Snakes on the Balearic Islands: An Invasion Tale with Implications for Native Biodiversity Conservation

Biological invasions are a major conservation threat for biodiversity worldwide. Islands are particularly vulnerable to invasive species, especially Mediterranean islands which have suffered human pressure since ancient times. In the Balearic archipelago, reptiles represent an outstanding case with more alien than native species. Moreover, in the last decade a new wave of alien snakes landed in the main islands of the archipelago, some of which were originally snake-free. The identification of the origin and colonization pathways of alien species, as well as the prediction of their expansion, is crucial to develop effective conservation strategies. In this study, we used molecular markers to assess the allochthonous status and the putative origin of the four introduced snake species (Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and Rhinechis scalaris) as well as ecological niche models to infer their patterns of invasion and expansion based on current and future habitat suitability. For most species, DNA sequence data suggested the Iberian Peninsula as the potential origin of the allochthonous populations, although the shallow phylogeographic structure of these species prevented the identification of a restricted source-area. For all of them, the ecological niche models showed a current low habitat suitability in the Balearic, which is however predicted to increase significantly in the next few decades under climate change scenarios. Evidence from direct observations and spatial distribution of the first-occurrence records of alien snakes (but also lizards and worm lizards) suggest the nursery trade, and in particular olive tree importation from Iberian Peninsula, as the main pathway of introduction of alien reptiles in the Balearic islands. This trend has been reported also for recent invasions in NE Spain, thus showing that olive trees transplantation may be an effective vector for bioinvasion across the Mediterranean. The combination of molecular and ecological tools used in this study reveals a promising approach for the understanding of the complex invasion process, hence guiding conservation management actions.     

Licensing of Primordial Germ Cells for Gametogenesis Depends on Genital Ridge Signaling

In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell licensing has been considered to be a cell-autonomous and gonad-independent event, based on observations that some PGCs, having migrated not to the gonad but to the adrenal gland, nonetheless enter meiosis in a time frame parallel to ovarian germ cells -- and do so regardless of the sex of the embryo. Here we test the hypothesis that germ cell licensing is cell-autonomous by examining the fate of PGCs in Gata4 conditional mutant (Gata4 cKO) mouse embryos. Gata4, which is expressed only in somatic cells, is known to be required for genital ridge initiation. PGCs in Gata4 cKO mutants migrated to the area where the genital ridge, the precursor of the gonad, would ordinarily be formed. However, these germ cells did not undergo licensing and instead retained characteristics of PGCs. Our results indicate that licensing is not purely cell-autonomous but is induced by the somatic genital ridge.     

Lactate Up-Regulates the Expression of Lactate Oxidation Complex-Related Genes in Left Ventricular Cardiac Tissue of Rats

Background

Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex.

Methods/Principal Findings

Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM) added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O₂ ^●-/H₂O₂) levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively) were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1α and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O₂ ^●-/H₂O₂ levels and up-regulation of MCT1, MCT4, LDH and PGC1α with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O₂ ^●-/H₂O₂.

Conclusions

Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O₂ ^●-/H₂O₂ driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in cardiac muscle.     

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

Background

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods

177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results

Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion

C+T raise is an early predictor for everolimus efficacy for patients with mRCC.     

The Relationship between Processing Speed and Regional White Matter Volume in Healthy Young People

Processing speed is considered a key cognitive resource and it has a crucial role in all types of cognitive performance. Some researchers have hypothesised the importance of white matter integrity in the brain for processing speed; however, the relationship at the whole-brain level between white matter volume (WMV) and processing speed relevant to the modality or problem used in the task has never been clearly evaluated in healthy people. In this study, we used various tests of processing speed and Voxel-Based Morphometry (VBM) analyses, it is involves a voxel-wise comparison of the local volume of gray and white, to assess the relationship between processing speed and regional WMV (rWMV). We examined the association between processing speed and WMV in 887 healthy young adults (504 men and 383 women; mean age, 20.7 years, SD, 1.85). We performed three different multiple regression analyses: we evaluated rWMV associated with individual differences in the simple processing speed task, word–colour and colour–word tasks (processing speed tasks with words) and the simple arithmetic task, after adjusting for age and sex. The results showed a positive relationship at the whole-brain level between rWMV and processing speed performance. In contrast, the processing speed performance did not correlate with rWMV in any of the regions examined. Our results support the idea that WMV is associated globally with processing speed performance regardless of the type of processing speed task.     

Music Training Increases Phonological Awareness and Reading Skills in Developmental Dyslexia: A Randomized Control Trial

There is some evidence for a role of music training in boosting phonological awareness, word segmentation, working memory, as well as reading abilities in children with typical development. Poor performance in tasks requiring temporal processing, rhythm perception and sensorimotor synchronization seems to be a crucial factor underlying dyslexia in children. Interestingly, children with dyslexia show deficits in temporal processing, both in language and in music. Within this framework, we test the hypothesis that music training, by improving temporal processing and rhythm abilities, improves phonological awareness and reading skills in children with dyslexia. The study is a prospective, multicenter, open randomized controlled trial, consisting of test, rehabilitation and re-test (ID NCT02316873). After rehabilitation, the music group (N = 24) performed better than the control group (N = 22) in tasks assessing rhythmic abilities, phonological awareness and reading skills. This is the first randomized control trial testing the effect of music training in enhancing phonological and reading abilities in children with dyslexia. The findings show that music training can modify reading and phonological abilities even when these skills are severely impaired. Through the enhancement of temporal processing and rhythmic skills, music might become an important tool in both remediation and early intervention programs.

Trial Registration

ClinicalTrials.gov NCT02316873     

Whole-Genome Analysis of Diversity and SNP-Major Gene Association in Peach Germplasm

Peach was domesticated in China more than four millennia ago and from there it spread world-wide. Since the middle of the last century, peach breeding programs have been very dynamic generating hundreds of new commercial varieties, however, in most cases such varieties derive from a limited collection of parental lines (founders). This is one reason for the observed low levels of variability of the commercial gene pool, implying that knowledge of the extent and distribution of genetic variability in peach is critical to allow the choice of adequate parents to confer enhanced productivity, adaptation and quality to improved varieties. With this aim we genotyped 1,580 peach accessions (including a few closely related Prunus species) maintained and phenotyped in five germplasm collections (four European and one Chinese) with the International Peach SNP Consortium 9K SNP peach array. The study of population structure revealed the subdivision of the panel in three main populations, one mainly made up of Occidental varieties from breeding programs (POP1OC_B), one of Occidental landraces (POP2OC_T) and the third of Oriental accessions (POP3OR). Analysis of linkage disequilibrium (LD) identified differential patterns of genome-wide LD blocks in each of the populations. Phenotypic data for seven monogenic traits were integrated in a genome-wide association study (GWAS). The significantly associated SNPs were always in the regions predicted by linkage analysis, forming haplotypes of markers. These diagnostic haplotypes could be used for marker-assisted selection (MAS) in modern breeding programs.