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https://www.readbyqxmd.com/read/28087238/lymphocyte-circadian-clocks-control-lymph-node-trafficking-and-adaptive-immune-responses
#1
David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien-Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer Haas, Werner Solbach, Henrik Oster, Christoph Scheiermann
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes...
January 6, 2017: Immunity
https://www.readbyqxmd.com/read/28087224/5-ht6-receptor-blockade-regulates-primary-cilia-morphology-in-striatal-neurons
#2
Matthew Brodsky, Adam J Lesiak, Alex Croicu, Nathalie Cohenca, Jane M Sullivan, John F Neumaier
The 5-HT6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT6 receptor function on cellular morphology has not been examined...
January 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28087126/cardiac-lymphatics-a-new-avenue-for-therapeutics
#3
REVIEW
Taina Vuorio, Annakaisa Tirronen, Seppo Ylä-Herttuala
Recent progress in lymphatic vessel biology and in novel imaging techniques has established the importance of the lymphatic vasculature as part of the cardiovascular system. The lymphatic vessel network regulates many physiological processes important for heart function such as fluid balance, transport of extravasated proteins, and trafficking of immune cells. Therefore, lymphangiogenic therapy could be beneficial in the treatment of cardiovascular diseases, for example by improving reverse cholesterol transport (RCT) from atherosclerotic lesions or by resolving edema and fibrosis after myocardial infarction...
January 10, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28078426/calreticulin-is-required-for-calcium-homeostasis-and-proper-pollen-tube-tip-growth-in-petunia
#4
Anna Suwińska, Piotr Wasąg, Przemysław Zakrzewski, Marta Lenartowska, Robert Lenartowski
Calreticulin is involved in stabilization of the tip-focused Ca (2+) gradient and the actin cytoskeleton arrangement and function that is required for several key processes driving Petunia pollen tube tip growth. Although the precise mechanism is unclear, stabilization of a tip-focused calcium (Ca(2+)) gradient seems to be critical for pollen germination and pollen tube growth. We hypothesize that calreticulin (CRT), a Ca(2+)-binding/buffering chaperone typically residing in the lumen of the endoplasmic reticulum (ER) of eukaryotic cells, is an excellent candidate to fulfill this role...
January 11, 2017: Planta
https://www.readbyqxmd.com/read/28077878/pla2g16-represents-a-switch-between-entry-and-clearance-of-picornaviridae
#5
Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J M van Kuppeveld, Anastassis Perrakis, Jan E Carette, Thijn R Brummelkamp
Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077874/asgard-archaea-illuminate-the-origin-of-eukaryotic-cellular-complexity
#6
Katarzyna Zaremba-Niedzwiedzka, Eva F Caceres, Jimmy H Saw, Disa Bäckström, Lina Juzokaite, Emmelien Vancaester, Kiley W Seitz, Karthik Anantharaman, Piotr Starnawski, Kasper U Kjeldsen, Matthew B Stott, Takuro Nunoura, Jillian F Banfield, Andreas Schramm, Brett J Baker, Anja Spang, Thijs J G Ettema
The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the 'Asgard' superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#7
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077622/ciliary-entry-of-kif17-is-dependent-on-its-binding-to-the-ift-b-complex-via-ift46-ift56-as-well-as-on-its-nuclear-localization-signal
#8
Teruki Funabashi, Yohei Katoh, Saki Michisaka, Masaya Terada, Maho Sugawa, Kazuhisa Nakayama
Cilia function as cellular antennae to sense and transduce extracellular signals. A number of proteins are specifically localized in cilia. Anterograde and retrograde ciliary protein trafficking are mediated by the IFT-B and IFT-A complexes in concert with kinesin-2 and dynein-2 motors, respectively. However, the role of KIF17, a homodimeric kinesin-2 protein, in protein trafficking has not been fully understood in vertebrate cilia. In this study, we first demonstrated by taking advantage of the visible immunoprecipitation assay, that KIF17 interacts with the IFT46-IFT56 dimer in the IFT-B complex through its C-terminal sequence located immediately upstream of the nuclear localization signal (NLS)...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28075478/high-expression-of-rab43-predicts-poor-prognosis-and-is-associated-with-epithelial-mesenchymal-transition-in-gliomas
#9
Ming-Zhi Han, Bin Huang, An-Jing Chen, Xin Zhang, Ran Xu, Jian Wang, Xin-Gang Li
The Ras-related GTP-binding protein (RAB) family plays an important role in regulating signal transduction and cellular processes including vesicle transport, cytoskeleton formation and membrane trafficking. More recently, several RAB members have been reported to promote tumorigenesis in many types of cancers. However, the clinical significance and potential function of RAB43 in gliomas remain unclear. Herein, we found that RAB43 was upregulated and positively correlated with the grade of progression in glioma patients by in silico analysis and immunohistochemistry (IHC)...
January 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074539/ritterostatin-gn1n-a-cephalostatin-ritterazine-bis-steroidal-pyrazine-hybrid-selectively-targets-grp78
#10
Andrew J Ambrose, Evelyne A Santos, Paula C Jimenez, Danilo D Rocha, Diego V Wilke, Paolo Beuzer, Josh Axelrod, Ananda Kumar Kanduluru, Philip L Fuchs, Hu Cang, Letícia V Costa-Lotufo, Eli Chapman, James J La Clair
Natural products discovered using agnostic approaches, unlike rationally designed or HTS obtained leads, offer the ability to reveal new biological pathways, and hence, serve as an important vehicle to unveil new avenues in drug discovery. The ritterazine-cephalostatin family of natural products displays robust and potent anti-tumor activities, with sub-nanomolar growth inhibition against multiple cell lines and potent activity in xenograft models. Herein, we use comparative cellular and molecular biological methods to uncover the ritterazine/cephalostatin mode of cytotoxic action (MOA) in human tumor cells...
January 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28073700/the-yeast-ste2p-g-protein-coupled-receptor-dimerizes-on-the-cell-plasma-membrane
#11
Orkun Cevheroğlu, Gözde Kumaş, Melinda Hauser, Jeffrey M Becker, Çağdaş D Son
Dimerization of G protein-coupled receptors (GPCR) may play an important role in maturation, internalization, signaling and/or pharmacology of these receptors. However, the location where dimerization occurs is still under debate. In our study, variants of Ste2p, a yeast mating pheromone GPCR, were tagged with split EGFP (enhanced green fluorescent protein) fragments inserted between transmembrane domain seven and the C-terminus or appended to the C-terminus. Bimolecular Fluorescence Complementation (BiFC) assay was used to determine where receptor dimerization occurred during protein trafficking by monitoring generation of EGFP fluorescence, which occurred upon GPCR dimerization...
January 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28071667/photogate-microscopy-to-track-single-molecules-in-crowded-environments
#12
Vladislav Belyy, Sheng-Min Shih, Jigar Bandaria, Yongjian Huang, Rosalie E Lawrence, Roberto Zoncu, Ahmet Yildiz
Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signalling and cargo transport. However, individual molecules often cannot be resolved inside cells due to their high density. Here we develop the PhotoGate technique that controls the number of fluorescent particles in a region of interest by repeatedly photobleaching its boundary. PhotoGate bypasses the requirement of photoactivation to track single particles at surface densities two orders of magnitude greater than the single-molecule detection limit...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28069747/a-targeted-rnai-screen-identifies-factors-affecting-diverse-stages-of-receptor-mediated-transcytosis
#13
Bradlee Nelms, Natasha Furtado Dalomba, Wayne Lencer
Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fcγ receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis...
January 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28069025/interaction-of-biomedical-nanoparticles-with-the-pulmonary-immune-system
#14
REVIEW
Fabian Blank, Kleanthis Fytianos, Emilie Seydoux, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Christophe von Garnier, Barbara Rothen-Rutishauser
Engineered nanoparticles (NPs) offer site-specific delivery, deposition and cellular uptake due to their unique physicochemical properties and were shown to modulate immune responses. The respiratory tract with its vast surface area is an attractive target organ for innovative immunomodulatory therapeutic applications by pulmonary administration of such NPs, enabling interactions with resident antigen-presenting cells (APCs), such as dendritic cells and macrophages. Depending on the respiratory tract compartment, e...
January 9, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28068562/epigenetic-histopathological-and-transcriptomic-effects-following-exposure-to-depleted-uranium-in-adult-zebrafish-and-their-progeny
#15
Kewin Gombeau, Jean-Paul Bourdineaud, Jean-Luc Ravanat, Olivier Armant, Virginie Camilleri, Isabelle Cavalie, Magali Floriani, Christelle Adam-Guillermin
This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20μgL(-1) of depleted uranium (DU) for six days upon DNA methylation, gene expression and the appearance of histopathological damage in their progeny. In the embryos at the 2-8 cell stage, the parental exposure induced significant DU accumulation, with levels seven times higher than those measured in the control embryos, but in larvae 96h post-fertilisation (hpf), uranium concentration had already returned to a level identical to that of the control larvae...
December 8, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28067790/rab10-interacts-with-the-male-germ-cell-specific-gtpase-activating-protein-during-mammalian-spermiogenesis
#16
Ying-Hung Lin, Chih-Chun Ke, Ya-Yun Wang, Mei-Feng Chen, Tsung-Ming Chen, Wei-Chi Ku, Han-Sun Chiang, Chung-Hsin Yeh
According to recent estimates, 2%-15% of couples are sterile, and approximately half of the infertility cases are attributed to male reproductive factors. However, the reasons remain undefined in approximately 25% of male infertility cases, and most infertility cases exhibit spermatogenic defects. Numerous genes involved in spermatogenesis still remain unknown. We previously identified Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs) through cDNA microarray analysis of human testicular tissues with spermatogenic defects...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28067475/the-chaperonin-tric-forms-an-oligomeric-complex-in-the-malaria-parasite-cytosol
#17
Natalie J Spillman, Josh R Beck, Suresh M Ganesan, Jacquin C Niles, Daniel E Goldberg
The malaria parasite exports numerous proteins into its host red blood cell (RBC). The trafficking of these exported effectors is complex. Proteins are first routed through the secretory system, into the parasitophorous vacuole (PV), a membranous compartment enclosing the parasite. Proteins are then translocated across the PV membrane in a process requiring ATP and unfolding. Once in the RBC compartment the exported proteins are then refolded and further trafficked to their final localizations. Chaperones are important in the unfolding and refolding processes...
January 9, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28067262/sec16a-is-critical-for-both-conventional-and-unconventional-secretion-of-cftr
#18
He Piao, Jiyoon Kim, Shin Hye Noh, Hee-Seok Kweon, Joo Young Kim, Min Goo Lee
CFTR is a transmembrane protein that reaches the cell surface via the conventional Golgi mediated secretion pathway. Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type CFTR and the disease-causing ΔF508-CFTR, which has folding and trafficking defects. Here, we show that Sec16A, the key regulator of conventional ER-to-Golgi transport, plays a critical role in the ER exit of protein cargos during unconventional secretion...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28066811/ph-dependent-cellular-internalization-of-paramagnetic-nanoparticle
#19
Branislava Janic, Mohammed Pi Bhuiyan, James R Ewing, Meser M Ali
A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated Gd44-G5 paramagnetic nanoparticle binds and fuses with cellular membrane at low pH, but not at normal physiological pH, and that it promotes cellular uptake...
August 26, 2016: ACS Sensors
https://www.readbyqxmd.com/read/28065935/two-birds-one-stone-dual-targeting-of-the-cancer-cell-surface-and-subcellular-mitochondria-by-the-galectin-3-binding-peptide-g3-c12
#20
Wei Sun, Lian Li, Qing-Qing Yang, Zhi-Rong Zhang, Yuan Huang
Active tumor-targeting approaches using specific ligands have drawn considerable attention over the years. However, a single ligand often fails to simultaneously target the cancer cell surface and subcellular organelles, which limits the maximum therapeutic efficacy of delivered drugs. We describe a polymeric delivery system modified with the G3-C12 peptide for sequential dual targeting. In this study, galectin-3-targeted G3-C12 peptide was conjugated onto the N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer for the delivery of D(KLAKLAK)2 (KLA) peptide...
January 9, 2017: Acta Pharmacologica Sinica
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