The extent of whole‐genome copy number alterations predicts aggressive features in primary melanomas

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP‐array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.     

BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism

Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells.     

Genomic Characterization of Phenylalanine Ammonia Lyase Gene in Buckwheat

Phenylalanine Ammonia Lyase (PAL) gene which plays a key role in bio-synthesis of medicinally important compounds, Rutin/quercetin was sequence characterized for its efficient genomics application. These compounds possessing anti-diabetic and anti-cancer properties and are predominantly produced by Fagopyrum spp. In the present study, PAL gene was sequenced from three Fagopyrum spp. (F. tataricum, F. esculentum and F. dibotrys) and showed the presence of three SNPs and four insertion/deletions at intra and inter specific level. Among them, the potential SNP (position 949^th bp G>C) with Parsimony Informative Site was selected and successfully utilised to individuate the zygosity/allelic variation of 16 F. tataricum varieties. Insertion mutations were identified in coding region, which resulted the change of a stretch of 39 amino acids on the putative protein. Our Study revealed that autogamous species (F. tataricum) has lower frequency of observed SNPs as compared to allogamous species (F. dibotrys and F. esculentum). The identified SNPs in F. tataricum didn’t result to amino acid change, while in other two species it caused both conservative and non-conservative variations. Consistent pattern of SNPs across the species revealed their phylogenetic importance. We found two groups of F. tataricum and one of them was closely related with F. dibotrys. Sequence characterization information of PAL gene reported in present investigation can be utilized in genetic improvement of buckwheat in reference to its medicinal value.     

Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer’s Disease

Background

Weight loss is common in people with Alzheimer’s disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown.

Aims

To assess weight loss as a predictor of dementia and AD in MCI.

Methods

One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight.

Results

Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5–6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4–8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD.

Conclusions

Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment.     

Source Odor,Intensity, and Exposure Pattern Affect Antipredatory Responses in the Subterranean Rodent Ctenomys talarum

Predation is a strong selective force, and prey species may show specific adaptations that allow recognition, avoidance, and defense against predators. Facing a situation of predatory risk, anxiety constitutes a reaction of adaptive value, allowing to evaluate the potential risk of this encounter as well as to generate a physiological and behavioral response. Previous studies in the subterranean rodent Ctenomys talarum revealed that exposure to predator odors (urine or fur) generates an anxiety state and induces behavioral changes. However, no differences between the responses generated by both odor sources were observed, although fur odors may indicate a higher level of predatory immanence. Therefore, the aim of this study was to evaluate the behavioral and physiological responses of C. talarum to different intensities of predator odors (urine and fur) and to the repeated exposition to the same odorous stimulus. When comparing the highest behavioral effects elicited by both predatory odors on C. talarum, our study supports the assumption that fur odors are more anxiogenic than urine, while the former provoked significant changes in the distance traveled, the number of arm entries and time in transparent arms in the elevated plus maze; cat urine only caused slight changes on those behavioral parameters. Furthermore, we also found that the intensity of natural predator odor presented to tuco‐tucos has a role on the appearance of defensive behaviors, although an amount‐dependent relationship between predator odor and anxiety levels was not observed. Finally, while individuals exposed for 1 day to fur odor displayed an evident anxiety state, those exposed repeatedly for 5 consecutive days did not differ with the control group in their behavioral response, indicating a clear habituation to the predatory cue. In our intensity and habituation experiments, we did not find differences in the measured physiological parameters among control individuals, exposed to different cues intensity (urine and fur odor) and exposed only once or for 5 days to fur odor. These results provide valuable evidence that the types of predatory odor, along with the frequency of exposition, are important determinants of the appearance, strength, and extinction of defensive behaviors in the subterranean rodent C. talarum.     

Ecological genetics of Italian peach‐potato aphid (Myzus persicae) populations in relation to geography,dispersal and insecticide resistance as studied using microsatellite and resistance markers

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The contribution of <Emphasis Type="Italic">Potamogeton crispus</Emphasis> to the phosphorus budget of an urban shallow lake: Lake Monger,Western Australia

Lake Monger (Perth, Western Australia) is a highly eutrophic lake, characterised by very low species richness of macrophytes with the dominance of Potamogeton crispus. Mesocosm experiments were performed using water and plants collected from the lake to determine the effects of vegetation decay on the phosphorus (P) concentrations in the overlying waters. After 2 weeks of experimental incubation of mesocosms with and without re-oxygenation, P concentrations in the water column were significantly higher, showing a quite similar effect of P. crispus on the phosphorus release in different mesocosms. The results of our study provide clear evidence that the P concentrations in overlying waters mainly depend upon the plant P content and developmental stage. Although many sources contribute to the nutrient load of Lake Monger, macrophyte harvesting, prior to its senescence, might constitute a significant in-lake measure for reducing the internal P load.