Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.     

COURSE TIMETABLING AT A TUNISIAN UNIVERSITY： A CASE STUDY

This paper deals with the Course Timetabling Problem at an institution in a Tunisian University. We introduce a heuristic procedure to construct a feasible timetable for all lectures and tutorials taken by different groups of each sub-section of any section. We describe the timetabling problem using a list of all specific hard and soft constraints. We formulate the problem as a set of linear constraints using two sets of binary variables corresponding to lectures and tutorials, respectively. This heuristic is illustrated with real data for a sub-section of the Faculty of Economics and Management Sciences of Sfax in Tunisia, and the resulting timetables are compared with those generated manually. The results of another full section have confirmed the good quality of the proposed heuristic when compared with the hand made solution.     

Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1

With the emergence of multidrug resistant (MDR) bacteria, it is imperative to develop new intervention strategies. Current antibiotics typically target pathogen rather than host-specific biochemical pathways. Here we have developed kinase inhibitors that prevent intracellular growth of unrelated pathogens such as Salmonella typhimurium and Mycobacterium tuberculosis. An RNA interference screen of the human kinome using automated microscopy revealed several host kinases capable of inhibiting intracellular growth of S. typhimurium. The kinases identified clustered in one network around AKT1 (also known as PKB). Inhibitors of AKT1 prevent intracellular growth of various bacteria including MDR-M. tuberculosis. AKT1 is activated by the S. typhimurium effector SopB, which promotes intracellular survival by controlling actin dynamics through PAK4, and phagosome-lysosome fusion through the AS160 (also known as TBC1D4)-RAB14 pathway. AKT1 inhibitors counteract the bacterial manipulation of host signalling processes, thus controlling intracellular growth of bacteria. By using a reciprocal chemical genetics approach, we identified kinase inhibitors with antibiotic properties and their host targets, and we determined host signalling networks that are activated by intracellular bacteria for survival.     

Sex-specific pheromones in a termite

Résumé La glande sternale des jeunes imagos et secrète une phéromone attractive pour les individus du sexe opposé. Les peuvent prendre une position d'appel indentique à celle connue des . Les imagos, mais pas les nymphes, reconnaissent les phéromones sexuelles de la phéromone de piste sécrétée par la glande sternale des nymphes.     

A new class of anthelmintics effective against drug-resistant nematodes

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.     

High-sensitive and temperature-self-calibrated tilted fiber grating biological sensing probe

High sensitivity biological sample measurement has been achieved by using a 10° tilted fiber Bragg grating sensing probe. Human acute leukemia cells with different intracellular densities were clearly discriminated by identifying their slight refraction index (RI) perturbations in the range from 1.3342 to 1.3344, combining with a temperature self-calibration property. We studied the relationship between the intracellular density of cells (S50 and S60) and their RIs, the experimental results provide a potential way to verify the hypothesis for "density alteration in non-physiological cells (DANCE)".