(Guanine Nucleotide-Binding Protein, Alpha Stimulating) is a complex gene that encodes the alpha subunit of the stimulatory G protein (Gα), critical for signaling through various G protein-coupled receptors. Inactivating genetic and epigenetic changes in , resulting in Gα deficiency, cause different variants of pseudohypoparathyroidism, which may manifest features of Albright hereditary osteodystrophy (AHO, a syndrome characterized by early-onset obesity and other developmental defects). Recent findings have linked Gα deficiency with isolated, severe, early-onset obesity, suggesting it as a potential, underrecognized cause of monogenic, non-syndromic obesity.
View Article and Find Full Text PDFAlbumin-coated gold nanoparticles display potential biomedical applications, including cancer research, infection treatment, and wound healing; however, elucidating their interaction with normal cells remains an area with limited exploration. In this study, gold nanorods (GNR) were prepared and coated with bovine serum albumin (BSA) to produce GNR-BSA. The functionalized nanoparticles were characterized based on their optical absorption spectra, morphology, surface charge, and quantity of attached protein.
View Article and Find Full Text PDFThe kinase suppressor of Ras 2 () gene is associated with monogenic obesity, and loss-of-function variants in have been identified in individuals with severe early-onset obesity. This study investigated variants in 9 pediatric patients with severe early-onset obesity in Qatar using whole genome sequencing among a cohort of 240 individuals. We focused on variants with a minor allele frequency (MAF) below 1% and a Combined Annotation Dependent Depletion (CADD) score above 13 to identify potential causative variants.
View Article and Find Full Text PDFIntroduction: Intermittent fasting (IF) represents a dietary intervention similar to caloric restriction, characterized by the strategic limitation of food consumption. Among the diverse array of practices for IF, Ramadan IF (RIF), a religious observance in Islam, mandates that healthy adult Muslims abstain from both food and drinks during daylight hours. In sports, researchers have extensively studied IF effects on health, including sleep and physical performance, but its impact on cognitive functions during RIF remains understudied.
View Article and Find Full Text PDFMutat Res Rev Mutat Res
May 2024
Background: GNAS (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes Gα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homoeostasis, and body weight. Genetic or epigenetic alterations in GNAS are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity.
View Article and Find Full Text PDFThe leptin-melanocortin pathway is pivotal in appetite and energy homeostasis. Pathogenic variants in genes involved in this pathway lead to severe early-onset monogenic obesity (MO). The gene plays a central role in leptin-melanocortin signaling, and heterozygous variants in this gene are the most common cause of MO.
View Article and Find Full Text PDFStore-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that complete knockout of STIM1 (STIM1-KO) using gene editing in metastatic MDA-MB-231 breast cancer cells results in faster migration and enhanced invasion capacity.
View Article and Find Full Text PDFStore-operated Ca entry (SOCE) is a ubiquitous Ca influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca stores following the activation of the endoplasmic reticulum (ER) Ca sensor STIM1, which recruits the plasma membrane (PM) Ca channel Orai1 at ER-PM junctions. STIM1 is phosphorylated dynamically, and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration.
View Article and Find Full Text PDFCa signaling is ubiquitous in eukaryotic cells and modulates many cellular events including cell migration. Directional cell migration requires the polarization of both signaling and structural elements. This polarization is reflected in various Ca signaling pathways that impinge on cell movement.
View Article and Find Full Text PDFRegulation of Ca signaling is critical for the progression of cell division, especially during meiosis to prepare the egg for fertilization. The primary Ca influx pathway in oocytes is Store-Operated Ca Entry (SOCE). SOCE is tightly regulated during meiosis, including internalization of the SOCE channel, Orai1.
View Article and Find Full Text PDFThe steroid hormone progesterone (P4) mediates many physiological processes through either nuclear receptors that modulate gene expression or membrane P4 receptors (mPRs) that mediate nongenomic signaling. mPR signaling remains poorly understood. Here we show that the topology of mPRβ is similar to adiponectin receptors and opposite to that of G-protein-coupled receptors (GPCRs).
View Article and Find Full Text PDFEndoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD.
View Article and Find Full Text PDFObjectives: The study objectives were to investigate Qatar pharmacy students' attitudes toward pharmaceutical care (PC), to identify the factors that influence their attitudes, and to recognize their perceived barriers for PC provision.
Methods: A cross-sectional and online survey of Qatar pharmacy students was conducted.
Results: Over 4 weeks, 46 surveys were submitted (88% response rate).