Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production.

In response to viral infection, how cells balance translational shutdown to limit viral replication and the induction of antiviral components like interferons (IFNs) is not well understood. Moreover, how distinct isoforms of IFN-induced oligoadenylate synthetase 1 (OAS1) contribute to this antiviral response also requires further elucidation. Here, we show that human, but not mouse, OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L. In contrast, both mouse and human OAS1 protect against West Nile virus infection by a mechanism distinct from canonical RNase L activation. OAS1 binds AU-rich elements (AREs) of specific mRNAs, including IFNß. This binding leads to the sequestration of IFNß mRNA to the endomembrane regions, resulting in prolonged half-life and continued translation. Thus, OAS1 is an ARE-binding protein with two mechanisms of antiviral activity: driving inhibition of translation but also a broader, non-canonical function of protecting IFN expression from translational shutdown.

Ashwagandha Diminishes Hippocampal Apoptosis Induced by Microwave Radiation by Acetylcholinesterase Dependent Neuro-Inflammatory Pathway in Male Coturnix coturnix Japonica.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Withania somnifera inhibits photorefractoriness which triggers neuronal apoptosis in both pre-optic and paraventricular hypothalamic area of Coturnix coturnix japonica: involvement of oxidative stress induced p53 dependent Caspase-3 mediated low immunoreactivity of estrogen receptor alpha.

Light has a very important function in the regulation of the normal physiology including the neuroendocrine system, biological rhythms, cognitive behavior, etc. The variation in photoperiod acts as a stressor due to imbalance in endogenous hormones. Estrogen and its receptors ER alpha and beta play a vital role in the control of stress response in birds. The study investigates the estrogenic effects of a well-known medicinal plant Withania somnifera (WS), mediated by estrogen receptor alpha (ERα) in the hypothalamic pre-optic area (POA) and paraventricular nuclei (PVN). Further the study elucidates its anti-oxidants and anti-apoptotic activities in the brain of Japanese quail. To validate this hypothesis, mature male quails were exposed to long day length for 3 months and then transferred to intermediate day length to become photorefractory (PR) while controls were still continued under long daylength. Supplementation of WS root extract in PR quail increases plasma estrogen and lowers corticosterone. Further, in PR quail the variation in light downregulates immunoreactivity of ERα, oxidative stress and antioxidant enzyme activities i.e. superoxide dismutase and catalase in the brain. Neuronal apoptosis was observed in the POA and PVN of PR quail as indicated by the abundant expression of Caspase-3 and p53 which reduces after the administration of WS root extract. The neuronal population also found to decrease in PR although it increased in WS administered quails. Further, the study concluded that change in photoperiod from 3 months exposure of 16L: 8D to 13.5L: 10.5D directly activates neuronal apoptosis via expression of Caspase3 and p53 expression in the brain and increases neuronal and gonadal oxidative stress while WS root extract reverses them via enhanced estrogen and its receptor ERα expression in the hypothalamic pre-optic and PVN area of Japanese quail.

Ethanol exposure of human pancreatic normal ductal epithelial cells induces EMT phenotype and enhances pancreatic cancer development in KC (Pdx1-Cre and LSL-KrasG12D ) mice.

Alcohol is a risk factor for pancreatic cancer. However, the molecular mechanism by which chronic alcohol consumption influences pancreatic cancer development is not well understood. We have recently demonstrated that chronic ethanol exposure of pancreatic normal ductal epithelial cells (HPNE) induces cellular transformation by generating cancer stem cells (CSCs). Here, we examined whether chronic ethanol treatment induces epithelial-mesenchymal transition in HPNE cells and promotes pancreatic cancer development in KC (Pdx1-Cre, and LSL-KrasG12D ) mice. Our data demonstrate that chronic ethanol exposure of HPNE cells induces SATB2 gene and those cells became highly motile. Ethanol treatment of HPNE cells results in downregulation of E-Cadherin and upregulation of N-Cadherin, Snail, Slug, Zeb1, Nanog and BMI-1. Suppression of SATB2 expression in ethanol-transformed HPNE cells inhibits EMT phenotypes. KC mice fed with an ethanol-containing diet show enhanced pancreatic cancer growth and development than those fed with a control diet. Pancreas isolated from KC mice fed with an ethanol-containing diet show higher expression of stem cell markers (CD133, CD44, CD24), pluripotency-maintaining factors (cMyc, KLF4, SOX-2, and Oct-4), N-Cadherin, EMT-transcription factors (Snail, Slug, and Zeb1), and lower expression of E-cadherin than those isolated from mice fed with a control diet. Furthermore, pancreas isolated from KC mice fed with an ethanol-containing diet show higher expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) and PTGS-2 (COX-2) gene than those isolated from mice fed with a control diet. These data suggest that chronic alcohol consumption may contribute to pancreatic cancer development by generating inflammatory signals and CSCs.

2.45 GHz microwave radiation induced oxidative stress: Role of inflammatory cytokines in regulating male fertility through estrogen receptor alpha in Gallus gallus domesticus.

Due to the growing number of gadgets emitting electromagnetic radiation (EMR), particularly microwave (MW) radiation, in our daily lives, it is believed that EMR have both long-term and short-term biological impacts that are quite concerning for avian as well as human health. Due to the negative impact of MW emitting equipment on the biological system this study looks into the mechanistic approach by which low-level of 2.45 GHz MW radiation causes an oxidative stress and inflammatory response in the testes micro-environment which further gets regulated by estrogen receptor alpha (ERα) expression in immature Gallus gallus domesticus leading to male infertility. Two weeks old immature male chickens were exposed to non-thermal low-level 2.45-GHz MW radiation for 2 h/day for 30 days (power density = 0.1264 mw/cm2 and SAR = 0.9978 W/kg). In the exposed group, morphometric examination of the testes revealed decreased testicular weight, volume and gonado-somatic index. Further, histological staining demonstrated a substantial reduction in the diameter of seminiferous tubules in the exposed group as compared to the control. The degree of oxidative stress was also determined showing an increase in oxidative stress parameters after exposure. The radiation exposed testes showed a significant increase in IL-1ß immunoreactivity and decline in IL-10 immunoreactivity, indicating a sense of MW radiation-induced oxidative stress-regulated inflammatory response. A substantial reduction in ERα expression was also observed in exposed testes by Western blotting. Our investigations conclude that testes being vulnerable to free radical damage become an easy target organ for MW exposure induced oxidative and inflammatory stress. Therefore it becomes evident that it may cause male infertility in chicks via downregulation of ER-α in testis.

Photoperiod dependent expression of estrogen receptor alpha in testes of Japanese quail: Involvement of Withania somnifera in apoptosis amelioration.

Light plays important function in the regulation of reproduction in vertebrates including birds. The prolonged long day length exposure causes reproductively inactive state or photorefractoriness in many avian species including Japanese quail. Withania somnifera (WS) is a medicinal plant known to have beneficial effects on stress and infertility. The study investigates the physiological effect of WS on the light-induced stress in quail mediated by estrogen receptor alpha. Quails were exposed to long day length for three months and then transferred into intermediate day length to make them photorefractory (PR) while controls under natural day length. Administration of Withania somnifera root extract (WSRE) in PR quail induces estrogen and decreases corticosterone in male Japanese quail. Immunoreactivity of ERα decreased in testis of PR quail and increased after oral administration of WSRE compared to control. Expression of ir-Caspase-3 and ir-p53 in the testis increased in PR while decreased in PR + WS. Histologically, seminiferous tubules size decreased in PR whereas increased in PR + WS quails. Scanning electron microscopic study reveals sperms in clusters with proper head and tail in control. In PR quails sperms were few and distorted while WSRE improved the sperm morphology. From the study, it is concluded that during photorefractoriness gonadal regression occurs due to testicular apoptosis which causes stress. WSRE helps to overcome stress and improve reproductive performance via increase in expression of ir-ERα during PR condition. Further, the stress ameliorating effect of WSRE in reducing apoptosis mediated by ir-Caspase-3 and ir-p53 in the testes is clearly evident in Japanese quail.

Stress and steroid interaction modulates expression of estrogen receptor alpha in the brain, pituitary, and testes of immature Gallus gallus domesticus.

In nature, food availability stimulates hypothalamo-pituitary-gonadal (HPG) axis while its scarcity induces stress, which further stimulates hypothalamo-pituitary-adrenal (HPA) axis producing a detrimental effect on the avian reproductive physiology. The present experiment was designed to examine the interaction of stress like food restriction and estradiol on male reproductive physiology with special emphasis on estrogen receptor alpha (ERα) as these play crucial role in reproduction. To achieve this, 60 day old White Leghorn immature cockrels were taken and divided into four groups (n = 8 per group). One group was provided with food and water ad libitum. Second group was food restricted (FR) for 9 h/day after 5 days, third and fourth were administered with estradiol benzoate (EB 0.5 mg/100g/day) for 12 days. Fourth group was FR for 9 h/day after 5 days of EB treatment till last day of experiment (EB + FR). Immunofluorescent localization of ERα was principally in the pre-optic area and paraventricular nuclei of hypothalamus and in anterior pituitary gland. ERα expression was highly reduced (from 40 AU to 20 AU) after FR in testis but it increased (50 AU) after EB administration, EB + FR reflects a diminishing pattern in the increment after EB. FR decreased plasma estradiol while EB increased it. Increased plasma corticosterone, hydrogen peroxide, malondialdehyde, and decreased anti-oxidant enzymes in brain and testis of all groups indicate oxidative stress in the HPG axis. The increased ERα after EB and a decrease with FR and EB + FR support their reproductive function. Estrogen and its receptor alpha are responsible for maintaining epithelial morphology but FR along with EB administration modulates the testicular development by significantly decreasing its size (p<.0001) and seminiferous tubules (p<.0001) and no sperm formation via highly reduced expression of ir-ERα in HPG axis. Our findings led us to conclude that stress like FR and estradiol induces testicular regression immature male chickens by modulating ir-ERα expression in the HPG axis thereby resulting in reduction in reproductive physiology.

Expression of estrogen receptor alpha in response to stress and estrogen antagonist tamoxifen in the shell gland of Gallus gallus domesticus: involvement of anti-oxidant system and estrogen.

Animals are frequently exposed to various kinds of environmental stressors and estrogen is known to play important role in stress response besides its crucial role in regulation of cellular proliferation, metabolic activity and reproduction. The study investigates the estrogen antagonist, tamoxifen (TM), mediated estrogen receptor alpha (ERα) expression, to modulate stress induced parameters in chickens. The study further explores the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) and malonaldehyde (MDA) in brain, ovary and shell gland during water deprivation (WD) and tamoxifen administration in sexually mature chicken. WD and TM administration both decrease the plasma estradiol while WD increases corticosterone. WD also elevates MDA concentration in the brain, ovary and shell gland while TM lowers it. WD and TM administration lowers the specific activity of SOD in brain and shell gland. In contrast, WD increases the specific activity of catalase, GPx and GR in the brain and shell gland, while TM decreases it. It appears that endogenous estradiol plays a crucial role in expression of antioxidant enzymes and tamoxifen acts as an antioxidant by reducing the oxidative stress in chicken. Abundant expression of ERα has been observed in the shell gland of egg laying birds while stress like water deprivation and TM down-regulates its expression. Thus, it can be concluded that expression of ERα in shell gland plays a predominant role in mediating estrogen action in response to water deprivation stress and tamoxifen.

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis.

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease. METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. CONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients.

Water and Food restriction decreases immunoreactivity of oestrogen receptor alpha and antioxidant activity in testes of sexually mature Coturnix coturnix japonica.

Food and water are closely associated with reproductive willingness in vertebrates. These are important for animals and their non-availability act as stressors which decrease sex steroid secretion suppressing reproductive behaviour. Oestrogen plays a crucial role in reproduction via its receptors alpha (ERα) and beta (ERß). This study tested the hypothesis that ERα in testes of male Japanese quail is regulated during water and food deprivations. The present study reveals that both water and food deprivations cause oxidative stress and subsequently decrease catalase and superoxide dismutase activity, while these increase malondialdehyde and hydrogen peroxide. Both deprivations reduce plasma oestradiol whereas elevate corticosterone level. The immunofluorescent localization of ERα in the testes occurs predominantly in the seminiferous tubules of control while reduces after both food and water deprivations. All types of spermatogenic cells were seen in control testis, while after water and food deprivations size of seminiferous tubules and spermatogenic cells population decreased. Scanning electron microscopic study exhibited fully mature sperms in clusters with head and elongated flagellum, whereas after water deprivation maximum sperms were distorted, scattered with highly reduced head. On food deprivation, only few sperms were seen with head and tail. Thus, taking into account the localization of ERα in testis, it is obvious that oestrogens produced locally are involved in regulation of spermatogenesis and spermiogenesis during stress.

Evaluation of ACC-deaminase-producing rhizobacteria to alleviate water-stress impacts in wheat (Triticum aestivum L.) plants.

Application of plant-growth-promoting rhizobacteria (PGPR) is an environmentally sustainable option to reduce the effects of abiotic and biotic stresses on plant growth and productivity. Bacteria isolated from rain-fed agriculture field soils in the Central Himalaya Kumaun region, India, were evaluated for the production of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. Those producing ACC deaminase in high amounts were evaluated for their potential to improve wheat (Triticum aestivum L.) plant growth under irrigated and water-stress conditions in two glasshouse experiments. Some of the isolates also showed other plant-growth-promoting (PGP) traits, e.g., N2 fixation, siderophore production, and phosphate solubilization; however, strains with higher ACC deaminase activity showed the greatest effects. These were Variovorax paradoxus RAA3; Pseudomonas spp. DPC12, DPB13, DPB15, DPB16; Achromobacter spp. PSA7, PSB8; and Ochrobactrum anthropi DPC9. In both simulated irrigated and water-stress conditions, a single inoculation of RAA3 and a consortium of DPC9 + DPB13 + DPB15 + DPB16 significantly improved wheat plant growth and foliar nutrient concentrations and caused significant positive changes in antioxidant properties compared with noninoculated plants especially under water stress. These findings imply that PGPB having ACC deaminase activity together with other PGP traits could potentially be effective inoculants to improve the growth of wheat plants in water-stressed rain-fed environments.

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease.

Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions.

Facilitating Clinical Studies in Rare Diseases.

In recent years, there have been many scientific advances and new collaborations for rare diseases research and, ultimately, the health of patients living with rare diseases. However, for too many rare diseases, there still is no effective treatment, and our understanding of the incidence, prevalence, and underlying etiology is incomplete. To facilitate the studies needed to answer the many open questions there is a great need for the active involvement of all stakeholders, most importantly of patient groups. Also, the creation of streamlined infrastructure for performing multi-site clinical studies is critical, as is the engagement of multi-disciplinary teams with shared focus on a group of diseases. Another essential component of such efforts is to collect standardized data so that downstream meta-analyses and data sharing can be facilitated. To ensure high-quality protocols and datasets, a central data management and coordinating center is important. Since there are more than 6000 rare diseases, instead of focusing on single rare disease, it is more impactful to create platforms and methods that can support a group of rare diseases.

Nutritional interventions in primary mitochondrial disorders: Developing an evidence base.

In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD.

Managing distance and covariate information with point-based clustering.

BACKGROUND: Geographic perspectives of disease and the human condition often involve point-based observations and questions of clustering or dispersion within a spatial context. These problems involve a finite set of point observations and are constrained by a larger, but finite, set of locations where the observations could occur. Developing a rigorous method for pattern analysis in this context requires handling spatial covariates, a method for constrained finite spatial clustering, and addressing bias in geographic distance measures. An approach, based on Ripley's K and applied to the problem of clustering with deliberate self-harm (DSH), is presented. METHODS: Point-based Monte-Carlo simulation of Ripley's K, accounting for socio-economic deprivation and sources of distance measurement bias, was developed to estimate clustering of DSH at a range of spatial scales. A rotated Minkowski L1 distance metric allowed variation in physical distance and clustering to be assessed. Self-harm data was derived from an audit of 2 years' emergency hospital presentations (n = 136) in a New Zealand town (population ~50,000). Study area was defined by residential (housing) land parcels representing a finite set of possible point addresses. RESULTS: Area-based deprivation was spatially correlated. Accounting for deprivation and distance bias showed evidence for clustering of DSH for spatial scales up to 500 m with a one-sided 95 % CI, suggesting that social contagion may be present for this urban cohort. CONCLUSIONS: Many problems involve finite locations in geographic space that require estimates of distance-based clustering at many scales. A Monte-Carlo approach to Ripley's K, incorporating covariates and models for distance bias, are crucial when assessing health-related clustering. The case study showed that social network structure defined at the neighbourhood level may account for aspects of neighbourhood clustering of DSH. Accounting for covariate measures that exhibit spatial clustering, such as deprivation, are crucial when assessing point-based clustering.

Assessment of genotoxic and mutagenic potential of hexavalent chromium in the freshwater fish Labeo rohita (Hamilton, 1822).

The present study was undertaken to investigate the genotoxicity and mutagenicity of sublethal concentrations of hexavalent chromium (potassium dichromate) in the Indian major carp, Labeo rohita. The 96 h LC50 value of potassium dichromate estimated was 118 mg L(-1) by probit analysis using SPSS (version 16.0) software. Based on 96 h LC50 value, three sublethal test concentrations of potassium dichromate (29.5, 59.0 and 88.5 mg L(-)(1)) were selected and specimens were exposed in vivo to these test concentrations for 96 h. The mutagenic and genotoxic effects of potassium dichromate were evaluated in gill and blood cells using micronucleus (MN) test and comet assay. In general, significant (p < 0.05) effects due to the concentrations and the exposure durations were observed in exposed specimens. The MN induction was highest at 96 h at all the test concentrations in the peripheral blood. A similar trend was observed for the DNA damage, measured in terms of percentage of tail DNA, in erythrocyte and gill cells. The study indicated hazardous effect of the hexavalent chromium to fish and other aquatic organisms and indirectly to human beings.

Assessment of pollution of river Ganges by tannery effluents using genotoxicity biomarkers in murrel fish, Channa punctatus (Bloch).

River pollution due to rapid industrialization and anthropogenic activities adversely affects the aquatic organisms, especially fish. Here, we assessed the genotoxicity, mutagenicity and bioaccumulative aspects of tannery effluents in freshwater murrel, Channa punctatus, an inhabitant of river Ganges. Test specimens were collected from three different polluted sites of the river within and nearby Kanpur area during different seasons and blood samples of these specimens were processed for comet assay and micronucleus test as genotoxicity biomarkers. A significantly (P < 0.05) higher micronuclei induction, nuclear abnormalities and % tail DNA was observed in the specimens collected from the polluted sites. Bioaccumulation studies in the muscle (1.202 µg/g) and gill tissues (< 0.300 µg/g) of the specimens revealed the concentration of chromium (core component of tanning industry) above the maximum permissible limits as prescribed by World Health Organization (WHO). The findings of the present analysis indicated contamination of river Ganges with tannery effluents which induce genotoxicity in fish with seasonal variation.

The Rare Diseases Clinical Research Network's organization and approach to observational research and health outcomes research.

Established in 2003 by the Office of Rare Diseases Research (ORDR), in collaboration with several National Institutes of Health (NIH) Institutes/Centers, the Rare Diseases Clinical Research Network (RDCRN) consists of multiple clinical consortia conducting research in more than 200 rare diseases. The RDCRN supports longitudinal or natural history, pilot, Phase I, II, and III, case-control, cross-sectional, chart review, physician survey, bio-repository, and RDCRN Contact Registry (CR) studies. To date, there have been 24,684 participants enrolled on 120 studies from 446 sites worldwide. An additional 11,533 individuals participate in the CR. Through a central data management and coordinating center (DMCC), the RDCRN's platform for the conduct of observational research encompasses electronic case report forms, federated databases, and an online CR for epidemiological and survey research. An ORDR-governed data repository (through dbGaP, a database for genotype and phenotype information from the National Library of Medicine) has been created. DMCC coordinates with ORDR to register and upload study data to dbGaP for data sharing with the scientific community. The platform provided by the RDCRN DMCC has supported 128 studies, six of which were successfully conducted through the online CR, with 2,352 individuals accrued and a median enrollment time of just 2 months. The RDCRN has built a powerful suite of web-based tools that provide for integration of federated and online database support that can accommodate a large number of rare diseases on a global scale. RDCRN studies have made important advances in the diagnosis and treatment of rare diseases.

Temporal variations in basicranium dimorphism of North Indians.

In recent years, several investigations have documented notable secular changes in human skull morphology. The present study is the next link in the series, addressing its possible effects in the cranial base in North Indian populations. The present study aims to examine the sexual dimorphism in cranial base of two temporally different samples of North Indian population to provide updated population specific osteometric standards. The contemporary and the subrecent samples are comprised of 158 (M 110; F 48) and 325 adult crania (M 206; F 119), respectively. Five variables of cranial base were measured, and data were subjected to discriminant function analysis using SPSS 16.0. The t-tests between the two temporally different samples showed significant sexual dimorphism and population variation. Contemporary females showed comparatively greater dimensions than subrecent. Contemporary population exhibited less sexual dimorphism than subrecent population. Factors associated with the changes in sexual dimorphism are likely to be a consequence of improved nutrition and population admixture in last 50 years. The accuracy of sex prediction ranged from 48.1 to 70.0 % in contemporary sample and 60.9 % to 77.2 % in subrecent sample. Overall, these findings support the conclusion that sexual dimorphism shows variation within few decades, so sex discriminating osteometric standards must be updated regularly.