Smith-Lemli-Opitz syndrome (SLOS) is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis. It is characterized by accumulation of 7-dehydrocholesterol (the immediate biosynthetic precursor of cholesterol in the Kandutsch-Russell pathway) and an altered cholesterol to total sterol ratio. Because SLOS is associated with neurological malfunction, exploring the function and trafficking of neuronal receptors and their interaction with membrane lipids under these conditions assume significance. In this work, we generated a cellular model of SLOS in HEK-293 cells stably expressing the human serotonin 1A receptor (an important neurotransmitter G-protein coupled receptor) using AY 9944, an inhibitor for the enzyme 3β-hydroxy-steroid-Δ 7 -reductase (7-DHCR). Using a quantitative flow cytometry based assay, we show that the plasma membrane population of serotonin 1A receptors was considerably reduced under these conditions without any change in total cellular expression of the receptor. Interestingly, the receptors were trafficked to sterol-enriched LysoTracker positive compartments, which accumulated under these conditions. To the best of our knowledge, our results constitute one of the first reports demonstrating intracellular accumulation and misregulated traffic of a neurotransmitter GPCR in SLOS-like conditions. We believe these results assume relevance in our overall understanding of the molecular basis underlying the functional relevance of neurotransmitter receptors in SLOS.

The biosynthesis of cholesterol, an essential component of higher eukaryotic membranes, was worked out by Konrad Bloch (and Feodor Lynen) in the 1960s and they received the Nobel Prize around that time in recognition of their pioneering contributions. An elegant consequence of this was a hypothesis proposed by Konrad Bloch (the Bloch hypothesis) which suggests that each subsequent intermediate in the cholesterol biosynthesis pathway is superior in supporting membrane function in higher eukaryotes relative to its precursor. In this review, we discuss an autosomal recessive metabolic disorder, known as Smith-Lemli-Opitz syndrome (SLOS), associated with a defect in the Kandutsch-Russell pathway of cholesterol biosynthesis that results in accumulation of the immediate precursor of cholesterol in its biosynthetic pathway (7-dehydrocholesterol) and an altered cholesterol to total sterol ratio. Patients suffering from SLOS have several developmental, behavioral and cognitive abnormalities for which no drug is available yet. We characterize SLOS as a manifestation of the Bloch hypothesis and review its molecular etiology and current treatment. We further discuss defective Hedgehog signaling in SLOS and focus on the role of the serotonin1A receptor, a representative neurotransmitter receptor belonging to the GPCR family, in SLOS. Notably, ligand binding activity and cellular signaling of serotonin1A receptors are impaired in SLOS-like condition. Importantly, cellular localization and intracellular trafficking of the serotonin1A receptor (which constitute an important determinant of a GPCR cellular function) are compromised in SLOS. We highlight some of the recent developments and emerging concepts in SLOS pathobiology and suggest that novel therapies based on trafficking defects of target receptors could provide new insight into treatment of SLOS.

Background: The World Health Organization Global TB report reported that TB ranks alongside HIV as a leading cause of death worldwide. Evidence based studies revealed that knowledge and awareness has a substantial impact on the prevention of HIV/AIDS and tuberculosis. This study was conducted to compare the awareness and knowledge of high school children regarding HIV and TB in the rural and urban areas and to assess the impact of educational intervention on the same.Methods: One school each from rural and urban field practice area was selected by purposive sampling technique. A total of 205 high school students were included in the study by total enumeration method. An interventional study was conducted regarding awareness and knowledge about TB and HIV/AIDS by means of health talk and help of audio visual aids. The data was collected in a predesigned self administered questionnaire by pretest and post test method.Results: The total of 205 students participated in the study. Majority of the respondent have correct knowledge regarding the causative agent of TB (38.5%) with 28.4% in rural and 48.5% in urban area. Moreover majority of the respondent correctly elicited the causative agent of HIV/AIDS (52.6%) with 44.1% in rural and 61.1% in urban area. Overall the intervention had a substantial effect on the awareness and knowledge level of the students regarding HIV/AIDS and tuberculosis.Conclusions: Although awareness among the masses is there but right knowledge and practice plays a pivotal role in improving the health status and awareness of the community.

Introduction:- Adolescence is the transitional stage of development between childhood and adulthood. Hall denoted this period as “Storm and Stress” and states “conflict at this developmental stage is normal” leading to psychosocial problems. This study is conducted to compare the psychosocial problems between adolescents in urban and rural area. Material and methods:- A Cross-sectional study was done in November 2018 in rural and urban schools of Dehradun. Data was collected through a structured questionnaire and analysed using Epi info software. Results:- A total of 170 students participated in the study out of which 111 were males and 59 females. Psychosocial problems were seen in 11.2% of study participants (11.7% in males and 10.1% in females. Conclusion and recommendations:- Psychosocial problems were seen on rise among adolescents and needs to be addressed at school level.