Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.

Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS).

Conserved cardiolipin-mitochondrial ADP/ATP carrier interactions assume distinct structural and functional roles that are clinically relevant.

The mitochondrial phospholipid cardiolipin (CL) promotes bioenergetics via oxidative phosphorylation (OXPHOS). Three tightly bound CLs are evolutionarily conserved in the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) which resides in the inner mitochondrial membrane and exchanges ADP and ATP to enable OXPHOS. Here, we investigated the role of these buried CLs in the carrier using yeast Aac2 as a model.

Monitoring and evaluation framework for hypertension programs. A collaboration between the Pan American Health Organization and World Hypertension League.

The Pan American Health Organization (PAHO)-World Hypertension League (WHL) Hypertension Monitoring and Evaluation Framework is summarized. Standardized indicators are provided for monitoring and evaluating national or subnational hypertension control programs. Five core indicators from the World Health Organization hearts initiative and a single PAHO-WHL core indicator are recommended to be used in all hypertension control programs.

The orphan nuclear receptor RORα and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn's disease.

Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that -deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition, and reduced fibroblast accumulation.

The orphan nuclear receptor ROR alpha and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn's disease.

Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that -deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition and reduced fibroblast accumulation.

Enteric Helminths Promote Salmonella Coinfection by Altering the Intestinal Metabolome.

Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional 3-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity.

Nutrient Deprivation Affects Salmonella Invasion and Its Interaction with the Gastrointestinal Microbiota.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne enteric pathogen and a major cause of gastroenteritis in humans. It is known that molecules derived from the human fecal microbiota downregulate S.

A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.

Unlabelled: Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models.

Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others.

Periodontal pathogens and tetracycline resistance genes in subgingival biofilm of periodontally healthy and diseased Dominican adults.

Objective: The objective of this study was to compare the periodontopathogen prevalence and tetracycline resistance genes in Dominican patients with different periodontal conditions.

Methods: Seventy-seven samples were collected from healthy, gingivitis, chronic (CP) and aggressive (AgP) periodontitis patients. Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, Parvimonas micra, Eikenella corrodens and Dialister pneumosintes and 11 resistance genes were studied by PCR.

Commensal-pathogen interactions in the intestinal tract: lactobacilli promote infection with, and are promoted by, helminth parasites.

The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other's persistence in the host remains unknown.

Influence of the microbiota on vaccine effectiveness.

Studies of the relationship between the microbiome and the development and function of the immune system are demonstrating novel concepts that could significantly alter the way we treat disease and promote wellness. Several diseases, including inflammatory bowel disease, allergy/asthma, and diabetes, are associated with changes in composition of the microbiome. Recent findings suggest novel complex mechanisms by which the microbiome impacts immune cell development and differentiation.

TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cells.

Background: CD248 is a cell surface glycoprotein, highly expressed by stromal cells and fibroblasts of tumors and inflammatory lesions, but virtually undetectable in healthy adult tissues. CD248 promotes tumorigenesis, while lack of CD248 in mice confers resistance to tumor growth. Mechanisms by which CD248 is downregulated are poorly understood, hindering the development of anti-cancer therapies.

Association between the Xba I polymorphism of APOB gene and plasma lipid level in Mexican patients with coronary artery disease.

Some studies, that consider polymorphisms of the apolipoprotein B (APOB) gene as risk factors for coronary artery disease (CAD), have reported discordant results. The aim of the present study was to search for associations between plasma lipid profiles with the DNA Xba I polymorphism of the APOB gene in CAD patients diagnosed by angiography (CAD+). In the present study we compared 114 Mexican patients (80 men and 34 women) with CAD+ and 132 control patients (59 men and 73 women) without evidence of ischemia or arterial damage (CAD-).

CD248: reviewing its role in health and disease.

CD248, also known as endosialin or tumor endothelial marker-1 (TEM-1), is a C-type lectin-like domain (CTLD) containing cell surface glycoprotein that is expressed by stromal cells of proliferating tissues during embryogenesis and postnatally in tumors and inflammatory lesions. Loss-of-function studies in mice support the notion that CD248 promotes tumor growth and inflammation, observations that are stimulating interest in evaluating this molecule as a therapeutic target. In spite of these advances, the mechanisms by which CD248 modulates cancer and inflammation remain largely enigmatic.

Discovery of DNA operators for TetR and MarR family transcription factors from Burkholderia xenovorans.

Determining transcription factor (TF) recognition motifs or operator sites is central to understanding gene regulation, yet few operators have been characterized. In this study, we used a protein-binding microarray (PBM) to discover the DNA recognition sites and putative regulons for three TetR and one MarR family TFs derived from Burkholderia xenovorans, which are common to the genus Burkholderia. We also describe the development and application of a more streamlined version of the PBM technology that significantly reduced the experimental time.

Analysis of Clostridium botulinum serotype E strains by using multilocus sequence typing, amplified fragment length polymorphism, variable-number tandem-repeat analysis, and botulinum neurotoxin gene sequencing.

A total of 41 Clostridium botulinum serotype E strains from different geographic regions, including Canada, Denmark, Finland, France, Greenland, Japan, and the United States, were compared by multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) analysis, variable-number tandem-repeat (VNTR) analysis, and botulinum neurotoxin (bont) E gene sequencing. The strains, representing environmental, food-borne, and infant botulism samples collected from 1932 to 2007, were analyzed to compare serotype E strains from different geographic regions and types of botulism and to determine whether each of the strains contained the transposon-associated recombinase rarA, involved with bont/E insertion. MLST examination using 15 genes clustered the strains into several clades, with most members within a cluster sharing the same BoNT/E subtype (BoNT/E1, E2, E3, or E6).

Evaluation of Bacillus anthracis and Yersinia pestis sample collection from nonporous surfaces by quantitative real-time PCR.

Aim: We will validate sample collection methods for recovery of microbial evidence in the event of accidental or intentional release of biological agents into the environment.

Methods And Results: We evaluated the sample recovery efficiencies of two collection methods - swabs and wipes - for both nonvirulent and virulent strains of Bacillus anthracis and Yersinia pestis from four types of nonporous surfaces: two hydrophilic surfaces, stainless steel and glass, and two hydrophobic surfaces, vinyl and plastic. Sample recovery was quantified using real-time qPCR to assay for intact DNA signatures.

Molecular mechanisms of Salmonella virulence and host resistance.

Salmonella species can cause typhoid fever and gastroenteritis in humans and pose a global threat to human health. In order to establish a successful infection, Salmonella utilize a large number of genes encoding a variety of virulence factors. Different animal models of infection have been used to better understand the mechanisms underlying each disease including cattle, rodents, and nematodes.

Nramp1 drives an accelerated inflammatory response during Salmonella-induced colitis in mice.

A recently developed model for enterocolitis in mice involves pre-treatment with the antibiotic streptomycin prior to infection with Salmonella enterica serovar Typhimurium (S. Typhimurium). The contribution of Nramp1/Slc11a1 protein, a critical host defence mechanism against S.

Multiplexed SNP genotyping using primer single-base extension (SBE) and microsphere arrays.

Single-nucleotide polymorphisms (SNPs), genome sites with single-base sequence differences between individual chromosomes, are the most common type of genetic variation. Single-base changes can result in disease phenotypes, confer susceptibility or resistance to toxins or pathogens, or serve as markers for distinct allelic segments of DNA, making SNPs an important emerging tool in both basic and clinical research. This unit presents detailed protocols for multiplexed SNP genotyping using primer single-base extension (SBE) adapted to microspheres and flow cytometry.

A murine intraperitoneal infection model reveals that host resistance to Campylobacter jejuni is Nramp1 dependent.

We tested the hypothesis that host resistance to Campylobacter jejuni is Nramp1 dependent. Following intraperitoneal (IP) inoculation of Nramp1+/+ and isogenic Nramp1-deficient (Nramp1-/-) mice C. jejuni primarily associated with mac1-positive cells in liver tissue.

Nramp1 expression by dendritic cells modulates inflammatory responses during Salmonella Typhimurium infection.

Host resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) is mediated by natural resistance-associated macrophage protein 1 (Nramp1/Slc11a1). Nramp1 is critical to host defence, as mice lacking Nramp1 fail to control bacterial replication and succumb to low doses of S.

Chronic enteric salmonella infection in mice leads to severe and persistent intestinal fibrosis.

Background & Aims: Intestinal fibrosis and stricture formation are serious complications of Crohn's disease, often requiring surgical intervention. Unfortunately, the mechanisms underlying intestinal fibrosis development are poorly understood, in part because of the lack of relevant animal models. Here, we present a novel murine model of severe and persistent intestinal fibrosis caused by chronic bacterial-induced colitis.

Variation in HLA class I antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer.

Background: Persistent infection with human papillomavirus type 16 (HPV16) is a primary etiological factor for the development of cervical cancer. Genes involved in antigen processing influence both the repertoire of antigens presented by HPV16-infected cells and the nature of HPV16-specific immune responses. Genetic variation in these genes may affect protein structure and function and, consequently, the ability of an individual to clear HPV infection.