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1.  Resuscitation Promoting Factors: a Family of Microbial Proteins in Survival and Resuscitation of Dormant Mycobacteria 
Indian Journal of Microbiology  2011;52(2):114-121.
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is an extraordinarily successful pathogen of humankind. It has been estimated that up to one-third of the world’s population is infected with M. tuberculosis, and this population is an important reservoir for disease reactivation. Resuscitation promoting factor (Rpf) is a secretory protein, which was first reported in Micrococcus luteus. There are five functionally redundant Rpf-like proteins found in M. tuberculosis. Rpf promotes the resuscitation of dormant bacilli to yield normal, viable colony forming bacteria. All Rpfs share a conserved domain of about 70 amino acids and possess a lysozyme-like activity. The structural studies of the conserved domain suggest that Rpfs could be considered as a c-type lysozyme and lytic transglycosylases. Recently a novel class of nitrophenylthiocyanates (NPT) inhibitors of the muralytic activity of Rpf were reported which opens a new approach in the study of cell-wall hydrolyzing enzymes. This review describes molecular and structural studies conducted on Rpf proteins, their role in the resuscitation of dormant bacteria, in the reactivation of latent infection and identification of low molecular weight inhibitors of resuscitation promoting factors.
doi:10.1007/s12088-011-0202-6
PMCID: PMC3386435  PMID: 23729870
Rpf; Latency; Dormancy; NPT; Antimicrobial compound
2.  Translation and validation of International Restless Leg Syndrome Study Group rating scale in Hindi language 
Objectives:
The objective of this study is to translate and validate the International Restless Leg Syndrome Study Group rating scale (IRLS) in Hindi language.
Materials and Methods:
Thirty one consecutive patients diagnosed of Restless Leg Syndrome (RLS) were included in the study. Control group comprised of 31 subjects not having any symptom of RLS. The scale was procured from MAPI research trust; and, permission for the translation was sought. The translation was done according to the guidelines provided by the publisher. After translation, final version of the scale was applied in both the groups to find out the reliability and clinical validity.
Results:
RLS group had a predominance of females, and they were younger than the male counterparts (Age=36.80 ± 10.46 years vs 45.18 ± 8.34 years; t=2.28; P=0.03). There was no difference in the mean age between groups (RLS=39.77 ± 10.44 years vs Non RLS=38.29 ± 11.29 years; t=-0.53; P=0.59). IRLS scores were significantly different between both groups on all items (P<0.001). Translated version showed high reliability (Cronbach's alpha=0.86). IRLS scores were significantly different between both groups on all items (P<0.001).
Conclusion:
Hindi version of IRLS is reliable and a clinically valid tool that can be applied in Hindi speaking population.
doi:10.4103/0972-2327.91939
PMCID: PMC3271463  PMID: 22346013
Hindi translation; International Restless Leg Syndrome Study Group rating scale; Restless Leg Syndrome; translation; validation
3.  Tree-Based Position Weight Matrix Approach to Model Transcription Factor Binding Site Profiles 
PLoS ONE  2011;6(9):e24210.
Most of the position weight matrix (PWM) based bioinformatics methods developed to predict transcription factor binding sites (TFBS) assume each nucleotide in the sequence motif contributes independently to the interaction between protein and DNA sequence, usually producing high false positive predictions. The increasing availability of TF enrichment profiles from recent ChIP-Seq methodology facilitates the investigation of dependent structure and accurate prediction of TFBSs. We develop a novel Tree-based PWM (TPWM) approach to accurately model the interaction between TF and its binding site. The whole tree-structured PWM could be considered as a mixture of different conditional-PWMs. We propose a discriminative approach, called TPD (TPWM based Discriminative Approach), to construct the TPWM from the ChIP-Seq data with a pre-existing PWM. To achieve the maximum discriminative power between the positive and negative datasets, the cutoff value is determined based on the Matthew Correlation Coefficient (MCC). The resulting TPWMs are evaluated with respect to accuracy on extensive synthetic datasets. We then apply our TPWM discriminative approach on several real ChIP-Seq datasets to refine the current TFBS models stored in the TRANSFAC database. Experiments on both the simulated and real ChIP-Seq data show that the proposed method starting from existing PWM has consistently better performance than existing tools in detecting the TFBSs. The improved accuracy is the result of modelling the complete dependent structure of the motifs and better prediction of true positive rate. The findings could lead to better understanding of the mechanisms of TF-DNA interactions.
doi:10.1371/journal.pone.0024210
PMCID: PMC3166302  PMID: 21912677
4.  IsoformEx: isoform level gene expression estimation using weighted non-negative least squares from mRNA-Seq data 
BMC Bioinformatics  2011;12:305.
Background
mRNA-Seq technology has revolutionized the field of transcriptomics for identification and quantification of gene transcripts not only at gene level but also at isoform level. Estimating the expression levels of transcript isoforms from mRNA-Seq data is a challenging problem due to the presence of constitutive exons.
Results
We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms. Validations based on in silico simulation of mRNA-Seq and qRT-PCR experiments with real mRNA-Seq data showed that IsoformEx could accurately estimate transcript expression levels. In comparisons with published methods, the transcript expression levels estimated by IsoformEx showed higher correlation with known transcript expression levels from simulated mRNA-Seq data, and higher agreement with qRT-PCR measurements of specific transcripts for real mRNA-Seq data.
Conclusions
IsoformEx is a fast and accurate algorithm to estimate transcript expression levels and gene expression levels, which takes into account short exons and alternative exons with a weighting scheme. The software is available at http://bioinformatics.wistar.upenn.edu/isoformex.
doi:10.1186/1471-2105-12-305
PMCID: PMC3180389  PMID: 21794104
5.  Insomnia Associated with Depressive Disorder: Primary, Secondary, or Mixed? 
Background:
Insomnia is a common problem that is known to occur during depression. However, literature still debates whether insomnia is part of depression or a separate entity.
Materials and Methods:
Subjects presenting with depressive disorder according to DSM-IV-Text Revision criteria were recruited after seeking informed consent. Clinical interview was performed with the help of Mini International Neuropsychiatric Interview Plus. Their demographic data and depression related history were recorded. Depression severity was assessed by using Hamilton Rating Scale for Depression. Diagnosis of insomnia was made with the help of International Classification of Sleep Disorders-2 criteria. Type of insomnia, its duration, and its relationship with depressive illness were specifically asked. If any subject fulfilled criteria for more than one type of insomnia, both were recorded. Statistical analysis was done with the help of statistical package for social sciences (SPSS) version 17.0. χ2 test, independent sample t test, and Pearson's correlation were performed.
Results:
A total of 54 subjects were enrolled in this study. Primary insomnia was seen in 40.7% cases and secondary insomnia in 58.8% cases; 27.3% subjects did not experience insomnia along with depressive disorder. In the primary insomnia category, adjustment insomnia was most prevalent (63.6%), and in secondary insomnia group, insomnia due to depressive disorder was most frequent (59.3%). Interestingly, primary insomnia often followed an onset of depressive illness (P=0.04), while secondary insomnia preceded it (c2 =11.1; P=0.004). The presence of either type of insomnias was not influenced by duration of depressive illness, number of depressive episodes, and duration of current depressive episode. On the other hand, duration of insomnia was positively correlated with total duration of depressive illness (P=0.003), number of episodes (P=0.04), and duration of current depressive episode (P<0.001).
Conclusion:
Primary insomnia is common in subjects with depression, and it usually follows depressive illness. On the other hand, secondary insomnia often precedes the onset of depressive illness. Duration of insomnia positively correlates with duration and frequency of depressive episodes.
doi:10.4103/0253-7176.92056
PMCID: PMC3271484  PMID: 22345834
Major depressive disorder; primary insomnia; secondary insomnia
6.  Translation and Validation of the Insomnia Severity Index in Hindi Language 
Aims and Objectives:
Translation of the Insomnia Severity Index from English to Hindi and Validation of the Hindi version.
Materials and Methods:
The translation process of the Insomnia Severity Index was initiated after obtaining due permission from the author of the original version of the same. Translation was carried out by using standard translation procedures, such as combined translation, decentering, and pretest method. The final version of the Insomnia Severity Index in Hindi was finally validated. A randomly selected sample size of 65 subjects was enrolled for the purpose of validation and testing the reliability of Hindi version of the Insomnia Severity Index. Insomnia was present in 45 subjects and they constituted the insomnia group. The rest 20 subjects did not have insomnia and were included in the control group. The Hindi version of the Insomnia Severity Index was applied to both the groups.
Results:
The total sample constituted of 50.8% males and 49.2% females. The mean age in the control group was 30.8±8.3 years and that in the insomnia group was 40.3±4 years (t=3.04; P=0.001). The translated version of the Insomnia Severity Index showed a reliability of 0.91 (Cronbach's α=0.91). This was not just simple translation, but many of the words were changed to adapt it for the local population.
Conclusion:
The Hindi version of the Insomnia Severity Index is a valid and reliable tool that can be administered for the assessment of severity of insomnia.
doi:10.4103/0253-7176.92060
PMCID: PMC3271495  PMID: 22345845
Hindi; insomnia; insomnia severity index; validation
7.  Kleine-Levin Syndrome and Idiopathic Hypersomnia: Spectrum Disorders 
Kleine–Levin syndrome (KLS) and idiopathic hypersomnia (IH) are primary sleep disorders of unknown etiologies, which often run a chronic course. The common core symptoms of these syndromes are hypersomnolence and sleep drunkenness, with periodic hypersomnolence and hyperphagia being the prominent symptoms of KLS. Psychiatric manifestations are common to both and include irritability, depression, apathy, inattention and poor concentration. Both disorders are diagnosed clinically and no specific laboratory investigation is available to confirm the diagnosis. We present a case highlighting the overlapping of the symptoms of KLS and IH, producing a complex clinical picture.
doi:10.4103/0253-7176.92048
PMCID: PMC3271500  PMID: 22345850
Hyperphagia; hypersomnolence; idiopathic hypersomnia; Kleine–Levin syndrome; periodic hypersomnolence
8.  Acyl Homoserine Lactones from Culture Supernatants of Pseudomonas aeruginosa Accelerate Host Immunomodulation 
PLoS ONE  2011;6(6):e20860.
The virulence of Pseudomonas aeruginosa is multifactorial and under the control of quorum sensing signals, such as acyl homoserine lactones (AHLs). The importance of these molecules in the establishment of infection has been previously reported. These molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response. To establish the immune modulating potential of quorum sensing signal molecules, previous studies have only used synthetic AHLs. However, there can be differences in the biological properties of synthetic and natural AHLs. The use of naturally extracted AHLs from the culture supernatant of P. aeruginosa is likely to simulate natural conditions more than the use of synthetic AHLs. Therefore, in the present study, the immune modulating potential of synthetic and naturally extracted AHLs was compared using a thymidine uptake assay, immunophenotyping and sandwich ELISA in order to assess mouse T-cell proliferation and production of Th1 and Th2 cytokines. Natural AHLs were able to suppress T-cell proliferation, even at low concentrations, compared to synthetic AHLs. The majority of cells undergoing proliferation were CD4+, as revealed by immunophenotyping. The inhibition of T-cells was stronger with natural AHLs compared to synthetic AHLs. Moreover, the natural AHLs were also able to shift immune responses away from host protective Th1 responses to pathogen protective Th2 responses.
doi:10.1371/journal.pone.0020860
PMCID: PMC3116856  PMID: 21698201
9.  The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains 
Retrovirology  2011;8:31.
Background
The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). This pathway emerges after long term failure of therapy, and is increasingly observed in the resource poor world, where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring.
Results
Single-genome sequencing (SGS) of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions; seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI susceptibility. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated ~44% replicative capacity of that at 4 months. This was further reduced to ~22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain.
Conclusions
We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains.
doi:10.1186/1742-4690-8-31
PMCID: PMC3113953  PMID: 21569325
10.  Comparison of clinical characteristics of migraine and tension type headache 
Indian Journal of Psychiatry  2011;53(2):134-139.
Context:
Migraine and tension type headache (TTH) are two most common types of primary headaches. Though the International Classification of Headache Disorders-2 (ICHD-2) describes the diagnostic criteria, even then in clinical practice, patients may not respect these boundaries resulting in the difficulty in diagnosis of these pains.
Materials and Methods:
This cross-sectional study involved 50 subjects in each of the two groups – migraine and TTH – after screening for the inclusion and exclusion criteria. Diagnosis was made according to the ICHD-2 criteria. Their clinical history was taken in detail and noted in a semi-structured performa. They were examined for the presence of a number of factors like pericranial tenderness and muscle parafunction. Statistical analysis was done with the help of SPSS v 11.0. To compare the non-parametric issues, chi-square test was run and continuous variables were analyzed using independent sample t test.
Results:
In general, migraineurs had progressive illness (χ2=9.45; P=0.002) with increasing severity (χ2=21.86; P<0.001), frequency (χ2=8.5; P=0.04) and duration of each headache episode (χ2=4.45; P=0.03) as compared to TTH subjects. Along with the headache, they more commonly suffered orthostatic pre-syncope (χ2=19.94; P<0.001), palpitations (42%vs.18% among TTH patients; χ2=6.87; P=0.009), nausea and vomiting (68% vs. 6% in TTH; χ2=41.22; P<0.001, and 38% vs. none in TTH; χ2=23.45, P<0.001, respectively), phonophobia (χ2=44.98; P<0.001), photophobia (χ2=46.53; P<0.001), and osmophobia (χ2=15.94; P<0.001). Their pain tended to be aggravated by head bending (χ2=50.17; P<0.001) and exercise (χ2=11.41; P<0.001). Analgesics were more likely to relieve pain in migraineurs (χ2=21.16; P<0.001). In addition, post-headache lethargy was more frequent among the migraineurs (χ2=22.01; P<0.001). On the other hand, stressful situations used to trigger TTH (χ2=9.33; P=0.002) and muscle parafunction was more common in TTH patients (46% vs. 20%; χ2=7.64; P=0.006). All the cranial autonomic symptoms were more common in migraineurs as compared to TTH subjects (conjunctival injection: χ2=10.74, P=0.001; lacrimation: χ2=17.82, P<0.001; periorbital swelling: χ2=23.45, P<0.001; and nasal symptoms: χ2=6.38, P=0.01).
Conclusion:
A number of symptoms that are presently not included in the ICHD-2 classification may help in differe-ntiating the migraine from the TTH.
doi:10.4103/0019-5545.82538
PMCID: PMC3136015  PMID: 21772645
Migraine; symptoms; tension type headache

Results 1-10 (10)