MIPSIM: similarity analysis of molecular interaction potentials

SUMMARY: MIPSIM is a computational package designed to analyse and compare 3D distributions of molecular interaction potentials (MIP) of series of biomolecules.     

Some vegetables (commonly consumed by humans) efficiently modulate bone metabolism

We have hypothesized that some vegetables which are part of the regular human diet may contain modulators of bone metabolism. To mimic a typical Western diet with large proportions of refined components, rats were pair-fed a semi-purified diet to which, in the treated animals, the dried material under investigation was added. Effects are expressed as % of untreated control. Bone parameters in rats were assessed in the proximal tibia by pQCT. Bone resorption (BR) was assessed by the urinary excretion of [3H]-tetracycline from prelabeled rats. Daily administration of 1 g of onion during 4 weeks increased total bone mineral content by 17.4% (p<0.05), trabecular bone mineral density by 13.6% (p<0.05). One g of onion/day administered to male rats blunted BR by 23-/+5% (p<0.05). Daily administration of onion to ovariectomized rats inhibited BR in a dose-dependent manner. At the highest dose (1.5 g of onion) BR was inhibited by 26-/+4% (p<0.01) as compared to 24-/+3% (p<0.001) for estradiol (27microg/kg/day). An additional 13 vegetables displayed significant effects on BR at the dose of 1g/day. Interestingly, 1g/day of soy did not inhibit BR in this model. Also, skimmed milk, meat and egg (all 1 g/day) were ineffective. Thus, common vegetables consumed by humans potently modulate bone metabolism in the rat. This opens the possibility to develop the basis for a low-cost, safe and effective nutritional approach to osteoporosis.     

Designing enzymatic kyotorphin synthesis in organic media with low water content

Design of enzymatic kyotorphin synthesis in low water media has been carried out as a function of enzyme nature, the immobilization support material and the reaction medium, by using N-benzoyl-L-tyrosine ethyl ester and L-argininamide as substrates. Native and chemically-glycated alpha-chymotrypsin deposited on supports with different degrees of aquaphilicity (celite, polypropylene PP, and polyamide PA6) were used as catalysts. Binary organic solvent systems of ethanol and different water-immiscible organic cosolvents (ethylacetate, tert-butanol, chloroform, toluene, n-hexane, and n-octane) were studied as reaction media at constant water content (3% v/v). The greater the water binding affinity of the support the lower the synthetic activity of deposited enzymes: the activity of the celite derivative was 4x greater than the polyamide derivative. The enzyme glycation process hardly modified the catalytic ability of the celite derivative, but resulted in a moderate increase in operational stability. The presence of hydrophobic organic cosolvents in the water/ethanol reaction medium significantly increased enzyme activity, whereas the selectivity of the reaction remained high. Hexane was shown to be the best cosolvent, the synthetic activity of the celite derivative in hexane-ethanol (77 : 20%, v/v) being 130x greater than that in 97% (v/v) ethanol.     

New developments in understanding the etiology of Parkinson's disease and in its treatment

Important recent advances have been made in understanding the etiology and pathogenesis of Parkinson's disease, as well as in developing novel treatments. Two newly identified genes, α-synuclein and parkin, have been linked to parkinsonism. In addition, disturbances to the normal basal ganglia circuits in Parkinson's patients are being described at both anatomical and physiological levels. These developments provide a strong scientific basis for novel medical and surgical strategies to treat the profound motor disturbances in patients with Parkinson's disease.     

Variable-Selection Emerges on Top in Empirical Comparison of Whole-Genome Complex-Trait Prediction Methods

Accurate prediction of complex traits based on whole-genome data is a computational problem of paramount importance, particularly to plant and animal breeders. However, the number of genetic markers is typically orders of magnitude larger than the number of samples (p >> n), amongst other challenges. We assessed the effectiveness of a diverse set of state-of-the-art methods on publicly accessible real data. The most surprising finding was that approaches with feature selection performed better than others on average, in contrast to the expectation in the community that variable selection is mostly ineffective, i.e. that it does not improve accuracy of prediction, in spite of p >> n. We observed superior performance despite a somewhat simplistic approach to variable selection, possibly suggesting an inherent robustness. This bodes well in general since the variable selection methods usually improve interpretability without loss of prediction power. Apart from identifying a set of benchmark data sets (including one simulated data), we also discuss the performance analysis for each data set in terms of the input characteristics.     

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71–0.94) and 0.67 (95%CI = 0.58–0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56–0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.     

Influenza Illness among Case-Patients Hospitalized for Suspected Dengue,El Salvador, 2012

We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.     

Modulation of CD6 function through interaction with Galectin-1 and -3

CD6 is a lymphocyte glycoprotein receptor that physically associates with the antigen-specific receptor complex at the center of the immunological synapse, where it interacts with its ligand CD166/ALCAM. The present work reports the carbohydrate-dependent interaction of CD6 and CD166/ALCAM with Galectin-1 and -3, two well-known soluble mammalian lectins. Both galectins interfered with superantigen-induced T cell proliferation and cell adhesion phenomena mediated by the CD6-CD166/ALCAM pair, while CD6 expression protected cells from galectin-induced apoptosis. The results suggest that interaction of Galectin-1 and -3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology.