Cardiorespiratory fitness, different measures of adiposity, and cancer mortality in men

Objective: The purpose was to examine the prospective relationship among cardiorespiratory fitness level (CRF), different measures of adiposity, and cancer mortality in men. Research Methods and Procedures: Participants were 38,410 apparently healthy men who completed a comprehensive baseline health examination between 1970 and 2001. Clinical measures included BMI, waist circumference (WC), percent body fat, and CRF quantified as duration of a maximal treadmill exercise test. Participants were divided into fifths of CRF, BMI, WC, and percent body fat. Hazard ratios were computed with Cox regression analysis. Results: During a mean follow‐up period of 17.2 ± 7.9 years, 1037 cancer deaths occurred. Adjusted hazard ratios across incremental BMI quintiles were 1.0, 1.23, 1.15, 1.39, and 1.72; those of WC were 1.0, 1.05, 1.03, 1.31, and 1.64; those of percent body fat were 1.0, 1.24, 1.17, 1.23, and 1.50; and those of CRF were 1.0, 0.70, 0.67, 0.70, and 0.49 (trend p < 0.01 for each). Further adjustment for CRF eliminated the significant trend in mortality risk across percent body fat groups and attenuated the trend in risk across BMI and WC groups. Adjustment of CRF for adiposity measures had little effect on mortality risk. When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), mortality rates (per 10,000 man‐years) were significantly lower in fit compared with unfit men within each stratum of BMI, WC, and percent body fat. Discussion: Higher levels of CRF are associated with lower cancer mortality risk in men, independently of several adiposity measures.     

Genetic mapping of a new set of microsatellite markers in a reference common bean (Phaseolus vulgaris) population BAT93 x Jalo EEP558

The present study describes a new set of 61 polymorphic microsatellite markers for beans and the construction of a genetic map using the BAT93 x Jalo EEP558 (BJ) population for the purpose of developing a reference linkage map for common bean (Phaseolus vulgaris). The main objectives were to integrate new microsatellites on the existing framework map of the BJ population, and to develop the first linkage map for the BJ population based exclusively on microsatellites. Of the total of 264 microsatellites evaluated for polymorphism, 42.8% showed polymorphism between the genitors. An integrated map was created totaling 199 mapped markers in 13 linkage groups, with an observed length of 1358 cM and a mean distance between markers of 7.23 cM. For the map constructed exclusively with microsatellites, 106 markers were placed in 12 groups with a total length of 606.8 cM and average distance of 6.8 cM. Linkage group designation and marker order for BM microsatellites generally agreed with previous mapping, while the new microsatellites were well distributed across the genome, corroborating the utility of the BJ population for a reference map. The extensive use of the microsatellites and the availability of a reference map can help in the development of other genetic maps for common bean through the transfer of information of marker order and linkage, which will allow comparative analysis and map integration, especially for future quantitative trait loci and association mapping studies.     

Neuromonitoreo no invasivo en unidades de cuidados intensivos en Colombia

Continuous non-invasive electroencephalographic monitoring is an essential technique for critical care patients as it shows directly and indirectly the patient’s brain activity and makes it possible to relate it with findings in the clinical status. It is highly sensitive, although its specificity is lower, so they can show alterations of the state of consciousness without clarifying the etiology.Continuous electroencephalographic recording in patients with altered levels of consciousness, seizures, and convulsive and non-convulsive status epilepticus has been increasing in recent years as real-time feedback of the cerebral function shows evolution changes and allows for the identification of electric and subclinical epileptic seizures that are highly important since they do not have clinical correlations.These findings in electroencephalographic monitoring also help to modify pharmacological and antiseizure treatments. For practitioners, they are advantageous when making timely decisions that impact the prognosis of the patient.     

Evolutionary biology of parasitic platyhelminths: The role of molecular phylogenetics

As our appreciation of the diversity within the flatworms has grown, so too has our curiosity about the ways in which these varied creatures are related to one another. In particular, the parasitic groups (trematodes, cestodes and monogeneans have been the focus of enquiry. Until recently, morphology, anatomy and life histories have provided the raw data for building hypotheses on relationships. Now, ultrastructural evidence, and most recently, molecular data from nucleic acid sequences, have been brought to bear on the topic. Here, David Blair, Andrés Campos, Michael Cummings and Juan Pedro Laclette discuss the ways in which molecular data, in particular, are helping us recognize the various lineages of flatworms.     

The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E

Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent degradation of cyclin E contributes to an orderly progression of the S phase. It has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2, an F-box protein and a substrate-targeting component of the SCF(SKP2) ubiquitin E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not with a cognate nonphosphorylated peptide. In vivo, expression of SKP2 induced cyclin E polyubiquitination and degradation. Conversion of Thr380 into nonphosphorylatable amino acids caused significant resistance of cyclin E to SKP2. The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression.     

FcgammaRIIb-mediated negative regulation of BCR signalling is associated with the recruitment of the MAPkinase-phosphatase, Pac-1, and the 3'-inositol phosphatase, PTEN

The low-affinity receptor for IgG, FcgammaRIIb, negatively regulates B cell antigen receptor (BCR)-mediated proliferative signalling. FcgammaRIIb has been reported to mediate this inhibition by uncoupling the BCR from the RasMAPkinase pathway. We now show that FcgammaRIIb-mediated negative feedback inhibition also correlates with induction of an Erk-associated phosphatase activity that reflects the rapid association of Erk and the MAPkinase phosphatase, Pac-1, and dephosphorylation and inactivation of ErkMAPkinase. This mechanism of abrogating ongoing ErkMAPkinase signalling therefore provides a rationale for rapid immune-complex-mediated feedback inhibition of active antigen-driven B cell responses. In addition, FcgammaRIIb signalling also induces the recruitment and activation of the 3'-inositol phosphatase, PTEN, which by antagonising PI 3kinase activity and inhibiting BCR-coupling to the anti-apoptotic kinase, Akt, provides an additional mechanism for FcgammaRIIb-mediated negative regulation of BCR-coupling to ErkMAPkinase, cell survival and proliferation.     

Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

A series of macrocyclic piperazinone compounds with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to be potent inhibitors of protein prenylation in cell culture. A hypothesis for the binding mode of compound 3o in FPTase is proposed.