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Andrew R Tee
Mammalian target of rapamycin (mTOR, now referred to as mechanistic target of rapamycin) is considered as the master regulator of cell growth. A definition of cell growth is a build-up of cellular mass through the biosynthesis of macromolecules. mTOR regulation of cell growth and cell size is complex, involving tight regulation of both anabolic and catabolic processes. Upon a growth signal input, mTOR enhances a range of anabolic processes that coordinate the biosynthesis of macromolecules to build cellular biomass, while restricting catabolic processes such as autophagy...
March 16, 2018: International Journal of Molecular Sciences
Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Michaël R Laurent
An overview of selected papers related to bone published in 2017 is provided. PURPOSE: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. METHODS: A PubMed search using the keyword "bone" and articles published in 2017. RESULTS: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation...
March 15, 2018: Archives of Osteoporosis
Angela Contreras, Magdalena Ribbeck, Guillermo D Gutiérrez, Pablo M Cañon, Sebastián N Mendoza, Eduardo Agosin
The effect of ethanol on the metabolism of Oenococcus oeni , the bacterium responsible for the malolactic fermentation (MLF) of wine, is still scarcely understood. Here, we characterized the global metabolic response in O. oeni PSU-1 to increasing ethanol contents, ranging from 0 to 12% (v/v). We first optimized a wine-like, defined culture medium, MaxOeno, to allow sufficient bacterial growth to be able to quantitate different metabolites in batch cultures of O. oeni . Then, taking advantage of the recently reconstructed genome-scale metabolic model iSM454 for O...
2018: Frontiers in Microbiology
Jiaxin Liu, Lei Chen, Jan Felix Joseph, Alexandra Naß, Anna Stoll, Xavier de la Torre, Francesco Botrè, Gerhard Wolber, Maria Kristina Parr, Matthias Bureik
Anabolic androgenic steroids (AAS) are misused very frequently in sport competitions as performance enhancing agents. One of the doping compounds that has been detected with increased frequency in the last few years is dehydrochloromethyltestosterone (DHCMT, 4-chloro-17β-hydroxy-17α-methylandrosta-1,4-dien-3-one; brand name Oral Turinabol). The long-term DHCMT metabolite 20βOH-NorDHCMT (4-chloro-17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one) was reported earlier to be detectable in urine samples for more than 22 days after DHCMT administration; however, purified reference material was not available so far...
February 26, 2018: Journal of Inorganic Biochemistry
Paul Glendenning, S A Paul Chubb, Samuel Vasikaran
Bone turnover marker (BTM's) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTM's reflect bone loss...
March 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Ji-Hye Kim, Ae Ri Kim, Yun Hui Choi, Aeryun Kim, Yongsung Sohn, Gye-Hyeong Woo, Jeong-Heon Cha, Eun-Jung Bak, Yun-Jung Yoo
BACKGROUND: Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups...
March 15, 2018: Journal of Translational Medicine
Teruyo Nakatani, Tiffany Chen, Joshua Johnson, Jennifer J Westendorf, Nicola C Partridge
Histone deacetylase 4 (Hdac4) is known to control chondrocyte hypertrophy and bone formation. We have previously shown that parathyroid hormone (PTH) regulates many aspects of Hdac4 function in osteoblastic cells in vitro; however, in vivo confirmation was previously precluded by pre-weaning lethality of the Hdac4 deficient mice. To analyze the function of Hdac4 in bone in mature animals, we generated mice with osteoblast lineage-specific knockout of Hdac4 (Hdac4ob-/- ) by crossing transgenic mice expressing Cre recombinase under the control of a 2...
March 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Diana Olvera, Rachel Stolzenfeld, Joan C Marini, Michelle S Caird, Kenneth M Kozloff
Osteogenesis imperfecta (OI) is a genetic disorder characterized by altered bone quality and imbalanced bone remodeling, leading to skeletal fractures which are most prominent during childhood. Treatments for OI have focused on restoring pediatric bone density and architecture to recover functional strength and consequently reduce fragility. Though antiresorptive agents like bisphosphonates (BP) are currently the most common intervention for the treatment of OI, a number of studies have shown efficacy of sclerostin antibody (SclAb) in inducing gains in bone mass and reducing fragility in OI mouse models...
March 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Patrycja Klimek, Tom Hildebrandt
OBJECTIVE: Theoretically, legal supplement use precedes and increases the risk for illicit appearance and performance enhancing drug (APED) use-also referred to as the gateway hypothesis. Little is known about associations between the speed of progression, or gap time, from legal to illicit APED use, and psychological risk factors, such as sociocultural influence, eating disorders, body image disturbance, and impulsivity. METHOD: The sample taken from two studies included 172 active steroid users (n = 143) and intense-exercising healthy controls (n = 29) between the ages of 18 and 60 (M = 34...
March 15, 2018: International Journal of Eating Disorders
D Burkard, T Beckett, E Kourtjian, C Messingschlager, R Sipahi, M Padley, J Stubbart
Teriparatide is an anabolic therapy used to treat patients with osteoporosis and is only approved for 2 years of treatment. This is the first study to look at two common osteoporosis drugs in maintaining its beneficial effects: denosumab and zoledronic acid. Denosumab treatment was associated with the greatest increase in bone mineral density (BMD) at the femoral neck and lumbar spine, an amount that was statistically greater than no treatment and zoledronic acid treatment. INTRODUCTION: Teriparatide, a hallmark treatment for osteoporosis, has been shown to increase BMD and bone turnover...
March 14, 2018: Osteoporosis International
Lars Kullmann, Michael P Krahn
The tumor suppressor LKB1 is an essential serine/threonine kinase, which regulates various cellular processes such as cell metabolism, cell proliferation, cell polarity, and cell migration. Germline mutations in the STK11 gene (encoding LKB1) are the cause of the Peutz-Jeghers syndrome, which is characterized by benign polyps in the intestine and a higher risk for the patients to develop intestinal and extraintestinal tumors. Moreover, mutations and misregulation of LKB1 have been reported to occur in most types of tumors and are among the most common aberrations in lung cancer...
March 15, 2018: Oncogene
Marcin Czarnoleski, Anna Maria Labecka, Dominika Dragosz-Kluska, Tomasz Pis, Katarzyna Pawlik, Filip Kapustka, Wincenty M Kilarski, Jan Kozłowski
Cell size plays a role in body size evolution and environmental adaptations. Addressing these roles, we studied body mass and cell size in Galliformes birds and Rodentia mammals and collected published data on their genome sizes. In birds, we measured erythrocyte nuclei and basal metabolic rates (BMRs). In birds and mammals, larger species consistently evolved larger cells for five cell types (erythrocytes, enterocytes, chondrocytes, skin epithelial cells, and kidney proximal tubule cells) and evolved smaller hepatocytes...
March 14, 2018: Biology Open
Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
Zhi Ruan, Hui Ma, Jing Li, Huiyong Liu, Haoruo Jia, Feng Li
Intervertebral disc degeneration is a complex disease involving genetic and environmental factors and multiple cellular processes. The role and expression of the lncRNA NEAT1 were assessed in intervertebral disc degeneration. NEAT1 expression was assessed in degenerative and control nucleus pulposus using RT-PCR. Western blotting and RT-PCR were also used to investigate p53 and p21 levels in nucleus pulposus tissues. NEAT1 function in degenerative nucleus pulposus cells was assessed with gain- and loss-of-function experiments...
January 1, 2018: Experimental Biology and Medicine
Liam Bagley, Nasser Al-Shanti, Steven Bradburn, Osamah Baig, Mark Slevin, Jamie S McPhee
BACKGROUND: Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for males and females. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship and fatigability adaptations to 12 weeks SIT. METHODS: Sixteen males and fifteen females (mean (SEM) age: 41 (±2...
March 12, 2018: Journal of Strength and Conditioning Research
Shalender Bhasin, Caroline M Apovian, Thomas G Travison, Karol Pencina, Lynn L Moore, Grace Huang, Wayne W Campbell, Zhuoying Li, Andrew S Howland, Ruo Chen, Philip E Knapp, Martha R Singer, Mitali Shah, Kristina Secinaro, Richard V Eder, Kathleen Hally, Haley Schram, Richelle Bearup, Yusnie M Beleva, Ashley C McCarthy, Erin Woodbury, Jennifer McKinnon, Geeta Fleck, Thomas W Storer, Shehzad Basaria
Importance: The Institute of Medicine set the recommended dietary allowance (RDA) for protein at 0.8 g/kg/d for the entire adult population. It remains controversial whether protein intake greater than the RDA is needed to maintain protein anabolism in older adults. Objective: To investigate whether increasing protein intake to 1.3 g/kg/d in older adults with physical function limitations and usual protein intake within the RDA improves lean body mass (LBM), muscle performance, physical function, fatigue, and well-being and augments LBM response to a muscle anabolic drug...
March 12, 2018: JAMA Internal Medicine
Alicia Bort, Sergio Quesada, Ágata Ramos-Torres, Marta Gargantilla, Eva María Priego, Sophie Raynal, Franck Lepifre, Jose M Gasalla, Nieves Rodriguez-Henche, Ana Castro, Inés Díaz-Laviada
The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness. This study reports the discovery of a new series of 2-oxindole derivatives whose AMPK modulatory ability, as well as the antitumoral profile in prostate cancer cells, was evaluated...
March 12, 2018: Scientific Reports
Beata Znorko, Dariusz Pawlak, Ewa Oksztulska-Kolanek, Tomasz Domaniewski, Anna Pryczynicz, Alicja Roszczenko, Joanna Rogalska, Paweł Lipowicz, Michał Doroszko, Malgorzata Michalina Brzoska, Krystyna Pawlak
Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and parathyroid hormone (PTH) play a central role in the regulation of bone turnover in chronic kidney disease (CKD), but their influence on bone mineral density (BMD) and strength remains unclear, particularly in children. We studied the clinical significance of OPG and RANKL in relation to PTH, femur weight, BMD, and bone biomechanical properties in growing rats after one month (CKD-1) and three months (CKD-3) of surgically-induced mild CKD...
March 9, 2018: Cytokine
Saratram Gopalakrishnan, Himadri B Pakrasi, Costas D Maranas
Completeness and accuracy of metabolic mapping models impacts the reliability of flux estimation in photoautotrophic systems. In this study, metabolic fluxes under photoautotrophic growth conditions in the widely-used cyanobacterium Synechocystis PCC 6803 are quantified by re-analyzing an existing dataset using genome-scale isotopic instationary13 C-Metabolic Flux Analysis (INST-MFA). The reconstructed carbon mapping model imSyn617 and implemented algorithmic updates afforded an approximately 48% reduction in computation time...
March 8, 2018: Metabolic Engineering
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