Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency.
Abstract The aging process is associated with chronic low-grade inflammation in both humans and rodents, commonly called inflammaging. At the same time, there is a gradual decline in the functional capacity of adaptive and innate immune systems, i.e., immunosenescence, a process not only linked to the aging process, but also encountered in several pathological conditions involving chronic inflammation. The hallmarks of immunosenescence include a decline in the numbers of naïve CD4+ and CD8+ T cells, an imbalance in the T cell subsets, and a decrease in T cell receptor (TCR) repertoire and signaling. Correspon...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Cell Mol Life Sci Source Type: research

Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword.
Abstract Helicobacter pylori (H. pylori) infection affects an estimated 4.4 billion people globally. Moreover, H. pylori presents the most significant risk factor for gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and it is the first example of bacterial infection linked to carcinogenesis. Here, we contend that H. pylori research, which focuses on a cancer-causing pathogen resident in a relatively accessible organ, the stomach, could constitute an exemplar for microbial-related carcinogenesis in less tractable organs, such as the pancreas and lung. In this context, molecular biolog...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2019 Category: Cytology Authors: Mentis AA, Boziki M, Grigoriadis N, Papavassiliou AG Tags: Cell Mol Life Sci Source Type: research

Protein S-nitrosylation in programmed cell death in plants.
Abstract Programmed cell death (PCD) is associated with different phases of plant life and provides resistance to different kinds of biotic or abiotic stress. The redox molecule nitric oxide (NO) is usually produced during the stress response and exerts dual effects on PCD regulation. S-nitrosylation, which NO attaches to the cysteine thiol of proteins, is a vital posttranslational modification and is considered as an essential way for NO to regulate cellular redox signaling. In recent years, a great number of proteins have been identified as targets of S-nitrosylation in plants, especially during PCD. S-nitrosyla...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2019 Category: Cytology Authors: Huang D, Huo J, Zhang J, Wang C, Wang B, Fang H, Liao W Tags: Cell Mol Life Sci Source Type: research

Integrin-independent support of cancer drug resistance by tetraspanin CD151.
Abstract Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer drugs (e.g., gefitinib and camptothecin), thus increasing apoptosis, as seen using cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), annexin V, and propidium iodide staining assays. Drug sensitization due to CD151 ablation is integrin-independent, because, (1) effects occurred in cells when integrin...
Source: Cellular and Molecular Life Sciences : CMLS - February 18, 2019 Category: Cytology Authors: Hwang S, Takimoto T, Hemler ME Tags: Cell Mol Life Sci Source Type: research

Targeting angiogenesis in Duchenne muscular dystrophy.
Abstract Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies which affect boys already at early childhood. Despite the fact that the primary cause of the disease, namely the lack of functional dystrophin is known already for more than 30 years, DMD still remains an incurable disease. Thus, an enormous effort has been made during recent years to reveal novel mechanisms that could provide therapeutic targets for DMD, especially because glucocorticoids treatment acts mostly symptomatic and exerts many side effects, whereas the effectiveness of genetic approaches...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Podkalicka P, Mucha O, Dulak J, Loboda A Tags: Cell Mol Life Sci Source Type: research

Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis.
Abstract Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures. However, looking into the multifactorial nature of AD and the overlapping pathology wit...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Dhiman K, Blennow K, Zetterberg H, Martins RN, Gupta VB Tags: Cell Mol Life Sci Source Type: research

Functional high-throughput screening reveals miR-323a-5p and miR-342-5p as new tumor-suppressive microRNA for neuroblastoma.
A, Gallego S, Segura MF Abstract Current therapies for most non-infectious diseases are directed at or affect functionality of the human translated genome, barely 2% of all genetic information. By contrast, the therapeutic potential of targeting the transcriptome, ~ 70% of the genome, remains largely unexplored. RNA therapeutics is an emerging field that widens the range of druggable targets and includes elements such as microRNA. Here, we sought to screen for microRNA with tumor-suppressive functions in neuroblastoma, an aggressive pediatric tumor of the sympathetic nervous system that requires the developme...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Soriano A, Masanas M, Boloix A, Masiá N, París-Coderch L, Piskareva O, Jiménez C, Henrich KO, Roma J, Westermann F, Stallings RL, Sábado C, de Toledo JS, Santamaria A, Gallego S, Segura MF Tags: Cell Mol Life Sci Source Type: research

Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria.
Abstract Oxygen is required for the survival of the majority of eukaryotic organisms, as it is important for many cellular processes. Eukaryotic cells utilize oxygen for the production of biochemical energy in the form of adenosine triphosphate (ATP) generated from the catabolism of carbon-rich fuels such as glucose, lipids and glutamine. The intracellular sites of oxygen consumption-coupled ATP production are the mitochondria, double-membraned organelles that provide a dynamic and multifaceted role in cell signalling and metabolism. Highly evolutionarily conserved molecular mechanisms exist to sense and respond t...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2019 Category: Cytology Authors: Thomas LW, Ashcroft M Tags: Cell Mol Life Sci Source Type: research

Nuclear pore protein TPR associates with lamin B1 and affects nuclear lamina organization and nuclear pore distribution.
nberková M, Čapek M, Fišer K, Hozák P Abstract The organization of the nuclear periphery is crucial for many nuclear functions. Nuclear lamins form dense network at the nuclear periphery and play a substantial role in chromatin organization, transcription regulation and in organization of nuclear pore complexes (NPCs). Here, we show that TPR, the protein located preferentially within the nuclear baskets of NPCs, associates with lamin B1. The depletion of TPR affects the organization of lamin B1 but not lamin A/C within the nuclear lamina as shown by stimulated emission depletion microscopy. F...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2019 Category: Cytology Authors: Fišerová J, Maninová M, Sieger T, Uhlířová J, Šebestová L, Efenberková M, Čapek M, Fišer K, Hozák P Tags: Cell Mol Life Sci Source Type: research

Contribution of the eighth transmembrane segment to the function of the CFTR chloride channel pore.
Abstract Our molecular understanding of the cystic fibrosis transmembrane conductance regulator (CFTR)-the chloride channel that is mutated in cystic fibrosis-has been greatly enhanced by a number of recent atomic-level structures of the protein in different conformations. One surprising aspect of these structures was the finding that the eighth of CFTR's 12 membrane-spanning segments (TM8) appeared close to the channel pore. Although functional evidence supports a role for other TMs in forming the pore, such a role for TM8 has not previously been reported. Here, we use patch-clamp recording to investigate the fun...
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2019 Category: Cytology Authors: Negoda A, Hogan MS, Cowley EA, Linsdell P Tags: Cell Mol Life Sci Source Type: research

Establishment and maintenance of blood-lymph separation.
Abstract Hippocratic Corpus, a collection of Greek medical literature, described the functional anatomy of the lymphatic system in the fifth century B.C. Subsequent studies in cadavers and surgical patients firmly established that lymphatic vessels drain extravasated interstitial fluid, also known as lymph, into the venous system at the bilateral lymphovenous junctions. Recent advances revealed that lymphovenous valves and platelet-mediated hemostasis at the lymphovenous junctions maintain life-long separation of the blood and lymphatic vascular systems. Here, we review murine models that exhibit failure of blood-...
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2019 Category: Cytology Authors: Janardhan HP, Trivedi CM Tags: Cell Mol Life Sci Source Type: research

Tumor-associated macrophages: a short compendium.
Abstract Macrophages play an important role in tissue development and homeostasis. They serve as a nexus between adaptive and innate immunity, and employ considerable plasticity. In cancer, they play a pivotal role in chronic inflammation and tumor growth either by directly stimulating the proliferation of cancer cells or by producing angiogenic and lymphangiogenic factors. Although numerous immune cells play an important role in the tumor microenvironment, tumor-associated macrophages (TAMs) are by far the most extensively studied. A better understanding of the role of TAMs in mediating chemo- and radiotherapy re...
Source: Cellular and Molecular Life Sciences : CMLS - February 12, 2019 Category: Cytology Authors: Prenen H, Mazzone M Tags: Cell Mol Life Sci Source Type: research

The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin.
We present the crystal structure of Iristatin at 1.76 Å resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN-γ production by different T-cell populations, IL-6 and IL-9 production by mast cells, and nitric oxide production by macrophages. Furthermore, Iristatin inhibited OVA antigen-induced CD4+ T-cell proliferation and leukocyte recruitment in vivo and in vitro. Our results indicate that Iristatin affects wide range of anti-tick immune responses in the vertebrate host and may be exploitable as an immunotherapeutic. ...
Source: Cellular and Molecular Life Sciences : CMLS - February 12, 2019 Category: Cytology Authors: Kotál J, Stergiou N, Buša M, Chlastáková A, Beránková Z, Řezáčová P, Langhansová H, Schwarz A, Calvo E, Kopecký J, Mareš M, Schmitt E, Chmelař J, Kotsyfakis M Tags: Cell Mol Life Sci Source Type: research

The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.
Abstract The nuclear pore is the gatekeeper of nucleocytoplasmic transport and signaling through which a vast flux of information is continuously exchanged between the nuclear and cytoplasmic compartments to maintain cellular homeostasis. A unifying and organizing principle has recently emerged that cements the notion that several forms of amyotrophic lateral sclerosis (ALS), and growing number of other neurodegenerative diseases, co-opt the dysregulation of nucleocytoplasmic transport and that this impairment is a pathogenic driver of neurodegeneration. The understanding of shared pathomechanisms that underpin ne...
Source: Cellular and Molecular Life Sciences : CMLS - February 11, 2019 Category: Cytology Authors: Ferreira PA Tags: Cell Mol Life Sci Source Type: research

N-acetylglucosaminyltransferases and nucleotide sugar transporters form multi-enzyme-multi-transporter assemblies in golgi membranes in vivo.
Abstract Branching and processing of N-glycans in the medial-Golgi rely both on the transport of the donor UDP-N-acetylglucosamine (UDP-GlcNAc) to the Golgi lumen by the SLC35A3 nucleotide sugar transporter (NST) as well as on the addition of the GlcNAc residue to terminal mannoses in nascent N-glycans by several linkage-specific N-acetyl-glucosaminyltransferases (MGAT1-MGAT5). Previous data indicate that the MGATs and NSTs both form higher order assemblies in the Golgi membranes. Here, we investigate their specific and mutual interactions using high-throughput FRET- and BiFC-based interaction screens. We show tha...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Khoder-Agha F, Sosicka P, Escriva Conde M, Hassinen A, Glumoff T, Olczak M, Kellokumpu S Tags: Cell Mol Life Sci Source Type: research

Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus.
ml;cs P, Pál B Abstract The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e., the presence or absence of the A-current, spike latency, and low threshold spikes). Although other electrophysiological characteristics of these neurons were also described (as high threshold membrane potential oscillations, great differences in spontaneous firing rate and the presence or absence of the M-current), sys...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Baksa B, Kovács A, Bayasgalan T, Szentesi P, Kőszeghy Á, Szücs P, Pál B Tags: Cell Mol Life Sci Source Type: research

Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer.
Abstract Exosomes represent an important group of extracellular vesicles with a defined size between 40 and 150 nm and cup-shaped construction which have a pivotal role in elimination of intracellular debris and intercellular signaling networks. A line of evidence revealed the impact of different types of exosomes in initiation, progression, and metastasis of gastric cancer (GC). These bioactive vesicles mediate tumor and stromal communication network through modulation of cell signaling for carcinogenesis and pre-metastatic niche formation in distant organs. Exosomes contain various cargos including DNAs (mi...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Kahroba H, Hejazi MS, Samadi N Tags: Cell Mol Life Sci Source Type: research

Alternative polyadenylation coordinates embryonic development, sexual dimorphism and longitudinal growth in Xenopus tropicalis.
Abstract RNA alternative polyadenylation contributes to the complexity of information transfer from genome to phenome, thus amplifying gene function. Here, we report the first X. tropicalis resource with 127,914 alternative polyadenylation (APA) sites derived from embryos and adults. Overall, APA networks play central roles in coordinating the maternal-zygotic transition (MZT) in embryos, sexual dimorphism in adults and longitudinal growth from embryos to adults. APA sites coordinate reprogramming in embryos before the MZT, but developmental events after the MZT due to zygotic genome activation. The APA transcript...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2019 Category: Cytology Authors: Zhou X, Zhang Y, Michal JJ, Qu L, Zhang S, Wildung MR, Du W, Pouchnik DJ, Zhao H, Xia Y, Shi H, Ji G, Davis JF, Smith GD, Griswold MD, Harland RM, Jiang Z Tags: Cell Mol Life Sci Source Type: research

Tight junction proteins at the blood-brain barrier: far more than claudin-5.
In conclusion, this complete Cldn/TAMP profile demonstrates the presence of up to a dozen TJ proteins in brain capillaries. Mouse and human share a similar and complex TJ profile in vivo, but this complexity is widely lost under in vitro conditions. PMID: 30734065 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2019 Category: Cytology Authors: Berndt P, Winkler L, Cording J, Breitkreuz-Korff O, Rex A, Dithmer S, Rausch V, Blasig R, Richter M, Sporbert A, Wolburg H, Blasig IE, Haseloff RF Tags: Cell Mol Life Sci Source Type: research

IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer.
Abstract Women with triple-negative breast cancer (TNBC) are generally treated by chemotherapy but their responsiveness may be blunted by DNA double-strand break (DSB) repair. We previously reported that IGFBP-3 forms nuclear complexes with EGFR and DNA-dependent protein kinase (DNA-PKcs) to modulate DSB repair by non-homologous end-joining (NHEJ) in TNBC cells. To discover IGFBP-3 binding partners involved in chemoresistance through stimulation of DSB repair, we analyzed the IGFBP-3 interactome by LC-MS/MS and confirmed interactions by coimmunoprecipitation and proximity ligation assay. Functional effects were de...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2019 Category: Cytology Authors: de Silva HC, Lin MZ, Phillips L, Martin JL, Baxter RC Tags: Cell Mol Life Sci Source Type: research

Therapeutic potential of menstrual blood-derived endometrial stem cells in cardiac diseases.
Abstract Despite significant developments in medical and surgical strategies, cardiac diseases remain the leading causes of morbidity and mortality worldwide. Numerous studies involving preclinical and clinical trials have confirmed that stem cell transplantation can help improve cardiac function and regenerate damaged cardiac tissue, and stem cells isolated from bone marrow, heart tissue, adipose tissue and umbilical cord are the primary candidates for transplantation. During the past decade, menstrual blood-derived endometrial stem cells (MenSCs) have gradually become a promising alternative for stem cell-based ...
Source: Cellular and Molecular Life Sciences : CMLS - February 5, 2019 Category: Cytology Authors: Liu Y, Niu R, Li W, Lin J, Stamm C, Steinhoff G, Ma N Tags: Cell Mol Life Sci Source Type: research

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.
Abstract Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature ...
Source: Cellular and Molecular Life Sciences : CMLS - February 4, 2019 Category: Cytology Authors: Samimi A, Ghanavat M, Shahrabi S, Azizidoost S, Saki N Tags: Cell Mol Life Sci Source Type: research

Evidence for skeletal muscle fiber type-specific expressions of mechanosensors.
Abstract Mechanosensors govern muscle tissue integrity and constitute a subcellular structure known as costameres. Costameres physically link the muscle extracellular matrix to contractile and signaling 'hubs' inside muscle fibers mainly via integrins and are localized beneath sarcolemmas of muscle fibers. Costameres are the main mechanosensors converting mechanical cues into biological events. However, the fiber type-specific costamere architecture in muscles is unexplored. We hypothesized that fiber types differ in the expression of genes coding for costamere components. By coupling laser microdissection to a mu...
Source: Cellular and Molecular Life Sciences : CMLS - January 30, 2019 Category: Cytology Authors: Mathes S, Vanmunster M, Bloch W, Suhr F Tags: Cell Mol Life Sci Source Type: research

Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo.
Abstract Biologic function of the majority of microRNAs (miRNAs) is still unknown. Uncovering the function of miRNAs is hurdled by redundancy among different miRNAs. The deletion of Dgcr8 leads to the deficiency in producing all canonical miRNAs, therefore, overcoming the redundancy issue. Dgcr8 knockout strategy has been instrumental in understanding the function of miRNAs in a variety of cells in vitro and in vivo. In this review, we will first give a brief introduction about miRNAs, miRNA biogenesis pathway and the role of Dgcr8 in miRNA biogenesis. We will then summarize studies performed with Dgcr8 knockout c...
Source: Cellular and Molecular Life Sciences : CMLS - January 29, 2019 Category: Cytology Authors: Guo WT, Wang Y Tags: Cell Mol Life Sci Source Type: research

Non-obesogenic doses of fatty acids modulate the functionality of the circadian clock in the liver.
Abstract Saturated fatty acids, such as palmitate, lead to circadian disruption in cell culture. Moreover, information regarding the effects of unsaturated fatty acids on circadian parameters is scarce. We aimed at studying the effects of low doses of saturated as well as unsaturated fatty acids on circadian metabolism in vivo and at deciphering the mechanism by which fatty acids convey their effect. Mice were fed non-obesogenic doses of palm or olive oil and hepatocytes were treated with palmitate and oleate. Mice fed non-obesogenic doses of palm oil showed increased signaling towards fatty acid synthesis, while ...
Source: Cellular and Molecular Life Sciences : CMLS - January 29, 2019 Category: Cytology Authors: Tal Y, Chapnik N, Froy O Tags: Cell Mol Life Sci Source Type: research

Determinants of stem cell lineage differentiation toward chondrogenesis versus adipogenesis.
Abstract Adult stem cells, also termed as somatic stem cells, are undifferentiated cells, detected among differentiated cells in a tissue or an organ. Adult stem cells can differentiate toward lineage specific cell types of the tissue or organ in which they reside. They also have the ability to differentiate into mature cells of mesenchymal tissues, such as cartilage, fat and bone. Despite the fact that the balance has been comprehensively scrutinized between adipogenesis and osteogenesis and between chondrogenesis and osteogenesis, few reviews discuss the relationship between chondrogenesis and adipogenesis. In t...
Source: Cellular and Molecular Life Sciences : CMLS - January 28, 2019 Category: Cytology Authors: Zhou S, Chen S, Jiang Q, Pei M Tags: Cell Mol Life Sci Source Type: research

Link between the unfolded protein response and dysregulation of mitochondrial bioenergetics in Alzheimer's disease.
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting more than 47.5 million people worldwide. Metabolic impairments are common hallmarks of AD, and amyloid-β (Aβ) peptide and hyperphosphorylated tau protein-the two foremost histopathological signs of AD-have been implicated in mitochondrial dysfunction. Many neurodegenerative disorders, including AD, show excessive amounts of mis-/unfolded proteins leading to an activation of the unfolded protein response (UPR). In the present study, we aimed to characterize the link between ER stress and bioenergetics defects under nor...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Poirier Y, Grimm A, Schmitt K, Eckert A Tags: Cell Mol Life Sci Source Type: research

The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways.
Abstract HMG box protein 1 (HBP1) is a transcription factor and a potent cell cycle inhibitor in normal and cancer cells. HBP1 activates or represses the expression of different cell cycle genes (such as CDKN2A, CDKN1A, and CCND1) through direct DNA binding, cofactor recruitment, chromatin remodeling, or neutralization of other transcription factors. Among these are LEF1, TCF4, and MYC in the WNT/beta-catenin pathway. HBP1 also contributes to oncogenic RAS-induced senescence and terminal cell differentiation. Collectively, these activities suggest a tumor suppressor function. However, HBP1 is not listed among freq...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Bollaert E, de Rocca Serra A, Demoulin JB Tags: Cell Mol Life Sci Source Type: research

Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks.
Abstract The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding and maintenance; some with overlapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive, assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. Here, we have used S. cerevisiae to understand how cells respond to different types of proteostasis impairments. We monitored the proteostasis status and transcriptome of single deletions of fourteen differen...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Ghosh A, Gangadharan A, Verma M, Das S, Matai L, Dash DP, Dash D, Mapa K, Chakraborty K Tags: Cell Mol Life Sci Source Type: research

The functional roles of exosomal long non-coding RNAs in cancer.
Abstract Exosomes are extracellular membranous vesicles that are secreted by various cell types. Exosomes have become indispensable facilitators in the exchange of information between cells. More importantly, exosomes perform a crucial role in a variety of diseases including cancers. Long non-coding RNAs (lncRNAs) are over 200 nucleotides long transcripts that exhibit no or limited protein-coding potentials. LncRNAs are an emerging group of regulatory RNAs and can be selectively packaged into exosomes. Exosomal lncRNAs play a central role in carcinogenesis and cancer progression by modulating tumor growth, metasta...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Wang M, Zhou L, Yu F, Zhang Y, Li P, Wang K Tags: Cell Mol Life Sci Source Type: research

The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD).
ard P Abstract NAFLD is currently the main cause of chronic liver disease in developed countries, and the number of NAFLD patients is growing worldwide. NAFLD often has similar symptoms to other metabolic disorders, including type 2 diabetes and obesity. Recently, the role of the gut microbiota in the pathophysiology of many diseases has been revealed. Regarding NAFLD, experiments using gut microbiota transplants to germ-free animal models showed that fatty liver disease development is determined by gut bacteria. Moreover, the perturbation of the composition of the gut microbiota has been observed in patients suff...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Safari Z, Gérard P Tags: Cell Mol Life Sci Source Type: research

Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus.
Abstract Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence and chronic hepatitis B. CRISPR/Cas9 nucleases can specifically target HBV cccDNA for decay, but off-target effects of nucleases in the human genome limit their clinical utility. CRISPR/Cas9 systems from four different species were co-expressed in cell lines with guide RNAs targeting conserved regions of the HBV genome. CRISPR/Cas9 systems from Streptococcus pyogenes (Sp) and Streptococcus thermophilus (St) targeting conserved regions of the HBV genome blocked HBV replication and, most importantly, r...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Kostyushev D, Brezgin S, Kostyusheva A, Zarifyan D, Goptar I, Chulanov V Tags: Cell Mol Life Sci Source Type: research

The SEACIT complex is involved in the maintenance of vacuole-mitochondria contact sites and controls mitophagy.
Abstract The major signaling pathway that regulates cell growth and metabolism is under the control of the target of rapamycin complex 1 (TORC1). In Saccharomyces cerevisiae the SEA complex is one of the TORC1 upstream regulators involved in amino acid sensing and autophagy. Here, we performed analysis of the expression, interactions and localization of SEA complex proteins under different conditions, varying parameters such as sugar source, nitrogen availability and growth phase. Our results show that the SEA complex promotes mitochondria degradation either by mitophagy or by general autophagy. In addition, the S...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Ma Y, Moors A, Camougrand N, Dokudovskaya S Tags: Cell Mol Life Sci Source Type: research

Mitochondrial stress triggers a pro-survival response through epigenetic modifications of nuclear DNA.
In conclusion, mitochondrial dysfunction leads to a "pro-survival" adaptive state that seems to be triggered by the differential methylation of nuclear genes. PMID: 30673822 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Mayorga L, Salassa BN, Marzese DM, Loos MA, Eiroa HD, Lubieniecki F, García Samartino C, Romano PS, Roqué M Tags: Cell Mol Life Sci Source Type: research

Testicular germ cell tumor: a comprehensive review.
Abstract Testicular tumors are the most common tumors in adolescent and young men and germ cell tumors (TGCTs) account for most of all testicular cancers. Increasing incidence of TGCTs among males provides strong motivation to understand its biological and genetic basis. Gains of chromosome arm 12p and aneuploidy are nearly universal in TGCTs, but TGCTs have low point mutation rate. It is thought that TGCTs develop from premalignant intratubular germ cell neoplasia that is believed to arise from the failure of normal maturation of gonocytes during fetal or postnatal development. Progression toward invasive TG...
Source: Cellular and Molecular Life Sciences : CMLS - January 22, 2019 Category: Cytology Authors: Batool A, Karimi N, Wu XN, Chen SR, Liu YX Tags: Cell Mol Life Sci Source Type: research

A disease causing ATLASTIN 3 mutation affects multiple endoplasmic reticulum-related pathways.
Abstract Atlastins (ATLs) are membrane-bound GTPases involved in shaping of the endoplasmic reticulum (ER). Mutations in ATL1 and ATL3 cause spastic paraplegia and hereditary sensory neuropathy. We here show that the sensory neuropathy causing ATL3 Y192C mutation reduces the complexity of the tubular ER-network. ATL3 Y192C delays ER-export by reducing the number of ER exit sites, reduces autophagy, fragments the Golgi and causes malformation of the nucleus. In cultured primary neurons, ATL3 Y192C does not localize to the growing axon, resulting in axon growth deficits. Patient-derived fibroblasts possess a tubular...
Source: Cellular and Molecular Life Sciences : CMLS - January 21, 2019 Category: Cytology Authors: Behrendt L, Kurth I, Kaether C Tags: Cell Mol Life Sci Source Type: research

Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice.
Abstract Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a component of the complex III in the respiratory chain. Its biological functions are unknown. Here, we showed that knockout of UQCRC1 led to embryonic lethality. Disrupting one UQCRC1 allele in mice (heterozygous mice) of both sexes did not affect their growth but reduced UQCRC1 mRNA and protein in the brain. These mice had decreased complex III formation, complex III activity and ATP content in the brain at baseline. They developed worsened neurological outcome after brain ischemia/hypoxia or focal brain ischemia compared with wild-type mice. T...
Source: Cellular and Molecular Life Sciences : CMLS - January 21, 2019 Category: Cytology Authors: Shan W, Li J, Xu W, Li H, Zuo Z Tags: Cell Mol Life Sci Source Type: research

A novel leptin receptor antagonist uncouples leptin's metabolic and immune functions.
Abstract Leptin links body energy stores to high energy demanding processes like reproduction and immunity. Based on leptin's role in autoimmune diseases and cancer, several leptin and leptin receptor (LR) antagonists have been developed, but these intrinsically lead to unwanted weight gain. Here, we report on the uncoupling of leptin's metabolic and immune functions based on the cross talk with the epidermal growth factor receptor (EGFR). We show that both receptors spontaneously interact and, remarkably, that this complex can partially overrule the lack of LR activation by a leptin antagonistic mutein. Moreover,...
Source: Cellular and Molecular Life Sciences : CMLS - January 18, 2019 Category: Cytology Authors: Zabeau L, Wauman J, Dam J, Van Lint S, Burg E, De Geest J, Rogge E, Silva A, Jockers R, Tavernier J Tags: Cell Mol Life Sci Source Type: research

The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?
Abstract Endogenous protease tissue-type plasminogen activator (tPA) has highly efficient fibrinolytic activity and its recombinant variants alteplase and tenecteplase are established as highly effective thrombolytic drugs for ischemic stroke. Endogenous tPA is constituted of five functional domains through which it interacts with a variety of substrates, binding proteins and receptors, thus having enzymatic and cytokine-like effects to act on all cell types of the brain. In the past 2 decades, numerous studies have explored the clinical relevance of endogenous tPA in neurological diseases, especially in isch...
Source: Cellular and Molecular Life Sciences : CMLS - January 17, 2019 Category: Cytology Authors: Zhu J, Wan Y, Xu H, Wu Y, Hu B, Jin H Tags: Cell Mol Life Sci Source Type: research

Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.
Abstract Receptor tyrosine kinases (RTKs) play key roles in various aspects of cell biology, including cell-to-cell communication, proliferation and differentiation, survival, and tissue homeostasis, and have been implicated in various diseases including cancer and neurodevelopmental disorders. Ligand-activated RTKs recruit adapter proteins through a phosphotyrosine (p-Tyr) motif that is present on the RTK and a p-Tyr-binding domain, like the Src homology 2 (SH2) domain found in adapter proteins. Notably, numerous combinations of RTK/adapter combinations exist, making it challenging to compare receptor activities ...
Source: Cellular and Molecular Life Sciences : CMLS - January 8, 2019 Category: Cytology Authors: Wintgens JP, Wichert SP, Popovic L, Rossner MJ, Wehr MC Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation.
Abstract LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in cis and/or in trans in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, and chromatin-modifier complexes. Given the versatility of these molecules to operate in different subcellular compartments, via different modes of action and with different target specificity, the interest in this...
Source: Cellular and Molecular Life Sciences : CMLS - January 3, 2019 Category: Cytology Authors: Fico A, Fiorenzano A, Pascale E, Patriarca EJ, Minchiotti G Tags: Cell Mol Life Sci Source Type: research

Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.
Abstract Neuronal nicotinic receptors containing α4 and β2 subunits assemble in two pentameric stoichiometries, (α4)3(β2)2 and (α4)2(β2)3, each with distinct pharmacological signatures; (α4)3(β2)2 receptors are strongly potentiated by the drug NS9283, whereas (α4)2(β2)3 receptors are unaffected. Despite this stoichiometry-selective pharmacology, the molecular identity of the target for NS9283 remains elusive. Here, studying (α4)3(β2)2 receptors, we show that mutations at either the principal face of the β2 subunit or the complementary face of t...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Mazzaferro S, Bermudez I, Sine SM Tags: Cell Mol Life Sci Source Type: research

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion.
ma TA Abstract Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) ...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Valdivieso ÁG, Clauzure M, Massip-Copiz MM, Cancio CE, Asensio CJA, Mori C, Santa-Coloma TA Tags: Cell Mol Life Sci Source Type: research

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.
Abstract The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox s...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Ruiz de Azua I, Lutz B Tags: Cell Mol Life Sci Source Type: research

Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.
Abstract Odorant receptors represent the largest family of mammalian G protein-coupled receptors. Phylogenetically, they are split into two classes (I and II). By analyzing the entire subclass I odorant receptors sequences, we identified two class I-specific and highly conserved motifs. These are predicted to face each other at the extra-cellular portion of the transmembrane domain, forming a vestibular site at the entrance to the orthosteric-binding cavity. Molecular dynamics simulation combined with site-directed mutagenesis and in vitro functional assays confirm the functional role of this vestibular site in li...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Bushdid C, de March CA, Topin J, Do M, Matsunami H, Golebiowski J Tags: Cell Mol Life Sci Source Type: research

Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer's disease.
CONCLUSION: Our results characterize TBX2 as a repressor of ADAM10 gene expression and suggest that this regulatory interaction is conserved across tissues and species. PMID: 30599067 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Reinhardt S, Schuck F, Stoye N, Hartmann T, Grimm MOW, Pflugfelder G, Endres K Tags: Cell Mol Life Sci Source Type: research

Cellular senescence is associated with reorganization of the microtubule cytoskeleton.
This study evaluated the cytoskeleton in two independent cellular models of kidney epithelium senescence. Our work identified multiple senescence-related alterations that impact microtubules and filamentous actin during interphase. Both filamentous systems reorganized profoundly when cells became senescent. As such, microtubule stability increased during senescence, making these filaments more resistant to disassembly in the cold or by nocodazole. Microtubule stabilization was accompanied by enhanced α-tubulin acetylation on lysine 40 and the depletion of HDAC6, the major deacetylase for α-tubulin lysine 40. Rh...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Moujaber O, Fishbein F, Omran N, Liang Y, Colmegna I, Presley JF, Stochaj U Tags: Cell Mol Life Sci Source Type: research

The dual face of glutamate: from a neurotoxin to a potential survival factor-metabolic implications in health and disease.
Abstract Glutamate is the major excitatory neurotransmitter in the central nervous system. Beyond this function, glutamate also plays a key role in intermediary metabolism in all organs and tissues, linking carbohydrate and amino acid metabolism via the tricarboxylic acid cycle. Under both physiological and pathological conditions, we have recently found that the ability of glutamate to fuel cell metabolism selectively relies on the activity of two main transporters: the sodium-calcium exchanger (NCX) and the sodium-dependent excitatory amino-acid transporters (EAATs). In ischemic settings, when glutamate is admin...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Magi S, Piccirillo S, Amoroso S Tags: Cell Mol Life Sci Source Type: research

Mechanisms protecting host cells against bacterial pore-forming toxins.
Abstract Pore-forming toxins (PFTs) are key virulence determinants produced and secreted by a variety of human bacterial pathogens. They disrupt the plasma membrane (PM) by generating stable protein pores, which allow uncontrolled exchanges between the extracellular and intracellular milieus, dramatically disturbing cellular homeostasis. In recent years, many advances were made regarding the characterization of conserved repair mechanisms that allow eukaryotic cells to recover from mechanical disruption of the PM membrane. However, the specificities of the cell recovery pathways that protect host cells against PFT...
Source: Cellular and Molecular Life Sciences : CMLS - December 27, 2018 Category: Cytology Authors: Brito C, Cabanes D, Sarmento Mesquita F, Sousa S Tags: Cell Mol Life Sci Source Type: research

Immune responses in cardiac repair and regeneration: a comparative point of view.
r DYR Abstract Immediately after cardiac injury, the immune system plays major roles in repair and regeneration as it becomes involved in a number of processes including damage-associated signaling, inflammation, revascularization, cardiomyocyte dedifferentiation and replenishment, and fibrotic scar formation/resolution. Recent studies have revealed that different immune responses occur in the various experimental models capable or incapable of cardiac regeneration, and that harnessing these immune responses might improve cardiac repair. In light of this concept, this review analyzes current knowledge about the im...
Source: Cellular and Molecular Life Sciences : CMLS - December 21, 2018 Category: Cytology Authors: Lai SL, Marín-Juez R, Stainier DYR Tags: Cell Mol Life Sci Source Type: research