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71.
Eric J Suh Matthew Y Remillard Aster Legesse-Miller Elizabeth L Johnson Johanna MS Lemons Talia R Chapman Joshua J Forman Mina Kojima Eric S Silberman Hilary A Coller 《Genome biology》2012,13(12):R121
Background
Although quiescence (reversible cell cycle arrest) is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts.Results
Using microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further.Conclusions
microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts. 相似文献72.
Luisa?Pastò Emilio?Portaccio Angelo?Ghezzi Bahia?Hakiki Marta?Giannini Lorenzo?Razzolini Elisa?Piscolla Laura?De Giglio Carlo?Pozzilli Damiano?Paolicelli Maria?Trojano Maria?Giovanna?Marrosu Francesco?Patti Loredana?La Mantia Gian?Luigi?Mancardi Claudio?Solaro Rocco?Totaro Maria?Rosaria?Tola Valeria?Di Tommaso Alessandra?Lugaresi Lucia?Moiola Vittorio?Martinelli Giancarlo?Comi Maria?Pia?AmatoEmail author and for the MS Study Group of the Italian Neurological Society 《BMC neurology》2012,12(1):165
Background
Few studies have systematically addressed the role of epidural analgesia and caesarean delivery in predicting the post-partum disease activity in women with Multiple Sclerosis (MS).The objective of this study was to assess the impact of epidural analgesia (EA) and caesarean delivery (CD) on the risk of post-partum relapses and disability in women with MS.Methods
In the context of an Italian prospective study on the safety of immunomodulators in pregnancy, we included pregnancies occurred between 2002 and 2008 in women with MS regularly followed-up in 21 Italian MS centers. Data were gathered through a standardized, semi-structured interview, dealing with pregnancy outcomes, breastfeeding, type of delivery (vaginal or caesarean) and EA. The risk of post-partum relapses and disability progression (1 point on the Expanded Disability Status Sclae, EDSS, point, confirmed after six months) was assessed through a logistic multivariate regression analysis.Results
We collected data on 423 pregnancies in 415 women. Among these, 349 pregnancies resulted in full term deliveries, with a post-partum follow-up of at least one year (mean follow-up period 5.5±3.1 years). One hundred and fifty-five patients (44.4%) underwent CD and 65 (18.5%) EA. In the multivariate analysis neither CD, nor EA were associated with a higher risk of post-partum relapses. Post-partum relapses were related to a higher EDSS score at conception (OR=1.42; 95% CI 1.11-1.82; p=0.005), a higher number of relapses in the year before pregnancy (OR=1.62; 95% CI 1.15-2.29; p=0.006) and during pregnancy (OR=3.07; 95% CI 1.40-6.72; p=0.005). Likewise, CD and EA were not associated with disability progression on the EDSS after delivery. The only significant predictor of disability progression was the occurrence of relapses in the year after delivery (disability progression in the year after delivery: OR= 4.00; 95% CI 2.0-8.2; p<0.001; disability progression over the whole follow-up period: OR= 2.0; 95% CI 1.2-3.3; p=0.005).Conclusions
Our findings, show no correlation between EA, CD and postpartum relapses and disability. Therefore these procedures can safely be applied in MS patients. On the other hand, post-partum relapses are significantly associated with increased disability, which calls for the need of preventive therapies after delivery.73.
Sherif M Amr Ahmad M Essam Amr MS Abdel-Meguid Ahmad M Kholeif Ashraf N Moharram Rashed ER El-Sadek 《Journal of brachial plexus and peripheral nerve injury》2009,4(1):1-17
Background
The superiority of a single stage combined anterior (first) posterior (second) approach and end-to-side side-to-side grafting neurorrhaphy in direct cord implantation was investigated as to providing adequate exposure to both the cervical cord and the brachial plexus, as to causing less tissue damage and as to being more extensible than current surgical approaches.Methods
The front and back of the neck, the front and back of the chest up to the midline and the whole affected upper limb were sterilized while the patient was in the lateral position; the patient was next turned into the supine position, the plexus explored anteriorly and the grafts were placed; the patient was then turned again into the lateral position, and a posterior cervical laminectomy was done. The grafts were retrieved posteriorly and side grafted to the anterior cord. Using this approach, 5 patients suffering from complete traumatic brachial plexus palsy, 4 adults and 1 obstetric case were operated upon and followed up for 2 years. 2 were C5,6 ruptures and C7,8T1 avulsions. 3 were C5,6,7,8T1 avulsions. C5,6 ruptures were grafted and all avulsions were cord implanted.Results
Surgery in complete avulsions led to Grade 4 improvement in shoulder abduction/flexion and elbow flexion. Cocontractions occurred between the lateral deltoid and biceps on active shoulder abduction. No cocontractions occurred after surgery in C5,6 ruptures and C7,8T1 avulsions, muscle power improvement extended into the forearm and hand; pain disappeared.Limitations include
spontaneous recovery despite MRI appearance of avulsions, fallacies in determining intraoperative avulsions (wrong diagnosis, wrong level); small sample size; no controls rule out superiority of this technique versus other direct cord reimplantation techniques or other neurotization procedures; intra- and interobserver variability in testing muscle power and cocontractions.Conclusion
Through providing proper exposure to the brachial plexus and to the cervical cord, the single stage combined anterior (first) and posterior (second) approach might stimulate brachial plexus surgeons to go more for direct cord implantation. In this study, it allowed for placing side grafts along an extensive donor recipient area by end-to-side, side-to-side grafting neurorrhaphy and thus improved results.Level of evidence
Level IV, prospective case series. 相似文献74.
The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals 下载免费PDF全文
Roeland Vanhauwaert Sabine Kuenen Roy Masius Adekunle Bademosi Julia Manetsberger Nils Schoovaerts Laura Bounti Serguei Gontcharenko Jef Swerts Sven Vilain Marina Picillo Paolo Barone Shashini T Munshi Femke MS de Vrij Steven A Kushner Natalia V Gounko Wim Mandemakers Vincenzo Bonifati Frederic A Meunier Sandra‐Fausia Soukup Patrik Verstreken 《The EMBO journal》2017,36(10):1392-1411
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in SynaptojaninRQ knock‐in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes. Using advanced imaging, we show that SynaptojaninRQ mutants accumulate the PI(3)P/PI(3,5)P2‐binding protein Atg18a on nascent synaptic autophagosomes, blocking autophagosome maturation at fly synapses and in neurites of human patient induced pluripotent stem cell‐derived neurons. Additionally, we observe neurodegeneration, including dopaminergic neuron loss, in SynaptojaninRQ flies. Thus, synaptojanin is essential for macroautophagy within presynaptic terminals, coupling protein turnover with synaptic vesicle cycling and linking presynaptic‐specific autophagy defects to Parkinson's disease. 相似文献
75.
G Rhys Williams MS 《BMC neurology》2001,1(1):2-6
Background and Purpose
Stroke, increasingly referred to as a "brain attack", is one of the leading causes of death and the leading cause of adult disability in the United States. It has recently been estimated that there were three quarters of a million strokes in the United States in 1995. The aim of this study was to replicate the 1995 estimate and examine if there was an increase from 1995 to 1996 by using a large administrative claims database representative of all 1996 US inpatient discharges. 相似文献76.
Estrella Klinzing MS Pechenik JA 《Journal of experimental marine biology and ecology》2000,252(2):255-279
Disproportionately large feeding structures have been used to infer food limitation in some marine invertebrate larvae, but few studies have investigated whether other factors alter larval morphology in similar ways. In this study, larvae of Crepidula fornicata were reared either at five different food concentrations of Isochrysis galbana (clone T-ISO) at a single temperature (22 degrees C) (Experiments I and II); or on three different phytoplankton species (Isochrysis galbana, Dunaliella tertiolecta, and Pavlova lutheri) at both high and low concentrations at a single temperature (22 degrees C) (Experiment III); or at high and low concentrations of Isochrysis galbana at four different temperatures between 16 and 25 degrees C (Experiment IV). Shell lengths and velar lobe dimensions were determined for individual larvae at intervals to monitor relative rates of velar and shell growth. In addition (Experiment V), fast growing and slow growing larvae in Experiment I were examined separately to determine whether velar lobes developed at similar rates (relative to shell growth) for fast and slow growing larvae within individual cultures. In general, velar lobes grew significantly larger, relative to shell length, when larvae were reared at low food concentrations (P<0.0001); for larvae of similar shell length, the velar lobes of those fed 1x10(4) cells ml(-1) were on average 17.7% larger than those of larvae fed 18x10(4) cells ml(-1) of T-ISO. In contrast, larvae fed different phytoplankton species at equivalently high food concentrations did not differ in relative velum size (P=0.2666), even though shell growth rates differed significantly for larvae raised on the different diets, indicating substantial variation in food quality. We also found that relative rates of velum and shell growth differed among fast and slow growing individuals within treatments. Temperature had no significant effect on relative rates of velar and shell growth within the 16-25 degrees C range tested (P=0.121), but may have altered the relationship between food concentration and relative velar growth. These results indicate that dramatically reduced food concentration induces disproportionate growth in the velar lobes of C. fornicata, but that interpretation of data from field-collected individuals of this species will be made difficult by the potentially confounding effects of temperature, food quality, and differences in individual growth potential. Assessments of food limitation using morphological measurements for field-collected larvae will need to be supplemented with other indicators before convincing conclusions about the extent of food limitation in C. fornicata can be drawn. 相似文献
77.
Effect of nitroxyl on the hamster retinal nitridergic pathway 总被引:1,自引:0,他引:1
Sáenz DA Bari SE Salido E Chianelli M Rosenstein RE 《Neurochemistry international》2007,51(6-7):424-432
There is a growing body of evidence on the role of nitric oxide (NO) in retinal physiology. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed by a number of diverse biochemical reactions. The aim of the present report was to comparatively analyze the effect of HNO and NO on the retinal nitridergic pathway in the golden hamster. For this purpose, sodium trioxodinitrate (Angeli's salt) and diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) were used as HNO and NO releasers, respectively. Angeli's salt and DEA/NO significantly decreased nitric oxide synthase activity. In addition, Angeli's salt (but not DEA/NO) significantly decreased l-arginine uptake. DEA/NO significantly increased cGMP accumulation at low micromolar concentrations, while Angeli's salt affected this parameter with a threshold concentration of 200muM. Although Angeli's salt and DEA/NO significantly diminished reduced glutathione and protein thiol levels in a similar way, DEA/NO was significantly more effective than AS in increasing S-nitrosothiol levels. None of these compounds increased retinal lipid peroxidation. These results suggest that HNO could regulate the hamster retinal nitridergic pathway by acting through a mechanism that only partly overlaps with that involved in NO response. 相似文献
78.
79.
80.
Genotoxicity of diacetoxyscirpenol (DAS) was studied on laboratory mice after intraperitoneal injection with single and repeated
doses. DAS was administrated at three different dose levels (0.5, 0.75, and 1.0 mg/kg body weight). The study was conducted
on both somatic and germ cells additional to the sperm morphology analysis. DAS treatment resulted in a significant reduction
(P<0.01) in mitotic activity at all levels of doses tested, confirming that DAS is a potent protein and DNA synthesis inhibitor.
At somatic cells (bone marrow) both structural and numerical chromosome abnormalities were observed. Single dose treatment
showed significant abnormalities only with high dose treatment. In contrast, at repeated dose similar abnormalities were also
observed with some significance but no systematic relation between the administrated dose and abnormalities ratio could be
settled. In germ cells (testicles), structural and numerical abnormalities were also observed. In general, the frequencies
of scored abnormalities at germ cells were lower than that the somatic cells. Sperm count test revealed a decrease in the
number of released sperm after toxin treatment. Abnormalities of sperm shape (head and tail) were observed, confirming the
positive correlation between cytogenetic damage and sperm abnormality.
The results also proved that DAS is a very toxic mycotoxin, in addition to inducing chromosomal abnormalities, it causes a
severe inhibition of DNA synthesis which subsequently affects the cell cycle and cell division. A good system for good harvesting
practice and good food technology can lower the risk for the consumers. 相似文献