Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure.
Krautwald S Abstract Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis. By using CRISPR/Cas9 technology, we found that knockout of Acsl4...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2017 Category: Cytology Authors: Müller T, Dewitz C, Schmitz J, Schröder AS, Bräsen JH, Stockwell BR, Murphy JM, Kunzendorf U, Krautwald S Tags: Cell Mol Life Sci Source Type: research

Carbon nanotubes as anti-bacterial agents.
Abstract Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacteri...
Source: Cellular and Molecular Life Sciences : CMLS - May 23, 2017 Category: Cytology Authors: Mocan T, Matea CT, Pop T, Mosteanu O, Buzoianu AD, Suciu S, Puia C, Zdrehus C, Iancu C, Mocan L Tags: Cell Mol Life Sci Source Type: research

Erratum to: BMP type II receptor as a therapeutic target in pulmonary arterial hypertension.
PMID: 28536788 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 23, 2017 Category: Cytology Authors: Orriols M, Gomez-Puerto MC, Ten Dijke P Tags: Cell Mol Life Sci Source Type: research

Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production.
Abstract Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons. A time- and dose-dependent accumulation of α-s...
Source: Cellular and Molecular Life Sciences : CMLS - May 22, 2017 Category: Cytology Authors: Tapias V, Hu X, Luk KC, Sanders LH, Lee VM, Timothy Greenamyre J Tags: Cell Mol Life Sci Source Type: research

The emerging link between O-GlcNAcylation and neurological disorders.
Abstract O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation partici...
Source: Cellular and Molecular Life Sciences : CMLS - May 22, 2017 Category: Cytology Authors: Ma X, Li H, He Y, Hao J Tags: Cell Mol Life Sci Source Type: research

ATP-induced Ca(2+)-signalling mechanisms in the regulation of mesenchymal stem cell migration.
Abstract The ability of cells to migrate to the destined tissues or lesions is crucial for physiological processes from tissue morphogenesis, homeostasis and immune responses, and also for stem cell-based regenerative medicines. Cytosolic Ca(2+) is a primary second messenger in the control and regulation of a wide range of cell functions including cell migration. Extracellular ATP, together with the cognate receptors on the cell surface, ligand-gated ion channel P2X receptors and a subset of G-protein-coupled P2Y receptors, represents common autocrine and/or paracrine Ca(2+) signalling mechanisms. The P2X receptor...
Source: Cellular and Molecular Life Sciences : CMLS - May 22, 2017 Category: Cytology Authors: Jiang LH, Mousawi F, Yang X, Roger S Tags: Cell Mol Life Sci Source Type: research

Hh signaling in regeneration of the ischemic heart.
Abstract Myocardial infarction (MI) is caused by the occlusion of a coronary artery due to underlying atherosclerosis complicated by localized thrombosis. The blockage of blood flow leads to cardiomyocyte (CM) death in the infarcted area. Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury; however, some pathways active during embryogenesis and silent during adult life are recruited in response to tissue injury. One such example is hedgehog (Hh) signaling. Hh is involved in the embryonic development of the heart and coronary vascular system. Pathological conditions including is...
Source: Cellular and Molecular Life Sciences : CMLS - May 18, 2017 Category: Cytology Authors: Dunaeva M, Waltenberger J Tags: Cell Mol Life Sci Source Type: research

Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells.
This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP...
Source: Cellular and Molecular Life Sciences : CMLS - May 18, 2017 Category: Cytology Authors: Kwok HH, Poon PY, Mak KH, Zhang LY, Liu P, Zhang H, Mak NK, Yue PY, Wong RN Tags: Cell Mol Life Sci Source Type: research

Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration.
Abstract Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well ...
Source: Cellular and Molecular Life Sciences : CMLS - May 17, 2017 Category: Cytology Authors: Fukuda T, Yanagi S Tags: Cell Mol Life Sci Source Type: research

Stress and the nonsense-mediated RNA decay pathway.
Abstract Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences. Recent work has demonstrated that a conserved and highly sel...
Source: Cellular and Molecular Life Sciences : CMLS - May 13, 2017 Category: Cytology Authors: Goetz AE, Wilkinson M Tags: Cell Mol Life Sci Source Type: research

Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies.
Buzás EI, Nagy G Abstract OBJECTIVE: Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis. METHODS: Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties ...
Source: Cellular and Molecular Life Sciences : CMLS - May 10, 2017 Category: Cytology Authors: Marton N, Kovács OT, Baricza E, Kittel Á, Győri D, Mócsai A, Meier FMP, Goodyear CS, McInnes IB, Buzás EI, Nagy G Tags: Cell Mol Life Sci Source Type: research

Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting.
Abstract Platelets are anucleated cells that circulate in the blood as sentinels of tissue integrity. In fact, they are rich in a plethora of proteins and other factors stored in different granules which they selectively release upon stimulation. Moreover, platelets synthesize a vast number of lipids and release various types of vesicles, including exosomes which are rich in genetic material. Platelets possess a central function to interact with other cell types, including inflammatory cells and cancer cells. Recent findings have enlightened the capacity of platelets to induce changes in the phenotype of cancer ce...
Source: Cellular and Molecular Life Sciences : CMLS - May 9, 2017 Category: Cytology Authors: Contursi A, Sacco A, Grande R, Dovizio M, Patrignani P Tags: Cell Mol Life Sci Source Type: research

FRET studies of various conformational states adopted by transthyretin.
Abstract Transthyretin (TTR) is an extracellular protein able to deposit into well-defined protein aggregates called amyloid, in pathological conditions known as senile systemic amyloidosis, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and leptomeningeal amyloidosis. At least three distinct partially folded states have been described for TTR, including the widely studied amyloidogenic state at mildly acidic pH. Here, we have used fluorescence resonance energy transfer (FRET) experiments in a monomeric variant of TTR (M-TTR) and in its W41F and W79F mutants, taking advantage of the presence of a...
Source: Cellular and Molecular Life Sciences : CMLS - May 6, 2017 Category: Cytology Authors: Ghadami SA, Bemporad F, Sala BM, Tiana G, Ricagno S, Chiti F Tags: Cell Mol Life Sci Source Type: research

Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor localization and activity during anaphase.
Gheber L Abstract The bipolar kinesin-5 motors perform essential functions in mitotic spindle dynamics. We previously demonstrated that phosphorylation of at least one of the Cdk1 sites in the catalytic domain of the Saccharomyces cerevisiae kinesin-5 Cin8 (S277, T285, S493) regulates its localization to the anaphase spindle. The contribution of these three sites to phospho-regulation of Cin8, as well as the timing of such contributions, remains unknown. Here, we examined the function and spindle localization of phospho-deficient (serine/threonine to alanine) and phospho-mimic (serine/threonine to aspartic acid) ...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2017 Category: Cytology Authors: Goldstein A, Siegler N, Goldman D, Judah H, Valk E, Kõivomägi M, Loog M, Gheber L Tags: Cell Mol Life Sci Source Type: research

Enzyme-substrate relationships in the ubiquitin system: approaches for identifying substrates of ubiquitin ligases.
Abstract Protein ubiquitylation is an important post-translational modification, regulating aspects of virtually every biochemical pathway in eukaryotic cells. Hundreds of enzymes participate in the conjugation and deconjugation of ubiquitin, as well as the recognition, signaling functions, and degradation of ubiquitylated proteins. Regulation of ubiquitylation is most commonly at the level of recognition of substrates by E3 ubiquitin ligases. Characterization of the network of E3-substrate relationships is a major goal and challenge in the field, as this expected to yield fundamental biological insights and ...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2017 Category: Cytology Authors: O'Connor HF, Huibregtse JM Tags: Cell Mol Life Sci Source Type: research

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension.
Abstract Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although the...
Source: Cellular and Molecular Life Sciences : CMLS - April 26, 2017 Category: Cytology Authors: Orriols M, Gomez-Puerto MC, Ten Dijke P Tags: Cell Mol Life Sci Source Type: research

Control of DNA integrity in skeletal muscle under physiological and pathological conditions.
Abstract Skeletal muscle is a highly oxygen-consuming tissue that ensures body support and movement, as well as nutrient and temperature regulation. DNA damage induced by reactive oxygen species is present in muscles and tends to accumulate with age. Here, we present a summary of data obtained on DNA damage and its implication in muscle homeostasis, myogenic differentiation and neuromuscular disorders. Controlled and transient DNA damage appears to be essential for muscular homeostasis and differentiation while uncontrolled and chronic DNA damage negatively affects muscle health. PMID: 28444416 [PubMed - as s...
Source: Cellular and Molecular Life Sciences : CMLS - April 25, 2017 Category: Cytology Authors: Bou Saada Y, Zakharova V, Chernyak B, Dib C, Carnac G, Dokudovskaya S, Vassetzky YS Tags: Cell Mol Life Sci Source Type: research

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair.
Abstract The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function. We review the current knowledge about these molecules as potential tar...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2017 Category: Cytology Authors: Lolli A, Penolazzi L, Narcisi R, van Osch GJVM, Piva R Tags: Cell Mol Life Sci Source Type: research

Emerging roles of calpain proteolytic systems in macrophage cholesterol handling.
Abstract Calpains are Ca(2+)-dependent intracellular proteases that play central roles in the post-translational processing of functional proteins. In mammals, calpain proteolytic systems comprise the endogenous inhibitor calpastatin as well as 15 homologues of the catalytic subunits and two homologues of the regulatory subunits. Recent pharmacological and gene targeting studies in experimental animal models have revealed the contribution of conventional calpains, which consist of the calpain-1 and -2 isozymes, to atherosclerotic diseases. During atherogenesis, conventional calpains facilitate the CD36-dependent u...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2017 Category: Cytology Authors: Miyazaki T, Miyazaki A Tags: Cell Mol Life Sci Source Type: research

Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway.
Abstract Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection. ISGs mark an elegant mechanism of anti-viral host d...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2017 Category: Cytology Authors: Raftery N, Stevenson NJ Tags: Cell Mol Life Sci Source Type: research

An efficient method to enrich for knock-out and knock-in cellular clones using the CRISPR/Cas9 system.
Abstract Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9 nuclease (CRISPR/Cas9) and Transcription Activator-Like Effector Nucleases (TALENs) are versatile tools for genome editing. Here we report a method to increase the frequency of Cas9-targeted cellular clones. Our method is based on a chimeric construct with a Blasticidin S Resistance gene (bsr) placed out-of-frame by a surrogate target sequence. End joining of the CRISPR/Cas9-induced double-strand break on the surrogate target can place the bsr in frame, thus providing temporary resistance to Blasticidin S: this is used to enric...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2017 Category: Cytology Authors: Niccheri F, Pecori R, Conticello SG Tags: Cell Mol Life Sci Source Type: research

IFT54 regulates IFT20 stability but is not essential for tubulin transport during ciliogenesis.
Abstract Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT-B complex and is also associated with cytoplasmic microtubules (MTs). Loss of IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled-coil (CC) domain binds IFT20. However, the precise function of these domains in vivo is not well understood. We showed that in Chla...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2017 Category: Cytology Authors: Zhu X, Liang Y, Gao F, Pan J Tags: Cell Mol Life Sci Source Type: research

S100A6 protein: functional roles.
Abstract S100A6 protein belongs to the A group of the S100 protein family of Ca(2+)-binding proteins. It is expressed in a limited number of cell types in adult normal tissues and in several tumor cell types. As an intracellular protein, S100A6 has been implicated in the regulation of several cellular functions, such as proliferation, apoptosis, the cytoskeleton dynamics, and the cellular response to different stress factors. S100A6 can be secreted/released by certain cell types which points to extracellular effects of the protein. RAGE (receptor for advanced glycation endproducts) and integrin β1 transduce s...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2017 Category: Cytology Authors: Donato R, Sorci G, Giambanco I Tags: Cell Mol Life Sci Source Type: research

Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.
Abstract Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell physiology through facilitating NAD(+) redox homeostasis and providing NAD(+) as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD(+) to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology. However, once administered to cells, NAM ...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2017 Category: Cytology Authors: Hwang ES, Song SB Tags: Cell Mol Life Sci Source Type: research

Methyl-accepting chemotaxis proteins: a core sensing element in prokaryotes and archaea.
Abstract Chemotaxis is the directed motility by means of which microbes sense chemical cues and relocate towards more favorable environments. Methyl-accepting chemotaxis proteins (MCPs) are the most common receptors in bacteria and archaea. They are arranged as trimers of dimers that, in turn, form hexagonal arrays in the cytoplasmic membrane or in the cytoplasm. Several different classes of MCPs have been identified according to their ligand binding region and membrane topology. MCPs have been further classified based on the length and sequence conservation of their cytoplasmic domains. Clusters of membrane-embed...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2017 Category: Cytology Authors: Salah Ud-Din AI, Roujeinikova A Tags: Cell Mol Life Sci Source Type: research

Ceramide synthase 2 deficiency aggravates AOM-DSS-induced colitis in mice: role of colon barrier integrity.
In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome. PMID: 28405720 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2017 Category: Cytology Authors: Oertel S, Scholich K, Weigert A, Thomas D, Schmetzer J, Trautmann S, Wegner MS, Radeke HH, Filmann N, Brüne B, Geisslinger G, Tegeder I, Grösch S Tags: Cell Mol Life Sci Source Type: research

Genome editing: a robust technology for human stem cells.
Abstract Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human dis...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2017 Category: Cytology Authors: Chandrasekaran AP, Song M, Ramakrishna S Tags: Cell Mol Life Sci Source Type: research

Vinculin in cell-cell and cell-matrix adhesions.
Abstract Vinculin was identified as a component of focal adhesions and adherens junctions nearly 40 years ago. Since that time, remarkable progress has been made in understanding its activation, regulation and function. Here we discuss the current understanding of the roles of vinculin in cell-cell and cell-matrix adhesions. Emphasis is placed on the how vinculin is recruited, activated and regulated. We also highlight the recent understanding of how vinculin responds to and transmits force at integrin- and cadherin-containing adhesion complexes to the cytoskeleton. Furthermore, we discuss roles of vinculin in bin...
Source: Cellular and Molecular Life Sciences : CMLS - April 11, 2017 Category: Cytology Authors: Bays JL, DeMali KA Tags: Cell Mol Life Sci Source Type: research

Ultrastructural localization of 5-methylcytosine on DNA and RNA.
Abstract DNA methylation is the major epigenetic modification and it is involved in the negative regulation of gene expression. Its alteration can lead to neoplastic transformation. Several biomolecular approaches are nowadays used to study this modification on DNA, but also on RNA molecules, which are known to play a role in different biological processes. RNA methylation is one of the most common RNA modifications and 5-methylcytosine presence has recently been suggested in mRNA. However, an analysis of nucleic acid methylation at electron microscope is still lacking. Therefore, we visualized DNA methylation sta...
Source: Cellular and Molecular Life Sciences : CMLS - April 8, 2017 Category: Cytology Authors: Masiello I, Biggiogera M Tags: Cell Mol Life Sci Source Type: research

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes.
Abstract Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, sig...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2017 Category: Cytology Authors: Dasmeh P, Kepp KP Tags: Cell Mol Life Sci Source Type: research

Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.
Abstract Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distrib...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2017 Category: Cytology Authors: Zhang ZJ, Jiang BC, Gao YJ Tags: Cell Mol Life Sci Source Type: research

Shaping the cellular landscape with Set2/SETD2 methylation.
Abstract Chromatin structure is a major barrier to gene transcription that must be disrupted and re-set during each round of transcription. Central to this process is the Set2/SETD2 methyltransferase that mediates co-transcriptional methylation to histone H3 at lysine 36 (H3K36me). Studies reveal that H3K36me not only prevents inappropriate transcriptional initiation from arising within gene bodies, but that it has other conserved functions that include the repair of damaged DNA and regulation of pre-mRNA splicing. Consistent with the importance of Set2/SETD2 in chromatin biology, mutations of SETD2, or mutations ...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2017 Category: Cytology Authors: McDaniel SL, Strahl BD Tags: Cell Mol Life Sci Source Type: research

Mitochondrial permeability transition in cardiac ischemia-reperfusion: whether cyclophilin D is a viable target for cardioprotection?
ov AV Abstract Growing number of studies provide strong evidence that the mitochondrial permeability transition pore (PTP), a non-selective channel in the inner mitochondrial membrane, is involved in the pathogenesis of cardiac ischemia-reperfusion and can be targeted to attenuate reperfusion-induced damage to the myocardium. The molecular identity of the PTP remains unknown and cyclophilin D is the only protein commonly accepted as a major regulator of the PTP opening. Therefore, cyclophilin D is an attractive target for pharmacological or genetic therapies to reduce ischemia-reperfusion injury in various animal ...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2017 Category: Cytology Authors: Javadov S, Jang S, Parodi-Rullán R, Khuchua Z, Kuznetsov AV Tags: Cell Mol Life Sci Source Type: research

Defining motility in the Staphylococci.
Abstract The ability of bacteria to move is critical for their survival in diverse environments and multiple ways have evolved to achieve this. Two forms of motility have recently been described for Staphylococcus aureus, an organism previously considered to be non-motile. One form is called spreading, which is a type of sliding motility and the second form involves comet formation, which has many observable characteristics associated with gliding motility. Darting motility has also been observed in Staphylococcus epidermidis. This review describes how motility is defined and how we distinguish between passive and...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2017 Category: Cytology Authors: Pollitt EJ, Diggle SP Tags: Cell Mol Life Sci Source Type: research

Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling.
Abstract Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4(+) T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4(+) T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3(+) regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), i...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2017 Category: Cytology Authors: Pasztoi M, Bonifacius A, Pezoldt J, Kulkarni D, Niemz J, Yang J, Teich R, Hajek J, Pisano F, Rohde M, Dersch P, Huehn J Tags: Cell Mol Life Sci Source Type: research

Protein arginine methylation: a prominent modification and its demethylation.
f A Abstract Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Promin...
Source: Cellular and Molecular Life Sciences : CMLS - March 31, 2017 Category: Cytology Authors: Wesche J, Kühn S, Kessler BM, Salton M, Wolf A Tags: Cell Mol Life Sci Source Type: research

Putting a brake on synaptic vesicle endocytosis.
Abstract In chemical synapses, action potentials evoke synaptic vesicle fusion with the presynaptic membrane at the active zone to release neurotransmitter. Synaptic vesicle endocytosis (SVE) then follows exocytosis to recapture vesicle proteins and lipid components for recycling and the maintenance of membrane homeostasis. Therefore, SVE plays an essential role during neurotransmission and is one of the most precisely regulated biological processes. Four modes of SVE have been characterized and both positive and negative regulators have been identified. However, our understanding of SVE regulation remains unclear...
Source: Cellular and Molecular Life Sciences : CMLS - March 30, 2017 Category: Cytology Authors: Wang YL, Zhang CX Tags: Cell Mol Life Sci Source Type: research

Mechanisms controlling diversification of olfactory sensory neuron classes.
Abstract Animals survive in harsh and fluctuating environments using sensory neurons to detect and respond to changes in their surroundings. Olfactory sensory neurons are essential for detecting food, identifying danger, and sensing pheromones. The ability to sense a large repertoire of different types of odors is crucial to distinguish between different situations, and is achieved through neuronal diversity within the olfactory system. Here, we review the developmental mechanisms used to establish diversity of olfactory sensory neurons in various model organisms, including Caenorhabditis elegans, Drosophila, and ...
Source: Cellular and Molecular Life Sciences : CMLS - March 29, 2017 Category: Cytology Authors: Hsieh YW, Alqadah A, Chuang CF Tags: Cell Mol Life Sci Source Type: research

Differential molecular regulation of processing and membrane expression of Type-I BMP receptors: implications for signaling.
Abstract The Type-I bone morphogenetic protein receptors (BMPRs), BMPR1A and BMPR1B, present the highest sequence homology among BMPRs, suggestive of functional similitude. However, sequence elements within their extracellular domain, such as signal sequence or N-glycosylation motifs, may result in differential regulation of biosynthetic processing and trafficking and in alterations to receptor function. We show that (i) BMPR1A and the ubiquitous isoform of BMPR1B differed in mode of translocation into the endoplasmic reticulum; and (ii) BMPR1A was N-glycosylated while BMPR1B was not, resulting in greater efficien...
Source: Cellular and Molecular Life Sciences : CMLS - March 29, 2017 Category: Cytology Authors: Hirschhorn T, Levi-Hofman M, Danziger O, Smorodinsky NI, Ehrlich M Tags: Cell Mol Life Sci Source Type: research

Mechanisms and consequences of intestinal dysbiosis.
Abstract The composition of the gut microbiota is in constant flow under the influence of factors such as the diet, ingested drugs, the intestinal mucosa, the immune system, and the microbiota itself. Natural variations in the gut microbiota can deteriorate to a state of dysbiosis when stress conditions rapidly decrease microbial diversity and promote the expansion of specific bacterial taxa. The mechanisms underlying intestinal dysbiosis often remain unclear given that combinations of natural variations and stress factors mediate cascades of destabilizing events. Oxidative stress, bacteriophages induction and the...
Source: Cellular and Molecular Life Sciences : CMLS - March 28, 2017 Category: Cytology Authors: Weiss GA, Hennet T Tags: Cell Mol Life Sci Source Type: research

BACE2 suppression promotes β-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression.
BACE2 suppression promotes β-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression. Cell Mol Life Sci. 2017 Mar 23;: Authors: Alcarraz-Vizán G, Castaño C, Visa M, Montane J, Servitja JM, Novials A Abstract BACE2 (β-site APP-cleaving enzyme 2) is a protease expressed in the brain, but also in the pancreas, where it seems to play a physiological role. Amyloidogenic diseases, including Alzheimer's disease and type 2 diabetes (T2D), share the accumulation of abnormally folded and insoluble proteins that interfere with cel...
Source: Cellular and Molecular Life Sciences : CMLS - March 23, 2017 Category: Cytology Authors: Alcarraz-Vizán G, Castaño C, Visa M, Montane J, Servitja JM, Novials A Tags: Cell Mol Life Sci Source Type: research

The acidic microenvironment as a possible niche of dormant tumor cells.
Abstract Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies. Here, we have particu...
Source: Cellular and Molecular Life Sciences : CMLS - March 22, 2017 Category: Cytology Authors: Peppicelli S, Andreucci E, Ruzzolini J, Laurenzana A, Margheri F, Fibbi G, Rosso MD, Bianchini F, Calorini L Tags: Cell Mol Life Sci Source Type: research

Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase.
This study suggests that the human HisRS genes, while descending from a common ancestor with dual function for both types of tRNA(His), have acquired highly specialized tRNA recognition properties through evolution. PMID: 28321488 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - March 20, 2017 Category: Cytology Authors: Lee YH, Chang CP, Cheng YJ, Kuo YY, Lin YS, Wang CC Tags: Cell Mol Life Sci Source Type: research

MicroRNA regulation and analytical methods in cancer cell metabolism.
Abstract The reprogramming of glucose metabolism from oxidative to glycolytic metabolism, known as the Warburg effect, is an anomalous characteristic of cancer cell metabolism. Recent studies have revealed a subset of microRNAs (miRNAs) that play critical roles in regulating the reprogramming of glucose metabolism in cancer cells. These miRNAs regulate cellular glucose metabolism by directly targeting multiple metabolic genes, including those encoding key glycolytic enzymes. In the first part of this review, we summarized the recent knowledge of miRNA regulation in the reprogramming of glucose metabolism in cancer...
Source: Cellular and Molecular Life Sciences : CMLS - March 20, 2017 Category: Cytology Authors: Zhang LF, Jiang S, Liu MF Tags: Cell Mol Life Sci Source Type: research

Erratum to: Mechanisms controlling germline cyst breakdown and primordial follicle formation.
PMID: 28315951 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2017 Category: Cytology Authors: Wang C, Zhou B, Xia G Tags: Cell Mol Life Sci Source Type: research

Kinetic analysis, size profiling, and bioenergetic association of DNA released by selected cell lines in vitro.
Abstract Although circulating DNA (cirDNA) analysis shows great promise as a screening tool for a wide range of pathologies, numerous stumbling blocks hinder the rapid translation of research to clinical practice. This is related directly to the inherent complexity of the in vivo setting, wherein the influence of complex systems of interconnected cellular responses and putative DNA sources creates a seemingly arbitrary representation of the quantitative and qualitative properties of the cirDNA in the blood of any individual. Therefore, to evaluate the potential of in vitro cell cultures to circumvent the difficult...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2017 Category: Cytology Authors: Aucamp J, Bronkhorst AJ, Peters DL, Van Dyk HC, Van der Westhuizen FH, Pretorius PJ Tags: Cell Mol Life Sci Source Type: research

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases.
Abstract Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleami...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Song P, Ramprasath T, Wang H, Zou MH Tags: Cell Mol Life Sci Source Type: research

Integration of mRNP formation and export.
r L Abstract Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA-protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Björk P, Wieslander L Tags: Cell Mol Life Sci Source Type: research

Development of anticancer agents targeting the Hedgehog signaling.
Abstract Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment. Here, we review the therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment. PMID: 28314894 [PubMed - as supplied by publisher] (Source: Cellular ...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Zhang X, Tian Y, Yang Y, Hao J Tags: Cell Mol Life Sci Source Type: research

Impairment of systemic DHA synthesis affects macrophage plasticity and polarization: implications for DHA supplementation during inflammation.
son A Abstract Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2017 Category: Cytology Authors: Talamonti E, Pauter AM, Asadi A, Fischer AW, Chiurchiù V, Jacobsson A Tags: Cell Mol Life Sci Source Type: research