Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Bacteria have evolved a variety of mechanisms for developing community-based biofilms. These bacterial aggregates are of clinical importance, as they are a major source of recurrent disease. Bacterial surface fibers (pili) permit adherence to biotic and abiotic substrates, often in a highly specific manner. The Escherichia coli common pilus (ECP) represents a remarkable family of extracellular fibers that are associated with both disease-causing and commensal strains. ECP plays a dual role in early-stage biofilm development and host cell recognition. Despite being the most common fimbrial structure, relatively little is known regarding its biogenesis, architecture, and function. Here we report atomic-resolution insight into the biogenesis and architecture of ECP. We also derive a structural model for entwined ECP fibers that not only illuminates interbacteria communication during biofilm formation but also provides a useful foundation for the design of novel nanofibers.     

Differential Pattern of Infection of Sylvatic Nymphs and Domiciliary Adults of Triatoma infestans with Trypanosoma cruzi Genotypes in Chile

Abstract. In Chile, the main vector of Chagas disease, Triatoma infestans, is under control after insecticide spraying. However, it has been found colonizing wild habitats. This study evaluated Trypanosoma cruzi infection of sylvatic and domiciliary T. infestans and identified their parasite genotypes. The sample studied was composed mainly of T. infestans sylvatic nymphs and domiciliary adults from a semi-urban area with human dwellings under vector control surveillance. Results showed prevalences of 57.7% in nymphs and 68.6% in adults. Hybridization tests showed a major T. cruzi lineage (TcI) circulating in sylvatic (93.3%) and domiciliary (100%) T. infestans. TcII, TcV, and TcVI were also detected, mainly in nymphs, suggesting differential adaptation of T. cruzi lineages among instars. We also discuss the origin of domiciliary individuals of T. infestans and the risk of human infection by triatomines of sylvatic foci that invade houses despite vector control programs.     

Increased nitric oxide production and gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats

The fetal lung is affected by maternal diabetes. Nuclear receptor PPARα regulates nitric oxide (NO) overproduction in different tissues. We aimed to determine whether fetal lung PPARα expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARα regulation of NO production in the fetal lung. Fetal lungs from control and diabetic rats were explanted on day 21 of gestation and evaluated for PPARα expression and NO production. Fetuses were injected with the PPARα ligand LTB(4) on days 19, 20 and 21, and the fetal lung explanted on day 21 to evaluate PPARα and the inducible isoform of NO synthase (iNOS). Besides, pregnant rats were fed with olive oil- and safflower oil-supplemented diets, enriched in PPAR ligands, for evaluation of fetal lung NO production and PPARα expression. We found reduced PPARα concentrations only in the lung from male fetuses from the diabetic group when compared to controls, although maternal diabetes led to NO overproduction in both male and female fetal lungs. Fetal activation of PPARα led to changes in lung PPARα expression only in female fetuses, although this treatment increased iNOS expression in both male and female fetuses in the diabetic group. Diets supplemented with olive oil and not with safflower oil led to a reduction in NO production in male and female fetal lungs. In conclusion, there are gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats, although PPARα activation prevents maternal diabetes-induced lung NO overproduction in both male and female fetuses.     

Preparation of iron oxide nanoparticles stabilized with biomolecules: Experimental and mechanistic issues

Nanoparticles (NPs) with magnetic properties based on magnetite (Fe₃O₄, MAG) modified with oleic acid (OA), chitosan (CS) and bovine serum albumin (BSA) have been prepared. A versatile method of synthesis was employed, involving two steps: (i) co-precipitation of MAG; and (ii) nanoprecipitation of macromolecules on as-formed MAG NPs. Experimental variables have been explored to determine the set of conditions that ensure suitable properties of NPs in terms of their size, functionality and magnetic properties. It was found that the presence of OA in Fe⁺²/Fe⁺³ solutions yields MAG NPs with lower aggregation levels, while increasing initial amounts of OA may change the capability of NPs to disperse in aqueous or organic media by modifying the stabilization mechanism. Incorporation of CS was verified through Fourier transform IR spectroscopy. This biopolymer stabilizes NPs by electrostatic repulsions leading to stable ferrofluids and minimal fraction of recoverable solid NPs. BSA was successfully added to NP formulations, increasing their functionality and probably their biocompatibility. In this case too stable ferrofluids were obtained, where BSA acts as a polyelectrolyte. From the proposed methodology it is possible to achieve a wide range of NPs magnetically active intended for several applications. The required properties may be obtained by varying experimental conditions.     

Immunological aspects in chronic lymphocytic leukemia (CLL) development

Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens-including apoptotic bodies-in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells.     

Post-mastectomy reconstruction: A risk-stratified comparative analysis of outcomes

IntroductionAlthough breast reconstruction following mastectomy plays a role in the psychological impact of breast cancer, only one in three women undergo reconstruction. Few multi-institutional studies have compared complication profiles of reconstructive patients to non-reconstructive.MethodsUsing the National Surgical Quality Improvement database, all patients undergoing mastectomy from 2006 to 2010, with or without reconstruction, were identified and risk-stratified using propensity scored quintiles. The incidence of complications and comorbidities were compared.ResultsOf 37,723 mastectomies identified, 30% received immediate breast reconstruction. After quintile matching for comorbidities, complications rates between reconstructive and non-reconstructives were similar. This trend was echoed across all quintiles, except in the sub-group with highest comorbidities. Here, the reconstructive patients had significantly more complications than the non-reconstructive (22.8% versus 7.0%, p < 0.001).ConclusionImmediate breast reconstruction is a well-tolerated surgical procedure. However, in patients with high comorbidities, surgeons must carefully counterbalance surgical risks with psychosocial benefits to maximize patient outcomes.Level of evidenceLevel 3     

Postimplant Behavior of Lightweight Polypropylene Meshes in an Experimental Model of Abdominal Hernia

Background. Over the years, reticular prostheses have undergone changes in their structure and composition to give rise to today's partially absorbable lightweight meshes. This study was designed to assess the biological and biomechanical behavior of these prostheses to establish whether they offer any advantages over nonabsorbable lightweight polypropylene prostheses. Materials and Methods. 7 × 5 cm defects were created in the anterior abdominal wall of New Zealand White rabbits and repaired by securing different prostheses to the edges of the defect with a running 4/0 polypropylene suture. The lightweight biomaterials compared were two nonabsorbable meshes: Parietene® and Optilene elastic®, and two partially absorbable prostheses: Vypro II® and Ultrapro®. At 14 and 90 days postimplant, tissue/prosthesis specimens were subjected to histological, immunohistochemical, shrinkage, and biomechanical analyses. Results. Adhesion formation on the peritoneum-facing surface of the meshes was significantly less extensive in the meshes with absorbable components at 90 days postimplant. The newly formed tissue around the prosthetic filaments was comprised of collagen fibers, fibroblasts, blood vessels, and macrophages. The partially absorbable meshes showed higher macrophage proportions (due to remnants of absorbable material and their structure) than the nonabsorbable meshes at 90 days, although differences were not significant. At 90 days postimplant, similar tensile strengths were recorded for all the implants. Conclusions. All the prosthetic materials induced good host tissue ingrowth, with no significant differences in tensile strength observed. Our findings suggest that partially absorbable lightweight prostheses could offer advantages over nonabsorbable lightweight meshes since less foreign material persists in the recipient, improving abdominal wall compliance.