Nitrogen fixation and carbon metabolism in legume nodules

A large amount of energy is utilized by legume nodules for the fixation of nitrogen and assimilation of fixed nitrogen (ammonia) into organic compounds. The source of energy is provided in the form of photosynthates by the host plant. Phosphoenol pyruvate carboxylase (PEPC) enzyme, which is responsible for carbon dioxide fixation in C4 and crassulacean acid metabolism plants, has also been found to play an important role in carbon metabolism in legume root nodule. PEPC-mediated CO2 fixation in nodules results in the synthesis of C4 dicarboxylic acids, viz. aspartate, malate, fumarate etc. which can be transported into bacteroids with the intervention of dicarboxylate transporter (DCT) protein. PEPC has been purified from the root nodules of few legume species. Information on the relationship between nitrogen fixation and carbon metabolism through PEPC in leguminous plants is scanty and incoherent. This review summarizes the various aspects of carbon and nitrogen metabolism in legume root nodules.     

Phenological characteristics of the tree layer of Kumaun Himalayan forests

The phenology of tree components of natural forests occurring between 350 and 2150 m in Kumaun Himalaya is descibed. All forests had more evergreen than deciduous taxa. The degree of evergreenness increased with increasing elevation and decreasing summer dryness. For most species (including all dominants) concentrated leafdrop and simultaneous leafing occurred during the warm-dry period of the year. About half of the species showed multiple leafing.All species had a sharp flowering peak in April. Wet-season flowering was rare. Most of the species flowered synchronously. In the sal- (Shorea robusta) and pine (Pinus roxburghii) forests a single peak of fruit maturation occurred in summer, while in other forests there also was a secondary peak in autumn.Nomenclature generally follows Osmaston (1926), the authority is given where the species is mentioned first.Financial support from the Department of Science and Technology, Government of India, is grategully acknowledged. We thank Dr. Y. P. S. Pangtey and Dr. J. C. Tewari for their help respectively in plant identification and ordination.     

Carbamylation promotes amyloidogenesis and induces structural changes in Tau-core hexapeptide fibrils

Background

Carbamylation is a non-enzymatic post-translational modification (PTM), which involves the covalent modification of N-terminus of protein or ε-amino group of Lys. The role of carbamylation in several age-related disorders is well documented, however, the relationship between carbamylation and neurodegenerative disorders including Alzheimer's disease remains uncharted.

Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients

Epigenetic mechanisms such as DNA methylation play important role in cancer. Epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prediction of disease prognosis. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for biomarker analyses. The aim of this study is to determine the correlation between methylation status of multiple cancer genes, p16(INK4A), p14(ARF), Cyclin D2 and Slit2 in invasive ductal carcinoma of the breast and paired serum DNA and clinicopathological parameters. Of the 36 breast cancer patients investigated, 31 (86%) tumors and 30 (83%) paired sera showed methylation of at least one of these 4 genes. Methylation frequencies varied from 27% for CyclinD2, 44% for p16(INK4A), 47% for p14(ARF) to 58% for Slit2. There was concordance between DNA methylation in tumor and paired serum DNA of each gene. This study underscores the potential utility of DNA methylation based screening of serum as a surrogate marker for tumor DNA methylation status of these genes in breast cancer. Further, expression profile of p16(INK4A) could be linked to epigenetic events, thus suggesting this pathway as a potential target for therapeutic strategies based on reversal of epigenetic silencing.     

Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties

As a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50=0.18 μM and IC50=0.168 μM, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 μM was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K(i)=2.9 μM).     

Biotinidase is a Novel Marker for Papillary Thyroid Cancer Aggressiveness

Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of biotinidase in thyroid cancer tissues and fine needle aspiration (FNA) samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients’ prognosis. Overall biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001). Comparison of aggressive and non-aggressive PTC showed decrease in overall biotinidase expression in the former (p = 0.001). Loss of overall biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR) = 3.1). We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic biotinidase on patient survival. Decreased nuclear expression of biotinidase was observed in PTC as compared to benign tissues (p<0.001). Upon stratification within PTC, nuclear expression was reduced in aggressive as compared to non-aggressive tumors (p<0.001). Kaplan-Meier survival analysis showed significant association of loss of nuclear biotinidase expression with reduced disease free survival (p = 0.014, HR = 5.4). Cytoplasmic biotinidase expression was reduced in aggressive thyroid cancers in comparison with non-aggressive tumors (p = 0.002, Odds ratio (OR) = 0.29) which was evident by its significant association with advanced T stage (p = 0.003, OR = 0.28), nodal metastasis (p<0.001, OR = 0.16), advanced TNM stage (p<0.001, OR = 0.21) and extrathyroidal extension (p = 0.001, OR = 0.23). However, in multivariate analysis extrathyroidal extension emerged as the most significant prognostic marker for aggressive thyroid carcinomas (p = 0.015, HR = 12.8). In conclusion, loss of overall biotinidase expression is a novel marker for thyroid cancer aggressiveness.     

Combining Healthcare-Based and Participatory Approaches to Surveillance: Trends in Diarrheal and Respiratory Conditions Collected by a Mobile Phone System by Community Health Workers in Rural Nepal

BackgroundSurveillance systems are increasingly relying upon community-based or crowd-sourced data to complement traditional facilities-based data sources. Data collected by community health workers during the routine course of care could combine the early warning power of community-based data collection with the predictability and diagnostic regularity of facility data. These data could inform public health responses to epidemics and spatially-clustered endemic diseases. Here, we analyze data collected on a daily basis by community health workers during the routine course of clinical care in rural Nepal. We evaluate if such community-based surveillance systems can capture temporal trends in diarrheal diseases and acute respiratory infections.MethodsDuring the course of their clinical activities from January to December 2013, community health workers recorded healthcare encounters using mobile phones. In parallel, we accessed condition-specific admissions from 2011–2013 in the hospital from which the community health program was based. We compared diarrhea and acute respiratory infection rates from both the hospital and the community, and assigned three categories of local disease activity (low, medium, and high) to each week in each village cluster with categories determined by tertiles. We compared condition-specific mean hospital rates across categories using ANOVA to assess concordance between hospital and community-collected data.ResultsThere were 2,710 cases of diarrhea and 373 cases of acute respiratory infection reported by community health workers during the one-year study period. At the hospital, the average weekly incidence of diarrhea and acute respiratory infections over the three-year period was 1.8 and 3.9 cases respectively per 1,000 people in each village cluster. In the community, the average weekly rate of diarrhea and acute respiratory infections was 2.7 and 0.5 cases respectively per 1,000 people. Both diarrhea and acute respiratory infections exhibited significant differences between the three categories of disease rate burden (diarrhea p = 0.009, acute respiratory infection p = 0.001) when comparing community health worker-collected rates to hospital rates.ConclusionCommunity-level data on diarrhea and acute respiratory infections modestly correlated with hospital data for the same condition in each village each week. Our experience suggests that community health worker-collected data on mobile phones may be a feasible adjunct to other community- and healthcare-related data sources for surveillance of such conditions. Such systems are vitally needed in resource-limited settings like rural Nepal.     

Identification of 14‐3‐3zeta associated protein networks in oral cancer

Advancements in genomics, proteomics, and bioinformatics have improved our understanding of gene/protein networks involved in intra‐ and intercellular communication and tumor–host interactions. Using proteomics integrated with bioinformatics, previously we reported overexpression of 14‐3‐3ζ in premalignant oral lesions and oral squamous cell carcinoma tissues in comparison with normal oral epithelium. 14‐3‐3ζ emerged as a novel molecular target for therapeutics and a potential prognostic marker in oral squamous cell carcinoma patients. However, the role of 14‐3‐3ζ in development and progression of oral cancer is not known yet. This study aimed to identify the 14‐3‐3ζ associated protein networks in oral cancer cell lines using IP–MS/MS and bioinformatics. A total of 287 binding partners of 14‐3‐3ζ were identified in metastatic (MDA1986) and nonmetastatic (SCC4) oral cancer cell lines including other 14‐3‐3 isoforms (2%), proteins involved in apoptosis (2%), cytoskeleton (9%), metabolism (16%), and maintenance of redox potential (2%). Our bioinformatics analysis revealed involvement of 14‐3‐3ζ in protein networks regulating cell cycle, proliferation, apoptosis, cellular trafficking, and endocytosis in oral cancer. In conclusion, our data revealed several novel protein interaction networks involving 14‐3‐3ζ in oral cancer progression and metastasis.     

Destabilization of cytoplasmic mouse mammary tumor RNA by heat shock: prevention by cycloheximide pretreatment

Thermal stress of cultured mouse mammary carcinoma cells results in a rapid loss of basal and glucocorticoid-stimulated mouse mammary tumor virus (MMTV) RNA. MMTV RNA is almost nondetectable within 1-2 hr after a shift in the culture temperature to 42 degrees. Actin mRNA is stable over this time period. Pretreatment of the cells with cycloheximide prevents the decay of MMTV RNA. Nuclear associated glucocorticoid receptor is not decreased but rather increased about 95% by the heat shock. The results show that heat shock has pronounced effects on expression of a glucocorticoid-regulated gene, and suggest that a nuclease, which is subject to rapid turnover, is stimulated by thermal stress.     

Synthesis of 16E-[3-methoxy-4-(2-aminoethoxy)benzylidene]androstene derivatives as potent cytotoxic agents

The synthesis and cytotoxic studies of a new series of 16E-arylidene androstene derivatives are reported herein. The impact of incorporating bis-tertiary amino functionalities in the steroid skeleton on cytotoxicity has also been observed. The compounds have been evaluated at National cancer Institute, Bethesda, Maryland, USA for their antineoplastic activity against various tumor cell lines. The synthesized 16E-arylidenosteroids exhibited significant cytotoxicity. Bis-tertiary amino steroid 29 possessing a diethylaminoalkoxy functionality was the most promising compound of the series with a total IP and SC score of 20 in in vivo hollow fiber assay and was selected for further detailed in vivo xenograft testing.