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IntroductionIndia has the second largest HIV epidemic in the world. Despite successes in epidemic control at the population level, a concentrated epidemic persists among gay and other men who have sex with men (MSM). However, India lags in implementation of biomedical prevention technologies, such as HIV pre-exposure prophylaxis (PrEP). In order to inform scale-up of new HIV prevention technologies, including those in the development pipeline, we assessed willingness to use oral PrEP, rectal microbicides, and HIV vaccines, and choices among product characteristics, among MSM in two major Indian cities.MethodsA cross-sectional survey was conducted with a discrete choice experiment (DCE), an established methodology for quantitively estimating end-user preferences in healthcare. Survey participants were randomly assigned to one of three questionnaire versions, each of which included a DCE for one prevention technology. Participants were recruited using chain-referral sampling by peer outreach workers, beginning with seeds in community-based organizations and public sex environments, in Chennai and Mumbai. DCE data were analyzed using random-parameters (mixed) logit (RPL) models.ResultsAmong participants (n = 600), median age was 25 years, with median monthly income of INR 9,000 (~US$125). Nearly one-third (32%) had completed a college degree and 82% were single/never married. A majority of participants (63%) reported condomless anal sex in the past month. The acceptability of all three products was universally high (≥90%). Across all three products, four attributes were significant predictors of acceptability-with efficacy consistently the most important attribute, and in decreasing order of preference, side-effects, dosing schedule, and venue. MSM varied in their preferences for product attributes in relation to their levels of education and income, and engagement in sex work and HIV risk behavior.ConclusionThis study provides empirical evidence to facilitate the integration of end users' preferences throughout design, testing, and dissemination phases of HIV prevention technologies. The findings also suggest action points and targets for interventions for diverse subgroups to support the effectiveness of combination HIV prevention among MSM in India.

PurposeSexual and gender minority and racialized populations experienced heightened vulnerability during the Covid-19 pandemic. Marginalization due to structural homophobia, transphobia and racism, and resulting adverse social determinants of health that contribute to health disparities among these populations, were exacerbated by the Covid-19 pandemic and public health measures to control it. We developed and tested a tailored online intervention (#SafeHandsSafeHearts) to support racialized lesbian, gay, bisexual, transgender, queer, and other persons outside of heteronormative and cisgender identities (LGBTQ+) in Toronto, Canada during the pandemic.MethodsWe used a quasi-experimental pre-test post-test design to evaluate the effectiveness of a 3-session, peer-delivered eHealth intervention in reducing psychological distress and increasing Covid-19 knowledge and protective behaviors. Individuals ≥18-years-old, resident in Toronto, and self-identified as sexual or gender minority were recruited online. Depressive and anxiety symptoms, and Covid-19 knowledge and protective behaviors were assessed at baseline, 2-weeks postintervention, and 2-months follow-up. We used generalized estimating equations and zero-truncated Poisson models to evaluate the effectiveness of the intervention on the four primary outcomes.ResultsFrom March to November 2021, 202 participants (median age, 27 years [Interquartile range: 23-32]) were enrolled in #SafeHandsSafeHearts. Over half (54.5%, n = 110) identified as cisgender lesbian or bisexual women or women who have sex with women, 26.2% (n = 53) cisgender gay or bisexual men or men who have sex with men, and 19.3% (n = 39) transgender or nonbinary individuals. The majority (75.7%, n = 143) were Black and other racialized individuals. The intervention led to statistically significant reductions in the prevalence of clinically significant depressive (25.4% reduction, p < .01) and anxiety symptoms (16.6% reduction, p < .05), and increases in Covid-19 protective behaviors (4.9% increase, p < .05), from baseline to postintervention.ConclusionWe demonstrated the effectiveness of a brief, peer-delivered eHealth intervention for racialized LGBTQ+ communities in reducing psychological distress and increasing protective behaviors amid the Covid-19 pandemic. Implementation through community-based organizations by trained peer counselors supports feasibility, acceptability, and the importance of engaging racialized LGBTQ+ communities in pandemic response preparedness. This trial is registered with ClinicalTrials.gov, number NCT04870723.

BackgroundDiabetes self-care behaviour plays a crucial role in managing the diabetes effectively and preventing complications. Patients with type 2 diabetes mellitus (T2DM) and health care professionals (HCPs) of rural areas often face unique challenges when it comes to diabetes self-care practices (SCPs). Therefore, this study aim to explore the perspectives of patients with T2DM and HCPs on diabetes SCPs.MethodsEight focus group discussions (FGDs) among individuals with T2DM and In-depth interviews (IDIs) with 15 HCPs were conducted in rural areas of Punjab, North India. Capability, Opportunity, Motivation, and Behaviour model (COM-B) was employed for thematic framework analyses.ResultsThe study participants perceived that a limited understanding of diabetes mellitus (DM), beliefs in alternative therapies, drug side effects, attitudes towards DM (psychological capability), comorbidities (physical capability), family support (social opportunity), financial and time constraints, and weather conditions (physical opportunity) contributed to lack of DM SCPs. Physicians' guidance and support were motivating them to adhere to SCPs, especially when aligned with their sense of self-efficacy (reflective motivation). HCPs constraints in providing patient-centred care are due to training limitations (psychological capability) and a lack of essential resources (physical opportunities). Participants expressed need for comprehensive diabetes care (automatic motivation) through structured diabetes education intervention to improve diabetes SCPs.ConclusionsThe study findings indicate that various factors influence diabetes SCPs from the perspectives of both patients with T2DM and HCPs and emphasizes the need for a multi-faceted approach to improve diabetes SCPs in rural areas. Implementing a structured diabetes self-care intervention strategy in rural areas may help for preventing and mitigating the impact of diabetes-related complications in rural areas.

B memory (BM) cell responses were evaluated using peripheral blood mononuclear cells that were collected and cryopreserved during a Phase 1 trial of two live Shigella sonnei vaccine candidates WRSs2 and WRSs3. An ELISpot assay was used to measure IgG+ and IgA+ BM cell responses against S. sonnei LPS, IVP and IpaB antigens. Analysis of BM cell responses at baseline, and on days 28 and 56 post vaccination indicate that after a single oral dose of WRSs2 and WRSs3, both groups of vaccinees induced IgG+ and IgA+ BM cell responses that were variable in magnitude among subjects and reached significance to IVP and IpaB at several doses. The responses generally peaked at d28 after vaccination. The baseline as well as post-vaccination levels of IgA+ BM cells were relatively higher than IgG+ BM cells, but the maximum fold-increase at d28/d56 over baseline was greater for IgG+ than IgA+ BM cell responses. Furthermore, at the three highest vaccine doses, >60-90% of subjects were considered responders indicating a ≥2-fold higher IgG+ BM cell responses to IVP and IpaB post vaccination, while fewer subjects indicated the same level of response to LPS.

School dropout is a significant concern universally. This paper investigates the incorporation of spatial dependency in estimating the topographical effect of school dropout rates in India. This study utilizes the secondary data on primary, upper primary, and secondary school dropout rates of the different districts of India available at the Unified District Information System for Education plus (UDISE+) for the year 2020 to contemplate the impact of these dropouts from one region to different regions in molding with promotion rate and repetition rate. The Global Moran's I, Univariate and Bivariate Local Indicators of Spatial Association, and spatial models are utilized to investigate the geographical variability and to find the possible relationship between dropout rates and the school-level factors at the district level. The outcomes provide clear spatial clustering and precisely highlight the hot zone dropout regions with high repetition and low promotion rates. Based on this study's results, educational administrators can make evidence-based decisions to reduce dropout rates in hot zones of various regions of India. Furthermore, futuristic studies focusing on linking spatial hot zones with causal factors will add consistent data in assisting policymakers in taking necessary measures to develop a sound education management system.

Introduction: India has the second largest HIV epidemic in the world. Despite successes in epidemic control at the population level, a concentrated epidemic persists among gay and other men who have sex with men (MSM). However, India lags in implementation of biomedical prevention technologies, such as HIV pre-exposure prophylaxis (PrEP). In order to inform scale-up of new HIV prevention technologies, including those in the development pipeline, we assessed willingness to use oral PrEP, rectal microbicides, and HIV vaccines, and choices among product characteristics, among MSM in two major Indian cities. Methods: A cross-sectional survey was conducted with a discrete choice experiment (DCE), an established methodology for quantitively estimating end-user preferences in healthcare. Survey participants were randomly assigned to one of three questionnaire versions, each of which included a DCE for one prevention technology. Participants were recruited using chain-referral sampling by peer outreach workers, beginning with seeds in community-based organizations and public sex environments, in Chennai and Mumbai. DCE data were analyzed using random-parameters (mixed) logit (RPL) models. Results: Among participants (n = 600), median age was 25 years, with median monthly income of INR 9,000 (~US$125). Nearly one-third (32%) had completed a college degree and 82% were single/never married. A majority of participants (63%) reported condomless anal sex in the past month. The acceptability of all three products was universally high (≥90%). Across all three products, four attributes were significant predictors of acceptability—with efficacy consistently the most important attribute, and in decreasing order of preference, side-effects, dosing schedule, and venue. MSM varied in their preferences for product attributes in relation to their levels of education and income, and engagement in sex work and HIV risk behavior. Conclusion: This study provides empirical evidence to facilitate the integration of end users' preferences throughout design, testing, and dissemination phases of HIV prevention technologies. The findings also suggest action points and targets for interventions for diverse subgroups to support the effectiveness of combination HIV prevention among MSM in India. [ABSTRACT FROM AUTHOR]

Purpose: Sexual and gender minority and racialized populations experienced heightened vulnerability during the Covid-19 pandemic. Marginalization due to structural homophobia, transphobia and racism, and resulting adverse social determinants of health that contribute to health disparities among these populations, were exacerbated by the Covid-19 pandemic and public health measures to control it. We developed and tested a tailored online intervention (#SafeHandsSafeHearts) to support racialized lesbian, gay, bisexual, transgender, queer, and other persons outside of heteronormative and cisgender identities (LGBTQ+) in Toronto, Canada during the pandemic. Methods: We used a quasi-experimental pre-test post-test design to evaluate the effectiveness of a 3-session, peer-delivered eHealth intervention in reducing psychological distress and increasing Covid-19 knowledge and protective behaviors. Individuals ≥18-years-old, resident in Toronto, and self-identified as sexual or gender minority were recruited online. Depressive and anxiety symptoms, and Covid-19 knowledge and protective behaviors were assessed at baseline, 2-weeks postintervention, and 2-months follow-up. We used generalized estimating equations and zero-truncated Poisson models to evaluate the effectiveness of the intervention on the four primary outcomes. Results: From March to November 2021, 202 participants (median age, 27 years [Interquartile range: 23–32]) were enrolled in #SafeHandsSafeHearts. Over half (54.5%, n = 110) identified as cisgender lesbian or bisexual women or women who have sex with women, 26.2% (n = 53) cisgender gay or bisexual men or men who have sex with men, and 19.3% (n = 39) transgender or nonbinary individuals. The majority (75.7%, n = 143) were Black and other racialized individuals. The intervention led to statistically significant reductions in the prevalence of clinically significant depressive (25.4% reduction, p <.01) and anxiety symptoms (16.6% reduction, p <.05), and increases in Covid-19 protective behaviors (4.9% increase, p <.05), from baseline to postintervention. Conclusion: We demonstrated the effectiveness of a brief, peer-delivered eHealth intervention for racialized LGBTQ+ communities in reducing psychological distress and increasing protective behaviors amid the Covid-19 pandemic. Implementation through community-based organizations by trained peer counselors supports feasibility, acceptability, and the importance of engaging racialized LGBTQ+ communities in pandemic response preparedness. This trial is registered with ClinicalTrials.gov, number NCT04870723. [ABSTRACT FROM AUTHOR]

Lyme disease is the most common vector-borne infectious disease in the United States. Post-treatment Lyme disease (PTLD) is a condition affecting 10-20% of patients in which symptoms persist despite antibiotic treatment. Cognitive complaints are common among those with PTLD, suggesting that brain changes are associated with the course of the illness. However, there has been a paucity of evidence to explain the cognitive difficulties expressed by patients with PTLD. This study administered a working memory task to a carefully screened group of 12 patients with well-characterized PTLD and 18 healthy controls while undergoing functional MRI (fMRI). A subset of 12 controls and all 12 PTLD participants also received diffusion tensor imaging (DTI) to measure white matter integrity. Clinical variables were also assessed and correlated with these multimodal MRI findings. On the working memory task, the patients with PTLD responded more slowly, but no less accurately, than did controls. FMRI activations were observed in expected regions by the controls, and to a lesser extent, by the PTLD participants. The PTLD group also hypoactivated several regions relevant to the task. Conversely, novel regions were activated by the PTLD group that were not observed in controls, suggesting a compensatory mechanism. Notably, three activations were located in white matter of the frontal lobe. DTI measures applied to these three regions of interest revealed that higher axial diffusivity correlated with fewer cognitive and neurological symptoms. Whole-brain DTI analyses revealed several frontal lobe regions in which higher axial diffusivity in the patients with PTLD correlated with longer duration of illness. Together, these results show that the brain is altered by PTLD, involving changes to white matter within the frontal lobe. Higher axial diffusivity may reflect white matter repair and healing over time, rather than pathology, and cognition appears to be dynamically affected throughout this repair process.

BackgroundThe increasing number of physicians leaving practice, especially hospitalists, has been well-documented. The most commonly examined factor associated with this exodus has been burnout. The COVID-19 pandemic has put a unique and unprecedented stress on hospitalists who have been at the front lines of patient care. Therefore, the investigation of burnout and its related factors in hospitalists is essential to preventing future physician shortages.ObjectiveThis study examined the relationship between burnout, second victim, and moral injury experiences before and during the COVID-19 pandemic among hospitalists.MethodsTwo anonymous cross-sectional surveys of hospitalists from a community hospital in the metropolitan Washington, DC area were conducted. One was conducted pre-COVID-19 (September-November 2019) and one was conducted during COVID-19 (July-August 2020). The surveys were sent to all full-time hospitalists via an online survey platform. A variety of areas were assessed including demographic (e.g., age, gender), work information (e.g., hours per week, years of experience), burnout, second victim experiences, well-being, and moral injury.ResultsBurnout rates among providers during these two time periods were similar. Second victim experiences remained prevalent in those who experienced burnout both pre and during COVID-19, but interestingly the prevalence increased in those without burnout during COVID-19. Moral injury was predictive of burnout during COVID-19.ConclusionWhile there were some factors that predicted burnout that were similar both pre- and during-pandemic, moral injury was unique to predicting burnout during COVID-19. With burnout as a contributing factor to future physician shortages, it is imperative that predictive factors in a variety of different environments are well understood to prevent future shortages. Hospitalists may be an excellent barometer of these factors given their presence on the front line during the pandemic, and their experiences need to be further explored so that targeted interventions aimed at addressing those factors may be created.

BackgroundGiven the rapid spread of COVID-19 and its associated morbidity and mortality, healthcare providers throughout the world have been forced to constantly update and change their care delivery models.ObjectiveTo assess the outcomes of COVID-19 hospitalized patients during the course of the pandemic in a well-integrated health system.MethodsThe study used data from the electronic health medical records to assess trends in clinical profile and outcomes of hospitalized adult COVID-19 patients hospitalized in our 5-hospital health system from March 2020-May 2021 (n = 6865). Integration of the health system began in February 2020 and was fully actualized by March 30, 2020.ResultsMortality decreased from 15% during first peak (March-May 2020; the rate includes 19% in March-April and 10% in May 2020) to 6% in summer-fall 2020, increased to 13% during the second peak (November 2020-January 2021), and dropped to 7% during the decline period (February-May 2021) (pConclusionsThe creation of a fully integrated health system allowed us to dynamically respond to the everchanging COVID-19 landscape. In this context, despite the increasing patient acuity, our mortality and resource utilization rates have improved during the pandemic.

IntroductionDespite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment.Materials and methodWe extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application.ResultsOf 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement ConclusionBaseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

The female gametophyte of flowering plants, called the embryo sac, develops from a haploid cell named the functional megaspore, which is specified after meiosis by the diploid sporophyte. In Arabidopsis, the functional megaspore undergoes three syncitial mitotic divisions followed by cellularization to form seven cells of four cell types including two female gametes. The plant hormone auxin is important for sporophytic developmental processes, and auxin levels are known to be regulated by biosynthesis and transport. Here, we investigated the role of auxin biosynthetic genes and auxin influx carriers in embryo sac development. We find that genes from the YUCCA/TAA pathway (YUC1, YUC2, YUC8, TAA1, TAR2) are expressed asymmetrically in the developing ovule and embryo sac from the two-nuclear syncitial stage until cellularization. Mutants for YUC1 and YUC2 exhibited defects in cell specification, whereas mutations in YUC8, as well as mutations in TAA1 and TAR2, caused defects in nuclear proliferation, vacuole formation and anisotropic growth of the embryo sac. Additionally, expression of the auxin influx carriers AUX1 and LAX1 were observed at the micropylar pole of the embryo sac and in the adjacent cells of the ovule, and the aux1 lax1 lax2 triple mutant shows multiple gametophyte defects. These results indicate that both localized auxin biosynthesis and auxin import, are required for mitotic divisions, cell expansion and patterning during embryo sac development.

BackgroundPlasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach, and investigate whether these associations are modified by lifestyle factors.MethodsThe study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing.ResultsThe 'A' allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p = 1.90 x 10-47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p = 7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of 'A' allele with cardiometabolic health status disappeared (p = 0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons).ConclusionsOur findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Before strategies to promote adiponectin modulation could be implemented, further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases.

The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner. Previously, mucosal immune responses were measured by assaying IgA- and IgG-ASC in peripheral blood mononuclear cells (PBMCs). In this report, the magnitude of the S. sonnei antigen-specific IgA- and IgG-ALS responses was measured and correlated with previously described ASCs, serum antibodies, fecal IgA and vaccine shedding. Overall, the magnitude of S. sonnei anti-Invaplex50 ALS was higher than that of LPS or IpaB, and both vaccines demonstrated a more robust IgA-ALS response than IgG; however, compared to WRSs3, the magnitude and percentage of responders were higher among WRSs2 recipients for IgA- or IgG-ALS. All WRSs2 vaccinees at the two highest doses responded for LPS and Invaplex50-specific IgA-ALS and 63–100% for WRSs3 vaccinees responded. Regardless of the vaccine candidate, vaccine dose or detecting antigen, the kinetics of ALS responses were similar peaking on days 7 to 9 and returning to baseline by day 14. The ALS responses were vaccine-specific since no responses were detected among placebo recipients at any time. A strong correlation and agreement between responders/non-responders were noted between ALS and other mucosal (ASC and fecal IgA) and systemic (serum antibody) immune responses. These data indicate that the ALS assay can be a useful tool to evaluate mucosal responses to oral vaccination, an observation noted with trials of other bacterial diarrheal pathogens. Furthermore, this data will guide the list of immunological assays to be conducted for efficacy trials in different populations. It is hoped that an antigen-specific-ALS titer may be a key mucosal correlate of protection, a feature not currently available for any Shigella vaccines candidates. https://clinicaltrials.gov/show/NCT01336699.

BackgroundThe use of Bayesian Structural Equation Model (BSEM) to evaluate the impact of TB on self-reported health related quality of life (HRQoL) of TB patients has been not studied.ObjectiveTo identify the factors that contribute to the HRQoL of TB patients using BSEM.MethodsThis is a latent variable modeling with Bayesian approach using secondary data. HRQoL data collected after one year from newly diagnosed 436 TB patients who were registered and successfully completed treatment at Government health facilities in Tiruvallur district, south India under the National TB Elimination Programme (NTEP) were used for this analysis. In this study, the four independent latent variables such as physical well-being (PW = PW1-7), mental well-being (MW = MW1-7), social well-being (SW = SW1-4) and habits were considered. The BSEM was constructed using Markov Chain Monte Carlo algorithm for identifying the factors that contribute to the HRQoL of TB patients who completed treatment.ResultsBayesian estimates were obtained using 46,300 observations after convergence and the standardized structural regression estimate of PW, MW, SW on HRQoL were 0.377 (pConclusionsThe current study demonstrated the application of BSEM in evaluating HRQoL. This methodology may be used to study precise estimates of HRQoL of TB patients in different time points.

Factors governing the distribution of organisms in the pelagic ocean are understudied. In this paper we describe environmental parameters and macrofouling assemblages on 11 buoys deployed in the Arabian Sea for an average duration of 322 days. Macrofoulants on all the mooring components extending from the sea-surface to a depth of 1800-4300 m were documented. Role of temperature, salinity, dissolved oxygen, biological productivity and zooplankton community in governing the macrofoulant distribution are described. Species composition, vertical zonation and wet biomass exhibited significant spatial variations. Lepas anatifera constituted more than 90% of foulant wet biomass on all moorings. Assemblages in the southeastern (SEAS), east-central (ECAS) and northeast (NEAS) regions were distinct. Density of L. anatifera on surface buoys were low in SEAS (0.2±0.09 no./cm2), high in ECAS (0.32±0.11 no./cm2) and moderate in NEAS (0.23±0.04no./cm2). Macrofoulants were observed up to a depth of 75 m in SEAS, 130 m in ECAS and 120 m in NEAS. The depth profile of macrofoulant assemblages on moorings could be related to the prevalent hypoxic condition. Vertical profiles of wet biomass on all moorings exhibited subsurface maxima at depth ranging from 10 to 20 m, consequent to the abundance of L. anatifera in a thermally stable depth of water column, wherein diurnal and semidiurnal temperature variability was minimal. We attribute the observed variation in fouling assemblages to dissolved oxygen levels, salinity and diurnal variability in temperature and salinity.

BACKGROUND:Unhealthy dietary behaviour-high intake of fat, sugar, and salt, and low intake of fruits and vegetables-is a major risk factor for chronic diseases. There is a lack of evidence-based interventions to promote healthy dietary intake among Indian populations. Therefore, we tested the effectiveness of an information technology-enabled 'SMART Eating' intervention to reduce the intake of fat, sugar and salt, and to increase the intake of fruits and vegetables. METHODS:In Chandigarh, a North Indian city, a cluster randomized controlled trial was implemented in twelve geographical clusters, based on the type of housing (i.e., LIG: Low-income group; MIG; Middle-income group, and HIG: High-income group-a proxy for socio-economic status). Computer-generated randomization was used to allocate clusters to intervention and comparison arms after pairing on the basis of socioeconomic status and geographical distance between clusters. The sample size was 366 families per arm (N = 732). One adult per family was randomly selected as an index case to measure the change in the outcomes. For behaviour change, a multi-channel communication approach was used, which included information technology-short message service (SMS), email, social networking app and 'SMART Eating' website, and interpersonal communication along with distribution of a 'SMART Eating' kit-kitchen calendar, dining table mat, and measuring spoons. The intervention was implemented at the family level over a period of six months. The comparison group received pamphlets on nutrition education. Outcome measurements were made at 0 and 6 months post-intervention at the individual level. Primary outcomes were changes in mean dietary intakes of fat, sugar, salt, and fruit and vegetables. Secondary outcomes included changes in body mass index (BMI), blood pressure, haemoglobin, fasting plasma glucose (FPG), and serum lipids. Mixed-effects linear regression models were used to determine the net change in the outcomes in the intervention group relative to the comparison group. RESULTS:Participants' mean age was 53 years, a majority were women (76%), most were married (90%) and 51% had completed a college degree. All families had mobile phones, and more than 90% of these families had access to Internet through mobile phones. The intervention group had significant net mean changes of -12.5 g/day (p

The ecology and distribution of many bacteria is strongly associated with specific eukaryotic hosts. However, the impact of such host association on bacterial ecology and evolution is not well understood. Bacteria from the genus Methylobacterium consume plant-derived methanol, and are some of the most abundant and widespread plant-associated bacteria. In addition, many of these species impact plant fitness. To determine the ecology and distribution of Methylobacterium in nature, we sampled bacteria from 36 distinct rice landraces, traditionally grown in geographically isolated locations in North-East (NE) India. These landraces have been selected for diverse phenotypic traits by local communities, and we expected that the divergent selection on hosts may have also generated divergence in associated Methylobacterium strains. We determined the ability of 91 distinct rice-associated Methylobacterium isolates to use a panel of carbon sources, finding substantial variability in carbon use profiles. Consistent with our expectation, across spatial scales this phenotypic variation was largely explained by host landrace identity rather than geographical factors or bacterial taxonomy. However, variation in carbon utilisation was not correlated with sugar exudates on leaf surfaces, suggesting that bacterial carbon use profiles do not directly determine bacterial colonization across landraces. Finally, experiments showed that at least some rice landraces gain an early growth advantage from their specific phyllosphere-colonizing Methylobacterium strains. Together, our results suggest that landrace-specific host-microbial relationships may contribute to spatial structure in rice-associated Methylobacterium in a natural ecosystem. In turn, association with specific bacteria may provide new ways to preserve and understand diversity in one of the most important food crops of the world.

BACKGROUND:Some guidelines state that in-person weight management interventions are more efficacious than those delivered digitally. However, digital programs are more scalable and accessible. We hypothesized that one-on-one health coaching via app-based video chat would simulate an in-person experience and help achieve outcomes comparable to those of in-person interventions. METHODS:A 12-month digital weight management intervention was provided to overweight or obese adults recruited from a large technology company. One-on-one health coaching sessions were offered during a 24-week intensive phase as well as subsequent maintenance phase. Focused on sustainable changes in activity and diet, the intervention incorporates SMART goals, in-app food and activity logs, Fitbit integration, as well as optional sleep and stress modules. Self-Determination Theory and the Transtheoretical Model are incorporated to drive behavior change. Multilevel mixed-effects models were used to analyze weight changes retrospectively. RESULTS:Six hundred eighty-three participants reported 29,051 weights. At 12 months, mean percent changes in body weight were -7.2% and -7.6% for overweight and obese groups, respectively. A weight change of -5% is commonly targeted for in-person weight management interventions. Observed weight loss exceeded this target by 2.2% (95% CI, 0.7% to 3.8%; P < .01) for the overweight group and 2.6% (95% CI, 1.4% to 3.9%; P < .01) for the obese group. CONCLUSIONS:Further research is needed with randomization to in-person or digital interventions. Though limited by an observational, retrospective design, preliminary results suggest that some digital weight management programs with one-on-one coaching may achieve outcomes comparable to those of robust, in-person interventions.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that results in variable severities of neurodegeneration. The understanding of MS has been limited by the inaccessibility of the affected cells and the lengthy timeframe of disease development. However, recent advances in stem cell technology have facilitated the bypassing of some of these challenges. Towards gaining a greater understanding of the innate potential of stem cells from people with varying degrees of disability, we generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells derived from stable and progressive MS patients, and then further differentiated them into oligodendrocyte (OL) lineage cells. We analyzed differentiation under both homeostatic and inflammatory conditions via sustained exposure to low-dose interferon gamma (IFNγ), a prominent cytokine in MS. We found that all iPSC lines differentiated into mature myelinating OLs, but chronic exposure to IFNγ dramatically inhibited differentiation in both MS groups, particularly if exposure was initiated during the pre-progenitor stage. Low-dose IFNγ was not toxic but led to an early upregulation of interferon response genes in OPCs followed by an apparent redirection in lineage commitment from OL to a neuron-like phenotype in a significant portion of the treated cells. Our results reveal that a chronic low-grade inflammatory environment may have profound effects on the efficacy of regenerative therapies.

The use of biopolymers as elicitors in controlling plant diseases is gaining momentum world-wide due to their eco-friendly and non-toxic nature. In the present study, we have used an algal biopolymer (sodium alginate) and tested its applicability as an elicitor in inducing resistance factors against Alternaria solani, which causes early blight disease in Solanum lycopersicum (tomato plant). We have pre-treated tomato plants with different concentrations of sodium alginate (0.2%, 0.4%, and 0.6%) before A. solani infection. We found that sodium alginate has effectively controlled the growth of A. solani. In addition, a significant increase in the expression levels of SOD was observed in response to pathogen infection. The increased protease inhibitors activity further suggest that sodium alginate restrict the development of A. solani infection symptoms in tomato leaves. This corroborates well with the cell death analysis wherein increased sodium alginate pre-treatment results in decreased cell death. Also, the expression profile analyses reveal the induction of genes only in sodium alginate-pretreated tomato leaves, which are implicated in plant defense mechanism. Taken together, our results suggest that sodium alginate can be used as an elicitor to induce resistance against A. solani in tomato plants.

The importance of accounting for social and behavioural processes when studying public health emergencies has been well-recognised. For infectious disease outbreaks in particular, several methods of incorporating individual behaviour have been put forward, but very few are based on established psychological frameworks. In this paper, we develop a decision framework based on the COM-B model of behaviour change to investigate the impact of individual decision-making on public health outcomes. We demonstrate the application of our decision framework in a proof-of-concept case study based on the 2009 A(H1N1) influenza pandemic in the UK. The National Pandemic Flu Service (NPFS) was set up in England during the pandemic as a means to provide antiviral (AV) treatment to clinically ill patients with influenza-like illness, via telephone calls or internet screening, thereby averting the need to see a doctor. The evaluated patients based on a clinical algorithm and authorised AV drugs for collection via community collection points. We applied our behavioural framework to evaluate the influence of human behaviour on AV collection rates, and subsequently to identify interventions that could help improve AV collection rates. Our model was validated against empirically collected pandemic data from 2009 in the UK. We also performed a sensitivity analysis to identify potentially effective interventions by varying model parameters. Using our behavioural framework in a proof-of-concept case study, we found that interventions geared towards increasing people's 'Capability' and 'Opportunity' are likely to result in increased AV collection, potentially resulting in fewer influenza-related hospitalisations and deaths. We note that important behavioural data from public health emergencies are largely scarce. Insights obtained from models such as ours can, not only be very useful in designing healthcare interventions, but also inform future data collection.

Recent advances in high-throughput technologies have resulted in a tremendous increase in the amount of omics data produced in plant science. This increase, in conjunction with the heterogeneity and variability of the data, presents a major challenge to adopt an integrative research approach. We are facing an urgent need to effectively integrate and assimilate complementary datasets to understand the biological system as a whole. The Semantic Web offers technologies for the integration of heterogeneous data and their transformation into explicit knowledge thanks to ontologies. We have developed the Agronomic Linked Data (AgroLD- www.agrold.org), a knowledge-based system relying on Semantic Web technologies and exploiting standard domain ontologies, to integrate data about plant species of high interest for the plant science community e.g., rice, wheat, arabidopsis. We present some integration results of the project, which initially focused on genomics, proteomics and phenomics. AgroLD is now an RDF (Resource Description Format) knowledge base of 100M triples created by annotating and integrating more than 50 datasets coming from 10 data sources-such as Gramene.org and TropGeneDB-with 10 ontologies-such as the Gene Ontology and Plant Trait Ontology. Our evaluation results show users appreciate the multiple query modes which support different use cases. AgroLD's objective is to offer a domain specific knowledge platform to solve complex biological and agronomical questions related to the implication of genes/proteins in, for instances, plant disease resistance or high yield traits. We expect the resolution of these questions to facilitate the formulation of new scientific hypotheses to be validated with a knowledge-oriented approach.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).

This paper uses care pathway and delay models to better understand the possible social reasons for maternal deaths in a city with good public and private health infrastructure. The findings can inform programmes to reduce maternal mortality. During 2007-15, 136 maternal deaths were reported in Chandigarh, India. Using World Health Organisation's verbal autopsy questionnaire, interviews were conducted with primary caregivers of 68 (50%) of the 136 deceased women, as majority of the families had returned to their native places. We used process-tracing techniques to construct the care pathways and identify delays, and explored open-ended responses using thematic analysis. The mean age of the deceased women was 27 years, 51% resided in slums, 32% were primigravida, 25% had their deliveries assisted by traditional birth attendants, and 23% had Caesarean section. Eight percent died at home, and 54% died in tertiary level facilities. Post-partum haemorrhage (26.5%), and complications of puerperium (25%) and labour/delivery (14.7%) were the reported medical causes. Male child preference and norms for home delivery were identified as the distal socio-cultural causes. Individual and family level factors included: shame on multiple pregnancies; fear of discrimination from providers; past successful deliveries at home leading to overconfidence and not seeking institutional care; and lack of awareness about family planning, antenatal care, and danger signs of pregnancy. Healthcare system factors were: non-availability of senior doctors at the time of consultation in the emergency that delayed initiation of immediate treatment, and lack of availability of life-saving equipment due to patient load. Empirical evidence was found on social causes of maternal deaths, which could have been prevented by appropriate actions at individual, family, societal, institutional and policy levels. This study identified potential preventable causes of primarily social origin, which could help in taking actionable steps at several levels to further reduce maternal deaths in India.

BACKGROUND:The incidence and prevalence of diabetes is increasing worldwide and it is the fifth leading cause of mortality accounting for over 3.8 million deaths annually. Despite the enormity of the diabetes-related health burdens, very few studies have evaluated the factors associated with mortality among people with diabetes in India. We sought to study the causes and predictors of mortality among urban Asian Indians with and without diabetes. METHODS AND FINDINGS:Of 2273 adults (27,850 person-years of follow-up) from the 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES), the cause of death could be ascertained in 552 individuals out of the 671 who had died (response rate 82.3%). Verbal autopsy was obtained from the family members of the deceased and this was adjudicated by trained physicians. The age-standardized mortality rate was 28.2 (95%CI 25.9-30.6) per 100,000 population. Mortality rates were significantly higher in individuals with diabetes compared to those without [27.9(95% CI 25.5-30.6) vs. 8.0 (6.6-9.9) per 1000 person years]. Compared to individuals of normal body mass index, underweight individuals had higher risk of mortality (Hazard ratio 1.49; 95% CI 1.11-2.0), whereas overweight and obese individuals did not show a higher risk. The population-attributable risk for all-cause mortality in the entire study cohort was highest for ischemic heart disease and diabetes. The excess mortality attributable to diabetes was highest in the age group of 51 to 70 years, and was mostly accounted for by renal disease (Rate ratio 5.68, 95%CI 2.43-6.23), ischemic heart disease (4.23,2.78-6.67), and cerebrovascular disease (4.00,1.87-9.81). CONCLUSION:Underweight (but not overweight or obesity) was strongly associated with mortality in this Asian Indian population. Ischemic heart disease and diabetes contributed the most to risk for all cause mortality. Excess mortality due to diabetes was higher in relatively younger individuals and was mostly accounted for by renal disease.

A multi-strategy community intervention, known as National Rural Health Mission (NRHM), was implemented in India from 2005 to 2012. By improving the availability of and access to better-quality healthcare, the aim was to reduce maternal and child health (MCH) inequalities. This study was planned to explore the perceptions and beliefs of stakeholders about extent of implementation and effectiveness of NRHM's health sector plans in improving MCH status and reducing inequalities. A total of 33 in-depth interviews (n = 33) with program managers, community representatives, mothers and 8 focus group discussions (n = 42) with health service providers were conducted from September to December 2013, in Haryana, post NRHM. Using NVivo software (version 9), an inductive applied thematic analysis was done based upon grounded theory, program theory of change and a framework approach. Almost all the participants reported that there was an improvement in overall health infrastructure through an increased availability of accredited social health activists, free ambulance services, and free treatment facilities in rural areas. This had increased the demand and utilization of MCH services, especially for those related to institutional delivery, even by the poor families. Service providers felt that acute shortage of human resources was a major health system level barrier. District-specific individual, community, and socio-political level barriers were also observed. Overall program managers, service providers and community representatives believed that NRHM had a role in improving MCH outcomes and in reduction of geographical and socioeconomic inequalities, through improvement in accessibility, availability and affordability of the MCH services in the rural areas and for the poor. Any reduction in gender-based inequalities, however, was linked to the adoption of small family sizes and an increase in educational levels.

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the 'T' allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction

PURPOSE:To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. METHODS:Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). RESULTS:Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. CONCLUSION:UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

'Candidatus Liberibacter solanacearum' (Lso) is a phloem-limited bacterium that severely affects important Solanaceae and Apiaceae crops, including potato, tomato, pepper, tobacco, carrot and celery. This bacterium is transmitted to solanaceous species by potato psyllid, Bactericera cockerelli, and to Apiaceae by carrot psyllids, including Trioza apicalis and Bactericera trigonica. Five haplotypes of Lso have so far been described, two are associated with solanaceous species and potato psyllids, whereas the other three are associated with carrot and celery crops and carrot psyllids. Little is known about cross-transmission of Lso to carrot by potato psyllids or to potato by carrot psyllids. Thus, the present study assessed whether potato psyllid can transmit Lso to carrot and whether Lso haplotypes infecting solanaceous species can also infect carrot and lead to disease symptom development. In addition, the stylet probing behavior of potato psyllid on carrot was assessed using electropenetrography (EPG) technology to further elucidate potential Lso transmission to Apiaceae by this potato insect pest. Results showed that, while potato psyllids survived on carrot for several weeks when confined on the plants under controlled laboratory and field conditions, the insects generally failed to infect carrot plants with Lso. Only three of the 200 carrot plants assayed became infected with Lso and developed characteristic disease symptoms. Lso infection in the symptomatic carrot plants was confirmed by polymerase chain reaction assay and Lso in the carrots was determined to be of the haplotype B, which is associated with solanaceous species. EPG results further revealed that potato psyllids readily feed on carrot xylem but rarely probe into the phloem tissue, explaining why little to no Lso infection occurred during the controlled laboratory and field cage transmission trials. Results of our laboratory and field transmission studies, combined with our EPG results, suggest that the risk of Lso infection and spread between psyllid-infested solanaceous and Apiaceae crops is likely to be negligible under normal field conditions.

Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the regulation of the extracellular signaling and structural matrix environment of cells and tissues. MMPs are considered as promising targets for the treatment of many diseases. Therefore, creation of database on the inhibitors of MMP would definitely accelerate the research activities in this area due to its implication in above-mentioned diseases and associated limitations in the first and second generation inhibitors. In this communication, we report the development of a new MMpI database which provides resourceful information for all researchers working in this field. It is a web-accessible, unique resource that contains detailed information on the inhibitors of MMP including small molecules, peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database provides the detailed molecular and structural details which are necessary for the drug discovery and development. The MMpI database contains physical properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank, PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI ID, IUPAC name, chemical structure and with the title of research article. The MMP inhibitors provided in MMpI database are optimized using Python-based Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI Database is unique and it is the only public database that contains and provides the complete information on the inhibitors of MMP. Database URL: http://clri.res.in/subramanian/databases/mmpi/index.php.

Stimulation of proteoglycan (PG) synthesis and deposition plays an important role in the pathophysiology of fibrosis and is an early and dominant feature of pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) is a major cytokine associated with fibrosis that induces excessive synthesis of matrix proteins, particularly PGs. Owing to the importance of PGs in matrix assembly and in mediating cytokine and growth factor signaling, a strategy based on the inhibition of PG synthesis may prevent excessive matrix PG deposition and attenuates profibrotic effects of TGF-β1 in lung fibroblasts. Here, we showed that 4-MU4-deoxy-β-D-xylopyranoside, a competitive inhibitor of β4-galactosyltransferase7, inhibited PG synthesis and secretion in a dose-dependent manner by decreasing the level of both chondroitin/dermatan- and heparin-sulfate PG in primary lung fibroblasts. Importantly, 4-MU4-deoxy-xyloside was able to counteract TGF-β1-induced synthesis of PGs, activation of fibroblast proliferation and fibroblast-myofibroblast differentiation. Mechanistically, 4-MU4-deoxy-xyloside treatment inhibited TGF-β1-induced activation of canonical Smads2/3 signaling pathway in lung primary fibroblasts. The knockdown of β4-galactosyltransferase7 mimicked 4-MU4-deoxy-xyloside effects, indicating selective inhibition of β4-galactosyltransferase7 by this compound. Collectively, this study reveals the anti-fibrotic activity of 4-MU4-deoxy-xyloside and indicates that inhibition of PG synthesis represents a novel strategy for the treatment of lung fibrosis.

Glyptapanteles Ashmead (Hymenoptera: Braconidae: Microgastrinae) is a cosmopolitan group of hyperdiverse parasitic wasps. The genus remains taxonomically challenging in India due to its highly speciose nature, morphological similarity amongst species and negligible host records. The Indian fauna is one of the most diverse and also the least studied. The present study is based on 60 populations reared from 35 host species, 100+ individual caterpillar rearings (1100 wasp specimens pinned and 2000 in alcohol) and from 12 different geographical locations of the country (11 states and one Union territory) that represent 26 provisional Glyptapanteles species within 8 species-groups. Out of 60 populations, phylogenetic analyses were performed on 38 based on mitochondrial cytochrome oxidase subunit I (COI) nucleotide sequences. Maximum likelihood and Bayesian inference methods displayed three and four major discrete Glyptapanteles clades, respectively. In clade A very few Indian species were grouped along with Neotropical and Thailand species. The other clades B and C grouped the majority of the Indian species and showed considerable host specificity in both the trees. All parasitic wasp species were gregarious in nature, except for two populations. Three different sets of data (morphology, host records, and COI) were integrated in order to generate accurate boundaries between species/species-groups. Illustrations of all parasitized caterpillars/cocoons and 42 habitus views of Glyptapanteles spp., distributional information, and GenBank accession numbers, are presented. The present study, perhaps the most comprehensive done to date in India, suggests the presence of several additional Glyptapanteles species, which were previously unrecognized.

The process of angiogenesis is a vital step towards the formation of malignant tumors. Anti-angiogenic peptides are therefore promising candidates in the treatment of cancer. In this study, we have collected anti-angiogenic peptides from the literature and analyzed the residue preference in these peptides. Residues like Cys, Pro, Ser, Arg, Trp, Thr and Gly are preferred while Ala, Asp, Ile, Leu, Val and Phe are not preferred in these peptides. There is a positional preference of Ser, Pro, Trp and Cys in the N terminal region and Cys, Gly and Arg in the C terminal region of anti-angiogenic peptides. Motif analysis suggests the motifs "CG-G", "TC", "SC", "SP-S", etc., which are highly prominent in anti-angiogenic peptides. Based on the primary analysis, we developed prediction models using different machine learning based methods. The maximum accuracy and MCC for amino acid composition based model is 80.9% and 0.62 respectively. The performance of the models on independent dataset is also reasonable. Based on the above study, we have developed a user-friendly web server named "AntiAngioPred" for the prediction of anti-angiogenic peptides. AntiAngioPred web server is freely accessible at http://clri.res.in/subramanian/tools/antiangiopred/index.html (mirror site: http://crdd.osdd.net/raghava/antiangiopred/).

The impact of pH and ionic strength on the mobility (individual and co-transport) and deposition kinetics of TiO2 and ZnO NPs in porous media was systematically investigated in this study. Packed column experiments were performed over a series of environmentally relevant ionic strengths with both NaCl (0.1-10 mM) and CaCl2 (0.01-0.1mM) solutions and at pH 5, 7, and 9. The transport of TiO2 NPs at pH 5 was not significantly affected by ZnO NPs in solution. At pH 7, a decrease in TiO2 NP transport was noted with co-existence of ZnO NPs, while at pH 9 an increase in the transport was observed. At pH 5 and 7, the transport of ZnO NPs was decreased when TiO2 NPs was present in the solution, and at pH 9, an increase was noted. The breakthrough curves (BTC) were noted to be sensitive to the solution chemistries; the decrease in the breakthrough plateau with increasing ionic strength was observed under all examined pH (5, 7, and 9). The retention profiles were the inverse of the plateaus of BTCs, as expected from mass balance considerations. Overall, the results from this study suggest that solution chemistries (ionic strength and pH) are likely the key factors that govern the individual and co-transport behavior of TiO2 and ZnO NPs in sand.

ObjectivesBroad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations.MethodsFrom 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement.ResultsAcross settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted.ConclusionsThis multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making.

Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at

The female gametophyte of flowering plants, called the embryo sac, develops from a haploid cell named the functional megaspore, which is specified after meiosis by the diploid sporophyte. In Arabidopsis, the functional megaspore undergoes three syncitial mitotic divisions followed by cellularization to form seven cells of four cell types including two female gametes. The plant hormone auxin is important for sporophytic developmental processes, and auxin levels are known to be regulated by biosynthesis and transport. Here, we investigated the role of auxin biosynthetic genes and auxin influx carriers in embryo sac development. We find that genes from the YUCCA/TAA pathway (YUC1, YUC2, YUC8, TAA1, TAR2) are expressed asymmetrically in the developing ovule and embryo sac from the two-nuclear syncitial stage until cellularization. Mutants for YUC1 and YUC2 exhibited defects in cell specification, whereas mutations in YUC8, as well as mutations in TAA1 and TAR2, caused defects in nuclear proliferation, vacuole formation and anisotropic growth of the embryo sac. Additionally, expression of the auxin influx carriers AUX1 and LAX1 were observed at the micropylar pole of the embryo sac and in the adjacent cells of the ovule, and the aux1 lax1 lax2 triple mutant shows multiple gametophyte defects. These results indicate that both localized auxin biosynthesis and auxin import, are required for mitotic divisions, cell expansion and patterning during embryo sac development.

Aminoglycosides, amikacin (AK) and kanamycin (KM) are second line anti-tuberculosis drugs used to treat tuberculosis (TB) and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and bioinformatic tools. Twelve proteins were found to have increased intensities (PDQuest Advanced Software) in resistant isolates and were identified as ATP synthase subunit alpha (Rv1308), Trigger factor (Rv2462c), Dihydrolipoyl dehydrogenase (Rv0462), Elongation factor Tu (Rv0685), Transcriptional regulator MoxR1(Rv1479), Universal stress protein (Rv2005c), 35kDa hypothetical protein (Rv2744c), Proteasome subunit alpha (Rv2109c), Putative short-chain type dehydrogenase/reductase (Rv0148), Bacterioferritin (Rv1876), Ferritin (Rv3841) and Alpha-crystallin/HspX (Rv2031c). Among these Rv2005c, Rv2744c and Rv0148 are proteins with unknown functions. Docking showed that both drugs bind to the conserved domain (Usp, PspA and SDR domain) of these hypothetical proteins and GPS-PUP predicted potential pupylation sites within them. Increased intensities of these proteins and proteasome subunit alpha might not only be neutralized/modulated the drug molecules but also involved in protein turnover to overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were found to be associated with iron regulation signifying the role of iron in resistance. Further research is needed to explore how these potential protein targets contribute to resistance of AK and KM.