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Alpha cell

Jitka Rybová, Ladislav Kuchar, Helena Hulková, Befekadu Asfaw, Robert Dobrovolný, Jakub Sikora, Vladimír Havlícek, Ludovít Škultéty, Jana Ledvinová
Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate - globotriaosylceramide (Gb3Cer) - B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease - FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Herein, we provide a comprehensive overview of the biochemical and structural abnormalities in pancreatic tissue from two male FD patients with blood group B...
March 14, 2018: Glycobiology
Christelle Sanchez, Gabriel Mazzucchelli, Cécile Lambert, Fanny Comblain, Edwin DePauw, Yves Henrotin
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone. DESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients...
2018: PloS One
Jeffrey Zielich, Elena Tzima, Eva Ayla Schröder, Faten Jemel, Barbara Conradt, Eric J Lambie
P5B ATPases are present in the genomes of diverse unicellular and multicellular eukaryotes, indicating that they have an ancient origin, and that they are important for cellular fitness. Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). The presence of an invariant PPALP motif within the putative substrate interaction pocket of transmembrane segment M4 suggests that all P5B ATPases might have similar transport specificity; however, the identity of the transport substrate(s) remains unknown...
2018: PloS One
Joseph D Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F Guimaraes, Darren A N Cook, Andrew Steven, Nico Van Rooijen, Judith E Allen, Stephen J Jenkins, Mark J Taylor
Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection...
March 16, 2018: PLoS Pathogens
Allison A Lindgren, Adam R Filipowicz, Julian B Hattler, Soon Ok Kim, Hye Kyung Chung, Marcelo J Kuroda, Edward M Johnson, Woong-Ki Kim
OBJECTIVE: HIV-1 infection of the brain and related cognitive impairment remain prevalent in HIV-1-infected subjects despite combination antiretroviral therapy. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a newly identified host restriction factor that blocks the replication of HIV-1 and other retroviruses in myeloid cells. Cell-cycle-regulated phosphorylation at residue Thr592 and viral protein X (Vpx)-mediated degradation of SAMHD1 have been shown to bypass SAMHD1 restriction in vitro...
March 15, 2018: AIDS
Haline G O Alvim, Jose Raimundo Correa, José A F Assumpção, Wender Alves da Silva, Marcelo Oliveira Rodrigues, Julio Lemos de Macedo, Mariana Fioramonte, Fabio Cesar Gozzo, Claudia C Gatto, Brenno A D Neto
The current manuscript describes the use of a heteropolyacid-containing task-specific ionic liquid, supported in imidazolium-based ionic liquids, as the catalyst for an efficient multicomponent synthesis of hexahydroimidazo[1,2-alpha]pyridine derivatives. The reactions conditions were fully optimized and the bridgehead nitrogen heterocycle derivatives could be obtained in just one hour exclusively as a single isomer (trans). Single crystal X-ray analysis confirmed the trans derivative as the only isomer. The mechanism of the reaction was investigated by ESI(+)-MS(/MS) and the use of the elegant charge-tag strategy allowed a catalytic cycle to be proposed for the current transformation and revealed the possibility of at least two reaction pathways...
March 16, 2018: Journal of Organic Chemistry
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
Huizhen Fan, Chunyan Jiang, Baoyuan Zhong, Jianwen Sheng, Ting Chen, Qingqing Chen, Jingtao Li, Hongchuan Zhao
Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF- α ), transforming growth factor beta 1 (TGF- β 1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism...
2018: Journal of Immunology Research
Onoufrios Tsavaris, Panagiota Economopoulou, Ioannis Kotsantis, Lazaros Reppas, Chrysanthi Avgerinou, Nikolaos Spathas, Maria Prevezanou, Amanda Psyrri
Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT), fibroblast growth factor receptor (FGFR), PDGFR, and vascular endothelial growth factor receptor (VEGFR) and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma...
2018: Frontiers in Oncology
Sheng Zhang, Chengrong Xie, Honghe Li, Kang Zhang, Jie Li, Xiaomin Wang, Zhenyu Yin
Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo. A large body of evidence supports a link between UPS11 and tumorigenesis. However, the clinical significance and biological function of USP11 in hepatocellular carcinoma (HCC) remains unclear. Here, USP11 expression was assessed by immunohistochemistry in a pilot series of 71 HCC clinical samples, and the association between USP11 expression and clinicopathological features and overall survival time was analyzed...
March 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kimberly R Kalli, Matthew S Block, Pashtoon M Kasi, Courtney L Erskine, Timothy J Hobday, Allan Dietz, Douglas Padley, Michael P Gustafson, Barath Shreeder, Danell Puglisi-Knutson, Daniel W Visscher, Toni Kay Mangskau, Glynn Wilson, Keith L Knutson
PURPOSE: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sophie Poty, Lynn C Francesconi, Michael R McDevitt, Michael J Morris, Jason S Lewis
With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their wide-spread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
He Wang, Jianjia Li, Xiaoyi Zhang, Tingting Ning, Dandan Ma, Yihong Ge, Shuaimei Xu, Yilin Hao, Buling Wu
To seek a potential target for periodontal tissue regeneration, this study aimed to explore the role of Integrin alpha 5 (ITGA5) in human periodontal ligament stem cells (PDLSCs). Transwell assay, Cell Counting Kit 8 (CCK8) assay, cell cycle assay, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot were used to investigate the effects of ITGA5 on PDLSC migration, proliferation and osteogenic differentiation. The in vivo effect was investigated by nude mice subcutaneous transplantation with cell and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) complex...
March 12, 2018: Journal of Proteomics
Yuichi Goto, Yoshihiro Uchino, Shin Sasaki, Nobuhisa Shirahama, Yoriko Nomura, Jun Akiba, Hiroto Ishikawa, Yoshito Akagi, Hiroyuki Tanaka, Koji Okuda
INTRODUCTION: We report a rare case of complete spontaneous necrosis of a hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT), as confirmed by resection. CASE PRESENTATION: A 64-year-old man was referred to our hospital for suspected HCC. Contrast-enhanced computed tomography (CECT) findings before admission revealed a 53-mm tumor in the posterior segment of the liver and were suspicious for PVTT in the right posterior PV. Both alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were elevated at 17,562 ng/mL and 153 mAU/mL, respectively...
March 7, 2018: International Journal of Surgery Case Reports
Carmen J Zamora-Sánchez, Aylin Del Moral-Morales, Ana M Hernández-Vega, Valeria Hansberg-Pastor, Ivan Salido-Guadarrama, Mauricio Rodríguez-Dorantes, Ignacio Camacho-Arroyo
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes...
March 15, 2018: International Journal of Molecular Sciences
Debanti Sengupta, Tae Jin Kim, Sepideh Almasi, Stuart Miller, Zsolt Marton, Vivek Nagarkar, Guillem Pratx
Radioluminescence microscopy is an emerging modality that can be used to image radionuclide probes with micron-scale resolution. This technique is particularly useful as a way to probe the metabolic behavior of single cells and to screen and characterize radiopharmaceuticals, but the quality of the images is critically dependent on the scintillator material used to image the cells. In this paper, we detail the development of a microscopy dish made of a thin-film scintillating material, Lu2O3:Eu, that could be used as the blueprint for a future consumable product...
March 15, 2018: Analyst
Byoung Il Je, Fang Xu, Qingyu Wu, Lei Liu, Robert Meeley, Joseph P Gallagher, Leo Corcilius, Richard J Payne, Madelaine E Bartlett, David Jackson
Meristems contain groups of indeterminate stem cells, which are maintained by a feedback loop between CLAVATA ( CLV ) and WUSCHEL ( WUS ) signaling. CLV signaling involves the secretion of the CLV3 peptide and its perception by a number of Leucine-Rich-Repeat (LRR) receptors, including the receptor-like kinase CLV1 and the receptor-like protein CLV2 coupled with the CORYNE (CRN) pseudokinase. CLV2, and its maize ortholog FASCIATED EAR2 (FEA2) appear to function in signaling by CLV3 and several related CLV3/EMBRYO-SURROUNDING REGION (CLE) peptide ligands...
March 15, 2018: ELife
Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Xiaoye Yang, Xiaoqun Shi, Jianbo Ji, Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs)...
November 2018: Drug Delivery
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