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Organ trafficking

Jason M Lindo, María Padilla-Romo
This study considers the effects of the kingpin strategy, an approach to fighting organized crime in which law-enforcement efforts focus on capturing the leaders of criminal organizations, on community violence in the context of Mexico's drug war. Newly constructed historical data on drug-trafficking organizations' areas of operation at the municipality level and monthly homicide data allow us to control for a rich set of fixed effects and to leverage variation in the timing of kingpin captures to estimate their effects...
February 21, 2018: Journal of Health Economics
Hanaa Safya, Amine Mellouk, Julie Legrand, Sylvain M Le Gall, Mohcine Benbijja, Colette Kanellopoulos-Langevin, Jean M Kanellopoulos, Pierre Bobé
A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5'-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RBlow Tconvs, but not CD45RBhigh Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RBlow Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression...
2018: Frontiers in Immunology
Emily K Herman, Lyto Yiangou, Diego M Cantoni, Christopher N Miller, Francine Marciano-Cabral, Erin Anthonyrajah, Joel B Dacks, Anastasios D Tsaousis
Although the Golgi apparatus has a conserved morphology of flattened stacked cisternae in most eukaryotes, it has lost the stacked organization in several lineages, raising the question of what range of morphologies is possible for the Golgi. In order to understand this diversity, it is necessary to characterise the Golgi in many different lineages. Here we identify the Golgi apparatus in Naegleria , the first description of an unstacked Golgi organelle in a non-parasitic eukaryote, other than fungi. We provide a comprehensive list of Golgi-associated membrane trafficking genes encoded in two species of Naegleria and show that nearly all are expressed in mouse-passaged N...
March 13, 2018: Journal of Cell Science
Hui Huang, Georg Kuenze, Jarrod A Smith, Keenan C Taylor, Amanda M Duran, Arina Hadziselimovic, Jens Meiler, Carlos G Vanoye, Alfred L George, Charles R Sanders
Mutations that induce loss of function (LOF) or dysfunction of the human KCNQ1 channel are responsible for susceptibility to a life-threatening heart rhythm disorder, the congenital long QT syndrome (LQTS). Hundreds of KCNQ1 mutations have been identified, but the molecular mechanisms responsible for impaired function are poorly understood. We investigated the impact of 51 KCNQ1 variants with mutations located within the voltage sensor domain (VSD), with an emphasis on elucidating effects on cell surface expression, protein folding, and structure...
March 2018: Science Advances
Jonas Reinholz, Christopher Diesler, Susanne Schöttler, Maria Kokkinopoulou, Sandra Ritz, Katharina Landfester, Volker Mailänder
The transport of nanocarriers through barriers like the gut in a living organism involves the transcytosis of these nanocarriers through the cell layer dividing two compartments. Understanding how this process works is not only essential to further developing strategies for a more effective nanocarrier transport system but also for providing fundamental insights into the barrier function as a means of protection against micro- and nanoplastics in the food chain. We therefore set out to investigate the different uptake mechanisms, intracellular trafficking and the routes for exocytosis for small polystyrene nanoparticles (PS-NPs ca...
March 9, 2018: Acta Biomaterialia
Alexander G Toth, Ojmarrh Mitchell
BACKGROUND: The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. METHODS: Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations...
March 7, 2018: International Journal on Drug Policy
Qiang-Nan Feng, Xin Liang, Sha Li, Yan Zhang
Pollen tube growth is an essential step for successful plant reproduction. Vacuolar trafficking and dynamic organization are important for pollen tube growth; however, the key proteins involved in these processes are not well understood. Here, we report that the ADAPTOR PROTEIN-3 (AP-3) complex and its tonoplast cargo PROTEIN S-ACYL TRANSFERASE10 (PAT10) are critical for pollen tube growth in Arabidopsis (Arabidopsis thaliana). AP-3 is a heterotetrameric protein complex consisting of four subunits, δ, β, µ, and σ...
March 9, 2018: Plant Physiology
Anna Kabanova, Vanessa Zurli, Cosima Tatiana Baldari
Cytotoxic immunity relies on specialized effector T cells, the cytotoxic T cells, which are endowed with specialized cytolytic machinery that permits them to induce death of their targets. Upon recognition of a target cell, cytotoxic T cells form a lytic immune synapse and by docking the microtubule-organizing center at the synaptic membrane get prepared to deliver a lethal hit of enzymes contained in lytic granules. New insights suggest that the directionality of lytic granule trafficking along the microtubules represents a fine means to tune the functional outcome of the encounter between a T cell and its target...
2018: Frontiers in Immunology
Luc Tappy
Compared with other carbohydrates, fructose-containing caloric sweeteners (sucrose, high-fructose corn syrup, pure fructose and fructose-glucose mixtures) are characterized by: a sweet taste generally associated with a positive hedonic tone; specific intestinal fructose transporters, i.e. GLUT5; a two-step fructose metabolism, consisting of the conversion of fructose carbones into ubiquitous energy substrates in splanchnic organs where fructolytic enzymes are expressed, and secondary delivery of these substrates to extrasplanchnic tissues...
March 7, 2018: Journal of Experimental Biology
Maren Mönnich, Louise Borgeskov, Loretta Breslin, Lis Jakobsen, Michaela Rogowski, Canan Doganli, Jacob M Schrøder, Johanne B Mogensen, Louise Blinkenkjær, Lea M Harder, Emma Lundberg, Stefan Geimer, Søren T Christensen, Jens S Andersen, Lars A Larsen, Lotte B Pedersen
The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling...
March 6, 2018: Cell Reports
Lael D Barlow, Eva Nývltová, Maria Aguilar, Jan Tachezy, Joel B Dacks
BACKGROUND: The Golgi apparatus is a central meeting point for the endocytic and exocytic systems in eukaryotic cells, and the organelle's dysfunction results in human disease. Its characteristic morphology of multiple differentiated compartments organized into stacked flattened cisternae is one of the most recognizable features of modern eukaryotic cells, and yet how this is maintained is not well understood. The Golgi is also an ancient aspect of eukaryotes, but the extent and nature of its complexity in the ancestor of eukaryotes is unclear...
March 7, 2018: BMC Biology
Laura F Gumy, Casper C Hoogenraad
The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts...
March 3, 2018: Current Opinion in Neurobiology
Cheri M Ackerman, Peter K Weber, Tong Xiao, Bao Thai, Tiffani J Kuo, Emily Zhang, Jennifer Pett-Ridge, Christopher J Chang
Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases...
March 6, 2018: Metallomics: Integrated Biometal Science
Ludmila Karen Dos Santos Silva, Ana Cláudia Dos Santos Pereira Andrade, Fábio Pio Dornas, Rodrigo Araújo Lima Rodrigues, Thalita Arantes, Erna Geessien Kroon, Cláudio Antônio Bonjardim, Jônatas Santos Abrahão
The giant viruses are the largest and most complex viruses in the virosphere. In the last decade, new members have constantly been added to this group. Here, we provide an in-depth descriptive analysis of the replication cycle of Cedratvirus getuliensis, one of the largest viruses known to date. We tracked the virion entry, the early steps of virus factory and particles morphogenesis, and during this phase, we observed a complex and unique sequential organization of immature particle elements, including horseshoe and rectangular compartments, revealed by transverse and longitudinal sections, respectively, until the formation of the final ovoid-shaped striped virion...
March 5, 2018: Scientific Reports
Staci L Haney, Yashpal S Chhonker, Michelle L Varney, Geoffrey Talmon, Daryl J Murry, Sarah A Holstein
Geranylgeranyl diphosphate synthase (GGDPS) is the enzyme in the isoprenoid biosynthesis pathway that catalyzes the synthesis of the 20-carbon isoprenoid GGPP, which serves as the isoprenoid donor for protein geranylgeranylation reactions. Rab proteins mediate vesicle trafficking within the cell and their activity is dependent on geranylgeranylation. Our prior work has demonstrated that agents that disrupt Rab geranylgeranylation disrupt monoclonal protein trafficking in myeloma cells, resulting in induction of the unfolded protein response pathway and apoptosis...
March 2, 2018: Investigational New Drugs
Colin Adrain, Sivan Henis-Korenblit, Pedro M Domingos
It was a sunny Ericeira, in Portugal, that received the participants of the EMBO Workshop on Proteostasis, from 17 to 21 November 2017. Most participants gave talks or presented posters concerning their most recent research results, and lively scientific discussions occurred against the backdrop of the beautiful Atlantic Ocean.Proteostasis is the portmanteau of the words protein and homeostasis, and it refers to the biological mechanisms controlling the biogenesis, folding, trafficking and degradation of proteins in cells...
March 1, 2018: Journal of Cell Science
Colin D Donohoe, Gábor Csordás, Andreia Correia, Marek Jindra, Corinna Klein, Bianca Habermann, Mirka Uhlirova
Interplay between apicobasal cell polarity modules and the cytoskeleton is critical for differentiation and integrity of epithelia. However, this coordination is poorly understood at the level of gene regulation by transcription factors. Here, we establish the Drosophila activating transcription factor 3 (atf3) as a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the tumor suppressors Scribble or Dlg1 induces atf3 expression via aPKC but independent of Jun-N-terminal kinase (JNK) signaling...
March 1, 2018: PLoS Genetics
Ritsuko Koga, Marie Kubota, Takao Hashiguchi, Yusuke Yanagi, Shinji Ohno
Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome...
February 28, 2018: Journal of Virology
Bahia Khalfaoui-Hassani, Hongjiang Wu, Crysten E Blaby-Haas, Yang Zhang, Federica Sandri, Andreia F Verissimo, Hans-Georg Koch, Fevzi Daldal
Cytochrome c oxidases are members of the heme-copper oxidase superfamily. These enzymes have different subunits, cofactors, and primary electron acceptors, yet they all contain identical heme-copper (CuB ) binuclear centers within their catalytic subunits. The uptake and delivery pathways of the CuB atom incorporated into this active site, where oxygen is reduced to water, are not well understood. Our previous work with the facultative phototrophic bacterium Rhodobacter capsulatus indicated that the copper atom needed for the CuB site of cbb 3 -type cytochrome c oxidase ( cbb 3 -Cox) is imported to the cytoplasm by a major facilitator superfamily-type transporter, CcoA...
February 27, 2018: MBio
Daniel J Kosman
Eukaryotic cells, whether free-living or organismal, rely on metallo-reductases to process environmental ferric iron and cupric copper prior to uptake. In addition, some free-living eukaryotes (e.g. fungi and algae) couple ferri-reduction to ferro-oxidation, a process catalyzed by a small cohort of multi-copper oxidases; in these organisms, the ferric iron product is a ligand for cell iron uptake via a ferric iron permease. In addition to their support of iron uptake in lower eukaryotes, ferroxidases support ferrous iron efflux in Chordata; in this process the release of the ferrous iron from the efflux transporter is catalyzed by its ferroxidation...
February 27, 2018: Metallomics: Integrated Biometal Science
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