The signature of long-standing balancing selection at the human defensin β-1 promoter

Analysis of the human beta defensin 1 promoter region in six human populations reveals a signature of balancing selection

Both selective and neutral processes drive GC content evolution in the human genome

<p>Abstract</p> <p>Background</p> <p>Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait.</p> <p>Results</p> <p>Here we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that biased gene conversion (BGC) has been playing a role in within-genome GC content variation. Yet, a distinct contribution to GC content evolution is accounted for by a selective process. Accordingly, we searched for independent evidences that GC content distribution does not conform to neutral expectations. Indeed, after correcting for possible biases, we show that intron GC content and size display isochore-specific correlations.</p> <p>Conclusion</p> <p>We consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and BGC in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes. This view might reconcile previous contrasting findings and add some theoretical background to recent evidences suggesting that GC content domains display different behaviors with respect to highly regulated biological processes such as developmentally-stage related gene expression and programmed replication timing during neural stem cell differentiation.</p

A complex selection signature at the human AVPR1B gene

<p>Abstract</p> <p>Background</p> <p>The vasopressin receptor type 1b (<it>AVPR1B</it>) is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common <it>AVPR1B </it>haplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses.</p> <p>Results</p> <p>Here we have analyzed the two exons of the gene and the data we present suggest that <it>AVPR1B </it>has been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg) in this region has been subjected to directional selection.</p> <p>Conclusion</p> <p>Although the underlying selective pressure(s) remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.</p

Percutaneous Alcohol Sclerotherapy of Simple Hepatic Cysts. Results From a Multicentre Survey in Italy

The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

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Report on first international workshop on robotic surgery in thoracic oncology

A workshop of experts from France, Germany, Italy, and the United States took place at Humanitas Research Hospital Milan, Italy, on February 10 and 11, 2016, to examine techniques for and applications of robotic surgery to thoracic oncology. The main topics of presentation and discussion were robotic surgery for lung resection; robot-assisted thymectomy; minimally invasive surgery for esophageal cancer; new developments in computer-assisted surgery and medical applications of robots; the challenge of costs; and future clinical research in robotic thoracic surgery. The following article summarizes the main contributions to the workshop. The Workshop consensus was that since video-assisted thoracoscopic surgery (VATS) is becoming the mainstream approach to resectable lung cancer in North America and Europe, robotic surgery for thoracic oncology is likely to be embraced by an increasing numbers of thoracic surgeons, since it has technical advantages over VATS, including intuitive movements, tremor filtration, more degrees of manipulative freedom, motion scaling, and high-definition stereoscopic vision. These advantages may make robotic surgery more accessible than VATS to trainees and experienced surgeons and also lead to expanded indications. However, the high costs of robotic surgery and absence of tactile feedback remain obstacles to widespread dissemination. A prospective multicentric randomized trial (NCT02804893) to compare robotic and VATS approaches to stages I and II lung cancer will start shortly

Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gen

Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution

Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some susceptibility alleles for autoimmune diseases may be maintained in human population due to past selective processes

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM)

Objectives Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. Methods Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). Results In the final round, 23 out of 24 items obtained agreement ( >= 8) and consensus ( 0.05). Conclusions The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making