Penicillin kills chlamydia following the fusion of bacteria with Lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice

The obligate intracellular bacterium Chlamydia exists as two distinct forms. Elementary bodies (EBs) are infectious and extra-cellular, whereas reticulate bodies (RBs) replicate within a specialized intracellular compartment termed an ‘inclusion’. Alternative persistent intra-cellular forms can be induced in culture by diverse stimuli such as IFNγ or adenosine/EHNA. They do not grow or divide but revive upon withdrawal of the stimulus and are implicated in several widespread human diseases through ill-defined in vivo mechanisms. β-lactam antibiotics have also been claimed to induce persistence in vitro. The present report shows that upon penicillin G (pG) treatment, inclusions grow as fast as those in infected control cells. After removal of pG, Chlamydia do not revert to RBs. These effects are independent of host cell type, serovar, biovar and species of Chlamydia. Time-course experiments demonstrated that only RBs were susceptible to pG. pG-treated bacteria lost their control over host cell apoptotic pathways and no longer expressed pre-16S rRNA, in contrast to persistent bacteria induced with adenosine/EHNA. Confocal and live-video microscopy showed that bacteria within the inclusion fused with lysosomal compartments in pG-treated cells. That leads to recruitment of cathepsin D as early as 3 h post pG treatment, an event preceding bacterial death by several hours. These data demonstrate that pG treatment of cultured cells infected with Chlamydia results in the degradation of the bacteria. In addition we show that pG is significantly more efficient than doxycycline at preventing genital inflammatory lesions in C. muridarum-C57Bl/6 infected mice. These in vivo results support the physiological relevance of our findings and their potential therapeutic applications

SUICIDE ON THE PATERNAL AND MATERNAL SIDES OF DEPRESSED-PATIENTS WITH A LIFETIME HISTORY OF ATTEMPTED-SUICIDE

The computational model of Slater, based on the analysis of ancestral secondary cases on the paternal and maternal sides of the subjects, was applied to depressed patients with a lifetime history of attempted suicide, either violent or nonviolent, in order to investigate possible modes of transmission of suicidal behavior. Among 549 patients, 15 had 2 or more ascendant first- and second-degree relatives who committed suicide. The results of the distribution of these cases were compatible with polygenic inheritance of suicidal behavior in depressed patients with a history of attempted suicide. In patients using violent methods, a significantly greater loading of ancestral secondary cases of suicide was observed on the maternal side and, in the nonviolent attempter group, on the paternal side

Responsiveness to siblings' need increases with age in vocally negotiating barn owl nestlings

In animal societies, individuals should optimize the way they behave in relation to the behavior displayed by their conspecifics. This social competence, i.e., the ability to adjust behavior to the social context, can vary between individuals, but also improve with age and experience. This aspect, although important, has rarely been studied. We tested whether the ability to adjust behavior to siblings develops with age in barn owl nestlings (Tyto alba). In this species, young siblings show intense social interactions referred to as Bsibling negotiation. Indeed, because parents bring a single indivisible food item at each visit to the nest, all the effort invested in sibling competition is only paid back in the nestling that is able to monopolize the food item. Therefore, before the arrival of parents, siblings vocally inform each other about their relative hunger level so that they can optimally invest in sibling competition, with the most vocal, and hence hungry, nestling momentarily deterring its siblings from competing. This process implies that siblings have the ability to adjust their behavior in relation to the behavior of their siblings, a process that could change with age. In a series of experiments, we examined how nestlings of different ages respond to the vocal behavior of siblings. We show here that older nestlings adjusted their vocal behavior more finely than younger nestlings in relation to the behavior of their siblings. Elders also more readily refrained from eating in front of a hungry sibling. These patterns could arise because owlets' social competence develops with age or because they adopt different competitive and cooperative strategies according to their age. Significance statement In sibling barn owls, competition for food brought by parents is settled by vocalization. Highly vocal owlets induce their siblings to call less and to let them eat in priority once parents are back with a prey item, a process referred to as Bsibling negotiation." Nestling barn owls adjust their investment in sibling competition according to two parameters: their hunger level and the vocal behavior of their siblings. We analyzed the relative importance of these two parameters in differently aged owlets. Younger owlets adjusted the intensity of vocalizing primarily in relation to their own hunger level, which was efficient in modifying older nestlings' behavior, as older nestlings readily withdrew from vocal contest and refrained from eating in front of highly vocal siblings. Hence, social adjustment changed with age in owlets, older ones being more sensitive to the signals of need of their siblings