Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma.

Background: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR)and confocal immunofluorescence. Results: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling Pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets

Difference in astringency of the main pea protein fractions

Interactions between food and saliva govern complex mouthfeel perceptions such as astringency. Herein, we present a study of the interactions of salivary proteins with the main pea protein fractions that are obtained by isoelectric and salt precipitation (legumin-rich, vicilin-rich and albumin-rich fractions). The sensory evaluations performed on protein solutions by trained panelists evidenced that all three protein fractions exhibit a basal level of astringency, but that the albumin fraction was perceived as the most astringent one. All three fractions induced significant but comparable loss of salivary lubrication. Yet, when compared to the other fractions, the albumin fraction showed the formation of a thicker and more rigid film on salivary conditioning film-coated sensors as measured using a quartz crystal microbalance with dissipation monitoring (QCM-D). We also present proteomics studies on the precipitates obtained from the mixtures of saliva and pea protein fractions. Protein identification finds a pool of salivary proteins involved in non-specific interactions with all the three pea protein fractions. Yet, 13 pea proteins specific to the albumin fraction were identified as being involved in specific interactions with salivary proteins. Several of these proteins are part of the plant defense mechanisms and are likely to interact with many salivary proteins. This could explain the higher number of salivary proteins found in the precipitate induced by the albumin fraction when compared to the other two. These quantitative results increase the understanding of the complex links between plant protein-salivary protein interactions and astringency

Future weather

The impact of climate change will manifest itself in our future weather. In the project Future Weather we investigated a number of these impact relevant weather conditions in the (present and) future climate. We focussed primarily on changes in precipitation extremes on different scales ranging from intense showers at local scales to multi-day precipitation extremes over the Rhine catchment area. On an intermediate scale, regional differences in precipitation within the Netherlands are studied. Finally, we considered a worst case scenario of a combined wind and discharge extreme

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa

Human influence on growing-period frosts like the early April 2021 in Central France

International audienceAbstract. In early April 2021 several days of harsh frost affected central Europe. This led to very severe damage in grapevine and fruit trees in France, in regions where young leaves had already unfolded due to unusually warm temperatures in the preceding month (March 2021). We analysed with observations and 172 climate model simulations how human-induced climate change affected this event over central France, where many vineyards are located. We found that, without human-caused climate change, such temperatures in April or later in spring would have been even lower by 1.2 ∘C (0.75 to 1.7 ∘C). However, climate change also caused an earlier occurrence of bud burst that we characterized in this study by a growing degree day index value. This shift leaves young leaves exposed to more winter-like conditions with lower minimum temperatures and longer nights, an effect that overcompensates the warming effect. Extreme cold temperatures occurring after the start of the growing season such as those of April 2021 are now 2 ∘C colder (0.5 to 3.3 ∘C) than in preindustrial conditions, according to observations. This observed intensification of growing-period frosts is attributable, at least in part, to human-caused climate change with each of the five climate model ensembles used here simulating a cooling of growing-period annual temperature minima of 0.41 ∘C (0.22 to 0.60 ∘C) since preindustrial conditions. The 2021 growing-period frost event has become 50 % more likely (10 %–110 %). Models accurately simulate the observed warming in extreme lowest spring temperatures but underestimate the observed trends in growing-period frost intensities, a fact that yet remains to be explained. Model ensembles all simulate a further intensification of yearly minimum temperatures occurring in the growing period for future decades and a significant probability increase for such events of about 30 % (20 %–40 %) in a climate with global warming of 2 ∘C