Organisms allocate energetic resources between essential cellular processes to maintain homeostasis and, in turn, maximize fitness. The nutritional regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in Caenorhabditis elegans.
View Article and Find Full Text PDFCaenorhabditis elegans proliferates poorly in the presence of abundant Actinobacteria from its natural ecology, but it is unknown why. Here, we show how perturbed levels of hydrogen sulfide modulate the growth rate of both C. elegans and Actinobacteria.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
The serine/threonine protein kinase SGK-1 is a downstream target of mTOR complex 2 (mTORC2) and is a conserved regulator of growth and metabolism. In , mutations in , which encodes an essential component of mTORC2, impairs lipid homeostasis and growth; however, these defects are partially suppressed by an activating mutation in SGK-1 , E116K. Here, we describe a stronger gain-of-function mutation in , L112F, that was identified in a forward genetic screen for suppressor mutations This allele will be useful in further dissecting the mTORC2 pathway and provides new insight into the role of this conserved residue in regulating SGK-1 kinase activity.
View Article and Find Full Text PDFThe conserved SKN-1A/Nrf1 transcription factor regulates the expression of proteasome subunit genes and is essential for maintenance of adequate proteasome function in animal development, aging, and stress responses. Unusual among transcription factors, SKN-1A/Nrf1 is a glycoprotein synthesized in the endoplasmic reticulum (ER). N-glycosylated SKN-1A/Nrf1 exits the ER and is deglycosylated in the cytosol by the PNG-1/NGLY1 peptide:N-glycanase.
View Article and Find Full Text PDFThe molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in partially suppress the vitellogenesis defects observed in the heterochronic mutants and both of which ectopically express at the adult developmental stage.
View Article and Find Full Text PDFOrganisms must appropriately allocate energetic resources between essential cellular processes to maintain homeostasis and in turn, maximize fitness. The nutritional and homeostatic regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern cellular metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in .
View Article and Find Full Text PDFIon channels are necessary for proper water and nutrient absorption in the intestine, which supports cellular metabolism and organismal growth. While a role for Na co-transporters and pumps in intestinal nutrient absorption is well defined, how individual K uniporters function to maintain ion homeostasis is poorly understood. Using , we show that a gain-of-function mutation in , which encodes a two-pore domain K ion channel orthologous to human KCNK3, facilitates nutrient absorption and suppresses the metabolic and developmental defects displayed by impaired intestinal MAP Kinase (MAPK) signaling.
View Article and Find Full Text PDFIncreasingly prevalent, nontuberculous mycobacteria (NTM) infections affect approximately 20% of people with cystic fibrosis (CF). Previous studies of CF sputum identified lower levels of the host metabolite itaconate in those infected with NTM. Itaconate can inhibit the growth of M.
View Article and Find Full Text PDFThe molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in partially suppress the vitellogenesis defects observed in the heterochronic mutants and both of which ectopically express at the adult developmental stage.
View Article and Find Full Text PDFDedicated genetic pathways regulate cysteine homeostasis. For example, high levels of cysteine activate cysteine dioxygenase, a key enzyme in cysteine catabolism in most animal and many fungal species. The mechanism by which cysteine dioxygenase is regulated is largely unknown.
View Article and Find Full Text PDFPeripheral vascular diseases (PVDs) represent a significant burden on global human health and healthcare systems. With continued growth in obesity and diabetes, it is likely that the incidence of these conditions will increase. As many PVDs remain undiagnosed, low-cost and easy to use diagnostic methods are required.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2023
Transcranial doppler (TCD) ultrasound probes are an invaluable tool in cerebral blood flow (CBF) studies. Their operation demands maintaining consistent pose on the subject throughout the experimental protocol. However, the displacement of the TCD probe during vestibular studies is common and substantially prolongs the experiment or even terminates it.
View Article and Find Full Text PDFTocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation.
View Article and Find Full Text PDFAnimals integrate developmental and nutritional signals before committing crucial resources to growth and reproduction; however, the pathways that perceive and respond to these inputs remain poorly understood. Here, we demonstrate that DRL-1 and FLR-4, which share similarity with mammalian mitogen-activated protein kinases, maintain lipid homeostasis in the C. elegans intestine.
View Article and Find Full Text PDFEffective monitoring of respiratory disturbances during sleep requires a sensor capable of accurately capturing chest movements or airflow displacement. Gold-standard monitoring of sleep and breathing through polysomnography achieves this task through dedicated chest/abdomen bands, thermistors, and nasal flow sensors, and more detailed physiology, evaluations via a nasal mask, pneumotachograph, and airway pressure sensors. However, these measurement approaches can be invasive and time-consuming to perform and analyze.
View Article and Find Full Text PDFDedicated genetic pathways regulate cysteine homeostasis. For example, high levels of cysteine activate cysteine dioxygenase, a key enzyme in cysteine catabolism in most animal and many fungal species. The mechanism by which cysteine dioxygenase is regulated is largely unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2022
Surveillance of mitochondrial status is coupled to defense responses such as drug detoxification, immunity, antiviral RNA interference (RNAi), and regulation of life span. A cytochrome p540 detoxification gene, , is specifically activated by mitochondrial dysfunction. The nuclear hormone receptor NHR-45 and the transcriptional Mediator component MDT-15/MED15 are required for the transcriptional activation of by mitochondrial mutations, gene inactivations, or toxins.
View Article and Find Full Text PDFHeart rate (HR) and respiratory rate (RR) are two vital parameters of the body medically used for diagnosing short/long-term illness. Out-of-the-body, non-skin-contact HR/RR measurement remains a challenge due to imprecise readings. "Invisible" wearables integrated into day-to-day garments have the potential to produce precise readings with a comfortable user experience.
View Article and Find Full Text PDFBackground: An anticipated surge in mental health service demand related to COVID-19 has motivated the use of novel methods of care to meet demand, given workforce limitations. Digital health technologies in the form of self-tracking technology have been identified as a potential avenue, provided sufficient evidence exists to support their effectiveness in mental health contexts.
Objective: This literature review aims to identify current and potential physiological or physiologically related monitoring capabilities of the Apple Watch relevant to mental health monitoring and examine the accuracy and validation status of these measures and their implications for mental health treatment.
A method to identify anticancer compounds in plants was proposed based on the hypothesis that these compounds are primarily present in plants to provide them with an ecological advantage over neighboring plants and other competitors. According to this view, identifying plants that contain compounds that inhibit or interfere with the development of other plant species may facilitate the discovery of novel anticancer agents. The method was developed and tested using , , , and , which are plant species known to possess compounds with cytotoxic activities.
View Article and Find Full Text PDFNontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are associated with significant morbidity and mortality and are increasing in prevalence. Host risk factors for NTM infection in CF are largely unknown. We hypothesize that the airway microbiota represents a host risk factor for NTM infection.
View Article and Find Full Text PDFBackground: Wearable technologies are increasingly popular. Yet their use remains low by older adults, who may stand the greatest benefit of use. While there is an abundance of research examining the performance, accuracy, specificity, and sensitivity of wearable devices, many barriers remain and need to be addressed to optimize uptake in clinical practice.
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