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Cellular and Molecular Life Sciences: CMLS

Assel Mussabekova, Laurent Daeffler, Jean-Luc Imler
The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway...
January 19, 2017: Cellular and Molecular Life Sciences: CMLS
Alexander Widiapradja, Prasad Chunduri, Scott P Levick
In addition to traditional neurotransmitters of the sympathetic and parasympathetic nervous systems, the heart also contains numerous neuropeptides. These neuropeptides not only modulate the effects of neurotransmitters, but also have independent effects on cardiac function. While in most cases the physiological actions of these neuropeptides are well defined, their contributions to cardiac pathology are less appreciated. Some neuropeptides are cardioprotective, some promote adverse cardiac remodeling and heart failure, and in the case of others their functions are unclear...
January 17, 2017: Cellular and Molecular Life Sciences: CMLS
L Dhers, L Ducassou, J-L Boucher, D Mansuy
Cytochrome P450 2U1 (CYP2U1) exhibits several distinctive characteristics among the 57 human CYPs, such as its presence in almost all living organisms with a highly conserved sequence, its particular gene organization with only five exons, its major location in thymus and brain, and its protein sequence involving an unusually long N-terminal region containing 8 proline residues and an insert of about 20 amino acids containing 5 arginine residues after the transmembrane helix. Few substrates, including fatty acids, N-arachidonoylserotonin (AS), and some drugs, have been reported so far...
January 12, 2017: Cellular and Molecular Life Sciences: CMLS
Andrew Paul Trotta, Jerry Edward Chipuk
Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease...
January 12, 2017: Cellular and Molecular Life Sciences: CMLS
Yuki Okada, Kosuke Yamaguchi
Pronuclear/zygotic stage is the very first stage of life. In this period, paternal pronucleus undergoes massive chromatin remodeling called "paternal reprogramming" including protamine-histone replacement and subsequent acquisition of epigenetic modifications. Although these consecutive events are required for the initiation of maternal-zygotic transition, the precise role of paternal reprogramming and its effect on subsequent embryonic development has been largely unknown to date. Recently, various new techniques, especially next-generation sequencing (NGS) and RNAi microinjection contribute to unveil the epigenetic transition from both paternal and maternal to early preimplantation embryos, suggesting not only the simple transcriptional regulation by transcription factors but also dynamic structural alteration of chromatin to initiate the wave of zygotic gene transcription...
January 3, 2017: Cellular and Molecular Life Sciences: CMLS
Yu Liu
Mesoderm posterior 1 is one of earliest markers of the nascent mesoderm. Its best-known function is driving the onset of the cardiovascular system. In the past decade, new evidence supports that Mesp1 acts earlier with greater breadth in cell fate decisions, and through cell-autonomous and cell non-autonomous mechanisms. This review summarizes these new aspects, with an emphasis on the upstream and downstream regulation around Mesp1 and how they may guide cell fate reprogramming.
January 3, 2017: Cellular and Molecular Life Sciences: CMLS
Nhat-Tu Le, Uday G Sandhu, Raymundo A Quintana-Quezada, Nguyet Minh Hoang, Keigi Fujiwara, Jun-Ichi Abe
Atherosclerosis rarely develops in the region of arteries exposed to undisturbed flow (u-flow, unidirectional flow). Instead, atherogenesis occurs in the area exposed to disturbed flow (d-flow, multidirectional flow). Based on these general pathohistological observations, u-flow is considered to be athero-protective, while d-flow is atherogenic. The fact that u-flow and d-flow induce such clearly different biological responses in the wall of large arteries indicates that these two types of flow activate each distinct intracellular signaling cascade in vascular endothelial cells (ECs), which are directly exposed to blood flow...
December 30, 2016: Cellular and Molecular Life Sciences: CMLS
Liliane Tetsi, Anne-Laure Charles, Stéphanie Paradis, Anne Lejay, Samy Talha, Bernard Geny, Claire Lugnier
Mitochondria play a critical role in skeletal muscle metabolism and function, notably at the level of tissue respiration, which conduct muscle strength as well as muscle survival. Pathological conditions induce mitochondria dysfunctions notably characterized by free oxygen radical production disturbing intracellular signaling. In that way, the second messengers, cyclic AMP and cyclic GMP, control intracellular signaling at the physiological and transcription levels by governing phosphorylation cascades. Both nucleotides are specifically and selectively hydrolyzed in their respective 5'-nucleotide by cyclic nucleotide phosphodiesterases (PDEs), which constitute a multi-genic family differently tissue distributed and subcellularly compartmentalized...
December 30, 2016: Cellular and Molecular Life Sciences: CMLS
Thomas Burn, Jorge Ivan Alvarez
The endothelium provides a strong barrier separating circulating blood from tissue. It also provides a significant challenge for immune cells in the bloodstream to access potential sites of infection. To mount an effective immune response, leukocytes traverse the endothelial layer in a process known as transendothelial migration. Decades of work have allowed dissection of the mechanisms through which immune cells gain access into peripheral tissues, and subsequently to inflammatory foci. However, an often under-appreciated or potentially ignored question is whether transmigrated leukocytes can leave these inflammatory sites, and perhaps even return across the endothelium and re-enter circulation...
December 26, 2016: Cellular and Molecular Life Sciences: CMLS
Marina El Haddad, Cécile Notarnicola, Brendan Evano, Nour El Khatib, Marine Blaquière, Anne Bonnieu, Shahragim Tajbakhsh, Gérald Hugon, Barbara Vernus, Jacques Mercier, Gilles Carnac
Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor...
December 26, 2016: Cellular and Molecular Life Sciences: CMLS
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
December 24, 2016: Cellular and Molecular Life Sciences: CMLS
Bryan A Nerger, Michael J Siedlik, Celeste M Nelson
Cell-generated forces drive an array of biological processes ranging from wound healing to tumor metastasis. Whereas experimental techniques such as traction force microscopy are capable of quantifying traction forces in multidimensional systems, the physical mechanisms by which these forces induce changes in tissue form remain to be elucidated. Understanding these mechanisms will ultimately require techniques that are capable of quantifying traction forces with high precision and accuracy in vivo or in systems that recapitulate in vivo conditions, such as microfabricated tissues and engineered substrata...
December 22, 2016: Cellular and Molecular Life Sciences: CMLS
Nikita Minhas, Meilang Xue, Christopher J Jackson
Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. In this study, we found that APC enhanced endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor...
December 22, 2016: Cellular and Molecular Life Sciences: CMLS
Jutta Steinberger, Jennifer Chu, Rayelle Itoua Maïga, Katia Sleiman, Jerry Pelletier
Biotherapeutics have revolutionized modern medicine by providing medicines that would not have been possible with small molecules. With respect to cancer therapies, this represents the current sector of the pharmaceutical industry having the largest therapeutic impact, as exemplified by the development of recombinant antibodies and cell-based therapies. In cancer, one of the most common regulatory alterations is the perturbation of translational control. Among these, changes in eukaryotic initiation factor 4F (eIF4F) are associated with tumor initiation, progression, and drug resistance in a number of settings...
December 21, 2016: Cellular and Molecular Life Sciences: CMLS
Scott G Wilcockson, Catherine Sutcliffe, Hilary L Ashe
Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by traversing complex cellular landscapes to instruct the fate of distant cells. In this review, we explore different strategies adopted by cells to modulate signaling molecule range to allow correct patterning. We describe mechanisms for restricting signaling range and highlight how such short-range signaling can be exploited to not only control the fate of adjacent cells, but also to generate graded signaling within a field of cells...
December 20, 2016: Cellular and Molecular Life Sciences: CMLS
Chen-Yun Chen, Yuan-Yuan Cheng, Christopher Y T Yen, Patrick C H Hsieh
Mouse embryonic stem cells (mESCs), characterized by their pluripotency and capacity for self-renewal, are driven by a complex gene expression program composed of several regulatory mechanisms. These mechanisms collaborate to maintain the delicate balance of pluripotency gene expression and their disruption leads to loss of pluripotency. In this review, we provide an extensive overview of the key pillars of mESC pluripotency by elaborating on the various essential transcription factor networks and signaling pathways that directly or indirectly support this state...
December 20, 2016: Cellular and Molecular Life Sciences: CMLS
Claudia P Spampinato
The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015...
December 20, 2016: Cellular and Molecular Life Sciences: CMLS
Adnan S Syed, Alfredo Sansone, Thomas Hassenklöver, Ivan Manzini, Sigrun I Korsching
All olfactory receptors identified in teleost fish are expressed in a single sensory surface, whereas mammalian olfactory receptor gene families segregate into different olfactory organs, chief among them the main olfactory epithelium expressing ORs and TAARs, and the vomeronasal organ expressing V1Rs and V2Rs. A transitional stage is embodied by amphibians, with their vomeronasal organ expressing more 'modern', later diverging V2Rs, whereas more 'ancient', earlier diverging V2Rs are expressed in the main olfactory epithelium...
December 18, 2016: Cellular and Molecular Life Sciences: CMLS
Wenyan Hu, Shengguo Li, Ji Yeon Park, Sridhar Boppana, Ting Ni, Miaoxin Li, Jun Zhu, Bin Tian, Zhi Xie, Mengqing Xiang
The development of the central nervous system (CNS) is a complex process that must be exquisitely controlled at multiple levels to ensure the production of appropriate types and quantity of neurons. RNA alternative polyadenylation (APA) contributes to transcriptome diversity and gene regulation, and has recently been shown to be widespread in the CNS. However, the previous studies have been primarily focused on the tissue specificity of APA and developmental APA change of whole model organisms; a systematic survey of APA usage is lacking during CNS development...
December 18, 2016: Cellular and Molecular Life Sciences: CMLS
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
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