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Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration.

J Endocrinol 2021 May;249(2):113-124

Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

Vitamin D deficiency is associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D-related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited to in vitro models and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in vivo have received little attention. Read More

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The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF).

EBioMedicine 2021 Apr 13;66:103325. Epub 2021 Apr 13.

Center for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada.

Background: The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition.

Methods: Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). Read More

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Genetic and epigenetic regulation in neoplasms composed of both germ cells and sex cord elements.

Pathol Res Pract 2021 Apr 2;222:153428. Epub 2021 Apr 2.

Department of Pathology and Urology, Indiana University School of Medicine, Van Nuys Medical Science Building 128, 635 Barnhill Drive, Indianapolis, IN, 46202-5120, United States. Electronic address:

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Patient-specific iPSC-derived cellular models of LGMDR1.

Stem Cell Res 2021 Apr 8;53:102333. Epub 2021 Apr 8.

Neuroscience Area, Biodonostia Research Institute, San Sebastian, Spain; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain; Department of Neuroscience, University of the Basque Country, San Sebastian, Spain; Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain. Electronic address:

Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Read More

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The influence of friendship and merit on children's resource allocation in three societies.

J Exp Child Psychol 2021 Apr 13;208:105149. Epub 2021 Apr 13.

Department of Psychology, University of California, Berkeley, Berkeley, CA 94705, USA; Minerva Research Group on the Origins of Human Self-Regulation, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.

Recent work has suggested that principles of fairness that seem like natural laws to the Western mind, such as sharing more of the spoils with those who contributed more, can in fact vary significantly across populations. To build a better understanding of the developmental roots of population differences with respect to fairness, we investigated whether 7-year-old children (N = 432) from three cultural backgrounds-Kenya, China, and Germany-consider friendship and merit in their distribution of resources and how they resolve conflicts between the two. We found that friendship had considerable and consistent influence as a cross-culturally recurrent motivation: children in all three cultures preferentially shared with a friend rather than with a neutral familiar peer. Read More

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Synthesis and evaluation of multi-target-directed ligands with BACE-1 inhibitory and Nrf2 agonist activities as potential agents against Alzheimer's disease.

Eur J Med Chem 2021 Apr 7;219:113441. Epub 2021 Apr 7.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Cumulative evidence suggests that β-amyloid and oxidative stress are closely related with each other and play key roles in the process of Alzheimer's disease (AD). Multitarget regulation of both pathways might represent a promising therapeutic strategy. Here, a series of selenium-containing compounds based on ebselen and verubecestat were designed and synthesized. Read More

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Involvement of salicylic acid in the response to potassium deficiency revealed by metabolomics.

Plant Physiol Biochem 2021 Apr 6;163:201-204. Epub 2021 Apr 6.

Research School of Biology, ANU College of Science, Australian National University, 2601, Canberra, ACT, Australia; Institut de Recherche en Horticulture et Semences, Université d'Angers, INRAe, 42 rue Georges Morel, 49070, Beaucouzé, France. Electronic address:

Potassium (K) deficiency has consequences not only on cellular ion balance and transmembrane potential but also on metabolism. In fact, several enzymes are K-dependent including enzymes in catabolism, causing an alteration in glycolysis and respiration. In addition, K deficiency is associated with the induction of specific pathways and accumulation of metabolic biomarkers, such as putrescine. Read More

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Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2.

Bioorg Med Chem 2021 Mar 24;38:116115. Epub 2021 Mar 24.

School of Chemistry, University of New South Wales (UNSW), Sydney, Australia. Electronic address:

Prolyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this work, a pharmacophore-based virtual high throughput screen was used to identify novel potential inhibitors of human PHD2. Read More

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Down-regulation of pro-necroptotic molecules blunts necroptosis during myogenesis.

Biochem Biophys Res Commun 2021 Apr 13;557:33-39. Epub 2021 Apr 13.

Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju, 27478, Republic of Korea; Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju, 27487, Republic of Korea.

Cell death and differentiation are closely related at the molecular level. Differentiation of skeletal muscle cells attenuates susceptibility to apoptosis. Necroptosis has recently been recognized as a form of regulated cell death but its role in myogenesis has not been studied. Read More

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The Caenorhabditis elegans homolog of human mitochondrial pyrimidine nucleotide transporter regulates glucose transport.

Biochem Biophys Res Commun 2021 Apr 13;557:117-121. Epub 2021 Apr 13.

Department of Chemistry and Bioengineering, Iwate University, 4 Ueda, Morioka, Iwate, 020-8551, Japan.

Caenorhabditis elegans T09F3.2 is a homolog of the human mitochondrial pyrimidine nucleotide transporter. We isolated a T09F3. Read More

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Balancing essential and non-essential metal bioavailability during hatchery rearing of Greenshell mussel (Perna canaliculus) larvae.

Ecotoxicol Environ Saf 2021 Apr 13;216:112194. Epub 2021 Apr 13.

Cawthron Institute, 98 Halifax Street East, Nelson, New Zealand.

The use of ethylenediaminetetraacetic acid (EDTA) during bivalve hatchery production is thought to improve larval yields due to the reduced exposure to toxic metals (such as Cu); however, few studies have focused on the bioavailability of metals during the rearing process. Greenshell™ mussels (Perna canaliculus) were reared for 48 h with and without EDTA (12 µM) exposure and larvae were subsequently raised to 21 days post-fertilisation with and without EDTA exposure. Survival, shell length, algal ingestion rate, swimming activity, total metal concentration in water, bioavailable metal concentrations and larval metal accumulation were monitored for the 21 day period. Read More

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Effect of biochar-immobilized Sphingomonas sp. PJ2 on bioremediation of PAHs and bacterial community composition in saline soil.

Chemosphere 2021 Mar 31;279:130427. Epub 2021 Mar 31.

College of Land and Environment, Shenyang Agricultural University, Shenyang, 110866, PR China; Key Laboratory of Northeast Arable Land Conservation of Ministry of Agriculture, Shenyang Agricultural University, Shenyang, 110866, PR China.

This study aimed to investigate the bioremediation efficiency and bacterial regulation mechanism of biochar-immobilized bacterium (BM) in polycyclic aromatic hydrocarbon (PAH)-contaminated saline soil by conducting pot experiments. In BM treatment, PAH-degrading strain Sphingomonas sp. PJ2 was inoculated into biochar produced at 400 °C and 600 °C using the pine needles (BM400 and BM600). Read More

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Person-specific networks in psychopathology: Past, present, and future.

Curr Opin Psychol 2021 Mar 19;41:59-64. Epub 2021 Mar 19.

University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), P.O. Box 30.001 (CC72), 9700 RB, Groningen, the Netherlands; University of Groningen, Faculty of Behavioural and Social Sciences, Department of Psychometrics and Statistics, Grote Kruisstraat 2/1, 9712 TS, Groningen, the Netherlands. Electronic address:

In the psychological network approach, mental disorders such as major depressive disorder are conceptualized as networks. The network approach focuses on the symptom structure or the connections between symptoms instead of the severity (i.e. Read More

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Carotenogenesis of Staphylococcus aureus: New insights and impact on membrane biophysical properties.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Apr 13:158941. Epub 2021 Apr 13.

Laboratory of Advanced Analytical Techniques in Natural Products (LATNAP), Chemistry Department, Universidad de los Andes, Bogotá, D.C., Colombia. Electronic address:

Staphyloxanthin (STX) is a saccharolipid derived from a carotenoid in Staphylococcus aureus involved in oxidative-stress tolerance and antimicrobial peptide resistance. STX influences the biophysical properties of the bacterial membrane and has been associated to the formation of lipid domains in the regulation of methicillin-resistance. In this work, a targeted metabolomics and biophysical characterization study was carried out to investigate the biosynthetic pathways of carotenoids, and their impact on the membrane biophysical properties. Read More

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A dosage-effect assessment of acute toxicology tests of microplastic exposure in filter-feeding fish.

Fish Shellfish Immunol 2021 Apr 13. Epub 2021 Apr 13.

Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Abundant microplastics was found in aquatic ecosystem and aquatic organisms, which raised many concerns in public. Silver carp (Hypophthalmichthys molitrix), a species filter-feeding planktivorous fish, feed on particle between 4 to 85 μm in size, and the respiratory process works together with feeding mechanism when filtering plankton from water. The aim of this study was to assess the physiological response of silver carp exposed to 5 μm polystyrene microspheres during 48 h of exposure followed by 48 h of depuration through the gill histology, and oxidative stress biomarkers in intestine. Read More

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AMPK signaling and its targeting in cancer progression and treatment.

Semin Cancer Biol 2021 Apr 13. Epub 2021 Apr 13.

Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston-Salem, NC, 27101, USA. Electronic address:

The intrinsic mechanisms sensing the imbalance of energy in cells are pivotal for cell survival under various environmental insults. AMP-activated protein kinase (AMPK) serves as a central guardian maintaining energy homeostasis by orchestrating diverse cellular processes, such as lipogenesis, glycolysis, TCA cycle, cell cycle progression and mitochondrial dynamics. Given that AMPK plays an essential role in the maintenance of energy balance and metabolism, managing AMPK activation is considered as a promising strategy for the treatment of metabolic disorders such as type 2 diabetes and obesity. Read More

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Structural basis for the regulation of inducible nitric oxide synthase by the SPRY domain-containing SOCS box protein SPSB2.

Nitric Oxide 2021 Apr 13. Epub 2021 Apr 13.

Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, 510632, China; Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, 510632, China; National Engineering Research Center of Genetic Medicine, Guangzhou, 510632, China. Electronic address:

Relatively high concentration of nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in response to a variety of stimuli is a source of reactive nitrogen species, an important weapon of host innate immune defense. The SPRY domain-containing SOCS box protein 2 (SPSB2) is a negative regulator of iNOS that modulates the life-time of iNOS. SPSB2 interacts with the N-terminal region of iNOS via a binding site on the SPRY domain of SPSB2, and recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, leading to its proteasomal degradation. Read More

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Regulatory density as a means to refine current regulatory approaches for increasingly complex medicines.

Drug Discov Today 2021 Apr 13. Epub 2021 Apr 13.

Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, WHO Collaborating Centre for Pharmaceutical Policy and Regulation, Utrecht University, Utrecht, The Netherlands.

The continuous scientific, societal, and technological advancements have shifted drug development toward increasingly complex and ever more targeted treatments. This creates new and unprecedented challenges for global regulatory systems. To address the increased risks and uncertainties of increasingly complex medicine, we advocate for a more tailored and flexible regulatory approach, which is explained here with the concept of 'regulatory density'. Read More

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TSH attenuates fatty acid oxidation in hepatocytes by reducing the mitochondrial distribution of miR-449a/449b-5p/5194.

Mol Cell Endocrinol 2021 Apr 13:111280. Epub 2021 Apr 13.

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Shandong University, Jinan, 250012, China. Electronic address:

The elevated thyroid-stimulating hormone (TSH) levels contribute to the abnormal expression/activity of several key hepatic lipid metabolism enzymes. Although miRNAs have been shown to play key roles in hepatic lipid metabolism and are found in isolated mitochondria, very little is known about the pathological and physiological significance of their mitochondrial distributions in regulating liver lipid metabolism. Here, we found that TSH significantly reduced the distribution of some miRNAs in mitochondria of hepatocytes, especially miR-449a, miR-449b-5p, and miR-5194. Read More

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Release of redox enzymes and micro-RNAs in extracellular vesicles, during infection and inflammation.

Free Radic Biol Med 2021 Apr 13. Epub 2021 Apr 13.

Department of Clinical Experimental Medicine, Brighton & Sussex Medical School, Brighton, BN19RY, United Kingdom.

Many studies reported that redox enzymes, particularly thioredoxin and peroxiredoxin, can be released by cells and act as soluble mediators in immunity. Recently, it became clear that peroxiredoxins can be secreted via the exosome-release route, yet it remains unclear how this exactly happens and why. This review will first introduce briefly the possible redox states of protein cysteines and the role of redox enzymes in their regulation. Read More

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Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers.

Biochim Biophys Acta Rev Cancer 2021 Apr 13:188538. Epub 2021 Apr 13.

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France.

Twenty mucin genes have been identified and classified in two groups (encoding secreted and membrane-bound proteins). Secreted mucins participate in mucus formation by assembling a 3-dimensional network via oligomerization, whereas membrane-bound mucins are anchored to the outer membrane mediating extracellular interactions and cell signaling. Both groups have been associated with carcinogenesis progression in epithelial cancers, and are therefore considered as potential therapeutic targets. Read More

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Adenosine 5'-monophosphate induces hypothermia and alters gene expressions in the brain and liver of chicks.

Brain Res Bull 2021 Apr 13. Epub 2021 Apr 13.

Laboratory of Animal Behavior and Physiology, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi, Hiroshima, 739-8528, Japan. Electronic address:

The adenosine A1 receptor is important for body temperature regulation in mammals; however, little is known about its function in avian species. In this study, we investigated the effects of the adenosine A1 receptor agonist and antagonist (adenosine 5'-monophosphate [5'-AMP] and 8 p-sulfophenyl theophylline [8-SPT], respectively) on thermoregulation in chickens. Male chicks were used in this study. Read More

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The NLRP3-related inflammasome modulates pain behavior in a rat model of trigeminal neuropathic pain.

Life Sci 2021 Apr 13:119489. Epub 2021 Apr 13.

Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. Electronic address:

Aims: Nod-like receptor family pyrin domain containing 3 (NLRP3) may play an important role in neuropathic pain. Treatment for trigeminal neuropathic pain remains a challenge, as common drugs either do not demonstrate beneficial therapeutic effects or induce intolerance in patients.

Main Methods: In a rat model of trigeminal neuropathic pain, pain caused by the malpositioning of dental implants is similar to that experienced by humans. Read More

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Roles of microRNAs in renal disorders related to primary podocyte dysfunction.

Life Sci 2021 Apr 13:119463. Epub 2021 Apr 13.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Through the regulation of gene expression, microRNAs (miRNAs) are capable of modulating vital biological processes, such as proliferation, differentiation, and apoptosis. Several mechanisms control the function of miRNAs, including translational inhibition and targeted miRNA degradation. Through utilizing high-throughput screening methods, such as small RNA sequencing and microarray, alterations in miRNA expression of kidneys have recently been observed both in rodent models and humans throughout the development of chronic kidney disease (CKD) and acute kidney injury (AKI). Read More

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Molecular cloning and characterization of CD63 in common carp infected with koi herpesvirus.

Dev Comp Immunol 2021 Apr 13:104102. Epub 2021 Apr 13.

Joint Laboratory of Guangdong Province and Hong Kong Regions on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address:

CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 (ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84. Read More

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Behav Brain Res 2021 Apr 13:113296. Epub 2021 Apr 13.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil. Electronic address:

Changes in 5-HT receptor (5-HTR)-mediated neurotransmission in the hippocampus have been associated with anxiety, depression and in the mode of action of antidepressant drugs. It has been commonly accepted that whereas the dorsal pole of the hippocampus (DH) is involved in cognitive processing, the ventral pole (VH) is associated with emotional regulation. However, to date, only a few studies have directly addressed the role played by VH 5-HTRs in anxiety and panic processing, and their results are conflicting. Read More

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Migratory state and patterns of steroid hormone regulation in the pectoralis muscle of a nomadic migrant, the pine siskin (Spinus pinus).

Gen Comp Endocrinol 2021 Apr 13:113787. Epub 2021 Apr 13.

School of Biological Sciences, Washington State University, Pullman, WA, USA.

The endocrine system is known to mediate responses to environmental change and transitions between different life stages (e.g., a non-breeding to a breeding life stage). Read More

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Juvenile hormone in spiders. Is this the solution to a mystery?

Gen Comp Endocrinol 2021 Apr 13:113781. Epub 2021 Apr 13.

University of Silesia in Katowice, Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, Bankowa 9, 40007 Katowice, Poland.

The juvenile hormone (JH) plays a crucial role in arthropod physiological processes, e.g., the regulation of metamorphosis, development, and reproduction (the vitellogenesis, the development of gonads, egg production). Read More

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Structure and thermodynamics of transient protein-protein complexes by chemometric decomposition of SAXS datasets.

Structure 2021 Apr 10. Epub 2021 Apr 10.

Centre de Biochimie Structurale (CBS), INSERM, CNRS and Université de Montpellier, 29, rue de Navacelles, 34090 Montpellier, France. Electronic address:

Transient biomolecular interactions play crucial roles in many cellular signaling and regulation processes. However, deciphering the structure of these assemblies is challenging owing to the difficulties in isolating complexes from the individual partners. The additive nature of small-angle X-ray scattering (SAXS) data allows for probing the species present in these mixtures, but decomposition into structural and thermodynamic information is difficult. Read More

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Mitochondrial state determines functionally divergent stem cell population in planaria.

Stem Cell Reports 2021 Apr 3. Epub 2021 Apr 3.

Integrative Chemical Biology, Institute for Stem Cell Science and Regenerative Medicine, Bengaluru, India. Electronic address:

Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared with their progenitors. Read More

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