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71.
Sabine Traver Elodie Scalici Tiffany Mullet Nicolas Molinari Claire Vincens Tal Anahory Samir Hamamah 《PloS one》2015,10(8)
Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7–10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66–0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management. 相似文献
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73.
Daniel Yakubovich Shai Berlin Uri Kahanovitch Moran Rubinstein Isabella Farhy-Tselnicker Boaz Styr Tal Keren-Raifman Carmen W. Dessauer Nathan Dascal 《PLoS computational biology》2015,11(11)
G protein-gated K+ channels (GIRK; Kir3), activated by Gβγ subunits derived from Gi/o proteins, regulate heartbeat and neuronal excitability and plasticity. Both neurotransmitter-evoked (Ievoked) and neurotransmitter-independent basal (Ibasal) GIRK activities are physiologically important, but mechanisms of Ibasal and its relation to Ievoked are unclear. We have previously shown for heterologously expressed neuronal GIRK1/2, and now show for native GIRK in hippocampal neurons, that Ibasal and Ievoked are interrelated: the extent of activation by neurotransmitter (activation index, Ra) is inversely related to Ibasal. To unveil the underlying mechanisms, we have developed a quantitative model of GIRK1/2 function. We characterized single-channel and macroscopic GIRK1/2 currents, and surface densities of GIRK1/2 and Gβγ expressed in Xenopus oocytes. Based on experimental results, we constructed a mathematical model of GIRK1/2 activity under steady-state conditions before and after activation by neurotransmitter. Our model accurately recapitulates Ibasal and Ievoked in Xenopus oocytes, HEK293 cells and hippocampal neurons; correctly predicts the dose-dependent activation of GIRK1/2 by coexpressed Gβγ and fully accounts for the inverse Ibasal-Ra correlation. Modeling indicates that, under all conditions and at different channel expression levels, between 3 and 4 Gβγ dimers are available for each GIRK1/2 channel. In contrast, available Gαi/o decreases from ~2 to less than one Gα per channel as GIRK1/2''s density increases. The persistent Gβγ/channel (but not Gα/channel) ratio support a strong association of GIRK1/2 with Gβγ, consistent with recruitment to the cell surface of Gβγ, but not Gα, by GIRK1/2. Our analysis suggests a maximal stoichiometry of 4 Gβγ but only 2 Gαi/o per one GIRK1/2 channel. The unique, unequal association of GIRK1/2 with G protein subunits, and the cooperative nature of GIRK gating by Gβγ, underlie the complex pattern of basal and agonist-evoked activities and allow GIRK1/2 to act as a sensitive bidirectional detector of both Gβγ and Gα. 相似文献
74.
Simone Lanini Alessandro Nanni Costa Vincenzo Puro Francesco Procaccio Paolo Antonio Grossi Francesca Vespasiano Andrea Ricci Sergio Vesconi Michael G. Ison Yehuda Carmeli Giuseppe Ippolito Donor-Recipient Infection Collaborative Study Group 《PloS one》2015,10(4)
Background
Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Methods and Findings
Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients’ mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.Conclusion
The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality. 相似文献75.
Reut Berger‐Tal Cristina Tuni Yael Lubin Deborah Smith Trine Bilde 《Evolution; international journal of organic evolution》2014,68(2):343-351
Inbreeding mating systems are uncommon because of inbreeding depression. Mating among close relatives can evolve, however, when outcrossing is constrained. Social spiders show obligatory mating among siblings. In combination with a female‐biased sex ratio, sib‐mating results in small effective populations. In such a system, high genetic homozygosity is expected, and drift may cause population divergence. We tested the effect of outcrossing in the social spider Stegodyphus dumicola. Females were mated to sib‐males, to a non‐nestmate within the population, or to a male from a distant population, and fitness traits of F1s were compared. We found reduced hatching success of broods from between‐population crosses, suggesting the presence of population divergence at a large geographical scale that may result in population incompatibility. However, a lack of a difference in offspring performance between inbred and outbred crosses indicates little genetic variation between populations, and could suggest recent colonization by a common ancestor. This is consistent with population dynamics of frequent colonizations by single sib‐mated females of common origin, and extinctions of populations after few generations. Although drift or single mutations can lead to population divergence at a relatively short time scale, it is possible that dynamic population processes homogenize these effects at longer time scales. 相似文献
76.
Yuya Hibino Peter A. Todd Sung-yin Yang Yehuda Benayahu James Davis Reimer 《Hydrobiologia》2014,722(1):31-43
Most studies characterize metacommunities based on a single snapshot of the spatial structure, which may be inadequate for taxa with high migratory behavior (e.g., fish). Here, we applied elements of metacommunity structure to examine variations in the spatial distributions of stream fishes over time and to explore possible structuring mechanisms. Although the major environmental gradients influencing species distributions remained largely the same in time, the best-fit pattern of metacommunity structure varied according to sampling occasion and whether or not we included non-native species in the analyses. Quasi-Clementsian and Clementsian structures were the predominant best-fit structures, indicating the importance of species turnover among sites and the existence of more or less discrete community boundaries. The environmental gradient most correlated with metacommunity structure was defined by altitude, area of artificial ponds in the catchment, and dissolved oxygen content. Our results suggest that the best-fit metacommunity structure of the native species can change in time in this catchment due to seasonal changes in distribution patterns. However, the distribution of non-native species throughout the landscape homogenizes the temporal variability in metacommunity structure of native species. Further studies are necessary from other regions to examine best-fit metacommunity structures of stream fishes within relatively short environmental gradients. 相似文献
77.
Mattan Hurevich Yftah Tal‐Gan Shoshana Klein Yaniv Barda Alexander Levitzki Chaim Gilon 《Journal of peptide science》2010,16(4):178-185
Cyclization of bioactive peptides, utilizing functional groups serving as natural pharmacophors, is often accompanied with loss of activity. The backbone cyclization approach was developed to overcome this limitation and enhance pharmacological properties. Backbone cyclic peptides are prepared by the incorporation of special building units, capable of forming amide, disulfide and coordinative bonds. Urea bridge is often used for the preparation of cyclic peptides by connecting two amine functionalized side chains. Here we present urea backbone cyclization as an additional method for the preparation of backbone cyclic peptide libraries. A straightforward method for the synthesis of crystalline Fmoc‐Nα [ω‐amino(Alloc)‐alkyl] glycine building units is presented. A set of urea backbone cyclic Glycogen Synthase Kinase 3 analogs was prepared and assessed for protein kinase B inhibition as anticancer leads. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
78.
ABSTRACT Here we address the personhood of patients in a permanent vegetative state (PVS), who fall outside categories of "alive" or "dead" and "subject" or "object." Drawing on fieldwork in an Israeli hospital, we examine multiple and shifting approaches to PVS patients, which are articulated in the course of caring for and living with them. We argue that, alongside the institutional definition of these patients as being in a PVS, which, as Kaufman showed, evokes irresolvable confusion as to their ontological nature, there appear and disappear other senses of their personhood. Allying with other studies of cognitively impaired patients (e.g., those with dementia and Alzheimer's), we explore this relational person-concept while demonstrating its situational nature. We analyze patients' admission to the hospital, showing how their essentialistic personhood is "emptied" and how and when their fluid, relational personhood appears and disappears, further showing how this personhood is reified by imagined life stories. 相似文献
79.
80.
p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway 总被引:1,自引:0,他引:1
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Sachs BD Baillie GS McCall JR Passino MA Schachtrup C Wallace DA Dunlop AJ MacKenzie KF Klussmann E Lynch MJ Sikorski SL Nuriel T Tsigelny I Zhang J Houslay MD Chao MV Akassoglou K 《The Journal of cell biology》2007,177(6):1119-1132
Clearance of fibrin through proteolytic degradation is a critical step of matrix remodeling that contributes to tissue repair in a variety of pathological conditions, such as stroke, atherosclerosis, and pulmonary disease. However, the molecular mechanisms that regulate fibrin deposition are not known. Here, we report that the p75 neurotrophin receptor (p75NTR), a TNF receptor superfamily member up-regulated after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1). We have discovered a new mechanism in which phosphodiesterase PDE4A4/5 interacts with p75NTR to enhance cAMP degradation. The p75NTR-dependent down-regulation of cAMP results in a decrease in extracellular proteolytic activity. This mechanism is supported in vivo in p75NTR-deficient mice, which show increased proteolysis after sciatic nerve injury and lung fibrosis. Our results reveal a novel pathogenic mechanism by which p75NTR regulates degradation of cAMP and perpetuates scar formation after injury. 相似文献