CD40, autophagy and Toxoplasma gondii

Toxoplasmagondii represents a pathogen that survives within host cells by preventing the endosomal-lysosomal compartments from fusing with the parasitophorous vacuoles. The dogma had been that the non-fusogenic nature of these vacuoles is irreversible. Recent studies revealed that this dogma is not correct. Cell-mediated immunity through CD40 re-routes the parasitophorous vacuoles to the lysosomal compartment by a process called autophagy. Autophagosome formation around the parasitophorous vacuole results in killing of the T. gondii. CD40-induced autophagy likely contributes to resistance against T. gondii particularly in neural tissue

Early Adolescent Depressive Symptoms: Prediction from Clique Isolation, Loneliness, and Perceived Social Acceptance

This study examined whether clique isolation predicted an increase in depressive symptoms and whether this association was mediated by loneliness and perceived social acceptance in 310 children followed from age 11–14 years. Clique isolation was identified through social network analysis, whereas depressive symptoms, loneliness, and perceived social acceptance were assessed using self ratings. While accounting for initial levels of depressive symptoms, peer rejection, and friendlessness at age 11 years, a high probability of being isolated from cliques from age 11 to 13 years predicted depressive symptoms at age 14 years. The link between clique isolation and depressive symptoms was mediated by loneliness, but not by perceived social acceptance. No sex differences were found in the associations between clique isolation and depressive symptoms. These results suggest that clique isolation is a social risk factor for the escalation of depressive symptoms in early adolescence. Implications for research and prevention are discussed

A wake-active locomotion circuit depolarizes a sleep-active neuron to switch on sleep

Sleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wake-active wake-promoting neurons in turn shut down sleep-active neurons, thus forming a bipartite flip-flop switch. However, how sleep is switched on is unclear because it is not known how wakefulness is translated into sleep-active neuron depolarization when the system is set to sleep. Using optogenetics in Caenorhabditis elegans, we solved the presynaptic circuit for depolarization of the sleep-active RIS neuron during developmentally regulated sleep, also known as lethargus. Surprisingly, we found that RIS activation requires neurons that have known roles in wakefulness and locomotion behavior. The RIM interneurons-which are active during and can induce reverse locomotion-play a complex role and can act as inhibitors of RIS when they are strongly depolarized and as activators of RIS when they are modestly depolarized. The PVC command interneurons, which are known to promote forward locomotion during wakefulness, act as major activators of RIS. The properties of these locomotion neurons are modulated during lethargus. The RIMs become less excitable. The PVCs become resistant to inhibition and have an increased capacity to activate RIS. Separate activation of neither the PVCs nor the RIMs appears to be sufficient for sleep induction; instead, our data suggest that they act in concert to activate RIS. Forward and reverse circuit activity is normally mutually exclusive. Our data suggest that RIS may be activated at the transition between forward and reverse locomotion states, perhaps when both forward (PVC) and reverse (including RIM) circuit activity overlap. While RIS is not strongly activated outside of lethargus, altered activity of the locomotion interneurons during lethargus favors strong RIS activation and thus sleep. The control of sleep-active neurons by locomotion circuits suggests that sleep control may have evolved from locomotion control. The flip-flop sleep switch in C. elegans thus requires an additional component, wake-active sleep-promoting neurons that translate wakefulness into the depolarization of a sleep-active neuron when the worm is sleepy. Wake-active sleep-promoting circuits may also be required for sleep state switching in other animals, including in mammals

The emerging modern face of mood disorders: a didactic editorial with a detailed presentation of data and definitions

The present work represents a detailed description of our current understanding and knowledge of the epidemiology, etiopathogenesis and clinical manifestations of mood disorders, their comorbidity and overlap, and the effect of variables such as gender and age. This review article is largely based on the 'Mood disorders' chapter of the Wikibooks Textbook of Psychiatry http://en.wikibooks.org/wiki/Textbook_of_Psychiatry/Mood_Disorders

Future-oriented constructs and their role in suicidal ideation and enactment

Despite the heavy focus upon risk factors for suicide, the presence or absence of protective factors are also instrumental in individuals’ vulnerability for developing suicidal ideation and behaviours. Future oriented constructs, including future thinking, future orientation, hope and optimism have been associated with suicidal ideation and behaviour; individuals who are less able to generate positive thoughts about the future, and those are less hopeful and optimistic are more likely to think about or engage in suicidal behaviours. The content and expectations of future thoughts as achievable also play a key role in their protective capacity. Within this chapter we discuss the relationships between future orientated constructs and suicidal ideation and behaviour, as well as potential mediators of these relationships, within the context of the new generation of ideation-to-action frameworks of suicidal behaviour. We also highlight challenges and opportunities for future research and intervention development for suicidal thoughts and behaviours using future oriented constructs