Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection

Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.     

A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis

Mycobacterium tuberculosis, which causes tuberculosis, is the greatest single infectious cause of mortality worldwide, killing roughly two million people annually. Estimates indicate that one-third of the world population is infected with latent M. tuberculosis. The synergy between tuberculosis and the AIDS epidemic, and the surge of multidrug-resistant clinical isolates of M. tuberculosis have reaffirmed tuberculosis as a primary public health threat. However, new antitubercular drugs with new mechanisms of action have not been developed in over thirty years. Here we report a series of compounds containing a nitroimidazopyran nucleus that possess antitubercular activity. After activation by a mechanism dependent on M. tuberculosis F420 cofactor, nitroimidazopyrans inhibited the synthesis of protein and cell wall lipid. In contrast to current antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity against both replicating and static M. tuberculosis. Lead compound PA-824 showed potent bactericidal activity against multidrugresistant M. tuberculosis and promising oral activity in animal infection models. We conclude that nitroimidazopyrans offer the practical qualities of a small molecule with the potential for the treatment of tuberculosis.     

3H-vitamin A and rat thyroid: Autoradiographic observations

Résumé Des études autoradiographiques démontrent la présence de radioactivité dans les cellules folliculaires et dans la colloïde de la thyroïde du rat à la suite de l'injection intrapéritonéale de l'acétate rétinyl-³H (acétate de la vitamine A). La radioactivité de la colloïde se manifeste seulement dans le tissu congelé vivant; elle disparaît lors de la préparation histologique ordinaire. Par contre, une partie de cette radioactivité reste liée aux cellules folliculaires, même après la préparation histologique habituelle.     

Virus-like particles in the opossum submandibular gland

Summary Numerous inclusion bodies (virus-like particles) were observed in the lumina of the intercellular canaliculi, mucous tubules and intralobular ducts of the opossum submandibular gland. The particles are spherical in outline, show an electron dense core, and are surrounded by a peripheral membrane.     

Energy-Theft Detection Issues for Advanced Metering Infrastructure in Smart Grid

With the proliferation of smart grid research, the Advanced Metering Infrastructure （AMI） has become the first ubiquitous and fixed computing platform. However, due to the unique characteristics of AMI, such as complex network structure, resource-constrained smart meter, and privacy-sensitive data, it is an especially challenging issue to make AMI secure. Energy theft is one of the most important concerns related to the smart grid implementation. It is estimated that utility companies lose more than S25 billion every year due to energy theft around the world. To address this challenge, in this paper, we discuss the background of AMI and identify major security requirements that AMI should meet. Specifically, an attack tree based threat model is first presented to illustrate the energy-theft behaviors in AMI. Then, we summarize the current AMI energy-theft detection schemes into three categories, i.e., classification-based, state estimation-based, and game theory-based ones, and make extensive comparisons and discussions on them. In order to provide a deep understanding of security vulnerabilities and solutions in AMI and shed light on future research directions, we also explore some open challenges and potential solutions for energy-theft detection.     

Uptake and autoradiographic demonstration of vitamin a and/or its metabolic derivatives in organ cultures of rat prostate

Résumé Des études autoradiographiques et chimiques montrent que chez le rat, des explants du lobe ventral de la prostate incorporent de l'acétate de rétynyl pendant 48 h. Les résultats différents obtenus par les 2 méthodes utilisées indiqueraient qu'il y a non seulement incorporation de la vitamine A mais aussi transformation de cette dernière en d'autres substances.