Molecular Physiology and Pathophysiology of Tight Junctions V. Assault of the tight junction by enteric pathogens

2000 ◽  
Vol 279 (6) ◽  
pp. G1129-G1134 ◽  
Author(s):  
Cynthia L. Sears
Keyword(s):  
Tight Junction ◽  
Virulence Factors ◽  
Enteric Pathogens ◽  
Junctional Complex ◽  
Polymorphonuclear Cells ◽  
Human Pathogens ◽  
Molecular Physiology ◽  
Novel Approach ◽  
Cellular Signal ◽  
The Impact

Studies of the impact of enteric pathogens and their virulence factors on the proteins comprising the tight junction and zonula adherens offer a novel approach to dissection of tight junctional complex regulation. Most studies to date provide only tantalizing clues that select pathogens may indeed assault the tight junctional complex. Information on critical human pathogens such as Campylobacter jejuni and Shigella and Salmonella subspecies is lacking. Mechanistic studies are currently sparse, but available results on pathogenic Escherichia coli and specific virulence factors such as the Rho-modifying and protease bacterial toxins indicate four major mechanisms by which these pathogens may act: 1) direct cleavage of tight junctional structural proteins; 2) modification of the actin cytoskeleton; 3) activation of cellular signal transduction; and 4) triggering transmigration of polymorphonuclear cells across the epithelial cell barrier. New therapeutics may evolve from detailed studies of these pathogens and the cellular processes and proteins they disrupt.

GENETIC SUSCEPTIBILITY TO IBD OPERATES VIA CONTROL OF APICAL JUNCTIONAL COMPLEXES

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Isabelle Hébert-Milette ◽  
Chloé Lévesque ◽  
Guy Charron ◽  
John Rioux
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Intestinal Inflammation ◽  
Protein Localization ◽  
Junctional Complex ◽  
Epithelial Permeability ◽  
3D Cultures ◽  
Apical Junctional Complex ◽  
Junction Protein ◽  
The Impact

Abstract Introduction Intestinal permeability is increased in unaffected 1st degree relatives of patients with inflammatory bowel disease (IBD), and is considered a risk factor for the development of IBD, likely increasing the interactions between intestinal microorganisms and the immune system. We recently reported that C1orf106, a gene located within a genomic region associated with IBD, regulates epithelial permeability. We further demonstrated that a rare coding variant within C1orf106 (p.Y333F) decreases protein stability and that lower levels of C1orf106 protein leads altered stability of adherens junctions (AJ) and to an increase in epithelial permeability. Hypothesis In addition to altering AJ, we believe that C1orf106 is also involved in the regulation of tight junction (TJ) formation, which also impacts epithelial permeability. Objectives The objectives of the project are to (a) validate the impact of C1orf106 on tight junctions and (b) verify the impact of C1orf106 IBD-associated variants on intestinal barrier integrity. Results We observed that knocking down the expression of C1orf106 in Caco-2 cells leads to a number of phenotypes in human epithelial monolayer (2D) and spheroid (3D) cultures that are associated with alterations in TJs. Specifically, when studying the dynamic reformation of TJ in 2D cultures after transient withdrawal of calcium, which is required for TJ stability, we observed that lower levels of C1orf106 resulted in (1) decreased recovery of barrier function as measured by transepithelial electrical resistance (TEER); (2) an alteration of tight junction protein localization; and (3) thickening of the circumferential actin belt. Moreover, in 3D cultures, we observed an altered spheroid formation associated with impaired epithelial polarization. In addition, our preliminary studies of human induced pluripotent stem cell (hiPSC)-derived epithelial cultures support that Y333F heterozygotes also have altered structure and function of their tight junctions. Conclusion Our observations indicate an important role of C1orf106 in apical junctional complex (AJC) formation likely mediated by a regulation of the circumferential actin belt. This can affect other functions of AJC, like the establishment of cell polarity. AJC formation is important for epithelial repair after an injury and its dysregulation impairs the formation of an impermeable epithelial barrier, which likely facilitates the passage of microorganisms and the induction and maintenance of intestinal inflammation.

Identification of human enteric pathogens in gull feces at Southwestern Lake Michigan bathing beaches

2008 ◽  
Vol 54 (12) ◽  
pp. 1006-1015 ◽  
Author(s):  
Julie Kinzelman ◽  
Sandra L. McLellan ◽  
Ashley Amick ◽  
Justine Preedit ◽  
Caitlin O. Scopel ◽  
...  
Keyword(s):  
Water Quality ◽  
Human Health ◽  
Human Health Risk ◽  
Enteric Pathogens ◽  
Human Pathogens ◽  
Fecal Indicator ◽  
Fecal Samples ◽  
Bathing Waters ◽  
Microbiological Methods ◽  
The Impact

Ring-billed ( Larus delawarensis Ord, 1815) and herring ( Larus argentatus Pontoppidan, 1763) gulls are predominant species of shorebirds in coastal areas. Gulls contribute to the fecal indicator burden in beach sands, which, once transported to bathing waters, may result in water quality failures. The importance of these contamination sources must not be overlooked when considering the impact of poor bathing water quality on human health. This study examined the occurrence of human enteric pathogens in gull populations at Racine, Wisconsin. For 12 weeks in 2004 and 2005, and 7 weeks in 2006, 724 gull fecal samples were examined for pathogen occurrence on traditional selective media (BBL CHROMagar-Salmonella, Remel Campy-BAP, 7% horse blood agar) or through the use of novel isolation techniques ( Campylobacter , EC FP5-funded CAMPYCHECK Project), and confirmed using polymerase chain reaction (PCR) for pathogens commonly harbored in gulls. An additional 226 gull fecal samples, collected in the same 12-week period in 2004, from a beach in Milwaukee, Wisconsin, were evaluated with standard microbiological methods and PCR. Five isolates of Salmonella (0.7%), 162 (22.7%) isolates of Campylobacter, 3 isolates of Aeromonas hydrophila group 2 (0.4%), and 28 isolates of Plesiomonas shigelloides (3.9%) were noted from the Racine beach. No occurrences of Salmonella and 3 isolates of Campylobacter (0.4%) were found at the Milwaukee beach. A subset of the 2004 samples was also examined for Giardia and Cryptosporidium and was found to be negative. Information as to the occurrence of human pathogens in beach ecosystems is essential to design further studies assessing human health risk and to determine the parameters influencing the fate and transport of pathogens in the nearshore environment.

scholarly journals Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1497
Author(s):  
Pansong Zhang ◽  
Qiao Guo ◽  
Zhihua Wei ◽  
Qin Yang ◽  
Zisheng Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mammalian Cells ◽  
Secretion System ◽  
Chinese Herbs ◽  
Infection Model ◽  
Lung Pathology ◽  
Promising Alternative ◽  
The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

scholarly journals The impact of bZIP Atf1ortholog global regulators in fungi

2021 ◽  
Author(s):  
Éva Leiter ◽  
Tamás Emri ◽  
Klaudia Pákozdi ◽  
László Hornok ◽  
István Pócsi
Keyword(s):  
Transcription Factors ◽  
Stress Response ◽  
Secondary Metabolite ◽  
Plant Pathogens ◽  
Leucine Zipper ◽  
Secondary Metabolite Production ◽  
Special Focus ◽  
Human Pathogens ◽  
Metabolite Production ◽  
The Impact

Abstract Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. Key points • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.

scholarly journals Brain drain and brain gain in Russia: Analyzing international migration of researchers by discipline using Scopus bibliometric data 1996–2020

2021 ◽  
Author(s):  
Alexander Subbotin ◽  
Samin Aref
Keyword(s):  
Brain Drain ◽  
Policy Development ◽  
Donor Country ◽  
International Mobility ◽  
Science System ◽  
Migration Rates ◽  
Net Migration ◽  
Novel Approach ◽  
Five Disciplines ◽  
The Impact

AbstractWe study international mobility in academia, with a focus on the migration of published researchers to and from Russia. Using an exhaustive set of over 2.4 million Scopus publications, we analyze all researchers who have published with a Russian affiliation address in Scopus-indexed sources in 1996–2020. The migration of researchers is observed through the changes in their affiliation addresses, which altered their mode countries of affiliation across different years. While only 5.2% of these researchers were internationally mobile, they accounted for a substantial proportion of citations. Our estimates of net migration rates indicate that while Russia was a donor country in the late 1990s and early 2000s, it has experienced a relatively balanced circulation of researchers in more recent years. These findings suggest that the current trends in scholarly migration in Russia could be better framed as brain circulation, rather than as brain drain. Overall, researchers emigrating from Russia outnumbered and outperformed researchers immigrating to Russia. Our analysis on the subject categories of publication venues shows that in the past 25 years, Russia has, overall, suffered a net loss in most disciplines, and most notably in the five disciplines of neuroscience, decision sciences, mathematics, biochemistry, and pharmacology. We demonstrate the robustness of our main findings under random exclusion of data and changes in numeric parameters. Our substantive results shed light on new aspects of international mobility in academia, and on the impact of this mobility on a national science system, which have direct implications for policy development. Methodologically, our novel approach to handling big data can be adopted as a framework of analysis for studying scholarly migration in other countries.

scholarly journals Analysis of High-Friction Surface Texture with Respect to Friction and Wear

Coatings ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 758
Author(s):  
Cibi Pranav ◽  
Minh-Tan Do ◽  
Yi-Chang Tsai
Keyword(s):  
Friction Coefficient ◽  
Surface Texture ◽  
Safety Concern ◽  
Future Research ◽  
Scanning System ◽  
Novel Approach ◽  
Texture Parameters ◽  
Aggregate Loss ◽  
Friction Surfaces ◽  
The Impact

High Friction Surfaces (HFS) are applied to increase friction capacity on critical roadway sections, such as horizontal curves. HFS friction deterioration on these sections is a safety concern. This study deals with characterization of the aggregate loss, one of the main failure mechanisms of HFS, using texture parameters to study its relationship with friction. Tests are conducted on selected HFS spots with different aggregate loss severity levels at the National Center for Asphalt Technology (NCAT) Test Track. Friction tests are performed using a Dynamic Friction Tester (DFT). The surface texture is measured by means of a high-resolution 3D pavement scanning system (0.025 mm vertical resolution). Texture data are processed and analyzed by means of the MountainsMap software. The correlations between the DFT friction coefficient and the texture parameters confirm the impact of change in aggregates’ characteristics (including height, shape, and material volume) on friction. A novel approach to detect the HFS friction coefficient transition based on aggregate loss, inspired by previous works on the tribology of coatings, is proposed. Using the proposed approach, preliminary outcomes show it is possible to observe the rapid friction coefficient transition, similar to observations at NCAT. Perspectives for future research are presented and discussed.

scholarly journals Reservoir-Induced Land Deformation: Case Study from the Grand Ethiopian Renaissance Dam

2021 ◽  
Vol 13 (5) ◽  
pp. 874
Author(s):  
Yu Chen ◽  
Mohamed Ahmed ◽  
Natthachet Tangdamrongsub ◽  
Dorina Murgulet
Keyword(s):  
Land Surface ◽  
Large Scale ◽  
Surface Deformation ◽  
Vertical Displacement ◽  
Nile River ◽  
Reservoir Volume ◽  
Novel Approach ◽  
Land Deformation ◽  
Large Scale Land ◽  
The Impact

The Nile River stretches from south to north throughout the Nile River Basin (NRB) in Northeast Africa. Ethiopia, where the Blue Nile originates, has begun the construction of the Grand Ethiopian Renaissance Dam (GERD), which will be used to generate electricity. However, the impact of the GERD on land deformation caused by significant water relocation has not been rigorously considered in the scientific research. In this study, we develop a novel approach for predicting large-scale land deformation induced by the construction of the GERD reservoir. We also investigate the limitations of using the Gravity Recovery and Climate Experiment Follow On (GRACE-FO) mission to detect GERD-induced land deformation. We simulated three land deformation scenarios related to filling the expected reservoir volume, 70 km3, using 5-, 10-, and 15-year filling scenarios. The results indicated: (i) trends in downward vertical displacement estimated at −17.79 ± 0.02, −8.90 ± 0.09, and −5.94 ± 0.05 mm/year, for the 5-, 10-, and 15-year filling scenarios, respectively; (ii) the western (eastern) parts of the GERD reservoir are estimated to move toward the reservoir’s center by +0.98 ± 0.01 (−0.98 ± 0.01), +0.48 ± 0.00 (−0.48 ± 0.00), and +0.33 ± 0.00 (−0.33 ± 0.00) mm/year, under the 5-, 10- and 15-year filling strategies, respectively; (iii) the northern part of the GERD reservoir is moving southward by +1.28 ± 0.02, +0.64 ± 0.01, and +0.43 ± 0.00 mm/year, while the southern part is moving northward by −3.75 ± 0.04, −1.87 ± 0.02, and −1.25 ± 0.01 mm/year, during the three examined scenarios, respectively; and (iv) the GRACE-FO mission can only detect 15% of the large-scale land deformation produced by the GERD reservoir. Methods and results demonstrated in this study provide insights into possible impacts of reservoir impoundment on land surface deformation, which can be adopted into the GERD project or similar future dam construction plans.

scholarly journals The Potential Role of Nonhuman Primate Models to Better Comprehend Early Life Immunity and Maternal Antibody Transfer

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 306
Author(s):  
Julie Sartoretti ◽  
Christiane S. Eberhardt
Keyword(s):  
Nonhuman Primate ◽  
Early Life ◽  
Cost Effective ◽  
Maternal Antibody ◽  
Maternal Antibodies ◽  
Immunological Methods ◽  
Human Pathogens ◽  
Childhood Immunization ◽  
Primate Model ◽  
The Impact

Early life immunity is a complex field of research and there are still gaps in knowledge regarding the detailed mechanism of maternal antibody transfer, the impact of maternal antibodies on infant vaccine responses and the ontogeny of human early life immunity. A comprehensive understanding is necessary to identify requirements for early life vaccines and to improve early childhood immunization. New immunological methods have facilitated performing research in the youngest, however, some questions can only be addressed in animal models. To date, mostly murine models are used to study neonatal and infant immunity since they are well-described, easy to use and cost effective. Given their limitations especially in the transfer biology of maternal antibodies and the lack of infectivity of numerous human pathogens, this opinion piece discusses the potential and prerequisites of the nonhuman primate model in studying early life immunity and maternal antibody transfer.

scholarly journals Towards a better understanding of the origins, chemical composition and aging of oxygenated organic aerosols: case study of a Mediterranean industrialized environment, Marseille

2013 ◽  
Vol 13 (15) ◽  
pp. 7875-7894 ◽  
Author(s):  
I. El Haddad ◽  
B. D'Anna ◽  
B. Temime-Roussel ◽  
M. Nicolas ◽  
A. Boreave ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Organic Aerosols ◽  
Industrial Emissions ◽  
Aerosol Mass Spectrometer ◽  
Statistical Confidence ◽  
Aerosol Mass ◽  
Novel Approach ◽  
Organic Markers ◽  
The Impact ◽  
First Time

Abstract. As part of the FORMES summer 2008 experiment, an Aerodyne compact time-of-flight aerosol mass spectrometer (cToF-AMS) was deployed at an urban background site in Marseille to investigate the sources and aging of organic aerosols (OA). France's second largest city and the largest port in the Mediterranean, Marseille, provides a locale that is influenced by significant urban industrialized emissions and an active photochemistry with very high ozone concentrations. Particle mass spectra were analyzed by positive matrix factorization (PMF2) and the results were in very good agreement with previous apportionments obtained using a chemical mass balance (CMB) approach coupled to organic markers and metals (El Haddad et al., 2011a). AMS/PMF2 was able to identify for the first time, to the best of our knowledge, the organic aerosol emitted by industrial processes. Even with significant industries in the region, industrial OA was estimated to contribute only ~ 5% of the total OA mass. Both source apportionment techniques suggest that oxygenated OA (OOA) constitutes the major fraction, contributing ~ 80% of OA mass. A novel approach combining AMS/PMF2 data with 14C measurements was applied to identify and quantify the fossil and non-fossil precursors of this fraction and to explicitly assess the related uncertainties. Results show with high statistical confidence that, despite extensive urban and industrial emissions, OOA is overwhelmingly non-fossil, formed via the oxidation of biogenic precursors, including monoterpenes. AMS/PMF2 results strongly suggest that the variability observed in the OOA chemical composition is mainly driven in our case by the aerosol photochemical age. This paper presents the impact of photochemistry on the increase of OOA oxygenation levels, formation of humic-like substances (HULIS) and the evolution of α-pinene SOA (secondary OA) components.

scholarly journals Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001–2018

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tina Perme ◽  
Daniel Golparian ◽  
Maja Bombek Ihan ◽  
Andrej Rojnik ◽  
Miha Lučovnik ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Virulence Factors ◽  
Late Onset ◽  
Group B Streptococcus ◽  
Genomic Diversity ◽  
Neonatal Disease ◽  
Phenotypic Characterisation ◽  
High Prevalence ◽  
Group B ◽  
The Impact

Abstract Background Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. Methods GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. Results Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. Conclusions A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

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