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Organ trafficking

Chiara Tersigni, Fiorella Di Nicuolo, Giuseppe Maulucci, Alessandro Rolfo, Domenica Giuffrida, Manuela Veglia, Marco De Spirito, Giovanni Scambia, Tullia Todros, Nicoletta Di Simone
BACKGROUND: Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration...
2016: PloS One
Catherine L Jackson, Laurence Walch, Jean-Marc Verbavatz
An evolutionarily conserved feature of cellular organelles is the distinct phospholipid composition of their bounding membranes, which is essential to their identity and function. Within eukaryotic cells, two major lipid territories can be discerned, one centered on the endoplasmic reticulum and characterized by membranes with lipid packing defects, the other comprising plasma-membrane-derived organelles and characterized by membrane charge. We discuss how this cellular lipid organization is maintained, how lipid flux is regulated, and how perturbations in cellular lipid homeostasis can lead to disease...
October 24, 2016: Developmental Cell
Toshifumi Fujiwara, Shiqiao Ye, Thiago Castro-Gomes, Caylin G Winchell, Norma W Andrews, Daniel E Voth, Kottayil I Varughese, Samuel G Mackintosh, Yunfeng Feng, Nathan Pavlos, Takashi Nakamura, Stavros C Manolagas, Haibo Zhao
Mutations of the Plekhm1 gene in humans and rats cause osteopetrosis, an inherited bone disease characterized by diminished bone resorption by osteoclasts. PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. However, the molecular mechanisms by which PLEKHM1 regulates lysosomal pathways remain unknown. Here, we generated germline and conditional Plekhm1-deficient mice. These mice displayed no overt abnormalities in major organs, except for an increase in trabecular bone mass. Furthermore, loss of PLEKHM1 abrogated the peripheral distribution of lysosomes and bone resorption in osteoclasts...
October 20, 2016: JCI Insight
Hermann Koepsell
Orally applied SGLT2 (SLC5A2) inhibitors that enter the blood and decrease renal reabsorption of glucose have been approved as antidiabetic drugs. They decrease blood glucose levels, slightly reduce body weight and blood pressure, and decrease the risk for diabetic nephropathy. The SGLT2 inhibitor empagliflozin has been shown to reduce the risk of severe cardiac failure. This review summarizes knowledge about the functions of SGLT2 and the pathophysiology of type 2 diabetes (T2D) and diabetic follow-up diseases...
October 20, 2016: Pharmacology & Therapeutics
Lena Diekmann, Marc Behrendt, Mahdi Amiri, Hassan Y Naim
BACKGROUND: Lactase phlorizin-hydrolase (LPH) is a membrane anchored type I glycoprotein of the intestinal epithelium that is composed of four homologous structural domains. The role of each distinct domain in the intramolecular organization and function of LPH is not completely understood. METHODS: Here, we analyzed the early events of LPH biosynthesis and trafficking by directed restructuring of the domain compositions. RESULTS: Removal of domain I (LPH∆1) results in a malfolded ER-localized protein...
October 21, 2016: Biochimica et Biophysica Acta
Henryka Długońska, Justyna Gatkowska
Extracellular vesicles – EV’s, including exosomes, are known to be essential tools of intercellular communication, enabling the exchange of information without direct contact between cells. Exosomes are secreted both in vitro and in vivo by single- and multi-cellular organisms, regardless of their type, and play an essential role in cell-to-cell communication. EV’s may carry various materials and ongoing studies have provided a new insight into their potential participation in various critical biological processes, including carcinogenesis, protein trafficking, immunostimulation and pathogenesis of infectious diseases...
October 1, 2016: Annals of Parasitology
Tao Peng, Howard C Hang
Over the past years, fluorescent proteins (e.g., green fluorescent proteins) have been widely utilized to visualize recombinant protein expression and localization in live cells. Although powerful, fluorescent protein tags are limited by their relatively large sizes and potential perturbation to protein function. Alternatively, site-specific labeling of proteins with small-molecule organic fluorophores using bioorthogonal chemistry may provide a more precise and less perturbing method. This approach involves site-specific incorporation of unnatural amino acids (UAAs) into proteins via genetic code expansion, followed by bioorthogonal chemical labeling with small organic fluorophores in living cells...
October 21, 2016: Journal of the American Chemical Society
Nidhi Singh, Priyanka Shah, Hemlata Dwivedi, Shikha Mishra, Renu Tripathi, Amogh A Sahasrabuddhe, Mohammad Imran Siddiqi
N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries...
October 21, 2016: Molecular BioSystems
A L J J Bronckers, R Jalali, J Lytton
Exposure of forming enamel to fluoride results into formation of hypomineralized enamel. We tested whether enamel hypomineralization was caused by lower expression of the NCKX4/SLC24A4 Ca(2+)-transporter by ameloblasts. Three commercial antibodies against NCKX4 were tested on enamel organs of wild-type and Nckx4-null mice, one of which (a mouse monoclonal) was specific. This antibody gave a prominent staining of the apical plasma membranes of maturation ameloblasts, starting at early maturation. The layer of immuno-positive ameloblasts contained narrow gaps without immunostaining or with reduced staining...
October 17, 2016: Calcified Tissue International
Michelle E Leslie, Sean W Rogers, Antje Heese
Callose deposition within the cell wall is a well-documented plant immune response to pathogenic organisms as well as to pathogen-/microbe- associated molecular patterns (P/MAMPs). However, the molecular mechanisms that modulate pathogen-induced callose deposition are less understood. We reported previously that Arabidopsis plants lacking the vesicle trafficking component DYNAMIN-RELATED PROTEIN 2B (DRP2B) display increased callose deposition in response to the PAMP flg22. Here, we show that increased number of flg22-induced callose deposits in drp2b leaves is fully dependent on the callose synthase POWDERY MILDEW RESISTANT 4 (PMR4)...
October 17, 2016: Plant Signaling & Behavior
Alissa Davis, Beth E Meyerson, Blessing Aghaulor, Katherine Brown, Adisyn Watson, Kathryn E Muessig, Ligang Yang, Joseph D Tucker
BACKGROUND: Increased trade between China and Uganda has fueled trafficking of female Ugandans into China. These women may face challenges accessing health services. This study focused on examining barriers to health care access among female Ugandan sex workers in China. METHODS: In 2014, we undertook in-depth interviews with 19 female Ugandan sex workers in Guangzhou, China. Interviews focused on barriers to health service access and were analyzed using an a priori coding framework followed by open-coding to capture emergent themes...
October 14, 2016: International Journal for Equity in Health
Helena de Fatima Magliarelli, Mariette Matondo, Gergő Mészáros, Alexander Goginashvili, Eric Erbs, Zhirong Zhang, Michael Mihlan, Christian Wolfrum, Ruedi Aebersold, Izabela Sumara, Romeo Ricci
Adaptation to changes in nutrient availability is crucial for cells and organisms. Posttranslational modifications of signaling proteins are very dynamic and are therefore key to promptly respond to nutrient deprivation or overload. Herein we screened for ubiquitylation of proteins in the livers of fasted and refed mice using a comprehensive systemic proteomic approach. Among 1641 identified proteins, 117 were differentially ubiquitylated upon fasting or refeeding. Endoplasmic reticulum (ER) and secretory proteins were enriched in the livers of refed mice in part owing to an ER-stress-mediated response engaging retro-translocation and ubiquitylation of proteins from the ER...
October 13, 2016: Cell Death & Disease
Daeeun Ki, Daisuke Sasayama, Hyung-Taeg Cho
Asymmetrically localized PIN-FORMED (PIN) auxin efflux carriers play key roles in regulating directional intercellular auxin movement, generating local auxin gradients, and diverse auxin-mediated growth and development. The polar localization of PINs is controlled by phosphorylation in the central hydrophilic loop (HL) of PINs. Although the M3 phosphorylation site, including phosphorylatable 5 Ser/Thr residues, is conserved among long HL-PINs, its native role has only been characterized in PIN3. In this study, we examined the role of M3 phosphorylation site of PIN1, PIN2, and PIN7 in intracellular trafficking, phosphorylation, and biological functions of those PINs in their native expressing tissues...
2016: Frontiers in Plant Science
K J Hornig, B A Burgess, N T Saklou, V Johnson, A Malmlov, D C Van Metre, P S Morley, S R Byers
BACKGROUND: Infection control is critical to providing high-quality patient care. Many veterinary teaching hospitals (VTHs) utilize footbaths or footmats at entrances and key control points throughout the facility to decrease trafficking of pathogenic microorganism on contaminated footwear. HYPOTHESIS/OBJECTIVES: To compare efficacy of 4 disinfectants used in footmats for decreasing bacterial contamination of footwear in a large animal hospital. ANIMALS: A single adult dairy cow was housed in a stall for 4 days to facilitate stall contamination with fecal material...
October 12, 2016: Journal of Veterinary Internal Medicine
Maximilian Billmann, Michael Boutros
RNA interference (RNAi) is a potent tool for perturbation of gene function in model organisms and human cells. In Drosophila, efficient RNAi enables screening approaches for components of cellular processes in vivo and in vitro. In cultured cells, measuring the effect of depleting gene products on a genome-wide scale can systematically associate gene function with diverse processes, such as cell growth and proliferation, signaling and trafficking. Here, we describe methods for RNAi experiments in cultured Drosophila cells with a focus on genome-wide loss-of-function screening...
2016: Methods in Molecular Biology
Huakun Zheng, Simiao Chen, Xiaofeng Chen, Shuyan Liu, Xie Dang, Chengdong Yang, Martha C Giraldo, Ely Oliveira-Garcia, Jie Zhou, Zonghua Wang, Barbara Valent
The Rab GTPase proteins play important roles in the membrane trafficking, and consequently protein secretion and development of eukaryotic organisms. However, little is known about the function of Rab GTPases in Magnaporthe oryzae. To further explore the function of Rab GTPases, we deleted the ortholog of the yeast Sec4p protein in M. oryzae, namely MoSEC4. The ΔMosec4 mutant is defective in polarized growth and conidiation, and it displays decreased appressorium turgor pressure and attenuated pathogenicity...
2016: Frontiers in Plant Science
Vandana Sharma, Rajaram Purushotham, Rupinder Kaur
The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival and virulence in the pathogenic yeast Candida glabrata Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA-sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption...
October 11, 2016: Journal of Biological Chemistry
S Liu, J M Shapiro, E Saloustros, C A Stratakis
Protein kinase A (PKA) is an important enzyme for all eukaryotic cells. PKA phosphorylates other proteins, thus, it is essential for the regulation of many diverse cellular functions, including cytoplasmic trafficking and signaling, organelle structure and mitochondrial oxidation, nuclear gene expression, the cell cycle, and cellular division. The PKA holoenzyme is composed of 2 regulatory and 2 catalytic subunits. Four regulatory (R1α, R1β, R2α, and R2β) and 4 catalytic subunits (Cα, Cβ, Cγ, and Prkx) have been identified, giving rise to mainly PKA-I (when the 2 regulatory subunits are either R1α or R1β), or PKA-II (when the 2 regulatory subunits are either R2α or R2β)...
October 11, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Maggy Hologne, François-Xavier Cantrelle, Gwladys Riviere, Florence Guillière, Xavier Trivelli, Olivier Walker
AMSH is one of the deubiquitinating enzymes associated in the regulation of endocytic cargo trafficking. It shows an exquisite selectivity for Lys63-linked polyubiquitin chains that are the main chains involved in cargo sorting. The first step requires the ESCRT-0 complex that comprises the STAM and Hrs proteins. Previous studies have shown that the presence of the STAM protein increases the efficiency of Lys63-linked polyubiquitin chain cleavage by AMSH, one of the deubiquitinating enzyme involved in lysosomal degradation...
October 7, 2016: Journal of Molecular Biology
M-O Timsit, F Kleinclauss, M F Mamzer Bruneel, R Thuret
OBJECTIVES: To review ethical, legal and technical aspects of living kidney donor surgery. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database ( and Embase ( using different associations of the following keywords: Donor nephrectomy; Kidney paired donation; Kidney transplantation; Laparoscopic nephrectomy; Living donor; Organs trafficking; Robotic assisted nephrectomy; Vaginal extraction...
October 6, 2016: Progrès en Urologie
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