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101.
D Pittet F Di Virgilio T Pozzan A Monod D P Lew 《The Journal of biological chemistry》1990,265(24):14256-14263
The effects of plasma membrane depolarization on cytosolic free calcium ([Ca2+]i) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) generation were investigated in the human promyelocytic cell line HL-60 differentiated with either dimethyl sulfoxide or retinoic acid into neutrophil-like cells. Increases in [Ca2+]i and accumulation of Ins(1,4,5)P3 were triggered by two chemoattractants fMet-Leu-Phe and leukotriene B4. Plasma membrane potential was depolarized by isoosmotic substitution of NaCl with KCl, by the pore-forming ionophore gramicidin D, or by long term treatment with ouabain. Both Ca2+ mobilization from intracellular stores and Ca2+ influx across the plasma membrane were reduced by prior depolarization of plasma membrane potential regardless of the procedure employed to collapse it. Agonist-induced generation of Ins(1,4,5)P3 was also reduced in parallel in pre-depolarized HL-60 cells. The present findings provide further evidence suggesting that plasma membrane potential can be an important modulator of agonist-activated second messenger generation in myelocytic cells. 相似文献
102.
Mathieu Dalibard Speranta-Maria Popescu Jean Maley François Baudin Mihaela-Carmen Melinte-Dobrinescu Bernard Pittet Tania Marsset Bernard Dennielou Laurence Droz Jean-Pierre Suc 《Geobios》2014
The essential characteristics of the vegetation dynamics of tropical Africa remain only partially known. This study assesses the succession of vegetation-types over Central Africa during the last two glacial/interglacial cycles. Analysis of core KZai 02, which contains pollen from the Zaire River watershed (latitudes 9°N–13°S), allows the investigation of long-term patterns of plant ecosystem development and their climatic causes. Core KZai 02 (18.20 m long) was recovered from 6°24.20′S/9°54.10′E in the uppermost axial edifice of the Zaire deep sea fan. The chronology of this sedimentary archive was established using nannofossils and correlations of pollen and total organic carbon signals with the nearby core GeoB1008. The pollen record indicates that: (i) glacials (MIS 6, 4, 2) are marked by the development of afromontane (Podocarpus) forest at high altitudes when central basin lowlands were occupied by Cyperaceae marshes and savannah; (ii) during interglacials (MIS 1, 5) lowland forests were developed, marked by the successive expansion of pioneer, warm-temperate, rain forests, and mangrove indicating sea-level rise; (iii) glacial-interglacial transitions (MIS 6/5, 2/1) display similar vegetation dynamics. The strong evidence of afromontane forest and the opening of the vegetation during glacials suggest a reduced latitudinal distribution of rainfall by the strengthening of the trade wind system. West African monsoon systems were enhanced during interglacials, allowing the progressive development of lowland forests. The development of rain and pioneer forests during glacial Heinrich stadials suggests an enhancement of water availability in tropical Africa associated with these high-latitude events. However, no augmentation of wind activity described by previous studies is evidenced by our pollen record. Similar vegetation successions during glacial/interglacial transitions suggest the diachronous and stepped intervention of CO2 (emphasizing the influence of temperature on plant ecosystems) and water availability. 相似文献
103.
Ronan Thibault Anne-Marie Makhlouf Michel P. Kossovsky Jimison Iavindrasana Marinette Chikhi Rodolphe Meyer Didier Pittet Walter Zingg Claude Pichard 《PloS one》2015,10(4)
Background
Indicators to predict healthcare-associated infections (HCAI) are scarce. Malnutrition is known to be associated with adverse outcomes in healthcare but its identification is time-consuming and rarely done in daily practice. This cross-sectional study assessed the association between dietary intake, nutritional risk, and the prevalence of HCAI, in a general hospital population.Methods and findings
Dietary intake was assessed by dedicated dieticians on one day for all hospitalized patients receiving three meals per day. Nutritional risk was assessed using Nutritional Risk Screening (NRS)-2002, and defined as a NRS score ≥ 3. Energy needs were calculated using 110% of Harris-Benedict formula. HCAIs were diagnosed based on the Center for Disease Control criteria and their association with nutritional risk and measured energy intake was done using a multivariate logistic regression analysis. From 1689 hospitalised patients, 1024 and 1091 were eligible for the measurement of energy intake and nutritional risk, respectively. The prevalence of HCAI was 6.8%, and 30.1% of patients were at nutritional risk. Patients with HCAI were more likely identified with decreased energy intake (i.e. ≤ 70% of predicted energy needs) (30.3% vs. 14.5%, P = 0.002). The proportion of patients at nutritional risk was not significantly different between patients with and without HCAI (35.6% vs.29.7%, P = 0.28), respectively. Measured energy intake ≤ 70% of predicted energy needs (odds ratio: 2.26; 95% CI: 1.24 to 4.11, P = 0.008) and moderate severity of the disease (odds ratio: 3.38; 95% CI: 1.49 to 7.68, P = 0.004) were associated with HCAI in the multivariate analysis.Conclusion
Measured energy intake ≤ 70% of predicted energy needs is associated with HCAI in hospitalised patients. This suggests that insufficient dietary intake could be a risk factor of HCAI, without excluding reverse causality. Randomized trials are needed to assess whether improving energy intake in patients identified with decreased dietary intake could be a novel strategy for HCAI prevention. 相似文献104.
Anie Azroyan Virna Cortez-Retamozo Richard Bouley Rachel Liberman Ye Chun Ruan Evgeny Kiselev Kenneth A. Jacobson Mikael J. Pittet Dennis Brown Sylvie Breton 《PloS one》2015,10(3)
Uncontrolled inflammation is one of the leading causes of kidney failure. Pro-inflammatory responses can occur in the absence of infection, a process called sterile inflammation. Here we show that the purinergic receptor P2Y14 (GPR105) is specifically and highly expressed in collecting duct intercalated cells (ICs) and mediates sterile inflammation in the kidney. P2Y14 is activated by UDP-glucose, a damage-associated molecular pattern molecule (DAMP) released by injured cells. We found that UDP-glucose increases pro-inflammatory chemokine expression in ICs as well as MDCK-C11 cells, and UDP-glucose activates the MEK1/2-ERK1/2 pathway in MDCK-C11 cells. These effects were prevented following inhibition of P2Y14 with the small molecule PPTN. Tail vein injection of mice with UDP-glucose induced the recruitment of neutrophils to the renal medulla. This study identifies ICs as novel sensors, mediators and effectors of inflammation in the kidney via P2Y14. 相似文献
105.
Molinges was located on an Upper Jurassic ramp system of low-energy regime that developed at the southern margin of the French
Jura platform. The sedimentary succession is characterized by the transition from a mixed siliciclastic-carbonate to a carbonate
depositional setting that occurred during a long-term shallowing-upward trend. The disappearance of siliciclastics is explained
by a climatic change, from humid and cold to drier and warmer conditions, previously identified in Late Oxfordian adjacent
basins. The base of the section shows marl-limestone alternations of outer ramp. In its middle part, the section displays
oncolitic marls, coral-microbialite beds and oncolitic limestones that deposited in a mid ramp position. Finally, the upper
section part is made of oolitic limestones of inner ramp. In outer- to mid-ramp settings submitted to terrigenous inputs,
the stacking pattern of deposits and facies evolution allow the identification of elementary, small-, medium-, and large-scale
sequences. Small amplitudes of sea-level variations probably controlled rapid shifts of facies belts and reef window occurrences.
In small-scale sequences, the coral beds developed during periods of sea-level rise. The decreasing rate of sea-level rise
is marked by the downramp shift of the oncolitic limestone belt that led to the demise of coral-microbialite beds. These bioconstructions
are mainly represented by thin biostromes in which corals never reach great sizes. The coral assemblages mainly include the
genera Enallhelia, Dimorpharaea, Thamnasteria, and some solitary forms (Montlivaltia and Epistreptophyllum). They suggest relatively low-mesotrophic conditions in marine waters during the edification of the primary framework. Relatively
cold water temperatures and periods of more elevated nutrient contents are probably responsible of the reduced coral development
and the formation of a large amount of microbialites. 相似文献
106.
Michele H Jones Jamie M Keck Catherine CL Wong Tao Xu John R Yates Mark Winey 《Cell cycle (Georgetown, Tex.)》2011,10(20):3435-3440
Phosphorylation of proteins is an important mechanism used to regulate most cellular processes. Recently, we completed an extensive phosphoproteomic analysis of the core proteins that constitute the Saccharomyces cerevisiae centrosome. Here, we present a study of phosphorylation sites found on the mitotic exit network (MEN) proteins, most of which are associated with the cytoplasmic face of the centrosome. We identified 55 sites on Bfa1, Cdc5, Cdc14 and Cdc15. Eight sites lie in cyclin-dependent kinase motifs (Cdk, S/T-P), and 22 sites are completely conserved within fungi. More than half of the sites were found in centrosomes from mitotic cells, possibly in preparation for their roles in mitotic exit. Finally, we report phosphorylation site information for other important cell cycle and regulatory proteins.Key words: in vivo phosphorylation, yeast centrosome, mitotic exit network (MEN), cell cycle, protein kinase, Cdk (cyclin-dependent kinase)/Cdc28, Plk1 (polo-like kinase)/Cdc5Reversible protein phosphorylation leads to changes in targeting, structure and stability of proteins and is used widely to modulate biochemical reactions in the cell. We are interested in phosphoregulation of centrosome duplication and function in the yeast Saccharomyces cerevisiae. Centrosomes nucleate microtubules and, upon duplication during the cell cycle, form the two poles of the bipolar mitotic spindle used to segregate replicated chromosomes into the two daughter cells. Timing and spatial cues are highly regulated to ensure that elongation of the mitotic spindle and separation of sister chromatids occur prior to progression into late telophase and initiation of mitotic exit. The mitotic exit network (MEN) regulates this timing through a complex signaling cascade activated at the centrosome that triggers the end of mitosis, ultimately through mitotic cyclin-dependent kinase (Cdk) inactivation (reviewed in ref. 1).The major components of the MEN pathway (Fig. 1) are a Ras-like GTPase (Tem1), an activator (Lte1) with homology to nucleotide exchange factors, a GTPase-activating protein (GAP) complex (Bfa1/Bub2), several protein kinases [Cdc5 (Plk1 in humans), Cdc15 and Dbf2/Mob1] and Cdc14 phosphatase (reviewed in ref. 2–5). Tem1 initiates the signal for the MEN pathway when switched to a GTP-active state. Prior to activation at anaphase, it is held at the centrosome in an inactive GDP-bound state by an inhibiting GAP complex, Bfa1/Bub2.6 The Bfa1/Bub2 complex and the inactive Tem1 are localized at the mother centrosome destined to move into the budded cell upon chromosome segregation, whereas the activator Lte1 is localized at the tip of the budded cell. These separate localizations ensure that Lte1 and Tem1 only interact in late anaphase, when the mitotic spindle elongates.7,8 Lte1 has been thought to activate Tem1 as a nucleotide exchange factor, although more recent evidence suggests that it may instead affect Bfa1 localization.9 In addition, full activation of Tem1 is achieved through Cdc5 phosphorylation of the negative regulator Bfa1 10 and potentially through phosphorylation of Lte1. GTP-bound Tem1 is then able to recruit Cdc15 to the centrosome, allowing for Dbf2 activation.3 The final step in the MEN pathway is release of Cdc14 from the nucleolus, which is at least partially due to phosphorylation by Dbf211 an leads to mitotic cyclin degradation and inactivation of the mitotic kinase.2Open in a separate windowFigure 1Schematic representation of the MEN proteins and pathway. MEN protein localization is shown within a metaphase cell when mitotic exit is inhibited and in a late anaphase cell when mitotic exit is initiated. Primary inhibition and activation events are described below the cells.Recently, we performed a large-scale analysis of phosphorylation sites on the 18 core yeast centrosomal proteins present in enriched centrosomal preparations.12 In total, we mapped 297 sites on 17 of the 18 proteins and described their cell cycle regulation, levels of conservation and demonstrated defects in centrosome assembly and function resulting from mutating selected sites. MEN proteins were also identified in the centrosome preparations. This was expected, because Nud1, one of the 18 core centrosome components, is known to recruit several MEN proteins to the centrosome13 as part of its function in mitotic exit.14,15 As phosphorylation is essential to several steps in the MEN pathway, beginning with recruitment of Bfa1/Bub2 by phosphorylated Nud1,15 we were interested in mapping in vivo phosphorylation sites on the MEN proteins associated with centrosomes and identifying when they occur during the cell cycle.We combined centrosome enrichment with mass spectrometry analysis to examine phosphorylation from asynchronously growing cells.12 Centrosomes were also prepared from cells arrested in G1 and mitosis12 to monitor potentially cell cycle-regulated sites. We obtained significant coverage of a number of the MEN proteins, several of which have human homologs (and33, column 1), of which eight sites lie within Cdk/Cdc28 motifs [S/T(P)], (23 Mob1 and Dbf2 are known phosphoproteins24 for which we observed peptide coverage but no phosphorylation. Surprisingly, we did not detect phosphorylation on Bub2 despite the high peptide coverage; it is possible that the mitotic centrosome preparations (using a Cdc20 depletion protocol) affect the phosphorylation state of Bub2, as Bub2 is required for mitotic exit arrest in cdc20 mutants.25 Additionally, specific phosphorylation sites have not been mapped on Bub2, suggesting that modifications on this protein may be difficult to observe by mass spectrometry. Lte1 does not localize to the centrosome, and we did not recover Lte1 peptides in our preparations. Many phosphorylation events on MEN proteins were observed in mitotic centrosomal preparations, most likely in preparation for their subsequent role in exit from mitosis (MEN Protein Sequence Coverage Total Sites S/T (P) Sites Human Homologs Bfa1 98% 35 2 N/A Cdc14 80% 10 2 CDC14A, 14B2 Cdc15 12% 3 1 MST1, STK4 Cdc5 41% 7 3 PLK1, PLK2, PLK3 Bub2 67% - - N/A Tem1 18% - - RAB22, RAB22A Mob1 13% - - MOB1B, 1A, 2A, 2B Dbf2 2% - - STK38, LATS1 TOTAL 55 8