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https://www.readbyqxmd.com/read/29040558/constitutively-active-fgfr3-disrupts-primary-cilium-length-and-ift20-trafficking-in-various-chondrocyte-models-of-achondroplasia
#1
Ludovic Martin, Nabil Kaci, Valentin Estibals, Nicolas Goudin, Meriem Garfa-Traore, Catherine Benoist-Lasselin, Emilie Dambroise, Laurence Legeai-Mallet
FGFR3 (fibroblast growth factor receptor 3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively-active FGFR3 perturbed PC length and the sorting and trafficking of IFT20 to the PC...
October 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29035720/an-internationally-standardized-species-identification-test-for-use-on-suspected-seized-rhinoceros-horn-in-the-illegal-wildlife-trade
#2
Kyle M Ewart, Greta J Frankham, Ross McEwing, Lucy M I Webster, Sherryn A Ciavaglia, Adrian M T Linacre, Dang Tat The, Kanitia Ovouthan, Rebecca N Johnson
Rhinoceros (rhino) numbers have dwindled substantially over the past century. As a result, three of the five species are now considered to be critically endangered, one species is vulnerable and one species is near-threatened. Poaching has increased dramatically over the past decade due to a growing demand for rhino horn products, primarily in Asia. Improved wildlife forensic techniques, such as validated tests for species identification of seized horns, are critical to aid current enforcement and prosecution efforts and provide a deterrent to future rhino horn trafficking...
October 7, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#3
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29031909/the-retromer-subunit-vps26-mediates-notch-signaling-during-drosophila-oogenesis
#4
Rebecca Starble, Nancy J Pokrywka
During endocytosis, molecules are internalized by the cell through the invagination of the plasma membrane. Endocytosis is required for proper cell function and for normal development in Drosophila. One component of the endocytic pathway is the retromer complex, which recycles transmembrane proteins to other parts of the cell such as the plasma membrane and the trans-Golgi network. Previous studies have shown that mutations to the retromer complex result in developmental defects in Drosophila. In humans, retromer dysfunction has been implicated in Alzheimer's and Parkinson's disease, but little is known about the role of the retromer complex in Drosophila oogenesis...
October 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/29030552/bad-lamp-controls-tlr9-trafficking-and-signalling-in-human-plasmacytoid-dendritic-cells
#5
Alexis Combes, Voahirana Camosseto, Prudence N'Guessan, Rafael J Argüello, Julie Mussard, Christophe Caux, Nathalie Bendriss-Vermare, Philippe Pierre, Evelina Gatti
Toll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1(+) late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3(+/)LAMP2(+/)LAMP1(-) endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29028839/interaction-of-the-human-respiratory-syncytial-virus-matrix-protein-with-cellular-adaptor-protein-complex-3-plays-a-critical-role-in-trafficking
#6
Casey Ward, Maciej Maselko, Christopher Lupfer, Meagan Prescott, Manoj K Pastey
Human Respiratory Syncytial Virus (HRSV) is a leading cause of bronchopneumonia in infants and the elderly. To date, knowledge of viral and host protein interactions within HRSV is limited and are critical areas of research. Here, we show that HRSV Matrix (M) protein interacts with the cellular adaptor protein complex 3 specifically via its medium subunit (AP-3Mu3A). This novel protein-protein interaction was first detected via yeast-two hybrid screen and was further confirmed in a mammalian system by immunofluorescence colocalization and co-immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/29024942/loss-of-myosin-vb-in-colorectal-cancer-is-a-strong-prognostic-factor-for-disease-recurrence
#7
Elisabeth Letellier, Martine Schmitz, Aurélien Ginolhac, Fabien Rodriguez, Pit Ullmann, Komal Qureshi-Baig, Sonia Frasquilho, Laurent Antunes, Serge Haan
BACKGROUND: Selecting the most beneficial treatment regimens for colorectal cancer (CRC) patients remains challenging due to a lack of prognostic markers. Members of the Myosin family, proteins recognised to have a major role in trafficking and polarisation of cells, have recently been reported to be closely associated with several types of cancer and might thus serve as potential prognostic markers in the context of CRC. METHODS: We used a previously established meta-analysis of publicly available gene expression data to analyse the expression of different members of the Myosin V family, namely MYO5A, 5B, and 5C, in CRC...
October 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29024922/isolation-and-whole-genome-analysis-of-endospore-forming-bacteria-from-heroin
#8
Jörn Kalinowski, Björn Ahrens, Arwa Al-Dilaimi, Anika Winkler, Daniel Wibberg, Uwe Schleenbecker, Christian Rückert, Roman Wölfel, Gregor Grass
Infections caused by endospore-forming bacteria have been associated with severe illness and death among persons who inject drugs. Analysis of the bacteria residing in heroin has thus been biased towards species that affect human health. Similarly, exploration of the bacterial diversity of seized street market heroin correlated with the skin microflora of recreational heroin users insofar as different Staphylococus spp. or typical environmental endospore formers including Bacillus cereus and other Bacilli outside the B...
October 4, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29023380/the-gut-microbiome-feelings-of-the-brain-a-perspective-for-non-microbiologists
#9
REVIEW
Aaron Lerner, Sandra Neidhöfer, Torsten Matthias
Objectives: To comprehensively review the scientific knowledge on the gut-brain axis. Methods: Various publications on the gut-brain axis, until 31 July 2017, were screened using the Medline, Google, and Cochrane Library databases. The search was performed using the following keywords: "gut-brain axis", "gut-microbiota-brain axis", "nutrition microbiome/microbiota", "enteric nervous system", "enteric glial cells/network", "gut-brain pathways", "microbiome immune system", "microbiome neuroendocrine system" and "intestinal/gut/enteric neuropeptides"...
October 12, 2017: Microorganisms
https://www.readbyqxmd.com/read/29021306/characterization-of-a-human-induced-pluripotent-stem-cell-derived-cardiomyocyte-model-for-the-study-of-variant-pathogenicity-validation-of-a-kcnj2-mutation
#10
Roselle Gélinas, Nabil El Khoury, Marie-A Chaix, Claudine Beauchamp, Azadeh Alikashani, Nathalie Ethier, Gabrielle Boucher, Louis Villeneuve, Laura Robb, Frédéric Latour, Blandine Mondesert, Lena Rivard, Philippe Goyette, Mario Talajic, Céline Fiset, John David Rioux
BACKGROUND: Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality. Long-QT syndrome could, therefore, benefit from having a standardized platform for functional characterization of candidate variants in the physiological context of human cardiomyocytes...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29021280/primary-cilium-formation-and-ciliary-protein-trafficking-is-regulated-by-the-atypical-map-kinase-mapk15-in-caenorhabditis-elegans%C3%A2-and-human-cells
#11
Anna Kazatskaya, Stefanie Kuhns, Nils J Lambacher, Julie E Kennedy, Andrea G Brear, Gavin J McManus, Piali Sengupta, Oliver E Blacque
Motile and immotile (or primary) cilia are microtubule-based structures that mediate multiple cellular functions including transduction of environmental cues, developmental signaling, cellular motility, and modulation of fluid flow. Although their core architectures are similar, motile and primary cilia exhibit marked structural differences that underlie distinct functional properties. However, the extent to which ciliogenesis mechanisms are shared between these different cilia types is not fully described...
October 11, 2017: Genetics
https://www.readbyqxmd.com/read/29021220/an-apicosome-initiates-self-organizing-morphogenesis-of-human-pluripotent-stem-cells
#12
Kenichiro Taniguchi, Yue Shao, Ryan F Townshend, Chari L Cortez, Clair E Harris, Sasha Meshinchi, Sundeep Kalantry, Jianping Fu, K Sue O'Shea, Deborah L Gumucio
Human pluripotent stem cells (hPSCs) self-organize into apicobasally polarized cysts, reminiscent of the lumenal epiblast stage, providing a model to explore key morphogenic processes in early human embryos. Here, we show that apical polarization begins on the interior of single hPSCs through the dynamic formation of a highly organized perinuclear apicosome structure. The membrane surrounding the apicosome is enriched in apical markers and displays microvilli and a primary cilium; its lumenal space is rich in Ca(2+) Time-lapse imaging of isolated hPSCs reveals that the apicosome forms de novo in interphase, retains its structure during mitosis, is asymmetrically inherited after mitosis, and relocates to the recently formed cytokinetic plane, where it establishes a fully polarized lumen...
October 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29020060/phosphatidylinositol-4-5-bisphosphate-is-required-for-kcnq1-kcne1-channel-function-but-not-anterograde-trafficking
#13
Alice A Royal, Andrew Tinker, Stephen C Harmer
The slow delayed-rectifier potassium current (IKs) is crucial for human cardiac action potential repolarization. The formation of IKs requires co-assembly of the KCNQ1 α-subunit and KCNE1 β-subunit, and mutations in either of these subunits can lead to hereditary long QT syndrome types 1 and 5, respectively. It is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. We previously identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that form a PIP2/phosphoinositide binding site...
2017: PloS One
https://www.readbyqxmd.com/read/29019810/management-of-patients-who-receive-an-organ-transplant-abroad-and-return-home-for-follow-up-care-recommendations-from-the-declaration-of-istanbul-custodian-group
#14
Beatriz Domínguez-Gil, Gabriel Danovitch, Dominique E Martin, Marta López-Fraga, Kristof Van Assche, Michele L Morris, Jacob Lavee, Gilad Erlich, Riadh Fadhil, Mirela Busic, Glynn Rankin, Mona Al-Rukhaimi, Philip O Connell, Jacqueline Chin, Triona Norman, Pablo Massari, Refaat Kamel, Francis L Delmonico
Eradicating transplant tourism depends upon complex solutions that include efforts to progress towards self-sufficiency in transplantation. Meanwhile, professionals and authorities are faced with medical, legal, and ethical problems raised by patients who return home after receiving an organ transplant abroad, particularly when the organ has been obtained through illegitimate means. In 2016, the Declaration of Istanbul Custodian Group convened an international, multidisciplinary workshop in Madrid, Spain, to address these challenges and provide recommendations for the management of these patients, which are presented in this paper...
October 11, 2017: Transplantation
https://www.readbyqxmd.com/read/29019354/iron-sulfur-cluster-biosynthesis-and-trafficking-impact-on-human-disease-conditions
#15
C Wachnowsky, I Fidai, J A Cowan
Iron-sulfur clusters (Fe-S) are one of the most ancient, ubiquitous and versatile classes of metal cofactors found in nature. Proteins that contain Fe-S clusters constitute one of the largest families of proteins, with varied functions that include electron transport, regulation of gene expression, substrate binding and activation, radical generation, and, more recently discovered, DNA repair. Research during the past two decades has shown that mitochondria are central to the biogenesis of Fe-S clusters in eukaryotic cells via a conserved cluster assembly machinery (ISC assembly machinery) that also controls the synthesis of Fe-S clusters of cytosolic and nuclear proteins...
October 11, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29016857/biallelic-mutation-of-unc50-encoding-a-protein-involved-in-achr-trafficking-is-responsible-for-arthrogryposis
#16
Emanuela Abiusi, Manuela D'Alessandro, Klaus Dieterich, Loic Quevarec, Sandrina Turczynski, Aurore-Cecile Valfort, Paulette Mezin, Pierre Simon Jouk, Marta Gut, Ivo Gut, Jean Louis Bessereau, Judith Melki
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Homozygosity mapping of disease loci combined with whole exome sequencing in a consanguineous family presenting with lethal AMC allowed the identification of a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4) in the index case. To assess the effect of the mutation, an equivalent mutation in the Caenorhabditis elegans orthologous gene was created using CRISPR/Cas9...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993644/membrane-trafficking-modulation-during-entamoeba-encystation
#17
Emily Herman, Maria A Siegesmund, Michael J Bottery, Ronny van Aerle, Maulood Mohammed Shather, Elisabet Caler, Joel B Dacks, Mark van der Giezen
Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Lectins and chitin are secreted to form the cyst wall, although little is known about the underlying membrane trafficking processes supporting encystation. As E. histolytica does not readily form cysts in vitro, we assessed membrane trafficking gene expression during encystation in the closely related model Entamoeba invadens...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28992183/er-stress-induced-aggresome-trafficking-of-htra1-protects-against-proteotoxicity
#18
Maximilian J Gerhardt, Joseph A Marsh, Margaux Morrison, Andrius Kazlauskas, Arogya Khadka, Stephan Rosenkranz, Margaret M DeAngelis, Magali Saint-Geniez, Sarah Melissa P Jacobo
High temperature requirement A1 (HtrA1) belongs to an ancient protein family that is linked to various human disorders. The precise role of exon 1-encoded N-terminal domains and how these influence the biological functions of human HtrA1 remain elusive. In this study, we traced the evolutionary origins of these N-terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hypothesized that human HtrA1 is implicated in unfolded protein response. In highly secretory cells of the retinal pigmented epithelia, endoplasmic reticulum (ER) stress upregulated HtrA1...
August 10, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28990113/downregulation-of-syt7-inhibits-glioblastoma-growth-by-promoting-cellular-apoptosis
#19
Bing Xiao, Jianbin Li, Yanghua Fan, Minhua Ye, Shigang Lv, Bin Xu, Yi Chai, Zhiqing Zhou, Miaojing Wu, Xingen Zhu
Synaptotagmin‑7 (SYT7) is a member of the synaptotagmin gene family, and encodes a protein that mediates the calcium‑dependent regulation of membrane trafficking during synaptic transmission. A previous study demonstrated that the expression of SYT7 is associated with prostate cancer and serves an important role in development of prostate cancer. However, the roles of SYT7 in the progression of glioma remain unknown. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis demonstrated that SYT7 was expressed in three human glioma cell lines...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28989857/jc-polyomavirus-attachment-and-entry-potential-sites-for-pml-therapeutics
#20
Colleen L Mayberry, Christian D S Nelson, Melissa S Maginnis
PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML...
September 2017: Current Clinical Microbiology Reports
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