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991.
Barbara Da Costa Elodie Dumon Laurence Le Moigno Sylvie Bodard Pierre Castelnau Thierry Letellier Christophe Rocher 《Journal of bioenergetics and biomembranes》2016,48(5):483-491
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice have been widely used to model the loss of dopaminergic neurons. As this treatment leads to basal ganglia degeneration, it was proposed that MPTP mice could be used as a model of Leigh syndrome. However, this mitochondrial pathology is biochemically characterized by a respiratory chain dysfunction. To determine if MPTP can affect in vivo mitochondria function, we measured the activities of mitochondrial respiratory chain complexes in several tissues. Our results show that MPTP affects mainly mitochondrial respiratory chain complex IV, as found in Leigh Syndrome, confirming that acute MPTP intoxicated mice are a good model of Leigh Syndrome. 相似文献
992.
Frank?Qian Ye?Feng Yonglan?Zheng Temidayo?O.?Ogundiran Oladosu?Ojengbede Wei?Zheng William?Blot Christine?B.?Ambrosone Esther?M.?John Leslie?Bernstein Jennifer?J.?Hu Regina?G.?Ziegler Sarah?Nyante Elisa?V.?Bandera Sue?A.?Ingles Michael?F.?Press Katherine?L.?Nathanson Anselm?Hennis Barbara?Nemesure Stefan?Ambs Laurence?N.?Kolonel Olufunmilayo?I.?Olopade Christopher?A.?Haiman Dezheng?HuoEmail author 《Human genetics》2016,135(10):1145-1159
MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82–0.95, P = 3.99 × 10?4), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology. 相似文献
993.
Important role of phosphoramido linkage in imidazole‐based dioleyl helper lipids for liposome stability and primary cell transfection
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![点击此处可从《The journal of gene medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
994.
β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a GLP‐1 receptor dependent and independent control
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Céline Gleizes Guillaume Kreutter Malak Abbas Mohamad Kassem Andrei Alexandru Constantinescu Julie Boisramé‐Helms Blandine Yver Laurence Kessler 《Journal of cellular and molecular medicine》2016,20(2):231-242
Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell‐derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon‐like peptide (GLP)‐1 analogue, is known to promote insulin secretion and β‐cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin‐m5f β‐cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross‐talk model. Methyl‐β‐cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N‐éthylmaleimide‐sensitive‐factor Attachment protein Receptor (SNARE)‐dependent exocytosis. Cytokines induced a two‐fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two‐fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD‐treated cells showed similar patterns. Cells pre‐treated by saturating concentration of the GLP‐1r antagonist exendin (9‐39), showed a partial abolishment of the liraglutide‐driven insulin secretion and liraglutide‐decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP‐1r‐dependent and ‐independent pathways. Our results confirm an integrative β‐cell response to GLP‐1 that targets receptor‐mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation‐driven procoagulant events. 相似文献
995.
Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study
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Carlos Celis‐Morales Cyril F.M. Marsaux Katherine M. Livingstone Santiago Navas‐Carretero Rodrigo San‐Cristobal Clare B. O'donovan Hannah Forster Clara Woolhead Rosalind Fallaize Anna L. Macready Silvia Kolossa Jacqueline Hallmann Lydia Tsirigoti Christina P. Lambrinou George Moschonis Magdalena Godlewska Agnieszka Surwio Keith Grimaldi Jildau Bouwman Yannis Manios Iwona Traczyk Christian A. Drevon Laurence D. Parnell Hannelore Daniel Eileen R. Gibney Lorraine Brennan Marianne C. Walsh Mike Gibney Julie A. Lovegrove J. Alfredo Martinez Wim H.M. Saris John C. Mathers 《Obesity (Silver Spring, Md.)》2016,24(4):962-969
996.
Véronique Morel Dominique Joly Christine Villatte Claude Dubray Xavier Durando Laurence Daulhac Catherine Coudert Delphine Roux Bruno Pereira Gisèle Pickering 《PloS one》2016,11(4)
BackgroundNeuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.MethodA randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy.ResultsData analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.ConclusionsThis study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.
Trial Registration
Clinicaltrials.gov NCT01536314相似文献997.
Berengere Beauquier-Maccotta Gihad E. Chalouhi Anne-Laure Picquet Aude Carrier Laurence Bussières Bernard Golse Yves Ville 《PloS one》2016,11(1)
Monochronioric (MC) twin pregnancies are considered as high-risk pregnancies with potential complications requiring in-utero interventions. We aimed to assess prenatal attachment, anxiety, post-traumatic stress disorder (PTSD) and depressive symptoms in MC pregnancies complicated with Twin-To-Twin-transfusion syndrome (TTTS) in comparison to uncomplicated monochorionic (UMC) and dichorionic pregnancies (DC). Auto-questionnaires were filled out at diagnosis of TTTS and at successive milestones. Prenatal attachment, PTSD, anxiety and perinatal depression were evaluated respectively by the Prenatal Attachment Inventory (PAI) completed for each twin, the Post-traumatic Checklist Scale (PCLS), the State-Trait Anxiety Inventory (STAI) and the Edinburgh Perinatal Depression Scale (EPDS). There was no significant difference in the PAI scores between the two twins. In the DC and UMC groups, PAI scores increased throughout pregnancy, whilst it didn’t for TTTS group. TTTS and DC had a similar prenatal attachment while MC mothers expressed a significantly higher attachment to their fetuses and expressed it earlier. At the announcement of TTTS, 72% of the patients present a score over the threshold at the EPDS Scale, with a higher score for TTTS than for DC (p = 0.005), and UMC (p = 0.007) at the same GA. 30% of mothers in TTTS group have PTSD during pregnancy. 50% of TTTS- patients present an anxiety score over the threshold (STAI-Scale), with a score significantly higher in TTTS than in UMC (p<0.001) or DC (p<0.001). The proportion of subject with a STAI–State over the threshold is also significantly higher in TTTS than in DC at 20 GW (p = 0.01) and at 26 GW (p<0.05). The STAI-state scores in UMC and DC increase progressively during pregnancy while they decrease significantly in TTTS. TTTS announcement constitutes a traumatic event during a pregnancy with an important risk of PTSD, high level of anxiety and an alteration of the prenatal attachment. These results should guide the psychological support provided to these patients. 相似文献
998.
Jennifer Bernard Evelyne Hutet Frédéric Paboeuf Tantely Randriamparany Philippe Holzmuller Renaud Lancelot Valérie Rodrigues Laurence Vial Marie-Frédérique Le Potier 《PloS one》2016,11(2)
African swine fever is a haemorrhagic disease in pig production that can have disastrous financial consequences for farming. No vaccines are currently available and animal slaughtering or area zoning to restrict risk-related movements are the only effective measures to prevent the spread of the disease. Ornithodoros soft ticks are known to transmit the African swine fever virus (ASFV) to pigs in farms, following the natural epidemiologic cycle of the virus. Tick saliva has been shown to modulate the host physiological and immunological responses during feeding on skin, thus affecting viral infection. To better understand the interaction between soft tick, ASFV and pig at the bite location and the possible influence of tick saliva on pig infection by ASFV, salivary gland extract (SGE) of Ornithodoros porcinus, co-inoculated or not with ASFV, was used for intradermal auricular inoculation. Our results showed that, after the virus triggered the disease, pigs inoculated with virus and SGE presented greater hyperthermia than pigs inoculated with virus alone. The density of Langerhans cells was modulated at the tick bite or inoculation site, either through recruitment by ASFV or inhibition by SGE. Additionally, SGE and virus induced macrophage recruitment each. This effect was enhanced when they were co-inoculated. Finally, the co-inoculation of SGE and virus delayed the early local spread of virus to the first lymph node on the inoculation side. This study has shown that the effect of SGE was powerful enough to be quantified in pig both on the systemic and local immune response. We believe this model should be developed with infected tick and could improve knowledge of both tick vector competence and tick saliva immunomodulation. 相似文献
999.
Yolanda K. Mueller Mathieu Bastard Patrick Nkemenang Eric Comte Geneviève Ehounou Sara Eyangoh Barbara Rusch Earnest Njih Tabah Laurence Toutous Trellu Jean-Francois Etard 《PLoS neglected tropical diseases》2016,10(4)
Background
Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis.Methododology/Principal Findings
Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0–98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2–84.7). Patients with intermediate BU probability needed to be tested by PCR.Conclusions/Significance
We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use. 相似文献1000.
Dr. Michael J. Rutten Robert G. Garrison C. Diane Moore A. Max Fiskin Laurence Y. Cheung 《Cell and tissue research》1989,258(3):555-561
Summary Electron-cytochemical localization of alkaline phosphatase activity was performed on G cells of Necturus maculosus antral mucosa. Alkaline phosphatase activity was localized to the nuclear membrane, the Golgi/endoplasmic reticulum, and the limiting membranes of G cell peptide-secretion vesicles. There was no specific localization of alkaline phosphatase activity to the plasma membrane. Treatment of the tissues with levamisole (an alkaline phosphatase inhibitor) did not markedly reduce the specific alkaline phosphatase activity. Specific lead deposition was reduced by removal of the substrate from the reaction mixture. The results from this study on N. maculosus G cells demonstrate that alkaline phosphatase activity can be found in a non-mammalian gastric endocrine cell and that specific activity was localized primarily to those intracellular structures involved with protein biosynthesis. 相似文献