The role of cytokines in the pathogenesis of experimental Legionella pneumophila infections

Legionnaires\u27 disease is an acute lobar pneumonia caused, primarily by the facultative intracellular pathogen Legionella pneumophila. This organism when inhaled by humans descends into the lower respiratory tract and parasitizes alveolar macrophages. L. pneumophila adhered to U-937 cells, A549 cells and peritoneal macrophages from A/J mice in an opsonin-independent fashion. Following attachment, the organism penetrated the cell membrane, replicated within these cells eventually inducing lysis. To better define the adhesion of L. pneumophila to host cells, an E. coli clone (LP 116), expressing the 25 kDa major outer membrane protein (MOMP) of L. pneumophila was used in binding studies. This MOMP-expressing clone showed a 5-fold increase in opsonin-independent binding to U-937 cells as compared to the parent E. coli strain and suggests that the 25 kDa MOMP of L. pneumophila functions as an adhesin. A major thrust of this study was to better define the cytokine response of the host during L. pneumophila infection. Challenge of macrophage-like U-937 cells with live, heat-killed or formalin-fixed L. pneumophila elicited the secretion of some cytokines while down-regulating others, suggesting that L. pneumophila modulates cytokine production in vitro. To develop a better understanding of the complexity of the immune response to L. pneumophila infection, an experimental model of Legionnaires\u27 disease in A/J mice was developed. A/J mice were challenged intratracheally with a sublethal dose of L. pneumophila to investigate bacterial replication and to characterize the progression of pneumonic disease. Challenge of mice with L. pneumophila resulted in an 8-fold increase in the numbers of L. pneumophila in the lungs within 24 h followed by gradual clearing of the organism. During infection with L. pneumophila, gross and histopathological evaluation indicated pneumonic infection. In addition, mice challenged with L. pneumophila produced both proinflammatory and immunoregulating cytokines as assayed from bronchoalveolar lavage fluids, lung homogenates and sera. This biphasic approach demonstrated that L. pneumophila elicits the expression of some cytokines while modifying the levels of other cytokines produced by macrophages. Furthermore, L. pneumophila induced a specific cytokine response in A/J mice following lung infection

Επιρροή Πλειομετρικής Προπόνησης στην Αλτική Ικανότητα Αθλητών Καλαθοσφαίρισης

Η παρούσα βιβλιογραφική ανασκόπηση έχει σκοπό να αναζητήσει επαρκή επιστημονικά ευρήματα, μέσω της διεθνούς βιβλιογραφίας, με κεντρικό θέμα την επιρροή της πλειομετρικής προπόνησης στην αλτική ικανότητα αθλητών καλαθοσφαίρισης. Ειδικότερα, θα παρουσιαστεί αναλυτικά η φυσιολογία της πλειομετρικής προπόνησης, οι φάσεις που την απαρτίζουν, καθώς επίσης και τα υπάρχοντα επιστημονικά δεδομένα που την συσχετίζουν με την αλτική ικανότητα. Επιπροσθέτως, θα αναλυθεί η σημαντικότητα της αλτικής ικανότητας στο άθλημα της καλαθοσφαίρισης και οι παράγοντες από τους οποίους εξαρτάται η βελτίωση της. Στη συνέχεια θα γίνει διαχωρισμός μεταξύ ανδρών και γυναικών καλαθοσφαιριστών, όσον αφορά τις αλλαγές στην αλτική τους ικανότητα έπειτα από προγράμματα πλειομετρικής προπόνησης και θα αναφερθούν τα αποτελέσματα για τα δύο φύλα. Τα γενικά συμπεράσματα που προέκυψαν από το σύνολο των ερευνών που χρησιμοποιήθηκαν στην εργασία αφορούν θετική συσχέτιση μεταξύ της ένταξης πλειομετρικής προπόνησης στα προγράμματα εκγύμνασης αθλητών καλαθοσφαίρισης και της βελτίωσης της αλτικής ικανότητας τόσο σε κάθετα όσο και σε οριζόντια άλματα, γεγονός που επισημαίνει την ύψιστη σημασία της ένταξης πλειομετρικών ασκήσεων στα προγράμματα εκγύμνασης των αθλητών και αθλητριών καλαθοσφαίρισης.ΟΧ

Endograft infection - treatment management and outcomes

Στόχος: Αυτή η μελέτη εξετάζει την την διαχείρηση και την αντιμετώπιση καθώς και τα αποτελέσματα της λοίμωξης των ενδοπροθεμάτων της θωρακικής και κοιλιακής αορτής μετά από ενδαγγειακή αποκατάσταση ανευρύσματος θωρακικής (TEVAR) και κοιλιακής αορτής (EVAR) στο Πανεπιστημιακό Νοσοκομείο «ΑΤΤΙΚΟΝ» Μέθοδος: Οι ασθενείς διαεγνώσθησαν με λοίμωξη ενδαγγειακού μοσχεύματος από μετά από EVAR/TEVAR μεταξύ 1ης Ιανουαρίου 2010 και 1ης Απριλίου 2023 και αναζητήθηκαν από βάση δεδομένων ενός κέντρου. Τα στοιχεία που περιλήφθησαν είναι δημογραφικά, συνοσηρότητες, ιατρική αντιμετώπιση και χειρουργική καθώς και τα αποτελέσματα αυτών. Αποτελέσματα: Λοίμωξη ενδομοσχεύματος διαγνώσθηκε σε 11 ασθενείς (EVAR, n9 TEVAR, n2). Η κλινική είκoνα στην είσοδό τους στο νοσοκομείο είχε πυρετό/φρίκια(63%) και αορτο-γαστρεντερικό συρίγγιο με αιμορραγία στο 54%. Τελικά 10 ασθενείς υπεβλήθησαν σε χειρουργείο. Αντικατάταστάση αορτής έγινε σε 8 ασθενείς , 6 με δημιουργία νέο-αορτο-λαγονίου συστήματος με αυτόλογες φλέβες, 2 με χρήση χειροποίητου διχαλωτού μοσχεύματος βόειου περικαρδίου και δύο απολίνωση αορτής και νέο μασχαλο-μηριαια παράκαμψη. Οι καλλιέργειες των ενδομοσχευμάτων ήταν κυρίως πολυμικροβιακές και gram + μικρόβια. Μέση παραμονή στο νοσοκομείο ήταν 34 ημέρες με περιεγχειρητική 30 ημερών θνητότητα στο 40%. Μόνο ένας ασθενής ακολούθησε αντιβιοτική αγωγή και απεβίωσε στην 28η ημέρα. Μέσος χρόνος παρακολούθησης 7,3 με επιβίωση των ασθενών 55% τον πρώτο μήνα, 46% τον δεύτερο μήνα, 18% τον τρίτο μήνα έως και τους 60 μήνες. Συμπεράσματα: Η λοίμωξη των αορτικών ενδομοσχευμάτων μπορεί να θεραπευθεί με με αφαίρεση τους και αντικατάσταση του αορτικού διαχασχού ή έξω-ανατομική παράκαμψη αλλά σχετίζεται με υψηλή πρώιμη μετεγχειρητική νοσηρότητα και θνητότητα.Objective: This study examined the medical and surgical management and outcomes of patients with endograft infection of the abdominal aorta or descending aorta after abdominal endovascular aortic repair (EVAR) or thoracic endovascular aortic repair (TEVAR) at Vascular department of Attikon university hospital. Methods: Patients diagnosed with infected aortic endografts after EVAR/TEVAR between January 1, 2010, and April 1, 2023, were reviewed using a one center database. The data that were included was demographic, comorbidity, medical management, surgical management, and outcomes. Results: An aortic endograft infection was diagnosed in 11 patients (EVAR, n =9 TEVAR, n =2 ) .Clinical findings at presentation included fever/chills (63%), and aortic fistula-gastrointestinal bleeding (54%). Finally, 10 patients underwent surgical management. In situ aortic replacement was performed in 8 patients (72%) using hand-made bovine pericardium graft in 2, neoaortoiliac system in 6 and 1(9%) patient underwent axillary-bi-femoral bypass. Graft cultures were primarily polymicrobial (54%), gram-positive 27%, gram -negative 36% and fungus 36%. Mean hospital length of stay was 34 (2-94) days, with perioperative 30-day and mortality of 40%. The one patient treated only medically died after 28 days. Mean follow-up was 7,3 months, with survival of 55% at first month, 46% at second month, 18% at third month and finally 18% up to 60 months. Conclusions: Aortic endograft infection can be eradicated by excision of the infected graft and in situ revascularization or extra-anatomic replacement. It is associated with high early postoperative morbidity and mortality and occasionally with a need for reinterventions for reinfection

Regulation of surface architecture by symbiotic bacteria mediates host colonization

Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host–symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host–symbiont mutualism

MHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation

N-linked glycans on class II MHC molecules are required for the presentation of glycoantigens, but not peptide antigens

Natural Transformation of Helicobacter pylori Involves the Integration of Short DNA Fragments Interrupted by Gaps of Variable Size

Helicobacter pylori are gram-negative bacteria notable for their high level of genetic diversity and plasticity, features that may play a key role in the organism's ability to colonize the human stomach. Homeologous natural transformation, a key contributor to genomic diversification, has been well-described for H. pylori. To examine the mechanisms involved, we performed restriction analysis and sequencing of recombination products to characterize the length, fragmentation, and position of DNA imported via natural transformation. Our analysis revealed DNA imports of small size (1,300 bp, 95% confidence limits 950–1850 bp) with instances of substantial asymmetry in relation to selectable antibiotic-resistance markers. We also observed clustering of imported DNA endpoints, suggesting a possible role for restriction endonucleases in limiting recombination length. Additionally, we observed gaps in integrated DNA and found evidence suggesting that these gaps are the result of two or more separate strand invasions. Taken together, these observations support a system of highly efficient short-fragment recombination involving multiple recombination events within a single locus

Glycobiology of immune responses

Unlike their protein roommates and their nucleic acid cousins, carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the non-template nature of their synthesis and the resulting heterogeneity. While this Annals of the NYAS issue does not claim to hold all of the answers, the goal is to highlight what is known about how carbohydrates and their binding partners, on the microbial (non-self), tumor (altered-self) and host (self) sides, cooperate within the immune system while identifying areas of great opportunity to those willing to take up the challenge. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as proteins, nucleic acids, and lipids. In this introductory article we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs and galectins) and their contribution to the biology of the immune responses in physiologic and pathologic settings.Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Van Kooyk, Yvette. VU University Amsterdam. VU University Medical Center; Países BajosFil: Cobb, Brian A.. Case Western Reserve University; Estados Unido

The Bioinformatics Virtual Coordination Network: An open-source and interactive learning environment

Lockdowns and “stay-at-home” orders, starting in March 2020, shuttered bench and field dependent research across the world as a consequence of the global COVID-19 pandemic. The pandemic continues to have an impact on research progress and career development, especially for graduate students and early career researchers, as strict social distance limitations stifle ongoing research and impede in-person educational programs. The goal of the Bioinformatics Virtual Coordination Network (BVCN) was to reduce some of these impacts by helping research biologists learn new skills and initiate computational projects as alternative ways to carry out their research. The BVCN was founded in April 2020, at the peak of initial shutdowns, by an international group of early-career microbiology researchers with expertise in bioinformatics and computational biology. The BVCN instructors identified several foundational bioinformatic topics and organized hands-on tutorials through cloud-based platforms that had minimal hardware requirements (in order to maximize accessibility) such as RStudio Cloud and MyBinder. The major topics included the Unix terminal interface, R and Python programming languages, amplicon analysis, metagenomics, functional protein annotation, transcriptome analysis, network science, and population genetics and comparative genomics. The BVCN was structured as an open-access resource with a central hub providing access to all lesson content and hands-on tutorials (https://biovcnet.github.io/). As laboratories reopened and participants returned to previous commitments, the BVCN evolved: while the platform continues to enable “a la carte” lessons for learning computational skills, new and ongoing collaborative projects were initiated among instructors and participants, including a virtual, open-access bioinformatics conference in June 2021. In this manuscript we discuss the history, successes, and challenges of the BVCN initiative, highlighting how the lessons learned and strategies implemented may be applicable to the development and planning of future courses, workshops, and training programs

The equilibria that allow bacterial persistence in human hosts

We propose that microbes that have developed persistent relationships with human hosts have evolved cross-signalling mechanisms that permit homeostasis that conforms to Nash equilibria and, more specifically, to evolutionarily stable strategies. This implies that a group of highly diverse organisms has evolved within the changing contexts of variation in effective human population size and lifespan, shaping the equilibria achieved, and creating relationships resembling climax communities. We propose that such ecosystems contain nested communities in which equilibrium at one level contributes to homeostasis at another. The model can aid prediction of equilibrium states in the context of further change: widespread immunodeficiency, changing population densities, or extinctions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62883/1/nature06198.pd