Advancement in biomarker based effective diagnosis of neonatal sepsis

Neonatal sepsis is considered as alarming medical emergency and becomes the common global reason of neonatal mortality. Non-specific symptoms and limitations of conventional diagnostic methods for neonatal sepsis mandate fast and reliable method to diagnose disease for point of care application. Recently, disease specific biomarkers have gained interest for rapid diagnosis that led to the development of electrochemical biosensor with enhanced specificity, sensitivity, cost-effectiveness and user-friendliness. Other than conventional biomarker C-reactive protein to diagnose neonatal sepsis, several potential biomarkers including Procalcitonin (PCT), Serum amyloid A (SAA) and other candidates are extensively investigated. The present review provides insights on advancements and diagnostic abilities of protein and nucleotide based biomarkers with their incorporation in developing electrochemical biosensors by employing novel fabrication strategies. This review provides an overview of most promising biomarker and its capability for neonatal sepsis diagnosis to fulfil future demand to develop electrochemical biosensor for point-of-care applications.</p

Dynamics of HEV viremia, fecal shedding and its relationship with transaminases and antibody response in patients with sporadic acute hepatitis E

<p>Abstract</p> <p>Background</p> <p>There is paucity of data regarding duration of fecal excretion and viremia on sequential samples from individual patients and its correlation with serum transaminases and antibody responses in patients with acute hepatitis E. This prospective study was undertaken at a tertiary care center in Northern India over 15 months. Only those patients of sporadic acute hepatitis E who were in their first week of illness and followed up weekly for liver function tests, IgM anti HEV antibody and HEV RNA in sera and stool were included. HEV RNA was done by RT - nPCR using two pairs of primers from RdRp region of ORF 1 of the HEV genome.</p> <p>Results</p> <p>Over a period of 15 months 60 patients met the inclusion criterion and were enrolled for the final analysis. The mean age of the patients was 29.2 ± 8.92 years, there were 39 males. The positivity of IgM anti HEV was 80% at diagnosis and 18.3% at 7th week, HEV RNA 85% at diagnosis and 6.6% at 7th week and fecal RNA 70% at the time of diagnosis and 20% at 4th week. The maximum duration of viremia detected was 42 days and fecal viral shedding was 28 days after the onset of illness.</p> <p>Conclusion</p> <p>Present study reported HEV RNA positivity in sera after normalization of transaminases. Fecal shedding was not seen beyond normalization of transaminases. However, viremia lasted beyond normalization of transaminases suggesting that liver injury is independent of viral replication.</p

Morphology of Atmospheric Particles over Semi-Arid Region (Jaipur, Rajasthan) of India: Implications for Optical Properties

The regional dust morphology and spectral refractive indices (RIs; governed by hematite, Fe2O3 content at short wavelengths) are key elements for ascertaining direct radiative forcing of mineral dust aerosols. To provide morphological features of background mineral dust from a semi-arid zone in the vicinity of the Thar Desert, we carried out an expedition to the Jaipur city during late winter of 2012. Morphological analysis reveals the predominance of "Layered", "Angular" and "Flattened" particles, while the frequency distribution of a total of 235 dust particles shows the aspect ratio, AR and circularity parameter, CIR (measures of particle's non-sphericity) typically similar to 1.4 and similar to 0.8, respectively. Sensitivity analysis at 550 nm wavelength reveals the equivalent sphere model may underestimate Single Scattering Albedo, SSA for the dust with low (similar to 1.1%) hematite by similar to 3.5%. Both underestimation (by similar to 5.6%) and overestimation (up to 9.1%) are probable in case of dust with high hematite content (similar to 5.68%). In addition, the effect of AR on the dust scattering is significant in case of dust with high hematite content. More such regionally representative dust morphological data are required for better estimation of regional radiative forcing of mineral dust aerosols

Functional Identification of Valerena-1,10-diene Synthase, a Terpene Synthase Catalyzing a Unique Chemical Cascade in the Biosynthesis of Biologically Active Sesquiterpenes in Valeriana officinalis

Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [13C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes

Critical weather limits for paddy rice under diverse ecosystems of India

Rice yields are largely influenced by variability in weather. Here, we demonstrate the effect of weather variables viz., maximum and minimum temperatures, rainfall, morning and evening relative humidity, bright sunshine hours on the yield of rice cv. Swarna, grown across five rice ecologies of India through field experiments during kharif (wet) season (Jun-Sept.). Critical thresholds of weather elements were identified for achieving above average, average and below average yield for each ecology. The investigation could determine how different weather elements individually and collectively affect rice yield in different rice ecosystems of India. While a sudden increase in minimum temperature by 8-10 °C (&gt; 30 °C) during reproductive period resulted in 40-50 per cent yield reduction at Mohanpur, a sudden decrease (&lt; 20 °C) caused yield decline at Dapoli. The higher yields may be attributed to a significant difference in bright sunshine hours between reproductive phases of above-average and below-average yield years (ranging from 2.8 to 7.8 hours during P5 stages and 1.7 to 5.1 during P4 stages). Rice cultivar Swarna performed differently at various sowing dates in a location as well as across locations (6650 kg ha-1 at Dapoli to 1101 kg ha-1 at Samastipur). It was also found that across all locations, the above average yield could be associated with higher range of maximum temperature compared to that of below average yield. Principal component analysis explained 77 per cent of cumulative variance among the variables at first growth stage, whereas 70 per cent at second growth stage followed by 74 per cent and 66 per cent at subsequent growth stages. We found that coastal locations, in contrast to inland ones, could maximize the yield potential of the cultivar Swarna, due to the longer duration of days between panicle initiation to physiological maturity. We anticipate that the location-specific thresholds of weather factors will encourage rice production techniques that are climate resilient

Genes Selectively Up-Regulated by Pheromone in White Cells Are Involved in Biofilm Formation in Candida albicans

To mate, MTL-homozygous strains of the yeast pathogen Candida albicans must switch from the white to opaque phase. Mating-competent opaque cells then release pheromone that induces polarization, a G1 block and conjugation tube formation in opaque cells of opposite mating type. Pheromone also induces mating-incompetent white cells to become adhesive and cohesive, and form thicker biofilms that facilitate mating. The pheromone response pathway of white cells shares the upstream components of that of opaque cells, but targets a different transcription factor. Here we demonstrate that the genes up-regulated by the pheromone in white cells are activated through a common cis-acting sequence, WPRE, which is distinct from the cis-acting sequence, OPRE, responsible for up-regulation in opaque cells. Furthermore, we find that these white-specific genes play roles in white cell biofilm formation, and are essential for biofilm formation in the absence of an added source of pheromone, suggesting either an autocrine or pheromone-independent mechanism. These results suggest an intimate, complex and unique relationship between switching, mating and MTL-homozygous white cell biofilm formation, the latter a presumed virulence factor in C. albicans

An indole alkaloid from a tribal folklore inhibits immediate early event in HSV-2 infected cells with therapeutic efficacy in vaginally infected mice.

Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the management of HSV-2 infections