Chromosome 16p11.2 deletions: another piece in the genetic puzzle of childhood obesity

Ipercaloric diet and reduced physical activity have driven the rise in the prevalence of childhood obesity over a relatively short time interval. Family and twin studies have led to the conclusion that the strong predicitve value of parental body mass index (BMI) mainly stems from genetic rather than environmental factors. Whereas the common polygenic obesity arises when an individual genetic make-up is susceptible to an environment that promotes energy consumption over energy expenditure, monogenic obesity, on the contrary, is the obesity associated with a single gene mutation, which is sufficient by itself to cause weight gain in a food abundant context. Genes involved in the leptin-melanocortin pathway are often mutated in these cases. The cumulative prevalence of monogenic obesity among children with severe obesity is about 5%

Water Pricing in Agriculture following the Water Framework Directive: A Systematic Review of the Literature

In October 2000, the Water Framework Directive (WFD) established a common framework for water management in Europe, thereby substantially reforming European water legislation. The Directive encourages the use of  economic instruments, including water pricing, to ensure water resource management and conservation. The aim of this systematic review was to establish the state of academic research on water pricing in connection with the WFD within the agriculture sector. It emerges that the issue of water pricing is very broad, site-specific and mostly, it faces multidisciplinary issues. Researchers should cross their conventional boundaries of investigation, trying to cut edges. While the Directive advocate for a larger implementation of economic instruments such as pricing, it seems that the large contribution from the economists is yet to come

TinderMIX : Time-dose integrated modelling of toxicogenomics data

Background: Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness. Results: We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure. Conclusions: To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.Peer reviewe

Widespread extrahepatic expression of acute-phase proteins in chicken (Gallus gallus) tissues

Acute Phase Proteins (APP) are plasma proteins that can modify their expression in response toinflammation caused by tissue injury, infections, immunological disorders, or stress. Although APP areproduced mainly in liver, extrahepatic production has been described (Marques et al., 2016; Lecchi etal., 2012). The aim of this work was to study the extrahepatic gene expression of five APP, namely α1-acid glycoprotein (AGP), Serum amyloid A (SAA), Haptoglobin-like protein (PIT54), C-rective protein(CRP) and Ovotransferrin (OVT) (O'Reilly and Eckersall, 2014) in different healthy chicken (Gallus gallus)tissues by quantitative real time PCR (qPCR) and immunohistochemistry to detect the precise locationof the proteins.APP gene expression was higher in liver compared with other tissues. mRNA coding for CRP, OVT andSAA was detected in all tissues involved in this study with a higher expression in gastrointestinal tract,respiratory system and lymphatic system. SAA expression was particularly high in cecal tonsil, lung,spleen and meckel’s diverticulum, whereas OVT showed a high expression in lung, bursa of Fabricius,pancreas, brain and adipose tissue. AGP and PIT54 was also detected in pericardial adipose tissue,spleen, kidney, lung, mucosa of proventriculus, mucosa of gizzard and pancreas but, oppositely to SAA,their mRNA was not detected in meckel’s diverticulum, cecal tonsil and bursa of Fabricius. These resultssuggest that each tissue is able to express different amount of APP even in healthy conditions andmount a local acute phase reaction. Immunohistochemistry to detect the precise location for AGP, OVTand SAA using available antibodies is ongoing

Evolution of clinical trials in ovarian cancer management over the past 20 years: never settle down, always go beyond

Purpose. A practice synthesis of available evidence-based medicine data in ovarian cancer (OC), aiming to provide directions for future research. Materials and Methods. We performed a systematic review. PubMed was searched for relevant OC trials between January 2000 and December 2019. Results. Out of 865 references screened, 199 trials were found eligible for inclusion. Most trials were multicenter (83.9%). There was a trend reduction in the number of patients enrolled/per study over the years. Studies testing targeted/biological therapies dominated the second decade (60 trials in 2010-2019 versus 2 trials in 2000-2009). The proportion of trials with positive survival and clinical outcomes significantly increased from 23.8% in early 2000s to 54.1% in the last 5 years. Trials with histology/molecular biomarker criteria were more likely to meet progression-free survival endpoint than those without these selection criteria (69.2% versus 32.6%). Conclusion. This systematic review suggests a trend of increased positive studies, mainly linked to precision medicine