An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice.

Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the glucocorticoid receptor in hepatocytes and adipocytes, is required for hypertriglyceridemia and hepatic steatosis induced by the synthetic glucocorticoid dexamethasone. Angptl4 has also been shown to be required for dexamethasone-induced hepatic ceramide production. Here, we further examined the role of ceramide-mediated signaling in hepatic dyslipidemia caused by chronic glucocorticoid exposure. Using a stable isotope-labeling technique, we found that dexamethasone treatment induced the rate of hepatic de novo lipogenesis and triglyceride synthesis. These dexamethasone responses were compromised in Angptl4-null mice (Angptl4-/-). Treating mice with myriocin, an inhibitor of the rate-controlling enzyme of de novo ceramide synthesis, serine palmitoyltransferase long-chain base subunit 1 (SPTLC1)/SPTLC2, decreased dexamethasone-induced plasma and liver triglyceride levels in WT but not Angptl4-/- mice. We noted similar results in mice infected with adeno-associated virus-expressing small hairpin RNAs targeting Sptlc2. Protein phosphatase 2 phosphatase activator (PP2A) and protein kinase Cζ (PKCζ) are two known downstream effectors of ceramides. We found here that mice treated with an inhibitor of PKCζ, 2-acetyl-1,3-cyclopentanedione (ACPD), had lower levels of dexamethasone-induced triglyceride accumulation in plasma and liver. However, small hairpin RNA-mediated targeting of the catalytic PP2A subunit (Ppp2ca) had no effect on dexamethasone responses on plasma and liver triglyceride levels. Overall, our results indicate that chronic dexamethasone treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis, resulting in lipid disorders

Antifungal potential of Azotobacter species and its metabolites against Fusarium verticillioides and biodegradation of fumonisin

Abstract Aims In the study, seven Plant Growth Promoting Rhizobacteria (PGPR) Azotobacter species were screened against three strains of Fusarium verticillioides to test its antifungal activity. Azotobacter strains were tested for the degradation of fumonisin produced by F. verticillioides. Secondary metabolites were isolated and characterized from the Azotobacter strains for the first time. Methods and Results Potential seven Azotobacter species antifungal activity was tested following the dual culture assay against three strains of Fusarium verticillioides namely FVM-42, FVM-86 and MTCC156 estimating the substantial zone of inhibition. Azotobacter species AZT-31 and AZT-50 strains significantly inhibited the growth of F. verticillioides recording drastic growth enhancement of maize under in-vitro conditions by calculating the infection incidence, vigour index and germination percentage. As confirmation, dereplication studies were conducted for the reconfirmation of Azotobacter strains by isolating from rhizoplane. Azotobacter strains played a key role in the degradation of fumonisin produced by F. verticillioides reporting 98% degradation at 2Â h of incubation with the pathogen. Furthermore, in the study first time, we have tried to isolate and characterize the secondary metabolites from the Azotobacter strains exhibiting six compounds from the species AZT-31 (2) and AZT-50 (4). Preliminary in-vitro experiments were carried out using the compounds extracted to check the reduction of infection incidence (90%) and increase in germination percentage upto 50 to 70% when compared to the test pathogen. Conclusion Azotobacter strains referred as PGPR on influencing the growth of plant by producing certain substances that act as stimulators on inhibiting the growth of the pathogen. Significance and Impact of the study The future perspective would be the production of an active combination of carboxamide compound and Azotobacter species for preventively controlling the phytopathogenic fungi of plants and crops and also towards the treatment of seeds

RAWEP - A Tool for Need Assessment among Rural Women

A need assessment is the process of identifying and determining how to bridge the gap between an organization's current and desired state. It is part of a planning process to determine gaps, or “needs,” and address areas for improvement or development. It can help decide where and how resources may be directed, for a specific intervention or method which works well in a rural context. Policymakers and funding agencies who are into rural community developmental activities assess the needs first, to understand the situation and make effective interventions. Rural awareness work experience programme (RAWEP) is an integrated component of B.Sc. (Hons.) Community Science introduced in to the syllabus of B.Sc. Home Science (Hons.) by Indian Council of Agricultural Research (ICAR), New Delhi, in the year 2002, which initially facilitates the students to understand the rural situations, status of technologies adopted by rural women, prioritize their problems and to develop skills & attitude working with farm families for overall development in rural areas, aiming at bringing improvement in quality of life of rural families. It gives the real-life exposure to the students through providing a close-knit interaction between students and rural families, giving a base for need assessment that exposes to different challenges and opportunities faced by the farm women, their changed role in household work and allied fields and initiate knowledge, understanding and skills among the rural women which leads to the overall development improving the quality of life of rural families. It also offers a firsthand experience to students to utilize knowledge gained in first three years and transfer simple and improved practices to the rural women. RAWEP is an effective tool to access the needs of rural folk, their challenges and opportunities, their changed role in household work and allied fields. Students get a unique opportunity to initiate knowledge, transfer skills to the rural women, which ultimately contributes to the overall development of their families. This article presents fallouts of their experiences in context of learnings viz. field experience, team work, experiential learning, address the problems at field level, exposure to administration and management issues in context of rural and farm women, planning and implementing of different need based capacity building programmes , collecting information through different methods, participation in developmental programmes, etc for their future field situations along with result in identification of ground reality and original problems, seek greater understanding, discover inventive answers and suggest methods to overcome the problems. Data was gathered based on fieldwork conducted at Meenavolu, Sudhaguda, Madhanpalli, Gundampalli, Kowta(B), Madhapur, Chennayapalem,Goliyathanda, Manugur, Dowthabad, Vedira, Mandhamarri, Kamaripet, villages from Peddapalli, Thadiparthi districts. The study perceives how RAWE programme was engaged to identify the needs and problems of the adopted villages

A Hybrid Machine Learning Model to Recognize and Detect Plant Diseases in Early Stages

This paper presents an improved Inception module to recognise and detect plant illnesses substituting the original convolutions with architecture based on modified-Xception (m-Xception). In addition, ResNet extracts features by prioritising logarithm calculations over softmax calculations to get more consistent classification outcomes. The model’s training utilised a two-stage transfer learning process to produce an effective model. The results of the experiments reveal that the suggested approach is capable of achieving the specified level of performance, with an average recognition fineness of 99.73 on the public dataset and 98.05 on the domestic dataset, respectively

Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases

The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation

Processing of spatial-frequency altered faces in schizophrenia: Effects of illness phase and duration

Low spatial frequency (SF) processing has been shown to be impaired in people with schizophrenia, but it is not clear how this varies with clinical state or illness chronicity. We compared schizophrenia patients (SCZ, n534), first episode psychosis patients (FEP, n522), and healthy controls (CON, n535) on a gender/facial discrimination task. Images were either unaltered (broadband spatial frequency, BSF), or had high or low SF information removed (LSF and HSF conditions, respectively). The task was performed at hospital admission and discharge for patients, and at corresponding time points for controls. Groups were matched on visual acuity. At admission, compared to their BSF performance, each group was significantly worse with low SF stimuli, and most impaired with high SF stimuli. The level of impairment at each SF did not depend on group. At discharge, the SCZ group performed more poorly in the LSF condition than the other groups, and showed the greatest degree of performance decline collapsed over HSF and LSF conditions, although the latter finding was not significant when controlling for visual acuity. Performance did not change significantly over time for any group. HSF processing was strongly related to visual acuity at both time points for all groups. We conclude the following: 1) SF processing abilities in schizophrenia are relatively stable across clinical state; 2) face processing abnormalities in SCZ are not secondary to problems processing specific SFs, but are due to other known difficulties constructing visual representations from degraded information; and 3) the relationship between HSF processing and visual acuity, along with known SCZ- and medication-related acuity reductions, and the elimination of a SCZ-related impairment after controlling for visual acuity in this study, all raise the possibility that some prior findings of impaired perception in SCZ may be secondary to acuity reductions

Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation

Intestinal stem cell (ISC) plasticity is thought to be regulated by broadly permissive chromatin shared between ISCs and their progeny. Here, we have used a Sox9EGFP reporter to examine chromatin across ISC differentiation. We find that open chromatin regions (OCRs) can be defined as broadly permissive or dynamic in a locus-specific manner, with dynamic OCRs found primarily in loci consistent with distal enhancers. By integrating gene expression with chromatin accessibility at transcription factor (TF) motifs in the context of Sox9EGFP populations, we classify broadly permissive and dynamic chromatin relative to TF usage. These analyses identify known and potential regulators of ISC differentiation via association with dynamic changes in chromatin. Consistent with computational predictions, Id3-null mice exhibit increased numbers of cells expressing the ISC-specific biomarker OLFM4. Finally, we examine the relationship between gene expression and 5-hydroxymethylcytosine (5hmC) in Sox9EGFP populations, which reveals 5hmC enrichment in absorptive lineage-specific genes. Our data demonstrate that intestinal chromatin dynamics can be quantitatively defined in a locus-specific manner, identify novel potential regulators of ISC differentiation and provide a chromatin roadmap for further dissecting cis regulation of cell fate in the intestine

A Study of Injury Patterns and Socio-Demographic Profiles of Victims of Intimate Partner Violence in Sri Lanka

Intimate partner violence (IPV) is a common global health problem. The injury pattern and socio-demographic profile of IPV in Sri Lanka may show variations to that seen in a western society due to socio-cultural differences. The objective of this study was to identify the injury pattern and the socio-demographic aspects of IPV in a Sri Lankan context. All the victims of IPV presented to the Teaching Hospital Peradeniya, Peradeniya, Sri Lanka from 2006 to 2011 were included in this study. There were 226 cases of IPV of which 96% were female. The majority were married and living together. They were less than 30 years of age, unemployed, with more than 2 children, had a poor education and were in the early phase of marriage. Seventy-two percent experienced physical violence resulting in contusions (72%) and abrasions (42%). A significant proportion (11%) did not have any visible injuries. The commonest area of injury was upper limbs (63%) with the head and face being involved in 54% of the cases. The majority (84%) were non grievous injuries inflicted by bare hands (58%) and feet (13%). Profiling of such victims would enable social and community workers to identify this vulnerable group for early intervention and prevention of such occurrences