Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC.
Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC. Cell Mol Life Sci. 2019 Nov 23;: Authors: Rovini A, Gurnev PA, Beilina A, Queralt-Martín M, Rosencrans W, Cookson MR, Bezrukov SM, Rostovtseva TK Abstract An intrinsically disordered neuronal protein α-synuclein (αSyn) is known to cause mitochondrial dysfunction, contributing to loss of dopaminergic neurons in Parkinson's disease. Through yet poorly defined mechanisms, αSyn crosses mitochondrial outer membrane and targets respiratory complexes lead...
Source: Cellular and Molecular Life Sciences : CMLS - November 22, 2019 Category: Cytology Authors: Rovini A, Gurnev PA, Beilina A, Queralt-Martín M, Rosencrans W, Cookson MR, Bezrukov SM, Rostovtseva TK Tags: Cell Mol Life Sci Source Type: research

Fructose-mediated effects on gene expression and epigenetic mechanisms associated with NAFLD pathogenesis.
Abstract Nonalcoholic fatty liver disease (NAFLD) is a chronic, frequently progressive condition that develops in response to excessive hepatocyte fat accumulation (i.e., steatosis) in the absence of significant alcohol consumption. Liver steatosis develops as a result of imbalanced lipid metabolism, driven largely by increased rates of de novo lipogenesis and hepatic fatty acid uptake and reduced fatty acid oxidation and/or disposal to the circulation. Fructose is a naturally occurring simple sugar, which is most commonly consumed in modern diets in the form of sucrose, a disaccharide comprised of one molecule of...
Source: Cellular and Molecular Life Sciences : CMLS - November 22, 2019 Category: Cytology Authors: DiStefano JK Tags: Cell Mol Life Sci Source Type: research

The common message of constraint-based optimization approaches: overflow metabolism is caused by two growth-limiting constraints.
ink B Abstract Living cells can express different metabolic pathways that support growth. The criteria that determine which pathways are selected in which environment remain unclear. One recurrent selection is overflow metabolism: the simultaneous usage of an ATP-efficient and -inefficient pathway, shown for example in Escherichia coli, Saccharomyces cerevisiae and cancer cells. Many models, based on different assumptions, can reproduce this observation. Therefore, they provide no conclusive evidence which mechanism is causing overflow metabolism. We compare the mathematical structure of these models. Although ran...
Source: Cellular and Molecular Life Sciences : CMLS - November 21, 2019 Category: Cytology Authors: de Groot DH, Lischke J, Muolo R, Planqué R, Bruggeman FJ, Teusink B Tags: Cell Mol Life Sci Source Type: research

Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons.
We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice,...
Source: Cellular and Molecular Life Sciences : CMLS - November 21, 2019 Category: Cytology Authors: Wang YZ, Fan H, Ji Y, Reynolds K, Gu R, Gan Q, Yamagami T, Zhao T, Hamad S, Bizen N, Takebayashi H, Chen Y, Wu S, Pleasure D, Lam K, Zhou CJ Tags: Cell Mol Life Sci Source Type: research

Correction to: EI24 tethers endoplasmic reticulum and mitochondria to regulate autophagy flux.
Abstract In the published article, few errors were noticed and this has been corrected with this erratum publication. PMID: 31754725 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 20, 2019 Category: Cytology Authors: Yuan L, Liu Q, Wang Z, Hou J, Xu P Tags: Cell Mol Life Sci Source Type: research

Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity.
Abstract DNA damage response (DDR) relies on swift and accurate signaling to rapidly identify DNA lesions and initiate repair. A critical DDR signaling and regulatory molecule is the posttranslational modification poly(ADP-ribose) (PAR). PAR is synthesized by a family of structurally and functionally diverse proteins called poly(ADP-ribose) polymerases (PARPs). Although PARPs share a conserved catalytic domain, unique regulatory domains of individual family members endow PARPs with unique properties and cellular functions. Family members PARP-1, PARP-2, and PARP-3 (DDR-PARPs) are catalytically activated in the pre...
Source: Cellular and Molecular Life Sciences : CMLS - November 20, 2019 Category: Cytology Authors: Eisemann T, Pascal JM Tags: Cell Mol Life Sci Source Type: research

Structural basis of homologous recombination.
Abstract Homologous recombination (HR) is a pathway to faithfully repair DNA double-strand breaks (DSBs). At the core of this pathway is a DNA recombinase, which, as a nucleoprotein filament on ssDNA, pairs with homologous DNA as a template to repair the damaged site. In eukaryotes Rad51 is the recombinase capable of carrying out essential steps including strand invasion, homology search on the sister chromatid and strand exchange. Importantly, a tightly regulated process involving many protein factors has evolved to ensure proper localisation of this DNA repair machinery and its correct timing within the cell cyc...
Source: Cellular and Molecular Life Sciences : CMLS - November 19, 2019 Category: Cytology Authors: Sun Y, McCorvie TJ, Yates LA, Zhang X Tags: Cell Mol Life Sci Source Type: research

Network reduction methods for genome-scale metabolic models.
Abstract Genome-scale metabolic models (GSMs) provide a comprehensive representation of cellular metabolism. GSMs provide a mechanistic link between cellular genotypes and metabolic phenotypes, and are thus widely used to analyze metabolism at the systems level. GSMs consist of hundreds or thousands of reactions. They have thus largely been analyzed with computationally efficient constraint-based methods such as flux-balance analysis, limiting their scope and phenotype prediction accuracy. Computationally more demanding but potentially more informative methods, such as kinetic and dynamic modeling, are currently l...
Source: Cellular and Molecular Life Sciences : CMLS - November 19, 2019 Category: Cytology Authors: Singh D, Lercher MJ Tags: Cell Mol Life Sci Source Type: research

Modelling mitochondrial ROS production by the respiratory chain.
Abstract ROS (superoxide and oxygen peroxide in this paper) play a dual role as signalling molecules and strong oxidizing agents leading to oxidative stress. Their production mainly occurs in mitochondria although they may have other locations (such as NADPH oxidase in particular cell types). Mitochondrial ROS production depends in an interweaving way upon many factors such as the membrane potential, the cell type and the respiratory substrates. Moreover, it is experimentally difficult to quantitatively assess the contribution of each potential site in the respiratory chain. To overcome these difficulties, mathema...
Source: Cellular and Molecular Life Sciences : CMLS - November 19, 2019 Category: Cytology Authors: Mazat JP, Devin A, Ransac S Tags: Cell Mol Life Sci Source Type: research

Multi-tissue to whole plant metabolic modelling.
Abstract Genome-scale metabolic models have been successfully applied to study the metabolism of multiple plant species in the past decade. While most existing genome-scale modelling studies have focussed on studying the metabolic behaviour of individual plant metabolic systems, there is an increasing focus on combining models of multiple tissues or organs to produce multi-tissue models that allow the investigation of metabolic interactions between tissues and organs. Multi-tissue metabolic models were constructed for multiple plants including Arabidopsis, barley, soybean and Setaria. These models were applied to ...
Source: Cellular and Molecular Life Sciences : CMLS - November 19, 2019 Category: Cytology Authors: Shaw R, Cheung CYM Tags: Cell Mol Life Sci Source Type: research

miR-378a: a new emerging microRNA in metabolism.
Abstract Metabolic diseases, such as type 2 diabetes or obesity, are the consequence of the disruption of the organism's metabolic pathways. The discovery of small non-coding RNAs-microRNAs (miRNAs)-as post-transcriptional gene regulators opened new doors for the development of novel strategies to combat said diseases. The two strands of miR-378a, miR-378a-3p, and miR-378a-5p are encoded in the Ppargc1b gene and have an active role in the regulation of several metabolic pathways such as mitochondrial metabolism and autophagy. Recent studies recognized miR-378a as an important regulator of energy and glucose homeos...
Source: Cellular and Molecular Life Sciences : CMLS - November 19, 2019 Category: Cytology Authors: Machado IF, Teodoro JS, Palmeira CM, Rolo AP Tags: Cell Mol Life Sci Source Type: research

Proline-dependent regulation of collagen metabolism.
Abstract This review is focused on recent data on the role of proline (Pro) in collagen biosynthesis and cellular metabolism. It seems obvious that one of the main substrates for collagen biosynthesis Pro is required to form collagen molecule. The question raised in this review is whether the Pro for collagen biosynthesis is synthesized "de novo", comes directly from degraded proteins or it is converted from other amino acids. Recent data provided evidence that extracellular Pro (added to culture medium) had significant, but relatively little impact on collagen biosynthesis in fibroblasts (the main colla...
Source: Cellular and Molecular Life Sciences : CMLS - November 17, 2019 Category: Cytology Authors: Karna E, Szoka L, Huynh TYL, Palka JA Tags: Cell Mol Life Sci Source Type: research

Mechanical instabilities of aorta drive blood stem cell production: a live study.
Abstract During embryogenesis of all vertebrates, haematopoietic stem/progenitor cells (HSPCs) extrude from the aorta by a complex process named endothelial-to-haematopoietic transition (EHT). HSPCs will then colonize haematopoietic organs allowing haematopoiesis throughout adult life. The mechanism underlying EHT including the role of each aortic endothelial cell (EC) within the global aorta dynamics remains unknown. In the present study, we show for the first time that EHT involves the remodelling of individual cells within a collective migration of ECs which is tightly orchestrated, resulting in HSPCs extrusion...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2019 Category: Cytology Authors: Poullet N, Golushko I, Lorman V, Travnickova J, Bureau C, Chalin D, Rochal S, Parmeggiani A, Kissa K Tags: Cell Mol Life Sci Source Type: research

Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution.
Abstract The compaction of DNA and the continuous action of DNA transactions, including transcription and DNA replication, create complex DNA topologies that require Type IIA Topoisomerases, which resolve DNA topological strain and control genome dynamics. The human TOP2 enzymes catalyze their reactions via formation of a reversible covalent enzyme DNA-protein crosslink, the TOP2 cleavage complex (TOP2cc). Spurious interactions of TOP2 with DNA damage, environmental toxicants and chemotherapeutic "poisons" perturbs the TOP2 reaction cycle, leading to an accumulation of DNA-protein crosslinks, and ultimat...
Source: Cellular and Molecular Life Sciences : CMLS - November 14, 2019 Category: Cytology Authors: Riccio AA, Schellenberg MJ, Williams RS Tags: Cell Mol Life Sci Source Type: research

Zygotic genome activation in the chicken: a comparative review.
Abstract Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is determined by an individual's own RNAs and proteins, in a process called the maternal-to-zygotic transition. Zygotic transcription is initially inactive, but is eventually activated by maternal transcription factors. The timing and molecular mechanisms involved in zygotic genome activation (ZGA) have been well-described in many species. Among birds, a transcriptome-based understanding of ZGA has only been explored in chickens by RNA sequen...
Source: Cellular and Molecular Life Sciences : CMLS - November 14, 2019 Category: Cytology Authors: Rengaraj D, Hwang YS, Lee HC, Han JY Tags: Cell Mol Life Sci Source Type: research

The link between endometrial stromal cell senescence and decidualization in female fertility: the art of balance.
Abstract Cell senescence seems to be an ambivalent biological phenomenon in many aspects. At the cellular level it is considered as an irreversible cell-cycle arrest commonly caused by the DNA damage. Senescent cells harbor a lot of impairments in various intracellular systems. Presence of senescent cells within tissues should ultimately lead to their malfunctioning. However, the interlink between cellular senescence and tissue/organismal functioning is far from always being unidirectional. The entangled and complex relationship between senescence and tissue-specific decidual differentiation of endometrial stromal...
Source: Cellular and Molecular Life Sciences : CMLS - November 14, 2019 Category: Cytology Authors: Deryabin P, Griukova A, Nikolsky N, Borodkina A Tags: Cell Mol Life Sci Source Type: research

Characterization of the dimeric CMG/pre-initiation complex and its transition into DNA replication forks.
Abstract The pre-initiation complex (pre-IC) has been proposed for two decades as an intermediate right before the maturation of the eukaryotic DNA replication fork. However, its existence and biochemical nature remain enigmatic. Here, through combining several enrichment strategies, we are able to isolate an endogenous dimeric CMG-containing complex (designated as d-CMG) distinct from traditional single CMG (s-CMG) and in vitro reconstituted dimeric CMG. D-CMG is assembled upon entry into the S phase and shortly matures into s-CMG/replisome, leading to the fact that only ~ 5% of the total CMG-contai...
Source: Cellular and Molecular Life Sciences : CMLS - November 14, 2019 Category: Cytology Authors: Liu L, Zhang Y, Zhang J, Wang JH, Cao Q, Li Z, Campbell JL, Dong MQ, Lou H Tags: Cell Mol Life Sci Source Type: research

The gut microbiome in tuberculosis susceptibility and treatment response: guilty or not guilty?
Abstract Although tuberculosis (TB) is a curable disease, it remains the foremost cause of death from a single pathogen. Globally, approximately 1.6 million people died of TB in 2017. Many predisposing factors related to host immunity, genetics and the environment have been linked to TB. However, recent evidence suggests a relationship between dysbiosis in the gut microbiome and TB disease development. The underlying mechanism(s) whereby dysbiosis in the gut microbiota may impact the different stages in TB disease progression, are, however, not fully explained. In the wake of recently emerging literature, the...
Source: Cellular and Molecular Life Sciences : CMLS - November 14, 2019 Category: Cytology Authors: Eribo OA, du Plessis N, Ozturk M, Guler R, Walzl G, Chegou NN Tags: Cell Mol Life Sci Source Type: research

Cellular secretion and cytotoxicity of transthyretin mutant proteins underlie late-onset amyloidosis and neurodegeneration.
Abstract Transthyretin amyloidosis (ATTR) is a progressive life-threatening disease characterized by the deposition of transthyretin (TTR) amyloid fibrils. Several pathogenic variants have been shown to destabilize TTR tetramers, leading to aggregation of misfolded TTR fibrils. However, factors that underlie the differential age of disease onset amongst amyloidogenic TTR variants remain elusive. Here, we examined the biological properties of various TTR mutations and found that the cellular secretory pattern of the wild-type (WT) TTR was similar to those of the late-onset mutant (Ala97Ser, p. Ala117Ser), stable mu...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2019 Category: Cytology Authors: Ibrahim RB, Yeh SY, Lin KP, Ricardo F, Yu TY, Chan CC, Tsai JW, Liu YT Tags: Cell Mol Life Sci Source Type: research

Structural biology of telomeres and telomerase.
Abstract Telomeres are protein-DNA complexes that protect chromosome ends from illicit ligation and resection. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA to counter telomere shortening. Human telomeres are composed of complexes between telomeric DNA and a six-protein complex known as shelterin. The shelterin proteins TRF1 and TRF2 provide the binding affinity and specificity for double-stranded telomeric DNA, while the POT1-TPP1 shelterin subcomplex coats the single-stranded telomeric G-rich overhang that is characteristic of all our chromosome ends. By capping chromosome ends, shelter...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2019 Category: Cytology Authors: Smith EM, Pendlebury DF, Nandakumar J Tags: Cell Mol Life Sci Source Type: research

Post-transcriptional regulation of insect metamorphosis and oogenesis.
Abstract Metamorphic transformation from larvae to adults along with the high fecundity is key to insect success. Insect metamorphosis and reproduction are governed by two critical endocrines, juvenile hormone (JH), and 20-hydroxyecdysone (20E). Recent studies have established a crucial role of microRNA (miRNA) in insect metamorphosis and oogenesis. While miRNAs target genes involved in JH and 20E-signaling pathways, these two hormones reciprocally regulate miRNA expression, forming regulatory loops of miRNA with JH and 20E-signaling cascades. Insect metamorphosis and oogenesis rely on the coordination of hormones...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Song J, Zhou S Tags: Cell Mol Life Sci Source Type: research

Host defense mechanisms against Mycobacterium tuberculosis.
Abstract Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death worldwide from a single infectious pathogen. Mtb is a paradigmatic intracellular pathogen that primarily invades the lungs after host inhalation of bacteria-containing droplets via the airway. However, the majority of Mtb-exposed individuals can spontaneously control the infection by virtue of a robust immune defense system. The mucosal barriers of the respiratory tract shape the first-line defense against Mtb through various mucosal immune responses. After arriving at the alveoli, the surviving myco...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Chai Q, Lu Z, Liu CH Tags: Cell Mol Life Sci Source Type: research

Genetic deletion of a short fragment of glucokinase in rabbit by CRISPR/Cas9 leading to hyperglycemia and other typical features seen in MODY-2.
In conclusion, this novel GCK mutant rabbit generated with the CRISPR/Cas9 system mimics most, if not all, histopathological and functional defects seen in MODY-2 patients such as hyperglycemia and will be a valuable rabbit model for preclinical studies and drug screening for diabetes as well as for studying the pathophysiological role of glucokinase. PMID: 31720743 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Song Y, Sui T, Zhang Y, Wang Y, Chen M, Deng J, Chai Z, Lai L, Li Z Tags: Cell Mol Life Sci Source Type: research

Structure and function relationships in mammalian DNA polymerases.
Abstract DNA polymerases are vital for the synthesis of new DNA strands. Since the discovery of DNA polymerase I in Escherichia coli, a diverse library of mammalian DNA polymerases involved in DNA replication, DNA repair, antibody generation, and cell checkpoint signaling has emerged. While the unique functions of these DNA polymerases are differentiated by their association with accessory factors and/or the presence of distinctive catalytic domains, atomic resolution structures of DNA polymerases in complex with their DNA substrates have revealed mechanistic subtleties that contribute to their specialization. In ...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Hoitsma NM, Whitaker AM, Schaich MA, Smith MR, Fairlamb MS, Freudenthal BD Tags: Cell Mol Life Sci Source Type: research

Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype.
Abstract SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbio...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Niska-Blakie J, Gopinathan L, Low KN, Kien YL, Goh CMF, Caldez MJ, Pfeiffenberger E, Jones OS, Ong CB, Kurochkin IV, Coppola V, Tessarollo L, Choi H, Kanagasundaram Y, Eisenhaber F, Maurer-Stroh S, Kaldis P Tags: Cell Mol Life Sci Source Type: research

Vertebrate cranial mesoderm: developmental trajectory and evolutionary origin.
Abstract Vertebrate cranial mesoderm is a discrete developmental unit compared to the mesoderm below the developing neck. An extraordinary feature of the cranial mesoderm is that it includes a common progenitor pool contributing to the chambered heart and the craniofacial skeletal muscles. This striking developmental potential and the excitement it generated led to advances in our understanding of cranial mesoderm developmental mechanism. Remarkably, recent findings have begun to unravel the origin of its distinct developmental characteristics. Here, we take a detailed view of the ontogenetic trajectory of cranial...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2019 Category: Cytology Authors: Vyas B, Nandkishore N, Sambasivan R Tags: Cell Mol Life Sci Source Type: research

Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease.
Abstract Hereditary fructose intolerance (HFI) is a rare inborn disease characterized by a deficiency in aldolase B, which catalyzes the cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate (Fru 1P) to triose molecules. In patients with HFI, ingestion of fructose results in accumulation of Fru 1P and depletion of ATP, which are believed to cause symptoms, such as nausea, vomiting, hypoglycemia, and liver and kidney failure. These sequelae can be prevented by a fructose-restricted diet. Recent studies in aldolase B-deficient mice and HFI patients have provided more insight into the pathogenesis of HFI, in...
Source: Cellular and Molecular Life Sciences : CMLS - November 11, 2019 Category: Cytology Authors: Buziau AM, Schalkwijk CG, Stehouwer CDA, Tolan DR, Brouwers MCGJ Tags: Cell Mol Life Sci Source Type: research

Diversity of macrophage phenotypes and responses in atherosclerosis.
Abstract The presence of macrophages within the plaque is a defining hallmark of atherosclerosis. Macrophages are exposed to various microenvironments such as oxidized lipids and cytokines which effect their phenotypic differentiation and activation. Classically, macrophages have been divided into two groups: M1 and M2 macrophages induced by T-helper 1 and T-helper 2 cytokines, respectively. However, for a decade, greater phenotypic heterogeneity and plasticity of these cells have since been reported in various models. In addition to M1 and M2 macrophage phenotypes, the concept of additional macrophage phenotypes ...
Source: Cellular and Molecular Life Sciences : CMLS - November 11, 2019 Category: Cytology Authors: Jinnouchi H, Guo L, Sakamoto A, Torii S, Sato Y, Cornelissen A, Kuntz S, Paek KH, Fernandez R, Fuller D, Gadhoke N, Surve D, Romero M, Kolodgie FD, Virmani R, Finn AV Tags: Cell Mol Life Sci Source Type: research

Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.
Abstract We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1...
Source: Cellular and Molecular Life Sciences : CMLS - November 11, 2019 Category: Cytology Authors: Vucicevic L, Misirkic M, Ciric D, Martinovic T, Jovanovic M, Isakovic A, Markovic I, Saponjic J, Foretz M, Rabanal-Ruiz Y, Korolchuk VI, Trajkovic V Tags: Cell Mol Life Sci Source Type: research

Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells.
Abstract Cell-based therapies using adult stem cells are promising options for the treatment of a number of diseases including autoimmune and cardiovascular disorders. Among these, vascular wall-derived mesenchymal stem cells (VW-MSCs) might be particularly well suited for the protection and curative treatment of vascular damage because of their tissue-specific action. Here we report a novel method for the direct conversion of human skin fibroblasts towards MSCs using a VW-MSC-specific gene code (HOXB7, HOXC6 and HOXC8) that directs cell fate conversion bypassing pluripotency. This direct programming approach usin...
Source: Cellular and Molecular Life Sciences : CMLS - November 10, 2019 Category: Cytology Authors: Steens J, Unger K, Klar L, Neureiter A, Wieber K, Hess J, Jakob HG, Klump H, Klein D Tags: Cell Mol Life Sci Source Type: research

Introduction to the multi-author-review: emerging advances in the structural chemistry of DNA strand break repair.
Abstract DNA strand breaks present a complex challenge for our cells, and the integrity of the DNA damage response machinery is critical for preventing cancer, premature aging, and neurodegenerative syndromes amongst other ailments. This multi-author review issue presents emerging topics relevant to understanding the fundamental structural mechanisms of DNA strand break sensing, signaling, and repair. PMID: 31712993 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 10, 2019 Category: Cytology Authors: Williams RS Tags: Cell Mol Life Sci Source Type: research

Tumor angiogenesis: causes, consequences, challenges and opportunities.
Abstract Tumor vascularization occurs through several distinct biological processes, which not only vary between tumor type and anatomic location, but also occur simultaneously within the same cancer tissue. These processes are orchestrated by a range of secreted factors and signaling pathways and can involve participation of non-endothelial cells, such as progenitors or cancer stem cells. Anti-angiogenic therapies using either antibodies or tyrosine kinase inhibitors have been approved to treat several types of cancer. However, the benefit of treatment has so far been modest, some patients not responding at all a...
Source: Cellular and Molecular Life Sciences : CMLS - November 5, 2019 Category: Cytology Authors: Lugano R, Ramachandran M, Dimberg A Tags: Cell Mol Life Sci Source Type: research

Response to "Concerns regarding Baksa et al., Cell Molec. Life Sci., 2019." by Edgar Garcia-Rill and Francisco J. Urbano (CMLS-D-18-0156R1).
Response to "Concerns regarding Baksa et al., Cell Molec. Life Sci., 2019." by Edgar Garcia-Rill and Francisco J. Urbano (CMLS-D-18-0156R1). Cell Mol Life Sci. 2019 Nov 06;: Authors: Pal B PMID: 31691836 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 5, 2019 Category: Cytology Authors: Pal B Tags: Cell Mol Life Sci Source Type: research

miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts cardiac development and electrical activity in zebrafish.
In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development. PMID: 31686119 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2019 Category: Cytology Authors: Guzzolino E, Pellegrino M, Ahuja N, Garrity D, D'Aurizio R, Groth M, Baumgart M, Hatcher CJ, Mercatanti A, Evangelista M, Ippolito C, Tognoni E, Fukuda R, Lionetti V, Pellegrini M, Cremisi F, Pitto L Tags: Cell Mol Life Sci Source Type: research

CFP1-dependent histone H3K4 trimethylation in murine oocytes facilitates ovarian follicle recruitment and ovulation in a cell-nonautonomous manner.
Abstract CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles. CFP1-dependent H3K4 trimethylation in oocytes was necessary to maintain the expression of key parac...
Source: Cellular and Molecular Life Sciences : CMLS - October 31, 2019 Category: Cytology Authors: Sha QQ, Jiang Y, Yu C, Xiang Y, Dai XX, Jiang JC, Ou XH, Fan HY Tags: Cell Mol Life Sci Source Type: research

Roles of vitamins in stem cells.
Abstract Stem cells can differentiate to diverse cell types in our body, and they hold great promises in both basic research and clinical therapies. For specific stem cell types, distinctive nutritional and signaling components are required to maintain the proliferation capacity and differentiation potential in cell culture. Various vitamins play essential roles in stem cell culture to modulate cell survival, proliferation and differentiation. Besides their common nutritional functions, specific vitamins are recently shown to modulate signal transduction and epigenetics. In this article, we will first review class...
Source: Cellular and Molecular Life Sciences : CMLS - October 31, 2019 Category: Cytology Authors: Godoy-Parejo C, Deng C, Zhang Y, Liu W, Chen G Tags: Cell Mol Life Sci Source Type: research

Targeting intrinsically disordered proteins involved in cancer.
We describe the outcomes of using these approaches in targeting IDPs involved in cancer, in the view to providing insight, to target IDPs in general. In a broad sense, the designed small molecules seem to target the most hydrophobic regions of the IDPs, hampering macromolecule (DNA or protein)-IDP interactions; furthermore, in most of the molecule-IDP complexes described so far, the protein remains disordered. PMID: 31667555 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - October 29, 2019 Category: Cytology Authors: Santofimia-Castaño P, Rizzuti B, Xia Y, Abian O, Peng L, Velázquez-Campoy A, Neira JL, Iovanna J Tags: Cell Mol Life Sci Source Type: research

Mechanisms of secretion and spreading of pathological tau protein.
Abstract Accumulation of misfolded and aggregated forms of tau protein in the brain is a neuropathological hallmark of tauopathies, such as Alzheimer's disease and frontotemporal lobar degeneration. Tau aggregates have the ability to transfer from one cell to another and to induce templated misfolding and aggregation of healthy tau molecules in previously healthy cells, thereby propagating tau pathology across different brain areas in a prion-like manner. The molecular mechanisms involved in cell-to-cell transfer of tau aggregates are diverse, not mutually exclusive and only partially understood. Intracellular acc...
Source: Cellular and Molecular Life Sciences : CMLS - October 29, 2019 Category: Cytology Authors: Brunello CA, Merezhko M, Uronen RL, Huttunen HJ Tags: Cell Mol Life Sci Source Type: research

Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes.
Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes. Cell Mol Life Sci. 2019 Oct 30;: Authors: Božić M, Verkhratsky A, Zorec R, Stenovec M Abstract Astrocytes are the key homeostatic cells in the central nervous system; initiation of reactive astrogliosis contributes to neuroinflammation. Pro-inflammatory cytokine interferon γ (IFNγ) induces the expression of the major histocompatibility complex class II (MHCII) molecules, involved in antigen presentation in reactive astrocytes. The pathway for M...
Source: Cellular and Molecular Life Sciences : CMLS - October 29, 2019 Category: Cytology Authors: Božić M, Verkhratsky A, Zorec R, Stenovec M Tags: Cell Mol Life Sci Source Type: research

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells.
This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation. PMID: 31664461 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - October 28, 2019 Category: Cytology Authors: Meneses-Salas E, García-Melero A, Kanerva K, Blanco-Muñoz P, Morales-Paytuvi F, Bonjoch J, Casas J, Egert A, Beevi SS, Jose J, Llorente-Cortés V, Rye KA, Heeren J, Lu A, Pol A, Tebar F, Ikonen E, Grewal T, Enrich C, Rentero C Tags: Cell Mol Life Sci Source Type: research

Protein kinases: master regulators of neuritogenesis and therapeutic targets for axon regeneration.
Abstract Proper neurite formation is essential for appropriate neuronal morphology to develop and defects at this early foundational stage have serious implications for overall neuronal function. Neuritogenesis is tightly regulated by various signaling mechanisms that control the timing and placement of neurite initiation, as well as the various processes necessary for neurite elongation to occur. Kinases are integral components of these regulatory pathways that control the activation and inactivation of their targets. This review provides a comprehensive summary of the kinases that are notably involved in regulat...
Source: Cellular and Molecular Life Sciences : CMLS - October 27, 2019 Category: Cytology Authors: Bennison SA, Blazejewski SM, Smith TH, Toyo-Oka K Tags: Cell Mol Life Sci Source Type: research

CircRNA: a rising star in gastric cancer.
Abstract In recent years, a large number of circRNAs have been identified in mammalian cells with high-throughput sequencing technologies and bioinformatics. The aberrant expression of circRNAs has been reported in many human diseases including gastric cancer (GC). The number of GC-related circRNAs with validated biological functions and mechanisms of action is growing. CircRNAs are critically involved in GC cell proliferation, apoptosis, migration, and invasion. CircRNAs have been shown to function as regulators of parental gene transcription and alternative splicing and miRNA sponges. Moreover, circRNAs have bee...
Source: Cellular and Molecular Life Sciences : CMLS - October 27, 2019 Category: Cytology Authors: Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W Tags: Cell Mol Life Sci Source Type: research

Kynurenic acid and cancer: facts and controversies.
Abstract Kynurenic acid (KYNA) is an endogenous tryptophan metabolite exerting neuroprotective and anticonvulsant properties in the brain. However, its importance on the periphery is still not fully elucidated. KYNA is produced endogenously in various types of peripheral cells, tissues and by gastrointestinal microbiota. Furthermore, it was found in several products of daily human diet and its absorption in the digestive tract was evidenced. More recent studies were focused on the potential role of KYNA in carcinogenesis and cancer therapy; however, the results were ambiguous and the biological activity of KYNA in...
Source: Cellular and Molecular Life Sciences : CMLS - October 27, 2019 Category: Cytology Authors: Walczak K, Wnorowski A, Turski WA, Plech T Tags: Cell Mol Life Sci Source Type: research

Deletion of Voltage-Dependent Anion Channel 1 knocks mitochondria down triggering metabolic rewiring in yeast.
nto V Abstract The Voltage-Dependent Anion-selective Channel (VDAC) is the pore-forming protein of mitochondrial outer membrane, allowing metabolites and ions exchanges. In Saccharomyces cerevisiae, inactivation of POR1, encoding VDAC1, produces defective growth in the presence of non-fermentable carbon source. Here, we characterized the whole-genome expression pattern of a VDAC1-null strain (Δpor1) by microarray analysis, discovering that the expression of mitochondrial genes was completely abolished, as consequence of the dramatic reduction of mtDNA. To overcome organelle dysfunction, Δpor1 cells do ...
Source: Cellular and Molecular Life Sciences : CMLS - October 25, 2019 Category: Cytology Authors: Magrì A, Di Rosa MC, Orlandi I, Guarino F, Reina S, Guarnaccia M, Morello G, Spampinato A, Cavallaro S, Messina A, Vai M, De Pinto V Tags: Cell Mol Life Sci Source Type: research

The RNA-RNA base pairing potential of human Dicer and Ago2 proteins.
Abstract The ribonuclease Dicer produces microRNAs (miRNAs) and small interfering RNAs that are handed over to Ago proteins to control gene expression by targeting complementary sequences within transcripts. Interestingly, a growing number of reports have demonstrated that the activity of Dicer may extend beyond the biogenesis of small regulatory RNAs. Among them, a report from our latest studies revealed that human Dicer facilitates base pairing of complementary sequences present in two nucleic acids, thus acting as a nucleic acid annealer. Accordingly, in this manuscript, we address how RNA structure influences ...
Source: Cellular and Molecular Life Sciences : CMLS - October 25, 2019 Category: Cytology Authors: Pokornowska M, Milewski MC, Ciechanowska K, Szczepańska A, Wojnicka M, Radogostowicz Z, Figlerowicz M, Kurzynska-Kokorniak A Tags: Cell Mol Life Sci Source Type: research

Human erythrocytes: cytoskeleton and its origin.
Abstract In the last few years, erythrocytes have emerged as the main determinant of blood rheology. In mammals, these cells are devoid of nuclei and are, therefore, unable to divide. Consequently, all circulating erythrocytes come from erythropoiesis, a process in the bone marrow in which several modifications are induced in the expression of membrane and cytoskeletal proteins, and different vertical and horizontal interactions are established between them. Cytoskeleton components play an important role in this process, which explains why they and the interaction between them have been the focus of much recent re...
Source: Cellular and Molecular Life Sciences : CMLS - October 24, 2019 Category: Cytology Authors: Nigra AD, Casale CH, Santander VS Tags: Cell Mol Life Sci Source Type: research

Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps.
Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently ind...
Source: Cellular and Molecular Life Sciences : CMLS - October 23, 2019 Category: Cytology Authors: Manda-Handzlik A, Bystrzycka W, Cieloch A, Glodkowska-Mrowka E, Jankowska-Steifer E, Heropolitanska-Pliszka E, Skrobot A, Muchowicz A, Ciepiela O, Wachowska M, Demkow U Tags: Cell Mol Life Sci Source Type: research

Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients.
Abstract Breast cancer is the most frequently occurring cancer among women worldwide. Human epidermal growth factor receptor 2 (HER2 or ErbB2) is overexpressed in between 20 and 25% of invasive breast cancers and is associated with poor prognosis. Trastuzumab, an anti-ErbB2 monoclonal antibody, reduces cancer recurrence and mortality in HER2-positive breast cancer patients, but unexpectedly induces cardiac dysfunction, especially when used in combination with anthracycline-based chemotherapy. Novel approved ErbB2-targeting drugs, including lapatinib, pertuzumab, and trastuzumab-emtansine, also potentially cause ca...
Source: Cellular and Molecular Life Sciences : CMLS - October 23, 2019 Category: Cytology Authors: Leemasawat K, Phrommintikul A, Chattipakorn SC, Chattipakorn N Tags: Cell Mol Life Sci Source Type: research

Running and swimming prevent the deregulation of the BDNF/TrkB neurotrophic signalling at the neuromuscular junction in mice with amyotrophic lateral sclerosis.
N, Tomàs J, Lanuza MA Abstract Nerve-induced muscle contraction regulates the BDNF/TrkB neurotrophic signalling to retrogradely modulate neurotransmission and protect the neuromuscular junctions and motoneurons. In muscles with amyotrophic lateral sclerosis, this pathway is strongly misbalanced and neuromuscular junctions are destabilized, which may directly cause the motoneuron degeneration and muscular atrophy observed in this disease. Here, we sought to demonstrate (1) that physical exercise, whose recommendation has been controversial in amyotrophic lateral sclerosis, would be a good option for its the...
Source: Cellular and Molecular Life Sciences : CMLS - October 22, 2019 Category: Cytology Authors: Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M, Garcia N, Tomàs J, Lanuza MA Tags: Cell Mol Life Sci Source Type: research

Tet3 regulates cellular identity and DNA methylation in neural progenitor cells.
Abstract TET enzymes oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), a process thought to be intermediary in an active DNA demethylation mechanism. Notably, 5hmC is highly abundant in the brain and in neuronal cells. Here, we interrogated the function of Tet3 in neural precursor cells (NPCs), using a stable and inducible knockdown system and an in vitro neural differentiation protocol. We show that Tet3 is upregulated during neural differentiation, whereas Tet1 is downregulated. Surprisingly, Tet3 knockdown led to a de-repression of pluripotency-associated genes such as Oct4, Nanog or Tcl1, wit...
Source: Cellular and Molecular Life Sciences : CMLS - October 22, 2019 Category: Cytology Authors: Santiago M, Antunes C, Guedes M, Iacovino M, Kyba M, Reik W, Sousa N, Pinto L, Branco MR, Marques CJ Tags: Cell Mol Life Sci Source Type: research