Plasma glutamine decreases immediately after surgery and is related to incisiveness

Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery.     

Drug treatment in the development of mismatch repair defective acute leukemia and myelodysplastic syndrome

DNA from therapy-related acute leukemia/myelodysplastic syndrome cases (tAL/MDS) from the GIMEMA [Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto] Archive was examined for the microsatellite instability (MSI(+)) phenotype that is diagnostic for defective DNA mismatch repair. More than 60% (16/25) of tAL/MDS cases were MSI(+) in contrast to <4% (0/28) of de novo cases. hMLH1 gene silencing was rare and evidence of promoter methylation was found in less than one-third of the MSI(+) cases. Among the GIMEMA patients who had been treated for breast cancer there was an apparent trend towards early onset primary breast disease. This suggests that there might be common predisposing factors for breast cancer and tAL/MDS. There were also three examples of mutations in the MRE11 gene among the 25 tAL/MDS cases suggesting that defective recombinational DNA repair may promote the development of secondary malignancy. MSI(+) tAL/MDS was significantly associated with previous chemotherapy and the frequency of MSI(+) among radiotherapy patients was considerably lower. In view of the established relationship between drug resistance and mismatch repair defects, we suggest that selection for therapeutic drug resistance may contribute to the incidence of MSI(+) tAL/MDS.     

Fine-scale genetic structure suggests low levels of short-range gene flow in a wolf population of the Italian Apennines

We investigated local gene flow in a high-density wolf (Canis lupus) population of the Italian Apennines, where no effective barrier to wolf dispersal was present. From 1998 to 2004 we examined wolf carcasses and non-invasively collected samples, focusing on three mountain districts, separated by two valleys, where wolf packs showed high spatial stability. Using nine autosomal microsatellites we successfully genotyped 177 samples, achieving the identification of 74 wolves. Genetic relatedness steeply decreased with increasing distance between sampling areas, thus suggesting that short-distance interpack migration is infrequent in this population. In addition, no individual from a central pack under intensive monitoring was sampled in the range of the surrounding packs over a 4-year period. The limited short-distance gene flow resulted in a cryptic genetic structure, which was revealed by Bayesian analysis. A different genetic cluster was found in each of the three mountain areas, and a small proportion of first-generation immigrants was detected. Overall, the present study suggests that local genetic differentiation in Italian wolves might arise from high spatial stability of packs and can be favoured by a combination of long-range dispersal, the attitude to mate between unrelated individuals and a high young mortality rate.     

Memory keeps you at home: a mechanistic model for home range emergence

Despite its central place in animal ecology no general mechanistic movement model with an emergent home-range pattern has yet been proposed. Random walk models, which are commonly used to model animal movement, show diffusion instead of a bounded home range and therefore require special modifications. Current approaches for mechanistic modeling of home ranges apply only to a limited set of taxa, namely territorial animals and/or central place foragers. In this paper we present a more general mechanistic movement model based on a biased correlated random walk, which shows the potential for home-range behavior. The model is based on an animal tracking a dynamic resource landscape, using a biologically plausible two-part memory system, i.e. a reference- and a working-memory. Our results show that by adding these memory processes the random walker produces home-range behavior as it gains experience, which also leads to more efficient resource use. Interestingly, home-range patterns, which we assessed based on home-range overlap and increase in area covered with time, require the combined action of both memory components to emerge. Our model has the potential to predict home-range size and can be used for comparative analysis of the mechanisms shaping home-range patterns.     

The cold-active lipase of Pseudomonas fragi. Heterologous expression, biochemical characterization and molecular modeling.

A recombinant lipase cloned from Pseudomonas fragi strain IFO 3458 (PFL) was found to retain significant activity at low temperature. In an attempt to elucidate the structural basis of this behaviour, a model of its three-dimensional structure was built by homology and compared with homologous mesophilic lipases, i.e. the Pseudomonas aeruginosa lipase (45% sequence identity) and Burkholderia cepacia lipase (38%). In this model, features common to all known lipases have been identified, such as the catalytic triad (S83, D238 and H260) and the oxyanion hole (L17, Q84). Structural modifications recurrent in cold-adaptation, i.e. a large amount of charged residues exposed at the protein surface, have been detected. Noteworthy is the lack of a disulphide bridge conserved in homologous Pseudomonas lipases that may contribute to increased conformational flexibility of the cold-active enzyme.     

SIMLR: A Tool for Large‐Scale Genomic Analyses by Multi‐Kernel Learning

SIMLR (S ingle‐cell I nterpretation via M ulti‐kernel L eaR ning), an open‐source tool that implements a novel framework to learn a sample‐to‐sample similarity measure from expression data observed for heterogenous samples, is presented here. SIMLR can be effectively used to perform tasks such as dimension reduction, clustering, and visualization of heterogeneous populations of samples. SIMLR was benchmarked against state‐of‐the‐art methods for these three tasks on several public datasets, showing it to be scalable and capable of greatly improving clustering performance, as well as providing valuable insights by making the data more interpretable via better a visualization. SIMLR is available on https://github.com/BatzoglouLabSU/SIMLR GitHub in both R and MATLAB implementations. Furthermore, it is also available as an R package on http://bioconductor.org     

Methylation of histone H3 at lysine 37 by Set1 and Set2 prevents spurious DNA replication

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