Custom Array Comparative Genomic Hybridization: the Importance of DNA Quality, an Expert Eye, and Variant Validation.

The presence of false positive and false negative results in the Array Comparative Genomic Hybridization (aCGH) design is poorly addressed in literature reports. We took advantage of a custom aCGH recently carried out to analyze its design performance, the use of several Agilent aberrations detection algorithms, and the presence of false results. Our study provides a confirmation that the high density design does not generate more noise than standard designs and, might reach a good resolution. We noticed a not negligible presence of false negative and false positive results in the imbalances call performed by the Agilent software. The Aberration Detection Method 2 (ADM-2) algorithm with a threshold of 6 performed quite well, and the array design proved to be reliable, provided that some additional filters are applied, such as considering only intervals with average absolute log2ratio above 0.3. We also propose an additional filter that takes into account the proportion of probes with log2ratio exceeding suggestive values for gain or loss. In addition, the quality of samples was confirmed to be a crucial parameter. Finally, this work raises the importance of evaluating the samples profiles by eye and the necessity of validating the imbalances detected

Assessing the Future Streetscape of Rimini Harbor Docks with Virtual Reality

The human factor plays an important role in the successful design of infrastructure to support sustainable mobility. By engaging users early in the design process, information can be obtained before physical environments are built, making designed spaces more attractive and safer for users. This study presents the collected data of a virtual reality (VR) application in which user perception has been evaluated within an urban redevelopment context. The area under consideration is the Canal of the Port of Rimini (Italy), a degraded area not connected to the city center. The redevelopment of degraded urban areas is the first step towards achieving the sustainability aims set out in the Sustainable Development Goals. Prior to this work, evaluation methods were developed in the decision-making process, considering different social, economic, and environmental aspects in order to obtain a priority scale of interventions for urban regeneration. Architectural solutions were proposed to represent targeted and specific interventions that are designed precisely for the context to which they are dedicated in order to make the Canal Port area a continuum with its urban context and to improve its perception by tourists and inhabitants. To assess these proposed infrastructure modifications, two models of VR were created, one relevant to the current condition and one representing the future condition after redevelopment of the area. Virtual visits to the Canal of the Port of Rimini were created under two scenarios, namely, the current situation and the future situation after redevelopment of the infrastructure. Then, human participants were involved through two different questionnaires. The first allowed participants validate the VR model created by comparing it with the real context, while the second served to evaluate the perceptions of users by comparing the two VR models of the canal before and after the intervention. The results of this empirical research highlight the benefits of engaging users early in the design process and improving the user experience before implementing renovation of the infrastructure

Lipoprotein (a) is increased in acute coronary syndromes (unstable angina pectoris and myocardial infarction), but it is not predictive of the severity of coronary lesions

Lipoprotein (a) [Lp(a)] concentrations were determined in 365 patients undergoing coronary angiography for stable angina (n = 159), unstable angina (n = 99), recent myocardial infarction (n = 45), and nonischemic heart disease (cardiomyopathy or valvular disease, n = 62, non-IHD). Mean +/- SD and median Lp(a) concentrations in stable angina (29.9 +/- 29.2;22 mg/dl) did not differ from those in non-IHD (26.9 +/- 26.3; 17), but were significantly lower than in patients with unstable angina (52.7 +/- 36.6; 58) and myocardial infarction (44.8 +/- 36.4; 34) (p0.01). Coronary angiography revealed that 261 patients, including 4 patients in the non-IHD group, had significant (or = 50%) coronary lesions. Lp(a) was higher in patients with (41 +/- 35; 32) than in those without (28 +/- 27; 19) angiographic evidence of significant coronary stenosis (p0.05) and showed a weak univariate correlation with the angiographic index (Total Score) of the severity of the disease (r = 0.106;p0.05). However, in the subgroup of 303 patients with stable/unstable angina or myocardial infarction, Lp(a) was predictive neither of angiographic presence nor of severity of coronary disease. Patients were then ranked according to the Total Score values. Among patients with comparable angiographic severity of coronary artery disease, Lp(a) appeared to be remarkably higher in patients with acute ischemic syndromes (unstable angina, myocardial infarction) than in patients with stable angina. In conclusion, Lp(a) was roughly twice as high in acute (unstable angina, myocardial infarction) than in chronic (stable angina) ischemic syndromes, but there was no difference between chronic stable angina and non-IHD.(ABSTRACT TRUNCATED AT 250 WORDS

Biodiversity, evolution and adaptation of fungi in extreme environments

Fungi play irreplaceable roles for ecosystem functioning. They may adopt different lifestyles, for example saprotrophs, symbionts or parasites: some species are cosmopolitan with a wide distribution and others, thanks to their ecological plasticity, may adapt to harsh environments precluded to most of life forms. In stressing conditions, their role is even more crucial for the recycling of organic matter or favoring nutrients uptake. When the conditions become really extreme and competition is low, fungi focus on extremotolerance and evolve peculiar competences to exploit natural or xenobiotic resources in the particular constrains imposed by the environment. This paper focuses on three different cases of fungal life in the extremes: hydrocarbon-polluted sites, extremely acidic substrates, and littoral dunes, aiming to give few but significant examples of the role of these fascinating organisms in peculiar habitats and the valuable biotechnological potentialities of the abilities they have evolved in response to such constrains

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Background: Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes. Results: A total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin. Conclusions: Our results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease

Contemplative Practices and Mental Training: Prospects for American Education

This article draws on research in neuroscience, cognitive science, developmental psychology, and education, as well as scholarship from contemplative traditions concerning the cultivation of positive development, to highlight a set of mental skills and socioemotional dispositions that are central to the aims of education in the 21st century. These include self‐regulatory skills associated with emotion and attention, self‐representations, and prosocial dispositions such as empathy and compassion. It should be possible to strengthen these positive qualities and dispositions through systematic contemplative practices, which induce plastic changes in brain function and structure, supporting prosocial behavior and academic success in young people. These putative beneficial consequences call for focused programmatic research to better characterize which forms and frequencies of practice are most effective for which types of children and adolescents. Results from such research may help refine training programs to maximize their effectiveness at different ages and to document the changes in neural function and structure that might be induced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92125/1/cdep240.pd

Free energy and molecular dynamics calculations for the cubic-tetragonal phase transition in zirconia

The high-temperature cubic-tetragonal phase transition of pure stoichiometric zirconia is studied by molecular dynamics (MD) simulations and within the framework of the Landau theory of phase transformations. The interatomic forces are calculated using an empirical, self-consistent, orthogonal tight-binding (SC-TB) model, which includes atomic polarizabilities up to the quadrupolar level. A first set of standard MD calculations shows that, on increasing temperature, one particular vibrational frequency softens. The temperature evolution of the free energy surfaces around the phase transition is then studied with a second set of calculations. These combine the thermodynamic integration technique with constrained MD simulations. The results seem to support the thesis of a second-order phase transition but with unusual, very anharmonic behaviour above the transition temperature

Hirschsprung disease, associated syndromes and genetics: A review

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.published_or_final_versio

A metagenomics study on Hirschsprung's disease associated enterocolitis: Biodiversity and gut microbial homeostasis depend on resection length and patient's clinical history

Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status. Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity. Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences. Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history

Neurofibromatosis

Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in an autosomal dominant fashion, this phacomatosis is classified into two genetically distinct subtypes characterized by multiple cutaneous lesions and tumors of the peripheral and central nervous system. Neurofibromatosis type 1 (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500 individuals and presents with a variety of characteristic abnormalities of the skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2), previously termed central neurofibromatosis, is much more rare occurring in less than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent in the late teens with a sudden loss of hearing due to the development of bi-or unilateral vestibular schwannomas. In addition NF2 patients may suffer from further nervous tissue tumors such as meningiomas or gliomas. This review summarizes the characteristic features of the two forms of NF and outlines commonalities and distinctions between NF1 and NF2