896 research outputs found
Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics
Alcohol dehydrogenases (ADH) participate in
the biosynthetic pathway of aroma volatiles in fruit by
interconverting aldehydes to alcohols and providing substrates
for the formation of esters. Two highly divergent
ADH genes (15% identity at the amino acid level) of
Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis)
have been isolated. Cm-ADH1 belongs to the
medium-chain zinc-binding type of ADHs and is highly
similar to all ADH genes expressed in fruit isolated so far.
Cm-ADH2 belongs to the short-chain type of ADHs. The
two encoded proteins are enzymatically active upon
expression in yeast. Cm-ADH1 has strong preference for
NAPDH as a co-factor, whereas Cm-ADH2 preferentially
uses NADH. Both Cm-ADH proteins are much more active
as reductases with Kms 10–20 times lower for the conversion
of aldehydes to alcohols than for the dehydrogenation
of alcohols to aldehydes. They both show strong preference
for aliphatic aldehydes but Cm-ADH1 is capable of
reducing branched aldehydes such as 3-methylbutyraldehyde,
whereas Cm-ADH2 cannot. Both Cm-ADH genes are
expressed specifically in fruit and up-regulated during
ripening. Gene expression as well as total ADH activity are
strongly inhibited in antisense ACC oxidase melons and in
melon fruit treated with the ethylene antagonist 1-methylcyclopropene
(1-MCP), indicating a positive regulation by
ethylene. These data suggest that each of the Cm-ADH
protein plays a specific role in the regulation of aroma
biosynthesis in melon fruit
Selected reactive oxygen species and antioxidant enzymes in common bean after Pseudomonas syringae pv. phaseolicola and Botrytis cinerea infection
Phaseolus vulgaris cv. Korona plants were
inoculated with the bacteria Pseudomonas syringae pv.
phaseolicola (Psp), necrotrophic fungus Botrytis cinerea
(Bc) or with both pathogens sequentially. The aim of the
experiment was to determine how plants cope with multiple
infection with pathogens having different attack strategy.
Possible suppression of the non-specific infection with
the necrotrophic fungus Bc by earlier Psp inoculation was
examined. Concentration of reactive oxygen species
(ROS), such as superoxide anion (O2
-) and H2O2 and
activities of antioxidant enzymes such as superoxide dismutase
(SOD), catalase (CAT) and peroxidase (POD) were
determined 6, 12, 24 and 48 h after inoculation. The
measurements were done for ROS cytosolic fraction and
enzymatic cytosolic or apoplastic fraction. Infection with
Psp caused significant increase in ROS levels since the
beginning of experiment. Activity of the apoplastic
enzymes also increased remarkably at the beginning of
experiment in contrast to the cytosolic ones. Cytosolic
SOD and guaiacol peroxidase (GPOD) activities achieved
the maximum values 48 h after treatment. Additional forms
of the examined enzymes after specific Psp infection were
identified; however, they were not present after single Bc
inoculation. Subsequent Bc infection resulted only in
changes of H2O2 and SOD that occurred to be especially
important during plant–pathogen interaction. Cultivar Korona
of common bean is considered to be resistant to Psp and mobilises its system upon infection with these bacteria.
We put forward a hypothesis that the extent of defence
reaction was so great that subsequent infection did not
trigger significant additional response
FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells
Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours
Communication Research
Contains reports on nine research projects.Bell Telephone Laboratories, Incorporate
Exploiting residue-level and profile-level interface propensities for usage in binding sites prediction of proteins
<p>Abstract</p> <p>Background</p> <p>Recognition of binding sites in proteins is a direct computational approach to the characterization of proteins in terms of biological and biochemical function. Residue preferences have been widely used in many studies but the results are often not satisfactory. Although different amino acid compositions among the interaction sites of different complexes have been observed, such differences have not been integrated into the prediction process. Furthermore, the evolution information has not been exploited to achieve a more powerful propensity.</p> <p>Result</p> <p>In this study, the residue interface propensities of four kinds of complexes (homo-permanent complexes, homo-transient complexes, hetero-permanent complexes and hetero-transient complexes) are investigated. These propensities, combined with sequence profiles and accessible surface areas, are inputted to the support vector machine for the prediction of protein binding sites. Such propensities are further improved by taking evolutional information into consideration, which results in a class of novel propensities at the profile level, i.e. the binary profiles interface propensities. Experiment is performed on the 1139 non-redundant protein chains. Although different residue interface propensities among different complexes are observed, the improvement of the classifier with residue interface propensities can be negligible in comparison with that without propensities. The binary profile interface propensities can significantly improve the performance of binding sites prediction by about ten percent in term of both precision and recall.</p> <p>Conclusion</p> <p>Although there are minor differences among the four kinds of complexes, the residue interface propensities cannot provide efficient discrimination for the complicated interfaces of proteins. The binary profile interface propensities can significantly improve the performance of binding sites prediction of protein, which indicates that the propensities at the profile level are more accurate than those at the residue level.</p
Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya
Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse
Prediction of binding hot spot residues by using structural and evolutionary parameters
In this work, we present a method for predicting hot spot residues by using a set of structural and evolutionary parameters. Unlike previous studies, we use a set of parameters which do not depend on the structure of the protein in complex, so that the predictor can also be used when the interface region is unknown. Despite the fact that no information concerning proteins in complex is used for prediction, the application of the method to a compiled dataset described in the literature achieved a performance of 60.4%, as measured by F-Measure, corresponding to a recall of 78.1% and a precision of 49.5%. This result is higher than those reported by previous studies using the same data set
Sequence-based identification of interface residues by an integrative profile combining hydrophobic and evolutionary information
<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions play essential roles in protein function determination and drug design. Numerous methods have been proposed to recognize their interaction sites, however, only a small proportion of protein complexes have been successfully resolved due to the high cost. Therefore, it is important to improve the performance for predicting protein interaction sites based on primary sequence alone.</p> <p>Results</p> <p>We propose a new idea to construct an integrative profile for each residue in a protein by combining its hydrophobic and evolutionary information. A support vector machine (SVM) ensemble is then developed, where SVMs train on different pairs of positive (interface sites) and negative (non-interface sites) subsets. The subsets having roughly the same sizes are grouped in the order of accessible surface area change before and after complexation. A self-organizing map (SOM) technique is applied to group similar input vectors to make more accurate the identification of interface residues. An ensemble of ten-SVMs achieves an MCC improvement by around 8% and F1 improvement by around 9% over that of three-SVMs. As expected, SVM ensembles constantly perform better than individual SVMs. In addition, the model by the integrative profiles outperforms that based on the sequence profile or the hydropathy scale alone. As our method uses a small number of features to encode the input vectors, our model is simpler, faster and more accurate than the existing methods.</p> <p>Conclusions</p> <p>The integrative profile by combining hydrophobic and evolutionary information contributes most to the protein-protein interaction prediction. Results show that evolutionary context of residue with respect to hydrophobicity makes better the identification of protein interface residues. In addition, the ensemble of SVM classifiers improves the prediction performance.</p> <p>Availability</p> <p>Datasets and software are available at <url>http://mail.ustc.edu.cn/~bigeagle/BMCBioinfo2010/index.htm</url>.</p
Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer
Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor-α) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1β was expressed in greatest (10–100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P=0.05, r=0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P=0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P=0.05 and P=0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1β overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential
signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P =
1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes
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