The genetic structure and connectivity in two sympatric rodent species with different life histories are similarly affected by land use disturbances

The negative impact of habitat fragmentation due to human activities may be different in different species that co-exist in the same area, with consequences on the development of environmental protection plans. Here we aim at understanding the effects produced by different natural and anthropic landscape features on gene flow patterns in two sympatric species with different specializations, one generalist and one specialist, sampled in the same locations. We collected and genotyped 194 wood mice (generalist species) and 199 bank voles (specialist species) from 15 woodlands in a fragmented landscape characterized by different potential barriers to dispersal. Genetic variation and structure were analyzed in the two species, respectively. Effective migration surfaces, isolation-by-resistance (IBR) analysis, and regression with randomization were used to investigate isolation-by-distance (IBD) and the relative importance of land cover elements on gene flow. We observed similar patterns of heterozygosity and IBD for both species, but the bank vole showed higher genetic differences among geographic areas. The IBR analysis suggests that (i) connectivity is reduced in both species by urban areas but more strongly in the specialist bank vole; (ii) cultivated areas act as dispersal corridors in both species; (iii) woodlands appear to be an important factor in increasing connectivity in the bank vole, and less so in the wood mouse. The difference in dispersal abilities between a generalist and specialist species was reflected in the difference in genetic structure, despite extensive habitat changes due to human activities. The negative effects of fragmentation due to the process of urbanization were, at least partially, mitigated by another human product, i.e., cultivated terrains subdivided by hedgerows, and this was true for both species

Investigating geographic and temporal genetic variation in the black grouse (Lyrurus tetrix) in the Italian Alps

The black grouse (Lyrurus tetrix) is a Galliform distributed across northern Eurasia, and is a game bird in most EU countries. Although the species is listed as ‘Least Concern’ by the IUCN, populations at the western and southern edges of its range are considered ‘Vulnerable’ due to increasing habitat fragmentation and human disturbance. Between 1995 and 2017, in collaboration with several hunting associations, we collected more than 600 black grouse samples across seven regions of the Italian Alps. Ten microsatellite markers (STRs) and 2442 Single Nucleotide Polymorphisms (SNPs) were analysed in large subsets of the collected data, with the aim of identifying environmental, temporal and anthropic factors that affect the distribution and level of genomic variation. The main factor shaping the genetic distances between populations based on STRs is the geographic distance between them (i.e. isolation-bydistance), but even the populations on the two extremes of our sampling area are very similar (Fst between the two regions = 0.053). SNP data supports the STR analysis. However, isolation-by-resistance methods for the larger STR data set show that both higher altitudes and urban areas inhibit movement of grouse between populations. While temporal analysis of STRs for the Trentino-Alto Adige region showed no significant change in the mean number of alleles and allelic size range between the two time frames studied (e.g. mean number of alleles 1995-1999: 8.8, 2009-2010: 8.2), and the expected heterozygosity was high in both time frames (1995-1999: 0.740, 2009-2010: 0.722). While black grouse population size is reportedly decreasing, our results suggest there is no measurable genetic impact from this trend. Hence this dataset provides a basis for future monitoring of genetic diversity in this charismatic alpine species

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Genetic variation in prehistoric Sardinia

We sampled teeth from 53 ancient Sardinian (Nuragic) individuals who lived in the Late Bronze Age and Iron Age, between 3,430 and 2,700 years ago. After eliminating the samples that, in preliminary biochemical tests, did not show a high probability to yield reproducible results, we obtained 23 sequences of the mitochondrial DNA control region, which were associated to haplogroups by comparison with a dataset of modern sequences. The Nuragic samples show a remarkably low genetic diversity, comparable to that observed in ancient Iberians, but much lower than among the Etruscans. Most of these sequences have exact matches in two modern Sardinian populations, supporting a clear genealogical continuity from the Late Bronze Age up to current times. The Nuragic populations appear to be part of a large and geographically unstructured cluster of modern European populations, thus making it difficult to infer their evolutionary relationships. However, the low levels of genetic diversity, both within and among ancient samples, as opposed to the sharp differences among modern Sardinian samples, support the hypothesis of the expansion of a small group of maternally related individuals, and of comparatively recent differentiation of the Sardinian gene pools. © Springer-Verlag 2007

mismatch repair deficiency mmrd in glioma patients pts frequency and correlation with clinical histological and molecular characteristics

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The p53 Codon 72 Pro/Pro Genotype Identifies Poor-Prognosis Neuroblastoma Patients: Correlation with Reduced Apoptosis and Enhanced Senescence by the p53-72P Isoform.

The p53 gene is rarely mutated in neuroblastoma, but codon 72 polymorphism that modulates its proapoptotic activity might influence cancer risk and clinical outcome. We investigated whether this polymorphism affects neuroblastoma risk and disease outcome and assessed the biologic effects of the p53-72R and p53-72P isoforms in p53-null cells. Comparison of 288 healthy subjects and 286 neuroblastoma patients revealed that the p53-72 polymorphism had no significant impact on the risk of developing neuroblastoma; however, patients with the Pro/Pro genotype had a shorter survival than those with the Arg/Arg or the Arg/Pro genotypes even in the stage 3 and 4 subgroup without MYCN amplification. By Cox regression analysis, the p53 Pro/Pro genotype seems to be an independent marker of poor prognosis (hazard ratio = 2.74; 95% confidence interval = 1.14\u20136.55, P = .014) together with clinical stage, MYCN status, and age at diagnosis. In vitro, p53-72P was less effective than p53-72R in inducing apoptosis and inhibiting survival of p53-null LAN-1 cells treated with etoposide, topotecan, or ionizing radiation but not taxol. By contrast, p53-72P was more effective in promoting p21-dependent accelerated senescence, alone or in the presence of etoposide. Thus, the p53-72 Pro/Pro genotype might be a marker of poor outcome independent of MYCN amplification, possibly improving risk stratification. Moreover, the lower apoptosis and the enhanced accelerated senescence by the p53-72P isoform in response to DNA damage suggest that patients with neuroblastoma with the p53-72 Pro/Pro genotype may benefit from therapeutic protocols that do not rely only on cytotoxic drugs that function, in part, through p53 activation