Association between Salmonella sp. and Yersinia enterocolitica infection in swine

Swine are known reservoirs for both Salmonella and Yersinia enterocolitica. Both are foodborne pathogens and can result in zoonotic disease if contamination of pork products occurs during harvest. The epidemiology of Y. enterocolitica and Salmonella in swine is not well understood. Previous reports from experimental studies in mice suggest that, vai quorum-sensing, Salmonella detects Y. enterocolitical signals, increasing Salmonella colonization

The Molecular Characterization of the Mitochondrial Calcium Uniporter

By buffering cytosolic calcium, mitochondria can shape the magnitude and duration of intracellular calcium transients, which in turn govern key physiological events. Although controlled uptake of calcium into the matrix influences the rate of ATP production, excess calcium within the matrix triggers non-specific permeabilization of the mitochondrial inner membrane, resulting in cell death. Despite its importance in cellular physiology, the molecular identity of the mitochondrial calcium uniporter remained a mystery for nearly five decades. Recently, an approach inspired by comparative genomics was used to identify two proteins required for high-capacity mitochondrial calcium uptake. These include MICU1, an EF-hand protein that may function as a regulatory component by sensing calcium, and MCU, the channel-forming subunit of the uniporter. In this work, I explore two distinct areas within the growing field of molecular mitochondrial calcium biology. First, I discuss the identification of a new protein, MICU1-paralog EFHA1, and present data that implicates it in mitochondrial calcium uptake. Subsequently, I describe efforts to establish an in vitro system to characterize the channel activity of MCU, including my contribution to the development of a liposome-based assay for calcium transport and preliminary work aimed at reconstituting MCU transport activity in proteoliposomes

Giant Pyogenic Granuloma in a Patient with Chronic Lymphocytic Leukemia

Pyogenic granuloma, also known as lobular capillary hemangioma, is a common benign vascular proliferative lesion that can present at any age on the skin or mucous membranes. Most lesions do not exceed 2 cm, but there are a handful of giant cutaneous pyogenic granulomas that have been reported, often in individuals with underlying immune dysfunction. Here, we report the first giant pyogenic granuloma in a patient with a hematological malignancy, chronic lymphocytic leukemia

Persona Humana: Comienzo de la existencia. Estatuto

El desarrollo del tema gira en torno a las maneras de lograr la reproducción humana y nos detenemos en el uso de técnicas de fecundación asistida (FIV). Así cuando el hecho nuevo de lograr fecundar y transitar los primeros días del desarrollo embrionario de manera extracorpórea, instala en el ámbito jurídico doctrinario y legislativo una discusión acerca de cuándo se produce la concepción: si con la fecundación o con la implantación, y la pregunta del deber ser: a partir de qué momento la ley emplaza al nasciturus como persona. También consideramos que mediante una ley especial (Estatuto) es necesario establecer qué conductas resultan Permitidas y cuales Prohibidas, con el fin de proteger embriones no implantados. Asimismo, planteamos si los medios de reproducción asistida son moralmente objetables y si existe algo inmoral en el proceso de procrear cuando está bajo el control de terceros.http://www.jndc.com.arFil: Cerutti, María del Carmen. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Plovanich, María Cristina. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Otras Derech

Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne

Importance Spironolactone has been shown to be an effective treatment option for hormonally mediated acne but can cause hyperkalemia. The prevalence of hyperkalemia among healthy young women taking spironolactone for acne is unclear. Objective To measure the rate of hyperkalemia in healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne. Design, Setting, and Participants Retrospective study of healthy young women taking spironolactone for acne. Data from December 1, 2000, through March 31, 2014, were obtained from a clinical data repository. Outpatient data were collected from 2 tertiary care centers in the United States. We analyzed rates of hyperkalemia in 974 healthy young women taking spironolactone for acne. We also analyzed 1165 healthy young women taking and not taking spironolactone to obtain a profile for the baseline rate of hyperkalemia in this population. Exclusion criteria were cardiovascular disease, renal failure, and the use of medications that affect the renin-angiotensin-aldosterone system. Main Outcomes and Measures The rate of hyperkalemia in healthy young women taking spironolactone for acne was calculated. Secondary measures included spironolactone prescriber profiles and potassium monitoring practices. Results There were 13 abnormal serum potassium measurements in 1802 measurements obtained among young women receiving spironolactone therapy, yielding a hyperkalemia rate of 0.72%, equivalent to the 0.76% baseline rate of hyperkalemia in this population. Repeat testing in 6 of 13 patients demonstrated normal values, suggesting that these measurements may have been erroneous. In the remaining 7 patients, no action was taken. Conclusions and Relevance The rate of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this population. Routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10-/- mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64Mb genome to 200-500X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host

Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni </it>infection produces a spectrum of clinical presentations in humans – including asymptomatic carriage, watery diarrhea, and bloody diarrhea – and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different <it>C. jejuni </it>strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model.</p> <p>Results</p> <p>In the comparative study, C57BL/6 interleukin-10^-/-mice were infected with seven genetically distinct <it>C. jejuni </it>strains. Four strains colonized the mice and caused disease; one colonized with no disease; two did not colonize. A DNA:DNA microarray comparison of the strain that colonized mice without disease to <it>C. jejuni </it>11168 that caused disease revealed that putative virulence determinants, including loci encoding surface structures known to be involved in <it>C. jejuni </it>pathogenesis, differed from or were absent in the strain that did not cause disease. In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted from watery to bloody diarrhea. Mice kept on an ~6% fat diet or switched from an ~12% fat diet to an ~6% fat diet just before infection with a non-adapted strain also exhibited increased incidence and severity of disease and decreased time to develop disease, although the effects of diet were only statistically significant in one experiment.</p> <p>Conclusion</p> <p><it>C. jejuni </it>strain genetic background and adaptation of the strain to the host by serial passage contribute to differences in disease manifestations of <it>C. jejuni </it>infection in C57BL/6 IL-10^-/-mice; differences in environmental factors such as diet may also affect disease manifestation. These results in mice reflect the spectrum of clinical presentations of <it>C. jejuni </it>gastroenteritis in humans and contribute to usefulness of the model in studying human disease.</p

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Genetic diversity in Campylobacter jejuni is associated with differential colonization of broiler chickens and C57BL/6J IL10-deficient mice

Previous studies have demonstrated that Campylobacter jejuni, the leading causative agent of bacterial food-borne disease in the USA, exhibits high-frequency genetic variation that is associated with changes in cell-surface antigens and ability to colonize chickens. To expand our understanding of the role of genetic diversity in the disease process, we analysed the ability of three C. jejuni human disease isolates (strains 11168, 33292 and 81-176) and genetically marked derivatives to colonize Ross 308 broilers and C57BL/6J IL10-deficient mice. C. jejuni colonized broilers at much higher efficiency (all three strains, 23 of 24 broilers) than mice (11168 only, 8 of 24 mice). C. jejuni 11168 genetically marked strains colonized mice at very low efficiency (2 of 42 mice); however, C. jejuni reisolated from mice colonized both mice and broilers at high efficiency, suggesting that this pathogen can adapt genetically in the mouse. We compared the genome composition in the three wild-type C. jejuni strains and derivatives by microarray DNA/DNA hybridization analysis; the data demonstrated a high degree of genetic diversity in three gene clusters associated with synthesis and modification of the cell-surface structures capsule, flagella and lipo-oligosaccharide. Finally, we analysed the frequency of mutation in homopolymeric tracts associated with the contingency genes wlaN (GC tract) and flgR (AT tracts) in culture and after passage through broilers and mice. C. jejuni adapted genetically in culture at high frequency and the degree of genetic diversity was increased by passage through broilers but was nearly eliminated in the gastrointestinal tract of mice. The data suggest that the broiler gastrointestinal tract provides an environment which promotes outgrowth and genetic variation in C. jejuni; the enhancement of genetic diversity at this location may contribute to its importance as a human disease reservoir

MICU2, a Paralog of MICU1, Resides within the Mitochondrial Uniporter Complex to Regulate Calcium Handling

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.National Institutes of Health (U.S.) (GM0077465)National Institutes of Health (U.S.) (DK080261