to the functional pleiotropy of TFs. Conclusion Our computational approach is complementary to focused experimental studies on TF functions, and the resulting knowledge can guide experimental design for the discovery of unknown roles of TFs in human disease and drug response

Metabolic syndrome after kidney transplantation.

BACKGROUND: Metabolic syndrome (MS) includes some risk factors for development of diabetes and cardiovascular disease, obesity (BMI > 30), high triglycerides, low HDL cholesterol, hypertension and impaired glucose tolerance. Following the definition of the Adult Treatment Panel III criteria, a diagnosis of MS was established when 3 or more factors were present. In renal transplant patients MS has been reported to negatively influence both patient and graft survivals. The present study sought to verify the effect of MS among our cases. METHODS: 298 cadaveric renal transplant recipients operated between January 1, 1996 and December 31, 2001 with absence of diabetes before transplantation, stable renal function 1 year posttransplantation and at least 4 years follow up were retrospectively evaluated from the end of the first post-operative year. RESULTS: 50 patients out of 298 (16,7%) had MS at the beginning of the study, including 37 of them with 3 and 13 with 4 risk factors. Only one patient with MS died of cardiovascular disease. Graft failure was observed in 23.5% MS patients versus 9,7% patients without the Syndrome (p:n.s.) Only Creatinine and the incidence of Cardiovascular Diseases at 4 years were statistically higher in MS patients (P < .001). CONCLUSIONS: These results suggested that MS is a risk factor for increasing CVD morbidity and decreased graft function, but early treatment of risk factors as soon as they become apparent can limit the adverse effects on patient and graft survival