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Cellular and Molecular Life Sciences: CMLS

Aroa Soriano, Marc Masanas, Ariadna Boloix, Núria Masiá, Laia París-Coderch, Olga Piskareva, Carlos Jiménez, Kai-Oliver Henrich, Josep Roma, Frank Westermann, Raymond L Stallings, Constantino Sábado, Josep Sánchez de Toledo, Anna Santamaria, Soledad Gallego, Miguel F Segura
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 development of new therapies...
February 15, 2019: Cellular and Molecular Life Sciences: CMLS
Kunal Dhiman, Kaj Blennow, Henrik Zetterberg, Ralph N Martins, Veer Bala Gupta
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...
February 15, 2019: Cellular and Molecular Life Sciences: CMLS
Paulina Podkalicka, Olga Mucha, Jozef Dulak, Agnieszka Loboda
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 aiming at the restoration of functional dystrophin is under the constant debate...
February 15, 2019: Cellular and Molecular Life Sciences: CMLS
Luke W Thomas, Margaret Ashcroft
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...
February 14, 2019: Cellular and Molecular Life Sciences: CMLS
Jindřiška Fišerová, Miloslava Maninová, Tomáš Sieger, Jana Uhlířová, Lenka Šebestová, Michaela Efenberková, Martin Čapek, Karel Fišer, Pavel Hozák
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...
February 14, 2019: Cellular and Molecular Life Sciences: CMLS
Harish P Janardhan, Chinmay M Trivedi
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...
February 13, 2019: Cellular and Molecular Life Sciences: CMLS
Alexander Negoda, Mairin S Hogan, Elizabeth A Cowley, Paul Linsdell
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...
February 13, 2019: Cellular and Molecular Life Sciences: CMLS
Jan Kotál, Natascha Stergiou, Michal Buša, Adéla Chlastáková, Zuzana Beránková, Pavlína Řezáčová, Helena Langhansová, Alexandra Schwarz, Eric Calvo, Jan Kopecký, Michael Mareš, Edgar Schmitt, Jindřich Chmelař, Michail Kotsyfakis
To successfully feed, ticks inject pharmacoactive molecules into the vertebrate host including cystatin cysteine protease inhibitors. However, the molecular and cellular events modulated by tick saliva remain largely unknown. Here, we describe and characterize a novel immunomodulatory cystatin, Iristatin, which is upregulated in the salivary glands of feeding Ixodes ricinus ticks. 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...
February 12, 2019: Cellular and Molecular Life Sciences: CMLS
Hans Prenen, Massimiliano Mazzone
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...
February 12, 2019: Cellular and Molecular Life Sciences: CMLS
Paulo A Ferreira
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...
February 11, 2019: Cellular and Molecular Life Sciences: CMLS
Fawzi Khoder-Agha, Paulina Sosicka, Maria Escriva Conde, Antti Hassinen, Tuomo Glumoff, Mariusz Olczak, Sakari Kellokumpu
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...
February 8, 2019: Cellular and Molecular Life Sciences: CMLS
Houman Kahroba, Mohammad Saeid Hejazi, Nasser Samadi
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...
February 8, 2019: Cellular and Molecular Life Sciences: CMLS
B Baksa, A Kovács, T Bayasgalan, P Szentesi, Á Kőszeghy, P Szücs, Balázs Pál
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), systematic assessment of these properties and correlation of them with morphological markers are still missing...
February 8, 2019: Cellular and Molecular Life Sciences: CMLS
Philipp Berndt, Lars Winkler, Jimmi Cording, Olga Breitkreuz-Korff, André Rex, Sophie Dithmer, Valentina Rausch, Rosel Blasig, Matthias Richter, Anje Sporbert, Hartwig Wolburg, Ingolf E Blasig, Reiner F Haseloff
At the blood-brain barrier (BBB), claudin (Cldn)-5 is thought to be the dominant tight junction (TJ) protein, with minor contributions from Cldn3 and -12, and occludin. However, the BBB appears ultrastructurally normal in Cldn5 knock-out mice, suggesting that further Cldns and/or TJ-associated marvel proteins (TAMPs) are involved. Microdissected human and murine brain capillaries, quickly frozen to recapitulate the in vivo situation, showed high transcript expression of Cldn5, -11, -12, and -25, and occludin, but also abundant levels of Cldn1 and -27 in man...
February 7, 2019: Cellular and Molecular Life Sciences: CMLS
Xiang Zhou, Yangzi Zhang, Jennifer J Michal, Lujiang Qu, Shuwen Zhang, Mark R Wildung, Weiwei Du, Derek J Pouchnik, Hui Zhao, Yin Xia, Honghua Shi, Guoli Ji, Jon F Davis, Gary D Smith, Michael D Griswold, Richard M Harland, Zhihua Jiang
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...
February 7, 2019: Cellular and Molecular Life Sciences: CMLS
Hasanthi C de Silva, Mike Z Lin, Leo Phillips, Janet L Martin, Robert C Baxter
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...
February 6, 2019: Cellular and Molecular Life Sciences: CMLS
Yanli Liu, Rongcheng Niu, Wenzhong Li, Juntang Lin, Christof Stamm, Gustav Steinhoff, Nan Ma
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 therapy due to their comprehensive advantages, which include their ability to be periodically and non-invasively collected, their abundant source material, their ability to be regularly donated, their superior proliferative capacity and their ability to be used for autologous transplantation...
February 5, 2019: Cellular and Molecular Life Sciences: CMLS
Azin Samimi, Majid Ghanavat, Saeid Shahrabi, Shirin Azizidoost, Najmaldin Saki
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...
February 4, 2019: Cellular and Molecular Life Sciences: CMLS
Sebastian Mathes, Mathias Vanmunster, Wilhelm Bloch, Frank Suhr
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...
January 30, 2019: Cellular and Molecular Life Sciences: CMLS
Yael Tal, Nava Chapnik, Oren Froy
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 olive oil increased signaling towards fatty acid oxidation...
January 29, 2019: Cellular and Molecular Life Sciences: CMLS
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