An integrated buoy-satellite based coastal water quality nowcasting system: India's pioneering efforts towards addressing UN ocean decade challenges.

The Indian coastal waters are stressed due to a multitude of factors, such as the discharge of industrial effluents, urbanization (municipal sewage), agricultural runoff, and river discharge. The coastal waters along the eastern and western seaboard of India exhibit contrasting characteristics in terms of seasonality, the magnitude of river influx, circulation pattern, and degree of anthropogenic activity. Therefore, understanding these processes and forecasting their occurrence is highly necessary to secure the health of coastal waters, habitats, marine resources, and the safety of tourists. This article introduces an integrated buoy-satellite based Water Quality Nowcasting System (WQNS) to address the unique challenges of water quality monitoring in Indian coastal waters and to boost the regional blue economy. The Indian National Centre for Ocean Information Services (INCOIS) has launched a first-of-its-kind WQNS, and positioned the buoys at two important locations along the east (Visakhapatnam) and west (Kochi) coast of India, covering a range of environmental conditions and tourist-intensive zones. These buoys are equipped with different physical-biogeochemical sensors, data telemetry systems, and integration with satellite-based observations for real-time data transmission to land. The sensors onboard these buoys continuously measure 22 water quality parameters, including surface current (speed and direction), salinity, temperature, pH, dissolved oxygen, phycocyanin, phycoerythrin, Coloured Dissolved Organic Matter, chlorophyll-a, turbidity, dissolved methane, hydrocarbon (crude and refined), scattering, pCO2 (water and air), and inorganic macronutrients (nitrite, nitrate, ammonium, phosphate, silicate). This real-time data is transmitted to a central processing facility at INCOIS, and after necessary quality control, the data is disseminated through the INCOIS website. Preliminary results from the WQNS show promising outcomes, including the short-term changes in the water column oxic and hypoxic regimes within a day in coastal waters off Kochi during the monsoon period, whereas effluxing of high levels of CO2 into the atmosphere associated with the mixing of water, driven by local depression in the coastal waters off Visakhapatnam. The system has demonstrated its ability to detect changes in the water column properties due to episodic events and mesoscale processes. Additionally, it offers valuable data for research, management, and policy development related to coastal water quality.

Unravelling tidal effect on zooplankton community structure in a tropical estuary.

The variability in zooplankton density and species composition in response to tidal oscillations were investigated in the lesser saline upper reaches (E1) and higher saline lower reaches (E2) of the Mahanadi Estuary, located at the mouth of the third largest river in Indian Peninsula. This is the first of its kind high frequency observation over the tidal cycle ranging from highest high tide to lowest low tide in this estuary revealing dynamic variability of zooplankton assemblages. Zooplankton abundance was higher during high tide in comparison to low tide, irrespective of salinity regimes. On the diurnal scale, it was higher at night in comparison to the day at both E1 and E2. The higher abundance of zooplankton groups such as Copepoda, Cladocera, and planktonic larvae during the night at E1 as well as E2 indicating an upward migration. Many of the zooplankton taxa (e.g., Pseudodiaptomus serricaudatus, Pseudodiaptomus sp., Acartia danae, Acrocalanus longicornis, Oithona sp., Corycaeus andrewsi) migrated towards E1 due to tidal effect during high tide and maintained their position even during low tide. In contrast, the prevalence of limnetic taxa (e.g., Brachionus rubens, Polyarthra vulgaris, Bosminopsis deitersi, Moina micrura, Heliodiaptomus sp.) at E2 during low tide indicated a predominant riverine source. The tidal variability of Brachyura (zoea and megalopa) revealed different emergence times that indicated dispersal of zoeas to the adjacent Bay of Bengal and the return of magalopa to the Mahanadi Estuary. Species diversity index was higher during high tide, and prominent at E2. At E1, marine, fresh, marine-brackish, and marine-brackish-fresh zooplankton species dominated during high tide, while brackish-fresh taxa dominated during low tide. Differently, E2 was enriched with marine, marine-brackish, and marine-brackish-fresh taxa during high tide, whereas fresh, brackish-fresh, and marine-fresh dominated during low tide. Salinity and suspended matter influenced the dominant zooplankton taxa at E2 and E1, respectively. Zooplankton assemblages exhibited a pattern of prominent diurnal-spatial variation in comparison to the tidal scale in the Mahanadi Estuary. Overall, this study documented a very high zooplankton diversity (92 taxa belonging to 13 groups) and significant variations in species abundance which highlighted the importance of carrying out sampling over the tidal cycle at contrasting salinity regimes.

Effect of Tidal Cycle on Escherichia coli Variability in a Tropical Estuary.

A faecal indicator bacteria, Escherichia coli (E. coli), is widely used in monitoring health of estuaries, where tidal amplitude plays a critical role in its variability. Mahanadi estuary, formed at the mouth of a major tropical river Mahanadi, has large socio-economic importance. This anthropogenically stressed estuary remains understudied with respect to E. coli. Hence, this study addressed E. coli variability in Mahanadi estuary with novel sampling strategy that can be implemented at other tropical estuaries. The sampling strategy includes simultaneous measurements, at lesser-saline upper-estuary and higher-saline lower-estuary, over a tidal cycle. Although no significant variability of E. coli was observed between upper and lower-estuary, overall average count was higher during low tide and lower during high tide attributed to salinity fluctuations. Intermittent surpass of E. coli counts above recommended limits in Mahanadi estuary, indicated potential health risk, thus demands for frequent water quality monitoring and management strategies.

Outcome and complications of living donor pediatric renal transplantation: Experience from a tertiary care center.

INTRODUCTION: We retrospectively reviewed the patient characteristics, outcome, and complications of renal transplantation in pediatric age group performed at our center and compared the results with various centers in India and other developed countries. MATERIALS AND METHODS: Patients younger than eighteen years of age who underwent renal transplantation from 2003 to 2014 at our institute were reviewed. Demographic data of the transplant recipients and donors, etiology of ESRD, mode of dialysis, surgical details of renal transplantation, immunosuppression, medical and surgical complications, and post-transplant follow-up were assessed. Graft survival was determined at 1, 3 and 5 years post-transplant. All data collected were entered into Microsoft excel program and analyzed using SPSS 20. Kaplan-Meier method was applied to determine the graft survival at 1, 3, and 5 years. The log-rank test was applied to test the statistical significance of the difference in survival between groups. RESULTS: Thirty-two children underwent transplantation comprising of 18 females and 14 males. The mean age was 14.5 years (range 10-17 years). The primary cause of renal failure was glomerular diseases in 53% (17/32) of patients. Seventeen postsurgical complications were noted in our series. Two grafts were lost over a follow-up of 5 years. The 1, 3, and 5 year graft survival rates were 96.7%, 92.9%, and 85%, respectively. There was no mortality. CONCLUSION: The etiology of ESRD in our region is different from that of developed countries. The mean age at which children undergo renal transplantation is higher. Graft survival at our center is comparable to that of developed nations. Renal transplantation can be safely performed in children with ESRD.

Pharmacologic reperfusion therapy with indigenous tenecteplase in 15,222 patients with ST elevation myocardial infarction - the Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase (TNK-tPA) in the management of patients with ST-elevation myocardial infarction (STEMI) in clinical practice. METHODS: Observational, prescription-event monitoring study. RESULTS: Data of 15,222 patients who had STEMI and received weight adjusted TNK injection was analyzed. Overall 95.43% patients had clinically successful thrombolysis (CST). In the different subgroups, hypertensives, diabetics, smokers and hyperlipidemic patients had CST rates comparable to the general patient data. CST rates were significantly lower in the elderly patients (>70 years; 92.11%; p < 0.0001), in patients with history of Ischemic Heart Disease (IHD, 93.86%; p = 0.0004) and in patients receiving delayed treatment (>6 h after onset of chest pain; 85.38%; p < 0.0001). CST was significantly higher in patients who received an early thrombolysis (<3 h after onset of chest pain; 96.54%; p = 0.006). Overall mortality was 1.69%, while it was significantly higher in the elderly (4.42%), patients with history of IHD (2.67%), females (2.93%) and in those who received delayed treatment (4.98%). The overall incidences of intracranial hemorrhage (ICH), bleeding excluding ICH, stroke and ventricular tachyarrhythmia were 0.39%, 2.01%, 0.16% and 2.35% respectively. Age >70 years, diabetes, hyperlipidemia and history of IHD were associated with a higher incidence of heart failure, myocardial re-infarction or ventricular tachyarrhythmias. However, incidence of ICH and bleeding other than ICH was comparable amongst all patient subgroups. CONCLUSION: This study confirms the safety and efficacy of indigenous tenecteplase in Indian patients with STEMI, including high risk subgroups. It also highlights the fact that delayed treatment denotes denial of benefits of pharmacologic reperfusion therapy.

Exploring the impact of southern ocean sea ice on the Indian Ocean swells.

The present study analyzes the impact of the Southern Ocean (SO) sea ice concentration on the north Indian Ocean (NIO) wave fields through swells using 6 years (2016-2021) of WAVEWATCH III (WWIII) simulations. We did two experimental runs of WWIII, one with sea ice concentration and winds as the forcing (W3with_ice) and the second run with only wind forcing (W3no_ice). Analysis shows the impact of the SO sea ice concentration on northward swell peaks in September-November, coinciding with the maximum sea ice extent in the Antarctic region of the Indian Ocean. W3no_ice simulations are biased more by ~ 60% and ~ 37% in significant wave height and period, respectively, against W3with_ice when compared with NIO mooring data. W3no_ice simulates low-frequency swells and travels fast towards NIO, with implications for operational oceanography. We have shown that the forecasts of the timing of high swell events along NIO coasts can be erroneous by ~ 12 h if the SO sea ice concentration is not included in the model. Further, W3no_ice could potentially produce false swell alerts along southeastern Australian coasts. In summary, our study highlights the importance of the SO sea ice concentration inclusion in the wave models to accurately simulate NIO waves.

Wave induced coastal flooding along the southwest coast of India during tropical cyclone Tauktae.

The coastal flood during the tropical cyclone Tauktae, 2021, at Chellanam coast, Kerala, India, has invited wide attention as the wave overtopping severely affected coastal properties and livelihood. We used a combination of WAVEWATCHIII and XBeach to study the coastal inundation during high waves. The effect of low-frequency waves and the rise in the coastal water level due to wave setup caused the inundation at Chellanam, even during low tide with negligible surge height. Wave setup raised the water level at the coast with steep slopes to more than 0.6 m and peaked during low tide, facilitating wave breaking at the nearshore region. The coastal regions adjacent to these steep slopes were subjected to severe inundation. The combined effect of long and short waves over wave setup formed extreme wave runups that flooded inland areas. At gently sloping beaches, the longwave component dominated and overtopped the seawalls and damaged households along the shoreline. The study emphasizes the importance of longwave and wave setup and its interaction with nearshore bathymetry during the high wave. The present study shall lead to the development of a coastal inundation prediction system for the low-lying hot spots using the combination of WAVEWATCHIII and XBeach models.

Building and Interpreting Artificial Neural Network Models for Biological Systems.

Biology has become a data driven science largely due to the technological advances that have generated large volumes of data. To extract meaningful information from these data sets requires the use of sophisticated modeling approaches. Toward that, artificial neural network (ANN) based modeling is increasingly playing a very important role. The "black box" nature of ANNs acts as a barrier in providing biological interpretation of the model. Here, the basic steps toward building models for biological systems and interpreting them using calliper randomization approach to capture complex information are described.

Neonatal thyroxine activation modifies epigenetic programming of the liver.

The type 2 deiodinase (D2) in the neonatal liver accelerates local thyroid hormone triiodothyronine (T3) production and expression of T3-responsive genes. Here we show that this surge in T3 permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increases H3K9me3 levels during post-natal days 1-5 (P1-P5), and results in methylation of 1,508 DNA sites (H-sites) in the adult mouse liver. These sites are associated with 1,551 areas of reduced chromatin accessibility (RCA) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,363 genes. There is strong spatial correlation between density of H-sites and RCA sites. Chromosome conformation capture (Hi-C) data reveals a set of 81 repressed genes with a promoter RCA in contact with an intergenic RCA ~300 Kbp apart, within the same topologically associating domain (χ2 = 777; p < 0.00001). These data explain how the systemic hormone T3 acts locally during development to define future expression of hepatic genes.

Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.

Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.

Response of coastal phytoplankton pigment composition to tropical cyclone Fani.

Phytoplankton pigment composition was evaluated during the pre-cyclone phase (PRCP) and post-cyclone phase (POCP) of tropical cyclone Fani in the coastal waters of the northwestern Bay of Bengal. The chromatographic analysis revealed higher pigment diversity and an increase in individual pigment concentration during POCP. Chlorophyll-a (chl-a) was the dominant pigment during PRCP and POCP, followed by fucoxanthin. However, chl-a and fucoxanthin concentrations increased 18- and 14-folds, respectively, during the POCP, signifying Bacillariophyta bloom. Complementing microscopy confirmed the dominance of the toxic Bacillariophyta species Pseudo-nitzschia pungens (reaching 5.47 × 104 cells l-1) during the POCP. The cyclone-induced nutrient recharge of the ambient medium could have promoted phytoplankton growth, causing the reappearance of diatom bloom during the later phase of the pre-southwest monsoon. Small-sized Prymnesiophyta and Cryptophyta were not detected microscopically; however, they were identified by chromatographic analysis through pigment markers during POCP.

Physicochemical controls on the initiation of phytoplankton bloom during the winter monsoon in the Arabian Sea.

Occurrence of phytoplankton bloom in the northern Arabian Sea (NAS) during the winter monsoon is perplexing. The convective mixing leads to a deeper and well-oxygenated (> 95% saturation) mixed layer. We encountered low chlorophyll conditions though the nutrient conditions were favorable for a bloom. The mean ratio of silicate (Si) to DIN (Dissolved Inorganic Nitrogen: nitrate + nitrite + ammonium) in the euphotic zone was 0.52 indicating a "silicate-stressed" condition for the proliferation of diatoms. Also, the euphotic depth was much shallower (~ 49 m) than the mixed layer (~ 110 m) suggesting the Sverdrup critical depth limitation in the NAS. We show that the bloom in this region initiates only when the mixed layer shoals towards the euphotic zone. Our observations further suggest that two primary factors, the stoichiometric ratio of nutrients, especially the Si/DIN ratio, in the mixed layer and re-stratification of the upper water column, govern the phytoplankton blooming in NAS during the later winter monsoon. The important finding of the present study is that the Sverdrup's critical depth limitation gives rise to the observed low chl-a concentration in the NAS, despite having enough nutrients.

Sequence periodicity in nucleosomal DNA and intrinsic curvature.

BACKGROUND: Most eukaryotic DNA contained in the nucleus is packaged by wrapping DNA around histone octamers. Histones are ubiquitous and bind most regions of chromosomal DNA. In order to achieve smooth wrapping of the DNA around the histone octamer, the DNA duplex should be able to deform and should possess intrinsic curvature. The deformability of DNA is a result of the non-parallelness of base pair stacks. The stacking interaction between base pairs is sequence dependent. The higher the stacking energy the more rigid the DNA helix, thus it is natural to expect that sequences that are involved in wrapping around the histone octamer should be unstacked and possess intrinsic curvature. Intrinsic curvature has been shown to be dictated by the periodic recurrence of certain dinucleotides. Several genome-wide studies directed towards mapping of nucleosome positions have revealed periodicity associated with certain stretches of sequences. In the current study, these sequences have been analyzed with a view to understand their sequence-dependent structures. RESULTS: Higher order DNA structures and the distribution of molecular bend loci associated with 146 base nucleosome core DNA sequence from C. elegans and chicken have been analyzed using the theoretical model for DNA curvature. The curvature dispersion calculated by cyclically permuting the sequences revealed that the molecular bend loci were delocalized throughout the nucleosome core region and had varying degrees of intrinsic curvature. CONCLUSIONS: The higher order structures associated with nucleosomes of C.elegans and chicken calculated from the sequences revealed heterogeneity with respect to the deviation of the DNA axis. The results points to the possibility of context dependent curvature of varying degrees to be associated with nucleosomal DNA.

The influence of boreal summer intra-seasonal oscillations on Indo-western Pacific Ocean surface waves.

The present study examines the influence of Boreal Summer Intra-Seasonal Oscillation (BSISO) on Tropical Indian Ocean surface waves using the latest version of ECMWF reanalysis (ERA5) during summer monsoon months June through August (JJA). BSISO is a distinct mode of ISO during JJA having a northward and eastward movement from the equatorial Indian Ocean to the western Pacific Ocean. Composite analysis of anomalies of significant wave heights (SWH), wind sea, swell, and mean wave period for 8 phases of BSISO has been carried out to understand its influence. SWH anomalies in response to BSISO's are phase-dependent. Negative SWH anomalies are noticed with strong northward and weak eastward propagation during the phases 1-3 in response to the easterly wind anomalies over the north Indian Ocean (NIO). During phases 5-7, high positive SWH anomalies (~ 0.5 m) in response to the westerly wind anomalies with northward and weak eastward propagation over NIO. Phases 4 and 8 behave like transition phases. In addition, enhanced (suppressed) SWH anomalies (~ 0.5 m) are seen during the active (break) spells of BSISO over NIO. Over the southern tip of India, negative (positive) SWH anomalies prevail during the active (break) conditions. This study clearly suggests that the wave forecast advisories during intra-seasonal time scales would be more useful for offshore and coastal activities during the summer monsoon.

Consensus and development of document for management of stabilized acute decompensated heart failure with reduced ejection fraction in India.

AIM: Ensuring adherence to guideline-directed medical therapy (GDMT) is an effective strategy to reduce mortality and readmission rates for heart failure (HF). Use of a checklist is one of the best tools to ensure GDMT. The aim was to develop a consensus document with a robust checklist for stabilized acute decompensated HF patients with reduced ejection fraction. While there are multiple checklists available, an India-specific checklist that is easy to fill and validated by regional and national subject matter experts (SMEs) is required. METHODOLOGY: A total of 25 Cardiology SMEs who consented to participate from India discussed data from literature, current evidence, international guidelines and practical experiences in two national and four regional meetings. RESULTS: Recommendations included HF management, treatment optimization, and patient education. The checklist should be filled at four time points- (a) transition from intensive care unit to ward, (b) at discharge, (c) 1st follow-up and (d) subsequent follow-up. The checklist is the responsibility of the consultant or the treating physician which can be delegated to a junior resident or a trained HF nurse. CONCLUSION: This checklist will ensure GDMT, simplify transition of care and can be used by all doctors across India. Institutions, associations, and societies should recommend this checklist for adaptability in public and private hospital. Hospital administrations should roll out policy for adoption of checklist by ensuring patient files have the checklist at the time of discharge and encourage practice of filling it diligently during follow-up visits.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.

Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.

Two-dimensional transcriptome profiling: identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens.

The expression of specific mRNA isoforms may uniquely reflect the biological state of a cell because it reflects the integrated outcome of both transcriptional and posttranscriptional regulation. In this study, we constructed a splicing array to examine approximately 1,500 mRNA isoforms from a panel of genes previously implicated in prostate cancer and identified a large number of cell type-specific mRNA isoforms. We also developed a novel "two-dimensional" profiling strategy to simultaneously quantify changes in splicing and transcript abundance; the results revealed extensive covariation between transcription and splicing in prostate cancer cells. Taking advantage of the ability of our technology to analyze RNA from formalin-fixed, paraffin-embedded tissues, we derived a specific set of mRNA isoform biomarkers for prostate cancer using independent panels of tissue samples for feature selection and cross-analysis. A number of cancer-specific splicing switch events were further validated by laser capture microdissection. Quantitative changes in transcription/RNA stability and qualitative differences in splicing ratio may thus be combined to characterize tumorigenic programs and signature mRNA isoforms may serve as unique biomarkers for tumor diagnosis and prognosis.

Statistical and artificial neural network-based analysis to understand complexity and heterogeneity in preeclampsia.

Preeclampsia is a pregnancy associated disease. It is characterized by high blood pressure and symptoms that are indicative of damage to other organ systems, most often involving the liver and kidneys. If left untreated, the condition could be fatal to mother and baby. This makes it important to delineate the complexities associated with the disease at a molecular level that would help develop methods for early diagnosis. In microarray-based studies, Textoris et al. and Mirzakhani et al. have analyzed the transcriptome with a view to identify biomarkers for preeclampsia. The current study has extensively analyzed these microarray data sets to understand the complexity and heterogeneity associated with preeclampsia. A statistical multiple comparisons-based approach has been used to identify features capable of distinguishing preeclampsia from normotensive cases. These features were then used to build an artificial neural network-based machine learning model that successfully classified the samples. Further, the machine learning model was used to delineate features critical for its internal representation by extending the calliper randomization approach to the analysis of microarray data. Functional analysis of the features identified by the calliper randomization approach revealed pathways that could be crucially involved in the mechanism of the underlying disease. Biological processes associated with the features identified have revealed among others, genes involved in reproductive processes to be differentially expressed.