USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))

Review on USP6 (ubiquitin specific protease 6 (Tre-2 oncogene)), with data on DNA, on the protein encoded, and where the gene is implicated

Thermodynamics of Competitive Molecular Channel Transport: Application to Artificial Nuclear Pores

In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probablity when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules

Prediction of Protein Domain with mRMR Feature Selection and Analysis

The domains are the structural and functional units of proteins. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop effective methods for predicting the protein domains according to the sequences information alone, so as to facilitate the structure prediction of proteins and speed up their functional annotation. However, although many efforts have been made in this regard, prediction of protein domains from the sequence information still remains a challenging and elusive problem. Here, a new method was developed by combing the techniques of RF (random forest), mRMR (maximum relevance minimum redundancy), and IFS (incremental feature selection), as well as by incorporating the features of physicochemical and biochemical properties, sequence conservation, residual disorder, secondary structure, and solvent accessibility. The overall success rate achieved by the new method on an independent dataset was around 73%, which was about 28–40% higher than those by the existing method on the same benchmark dataset. Furthermore, it was revealed by an in-depth analysis that the features of evolution, codon diversity, electrostatic charge, and disorder played more important roles than the others in predicting protein domains, quite consistent with experimental observations. It is anticipated that the new method may become a high-throughput tool in annotating protein domains, or may, at the very least, play a complementary role to the existing domain prediction methods, and that the findings about the key features with high impacts to the domain prediction might provide useful insights or clues for further experimental investigations in this area. Finally, it has not escaped our notice that the current approach can also be utilized to study protein signal peptides, B-cell epitopes, HIV protease cleavage sites, among many other important topics in protein science and biomedicine

Adolescent survey non-response and later risk of death. A prospective cohort study of 78 609 persons with 11-year follow-up

<p>Abstract</p> <p>Background</p> <p>Non-response in survey studies is a growing problem and, being usually selective, it leads to under- or overestimation of health outcomes in the follow-up. We followed both respondents and non-respondents by registry linkage to determine whether there is a risk of death, related to non-response at baseline.</p> <p>Methods</p> <p>Sample data of biennial surveys to 12-18-year-old Finns in 1979–1997 were linked with national death registry up to 2001. The number of respondents was 62 528 (79.6%) and non-respondents 16 081 (20.4%). The average follow-up was 11.1 years, totalling 876 400 person-years. The risk of death between non-respondents and respondents was estimated by hazard ratios (HR).</p> <p>Results</p> <p>The number of deaths per 100 000 person-years were 229 in non-respondents and 447 in respondents (HR 2.0, 95% CI: 1.5–2.6). The hazard ratios of death were for intoxication 3.2 (95% CI: 1.9–5.4), for disease 3.1 (95% CI: 2.2–4.1), for violence-related injury 2.0 (95% CI: 1.5–2.6) and for unintentional injury 1.8 (95% CI: 1.3–2.4) in non-respondents vs. respondents. The association between non-response and death increased with age at baseline, and the increase persisted after the age of 25.</p> <p>Conclusion</p> <p>Our study demonstrated significantly increased rates of death among adolescent non-respondents in a follow-up. The highest hazard ratios were seen in disease- and violence-related deaths. The death rate varied between respondents and non-respondents by death type. Increased rates of death persisted beyond the age of 25.</p

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

Factors associated with dental caries among institutionalized residents with schizophrenia in Taiwan: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little research has been done on the relationship between dental caries and the personal characteristics of institutionalized residents diagnosed with schizophrenia. This study investigates the individual and treatment factors associated with the dental caries among institutionalized residents with schizophrenia in Taiwan.</p> <p>Methods</p> <p>An oral health survey of institutionalized residents with schizophrenia in the largest public psychiatric hospital was conducted in Taiwan in 2006. Based on this data, multiple logistic analyses were used to determine the relationship between some explanatory variables and the outcome variables of dental caries among subjects with schizophrenia.</p> <p>Results</p> <p>Among the 1,108 subjects with schizophrenia, age was the only variable independently associated with DMFT > 8 (OR = 7.74, 95% CI = 3.86-15.55, p < 0.001 in comparison to residents aged 65 + years vs. 20-44 years; OR = 3.06, 95% CI = 2.03-4.61, p < 0.001 in comparison to residents aged 55-64 years vs. 20-44 years) after making adjustments for other explanatory variables. In addition, those with an education of only elementary school (OR = 1.67, 95% CI = 1.08-2.56, p = 0.021), low income (OR = 1.58, 95% CI = 1.02-2.44, p = 0.039), and length of stay (LOS) of > 10 years (OR = 2.09, 95% CI = 1.30-3.37, p = 0.002) were associated with a care index < 54.7%. Older age, lower educational level, and longer hospital stays were associated with number of remaining teeth being < 24.</p> <p>Conclusions</p> <p>Aging was the most important factor related to a high level of dental caries. Low educational level, low income, and LOS were also associated with the indicators of dental caries among institutionalized subjects with schizophrenia. It is necessary to address the treatment factors such as prolonged stay in institutions when decision-makers are planning for preventive strategies of oral health for institutionalized residents with schizophrenia.</p

Identification of Potent EGFR Inhibitors from TCM Database@Taiwan

Overexpression of epidermal growth factor receptor (EGFR) has been associated with cancer. Targeted inhibition of the EGFR pathway has been shown to limit proliferation of cancerous cells. Hence, we employed Traditional Chinese Medicine Database (TCM Database@Taiwan) (http://tcm.cmu.edu.tw) to identify potential EGFR inhibitor. Multiple Linear Regression (MLR), Support Vector Machine (SVM), Comparative Molecular Field Analysis (CoMFA), and Comparative Molecular Similarities Indices Analysis (CoMSIA) models were generated using a training set of EGFR ligands of known inhibitory activities. The top four TCM candidates based on DockScore were 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid, and all had higher binding affinities than the control Iressa®. The TCM candidates had interactions with Asp855, Lys716, and Lys728, all which are residues of the protein kinase binding site. Validated MLR (r² = 0.7858) and SVM (r² = 0.8754) models predicted good bioactivity for the TCM candidates. In addition, the TCM candidates contoured well to the 3D-Quantitative Structure-Activity Relationship (3D-QSAR) map derived from the CoMFA (q² = 0.721, r² = 0.986) and CoMSIA (q² = 0.662, r² = 0.988) models. The steric field, hydrophobic field, and H-bond of the 3D-QSAR map were well matched by each TCM candidate. Molecular docking indicated that all TCM candidates formed H-bonds within the EGFR protein kinase domain. Based on the different structures, H-bonds were formed at either Asp855 or Lys716/Lys728. The compounds remained stable throughout molecular dynamics (MD) simulation. Based on the results of this study, 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid are suggested to be potential EGFR inhibitors.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University (CMU98-TCM)China Medical University (CMU99-TCM)China Medical University (CMU99-S-02)China Medical University (CMU99-ASIA-25)China Medical University (CMU99-ASIA-26)China Medical University (CMU99-ASIA-27)China Medical University (CMU99-ASIA-28)Asia UniversityTaiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

An ALMA survey of the SCUBA-2 Cosmology Legacy Survey UKIDSS/UDS field: halo masses for submillimetre galaxies

We present an analysis of the spatial clustering of a large sample of high-resolution, interferometically identified, submillimetre galaxies (SMGs). We measure the projected cross-correlation function of ∼350 SMGs in the UKIDSS Ultra Deep-Survey Field across a redshift range of z = 1.5–3 utilizing a method that incorporates the uncertainties in the redshift measurements for both the SMGs and cross-correlated galaxies through sampling their full probability distribution functions. By measuring the absolute linear bias of the SMGs, we derive halo masses of log10(Mhalo[h−1M⊙]) ∼ 12.8 with no evidence of evolution in the halo masses with redshift, contrary to some previous work. From considering models of halo mass growth rates, we predict that the SMGs will reside in haloes of mass log10(Mhalo[h−1M⊙]) ∼ 13.2 at z = 0, consistent with the expectation that the majority of z = 1.5–3 SMGs will evolve into present-day spheroidal galaxies. Finally, comparing to models of stellar-to-halo mass ratios, we show that SMGs may correspond to systems that are maximally efficient at converting their gas reservoirs into stars. We compare them to a simple model for gas cooling in haloes that suggests that the unique properties of the SMG population, including their high levels of star formation and their redshift distribution, are a result of the SMGs being the most massive galaxies that are still able to accrete cool gas from their surrounding intragalactic medium