Effects of the restoration actions to combat desertification on soils: the practice project study site in Pula (Sardinia, Italy)

Land Degradation and Desertification affect much of the world’s drylands, resulting in a significant loss of biological and economic productivity. Responding to desertification by improving the efficiency of land and resource management represents a crucial step towards social welfare in drylands. However, the evaluation of the actions to combat desertification remains limited. The PRACTICE EC-FP7 project develops and tests integrated evaluation protocols to assess the effectiveness of restoration practices in a network of study sites distributed among the most LD affected regions of the world

Keratitis-ichthyosis-deafness syndrome, atypical connexin GJB2 genemutation, and peripheral T-cell lymphoma: more than a random association?

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by a variety of skin lesions— that is, palmoplantar keratoderma, thickening of the skin, and erythematous verrucous lesions—neurosensorial hypoacusia, and keratitis with a variable degree of visual impairment. Both sporadic and familial forms of the syndrome have been described, the latter usually showing a dominant pattern of inheritance. The molecular lesion responsible for the syndrome typically involves the connexin 26 (Cx26) gene (GJB2). Most patients display the heterozygous c.148G→A mutation causing the substitution of an aspartic acid for an asparagine at position 50 (p.Asp50Asn), while a few of them show the c.50C→T mutation, implying the substitution of a serine for a phenylalanine at position 17 (p.Ser17Phe). However, even a mutation in the connexin 30 (Cx30) gene (GJB6) has been found in a typical KID patient, thus suggesting a genetic heterogeneity of the syndrome. As connexins are a large family of small integral membrane proteins which influence tissue cornification by modulating the establishment of direct cell-cell communication through gap junction channels, it is likely that defects involving this class of proteins are at the basis of the wellknown increased incidence of squamous cell carcinoma in KID patients

Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses

A Novel null homozygous mutation confirms <i>CACNA2D2</i> as a gene mutated in epileptic encephalopathy

Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding α2δ-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel functionality has been identified in a single family. In the same family, a rare CELSR3 polymorphism also segregated with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to consanguineous parents, we performed whole exome sequencing (WES) for homozygosity mapping and mutation detection. WES identified extended autozygosity on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA (p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished α2δ-2 expression. In summary, we identified a novel null CACNA2D2 mutation associated to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model. Molecular and statistical analyses together argued in favor of a causal contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3, although potentially damaging, is likely incidental

Relative impact of indels versus SNPs on complex disease

It is unclear whether insertions and deletions (indels) are more likely to influence complex traits than abundant single‐nucleotide polymorphisms (SNPs). We sought to understand which category of variation is more likely to impact health. Using the SardiNIA study as an exemplar, we characterized 478,876 common indels and 8,246,244 common SNPs in up to 5,949 well‐phenotyped individuals from an isolated valley in Sardinia. We assessed association between 120 traits, resulting in 89 nonoverlapping‐associated loci.We evaluated whether indels were enriched among credible sets of potential causal variants. These credible sets included 1,319 SNPs and 88 indels. We did not find indels to be significantly enriched. Indels were the most likely causal variant in seven loci, including one locus associated with monocyte count where an indel with causality and mechanism previously demonstrated (rs200748895:TGCTG/T) had a 0.999 posterior probability. Overall, our results show a very modest and nonsignificant enrichment for common indels in associated loci.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/1/gepi22175_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/2/gepi22175-sup-0001-Gagliano-Supplementary.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/3/gepi22175.pd

Detection of phylogenetically informative polymorphisms in the entire euchromatic portion of human Y chromosome from a Sardinian sample

Background: Next-Generation Sequencing methods have led to a great increase in phylogenetically useful markers within the male specific portion of the Y chromosome, but previous studies have limited themselves to the study of the X-degenerate regions. Methods: DNA was extracted from peripheral blood samples of adult males whose paternal grandfathers were born in Sardinia. The DNA samples were sequenced, genotyped and subsequently analysed for variant calling for approximately 23.1 Mbp of the Y chromosome. A phylogenetic tree was built using Network 4.6 software. Results: From low coverage whole genome sequencing of 1,194 Sardinian males, we extracted 20,155 phylogenetically informative single nucleotide polymorphisms from the whole euchromatic region, including the X-degenerate, X-transposed, and Ampliconic regions, along with variants in other unclassified chromosome intervals and in the readable sequences of the heterochromatic region. Conclusions: The non X-degenerate classes contain a significant portion of the phylogenetic variation of the whole chromosome and their inclusion in the analysis, almost doubling the number of informative polymorphisms, refining the known molecular phylogeny of the human Y chromosome

Systemic Administration of Orexin a Loaded Liposomes Potentiates Nucleus Accumbens Shell Dopamine Release by Sucrose Feeding

Orexin neurons originate in the lateral and dorsomedial hypothalamus and perifornical area and produce two different neuropeptides: orexin A (OxA) and orexin B (OxB), which activate OxR1 and OxR2 receptors. In the lateral hypothalamus (LH) orexin neurons are involved in behavior motivated by natural rewards such as palatable food (sugar, high-fat food) and it has been demonstrated similarly that the orexin signaling in the ventral tegmental area (VTA) is implicated in the intake of high-fat food. The VTA is an important area involved in reward processing. Given the involvement of nucleus accumbens (NAc) shell dopamine (DA) in motivation for food, we intended to investigate the effect of OxA on the basal and feeding-activated DA transmission in the NAc shell. OxA is a large peptide and does not cross the blood–brain barrier and for this reason was loaded on two kinds of liposomes: anti-transferrin-monoclonal antibodies (OX26-mAb) and lactoferrin-modified stealth liposomes. The effect of IV administration of both OxA liposomes on NAc shell DA was studied by microdialysis in freely moving rats. OxA, administered using both kinds of liposomes, produced a delayed and transitory increase in dialysate DA in the NAc shell, strongly and lastingly potentiated the increase in dialysate DA elicited by sucrose pellet consumption and increased the number of eaten pellets. These effects of OxA on DA transmission and feeding were prevented by the OxR1 antagonist SB 334867. Hence, OxA acting on VTA OxR1 can facilitate sucrose-stimulated NAc shell DA transmission directly by increasing the basal activity of VTA DA neurons that send their projections to the NAc shell

A Comparison of Y-Chromosome variation in Sardinia and Anatolia is more consistent with cultural rather than demic diffusion of agriculture

Two alternative models have been proposed to explain the spread of agriculture in Europe during the Neolithic period. The demic diffusion model postulates the spreading of farmers from the Middle East along a Southeast to Northeast axis. Conversely, the cultural diffusion model assumes transmission of agricultural techniques without substantial movements of people. Support for the demic model derives largely from the observation of frequency gradients among some genetic variants, in particular haplogroups defined by single nucleotide polymorphisms (SNPs) in the Y-chromosome. A recent network analysis of the R-M269 Y chromosome lineage has purportedly corroborated Neolithic expansion from Anatolia, the site of diffusion of agriculture. However, the data are still controversial and the analyses so far performed are prone to a number of biases. In the present study we show that the addition of a single marker, DYSA7.2, dramatically changes the shape of the R-M269 network into a topology showing a clear Western-Eastern dichotomy not consistent with a radial diffusion of people from the Middle East. We have also assessed other Y-chromosome haplogroups proposed to be markers of the Neolithic diffusion of farmers and compared their intra-lineage variation—defined by short tandem repeats (STRs)—in Anatolia and in Sardinia, the only Western population where these lineages are present at appreciable frequencies and where there is substantial archaeological and genetic evidence of pre-Neolithic human occupation. The data indicate that Sardinia does not contain a subset of the variability present in Anatolia and that the shared variability between these populations is best explained by an earlier, pre-Neolithic dispersal of haplogroups from a common ancestral gene pool. Overall, these results are consistent with the cultural diffusion and do not support the demic model of agriculture diffusion

Sex-Specific Parental Effects on Offspring Lipid Levels

Background: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability. Methods and Results: In this study, we analyzed the role of parental levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL‐C, HDL‐C, and TG levels. We performed comparisons among different sex‐specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent‐of‐origin effect explains as much as ≈15% and it does so in a sex‐specific way. This observation is not owing to shared environment, given that spouse‐pair correlations were negligible (\u3c1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels. Conclusions: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age‐matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia