Phylogenetic analysis of the SAP30 family of transcriptional regulators reveals functional divergence in the domain that binds the nuclear matrix

Background: Deacetylation of histones plays a fundamental role in gene silencing, and this is mediated by a corepressor complex containing Sin3 as an essential scaffold protein. In this report we examine the evolution of two proteins in this complex, the Sin3-associated proteins SAP30L and SAP30, by using an archive of protein sequences from 62 species.Results: Our analysis indicates that in tetrapods SAP30L is more similar than SAP30 to the ancestral protein, and the two copies in this group originated by gene duplication which occurred after the divergence of Actinopterygii and Sarcopterygii about 450 million years ago (Mya). The phylogenetic analysis and biochemical experiments suggest that SAP30 has diverged functionally from the ancestral SAP30L by accumulating mutations that have caused attenuation of one of the original functions, association with the nuclear matrix. This function is mediated by a nuclear matrix association sequence, which consists of a conserved motif in the C-terminus and the adjacent nucleolar localization signal (NoLS).Conclusion: These results add further insight into the evolution and function of proteins of the SAP30 family, which share many characteristic with nuclear scaffolding proteins that are intimately involved in regulation of gene expression. Furthermore, SAP30L seems essential to eukaryotic biology, as it is found in animals, plants, fungi, as well as some taxa of unicellular eukaryotes

A comparative study of selected classification accuracy in user profiling

In recent years the used of personalization in service provisioning applications has been very popular. However, effective personalization cannot be achieved without accurate user profiles. A number of classification algorithms have been used to classify user related information to create accurate user profiles. In this study four different classification algorithms which are; naive Bayesian (NB), Bayesian Networks (BN), lazy learning of Bayesian rules (LBR) and instance-based learner (IB1) are compared using a set of user profile data. According to our simulation results NB and IB1 classifiers have the highest classification accuracy with the lowest error rate

Classification accuracy performance of Naïve Bayesian (NB), Bayesian Networks (BN), Lazy Learning of Bayesian Rules(LBR) and Instance-Based Learner (IB1) - comparative study

In recent years the used of personalization in service provisioning applications has been very popular. However, effective personalization cannot be achieved without accurate user profiles. A number of classification algorithms have been used to classify user related information to create accurate user profiles. In this study four different classification algorithms which are; naive Bayesian (NB), Bayesian networks (BN), lazy learning of Bayesian rules (LBR) and instance-based learner (IB1) are compared using a set of user profile data. According to our simulation results NB and IB1 classifiers have the highest classification accuracy with the lowest error rate. The obtained simulation results have been evaluated against the existing works of support vector machines (SVMs), decision trees (DTs) and neural networks (NNs)

Investigation of Mobile IPv6 and SIP integrated architectures for IMS and VoIP applications

Mobile IPv6 and SIP are protocols designed to support different types of mobility. Mobile IPv6 has been used to support mobility in IP networks and SIP has been used for voice over IP applications. It is the signalling protocol of the IP multimedia subsystem (IMS). In this paper both protocols have been simulated and compared in order to observe their performance for voice over IP (VoIP) applications. In this paper the architectures proposed by researchers in order to combine mobile IPv6 and SIP have also been investigated and compared to analyse their advantages and disadvantages. A network scenario, running mobile IPv6 and SIP for IMS, has also been simulated in order to evaluate the performance offered by the two protocols and to compare them with the results from the simulation of the pure mobile IPv6 and SIP architectures. The comparison shows that the combined scenario offers better performance similar to the one obtained using only mobile IPv6 with route optimization. The scenario simulated was also compared with the integrated architectures for mobile IPv6 and SIP that were investigated

webGQT: A Shiny Server for Genotype Query Tools for Model-Based Variant Filtering

Genotype Query Tools (GQT) were developed to discover disease-causing variations from billions of genotypes and millions of genomes, processes data at substantially higher speed over other existing methods. While GQT has been available to a wide audience as command-line software, the difficulty of constructing queries among non-IT or non-bioinformatics researchers has limited its applicability. To overcome this limitation, we developed webGQT, an easy-to-use tool with a graphical user interface. With pre-built queries across three modules, webGQT allows for pedigree analysis, case-control studies, and population frequency studies. As a package, webGQT allows researchers with less or no applied bioinformatics/IT experience to mine potential disease-causing variants from billions. Results webGQT offers a flexible and easy-to-use interface for model-based candidate variant filtering for Mendelian diseases from thousands to millions of genomes at a reduced computation time. Additionally, webGQT provides adjustable parameters to reduce false positives and rescue missing genotypes across all modules. Using a case study, we demonstrate the applicability of webGQT to query non-human genomes. In addition, we demonstrate the scalability of webGQT on large data sets by implementing complex population-specific queries on the 1000 Genomes Project Phase 3 data set, which includes 8.4 billion variants from 2504 individuals across 26 different populations. Furthermore, webGQT supports filtering single-nucleotide variants, short insertions/deletions, copy number or any other variant genotypes supported by the VCF specification. Our results show that webGQT can be used as an online web service, or deployed on personal computers or local servers within research groups. Availability webGQT is made available to the users in three forms: 1) as a webserver available at https://vm1138.kaj.pouta.csc.fi/webgqt/, 2) as an R package to install on personal computers, and 3) as part of the same R package to configure on the user's own servers. The application is available for installation at https://github.com/arumds/webgqt.Peer reviewe

Cost analysis of antiretroviral agents available in India

Background: AIDS is one of the most prevalent causes of death due to infectious origin which requires a lifelong therapy. There is variation in prices of antiretroviral drugs available in Indian market. Thus, a study was planned to find out variation in prices of antiretroviral drugs either as a single drug or in combination and to evaluate the difference in cost of various brands of the same antiretroviral drugs by calculating percentage variation in cost in Indian rupees.Methods: Cost of antiretroviral drugs manufactured by different pharmaceutical companies, in the same strength and dosage forms was obtained from “Current Index of Medical Specialties” July-October 2014 and “Indian Drug Review” Vol. XXI, Issue No. 4, 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in cost was calculated.Results: Percentage variation in cost for antiretroviral drugs marketed in India was found to be zidovudine (100 mg) - 436%, lamivudine (100 mg) - 268%, tenofovir (300 mg) - 149.5%, didanosine (250 mg) - 73.75%, indinavir (400 mg) - 35.26%. Among the combination therapy, price variation was lamivudine + zidovudine (150 + 300 mg) - 314%, lamivudine + stavudine (150 + 40 mg) - 105%, lopinavir + ritonavir (133.3 + 33 mg) - 25%.Conclusion: There is wide variation in the prices of antiretroviral agents available in the market. Regulatory authorities, pharma companies, physicians should maximize their efforts to reduce the cost of drugs

Cure of human immunodeficiency virus/acquired immune deficiency syndrome: promising future prospects at horizon

Acquired immune deficiency syndrome (AIDS) is a disease caused by humanimmunodeficiency virus and characterized by profound immunosuppression thatleads to opportunistic infections, secondary neoplasms, and neurologic complications.AIDS is among the leading causes of death worldwide. Current therapeutic optionsare directed only toward management of AIDS, but not toward its prevention or cure.In addition, it also possesses numerous problems like drug resistance, drug toxicity,drug interactions, non-adherence to therapy, life-long and expensive treatment, etc.Recent years in drug development have shown promising prospects for prevention/treatment/cure of AIDS like histone deacetylase inhibitors, Vpu ion channel inhibitors,viral decay acceleration, maturation inhibitors, tat antagonists, gene/stem cell therapy,and antiretroviral vaccines

Thoracic high resolution CT using the modified VetMousetrap (TM) device is a feasible method for diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers

Canine idiopathic pulmonary fibrosis is a chronic, progressive interstitial lung disease particularly prevalent in West Highland White Terriers. In the present prospective pilot study, we evaluated the feasibility of modified VetMousetrap (TM) device in high resolution CT to detect idiopathic pulmonary fibrosis in West Highland White Terriers. Twelve awake West Highland White Terriers with canine idiopathic pulmonary fibrosis and 24 clinically healthy West Highland White Terriers were scanned using a helical dual slice scanner utilizing VetMousetrap (TM) device without or with minimal chemical restraint with butorphanol. Three evaluators blindly assessed the images for image quality and the presence of canine idiopathic pulmonary fibrosis related imaging findings such as ground glass opacity and reticular opacities. Additionally, the attenuation of the lung was quantified with ImageJ software using histogram analysis of density over the lung fields. Computed tomography was successfully completed and motion artifact ranked in statistical analysis barely noticeable to mild in all dogs. The agreement between imaging findings and clinical status was very good with overall kappa value 0.91 and percentage of agreement of 94%. There was also very good intraobserver (kappa(range) = 0.79-0.91) and interobserver agreement (kappa = 0.94). Moderate to severe ground glass opacity was present in all affected dogs. In the ImageJ analysis, a significant difference in lung attenuation between the study groups was observed. We conclude that modified VetMousetrap (TM) device is applicable in diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers avoiding anesthetic risk in these often severely hypoxic patients.Peer reviewe

Metabolome of canine and human saliva: a non-targeted metabolomics study

Introduction Saliva metabolites are suggested to reflect the health status of an individual in humans. The same could be true with the dog (Canis lupus familiaris), an important animal model of human disease, but its saliva metabolome is unknown. As a non-invasive sample, canine saliva could offer a new alternative material for research to reveal molecular mechanisms of different (patho)physiological stages, and for veterinary medicine to monitor dogs' health trajectories. Objectives To investigate and characterize the metabolite composition of dog and human saliva in a non-targeted manner. Methods Stimulated saliva was collected from 13 privately-owned dogs and from 14 human individuals. We used a non-targeted ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) method to measure metabolite profiles from saliva samples. Results We identified and classified a total of 211 endogenous and exogenous salivary metabolites. The compounds included amino acids, amino acid derivatives, biogenic amines, nucleic acid subunits, lipids, organic acids, small peptides as well as other metabolites, like metabolic waste molecules and other chemicals. Our results reveal a distinct metabolite profile of dog and human saliva as 25 lipid compounds were identified only in canine saliva and eight dipeptides only in human saliva. In addition, we observed large variation in ion abundance within and between the identified saliva metabolites in dog and human. Conclusion The results suggest that non-targeted metabolomics approach utilizing UHPLC-qTOF-MS can detect a wide range of small compounds in dog and human saliva with partially overlapping metabolite composition. The identified metabolites indicate that canine saliva is potentially a versatile material for the discovery of biomarkers for dog welfare. However, this profile is not complete, and dog saliva needs to be investigated in the future with other analytical platforms to characterize the whole canine saliva metabolome. Furthermore, the detailed comparison of human and dog saliva composition needs to be conducted with harmonized study design.Peer reviewe

Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs

Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic seizures occurring mainly during relaxation periods, a juvenile age of onset and generalized tonic-clonic seizures in one-third of patients. An 8-month-old female intact RR was presented for myoclonic seizures and staring episodes that both started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous mutant genotype. Unsedated wireless video-electroencephalography (EEG) identified frequent, bilaterally synchronous, generalized 4 Hz spike-and-wave complexes (SWC) during the staring episodes in addition to the characteristic myoclonic seizures with generalized 4-5 Hz SWC or 4-5 Hz slowing. Photic stimulation did not evoke a photoparoxysmal response. Repeat video-EEG 2 months after initiation of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic seizures, and absence seizures were no longer evident. Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which reinforces its parallels to JME in humans.Peer reviewe