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61.
Champica K. Bodinayake Ajith DeS Nagahawatte Vasantha Devasiri Niroshana J. Dahanayake Gaya B. Wijayaratne Nayani P. Weerasinghe Madureka Premamali Tianchen Sheng Bradly P. Nicholson Harshanie A. Ubeysekera Ruvini MP Kurukulasooriya Aruna D. de Silva Truls
stbye Christopher W. Woods L Gayani Tillekeratne 《PLoS neglected tropical diseases》2021,15(12)
BackgroundHealthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future.Methods/Principal findingsFrom June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/μL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization.ConclusionsOne-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries. 相似文献
62.
VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy 下载免费PDF全文
Chrisovalantis Papadopoulos Philipp Kirchner Monika Bug Daniel Grum Lisa Koerver Nina Schulze Robert Poehler Alina Dressler Sven Fengler Khalid Arhzaouy Vanda Lux Michael Ehrmann Conrad C Weihl Hemmo Meyer 《The EMBO journal》2017,36(2):135-150
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin‐directed AAA‐ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo‐Lysosomal Damage Response. Together, they act downstream of K63‐linked ubiquitination and p62 recruitment, and selectively remove K48‐linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation. Lysosomal clearance is also compromised in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damaged lysosomes accumulate in affected patient tissue carrying the mutation. Moreover, we show that p97 helps clear late endosomes/lysosomes ruptured by endocytosed tau fibrils. Thus, our data reveal an important mechanism of how p97 maintains lysosomal homeostasis, and implicate the pathway as a modulator of degenerative diseases. 相似文献
63.
The invasive freshwater snail Tarebia granifera (Lamarck, 1822) was first reported in South Africa in 1999 and it has become widespread across the country, with some evidence to suggest that it reduces benthic macroinvertebrate biodiversity. The current study aimed to identify the primary abiotic drivers behind abundance patterns of T. granifera, by comparing the current abundance of the snail in three different regions, and at three depths, of the highly modified Nseleni River in KwaZulu-Natal, South Africa. Tarebia granifera was well established throughout the Nseleni River system, with an overall preference for shallow waters and seasonal temporal patterns of abundance. Although it is uncertain what the ecological impacts of the snail in this system are, its high abundances suggest that it should be controlled where possible and prevented from invading other systems in the region. 相似文献
64.
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66.
Background
Exposure of cells to environmental stress conditions can lead to the interruption of several intracellular processes, in particular those performed by macromolecular complexes such as the spliceosome. 相似文献67.
Background
Glycosyl transferases transfer glycosyl groups onto their substrate. Localization partially defines their function. Glycosyl transferase 25 domain 1 (GLT25D1) was recently shown to have galactosyltransferase activity towards collagens and another well known substrate, mannose binding lectin (MBL). To gain more insight in the role of galactosylation of lysines in the Gly-X-Lys repeats of collagenous proteins, we investigated the subcellular localization of GLT25D1. 相似文献68.
Rahul Rai Suresh K. Verma David Kim Veronica Ramirez Elizabeth Lux Chengjin Li 《Epigenetics》2017,12(11):1004-1013
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300—p300 with intrinsic factor acetyltransferase activity—is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis. Additionally, we examine the effects of L002 on cellular pro-fibrogenic processes and provide mechanistic insights into its antifibrogenic action. Utilizing cardiac fibroblasts, podocytes, and mesangial cells, we demonstrate that L002 blunts FATp300-mediated acetylation of specific histones. Further, incubating cells with L002 suppresses several pro-fibrogenic processes including cellular proliferation, migration, myofibroblast differentiation and collagen synthesis. Importantly, systemic administration of L002 in mice reduces hypertension-associated pathological hypertrophy, cardiac fibrosis and renal fibrosis. The anti-hypertrophic and anti-fibrotic effects of L002 were independent of blood pressure regulation. Our work solidifies the role of epigenetic regulator FATp300 in fibrogenesis and establishes it as a pharmacological target for reducing pathological matrix remodeling and associated pathologies. Additionally, we discover a new therapeutic role of L002, as it ameliorates hypertension-induced cardio-renal fibrosis and antagonizes pro-fibrogenic responses in fibroblasts, podocytes and mesangial cells. 相似文献
69.
Cadmium uptake,localization and stress-induced morphogenic response in the fern Pteris vittata 总被引:1,自引:0,他引:1
Mirko Balestri Alessio Ceccarini Laura Maria Costantina Forino Ivan Zelko Michal Martinka Alexander Lux Monica Ruffini Castiglione 《Planta》2014,239(5):1055-1064
Cadmium uptake, tissue localization and structural changes induced at cellular level are essential to understand Cd tolerance in plants. In this study we have exposed plants of Pteris vittata to different concentrations of CdCl2 (0, 30, 60, 100 μM) to evaluate the tolerance of the fern to cadmium. Cadmium content determination and its histochemical localization showed that P. vittata not only takes up, but also transports and accumulates cadmium in the aboveground tissues, delocalizing it mainly in the less bioactive tissues of the frond, the trichomes and the scales. Cadmium tolerance in P. vittata was strictly related to morphogenic response induced by the metal itself in the root system. Adaptive response regarded changes of the root apex size, the developmental pattern of root hairs, the differentiation of xylem elements and endodermal suberin lamellae. All the considered parameters suggest that, in our experimental conditions, 60 μM of Cd may represent the highest concentration that P. vittata can tolerate; indeed this Cd level even improves the absorbance features of the root and allows good transport and accumulation of the metal in the fronds. The results of this study can provide useful information for phytoremediation strategies of soils contaminated by Cd, exploiting the established ability of P. vittata to transport, delocalize in the aboveground biomass and accumulate polluting metals. 相似文献
70.
Stewart AK Shmukler BE Vandorpe DH Rivera A Heneghan JF Li X Hsu A Karpatkin M O'Neill AF Bauer DE Heeney MM John K Kuypers FA Gallagher PG Lux SE Brugnara C Westhoff CM Alper SL 《American journal of physiology. Cell physiology》2011,301(6):C1325-C1343
Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li(+) and (86)Rb(+), with secondarily increased (86)Rb(+) influx sensitive to ouabain and to bumetanide. Increased RhAG-associated (14)C-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li(+), (86)Rb(+), and (14)C-MA were pharmacologically distinct, and Li(+) uptakes associated with RhAG and RhAG F65S were differentially inhibited by NH(4)(+) and Gd(3+). RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH(3)/NH(4)(+), but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA(+)). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH(4)Cl, but MA/MA(+) elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li(+) substitution or bath addition of 5 mM NH(4)Cl or MA/MA(+). These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH(3)/NH(4)(+) and MA/MA(+); 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA(+) transport, and decreased NH(3)/NH(4)(+)-associated depolarization; and 3) RhAG transports NH(3)/NH(4)(+) and MA/MA(+) by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms. 相似文献