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61.
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.  相似文献   
62.
Hemojuvelin (HJV) is an important regulator of iron metabolism. Membrane-anchored HJV up-regulates expression of the iron regulatory hormone, hepcidin, through the bone morphogenic protein (BMP) signaling pathway by acting as a BMP co-receptor. HJV can be cleaved by the furin family of proprotein convertases, which releases a soluble form of HJV that suppresses BMP signaling and hepcidin expression by acting as a decoy that competes with membrane HJV for BMP ligands. Recent studies indicate that matriptase-2 binds and degrades HJV, leading to a decrease in cell surface HJV. In the present work, we show that matriptase-2 cleaves HJV at Arg(288), which produces one major soluble form of HJV. This shed form of HJV has decreased ability to bind BMP6 and does not suppress BMP6-induced hepcidin expression. These results suggest that the matriptase-2 and proprotein convertase-cleavage products have different roles in the regulation of hepcidin expression.  相似文献   
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温带森林展叶物候学   总被引:1,自引:0,他引:1  
杜彦君 《生物多样性》2013,21(1):111-116
物候学是研究自然事件的周期性变化的科学,是一门古老的传统学科.在全球温带地区,春季开始时问已经显著提前.随着气候变化日益得到关注,物候学也重新引起了人们的重视.植物在春季的展叶对温度特别敏感,展叶时间决定着许多基本的生态系统过程,因此,近年来生态学家们对展叶物候学表现出极大兴趣.本文综述了最新文献,介绍了展叶物候的不同研究方法、温带木本植物展叶的控制因子,以及气候变化对展叶物候的影响.除了传统的地面监测方法之外,一些使用遥感和专用相机的新方法已经被用来在更大尺度上监测春季开始时间.未来的研究工作应聚焦于植物的展叶物候如何应对气候变化,及其对不同营养级物种问相互作用的影响.  相似文献   
65.
BackgroundEnterotoxigenic Escherichia coli (ETEC) is one of the top aetiologic agents of diarrhea in children under the age of 5 in low-middle income countries (LMICs). The lack of point of care diagnostic tools for routine ETEC diagnosis results in limited data regarding the actual burden and epidemiology in the endemic areas. We evaluated performance of the novel Rapid LAMP based Diagnostic Test (RLDT) for detection of ETEC in stool as a point of care diagnostic assay in a resource-limited setting.MethodsWe conducted a cross-sectional study of 324 randomly selected stool samples from children under 5 presenting with moderate to severe diarrhea (MSD). The samples were collected between November 2012 to September 2013 at selected health facilities in Zambia. The RLDT was evaluated by targeting three ETEC toxin genes [heat labile toxin (LT) and heat stable toxins (STh and STp)]. Quantitative PCR was used as the “gold standard” to evaluate the diagnostic sensitivity and specificity of RLDT for detection of ETEC. We additionally described the prevalence and seasonality of ETEC.ResultsThe study included 324 participants, 50.6% of which were female. The overall prevalence of ETEC was 19.8% by qPCR and 19.4% by RLDT. The children between 12 to 59 months had the highest prevalence of 22%. The study determined ETEC toxin distribution was LT 28/321(9%), ST 18/321(6%) and LT/ST 16/321(5%). The sensitivity and specificity of the RLDT compared to qPCR using a Ct 35 as the cut-off, were 90.7% and 97.5% for LT, 85.2% and 99.3% for STh and 100% and 99.7% for STp, respectively.ConclusionThe results of this study suggest that RLDT is sufficiently sensitive and specific and easy to implement in the endemic countries. Being rapid and simple, the RLDT also presents as an attractive tool for point-of-care testing at the health facilities and laboratories in the resource-limited settings.  相似文献   
66.
Background:Multiple organ dysfunctions have been linked to exposure to polycyclic aromatic hydrocarbons (PAH) and oxidative stress (OS), oxidative DNA damage, and inflammatory response to PAH have been implicated. The biomarkers of OS (malondialdehyde (MDA), total plasma peroxide (TPP), total antioxidant capacity (TAC), glutathione (GSH), nitric oxide (NO), oxidative stress index (OSI)); 8-hydroxy-2-deoxyguanosine (8-OHdG)); tumor necrosis factor-alpha (TNF-α)); 1-hydroxy pyrene (1-HOP)), serum and urine creatinine, uric acid (UA), estimated glomerular filtration rate (eGFR) and peak expiratory flow rate (PEFR) were assessed in barbecue makers. Methods:One hundred barbecue makers and 50 controls were enrolled into the study. Serum and urine creatinine, UA, TAC, MDA, GSH, NO and TPP were estimated by colorimetry, 8-OHdG and TNF-α by ELISA, PEFR using peak flow meter, 1-HOP by HPLC, eGFR and OSI by calculation. Results:Barbecue makers had lower TAC, PEFR, and higher TNF-α and OS compared to controls (p<0.05). Higher TNF-α, lipid peroxidation, and lower antioxidants were observed in barbecue makers who had worked for >5years compared to <5years (p <0.05). Increasing number of working hours was associated with higher NO, lipid peroxidation, OS and lower antioxidants in barbecue makers (p <0.05). Positive associations were observed between 1-HOP and TPP (r=0.570, p=0.000), OSI (r=0.299, p=0.035) and negative association between TAC and TNF-α (r=-0.209, p=0.037), MDA (r=-0.265, p=0.008) in barbecue makers. Conclusion:Increased lipid peroxidation, OS, inflammation and depressed antioxidants and lung function observed in barbecue makers suggest increased risk of chronic lung conditions which may be associated with exposure to PAH in barbecue fumes.Key Words: Inflammation, Kidney, Lipid Peroxidation, Lung, Oxidative Stress, Polycyclic Aromatic Hydrocarbon  相似文献   
67.
Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA. It involves a one-step fluorescent in situ hybridization approach followed by fluorescence microscopy imaging. Our method reliably identified ALT in cancer cell lines from different tumor entities and was validated in three established models of ALT induction and suppression. Furthermore, we successfully applied ALT-FISH to spatially resolve ALT activity in primary tissue sections from leiomyosarcoma and neuroblastoma tumors. Thus, our assay provides insights into the heterogeneity of ALT tumors and is suited for high-throughput applications, which will facilitate screening for ALT-specific drugs.  相似文献   
68.
Protein phosphatase 1 (PP1) is a key enzyme for Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the Plasmodium berghei leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of Plasmodium PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of Plasmodium oocyst development through its interaction with PbLRR1.  相似文献   
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In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development.  相似文献   
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