RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Diagnostic accuracy of non-specialist versus specialist health workers in diagnosing hearing loss and ear disease in Malawi.

OBJECTIVE: To determine whether a non-specialist health worker can accurately undertake audiometry and otoscopy, the essential clinical examinations in a survey of hearing loss, instead of a highly skilled specialist (i.e. ENT or audiologist). METHODS: A clinic-based diagnostic accuracy study was conducted in Malawi. Consecutively sampled participants ≥ 18 years had their hearing tested using a validated tablet-based audiometer (hearTest) by an audiologist (gold standard), an audiology officer, a nurse and a community health worker (CHW). Otoscopy for diagnosis of ear pathologies was conducted by an ENT specialist (gold standard), an ENT clinical officer, a CHW, an ENT nurse and a general nurse. Sensitivity, specificity and kappa (κ) were calculated. 80% sensitivity, 70% specificity and kappa of 0.6 were considered adequate. RESULTS: Six hundred and seventeen participants were included. High sensitivity (>90%) and specificity (>85%) in detecting bilateral hearing loss was obtained by all non-specialists. For otoscopy, sensitivity and specificity were >80% for all non-specialists in diagnosing any pathology except for the ENT nurse. Agreement in diagnoses for the ENT clinical officer was good (κ = 0.7) in both ears. For other assessors, moderate agreement was found (κ = 0.5). CONCLUSION: A non-specialist can be trained to accurately assess hearing using mobile-based audiometry. However, accurate diagnosis of ear conditions requires at least an ENT clinical officer (or equivalent). Conducting surveys of hearing loss with non-specialists could lower costs and increase data collection, particularly in low- and middle-income countries, where ENT specialists are scarce

Radiation induced angiosarcoma a sequela of radiotherapy for breast cancer following conservative surgery

Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy following conservative breast surgery. They are very rare tumors and often their diagnosis is delayed due to their benign appearance and difficulty in differentiation from radiation induced skin changes. Therefore it is very important that clinicians are aware of their existence. We report here a case of RIA followed by discussion and review of literature

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules — the SPUtNIk study

$\textbf{Introduction:}$ Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrastenhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. $\textbf{Methods and analysis:}$ The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) ($^{18}$FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for $^{18}$FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. $\textbf{Ethics and dissemination:}$ Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals.The trial is funded by the National Institute for Health Research HTA Programme (grant no: 09/22/117) and is being run by Southampton Clinical Trials Unit, directed by Professor Gareth Griffiths and part funded by Cancer Research UK. NRQ and RCR are part funded by the Cambridge Biomedical Research Centre and the Cancer Research Network: Eastern

Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Seroprevalence of hepatitis C in type 2 diabetes: evidence for a positive association

<p>Abstract</p> <p>Background</p> <p>There is a growing body of literature on the relationship of Hepatitis C virus infection (HCV) and type 2 diabetes mellitus (T2DM). However, there are certain gaps in literature and the data is inconclusive. This study was, therefore, carried out to determine the prevalence of HCV infection in diabetic patients and to elucidate the presence of any possible relationship between HCV and T2DM in this region.</p> <p>Methods</p> <p>Serologic testing for anti-HCV antibody was done on a sample of 3000 individuals with T2DM visiting Diabetes Clinic of Nishtar Medical College Hospital, Multan and 10,000 volunteer blood donors visiting blood bank of the same hospital during the study period using Accurate rapid immunochromatographic kits which was later confirmed by using Chemelex S.A third generation ELISA kit for positive cases. Data about various variables was collected from diabetic patients using a structured questionnaire after taking informed consent.</p> <p>Results</p> <p>Prevalence rate of 13.7% for HCV infection was recorded among subjects having T2DM with seropositivity rate of 4.9% among the control group of volunteer blood donors without diabetes. The patients with T2DM were more likely to have HCV infection as compared to the control group (OR = 3.03, 95%CI = 2.64-3.48, p = 0.001). Diabetic patients with age above 55 years had higher prevalence rate as compared to younger individuals. Male patients had significantly high seropositivity as compared to female patients (15.3% vs. 12.4%, p = 0.02). Those with duration of diabetes 11 years and above and the ones with good glycemic control had higher seroprevalence rates of 18.2% and 18.7% respectively. There was no statistically significant difference among subjects when the distribution of HCV was studied on the basis of marital status, locality, or family history of diabetes.</p> <p>Conclusions</p> <p>The results show that there is a strong association between HCV and T2DM in the region as evident from significantly higher prevalence of HCV infection in diabetics as compared to the control group in the present study.</p

Random UV-C mutagenesis of Scheffersomyces (formerly Pichia) stipitis NRRL Y-7124 to improve anaerobic growth on lignocellulosic sugars

Scheffersomyces (formerly Pichia) stipitis NRRL Y-7124 was mutagenized using UV-C irradiation to produce yeast strains for anaerobic conversion of lignocellulosic sugars to ethanol. UV-C irradiation potentially produces large numbers of random mutations broadly and uniformly over the whole genome to generate unique strains. Wild-type cultures of S. stipitis NRRL Y-7124 were subjected to UV-C (234 nm) irradiation targeted at approximately 40% cell survival. When surviving cells were selected in sufficient numbers via automated plating strategies and cultured anaerobically on xylose medium for 5 months at 28°C, five novel mutagenized S. stipitis strains were obtained. Variable number tandem repeat analysis revealed that mutations had occurred in the genome, which may have produced genes that allowed the anaerobic utilization of xylose. The mutagenized strains were capable of growing anaerobically on xylose/glucose substrate with higher ethanol production during 250- to 500-h growth than a Saccharomyces cerevisiae yeast strain that is the standard for industrial fuel ethanol production. The S. stipitis strains resulting from this intense multigene mutagenesis strategy have potential application in industrial fuel ethanol production from lignocellulosic hydrolysates