Predominant genera of fecal microbiota in children with atopic dermatitis are not altered by intake of probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07

The effect of probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 on the composition of the Lactobacillus group, Bifidobacterium and the total bacterial population in feces from young children with atopic dermatitis was investigated. The study included 50 children randomized to intake of one of the probiotic strain or placebo. Microbial composition was characterized by denaturing gradient gel electrophoresis, quantitative PCR and, in a subset of subjects, by pyrosequencing of the 16S rRNA gene. The core population of the Lactobacillus group was identified as Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus oris, Leuconostoc mesenteroides, while the bifidobacterial community included Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium longum and Bifidobacterium catenulatum. The fecal numbers of L. acidophilus and B. lactis increased significantly after intervention, indicating survival of the ingested bacteria. The levels of Bifidobacterium correlated positively (P=0.03), while the levels of the Lactobacillus group negatively (P=0.01) with improvement of atopic eczema evaluated by the Severity Scoring of Atopic Dermatitis index. This correlation was observed across the whole study cohort and not attributed to the probiotic intake. The main conclusion of the study is that administration of L. acidophilus NCFM and B. lactis Bi-07 does not affect the composition and diversity of the main bacterial populations in feces.     

Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells

NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus‐infected cells. Given the vast diversity of receptors expressed on NK cells we seek to identify receptors involved in the recognition of HIV‐1‐infected cells. By combining an unbiased large‐scale screening approach with a functional assay, we identify TRAIL to be associated with NK cell degranulation against HIV‐1‐infected target cells. Further investigating the underlying mechanisms, we demonstrate that TRAIL is able to elicit multiple effector functions in human NK cells independent of receptor‐mediated induction of apoptosis. Direct engagement of TRAIL not only results in degranulation but also IFNγ production. Moreover, TRAIL‐mediated NK cell activation is not limited to its cognate death receptors but also decoy receptor I, adding a new perspective to the perceived regulatory role of decoy receptors in TRAIL‐mediated cytotoxicity. Based on these findings, we propose that TRAIL not only contributes to the anti‐HIV‐1 activity of NK cells but also possesses a multifunctional role beyond receptor‐mediated induction of apoptosis, acting as a regulator for the induction of different effector functions.     

Rosiglitazone Treatment of Type 2 Diabetic db/db Mice Attenuates Urinary Albumin and Angiotensin Converting Enzyme 2 Excretion

Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2. Renal ACE2 and ADAM17 were significantly increased in db/db mice compared to controls. We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice. Rosiglitazone treatment of db/db mice normalized hyperglycemia, attenuated renal injury and decreased urinary ACE2 and renal ADAM17 protein expression. Urinary excreted ACE2 is enzymatically active. Western blot analysis of urinary ACE2 demonstrated two prominent immunoreactive bands at approximately 70 & 90 kDa. The predominant immunoreactive band is approximately 20 kDa shorter than the one demonstrated for kidney lysate, indicating possible ectodomain shedding of active renal ACE2 in the urine. Therefore, it is tempting to speculate that renoprotection of rosiglitazone could be partially mediated via downregulation of renal ADAM17 and ACE2 shedding. In addition, there was a positive correlation between blood glucose, urinary albumin, plasma glucagon, and triglyceride levels with urinary ACE2 excretion. In conclusion, urinary ACE2 could be used as a sensitive biomarker of diabetic nephropathy and for monitoring the effectiveness of renoprotective medication.     

Contribution of the different planktonic microbial assemblages to ETS activity in the Ligurian frontal area: north-west Mediterranean Sea

Spatial and size distribution of micro-organisms and their ETSactivity has been investigated in Ligurian Sea surface watersalong the Nice-Calvi transect across frontal areas from 18 to37 km offshore (TOMOFRONT 1 and 2 cruises, April 1988 and April-May1989 respectively). Aplastidic and plastidic nanoflagellatesand aplastidic picoflagellates were present in numbers closeto 0.25 x 10⁴ cells ml^–1, whereas plastidic picoflagellatesaccounted for about half this number. Correlations have beenevidenced between plastidic and aplastidic micro-organisms withinthe same size group, suggesting that they belong to a well-definedecosystem. The highest correlation between total ETS activityand abundance of the considered size groups was observed fornanoflagellates (r = 0.94, n = 22, and r = 0.90, n = 22 foraplastidic and plastidic cells respectively). The importanceof the role of nanoflagellates in surface waters, with respectto the overall ETS activity, was supported by results from sizefractionation which assigned to the 3–10 µm sizerange a 73.3% contribution to overall ETS activity. Resultsemphasize analysing global ETS activity of natural samples inorder to derive relationships between the different populationspresent in the sampled water. It is suggested that couplingflow cytometry to the ETS approach should be very helpful inthat respect.     

Tick-borne nyamanini virus replicates in the nucleus and exhibits unusual genome and matrix protein properties

Tick-borne Nyamanini virus (NYMV) is the prototypic member of a recently discovered genus in the order Mononegavirales, designated Nyavirus. The NYMV genome codes for six distinct genes. Sequence similarity and structural properties suggest that genes 1, 5, and 6 encode the nucleoprotein (N), the glycoprotein (G), and the viral polymerase (L), respectively. The function of the other viral genes has been unknown to date. We found that the third NYMV gene codes for a protein which, when coexpressed with N and L, can reconstitute viral polymerase activity, suggesting that it represents a polymerase cofactor. The second viral gene codes for a small protein that inhibits viral polymerase activity and further strongly enhances the formation of virus-like particles when coexpressed with gene 4 and the viral glycoprotein G. This suggests that two distinct proteins serve a matrix protein function in NYMV as previously described for members of the family Filoviridae. We further found that NYMV replicates in the nucleus of infected cells like members of the family Bornaviridae. NYMV is a poor inducer of beta interferon, presumably because the viral genome is 5' monophosphorylated and has a protruding 3' terminus as observed for bornaviruses. Taken together, our results demonstrate that NYMV possesses biological properties previously regarded as typical for filoviruses and bornaviruses, respectively.     

Effective Population Size Dynamics and the Demographic Collapse of Bornean Orang-Utans

Bornean orang-utans experienced a major demographic decline and local extirpations during the Pleistocene and Holocene due to climate change, the arrival of modern humans, of farmers and recent commercially-driven habitat loss and fragmentation. The recent loss of habitat and its dramatic fragmentation has affected the patterns of genetic variability and differentiation among the remaining populations and increased the extinction risk of the most isolated ones. However, the contribution of recent demographic events to such genetic patterns is still not fully clear. Indeed, it can be difficult to separate the effects of recent anthropogenic fragmentation from the genetic signature of prehistoric demographic events. Here, we investigated the genetic structure and population size dynamics of orang-utans from different sites. Altogether 126 individuals were analyzed and a full-likelihood Bayesian approach was applied. All sites exhibited clear signals of population decline. Population structure is known to generate spurious bottleneck signals and we found that it does indeed contribute to the signals observed. However, population structure alone does not easily explain the observed patterns. The dating of the population decline varied across sites but was always within the 200–2000 years period. This suggests that in some sites at least, orang-utan populations were affected by demographic events that started before the recent anthropogenic effects that occurred in Borneo. These results do not mean that the recent forest exploitation did not leave its genetic mark on orang-utans but suggests that the genetic pool of orang-utans is also impacted by more ancient events. While we cannot identify the main cause for this decline, our results suggests that the decline may be related to the arrival of the first farmers or climatic events, and that more theoretical work is needed to understand how multiple demographic events impact the genome of species and how we can assess their relative contributions.     

SIRT1 and c-Myc Promote Liver Tumor Cell Survival and Predict Poor Survival of Human Hepatocellular Carcinomas

The increased expression of SIRT1 has recently been identified in numerous human tumors and a possible correlation with c-Myc oncogene has been proposed. However, it remains unclear whether SIRT1 functions as an oncogene or tumor suppressor. We sought to elucidate the role of SIRT1 in liver cancer under the influence of c-Myc and to determine the prognostic significance of SIRT1 and c-Myc expression in human hepatocellular carcinoma. The effect of either over-expression or knock down of SIRT1 on cell proliferation and survival was evaluated in both mouse and human liver cancer cells. Nicotinamide, an inhibitor of SIRT1, was also evaluated for its effects on liver tumorigenesis. The prognostic significance of the immunohistochemical detection of SIRT1 and c-Myc was evaluated in 154 hepatocellular carcinoma patients. SIRT1 and c-Myc regulate each other via a positive feedback loop and act synergistically to promote hepatocellular proliferation in both mice and human liver tumor cells. Tumor growth was significantly inhibited by nicotinamide in vivo and in vitro. In human hepatocellular carcinoma, SIRT1 expression positively correlated with c-Myc, Ki67 and p53 expression, as well as high á-fetoprotein level. Moreover, the expression of SIRT1, c-Myc and p53 were independent prognostic indicators of hepatocellular carcinoma. In conclusion, this study demonstrates that SIRT1 expression supports liver tumorigenesis and is closely correlated with oncogenic c-MYC expression. In addition, both SIRT1 and c-Myc may be useful prognostic indicators of hepatocellular carcinoma and SIRT1 targeted therapy may be beneficial in the treatment of hepatocellular carcinoma.     

Microrheology of hyaluronan solutions: implications for the endothelial glycocalyx

The endothelial glycocalyx (EG) is a complex biopolymer network produced by vascular endothelial cells that forms a layer with multiple functions at the luminal side of blood vessels. The EG acts as an anti-adhesive protection layer, as a molecular sieve, as a chemical sensor site, and as a mechanotransducer of fluid shear stress to the underlying cell layer. A major component involved in these processes is the highly hydrated glycosaminoglycan (GAG) hyaluronan (HA). Here we used laser interferometry to measure the broadband mechanical response of reconstituted HA solutions at close to physiological conditions. HA showed rheological behavior consistent with that of a flexible polymer. The elastic behavior observed for entangled HA networks showed reptational relaxation with a large distribution of time scales, which disappeared quickly (15 min) with the addition of hyaluronidase (HAase). We conclude that the broadband mechanical probing of model systems (HA solutions) provides quantitative data that are crucial to understand the mechanical response of the EG in vivo and its role in mechanosensing.