Genetic Variation and Atherosclerosis

A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis.     

Do Current Stability Scores After MPFL Reconstruction Correlate With Patient Satisfaction Postoperatively?

BackgroundPatellar dislocation can lead to instability, pain, limited function, and recurrent dislocations. Medial patellofemoral ligament (MPFL) reconstruction leads to favorable patient reported outcomes, but many patients fail to return to previous activity levels. The purpose of this study is to determine how well patients do after MPFL reconstruction and to determine the most important factors for evaluation of patellar instability following MPFL reconstruction.MethodsAfter IRB approval, a retrospective chart review was performed on all patients who underwent MPFL reconstruction from January 2006 to January 2014 by two board-certified sports orthopaedic surgeons. Patients were then contacted to complete a follow-up questionnaire about satisfaction, functional status, pain, and patellar stability. Patients with at least one-year of follow-up data, a complete data set, and a completed questionnaire were included in the final analysis. Charts of 100 patients were reviewed and 54 patients met all criteria for inclusion in the study. Chi-square analysis, t-tests, and multivariate and univariate logistic regression models were used to estimate the effects of multiple variables on return to activity, satisfaction, and function while controlling for covariates with p<0.05 considered significant.ResultsWhen asked about subluxation, 20% (11/54) reported recurrent patellar subluxation (without re-dislocation). Of the 11 patients who reported re-subluxation, 54% (6/11) reported being highly satisfied (rating of 9-10/10) with the outcome of their knee. Of the 54 patients, 54% (29/54) did not return to previous levels of activity, nevertheless, 31% (9/29) of these 29 patients reported being highly satisfied with the outcome of their knee.ConclusionPatients report high levels of satisfaction even if they have recurrent instability or are unable to return to prior activity levels. Current scoring systems do not accurately depict patients’ post-operative outcomes after MPFL Reconstruction. Level of Evidence: III     

CHILL-COMA TOLERANCE, A MAJOR CLIMATIC ADAPTATION AMONG DROSOPHILA SPECIES

Abstract.— Most drosophilid species can be classified either as temperate or tropical. Adults of species were submitted to a cold treatment (0°C) and then brought back to ambient temperature. They generally exhibited a chill coma and the time needed to recover was measured. We found in a set of 26 temperate species that recovery was rapid (average 1.8 min, range 0.15–4.9). In contrast, a long recovery time (average 56 min, range 24–120) was observed for 48 tropical species. A few species, like Drosophila melanogaster, are cosmopolitan and can proliferate under temperate and tropical climates. In 9 of 10 such species, slight genetic differences were found: a shorter recovery in temperate than in tropical populations. Comparing physiological data to phylogeny suggests that chill‐coma tolerance has been a recurrent adaptation that is selected for in cold climates but tends to disappear under a permanently warm environment. This major climatic adaptation, evidenced in drosophilids, seems to occur in other insect groups also.     

Xylarinase: a novel clot busting enzyme from an endophytic fungus Xylaria curta

Xylarinase is a bi-functional fibrinolytic metalloprotease isolated from the culture filtrate of endophytic fungus Xylaria curta which is monomeric with a molecular mass of ～33.76?kDa. The enzyme displayed both plasmin and tissue plasminogen activator like activity under in vitro conditions. It hydrolyses Aα and Bβ chains of the fibrinogen. Optimal fibrinolytic activity of xylarinase is observed at 35?°C, pH 8. Ca²⁺ stimulated the fibrinolytic activity of xylarinase while Fe²⁺ and Zn²⁺ inhibited suggesting it to be a metalloprotease. The K_m and V_max values of xylarinase were 240.9?μM and 1.10?U/ml for fibrinogen and 246?μM and 1.22?U/ml for fibrin, respectively. Xylarinase was found to prolong the activated partial thromboplastin time and prothrombin time. The N-terminal sequence of xylarinase (SNGPLPGGVVWAG) did not show any homology with previously known fibrinolytic enzymes. Thus xylarinase is a novel fibrinolytic metalloprotease which could be possibly used as a new clot busting enzyme.     

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg²⁺) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg²⁺ is unknown. Here, we show that Mg²⁺, acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA–DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae, magnesium ions guided by cell membrane Mg²⁺ transporters Alr1/2 act via Mg²⁺-sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg²⁺ in a process that is dependent on the TRPM7 Mg²⁺ transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg²⁺ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes.     

Dual-frequency dielectrophoretic levitation of Canola protoplasts

A novel dual-frequency excitation technique is introduced which permits investigation of the low-frequency dispersion of Canola plant protoplasts using feedback-controlled dielectrophoretic levitation. The upper and intermediate frequency spectra obtained using the new technique are generally consistent with previous work. However, below some cross-over frequency f_OL, the protoplasts exhibit an apparent positive dielectrophoretic response that is not predicted by conventional theory. This cross-over frequency is linearly related to suspension conductivity, virtually independent of the suspension pH, and inversely proportional to the square of the cell radius. Examination of the complex Clausius-Mossotti polarization coefficient reveals that the observed positive dielectrophoretic response can not be accounted for in terms of Maxwell-Wagner polarization associated with a conventional layered model for the protoplast. The failure of straightforward enhancements to the protoplast model in explaining the low frequency behavior may indicate the presence of an electrophoretic contribution to the net observable force on the particle. To account for such fluid mechanical effects, it will be necessary to modify the existing dielectrophoretic force formulation.     

Product Cum Difference Method of Estimation Using two Auxiliary Variables

Product method of estimation (MURTHY, 1964) using supplementary information on an auxiliary variable having high negative correlation with the main variable under our study, is well known. In this paper, we propose product-cum-difference method of estimation for the population total and the product of population parameters when supplementary information is available on two auxiliary variables. A comparison of product-cum-difference method of estimation with the usual product method of estimation using single auxiliary character and the estimators by SINGH (1965) for the estimation of product of population parameters has been made along with an empirical study.