Fecal Enterobacteriales enrichment is associated with increased in vivo intestinal permeability in humans

Type 2 diabetes (T2D) has been linked with increased intestinal permeability, but the clinical significance of this phenomenon remains unknown. The objective of this study was to investigate the potential link between glucose control, intestinal permeability, diet and intestinal microbiota in patients with T2D. Thirty‐two males with well‐controlled T2D and 30 age‐matched male controls without diabetes were enrolled in a case–control study. Metabolic parameters, inflammatory markers, endotoxemia, and intestinal microbiota in individuals subdivided into high (HP) and normal (LP) colonic permeability groups, were the main outcomes. In T2D, the HP group had significantly higher fasting glucose (P = 0.034) and plasma nonesterified fatty acid levels (P = 0.049) compared with the LP group. Increased colonic permeability was also linked with altered abundances of selected microbial taxa. The microbiota of both T2D and control HP groups was enriched with Enterobacteriales. In conclusion, high intestinal permeability was associated with poorer fasting glucose control in T2D patients and changes in some microbial taxa in both T2D patients and nondiabetic controls. Therefore, enrichment in the gram‐negative order Enterobacteriales may characterize impaired colonic permeability prior to/independently from a disruption in glucose tolerance

Options for Orbifold-GUT Model Building from Five-Dimensional Supergravity

This is the first paper of a series that will examine the options for embedding supersymmetric orbifold-GUTs into five-dimensional N=2 Yang-Mills-Einstein supergravity theories (YMESGTs). In particular, we focus on the allowed couplings of charged hypermultiplets in the lowest dimensional reps of the gauge groups SU(5), SO(10) and E(6). Our results are within the classification of homogeneous quaternionic scalar manifolds. In the minimal coupling of a generation of bulk matter hypermultiplets, supergravity requires the field content of an SO(10) scenario. In the minimal coupling of $n$ bulk generations of matter and higgs hypermultiplets, supergravity requires the field content of an E(6) scenario. We also discuss the coupling of tensors and non-compact gaugings in 5D YMESGTs, which can serve as alternative ways to obtain four-dimensional Higgs sectors. Charged tensor couplings seem to be difficult to work with phenomenologically since a U(1) gauge factor is always required when they are present, and it is not clear if tensors can be put in unified multiplets with other fields, if this is desired. This seems to imply that tensor coulpings in GUT scenarios may be better suited in higher dimensional settings. The non-compact gaugings discussed here are simple, and offer a novel unification scenario in which the supergravity and vector multiplets are connected by gauge transformations. The main points are summarized in tables and the conclusion. Although the discussion is in the spirit of a "bottom-up" approach, M-theory is taken as a motivating background.Comment: V.2 Significant changes: shortened, typos corrected, main focus of paper emphasized. Submitted to Nucl. Phys.

High sensitivity and specificity of a 5-analyte protein and microRNA biosignature for identification of active tuberculosis.

Objectives: Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response to therapy are urgently needed. This study examined the biomarker capacity of a panel of plasma proteins alone, and in conjunction with a previously identified miRNA signature, to identify active TB disease. Methods: The expression of nine proteins (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF and Eotaxin) was measured in the plasma of 100 control subjects and 100 TB patients, at diagnosis (treatment naïve) and over the course of treatment (1-, 2- and 6-month intervals). The diagnostic performance of the nine proteins alone, and with the miRNA, was assessed. Results: Six proteins were significantly up-regulated in the plasma of TB patients at diagnosis compared to controls. Receiver operator characteristic curve analysis demonstrated that IP-10 with an AUC = 0.874, sensitivity of 75% and specificity of 87% was the best single biomarker candidate to distinguish TB patients from controls. IP-10 and IL-6 levels fell significantly within one month of commencing treatment and may have potential as indicators of a positive response to therapy. The combined protein and miRNA panel gave an AUC of 1.00. A smaller panel of only five analytes (IP-10, miR-29a, miR-146a, miR-99b and miR-221) showed an AUC = 0.995, sensitivity of 96% and specificity of 97%. Conclusions: A novel combination of miRNA and proteins significantly improves the sensitivity and specificity as a biosignature over single biomarker candidates and may be useful for the development of a non-sputum test to aid the diagnosis of active TB disease

Cortisol and testosterone accumulation in a low pH recirculating aquaculture system for rainbow trout (Oncorhynchus mykiss)

Steroids accumulate in recirculating aquaculture system (RAS), although explanatory factors for such accumulation are still poorly explored. This study investigated the effect of water exchange rate and pH in six replicated RAS on the concentration of the stress hormone cortisol in rainbow trout blood plasma and in the holding water and of the sex steroids testosterone, 11-ketotestosterone (11-KT) and 17,20-dihydroxypregn-4-en-3-one (17,20-P) over a 70-day experimental period. Three combinations of water exchange rate and pH were used each treatment, with two replications: (i) high water exchange rate (+/- 1700Lkg(-1) feed) and neutral pH (+/- 7.3), (ii) low water exchange rate (+/- 500Lkg(-1) feed) and neutral pH (+/- 7.3) and (iii) low water exchange rate (+/- 500Lkg(-1) feed) and low pH (+/- 5.8). Plasma cortisol concentrations at day 70 were higher (24.4 +/- 9.5ngmL(-1)) for fish kept at low pH when compared to fish kept at neutral pH (12.0 +/- 0.1 and 8.7 +/- 0.2ngmL(-1)). Water cortisol and testosterone concentrations at day 35 were higher at low pH than at neutral pH, whereas water 11-KT and 17,20-P did not differ among treatments. At day 70, there were no significant differences between low and high pH. These results demonstrate that low pH contributes to increased plasma cortisol concentrations and to its accumulation in water, possibly indicating a stress response to low pH. The higher concentration of testosterone but not of the other sex hormones point to unspecified reproductive effects that need further investigation.PhD scholarship - FCT - the National Foundation for Science and Technology of Portugal through QREN-POPH Advanced Training European Social Fund and National funds (MEC) [SFRH/BD/65673/2009]info:eu-repo/semantics/publishedVersio

Art therapy after stroke: Evidence and a need for further research

This is the post-print version of the final paper published in The Arts in Psychotherapy. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.This review presents available evidence regarding the benefits of art therapy and therapeutic arts interventions for stroke survivors. Whilst available evidence is very limited, it suggests that art therapy may address many of the diverse cognitive, emotional and functional needs of people disabled by stroke. Attention, spatial processing, sequencing and planning seem to improve among those who persist with art therapy. Use of the stroke-affected limb may increase. Several studies report improvements in social interaction, and emotional expression. Most published reports offer single case examples, which are idiographic and illuminating. Nonetheless, the brevity of these reports, the reliance on therapist's own accounts, and uncertainties surrounding case selection make generalization of the findings uncertain. There is a pressing need for multi-method research studies. These could use quantitative standardized scales to explore changes in stroke survivors’ physical and emotional functioning, and qualitative enquiry to gain the insights of stroke survivors concerning the art therapy process. Such research designs might help to establish a better recognized role for art therapy within multidisciplinary stroke rehabilitation programs

Transcriptional regulation of the urokinase receptor (u-PAR) - A central molecule of invasion and metastasis

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappaB). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future

Clinical Aspects of Feline Retroviruses: A Review

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats

Total loss of MHC class I is an independent indicator of good prognosis in breast cancer

Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-β2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the β2m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-β2m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and β2m = 0.018)

GenoCAD for iGEM: a grammatical approach to the design of standard-compliant constructs

One of the foundations of synthetic biology is the project to develop libraries of standardized genetic parts that could be assembled quickly and cheaply into large systems. The limitations of the initial BioBrick standard have prompted the development of multiple new standards proposing different avenues to overcome these shortcomings. The lack of compatibility between standards, the compliance of parts with only some of the standards or even the type of constructs that each standard supports have significantly increased the complexity of assembling constructs from standardized parts. Here, we describe computer tools to facilitate the rigorous description of part compositions in the context of a rapidly changing landscape of physical construction methods and standards. A context-free grammar has been developed to model the structure of constructs compliant with six popular assembly standards. Its implementation in GenoCAD makes it possible for users to quickly assemble from a rich library of genetic parts, constructs compliant with any of six existing standards