TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development

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Weight loss moderately affects the mixed meal challenge response of the plasma metabolome and transcriptome of peripheral blood mononuclear cells in abdominally obese subjects

Introduction

The response to dietary challenges has been proposed as a more accurate measure of metabolic health than static measurements performed in the fasted state. This has prompted many groups to explore the potential of dietary challenge tests for assessment of diet and lifestyle induced shifts in metabolic phenotype.

Objectives

We examined whether the response to a mixed-meal challenge could provide a readout for a weight loss (WL)-induced phenotype shift in abdominally obese male subjects. The underlying assumption of a mixed meal challenge is that it triggers all aspects of phenotypic flexibility and provokes a more prolonged insulin response, possibly allowing for better differentiation between individuals.

Methods

Abdominally obese men (n?=?29, BMI?=?30.3?±?2.4 kg/m²) received a mixed-meal challenge prior to and after an 8-week WL or no-WL control intervention. Lean subjects (n?=?15, BMI?=?23.0?±?2.0 kg/m²) only received the mixed meal challenge at baseline to have a benchmark for WL-induced phenotype shifts.

Results

Levels of several plasma metabolites were significantly different between lean and abdominally obese at baseline as well as during postprandial metabolic responses. Genes related to oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) were expressed at higher levels in abdominally obese subjects as compared to lean subjects at fasting, which was partially reverted after WL. The impact of WL on the postprandial response was modest, both at the metabolic and gene expression level in PBMCs.

Conclusion

We conclude that mixed-meal challenges are not necessarily superior to measurements in the fasted state to assess metabolic health. Furthermore, the mechanisms accounting for the observed differences between lean and abdominally obese in the fasted state are different from those underlying the dissimilarity observed during the postprandial response.

     

Listeria monocytogenes wall teichoic acid decoration in virulence and cell‐to‐cell spread

Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes, mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral‐virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA‐binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant – which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell‐to‐cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter – suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non‐antibiotic therapeutics for gram positive infections. © 2016 John Wiley & Sons Ltd     

Simultaneous Functionalization and Reduction of Magnetic Graphene Oxide by l-Histidine and its Application for Magnetic Separation/Preconcentration of Antioxidant Trace Elements

Biological Trace Element Research - In the present study, for the first time, the magnetic graphene oxide was simultaneously functionalized and reduced with the aim of imidazole-based l-histidine...     

Epidemiology of leptospirosis in Tanzania: A review of the current status,serogroup diversity and reservoirs

BackgroundTanzania is among the tropical countries of Sub-Saharan Africa with the environmental conditions favorable for transmission of Leptospira. Leptospirosis is a neglected zoonotic disease, and although there are several published reports from Tanzania, the epidemiology, genetic diversity of Leptospira and its host range are poorly understood.MethodsWe conducted a comprehensive review of human and animal leptospirosis within the 26 regions of the Tanzanian mainland. Literature searches for the review were conducted in PubMed and Google Scholar. We further manually identified studies from reference lists among retrieved studies from the preliminary search.ResultsWe identified thirty-four studies describing leptospirosis in humans (n = 16), animals (n = 14) and in both (n = 4). The number of studies varied significantly across regions. Most of the studies were conducted in Morogoro (n = 16) followed by Kilimanjaro (n = 9) and Tanga (n = 5). There were a range of study designs with cross-sectional prevalence studies (n = 18), studies on leptospirosis in febrile patients (n = 13), a case control study in cattle (n = 1) and studies identifying novel serovars (n = 2). The most utilized diagnostic tool was the microscopic agglutination test (MAT) which detected antibodies to 17 Leptospira serogroups in humans and animals. The Leptospira serogroups with the most diverse hosts were Icterohaemorrhagiae (n = 11), Grippotyphosa (n = 10), Sejroe (n = 10), Pomona (n = 9) and Ballum (n = 8). The reported prevalence of Leptospira antibodies in humans ranged from 0.3–29.9% and risk factors were associated with occupational animal contact. Many potential reservoir hosts were identified with the most common being rodents and cattle.ConclusionLeptospirosis is prevalent in humans and animals in Tanzania, although there is regional and host variation in the reports. Many regions do not have information about the disease in either humans or their animal reservoirs. More studies are required to understand human leptospirosis determinants and the role of livestock in leptospirosis transmission to humans for the development of appropriate control strategies.     

Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines

Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), with substantial roles in human reproduction and in endocrine-responsive tumours. Recently a novel beta subunit named betaE was described, although it is still unclear if normal or cancerous cervical epithelial cells as well as cervical cancer cell lines can synthesise the novel inhibin-betaE subunit. About 4 normal cervical tissue samples together with 10 specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemical analyzed. Additionally, two cervical carcinoma cell lines (HeLa and CaSki) were analyzed by immunofluorescence and RT–PCR for the expression of this novel subunit. We demonstrated for the first time an immunolabelling of the inhibin-betaE subunit in normal and malignant cervical tissue, as well as cervical cancer cells. Although the physiological role is still quite unclear in cervical tissue, inhibin-βE might play important roles in carcinogenesis. Moreover, the synthesis of this subunit in cervical carcinoma cell lines of squamous and glandular epithelial origins also allows the use of these cell lines in elucidating its functions in cervical cancer pathogenesis. However, since the expression of the inhibin-βE is minimal in HeLa cells as assessed by immunofluorescence and RT–PCR, the CaSki cell line might be a better model for further functional experiments regarding cervical cancer pathogenesis.