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1.  Pulmonary hypertension due to presence of isolated partial anomalous pulmonary venous connection: A case report 
Anomalous pulmonary venous return is an uncommon congenital malformation which can be broadly categorized into partial or total, of which the former is more common. The anomaly is considered to be partial if some of the pulmonary veins drain into the systemic circulation and total if all the pulmonary veins drain into systemic circulation. Isolated partial anomalous pulmonary venous return (PAPVC) is an uncommon finding and is a very uncommon cause of pulmonary arterial hypertension. Whilst many patients with PAPVC remain asymptomatic, some may present at a later age with symptoms related to left-to-right shunt, pulmonary hypertension and right heart failure. We are presenting an interesting case report of an 18 years old patient who presented with exertional dyspnea and fatigue conforming to NYHA class II symptom status. Trans-esophageal echocardiography revealed isolated obstructive PAPVC as the cause for pulmonary hypertension without other demonstrable left-to-right shunts.
PMCID: PMC3953709  PMID: 24653588
Partial anomalous pulmonary venous connection; Pulmonary hypertension; Trans-esophageal echocardiography
2.  Coronary artery disease in patients undergoing cardiac surgery for non-coronary lesions in a tertiary care centre 
Indian Heart Journal  2014;66(1):52-56.
The objective of the present study was to determine the prevalence of coronary artery disease (CAD) in patients undergoing surgery for various valvular as well as non-valvular cardiac pathologies.
Patients with various valvular and non-valvular pathologies were selected. All patients with age ≥40 years and an indication for open heart surgery underwent pre-operative coronary angiogram and were included in the study.
The mean age was 51.5 ± 9.02 years. 178 (59.3%) patients were males and 122 (40.7%) patients were females. Out of 300 patients, 270 (90%) patients had valvular heart disease (VHD) and 30 (10%) patients had non-valvular heart disease. Rheumatic heart disease (RHD), mitral valve prolapse (MVP), degenerative aortic valve disease (DAVD) and bicuspid aortic valve (BAV) was present in 161 (53.7%), 17 (5.7%), 60 (20%) and 32 (10.7%) patients respectively. Overall, 26 (8.7%) patients were found to have significant CAD. CAD was significantly more common in patients with VHD as compared to patients with other etiologies (1 patient, 3.3%, p < 0.05). In the valvular group, DAVD patients had maximum prevalence of CAD (14 patients, 23.4%, p < 0.05). In the group with CAD, the presence of variables such as age >60 years, male sex, typical angina, HT, dyslipidemia and smoking were significantly greater as compared to those with normal coronaries.
The overall prevalence of CAD among patients undergoing non-coronary cardiac surgery is 8.7%. Coronary artery disease is relatively uncommon in patients with rheumatic VHD (4.9%), while its prevalence is highest in DAVD (23.4%).
PMCID: PMC3946445  PMID: 24581096
Coronary artery disease; Prevalence; Preoperative coronary angiogram
5.  Dothiepin-induced transient hypomania and extrapyramidal syndrome 
Indian Journal of Psychiatry  2013;55(4):383-385.
A case has been reported here, who developed transient hypomanic symptoms as well as extrapyramidal symptoms after being switched from sertraline to dothiepin therapy. The possible mechanisms and clinical implications of the same are discussed.
PMCID: PMC3890912  PMID: 24459312
Dothiepin; extrapyramidal syndrome; hypomania
6.  Pleiotropy of chemically modified tetracycline in periodontitis 
PMCID: PMC3778596  PMID: 24082703
7.  Comparative evaluation of decalcified freeze dried bone allograft with and without local doxycycline in non-contained human periodontal infrabony defects 
Doxycycline has been advocated as useful adjuncts in periodontal therapy not only due to their antimicrobial actions, but also to their recently recognized anti-collagenolytic, anti-inflammatory, osteoclast inhibitory and fibroblast stimulating property. The purpose of the present cohort study was to evaluate the regenerative outcomes of bone graft with or without local doxycycline in non-contained infrabony periodontal defects.
Materials and Methods:
16 one or two wall infrabony defects, in 11 patients suffering from moderate to severe chronic periodontitis, aged 35-60 years, were randomly divided for bone graft, alone (control) and with doxycycline (test) for the study. At baseline, after 3 months and after 6 months of post-operative period, pocket probing depth (PPD), clinical attachment level (CAL), radiological bone fill (RBF) and alveolar height reduction were recorded. Analysis of variance and Newman-Keuls post-hoc test were used or statistical analysis. A two-tailed probability (P) value P < 0.05 was considered to be statistically significant.
For the control group PPD reduction 2.00 ± 0.18 mm, CAL gain 1.38 ± 0.17 mm, RBF 0.63 ± 0.27 mm (18.0%) was observed while in the test group PPD reduction 2.00 ± 0.38 mm, CAL gain 1.25 ± 0.31 mm, RBF 0.75 ± 0.31 mm (20.7%) was evaluated. While alveolar height reduction for the control group and test group was 13% and 12.5% respectively.
The study confirmed no added benefits of local doxycycline, as compared with bone graft alone, for regeneration of non-contained human periodontal infrabony defects.
PMCID: PMC3800413  PMID: 24174730
Decalcified freeze dried bone allograft; doxycycline; infrabony defects and periodontal regeneration
8.  A validated regulatory network for Th17 cell specification 
Cell  2012;151(2):289-303.
Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other essential transcription factors (TFs). We have used an iterative systems approach, combining genome-wide TF occupancy, expression profiling of TF mutants, and expression time series to delineate the Th17 global transcriptional regulatory network. We find that cooperatively-bound BATF and IRF4 contribute to initial chromatin accessibility, and with STAT3 initiate a transcriptional program that is then globally tuned by the lineage-specifying TF RORγt, which plays a focal deterministic role at key loci. Integration of multiple datasets allowed inference of an accurate predictive model that we computationally and experimentally validated, identifying multiple new Th17 regulators, including Fosl2, a key determinant of cellular plasticity. This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease.
PMCID: PMC3503487  PMID: 23021777
9.  Synthesis and Bioevaluation of 125I-Labeled Gold Nanorods 
Nanotechnology  2011;22(13):135102.
A novel technique is discribed to monitor in vivo behaviors of gold nanorods (GNRs) using γ-imaging. GNRs were radiolabeled using [125I] sodium iodide in a simple and fast manner with high yield and without disturbing optical properties. Radiolabeled GNRs were successfully visualized by radioisotope tag, allowing longitudinal in vivo studies to be performed repeatedly in the same animal. The preliminary biodistribution study showed that PEGylated GNRs have much longer blood circulation times and clear out faster, while bare GNRs accumulate quickly in the liver after systematic administration. The highly efficient method reported here provides an extensively useful tool for guidance of design and development of new gold nanoparticles as target-specific agents for both diagnostics and photothermal therapy.
PMCID: PMC3139686  PMID: 21343651
Gold nanorods; Iodine-125; γ-imaging; Radiolabeled nanoparticles; PEGylation
10.  Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project 
Gerstein, Mark B. | Lu, Zhi John | Van Nostrand, Eric L. | Cheng, Chao | Arshinoff, Bradley I. | Liu, Tao | Yip, Kevin Y. | Robilotto, Rebecca | Rechtsteiner, Andreas | Ikegami, Kohta | Alves, Pedro | Chateigner, Aurelien | Perry, Marc | Morris, Mitzi | Auerbach, Raymond K. | Feng, Xin | Leng, Jing | Vielle, Anne | Niu, Wei | Rhrissorrakrai, Kahn | Agarwal, Ashish | Alexander, Roger P. | Barber, Galt | Brdlik, Cathleen M. | Brennan, Jennifer | Brouillet, Jeremy Jean | Carr, Adrian | Cheung, Ming-Sin | Clawson, Hiram | Contrino, Sergio | Dannenberg, Luke O. | Dernburg, Abby F. | Desai, Arshad | Dick, Lindsay | Dosé, Andréa C. | Du, Jiang | Egelhofer, Thea | Ercan, Sevinc | Euskirchen, Ghia | Ewing, Brent | Feingold, Elise A. | Gassmann, Reto | Good, Peter J. | Green, Phil | Gullier, Francois | Gutwein, Michelle | Guyer, Mark S. | Habegger, Lukas | Han, Ting | Henikoff, Jorja G. | Henz, Stefan R. | Hinrichs, Angie | Holster, Heather | Hyman, Tony | Iniguez, A. Leo | Janette, Judith | Jensen, Morten | Kato, Masaomi | Kent, W. James | Kephart, Ellen | Khivansara, Vishal | Khurana, Ekta | Kim, John K. | Kolasinska-Zwierz, Paulina | Lai, Eric C. | Latorre, Isabel | Leahey, Amber | Lewis, Suzanna | Lloyd, Paul | Lochovsky, Lucas | Lowdon, Rebecca F. | Lubling, Yaniv | Lyne, Rachel | MacCoss, Michael | Mackowiak, Sebastian D. | Mangone, Marco | McKay, Sheldon | Mecenas, Desirea | Merrihew, Gennifer | Miller, David M. | Muroyama, Andrew | Murray, John I. | Ooi, Siew-Loon | Pham, Hoang | Phippen, Taryn | Preston, Elicia A. | Rajewsky, Nikolaus | Rätsch, Gunnar | Rosenbaum, Heidi | Rozowsky, Joel | Rutherford, Kim | Ruzanov, Peter | Sarov, Mihail | Sasidharan, Rajkumar | Sboner, Andrea | Scheid, Paul | Segal, Eran | Shin, Hyunjin | Shou, Chong | Slack, Frank J. | Slightam, Cindie | Smith, Richard | Spencer, William C. | Stinson, E. O. | Taing, Scott | Takasaki, Teruaki | Vafeados, Dionne | Voronina, Ksenia | Wang, Guilin | Washington, Nicole L. | Whittle, Christina M. | Wu, Beijing | Yan, Koon-Kiu | Zeller, Georg | Zha, Zheng | Zhong, Mei | Zhou, Xingliang | Ahringer, Julie | Strome, Susan | Gunsalus, Kristin C. | Micklem, Gos | Liu, X. Shirley | Reinke, Valerie | Kim, Stuart K. | Hillier, LaDeana W. | Henikoff, Steven | Piano, Fabio | Snyder, Michael | Stein, Lincoln | Lieb, Jason D. | Waterston, Robert H.
Science (New York, N.Y.)  2010;330(6012):1775-1787.
We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor–binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor–binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
PMCID: PMC3142569  PMID: 21177976
11.  The CRIT framework for identifying cross patterns in systems biology and application to chemogenomics 
Genome Biology  2011;12(3):R32.
Biological data is often tabular but finding statistically valid connections between entities in a sequence of tables can be problematic - for example, connecting particular entities in a drug property table to gene properties in a second table, using a third table associating genes with drugs. Here we present an approach (CRIT) to find connections such as these and show how it can be applied in a variety of genomic contexts including chemogenomics data.
PMCID: PMC3129682  PMID: 21453526
12.  Detection and monitoring of the multiple inflammatory responses by photoacoustic molecular imaging using selectively targeted gold nanorods 
Biomedical Optics Express  2011;2(3):645-657.
In vitro cell experiments have been performed to detect and monitor the upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin simultaneously by photoacoustic molecular imaging (PMI). Human umbilical vein endothelial cells (HUVECs) were grown on gelatin-coated glass slides and stimulated with inflammatory cytokines to induce the expression of the inflammatory biomarkers, ICAM-1 and E-selectin. Gold nanorods (GNRs) of aspect ratio (AR) 1:3 with absorption centered at 715 nm conjugated to anti-ICAM-1 antibody and GNRs of AR 1:3.5 with absorption centered at 800 nm conjugated to anti-E-selectin were exposed to HUVECs with different stimulation conditions. A focused high frequency ultrasonic transducer (60 MHz, f/1.5) was used to scan the photoacoustic (PA) signal over the top surface of the cell containing slides. Averaged PA signal intensity from the stimulated cells was about 3 folds higher (~10 dB) compared to the un-stimulated cells for both ICAM-1 and E-selectin. The strong binding of GNRs to the stimulated HUVEC cells was evidenced by fluorescence imaging. Exposure of HUVEC cells to GNRs conjugated to isotype control antibodies confirms a low level non-specific binding. Also, at 0, 2, 6, and 24 hours after inflammatory stimulation, the HUVECs were exposed to GNRs conjugated anti-ICAM-1 antibody and anti-E-selectin antibody. PA intensity at each stage of inflammation compares well with fluorescence imaging and rt-PCR quantification.
PMCID: PMC3047369  PMID: 21412469
(000.0000) General; (000.2700) General science
13.  RSEQtools: a modular framework to analyze RNA-Seq data using compact, anonymized data summaries 
Bioinformatics  2010;27(2):281-283.
Summary: The advent of next-generation sequencing for functional genomics has given rise to quantities of sequence information that are often so large that they are difficult to handle. Moreover, sequence reads from a specific individual can contain sufficient information to potentially identify and genetically characterize that person, raising privacy concerns. In order to address these issues, we have developed the Mapped Read Format (MRF), a compact data summary format for both short and long read alignments that enables the anonymization of confidential sequence information, while allowing one to still carry out many functional genomics studies. We have developed a suite of tools (RSEQtools) that use this format for the analysis of RNA-Seq experiments. These tools consist of a set of modules that perform common tasks such as calculating gene expression values, generating signal tracks of mapped reads and segmenting that signal into actively transcribed regions. Moreover, the tools can readily be used to build customizable RNA-Seq workflows. In addition to the anonymization afforded by MRF, this format also facilitates the decoupling of the alignment of reads from downstream analyses.
Availability and implementation: RSEQtools is implemented in C and the source code is available at
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC3018817  PMID: 21134889
14.  Comparison and calibration of transcriptome data from RNA-Seq and tiling arrays 
BMC Genomics  2010;11:383.
Tiling arrays have been the tool of choice for probing an organism's transcriptome without prior assumptions about the transcribed regions, but RNA-Seq is becoming a viable alternative as the costs of sequencing continue to decrease. Understanding the relative merits of these technologies will help researchers select the appropriate technology for their needs.
Here, we compare these two platforms using a matched sample of poly(A)-enriched RNA isolated from the second larval stage of C. elegans. We find that the raw signals from these two technologies are reasonably well correlated but that RNA-Seq outperforms tiling arrays in several respects, notably in exon boundary detection and dynamic range of expression. By exploring the accuracy of sequencing as a function of depth of coverage, we found that about 4 million reads are required to match the sensitivity of two tiling array replicates. The effects of cross-hybridization were analyzed using a "nearest neighbor" classifier applied to array probes; we describe a method for determining potential "black list" regions whose signals are unreliable. Finally, we propose a strategy for using RNA-Seq data as a gold standard set to calibrate tiling array data. All tiling array and RNA-Seq data sets have been submitted to the modENCODE Data Coordinating Center.
Tiling arrays effectively detect transcript expression levels at a low cost for many species while RNA-Seq provides greater accuracy in several regards. Researchers will need to carefully select the technology appropriate to the biological investigations they are undertaking. It will also be important to reconsider a comparison such as ours as sequencing technologies continue to evolve.
PMCID: PMC3091629  PMID: 20565764
15.  Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response 
PLoS Genetics  2010;6(2):e1000848.
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
Author Summary
The C. elegans transcription factor PHA-4 is a member of the highly conserved FOXA family of transcription factors. These factors act as master regulators of organ development by controlling how genes are turned off and on as tissues are formed. Additionally they regulate genes in response to nutrient levels and control both longevity and survival of the organism. However, the extent to which these factors control similar or distinct gene targets for each of these functions is unknown. For this reason, we have used the technique of chromatin immunoprecipitation followed by deep sequencing (ChIP–Seq), to define the target binding sites of PHA-4 on a genome-wide scale, when it is either functioning as an organ identity regulator or in response to environmental stress. Our data clearly demonstrate distinct sets of biologically relevant target genes for the transcription factor PHA-4 under these two different conditions. Not only have we defined PHA-4 targets, but we established an experimental ChIP–Seq pipeline to facilitate the identification of binding sites for many transcription factors in the future.
PMCID: PMC2824807  PMID: 20174564
16.  An approach to compare genome tiling microarray and MPSS sequencing data for transcript mapping 
BMC Research Notes  2009;2:211.
We are correcting the abstract of our published article ([1]). The sentence that starts "We observe that 4.5% of MPSS tags...." was not scientifically complete in the original abstract, having only two of the four numbers required to describe a comparison of two technologies in two different organisms. The abstract below more accurately describes our findings, as documented in Figure 1 of the manuscript.
PMCID: PMC2770075
17.  An approach to comparing tiling array and high throughput sequencing technologies for genomic transcript mapping 
BMC Research Notes  2009;2:150.
There are two main technologies for transcriptome profiling, namely, tiling microarrays and high-throughput sequencing. Recently there has been a tremendous amount of excitement about the latter because of the advent of next-generation sequencing technologies and its promises. Consequently, the question of the moment is how these two technologies compare. Here we attempt to develop an approach to do a fair comparison of transcripts identified from tiling microarray and MPSS sequencing data.
This comparison is a challenging task because the sequencing data is discrete while the tiling array data is continuous. We use the published rice and Arabidopsis datasets which provide currently best matched sets of arrays and sequencing experiments using a slightly earlier generation of sequencing, the MPSS tag sequencing technology. After scoring the arrays consistently in both the organisms, a first pass comparison reveals a surprisingly small overlap in transcripts of 22% and 66% respectively, in rice and Arabidopsis. However, when we do the analysis in detail, we find that this is an underestimate. In particular, when we map the probe intensities onto the sequencing tags and then look at their intensity distribution, we see that they are very similar to exons. Furthermore, restricting our comparison to only protein-coding gene loci revealed a very good overlap between the two technologies.
Our approach to compare genome tiling microarray and MPSS sequencing data suggests that there is actually a reasonable overlap in transcripts identified by the two technologies. This overlap is distorted by the scoring and thresholding in the tiling array scoring procedure.
PMCID: PMC2764720  PMID: 19630981

Results 1-17 (17)