Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I-IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype-phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported "lethal clusters" were causative of OI types I-IV. Some discrepancies have been highlighted also considering the "50-55 nucleotides rule," as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients

Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71–82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan1 Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets

NEMATODE COLONIZATION OF PYRITE CINDER-POLLUTED SOIL

The nematofauna was studied in the early stages of a remediation trial at an industrial site where pyrite cinders had accumulated for 40 years in a large area and were then covered with mineral soil. The cinders were contaminated with several metals and metalloids. The soil of the experimental plots was derived from the mixture of cinders with the covering soil in a 1:1 ratio. Plots were amended with manure and sown with 3 metal resistant plants: Sorghum bicolor L., Helianthus annuus L., and Arundo donax L. Samples were taken : a) at the beginning of the trial on the pyrite cinders and covering soil, separately; b) from the mixture before the application of manure; c) from cultivated plots. Nematode communities were compared by using general composition, trophic structure, biodiversity and ecology indices. Nematofauna and other soil fauna were not detected in the pyrite cinders. Nematodes were recorded in the covering soil and after mixing with the cinders. In these early stages of the remediation process, amending and cropping increased nematode abundance and biodiversity compared to the initial situation of the pyrite cinders. The nematode community structures and all calculated indices showed an increase in the quality of the soil after the remediation process. Our results showed that phytoremediation brought about the repopulation of an extremely compromised area. Moreover, the analysis of nematofauna could be a useful tool for assessing the degree of soil disturbance and soil remediation

Home and neighbourhood correlates of BMI among children living in socioeconomically disadvantaged neighbourhoods

A detailed understanding of the underlying drivers of obesity-risk behaviours is needed to inform prevention initiatives, particularly for individuals of low socioeconomic position who are at increased risk of unhealthy weight gain. However, few studies have concurrently considered factors in the home and local neighbourhood environments, and little research has examined determinants among children from low socioeconomic backgrounds. The present study examined home, social and neighbourhood correlates of BMI (kg/m2) in children living in disadvantaged neighbourhoods. Cross-sectional data were collected from 491 women with children aged 5–12 years living in forty urban and forty rural socioeconomically disadvantaged areas (suburbs) of Victoria, Australia in 2007 and 2008. Mothers completed questionnaires about the home environment (maternal efficacy, perceived importance/beliefs, rewards, rules and access to equipment), social norms and perceived neighbourhood environment in relation to physical activity, healthy eating and sedentary behaviour. Children\u27s height and weight were measured at school or home. Linear regression analyses controlled for child sex and age. In multivariable analyses, children whose mothers had higher efficacy for them doing physical activity tended to have lower BMI z scores (B = − 0·04, 95 % CI − 0·06, − 0·02), and children who had a television (TV) in their bedroom (B = 0·24, 95 % CI 0·04, 0·44) and whose mothers made greater use of food as a reward for good behaviour (B = 0·05, 95 % CI 0·01, 0·09) tended to have higher BMI z scores. Increasing efficacy among mothers to promote physical activity, limiting use of food as a reward and not placing TV in children\u27s bedrooms may be important targets for future obesity prevention initiatives in disadvantaged communities

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Alternative method to visualize receptor dynamics in cell membranes

There is a close relation between membrane receptor dynamics and their behavior. Several microscopy techniques have been developed to study protein dynamics in live cells such as the Fluorescence Recovery After Photobleaching (FRAP) or the Single Particle Tracking (SPT). These methodologies require expensive instruments, are time consuming, allow the analysis of a small portion of the cell or an extremely small number of receptors at a time. Here we propose a time-saving approach that allows to visualize the entire receptor pool and its localization in time. This protocol requires an epifluorescence microscope equipped for structured illuminated sectioning and for live cell imaging. It can be applied to characterize membrane receptor and multi-protein complex and their response to activators or inhibitors. Image acquisition and analysis can be performed in two days, while cells and substratum preparation require a few minutes a day for three days

Finger creases lend a hand in Kabuki syndrome.

International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS

Smart valorization of waste biomass: Exhausted lemon peels, coffee silverskins and paper wastes for the production of levulinic acid

In recent years, the replacement of fossil resources with renewable ones has focused great interest, expecially as regards the production of new valuable bio-products and bio-fuels, in progressive replacement of the traditional petroleum-based ones.The Waste Management Policy strongly encourages the valorization of waste biomasses into added-value bio-chemicals, instead of their traditional combustion for energy recovery or, even worse, of their landfill disposal. In this context, the acid-catalysed hydrothermal conversion of negative-value bio-wastes into levulinic acid (LA) represents a smart exploitation possibility, already developed and optimized on pilot-scale, and widely adaptable to different kinds of feedstocks. In this work, the LA production was investigated starting from two bio-wastes deriving from industrial Italian food-processing, e.g.exhausted lemon peels and coffee silverskins, together with that of a clean cellulose powder, which derives from the cutting operations occurring during the tissue paper production. The effect of the main reaction parameters on the LA synthesis, in particular the concentration of the acid catalyst, the biomass loading, the reaction temperature/time and, additionally, the effect of an upstream milder acid pretreatment, was investigated and discussed. Moreover, in the case of coffee silverskin, a preliminary extraction step of the water-soluble phenolics has further improved the fractionation and exploitation of this waste biomass. These compounds have been proposed as natural antioxidants, which represent very valuable niche products for nutraceutical uses. The described examples confirm the feasibility of an integrated valorization of the waste biomass, well in agreement with the Biorefinery concept

Changes to the gut microbiota of a wild juvenile passerine in a multidimensional urban mosaic

Urbanisation is a major anthropogenic perturbation presenting novel ecological and evolutionary challenges to wild populations. Symbiotic microorganisms residing in the gastrointestinal tracts (gut) of vertebrates have mutual connections with host physiology and respond quickly to environmental alterations. However, the impact of anthropogenic changes and urbanisation on the gut microbiota remains poorly understood, especially in early development. To address this knowledge gap, we characterised the gut microbiota of juvenile great tits ( Parus major ) reared in artificial nestboxes and in natural cavities in an urban mosaic, employing two distinct frameworks characterising the urban space. Microbial diversity was influenced by cavity type. Alpha diversity was affected by the amount of impervious surface surrounding the breeding location, and positively correlated with tree cover density. Community composition differed between urban and rural sites: these alterations covaried with sound pollution and distance to the city centre. Overall, the microbial communities reflect and are possibly influenced by the heterogeneous environmental modifications that are typical of the urban space. Strikingly, the choice of framework and environmental variables characterising the urban space can influence the outcomes of such ecological studies. Our results open new perspectives to investigate the impact of microbial symbionts on the adaptive capacity of their hosts