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- Fisher, Oliver M., et al.
(författare)
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High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 22:7, s. 2431-2438
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Tidskriftsartikel (refereegranskat)abstract
- Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. Median CTSE mRNA expression levels were a parts per thousand yen1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.
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- Koenigk, Torben, et al.
(författare)
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Impact of Arctic sea ice variations on winter temperature anomalies in northern hemispheric land areas
- 2019
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 52:5-6, s. 3111-3137
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Tidskriftsartikel (refereegranskat)abstract
- Coordinated numerical ensemble experiments with six different state-of-the-art atmosphere models have been used in order to evaluate the respective impact of the observed Arctic sea ice and sea surface temperature (SST) variations on air temperature variations in mid and high latitude land areas. Two sets of experiments have been designed; in the first set (EXP1), observed daily sea ice concentration and SST variations are used as lower boundary forcing over 1982-2014 while in the second set (EXP2) the SST variations are replaced by the daily SST climatology. The observed winter 2m air temperature (T2m) variations are relatively well reproduced in a number of mid and high latitude land areas in EXP1, with best agreement in southwestern North America and northern Europe. Sea ice variations are important for the interannual T2m variations in northern Europe but have limited impact on all other mid and high latitude land regions. In particular, sea ice variations do not contribute to the observed opposite variations in the Arctic and mid latitude in our model experiments. The spread across ensemble members is large and many ensemble members are required to reproduce the observed T2m variations over northern Europe in our models. The amplitude of T2m anomalies in the coldest observed winters over northern Europe is not reproduced by our multi-model ensemble means. However, the sea ice conditions in these respective winters and mainly the thermodynamic response to the ice anomalies lead to an enhanced likelihood for occurrence of colder than normal winters and extremely cold winters. Still, the main reason for the observed extreme cold winters is internal atmospheric dynamics. The coldest simulated northern European winters in EXP1 and EXP2 between 1982 and 2014 show the same large scale T2m and atmospheric circulation anomaly patterns as the observed coldest winters, indicating that the models are well able to reproduce the processes, which cause these cold anomalies. The results are robust across all six models used in this study.
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- Niu, Mengyao, et al.
(författare)
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Fungal oxylipins direct programmed developmental switches in filamentous fungi
- 2020
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Ingår i: Nature Communications. - : NATURE RESEARCH. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Filamentous fungi differentiate along complex developmental programs directed by abiotic and biotic signals. Currently, intrinsic signals that govern fungal development remain largely unknown. Here we show that an endogenously produced and secreted fungal oxylipin, 5,8-diHODE, induces fungal cellular differentiation, including lateral branching in pathogenic Aspergillus fumigatus and Aspergillus flavus, and appressorium formation in the rice blast pathogen Magnaporthe grisea. The Aspergillus branching response is specific to a subset of oxylipins and is signaled through G-protein coupled receptors. RNA-Seq profiling shows differential expression of many transcription factors in response to 5,8-diHODE. Screening of null mutants of 33 of those transcription factors identifies three transcriptional regulators that appear to mediate the Aspergillus branching response; one of the mutants is locked in a hypo-branching phenotype, while the other two mutants display a hyper-branching phenotype. Our work reveals an endogenous signal that triggers crucial developmental processes in filamentous fungi, and opens new avenues for research on the morphogenesis of filamentous fungi.
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- Rzeznicka, Kamila, et al.
(författare)
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Xantha-l encodes a membrane subunit of the aerobic Mg-protoporphyrin IX monomethyl ester cyclase involved in chlorophyll biosynthesis
- 2005
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:16, s. 5886-5891
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Tidskriftsartikel (refereegranskat)abstract
- Chlorophyll biosynthesis is a process involving approximate to 20 different enzymatic steps. Half of these steps are common to the biosynthesis of other tetrapyrroles, such as heme. one of the least understood enzymatic steps is formation of the isocyclic ring, which is a characteristic feature of all (bacterio)chlorophyll molecules. In chloroplasts, formation of the isocyclic ring is an aerobic reaction catalyzed by Mg-protoporphyrin IX monomethyl ester cyclase. An in vitro assay for the aerobic cyclase reaction required membrane-bound and soluble components from the chloroplasts. Extracts from barley (Hordeum vulgare Q mutants at the Xantha-1 and Viridis-k loci showed no cyclase activity. Fractionation of isolated plastids by Percoll gradient centrifugation showed that xantha-1 and viridis-k mutants are defective in components associated with chloroplast membranes. The Xantha-1 gene, corresponding to Arabidopsis thaliana CHL27, Rubrivivax gelatinosus acsF, Chlamydomonas reinhardtii CRD1, and CTH1 and situated at the short arm of barley chromosome 3 (3H), was cloned, and the mutations in xantha-l(35), xantha-l(81), and xantha-l(82) were characterized. This finding connected biochemical and genetic data because it demonstrated that Xantha-1 encodes a membrane-bound cyclase subunit. The evidence suggests that the aerobic cyclase requires at least one soluble and two membrane-bound components.
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