ObjectiveThis study examined the prevalence and factors associated with depression among adolescents attending higher secondary schools in the Pokhara Metropolitan City of Nepal.DesignA cross-sectional study design was adopted.SettingFour randomly selected higher secondary schools of Pokhara Metropolitan, Nepal.Participants312 randomly sampled higher secondary school students.MethodsThe Center for Epidemiologic Studies Depression Scale was used to assess the level of depression among students. The data collected through a self-administered questionnaire were analysed using descriptive statistical methods such as frequency and percentage. χ2 test and unadjusted OR (UOR) were calculated to assess the statistical relationship between depression and various variables at 95% CI, with level of significance at p<0.05.ResultsThe study found a high prevalence of depression among high school students, with more than two-fifths (44.2%) of students having depression. Furthermore, almost a quarter (25.3%) of the students were noted to have mild depression and 18.9% of the students expressed major depression. Students who had low perceived social support (UOR: 3.604; 95% CI 2.088 to 6.220), did not share their problems with anyone (UOR: 1.931; 95% CI 1.228 to 3.038) and had low self-esteem (UOR: 5.282; 95% CI 2.994 to 9.319) were at higher odds of being depressed.ConclusionA high prevalence of depression was observed among high school students. It was also observed that students’ level of perceived social support, self-esteem and help-seeking behaviour are somehow related to their mental well-being. Hence, improving social support and self-esteem may alleviate depression and mental distress among these adolescents.

Lysenin, a pore-forming protein extracted from the coelomic fluid of the earthworm Eisenia foetida, manifests cytolytic activity by inserting large conductance pores in host membranes containing sphingomyelin. In the present study, we found that adenosine phosphates control the biological activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least. ATP removal from the bulk solutions by buffer exchange quickly reinstated the macroscopic conductance and demonstrated reversibility. Singlechannel experiments pointed to an inhibition mechanism that most probably relies on electrostatic binding and partial occlusion of the channel-conducting pathway, rather than ligand gating induced by the highly charged phosphates. The Hill analysis of the changes in macroscopic conduction as a function of the inhibitor concentration suggested cooperative binding as descriptive of the inhibition process. Ionic screening significantly reduced the ATP inhibitory efficacy, in support of the electrostatic binding hypothesis. In addition to conductance modulation, purinergic control over the biological activity of lysenin channels has also been observed to manifest as changes of the voltage-induced gating profile. Our analysis strongly suggests that not only the inhibitor's charge but also its ability to adopt a folded conformation may explain the differences in the observed influence of ATP, ADP, and AMP on lysenin's biological activity.

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All cell membranes are packed with proteins. The ability to investigate the regulatory mechanisms of protein channels in experimental conditions mimicking their congested native environment is crucial for understanding the environmental physicochemical cues that may fundamentally contribute to their functionality in natural membranes. Here we report on investigations of the voltage-induced gating of lysenin channels in congested conditions experimentally achieved by increasing the number of channels inserted into planar lipid membranes. Typical electrophysiology measurements reveal congestion-induced changes to the voltage-induced gating, manifested as a significant reduction of the response to external voltage stimuli. Furthermore, we demonstrate a similar diminished voltage sensitivity for smaller populations of channels by reducing the amount of sphingomyelin in the membrane. Given lysenin’s preference for targeting lipid rafts, this result indicates the potential role of the heterogeneous organization of the membrane in modulating channel functionality. Our work indicates that local congestion within membranes may alter the energy landscape and the kinetics of conformational changes of lysenin channels in response to voltage stimuli. This level of understanding may be extended to better characterize the role of the specific membrane environment in modulating the biological functionality of protein channels in health and disease.

SUMMARY Store-operated Orai1 calcium channels function as highly Ca 2+ -selective ion channels and are broadly expressed in many tissues including the central nervous system, but their contributions to cognitive processing are largely unknown. Here, we report that many measures of synaptic, cellular, and behavioral models of learning are markedly attenuated in mice lacking Orai1 in forebrain excitatory neurons. Results with focal glutamate uncaging in hippocampal neurons support an essential role of Orai1 channels in amplifying NMDA-receptor-induced dendritic Ca 2+ transients that drive activity-dependent spine morphogenesis and long-term potentiation at Schaffer collateral-CA1 synapses. Consistent with these signaling roles, mice lacking Orai1 in pyramidal neurons (but not interneurons) exhibit striking deficits in working and associative memory tasks. These findings identify Orai1 channels as essential regulators of dendritic spine Ca 2+ signaling, synaptic plasticity, and cognition.