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Cellular and Molecular Life Sciences: CMLS

Patricio Atanes, Inmaculada Ruz-Maldonado, Ross Hawkes, Bo Liu, Min Zhao, Guo Cai Huang, Israa Mohammed Al-Amily, Albert Salehi, Stefan Amisten, Shanta J Persaud
INTRODUCTION: Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets. MATERIALS AND METHODS: GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC...
February 17, 2018: Cellular and Molecular Life Sciences: CMLS
Guy A Rutter, David J Hodson
The original version of this article unfortunately contained a mistake. Legends of Figures 1 and 2 were interchanged. The correct versions are given below.
February 15, 2018: Cellular and Molecular Life Sciences: CMLS
Srdja Drakulic, Jay Rai, Steen Vang Petersen, Monika M Golas, Bjoern Sander
The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and progressive neurodegeneration. The majority of cases are caused by variants in the gene encoding the PDC subunit E1α. The molecular effects of the variants, however, remain poorly understood. Using yeast as a eukaryotic model system, we have studied the substitutions A189V, M230V, and R322C in yeast E1α (corresponding to the pathogenic variants A169V, M210V, and R302C in human E1α) and evaluated how substitutions of single amino acid residues within different functional E1α regions affect PDC structure and activity...
February 14, 2018: Cellular and Molecular Life Sciences: CMLS
Alexander Negoda, Elizabeth A Cowley, Yassine El Hiani, Paul Linsdell
Cystic fibrosis can be treated by potentiators, drugs that interact directly with the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel to increase its open probability. These substances likely target key conformational changes occurring during channel opening and closing, however, the molecular bases of these conformational changes, and their susceptibility to manipulation are poorly understood. We have used patch clamp recording to identify changes in the three-dimensional organization of the extracellularly accessible parts of the CFTR protein during channel opening and closing...
February 14, 2018: Cellular and Molecular Life Sciences: CMLS
Nasibeh Karimi, Aleksander Cvjetkovic, Su Chul Jang, Rossella Crescitelli, Mohammad Ali Hosseinpour Feizi, Rienk Nieuwland, Jan Lötvall, Cecilia Lässer
The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8-12, while the bulk of the plasma proteins was present in fractions 11-28...
February 13, 2018: Cellular and Molecular Life Sciences: CMLS
Giel Tanghe, Corinne Urwyler-Rösselet, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, Wim Declercq
RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state...
February 12, 2018: Cellular and Molecular Life Sciences: CMLS
Lin Long, Xiao-Xiao Pang, Fei Lei, Jia-Sheng Zhang, Wei Wang, Lian-Di Liao, Xiu-E Xu, Jian-Zhong He, Jian-Yi Wu, Zhi-Yong Wu, Li-Dong Wang, De-Chen Lin, En-Min Li, Li-Yan Xu
The human riboflavin transporter-3 (encoded by SLC52A3) plays a prominent role in riboflavin absorption. Interestingly, abnormal expression patterns of SLC52A3 in multiple types of human cancers have been recently noted. However, the molecular mechanisms underlying its dysregulation remain unclear. In this study, we find that SLC52A3 has two transcript variants that differ in the transcriptional start site, and encode different proteins: SLC52A3a and SLC52A3b. Importantly, aberrant expressions of SLC52A3 are associated with stepwise development of esophageal squamous cell carcinoma (ESCC) as well as the survival rates of ESCC patients...
February 10, 2018: Cellular and Molecular Life Sciences: CMLS
Noel A Warren, Georgios Voloudakis, Yonejung Yoon, Nikolaos K Robakis, Anastasios Georgakopoulos
Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-α, and increases MLC2 phosphorylation...
February 10, 2018: Cellular and Molecular Life Sciences: CMLS
Stefano Sala, Christophe Ampe
Nuclear receptors are ligand-activated transcription factors that partake in several biological processes including development, reproduction and metabolism. Over the last decade, evidence has accumulated that group 2, 3 and 4 LIM domain proteins, primarily known for their roles in actin cytoskeleton organization, also partake in gene transcription regulation. They shuttle between the cytoplasm and the nucleus, amongst other as a consequence of triggering cells with ligands of nuclear receptors. LIM domain proteins act as important coregulators of nuclear receptor-mediated gene transcription, in which they can either function as coactivators or corepressors...
February 10, 2018: Cellular and Molecular Life Sciences: CMLS
Chao Liu, Yanjie Ma, Yongliang Shang, Ran Huo, Wei Li
The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
Andrew A Walker, Maria José Hernández-Vargas, Gerardo Corzo, Bryan G Fry, Glenn F King
True Bugs (Insecta: Heteroptera) produce venom or saliva with diverse bioactivities depending on their feeding strategies. However, little is known about the molecular evolution of the venom toxins underlying these biological activities. We examined venom of the giant fish-killing water bug Lethocerus distinctifemur (Insecta: Belostomatidae) using infrared spectroscopy, transcriptomics, and proteomics. We report 132 venom proteins including putative enzymes, cytolytic toxins, and antimicrobial peptides. Over 73% (96 proteins) showed homology to venom proteins from assassin bugs (Reduviidae), including 21% (28 proteins from seven families) not known from other sources...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
Gengyang Shen, Hui Ren, Qi Shang, Ting Qiu, Xiang Yu, Zhida Zhang, Jinjing Huang, Wenhua Zhao, Yuzhuo Zhang, De Liang, Xiaobing Jiang
Autophagy takes part in regulating the eukaryotic cells function and the progression of numerous diseases, but its clinical utility has not been fully developed yet. Recently, mounting evidences highlight an important correlation between autophagy and bone homeostasis, mediated by osteoclasts, osteocytes, bone marrow mesenchymal stem cells, and osteoblasts, and autophagy plays a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The combinations of autophagy activators/inhibitors with anti-GIOP first-line drugs or some new autophagy-based manipulators, such as regulation of B cell lymphoma 2 family proteins and caspase-dependent clearance of autophagy-related gene proteins, are likely to be the promising approaches for GIOP clinical treatments...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
Ana L Santos, Giulio Preta
Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular signalling...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
Silvia H De Paoli, Tseday Z Tegegn, Oumsalama K Elhelu, Michael B Strader, Mehulkumar Patel, Lukas L Diduch, Ivan D Tarandovskiy, Yong Wu, Jiwen Zheng, Mikhail V Ovanesov, Abdu Alayash, Jan Simak
Platelet extracellular vesicles (PEVs) have emerged as potential mediators in intercellular communication. PEVs exhibit several activities with pathophysiological importance and may serve as diagnostic biomarkers. Here, imaging and analytical techniques were employed to unveil morphological pathways of the release, structure, composition, and surface properties of PEVs derived from human platelets (PLTs) activated with the thrombin receptor activating peptide (TRAP). Based on extensive electron microscopy analysis, we propose four morphological pathways for PEVs release from TRAP-activated PLTs: (1) plasma membrane budding, (2) extrusion of multivesicular α-granules and cytoplasmic vacuoles, (3) plasma membrane blistering and (4) "pearling" of PLT pseudopodia...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
Boxiao Wang, Stephanie Thurmond, Rong Hai, Jikui Song
Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses...
February 8, 2018: Cellular and Molecular Life Sciences: CMLS
Jihye Choi, Kwang-Hyun Baek
Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin-proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery...
February 8, 2018: Cellular and Molecular Life Sciences: CMLS
Marie-Chantal Grégoire, Frédéric Leduc, Martin H Morin, Tiphanie Cavé, Mélina Arguin, Martin Richter, Pierre-Étienne Jacques, Guylain Boissonneault
De novo germline mutations arise preferentially in male owing to fundamental differences between spermatogenesis and oogenesis. Post-meiotic chromatin remodeling in spermatids results in the elimination of most of the nucleosomal supercoiling and is characterized by transient DNA fragmentation. Using three alternative methods, DNA from sorted populations of mouse spermatids was used to confirm that double-strand breaks (DSB) are created in elongating spermatids and repaired at later steps. Specific capture of DSB was used for whole-genome mapping of DSB hotspots (breakome) for each population of differentiating spermatids...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
Alan N Engelman, Parmit K Singh
Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
Pauline De Berdt, Pauline Bottemanne, John Bianco, Mireille Alhouayek, Anibal Diogenes, Amy Llyod, Jose Gerardo-Nava, Gary A Brook, Véronique Miron, Giulio G Muccioli, Anne des Rieux
Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
Jin Zhang, Guan Wang, Yuxin Zhou, Yi Chen, Liang Ouyang, Bo Liu
Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
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