6,320 results match your criteria Cellular and molecular life sciences : CMLS[Journal]


Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.

Cell Mol Life Sci 2020 Jul 11. Epub 2020 Jul 11.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, 410078, China.

The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. Read More

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http://dx.doi.org/10.1007/s00018-020-03581-0DOI Listing

Bassoon inhibits proteasome activity via interaction with PSMB4.

Cell Mol Life Sci 2020 Jul 10. Epub 2020 Jul 10.

Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.

Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Read More

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http://dx.doi.org/10.1007/s00018-020-03590-zDOI Listing

Macroglial diversity: white and grey areas and relevance to remyelination.

Cell Mol Life Sci 2020 Jul 9. Epub 2020 Jul 9.

Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV, Groningen, the Netherlands.

Macroglia, comprising astrocytes and oligodendroglial lineage cells, have long been regarded as uniform cell types of the central nervous system (CNS). Although regional morphological differences between these cell types were initially described after their identification a century ago, these differences were largely ignored. Recently, accumulating evidence suggests that macroglial cells form distinct populations throughout the CNS, based on both functional and morphological features. Read More

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http://dx.doi.org/10.1007/s00018-020-03586-9DOI Listing

Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.

Cell Mol Life Sci 2020 Jul 8. Epub 2020 Jul 8.

The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.

AlkB homologs (ALKBH) are a family of specific demethylases that depend on Fe and α-ketoglutarate to catalyze demethylation on different substrates, including ssDNA, dsDNA, mRNA, tRNA, and proteins. Previous studies have made great progress in determining the sequence, structure, and molecular mechanism of the ALKBH family. Here, we first review the multi-substrate selectivity of the ALKBH demethylase family from the perspective of sequence and structural evolution. Read More

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http://dx.doi.org/10.1007/s00018-020-03594-9DOI Listing

RBM38 in cancer: role and mechanism.

Cell Mol Life Sci 2020 Jul 8. Epub 2020 Jul 8.

College of Biology, Hunan University, Changsha, 410082, China.

Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. Read More

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http://dx.doi.org/10.1007/s00018-020-03593-wDOI Listing

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.

Cell Mol Life Sci 2020 Jul 4. Epub 2020 Jul 4.

Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy.

The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Read More

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http://dx.doi.org/10.1007/s00018-020-03580-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334636PMC

Glial cells in Parkinson´s disease: protective or deleterious?

Cell Mol Life Sci 2020 Jul 2. Epub 2020 Jul 2.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.

Glial cells have been identified more than 100 years ago, and are known to play a key role in the central nervous system (CNS) function. A recent piece of evidence is emerging showing that in addition to the capacity of CNS modulation and homeostasis, glial cells are also being looked like as a promising cell source not only to study CNS pathologies initiation and progression but also to the establishment and development of new therapeutic strategies. Thus, in the present review, we will discuss the current evidence regarding glial cells' contribution to neurodegenerative diseases as Parkinson's disease, providing cellular, molecular, functional, and behavioral data supporting its active role in disease initiation, progression, and treatment. Read More

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http://dx.doi.org/10.1007/s00018-020-03584-xDOI Listing

Neural glycomics: the sweet side of nervous system functions.

Cell Mol Life Sci 2020 Jul 1. Epub 2020 Jul 1.

Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, 515041, Guangdong, China.

The success of investigations on the structure and function of the genome (genomics) has been paralleled by an equally awesome progress in the analysis of protein structure and function (proteomics). We propose that the investigation of carbohydrate structures that go beyond a cell's metabolism is a rapidly developing frontier in our expanding knowledge on the structure and function of carbohydrates (glycomics). No other functional system appears to be suited as well as the nervous system to study the functions of glycans, which had been originally characterized outside the nervous system. Read More

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http://dx.doi.org/10.1007/s00018-020-03578-9DOI Listing

The proteostasis guardian HSF1 directs the transcription of its paralog and interactor HSF2 during proteasome dysfunction.

Cell Mol Life Sci 2020 Jun 30. Epub 2020 Jun 30.

Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133, Rome, Italy.

Protein homeostasis is essential for life in eukaryotes. Organisms respond to proteotoxic stress by activating heat shock transcription factors (HSFs), which play important roles in cytoprotection, longevity and development. Of six human HSFs, HSF1 acts as a proteostasis guardian regulating stress-induced transcriptional responses, whereas HSF2 has a critical role in development, in particular of brain and reproductive organs. Read More

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http://dx.doi.org/10.1007/s00018-020-03568-xDOI Listing

Engineered-extracellular vesicles as an optimistic tool for microRNA delivery for osteoarthritis treatment.

Cell Mol Life Sci 2020 Jun 29. Epub 2020 Jun 29.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Worldwide, osteoarthritis (OA) is one of the most common chronic diseases. In OA, profiling gene expression changes occur and cartilage tissue homeostasis is lost. Suggestions for OA treatment include regulation of gene expressions via the use of microRNAs (miRNAs). Read More

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http://dx.doi.org/10.1007/s00018-020-03585-wDOI Listing

Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme.

Cell Mol Life Sci 2020 Jun 29. Epub 2020 Jun 29.

Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.

Plexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and find that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Read More

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http://dx.doi.org/10.1007/s00018-020-03571-2DOI Listing

Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury.

Cell Mol Life Sci 2020 Jun 28. Epub 2020 Jun 28.

Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.

Apoptosis, necrosis and autophagy-dependent cell death are the three major types of cell death. Traditionally, necrosis is thought as a passive and unregulated form of cell death. However, certain necrosis can also occur in a highly regulated manner, referring to regulated necrosis. Read More

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http://dx.doi.org/10.1007/s00018-020-03587-8DOI Listing

L-serine synthesis via the phosphorylated pathway in humans.

Cell Mol Life Sci 2020 Jun 27. Epub 2020 Jun 27.

Department of Biotechnology and Life Sciences, University of Insubria, Via J. H. Dunant 3, 21100, Varese, Italy.

L-serine is a nonessential amino acid in eukaryotic cells, used for protein synthesis and in producing phosphoglycerides, glycerides, sphingolipids, phosphatidylserine, and methylenetetrahydrofolate. Moreover, L-serine is the precursor of two relevant coagonists of NMDA receptors: glycine (through the enzyme serine hydroxymethyltransferase), which preferentially acts on extrasynaptic receptors and D-serine (through the enzyme serine racemase), dominant at synaptic receptors. The cytosolic "phosphorylated pathway" regulates de novo biosynthesis of L-serine, employing 3-phosphoglycerate generated by glycolysis and the enzymes 3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase (the latter representing the irreversible step). Read More

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http://dx.doi.org/10.1007/s00018-020-03574-zDOI Listing
June 2020
5.808 Impact Factor

Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.

Cell Mol Life Sci 2020 Jun 27. Epub 2020 Jun 27.

Department of Pharmacology, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA.

Diabetes affects millions of people worldwide. This devastating disease dramatically increases the risk of developing cardiovascular disorders. A hallmark metabolic abnormality in diabetes is hyperglycemia, which contributes to the pathogenesis of cardiovascular complications. Read More

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http://dx.doi.org/10.1007/s00018-020-03582-zDOI Listing

ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.

Cell Mol Life Sci 2020 Jun 26. Epub 2020 Jun 26.

INSERM, U1016, Institut Cochin, CNRS, UMR8104, Université de Paris, 22 rue Méchain, 75014, Paris, France.

The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Read More

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http://dx.doi.org/10.1007/s00018-020-03577-wDOI Listing

KHK inhibition for the treatment of hereditary fructose intolerance and nonalcoholic fatty liver disease: a double-edged sword.

Cell Mol Life Sci 2020 Jun 26. Epub 2020 Jun 26.

Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul RS, Brazil.

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http://dx.doi.org/10.1007/s00018-020-03575-yDOI Listing

Functional impact of HIV-1 Tat on cells of the CNS and its role in HAND.

Cell Mol Life Sci 2020 Jun 23. Epub 2020 Jun 23.

Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th St, Philadelphia, PA, 19102, USA.

Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) is a potent mediator involved in the development of HIV-1-associated neurocognitive disorders (HAND). Tat is expressed even in the presence of antiretroviral therapy (ART) and is able to enter the central nervous system (CNS) through a variety of ways, where Tat can interact with microglia, astrocytes, brain microvascular endothelial cells, and neurons. The presence of low concentrations of extracellular Tat alone has been shown to lead to dysregulated gene expression, chronic cell activation, inflammation, neurotoxicity, and structural damage in the brain. Read More

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http://dx.doi.org/10.1007/s00018-020-03561-4DOI Listing

New insights into anti-Müllerian hormone role in the hypothalamic-pituitary-gonadal axis and neuroendocrine development.

Cell Mol Life Sci 2020 Jun 20. Epub 2020 Jun 20.

Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience and Cognition, 59000, Lille, France.

Research into the physiological actions of anti-Müllerian hormone (AMH) has rapidly expanded from its classical role in male sexual differentiation to the regulation of ovarian function, routine clinical use in reproductive health and potential use as a biomarker in the diagnosis of polycystic ovary syndrome (PCOS). During the past 10 years, the notion that AMH could act exclusively at gonadal levels has undergone another paradigm shift as several exciting studies reported unforeseen AMH actions throughout the Hypothalamic-Pituitary-Gonadal (HPG) axis. In this review, we will focus on these findings reporting novel AMH actions across the HPG axis and we will discuss their potential impact and significance to better understand human reproductive disorders characterized by either developmental alterations of neuroendocrine circuits regulating fertility and/or alterations of their function in adult life. Read More

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http://dx.doi.org/10.1007/s00018-020-03576-xDOI Listing

KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers.

Cell Mol Life Sci 2020 Jun 19. Epub 2020 Jun 19.

School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China.

KDEL receptor cycles between the ER and the Golgi to retrieve ER-resident chaperones that get leaked to the secretory pathway during protein export from the ER. Recent studies have shown that a fraction of KDEL receptor may reside in the plasma membrane and function as a putative cell surface receptor. However, the trafficking itinerary and mechanism of cell surface expressed KDEL receptor remains largely unknown. Read More

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http://dx.doi.org/10.1007/s00018-020-03570-3DOI Listing

Epigenetic control of natriuretic peptides: implications for health and disease.

Cell Mol Life Sci 2020 Jun 18. Epub 2020 Jun 18.

IRCCS Neuromed, Pozzilli, Isernia, Italy.

The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to preserve regular functions and health. The concentration level of each component of the family is of crucial importance to guarantee a proper control of both systemic and local cardiovascular functions. A fine equilibrium between gene expression, protein secretion and clearance is needed to achieve the final optimal level of NPs. Read More

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http://dx.doi.org/10.1007/s00018-020-03573-0DOI Listing

Tumour dormancy in inflammatory microenvironment: A promising therapeutic strategy for cancer-related bone metastasis.

Cell Mol Life Sci 2020 Jun 16. Epub 2020 Jun 16.

Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Cancer metastasis is a unique feature of malignant tumours. Even bone can become a common colonization site due to the tendency of solid tumours, including breast cancer (BCa) and prostate cancer (PCa), to metastasize to bone. Currently, a previous concept in tumour metabolism called tumour dormancy may be a promising target for antitumour treatment. Read More

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http://dx.doi.org/10.1007/s00018-020-03572-1DOI Listing

Revisiting respiratory syncytial virus's interaction with host immunity, towards novel therapeutics.

Cell Mol Life Sci 2020 Jun 16. Epub 2020 Jun 16.

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Every year there are > 33 million cases of Respiratory Syncytial Virus (RSV)-related respiratory infection in children under the age of five, making RSV the leading cause of lower respiratory tract infection (LRTI) in infants. RSV is a global infection, but 99% of related mortality is in low/middle-income countries. Unbelievably, 62 years after its identification, there remains no effective treatment nor vaccine for this deadly virus, leaving infants, elderly and immunocompromised patients at high risk. Read More

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http://dx.doi.org/10.1007/s00018-020-03557-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298439PMC

How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?

Cell Mol Life Sci 2020 Jun 8. Epub 2020 Jun 8.

Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.

In men with oligozoospermia, Robertsonian translocations (RobTs) are the most common type of autosomal aberrations. The most commonly occurring types are rob(13;14) and rob(14;21), and other types of RobTs are described as 'rare' cases. Based on molecular research, all RobTs can be broadly classified into Class 1 and Class 2. Read More

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http://dx.doi.org/10.1007/s00018-020-03560-5DOI Listing

A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine : "A gut feeling".

Cell Mol Life Sci 2020 Jun 6. Epub 2020 Jun 6.

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525, Nijmegen, The Netherlands.

The human body is able to process and transport a complex variety of carbohydrates, unlocking their nutritional value as energy source or as important building block. The endogenous glycosyl hydrolases (glycosidases) and glycosyl transporter proteins located in the enterocytes of the small intestine play a crucial role in this process and digest and/or transport nutritional sugars based on their structural features. It is for these reasons that glycosidases and glycosyl transporters are interesting therapeutic targets to combat sugar related diseases (such as diabetes) or to improve drug delivery. Read More

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http://dx.doi.org/10.1007/s00018-020-03564-1DOI Listing

Metabolic heterogeneity and adaptability in brain tumors.

Cell Mol Life Sci 2020 Jun 6. Epub 2020 Jun 6.

Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, FL, USA.

The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of tumor cells to modify their genetic landscape and adapt metabolically, subverts therapeutic efficacy, and inevitably instigates therapeutic resistance. To overcome these challenges and develop effective therapeutic strategies targeting essential metabolic processes, it is necessary to identify the mechanisms underlying heterogeneity and define metabolic preferences and liabilities of malignant cells. Read More

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http://dx.doi.org/10.1007/s00018-020-03569-wDOI Listing

How CD40L reverse signaling regulates axon and dendrite growth.

Cell Mol Life Sci 2020 Jun 6. Epub 2020 Jun 6.

School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, Wales.

CD40-activated CD40L reverse signaling is a major physiological regulator of axon and dendrite growth from developing hippocampal pyramidal neurons. Here we have studied how CD40L-mediated reverse signaling promotes the growth of these processes. Cultures of hippocampal pyramidal neurons were established from Cd40 mouse embryos to eliminate endogenous CD40/CD40L signaling, and CD40L reverse signaling was stimulated by a CD40-Fc chimera. Read More

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http://dx.doi.org/10.1007/s00018-020-03563-2DOI Listing

Contribution of neural crest-derived stem cells and nasal chondrocytes to articular cartilage regeneration.

Cell Mol Life Sci 2020 Jun 5. Epub 2020 Jun 5.

Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, 64 Medical Center Drive, PO Box 9196, Morgantown, WV, 26506-9196, USA.

Due to poor self-regenerative potential of articular cartilage, stem cell-based regeneration becomes a hopeful approach for the treatment of articular cartilage defects. Recent studies indicate that neural crest-derived cells (NCDCs) have the potential for repairing articular cartilage with even greater chondrogenic capacity than mesoderm-derived cells (MDCs): a conventional stem cell source for cartilage regeneration. Given that NCDCs originate from a different germ layer in the early embryo compared with MDCs that give rise to articular cartilage, a mystery remains regarding their capacity for articular cartilage regeneration. Read More

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http://dx.doi.org/10.1007/s00018-020-03567-yDOI Listing

Stress granule subtypes: an emerging link to neurodegeneration.

Cell Mol Life Sci 2020 Jun 4. Epub 2020 Jun 4.

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, MA, USA.

Stress Granules (SGs) are membraneless cytoplasmic RNA granules, which contain translationally stalled mRNAs, associated translation initiation factors and multiple RNA-binding proteins (RBPs). They are formed in response to various stresses and contribute to reprogramming of cellular metabolism to aid cell survival. Because of their cytoprotective nature, association with translation regulation and cell signaling, SGs are an essential component of the integrated stress response pathway, a complex adaptive program central to stress management. Read More

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http://dx.doi.org/10.1007/s00018-020-03565-0DOI Listing

Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress.

Cell Mol Life Sci 2020 Jun 3. Epub 2020 Jun 3.

Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge, UK.

The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as 'developmental programming', whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pathways and epigenetic mechanisms that are dysregulated in metabolic organs of the fetus and adult programmed due to an adverse gestational environment. Read More

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http://dx.doi.org/10.1007/s00018-020-03566-zDOI Listing

Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.

Cell Mol Life Sci 2020 May 31. Epub 2020 May 31.

Developmental Neurobiology Unit, GIGA Stem Cells/Neurosciences, University of Liège, Quartier Hopital (CHU), Avenue Hippocrate, 15, 4000, Liege, Belgium.

A persistent dogma in neuroscience supported the idea that terminally differentiated neurons permanently withdraw from the cell cycle. However, since the late 1990s, several studies have shown that cell cycle proteins are expressed in post-mitotic neurons under physiological conditions, indicating that the cell cycle machinery is not restricted to proliferating cells. Moreover, many studies have highlighted a clear link between cell cycle-related proteins and neurological disorders, particularly relating to apoptosis-induced neuronal death. Read More

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http://dx.doi.org/10.1007/s00018-020-03548-1DOI Listing

Saccharomyces cerevisiae rDNA as super-hub: the region where replication, transcription and recombination meet.

Cell Mol Life Sci 2020 May 31. Epub 2020 May 31.

Dipartimento di Biologia e Biotecnologie, Università di Roma, Sapienza, Rome, Italy.

Saccharomyces cerevisiae ribosomal DNA, the repeated region where rRNAs are synthesized by about 150 encoding units, hosts all the protein machineries responsible for the main DNA transactions such as replication, transcription and recombination. This and its repetitive nature make rDNA a unique and complex genetic locus compared to any other. All the different molecular machineries acting in this locus need to be accurately and finely controlled and coordinated and for this reason rDNA is one of the most impressive examples of highly complex molecular regulated loci. Read More

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http://dx.doi.org/10.1007/s00018-020-03562-3DOI Listing

Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.

Cell Mol Life Sci 2020 May 29. Epub 2020 May 29.

Unité Récepteurs-Canaux, Institut Pasteur, UMR 3571, CNRS, 75015, Paris, France.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ion channels expressed in the central nervous systems. nAChRs containing the α4, β2 and α5 subunits are specifically involved in addictive processes, but their functional architecture is poorly understood due to the intricacy of assembly of these subunits. Here we constrained the subunit assembly by designing fully concatenated human α4β2 and α4β2α5 receptors and characterized their properties by two-electrodes voltage-clamp electrophysiology in Xenopus oocytes. Read More

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http://dx.doi.org/10.1007/s00018-020-03558-zDOI Listing

Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2.

Cell Mol Life Sci 2020 May 28. Epub 2020 May 28.

Institute of Clinical Pharmacology, Goethe-University Frankfurt, Faculty of Medicine, Frankfurt, Germany.

Recent studies suggest that synaptic lysophosphatidic acids (LPAs) augment glutamate-dependent cortical excitability and sensory information processing in mice and humans via presynaptic LPAR2 activation. Here, we studied the consequences of LPAR2 deletion or antagonism on various aspects of cognition using a set of behavioral and electrophysiological analyses. Hippocampal neuronal network activity was decreased in middle-aged LPAR2 mice, whereas hippocampal long-term potentiation (LTP) was increased suggesting cognitive advantages of LPAR2 mice. Read More

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http://dx.doi.org/10.1007/s00018-020-03553-4DOI Listing

The role of SIRT3-mediated mitochondrial homeostasis in osteoarthritis.

Cell Mol Life Sci 2020 May 28. Epub 2020 May 28.

Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Osteoarthritis is the most common degenerative joint disease and causes major pain and disability in adults. It has been reported that mitochondrial dysfunction in chondrocytes is associated with osteoarthritis. Sirtuins are a family of nicotinamide adenine dinucleotide-dependent histone deacetylases that have the ability to deacetylate protein targets and play an important role in the regulation of cell physiological and pathological processes. Read More

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http://dx.doi.org/10.1007/s00018-020-03497-9DOI Listing

Programmed genome rearrangements in ciliates.

Cell Mol Life Sci 2020 May 27. Epub 2020 May 27.

Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012, Bern, Switzerland.

Ciliates are a highly divergent group of unicellular eukaryotes with separate somatic and germline genomes found in distinct dimorphic nuclei. This characteristic feature is tightly linked to extremely laborious developmentally regulated genome rearrangements in the development of a new somatic genome/nuclei following sex. The transformation from germline to soma genome involves massive DNA elimination mediated by non-coding RNAs, chromosome fragmentation, as well as DNA amplification. Read More

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http://dx.doi.org/10.1007/s00018-020-03555-2DOI Listing

Heparanase, cell signaling, and viral infections.

Cell Mol Life Sci 2020 May 27. Epub 2020 May 27.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor St, Chicago, IL, 60612, USA.

Heparanase (HPSE) is a multifunctional protein endowed with many non-enzymatic functions and a unique enzymatic activity as an endo-β-D-glucuronidase. The latter allows it to serve as a key modulator of extracellular matrix (ECM) via a well-regulated cleavage of heparan sulfate side chains of proteoglycans at cell surfaces. The cleavage and associated changes at the ECM cause release of multiple signaling molecules with important cellular and pathological functions. Read More

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http://dx.doi.org/10.1007/s00018-020-03559-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252873PMC
May 2020
5.808 Impact Factor

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas.

Cell Mol Life Sci 2020 May 27. Epub 2020 May 27.

Department of Dermatology, University of Turku and Turku University Hospital, Hämeentie 11 TE6, 20520, Turku, Finland.

Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes. Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g. Read More

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http://dx.doi.org/10.1007/s00018-020-03554-3DOI Listing

Updating dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2): molecular basis, functions and role in diseases.

Cell Mol Life Sci 2020 May 27. Epub 2020 May 27.

Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Avda. Menéndez Pidal s/n., 14004, Córdoba, Spain.

Members of the dual-specificity tyrosine-regulated kinase (DYRKs) subfamily possess a distinctive capacity to phosphorylate tyrosine, serine, and threonine residues. Among the DYRK class II members, DYRK2 is considered a unique protein due to its role in disease. According to the post-transcriptional and post-translational modifications, DYRK2 expression greatly differs among human tissues. Read More

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http://dx.doi.org/10.1007/s00018-020-03556-1DOI Listing

Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways.

Cell Mol Life Sci 2020 May 26. Epub 2020 May 26.

Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia.

Modification of the cancer-associated chromatin landscape in response to therapeutic DNA damage influences gene expression and contributes to cell fate. The central histone mark H2Bub1 results from addition of a single ubiquitin on lysine 120 of histone H2B and is an important regulator of gene expression. Following treatment with a platinum-based chemotherapeutic, there is a reduction in global levels of H2Bub1 accompanied by an increase in levels of the tumor suppressor p53. Read More

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http://dx.doi.org/10.1007/s00018-020-03552-5DOI Listing

The formin INF2 in disease: progress from 10 years of research.

Cell Mol Life Sci 2020 May 25. Epub 2020 May 25.

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.

Formins are a conserved family of proteins that primarily act to form linear polymers of actin. Despite their importance to the normal functioning of the cytoskeleton, for a long time, the only two formin genes known to be a genetic cause of human disorders were DIAPH1 and DIAPH3, whose mutation causes two distinct forms of hereditary deafness. In the last 10 years, however, the formin INF2 has emerged as an important target of mutations responsible for the appearance of focal segmental glomerulosclerosis, which are histological lesions associated with glomerulus degeneration that often leads to end-stage renal disease. Read More

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http://dx.doi.org/10.1007/s00018-020-03550-7DOI Listing

Regulation of the expression of the estrogen related receptors (ERRs).

Cell Mol Life Sci 2020 May 24. Epub 2020 May 24.

Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, 32-34 Avenue Tony Garnier, 69007, Lyon, France.

Estrogen related receptors (ERRα, β and γ in mammals) are orphan members of the nuclear receptor superfamily acting as transcription factors. ERRs are expressed in several tissues and cells and they display various physiological and pathological functions, controlling, amongst others and depending on the receptor, bone homeostasis, energy metabolism, embryonic stem cell pluripotency, and cancer progression. In contrast to classical nuclear receptors, the activities of the ERRs are not controlled by a natural ligand. Read More

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http://dx.doi.org/10.1007/s00018-020-03549-0DOI Listing

Metabolism and growth adaptation to environmental conditions in Drosophila.

Cell Mol Life Sci 2020 May 24. Epub 2020 May 24.

Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Read More

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http://dx.doi.org/10.1007/s00018-020-03547-2DOI Listing

TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.

Cell Mol Life Sci 2020 May 23. Epub 2020 May 23.

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.

Squamous cell carcinoma (SCC) is an aggressive malignancy that can originate from various organs. TP63 is a master regulator that plays an essential role in epidermal differentiation. It is also a lineage-dependent oncogene in SCC. Read More

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http://dx.doi.org/10.1007/s00018-020-03539-2DOI Listing
May 2020
5.808 Impact Factor

Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus.

Cell Mol Life Sci 2020 May 23. Epub 2020 May 23.

Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have here investigated whether changes in these lipids might be important for regulation of transport to the Golgi using the protein toxin ricin. Modulation of DAG and PA levels using DAG kinase (DGK) and phospholipase D (PLD) inhibitors gave a strong increase in retrograde ricin transport, but had little impact on ricin recycling or degradation. Read More

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http://dx.doi.org/10.1007/s00018-020-03551-6DOI Listing

TGF-β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44.

Cell Mol Life Sci 2020 May 21. Epub 2020 May 21.

Department of Urology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.

CD44 is a marker of cancer stem cell (CSC) in many types of tumors. Alternative splicing of its 20 exons generates various CD44 isoforms that have different tissue specific expression and functions, including the CD44 standard isoform (CD44s) encoded by the constant exons and the CD44 variant isoforms (CD44v) with variant exon insertions. Switching between the CD44v and CD44s isoforms plays pivotal roles in tumor progression. Read More

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http://dx.doi.org/10.1007/s00018-020-03544-5DOI Listing
May 2020
5.808 Impact Factor

Studies of ApoD and ApoDApoE mice uncover the APOD significance for retinal metabolism, function, and status of chorioretinal blood vessels.

Cell Mol Life Sci 2020 May 21. Epub 2020 May 21.

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USA.

Apolipoprotein D (APOD) is an atypical apolipoprotein with unknown significance for retinal structure and function. Conversely, apolipoprotein E (APOE) is a typical apolipoprotein with established roles in retinal cholesterol transport. Herein, we immunolocalized APOD to the photoreceptor inner segments and conducted ophthalmic characterizations of ApoD and ApoDApoE mice. Read More

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http://dx.doi.org/10.1007/s00018-020-03546-3DOI Listing

Functional circuits and signal processing in the enteric nervous system.

Cell Mol Life Sci 2020 May 18. Epub 2020 May 18.

Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.

The enteric nervous system (ENS) is an extensive network comprising millions of neurons and glial cells contained within the wall of the gastrointestinal tract. The major functions of the ENS that have been most studied include the regulation of local gut motility, secretion, and blood flow. Other areas that have been gaining increased attention include its interaction with the immune system, with the gut microbiota and its involvement in the gut-brain axis, and neuro-epithelial interactions. Read More

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http://dx.doi.org/10.1007/s00018-020-03543-6DOI Listing

Staphylococcus aureus impairs cutaneous wound healing by activating the expression of a gap junction protein, connexin-43 in keratinocytes.

Cell Mol Life Sci 2020 May 14. Epub 2020 May 14.

Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Chronic wounds have been considered as major medical problems that may result in expensive healthcare. One of the common causes of chronic wounds is bacterial contamination that leads to persistent inflammation and unbalanced host cell immune responses. Among the bacterial strains that have been identified from chronic wounds, Staphylococcus aureus is the most common strain. Read More

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http://dx.doi.org/10.1007/s00018-020-03545-4DOI Listing

miRNA regulation of social and anxiety-related behaviour.

Cell Mol Life Sci 2020 May 14. Epub 2020 May 14.

Lab of Systems Neuroscience, Department of Health Science and Technology, Institute for Neuroscience, Swiss Federal Institute of Technology ETH, Zurich, Switzerland.

Neuropsychiatric disorders, including autism spectrum disorders (ASD) and anxiety disorders are characterized by a complex range of symptoms, including social behaviour and cognitive deficits, depression and repetitive behaviours. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their aetiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as a new gene regulatory layer in the pathophysiology of mental illness. Read More

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http://dx.doi.org/10.1007/s00018-020-03542-7DOI Listing

TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.

Cell Mol Life Sci 2020 May 14. Epub 2020 May 14.

Université Clermont Auvergne, CNRS, Inserm, GReD, 63000, Clermont-Ferrand, France.

The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Read More

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http://dx.doi.org/10.1007/s00018-020-03541-8DOI Listing