Sptlc1 is essential for myeloid differentiation and hematopoietic homeostasis

Serine palmitoyltransferase (SPT) long-chain base subunit 1 (SPTLC1) is 1 of the 2 main catalytic subunits of the SPT complex, which catalyzes the first and rate-limiting step of sphingolipid biosynthesis. Here, we show that Sptlc1 deletion in adult bone marrow (BM) cells results in defective myeloid differentiation. In chimeric mice from noncompetitive BM transplant assays, there was an expansion of the Lin- c-Kit+ Sca-1+ compartment due to increased multipotent progenitor production, but myeloid differentiation was severely compromised. We also show that defective biogenesis of sphingolipids in the endoplasmic reticulum (ER) leads to ER stress that affects myeloid differentiation. Furthermore, we demonstrate that transient accumulation of fatty acid, a substrate for sphingolipid biosynthesis, could be partially responsible for the ER stress. Independently, we find that ER stress in general, such as that induced by the chemical thapsigargin or the fatty acid palmitic acid, compromises myeloid differentiation in culture. These results identify perturbed sphingolipid metabolism as a source of ER stress, which may produce diverse pathological effects related to differential cell-type sensitivity

Sustainable Health in the Times of SDGs- Voices from the Margins

The present chapter reflects on health care availability, utilization and pattern of morbidity in the slum. The first part deals with the general profile of the public health, proximate causes of the ill health, which provides insight about the general profile of the infrastructure and basic amenities position vis a vis slum. The second part is related the health care utilization in slums namely services of the medical institutions, charges of the private medical institutions and clinics, source of treatment, reason for choosing the source of treatment, satisfaction with the treatment, user charge. This section also includes access to the health care services in the slums and the mode of transport used for the utilization of the health care services. The third aspect of the study is related to the pattern of morbidity in slums includes illness in the last month, ailment on the survey date, hospitalisation in one year, average morbidity and hospitalisation rate in one year of three slums, type of ailment, ailment of the head of the household, ailment of the family members, no of days of inactivity and lastly analysis of the common problems and health status of slum dwellers, treatment sought and the proximate reasons for the ailments in slums been done

Drosophila melanogaster Scramblases modulate synaptic transmission

Scramblases are a family of single-pass plasma membrane proteins, identified by their purported ability to scramble phospholipids across the two layers of plasma membrane isolated from platelets and red blood cells. However, their true in vivo role has yet to be elucidated. We report the generation and isolation of null mutants of two Scramblases identified in Drosophila melanogaster. We demonstrate that flies lacking either or both of these Scramblases are not compromised in vivo in processes requiring scrambling of phospholipids. Instead, we show that D. melanogaster lacking both Scramblases have more vesicles and display enhanced recruitment from a reserve pool of vesicles and increased neurotransmitter secretion at the larval neuromuscular synapses. These defects are corrected by the introduction of a genomic copy of the Scramb 1 gene. The lack of phenotypes related to failure of scrambling and the neurophysiological analysis lead us to propose that Scramblases play a modulatory role in the process of neurotransmission

Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype

ASSOCIATION OF THE IMPACT OF POSTNATAL NUTRITION ON THE GROWTH OF PRETERM INFANTS

Objectives: The objectives of the study were to measure the actual daily amount of each nutrient (protein, glucose, and fat) energy and fluid as per current ESPGHAN guidelines for preterm infants and to analyze the role of nutrients at different gestational age on growth and weight of preterm infants. Material and Methods: An observational and prospective cohort study was conducted from January 1, 2018, to December 31, 2018. This study included all preterm infants born <34 weeks gestational age admitted in the neonatal intensive care unit during this period at Mahatma Gandhi Medical College and Hospital. A total of 120 preterm neonates were studied. Results: There were mean weight, length, and head circumference continues to rise till the study end. Mean energy at birth was also continues to rise till the end. Conclusion: In the study, proper nutritional supplement as per ESPHAGEN guidelines was used for the development of preterm infant. The study showed that there were statistically significant results with anthropometry parameters with preterm baby growth in all domains

dagLogo: An R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data

Sequence logos have been widely used as graphical representations of conserved nucleic acid and protein motifs. Due to the complexity of the amino acid (AA) alphabet, rich post-translational modification, and diverse subcellular localization of proteins, few versatile tools are available for effective identification and visualization of protein motifs. In addition, various reduced AA alphabets based on physicochemical, structural, or functional properties have been valuable in the study of protein alignment, folding, structure prediction, and evolution. However, there is lack of tools for applying reduced AA alphabets to the identification and visualization of statistically significant motifs. To fill this gap, we developed an R/Bioconductor package dagLogo, which has several advantages over existing tools. First, dagLogo allows various formats for input sets and provides comprehensive options to build optimal background models. It implements different reduced AA alphabets to group AAs of similar properties. Furthermore, dagLogo provides statistical and visual solutions for differential AA (or AA group) usage analysis of both large and small data sets. Case studies showed that dagLogo can better identify and visualize conserved protein sequence patterns from different types of inputs and can potentially reveal the biological patterns that could be missed by other logo generators

Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase beta and regulates complex V activity

Adenosine triphosphate (ATP) synthase beta, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase beta is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase beta and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase beta, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from wild-type and dsirt2 mitochondria identified the Drosophila mitochondrial acetylome and revealed dSirt2 as an important regulator of mitochondrial energy metabolism. Additionally, we unravel a ceramide-NAD(+)-sirtuin axis wherein increased ceramide, a sphingolipid known to induce stress responses, resulted in depletion of NAD(+) and consequent decrease in sirtuin activity. These results provide insight into sirtuin-mediated regulation of complex V and reveal a novel link between ceramide and Drosophila acetylome

Tooth Mobility among Patients visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study

Introduction: Periodontitis is a chronic inflammatory disease that results in the destruction of supporting tissue and bone leading to tooth mobility. Tooth mobility if untreated can lead to tooth loss. However, very few studies exist for its assessment. The aim of this study was to find out the prevalence of tooth mobility among patients visiting a tertiary care centre. Methods: This descriptive cross-sectional study was conducted among individuals visiting a tertiary care dental hospital from 1st April to 30th June 2022 after obtaining ethical clearance from the Institutional Review Committee (Reference number: 2202202202). Individuals more than 13 years who gave consent and fulfilled the study criteria were enrolled. Tooth mobility was assessed using Lindhe and Nyman’s classification. Proforma also included demographics, simplified oral hygiene index, gingival index, body mass index, and smoking status. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 163 patients, 65 (39.88%) patients (32.36-47.40, 95% Confidence Interval) had tooth mobility. Conclusions: The prevalence of tooth mobility was higher than in studies done in similar settings

Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice

Ceramide transfer protein (CERT) functions in the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi. In this study, we show that CERT is an essential gene for mouse development and embryonic survival and, quite strikingly, is critical for mitochondrial integrity. CERT mutant embryos accumulate ceramide in the ER but also mislocalize ceramide to the mitochondria, compromising their function. Cells in mutant embryos show abnormal dilation of the ER and degenerating mitochondria. These subcellular changes manifest as heart defects and cause severely compromised cardiac function and embryonic death around embryonic day 11.5. In spite of ceramide accumulation, CERT mutant mice do not die as a result of enhanced apoptosis. Instead, cell proliferation is impaired, and expression levels of cell cycle–associated proteins are altered. Individual cells survive, perhaps because cell survival mechanisms are activated. Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways

Phosphatidic acid phospholipase A1 mediates ER-Golgi transit of a family of G protein-coupled receptors

The coat protein II (COPII)-coated vesicular system transports newly synthesized secretory and membrane proteins from the endoplasmic reticulum (ER) to the Golgi complex. Recruitment of cargo into COPII vesicles requires an interaction of COPII proteins either with the cargo molecules directly or with cargo receptors for anterograde trafficking. We show that cytosolic phosphatidic acid phospholipase A1 (PAPLA1) interacts with COPII protein family members and is required for the transport of Rh1 (rhodopsin 1), an N-glycosylated G protein-coupled receptor (GPCR), from the ER to the Golgi complex. In papla1 mutants, in the absence of transport to the Golgi, Rh1 is aberrantly glycosylated and is mislocalized. These defects lead to decreased levels of the protein and decreased sensitivity of the photoreceptors to light. Several GPCRs, including other rhodopsins and Bride of sevenless, are similarly affected. Our findings show that a cytosolic protein is necessary for transit of selective transmembrane receptor cargo by the COPII coat for anterograde trafficking