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Tecoma stans a woody shrubs belonging to the Bignoniaceae family and is commonly known as Pelli Kaner. The present paper shows various pharmacognostic standards such as taxonomy of leaf which shows leaf is found to be simple with the alternate arrangement, serrulate margin with obovate shape, obtuse apex and oblique, rounded base, pinnate venation. Secondly, microscopic characters are determined by cutting its leaf transverse section as well as powder microscopy, these studies provide various information about the arrangement of cell-like xylem, phloem, the upper and lower epidermis. Vein islet and vein termination number etc. Physical and chemical parameters such as total ash, acid insoluble ash, water-soluble ash, moisture content, water-soluble, and extractive value of leaf are calculated. Various chemical reagents are used to identify the chemical nature of leaf extract. Ethanolic extract of leaf is found to be active and 200 and 400 mg when in vivo evaluated for hepatoprotective activity. Ethanolic extract of the leaf also contains total phenolic content of 1.36 ± 0.02 mg/gm of dried extract equivalent to Gallic acid, the total flavonoids content of the extract was evaluated to be 4.41± 0.02 mg/gram and potential antioxidant activity which is comparable to the standards.

Environmental factors like ionizing radiation induced generation of reactive oxygen species (ROS) cause macromolecular damage under physiological conditions. Proteins are the potential targets of ROS induced oxidative damage because of their abundance and their critical functions in the biological systems. The present study investigates the protective potential of ethyl pyruvate (EP) against ionizing radiation induced oxidative damage of bovine serum albumin (BSA) using spectroscopic, biochemical and SDS-PAGE techniques. Spectroscopic data shows that EP prevents the build up of protein damage markers like bityrosine formation and oxidation of tryptophan. Protein melting studies shows that the melting temperature (Tm) of the irradiated protein does not change significantly in the presence of EP. Biochemical assays indicate that ionizing radiation causes the generation of carbonyls and malondialdehyde and the loss of thiol content in proteins that is prevented by EP. The SDS-PAGE profile of gamma irradiated BSA shows the radioprotective effect of EP. These results indicate the radiation induced oxidative and molecular changes in the protein and that the EP protected the BSA from these modifications. Therefore, these results imply that EP has a good antiradical property and hence it can be proposed as a good radioprotective agent.

Twelve wheat genotypes with variable grain hardness were evaluated for grain, flour, pasting, dough rheological properties, high molecular weight glutenin subunits (HMW-GS) and their relationship with cookie quality characteristics. The degree of hardness played an important role in the expression of characters under study. Genotypes with higher grain hardness index (GHI) showed higher dough development time and dough stability. GHI and solvent retention capacity were positively related to each other and negatively to spread factor. GluD1 locus of majority of hard wheat genotypes showed 5 + 10 subunit while soft wheat (SW) genotypes with 2 + 12 subunit related to gluten quality and dough properties. Overall, variation in subunits at GluD1 locus led to greater variation amongst studied genotypes followed by GluB1 and GluA1. Subunits Null at GluA1, 20, 7 + 8 and 7 + 9 at GluB1, and 2 + 12 and 5 + 10 at GluD1 showed a profound effect on flour, dough and cookie quality. Distribution of different HMW-GS, gluten characteristics and GHI, thus emerged as major parameters for selection of wheat genotypes for development of cookies. SW (QBP 13–11) with the lowest GHI and HMW-GS profile (2*, 7 and 2 + 12 subunit) showed the highest cookie SF and the lowest BS, thereby, turning out to be the best suitable genotype for producing cookies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05272-5.

A new bread wheat variety HI 1633 (Pusa Vani) has been released and notified by the Central Sub-Committee on Crop Standards, Notification and Release of Varieties for Agricultural Crops, Government of India for commercial cultivation under irrigated and late sown conditions of Peninsular Zone of India. HI 1633 has average yield of 41.7 q ha-1 and showed superiority over checks. The potential yield of HI 1633 is 65.8 q ha-1 and found resistant to black and brown rusts. HI 1633 found to have excellent chapati quality (7.63), biscuit quality (7.08), high grain hardness (>80.0), test weight (80.3 kg hl-1) and sedimentation value (45.0 ml). It has high protein content (12.4 %) and presence of 5+10 subunit of Glu-D1 reflecting higher gluten strength. It has good amount of micronutrients viz., iron (41.6 ppm) and zinc (41.1 ppm) content making it rich in nutritional qualities. This variety has been recommended for irrigated late sown conditions and would contribute to increasing wheat production and alleviate the socio-economic status of farmers of Peninsular zone in India.

Natural killer (NK)/T-cell lymphomas and large granular lymphocyte (LGL) leukemia are rare lymphoproliferative malignancies with fundamental different prognosis. While NK/T-cell lymphoma and NK-cel...

Falcipain-2 (FP2) is a papain family cysteine protease and a key member of the hemoglobin degradation pathway, a process that is required at erythrocytic stages of Plasmodium falciparum to obtain amino acids. In this study, we report a set of 10 quinoline-triazole-based compounds (T1–T10) which exhibit a good binding affinity for FP2, inhibit its catalytic activity at micromolar concentrations and thereby arrest the parasite growth. Compounds T4 and T7 inhibited FP2 with IC50 values of 16.16 μM and 25.64 μM respectively. Both the compounds T4 and T7 arrested the development of P. falciparum at the trophozoite stage with an EC50 value 21.89 μM and 49.88 μM. These compounds also showed morphological and food-vacuole abnormalities like E-64, a known inhibitor of FP2. Our results thus identify the quinoline-triazole-based compounds as a probable starting point for the design of FP2 inhibitors and they should be further investigated as potential antimalarial agents.

HI 1628 has average yield of 50.4 q/ha over the zone and showed significant superiority over the checks; with a potential yield of 65.1 q/ha. It has shown excellent and wider adaptation and significantly superior performance across different irrigation regimes over the checks with an average yield of 45.5q/ha. It showed high levels of field resistance to yellow and brown rusts. It is a good quality bread wheat genotype with excellent chapati quality (7.56), bread quality (7.64), biscuit spread factor (8.27) and high sedimentation value (56.6 ml). It has high protein content (~11 %) and protein quality (Glu score of 8/10) for high molecular weight subunits and presence of 5+10 subunit of Glu-D1 reflecting higher gluten strength in this genotype.

HI 8805 has average yield of 30.4 q/ha over the zone and showed significant superiority over the checks; with a potential yield of 35.4 q/ha. It has shown excellent and wider adaptation and significantly superior performance across different irrigation regimes over the checks with an average yield of 30.7q/ha. It showed high levels of field resistance to black and brown rusts. It has high protein content (12.8%), yellow pigment content (4.9 PPM), test weight (83.7 kg/hl), sedimentation value (42 ml), iron content (40.4 ppm), zinc content (33.9 ppm) with an overall pasta acceptability (5.7).

Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/– or Map1lc3B–/–) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6–/Y) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1–/–, Map1lc3B–/–, and Hdac6–/Y mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD.

Objectives Maternal sepsis is a life-threatening condition. Biomarkers have been found to be useful in early detection of sepsis in the critical care setting. We aimed to determine the diagnostic performance of different biomarkers such as procalcitonin, C-reactive protein (CRP), absolute eosinophil count, and activated partial thromboplastin time (aPTT) in maternal sepsis. Methods A total of 35 patients were enrolled in this prospective observational study. Patients with suspected sepsis were evaluated for multi-organ dysfunction. The blood samples for testing of these biomarker levels were obtained at the time of enrollment in the study (day 1), and on day 3 and day 7. Trends of each marker were followed and correlated with the clinical picture. Results Of 35 enrolled patients, 30 completed the study. Among these, 18 had sepsis and 12 were designated as without sepsis. Sensitivities of procalcitonin, CRP, aPTT, and absolute eosinophil count were 83.33%, 77.78%, 55.56%, and 58.82% whereas their specificities were 66.67%, 75.0%, 100%, and 75%, respectively. Area under the curve was highest for procalcitonin (0.813) followed in decreasing order by CRP (0.778), aPTT (0.731), and eosinophil count (0.642), respectively. Conclusion Procalcitonin and CRP may be used as a valuable adjunct in the clinical stepwise approach for the prompt diagnosis of maternal sepsis.

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 µM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.

The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as proof-of-concept with isolated proteins and/or inactivated bacteria. We have engineered a plasmid-based, complement receptor-targeting platform that is readily applicable to live forms of multiple gram-negative bacteria, including, but not limited to, Escherichia coli, Klebsiella pneumoniae, and Francisella tularensis. Using F. tularensis as a model, we find that targeted bacteria show increased binding and uptake by macrophages, which coincides with increased p38 and p65 phosphorylation. Mice vaccinated with targeted bacteria produce higher titers of specific antibody that recognizes a greater diversity of bacterial antigens. Following challenge with homologous or heterologous isolates, these mice exhibited less weight loss and/or accelerated weight recovery as compared to counterparts vaccinated with non-targeted immunogens. Collectively, these findings provide proof-of-concept for plasmid-based, complement receptor-targeting of live gram-negative bacteria.

Cancer stem cells (CSC) are highly resistant to conventional chemotherapeutic drugs. YAP1 and STAT3 are the two transcription factors that facilitate the therapeutic resistance and expansion of CSCs. The objective of this study was to understand the cross-talk between YAP1 and STAT3 activities and to determine the therapeutic efficacy of targeting dual CSC-regulating pathways (YAP1 and STAT3) combined with chemotherapy in lung adenocarcinoma. Here, we showed that YAP1 contributes to CSC regulation and enhances tumor formation while suppressing apoptosis. Mechanistically, YAP1 promotes phosphorylation of STAT3 by upregulating IL6. In lung adenocarcinoma clinical specimens, YAP1 expression correlated with that of IL6 (P < 0.01). More importantly, YAP1 and phosphorylated STAT3 (pSTAT3) protein expressions were significantly correlated (P < 0.0001) in primary lung adenocarcinoma as determined by IHC. Immunoblotting of 13 lung adenocarcinoma patient-derived xenografts (PDX) showed that all YAP1-expressing PDXs also exhibited pSTAT3. Additional investigations revealed that chemotherapy resistance and malignant stemness were influenced by upregulating NANOG, OCT4, and SOX2, and the expression of these targets significantly attenuated by genetically and pharmacologically hindering the activities of YAP1 and STAT3 in vivo and in vitro. Therapeutically, the dual inhibition of YAP1 and STAT3 elicits a long-lasting therapeutic response by limiting CSC expansion following chemotherapy in cell line xenograft and PDX models of lung adenocarcinoma. Collectively, these findings provide a conceptual framework to target the YAP1 and STAT3 pathways concurrently with systemic chemotherapy to improve the clinical management of lung adenocarcinoma, based on evidence that these two pathways expand CSC populations that mediate resistance to chemotherapy.

The plant microbiome is known to play a significant role in improving plant productivity and quality of produce, and the endophytic component was explored toward developing inoculants for enhancing micronutrient concentration in grains. A set of 213 endophytes (201 bacteria and 12 fungi) were isolated, from a set of 13 wheat genotypes, identified through preliminary screening as low and high iron and zinc accumulating genotypes. A pot experiment, with two low accumulator genotypes and eight selected endophytes, was undertaken, followed by field evaluation with both high and low Zn or Fe accumulator genotypes. Screening of these endophytes identified 11 bacteria and 2 fungi as being efficient for zinc solubilization, while 10 bacteria and 2 fungi were promising siderophore producers. Zinc and iron uptake were enhanced by one to several folds over the recommended dose of NPK (RDF) in the pot experiment. Two sets of promising endophytes, identified as Bacillus subtilis (DS-178) and Arthrobacter sp. (DS-179) for zinc accumulation, and Arthrobacter sulfonivorans (DS-68) and Enterococcus hirae (DS-163) for iron acquisition in grains, were selected. Significant increase of 14–20% in plant growth and yield was recorded in field experiment, with 75% increase, over RDF, in terms of Fe or Zn accumulation in wheat grains. Phytic acid, an anti-nutritional factor, was significantly lower in grains from endophyte inoculated treatments in the wheat genotypes evaluated. This illustrated the promise of these endophytes in improving both the translocation of micronutrients and enhancing the quality of wheat grains.

Sulphur mustard is a lethal chemical warfare agent, known for its vesicant or blistering action on skin and mucous membrane. 2-chloroethylphenyl sulphide (CEPS) is a simulant of sulphur mustard. In the present study, the binding interaction of CEPS with bovine serum albumin (BSA) was investigated to determine its binding potential with skin proteins. The binding interactions studies were performed using UV–Vis absorbance, steady-state fluorescence, synchronous fluorescence, circular dichroism techniques. It is observed in UV–Vis absorption study, absorbance of BSA at 280 nm increases with a slight blue shift in the presence of CEPS indicated a complex formation between CEPS and BSA. Fluorescence quenching of emission intensity of BSA in the presence of CEPS indicated change in the microenvironment of fluorophores (Tryptophan residues). Stern-Volmer plot showed an inverse relationship between quenching (Ksv) and temperature. Thus, the quenching is operative via static quenching. The binding parameters suggested the role of non-covalent interactions and involvement of single set of equivalent binding sites. Change in thermodynamic parameters suggested that the binding is essentially enthalpy driven and spontaneous in nature. A synchronous fluorescence of BSA spectra in the presence of CEPS causes maximum change around the microenvironment of Tryptophan residues than Tyrosine residues. The intermolecular distance between the donor (BSA) and acceptor (CEPS) molecule was 3.5 nm as calculated from FRET analysis and indicated no significant transfer of energy between donor and acceptor. CD spectrum confirmed the changes in secondary structure of BSA upon binding with CEPS. The esterase enzyme activity of BSA in presence of CEPS showed a decrease in enzyme activity. The binding interactions were modeled in binding pockets using molecular docking calculations.

Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival. Since life of the parasite utterly depends on pyrimidine biosynthesis, so it can be used as an apt drug target for malaria eradication. In addition to this, DHODH is also present in human and their active sites have significant structural dissimilarities, so the development of selective inhibitors may prove to be a milestone in search of new antimalarials. Inhibitors of human DHODH have been used to treat autoimmune diseases such as, rheumatoid arthritis or multiple sclerosis and have been investigated in the treatment of cancer, viral diseases, as well as in plant pathology. Here, we have reviewed the important role of DHODH as a viable drug target against malaria, its importance for the survival of the parasite, and DHODH inhibitors reported so far. The rate of success of the reported DHODH inhibitors and further required improvements have also been accounted.

Th17 cells are critical drivers of autoimmune diseases and immunopathology. There is an unmet need to develop therapies targeting pathogenic Th17 cells for the treatment of autoimmune disorders. Here, we report that anxiolytic FGIN-1-27 inhibits differentiation and pathogenicity of Th17 cells in vitro and in vivo using the experimental autoimmune encephalomyelitis (EAE) model of Th17 cell-driven pathology. Remarkably, we found that the effects of FGIN-1-27 were independent of translocator protein (TSPO), the reported target for this small molecule, and instead were driven by a metabolic switch in Th17 cells that led to the induction of the amino acid starvation response and altered cellular fatty acid composition. Our findings suggest that the small molecule FGIN-1-27 can be re-purposed to relieve autoimmunity by metabolic reprogramming of pathogenic Th17 cells.

Here, we report on the isolation of bacterial isolates from Himalayan niches, which produced extracellular l-asparaginase with low/no glutaminase activity. From the 235 isolates, 85 asparaginase positive bacterial isolates were identified by qualitative screening using optimized chromogenic dyes assay. Optimized concentration of different dyes revealed maximum color visualization in phenol red (0.003%). The diversity analysis of asparaginase positive isolates revealed that Proteobacteria (83%) are the most dominant, followed by Actinobacteria (12%), Firmicutes (3%), and Bacteriodetes (2%). Eleven isolates, which represented seven Pseudomonas species, one species each of the genus Arthrobacter, Janthinobacterium, Lelliottia, and Rahnella, were selected for further studies based on highest zone ratio and novel aspects for l-asparaginase production. Of these, five isolates, namely, Pseudomonas sp. PCH133, Pseudomonas sp. PCH146, Pseudomonas sp. PCH182, Rahnella sp. PCH162, and Arthrobacter sp. PCH138, produced l-asparaginase without glutaminase activity after 55 h of growth with the former isolate showing the highest l-asparaginase activity (1.67 U/ml). Interestingly, this is the first report of l-asparaginase production by members of the genera Janthinobacterium, Rahnella, and Lelliottia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-019-1810-9) contains supplementary material, which is available to authorized users.

Phosmet exerts its neurotoxicity by inhibiting acetylcholinesterase that catalyzes the degradation of acetylcholine (a neurotransmitter). Serum proteins are known to influence the biodistribution of various endogenous and exogenous compounds. In the present study, the binding interactions of phosmet with bovine serum albumin (BSA) was investigated to determine the free concentration of phosmet for its neurotoxicity. The binding mechanism was studied using fluorescence, UV–Vis absorption spectroscopy, circular dichroism (CD), and molecular docking techniques. UV–Vis absorption data showed an increase in absorbance of BSA upon binding with phosmet with a slight red-shift in the peak around 280 nm. Intrinsic fluorescence of BSA was quenched in the presence of phosmet. The quenching was observed to be inversely correlated to the temperature that indicated the formation of ground state non-fluorescent complex (static quenching). Binding constant values and n values for the binding of phosmet with BSA at three different temperatures confirmed non-covalent binding interactions with a single set of equivalent binding sites. Thermodynamic parameters ∆G (−137.40 ± 3.58 kJ mol−1); ΔH (−16.33 ± 5.28 kJ mol−1) and ΔS(−469 ± 12.45 kJ mol−1) confirmed that the binding was spontaneous and non-covalent interactions like electrostatic, hydrogen bonding and van der Waals forces played an important role in the binding. The CD data indicated the conformational change in BSA upon binding with phosmet which resulted in a change in the melting temperature. Molecular docking presented the binding model for BSA-phosmet complex and displayed that non-covalent interactions played a significant role in the binding mechanism.

Loss of function mutations in Kelch Like ECH Associated Protein 1 (KEAP1) or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2) are common in non-small cell lung cancer (NSCLC) and is associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ~400,000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to the Neh1, the Cap ‘N’ Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs such as doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells compared to single agents alone. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant anti-tumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aβ aggregation and antioxidant activity.

Metformin is a biguanide class of drug used for the treatment of diabetes mellitus. It is well known that serum protein-ligand binding interaction significantly influence the biodistribution of a drug. Current study was performed to characterize the binding mechanism of metformin with serum albumin. The binding interaction of the metformin with bovine serum albumin (BSA) was examined using UV–Vis absorption spectroscopy, fluorescence, circular dichroism, density functional theory and molecular docking studies. Absorption spectra and fluorescence emission spectra pointed out the weak binding of metformin with BSA as was apparent from the slight change in absorbance and fluorescence intensity of BSA in presence of metformin. Circular dichroism study implied the significant change in the conformation of BSA upon binding with metformin. Density functional theory calculations showed that metformin has non-planar geometry and has two energy states. The docking studies evidently signified that metformin could bind significantly to the three binding sites in BSA via hydrophobic, hydrogen bonding and electrostatic interactions. The data suggested the existence of non-covalent specific binding interaction in the complexation of metformin with BSA. The present study will certainly contribute to the development of metformin as a therapeutic molecule.

For primates that may unexpectedly die, spermatozoa recovered from the epididymis can be used for assisted reproductive technologies (ART). However, in cases of unsuccessful epididymal sperm retrieval, adult testes are the only source of sperm. This study reports cryopreservation of testicular tissue of three adult primates (mandrill, chimpanzee, and marmoset). For successful cryopreservation, optimization of concentrations of commonly used cryoprotectant such as dimethyl sulfoxide (DMSO) and combinations of foetal bovine serum (FBS) and DMSO is essential. Testicular tissues were cryopreserved in 10 % DMSO (D10) with 80 % FBS (D10S80) or 20 % DMSO (D20) with 20 % FBS (D20S20). The cryopreserved testes were evaluated for efficacy of cryopreservation by assessing the viability and acrosome status of retrieved sperm, expression of spermatozoa- and spermatid-specific proteins (PRM2 and TNP1) by immunohistochemistry, and expression of pro- and anti-apoptosis- (BAX/BCL2 ratio), early apoptosis- (Annexin V), and cell proliferation-specific (PCNA) proteins by western blot analysis. The results suggest that mandrill testis can be effectively cryopreserved in D10S80, marmoset testis in D10S80 and D20S20, whereas chimpanzee testis in D20.

Various in vitro and in vivo studies have shown the anti-inflammatory and anticancer potential role of ethyl pyruvate. Bio-distribution of drugs is significantly influenced by the drug-serum protein binding. Therefore, the binding mechanism of the ethyl pyruvate with bovine serum albumin was investigated using UV–vis absorption, fluorescence, circular dichroism, isothermal titration calorimetry and molecular docking techniques. Absorption and fluorescence quenching studies indicated the binding of ethyl pyruvate with protein. Circular dichroism spectra of bovine serum albumin confirmed significant change in the conformation of protein upon binding. Thermodynamic data confirmed that ethyl pyruvate binds to bovine serum albumin at the two different sites with high affinity. Binding of ethyl pyruvate to bovine serum albumin involves hydrogen bonding, van der Waal and hydrophobic interactions. Further, docking studies indicated that ethyl pyruvate could bind significantly at the three binding sites. The results will definitely contribute to the development of ethyl pyruvate as drug.

The relationship between protein molecular weight (MW) distribution, quality characteristics and muffin making properties amongst Indian wheat varieties were evaluated. Flours from varieties with higher grain weight showed lower proportion of fine particles. Lactic acid solvent retention capacity (LASRC), sedimentation value (SV) and dough stability (DS) correlated with the proportion of 0–55 μm size particles. Paste peak viscosity and breakdown viscosity showed positive correlation with polymeric protein and negatively with monomeric protein, α-amylase activity and sodium carbonate solvent retention capacity (NaSRC). Gluten strength indicators such as DS, dough development time (DDT), LASRC and gluten index (GI) were positively related to polymeric protein and negatively to monomeric protein. Both G’ and G ″ were correlated significantly with GI, LASRC, DS and DDT. The varieties that possesses high MW glutenin subunits combinations of 91 kDa + 84 kDa + 78 kDa + 74 kDa showed lower G ’ and G ″. Muffin volume was positively correlated with gluten content and LASRC.

Mushrooms are extraordinarily nutritious products, can be produced from lignocellulosic waste materials. The present study was conducted on oyster mushroom Pleurotus sajor-caju with different substrates viz., wheat straw, paddy straw, soybean straw and maize stalks and leaves. Amongst the different substrates wheat straw was found significantly higher in respect of maximum flushes (3.4), number (171.03) and weight of sporophores (4.05 g) as well as yield of sporophores (694.38 g/kg straw). The other substrates gave optimum yield such as paddy straw (619.72 g/kg straw). The lowest yield was observed in maize stalk and leaves (425.30 g/kg straw).

Bromo-Noscapine (BrNs) is a tubulin-binding cytotoxic agent with significant activity against breast and lung cancer. The mechanistic interaction insight into the binding of bovine serum albumin (BSA) with BrNs can provide critical information about the pharmacodynamics and pharmacokinetics properties. Here, various spectroscopic techniques and computational methods were employed to understand the dynamics of BrNs and BSA interaction. The intrinsic fluorescence of BSA was quenched by BrNs through a static quenching procedure. The stoichiometry of BrNs-BSA complex was 1:1 and binding constant of the complex was in the order of 103 M−1 at 298 K. Based on thermodynamic analysis, it was deduced that binding process of the BrNs with BSA was spontaneous and exothermic, and the major forces between BrNs and BSA were van der waals forces and hydrogen bonding. Moreover, results of FT-IR, CD, UV spectra concluded significant conformational change in BSA on binding with BrNs. The in vitro findings were further confirmed by in silico assays. Molecular docking showed strong interactions with score of −8.08 kcal/mol. Molecular dynamics simulation analysis also suggested the stable binding with lower deviation in RMSD and RMSF values through persistent long simulation run. This study suggests optimal efficiency of diffusion of the BrNs into the bloodstream for the treatment of cancer.

Oncogenic Kras mutations are one of the most common alterations in non-small cell lung cancer and are associated with poor response to treatment and reduced survival. Driver oncogenes, such as Kras are now appreciated for their ability to promote tumor growth via up-regulation of anabolic pathways. Therefore, we wanted to identify metabolic vulnerabilities in Kras-mutant lung cancer. Using the Kras(LSL-G12D) lung cancer model, we show that mutant Kras drives a lipogenic gene-expression program. Stable-isotope analysis reveals that mutant Kras promotes de novo fatty acid synthesis in vitro and in vivo. The importance of fatty acid synthesis in Kras-induced tumorigenesis was evident by decreased tumor formation in Kras(LSL-G12D) mice after treatment with a fatty acid synthesis inhibitor. Importantly, with gain and loss of function models of mutant Kras, we demonstrate that mutant Kras potentiates the growth inhibitory effects of several fatty acid synthesis inhibitors. These studies highlight the potential to target mutant Kras tumors by taking advantage of the lipogenic phenotype induced by mutant Kras.—Singh, A., Ruiz, C., Bhalla, K., Haley, J. A., Li, Q. K., Acquaah-Mensah, G., Montal, E., Sudini, K. R., Skoulidis, F., Wistuba, I. I., Papadimitrakopoulou, V., Heymach, J. V., Boros, L. G., Gabrielson, E., Carretero, J., Wong, K.-K., Haley, J. D., Biswal, S., Girnun, G. D. De novo lipogenesis represents a therapeutic target in mutant Kras non-small cell lung cancer.

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

This paper presents a methodological framework for predicting C stock in Avicennia marina stands in the Thane creek of Mumbai. This methodology combines ground-based (GB) and remote sensing (RS) approaches for C stock estimation. RS based approach use Normalized differential vegetation index (NDVI), Light use efficiency (LUE) and Photo-synthetically Active Radiation (PAR) as the most important parameters for C stock estimation. The sensitivity of NDVI values to aerosols, water vapor and ozone was removed using the 6S radiative transfer code. The difference in NDVI values before and after atmospheric correction was assessed using student’s t-test and was found to be statistically significant. The total carbon stock of the area was observed to be about 39.7188 t/ha. The bias estimation between C stock calculated using allometry and RS approaches confirmed the prediction accuracy and validated both the techniques (R 2 = 0.964 and bias = 0.915 %). The paper, thus, reports a statistically robust framework, which is a combination of the RS and GB approaches, and can be used for estimating the biomass and carbon stock of any ecosystem. This framework is especially effective where forest inventory data is unavailable, the site is geographically inaccessible or harvesting of mangroves or other trees is prohibited.

Triticin, a legumin-like storage protein of wheat endosperm, was discovered nearly three decades ago but so far there is no report on its effect on the processing quality of wheat that is thought to be determined primarily by prolamins, its major seed storage proteins. To investigate the effect of different classes of seed proteins on wheat quality using a genetic reconstitution approach, we produced 31 near-isogenic lines (NILs) with different alleles of triticin, high molecular weight glutenin subunits (HMW-GS), low molecular weight glutenin subunits (LMW-GS), gliadins and albumins in a common genetic background of wheat variety HD2329 and analysed different quality parameters over a period of 4 years. The NILs did not differ in their flour protein content, but showed significant differences in SDS-sedimentation volume, Farinograph dough stability, bread loaf volume and chapati quality score. Main focus was on triticin for which two NILs with alleles Tri-A1a and Tri-D1a derived from a high-quality Indian wheat variety K68 were analysed. Positive effects of these triticin alleles on dough physical properties, bread loaf volume and chapatti quality score were quite large, comparable to the widely known effect of HMW-GS 5 + 10. Specific alleles of HMW-GS, Glu-A1a (subunit 1), Glu-B1b (subunits 7 + 8), Glu-B1i (subunits 17 + 18) and Glu-D1d (subunits 5 + 10) showed strong positive effects, whereas null allele Glu-A1c showed negative effect on the quality of recipient variety HD2329. Similarly, different alleles of LMW-GS showed varying effects with Glu-A3d, Glu-A3e and Glu-D5a showing positive effects, Glu-A3c showing negative effect and Glu-A3a showing no significant effect. Gliadin alleles generally showed negative effects, whereas albumins showed no significant effect. While results with glutenin and gliadin alleles were as expected, we show here for the first time a significant effect of triticin on the wheat flour quality, suggesting that end-use quality of wheat varieties can be improved by combining specific alleles of triticin.

Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell’s organellar ‘canary in a coal mine’. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. Ft-induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1β, IL-6, IL-12p70, and IFN-γ during late-phase tularemia (⩾72 h), but are absent early during infection.

Aberrant type 2 responses underlie the pathologies in allergic diseases like asthma, yet, our understanding of the mechanisms that drive them remains limited. Recent evidence suggests that dysregulated innate immune factors can perpetuate asthma pathogenesis. In susceptible individuals, allergen exposure triggers the activation of complement, a major arm of innate immunity, leading to the aberrant generation of the C3a anaphylatoxin. C3 and C3a have been shown to be important for the development of Th2 responses, yet remarkably, the mechanisms by which C3a regulates type 2 immunity are relatively unknown. We demonstrate a central role for C3a in driving type 2 innate lymphoid cells (ILC2)-mediated inflammation in response to allergen and IL-33. Our data suggests that ILC2 recruitment is C3a-dependent. Further, we show that ILC2s directly respond to C3a, promoting type 2 responses by specifically: (1) inducing IL-13 and granulocyte-macrophage colony-stimulating factor, whereas inhibiting IL-10 production from ILC2; and (2) enhancing their antigen-presenting capability during ILC-T-cell cross-talk. In summary, we identify a novel mechanism by which C3a can mediate aberrant type 2 responses to aeroallergen exposure, which involves a yet unrecognized cross-talk between two major innate immune components-complement and group 2 innate lymphoid cells.

Determination of age of an individual whether living or dead, is a vexing problem for a medical expert.1 Extensive work has been carried out on the theme in different states of India and abroad as well. However, very little work has been reported with reference to Agra population. Present work was undertaken in 200 school going children with known chronological age. In this study lower end of femur fuses at 16-17 years range i.e. average 16.5 years in females and 17-18 years range i.e. average 17.5 years in males. The epiphyseal union in females occurs earlier than male by 1 year.

Gluten is the most abundant storage protein of wheat representing about 80 % of the total grain proteins and is composed of gliadins and glutenins. Glutenins are composed of high molecular weight (HMW) and low molecular weight (LMW) glutenin subunits which can be detected by SDS-PAGE. HMWGS are coded by three different loci namely Glu-A1, Glu-B1 and Glu-D1. Allelic diversity of protein subunits at these three loci was used to study the genetic relatedness of 35 bread wheat genotypes and their effect on bread making quality. Clustering of the genotypes revealed institutional, zonal and temporal prevalence of particular subunit combinations in the varieties. A novel HMW glutenin subunit designated as ‘17*’ reported earlier was confirmed in the land race Pissi-local. Allelic variation at the Glu-D1 locus was found to be an important determinant of bread making quality and allele of Glu-D1 encoding the subunits ‘5 + 10’ was superior to its allelic counterpart, encoding ‘2 + 12’. One new subunit ‘122’ (coded by Glu-D1-2) earlier reported in Indian cultivar C 306 was found to be present in three more varieties with similar parentage. Effect of this subunit relative to the ‘2 + 12’ subunit on bread making quality is reported in this study. The effect of allelic variation at Glu-A1 and Glu-B1 loci on the loaf volume was dependent on the alleles present at the Glu-D1 locus. Epistatic effect among the three ‘Glu-1’ loci was detected with respect to bread loaf volume.

Aim: The cerebrospinal fluid concentrations of Lactate dehydrogenase (LDH) were studied in patients with pyogenic, tubercular and viral meningitis in different age and sex group. Material and methods: A total of 160 cases, aged between 1 month and 60 years, including patients with bacterial meningitis (n=50), pyogenic meningitis (n=46), viral meningitis (n=24) and a control group (n=40), were analyzed on the basis of data from the initial clinical examinations. Results:Significant increase in LDH level (P

Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well documented. Telomeres are confined to guanine rich ends of chromosomes. Owing to its self-association properties, it adopts G-quadruplex structures and hampers the overexpression of telomerase in the cancer cells. Guanine, being the most oxidation prone nucleobase, when structured in G-quadruplex entity, is found to respond peculiarly towards oxidative stress. Interestingly, this non-Watson–Crick structural feature exists abundantly in promoters of various oncogenes, exons and other genomic locations. The involvement of G-quadruplex architecture in oncogene promoters is well recognized in gene regulation processes. Development of small molecules aimed to target G-quadruplex structures, have found to alter the overexpression of oncogenes. The interaction may lead to the obstruction of diseased cell having elevated level of reactive oxygen species (ROS). Thus, presence of short guanine tracts (Gn) forming G-quadruplexes suggests its critical role in oxidative genome damage. Present review is a modest attempt to gain insight on the association of oxidative stress and G-quadruplexes, in various biological processes.

The paper suggests a framework for the estimation of biomass and, ultimately, the amount of carbon sequestered in Avicennia marina stands of Mumbai region in Thane creek. The literature-adopted framework for estimating biomass uses a direct (Carbon, Hydrogen and Nitrogen (CHN) analysis), an indirect (allometry and remote sensing) and a hybrid approach. The study area has Avicennia marina as a dominant species. The carbon content was estimated using allometry and CHN analysis and further refined with GIS techniques. The Diameter at Breast Height (DBH) of 1,726 trees at 49 different locations in the study area was measured for estimating total biomass. A CHN analysis of leaf and soil samples was performed to determine the carbon content and the data extrapolated using geostatistical analysis. Using allometry and a GIS hybrid approach, the estimated carbon stock was 34.14769 tons per hectare. The regression model developed may be useful for estimating the carbon stock of areas that are inaccessible for conducting allometric measurements or gathering samples for CHN analysis. The study attempts to improve the estimates of the carbon content by including geostatistical analysis as a final step for allometry and combines CHN analysis for better conversion of biomass to carbon content.

An experiment was conducted to study the phenotypic and genotypic variance, heritability, genetic advance, correlation coefficients and path analysis for yield and physiological traits under rainfed condition. High estimates of heritability were recorded for early ground cover, chlorophyll content, flag leaf area, protein percent, and relative water content. Positive and significant correlation were recorded for early ground cover (0.662**), flag leaf area (0.390*), relative water content (0.589**) and canopy temperature depression (0.698**) with grain yield. The path coefficients were studied for all the traits. Early ground cover, flag leaf area, relative water content, canopy temperature depression had positive direct effects on grain yield per plot. Early ground cover, flag leaf area, relative water content and canopy temperature depression had direct positive effect on yield both at genotypic and phenotypic levels across the two environments. This suggests the possibilities of improvement of these characters through selection.

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3− CD4+ T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis ‘AITL’ was assessed by comparing the frequency of sCD3− CD4+ T cells in leukemic AITL patients and in patients with other leukemic CD4+ T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3− CD4+ T cells was detected (mean percentage of sCD3− CD4+ T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1–51.8%). In contrast, sCD3− CD4+ T cells were found in only 1/40 patients with other leukemic CD4+ T cell lymphomas (one patient with mycosis fungoides). sCD3− CD4+ T cells have a high positive predictive value (94%) for the diagnosis ‘AITL’. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted. Copyright © 2013 John Wiley & Sons, Ltd.

A study was conducted to evaluate the genetic divergence for morphological and phenological traits under rainfed conditions in wheat. Seed material comprised of the 294 wheat genotypes used for this study and grouped into six clusters. Among the six clusters, cluster IV contained 86 and cluster I had 68 genotypes, followed by 12 genotypes in cluster V. Fifty one genotypes were grouped in cluster VI and 52 were included in cluster II, while cluster III was represented by 27 genotypes. Maximum cluster mean for the character grain yield per plot was observed for the cluster III (667.1) followed by cluster V (559.3). The minimum cluster mean under the rainfed conditions was observed for the cluster IV (269.3). Intra cluster distance was maximum for cluster III (3.125). The highest inter cluster distance was noted between cluster II and cluster IV (4.997). Parentage of 294 genotypes revealed that genotypes belonging to different eco-geographical areas were included in the same cluster. This indicated that there was no association between clustering pattern and eco-geographical distribution of genotypes.

Aims: The aim of the study is to establish the correlation among CRP(C reactive protein), ESR (erythrocyte sedimentation rate) and Rheumatoid factor in case of HLA-B27 positive and negative patients in comparison to healthy control. Materials and Methods: Eighty patients were selected for study in which 40 with AS 40 controls. The clinical and laboratory data including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and HLA-B27 of patients were recorded. Results: The mean age of 40 patients was 31.6 ± 9.77 years. HLA-B27 was positive in 48 patients (60%) and it was found that disease activity was significantly associated with serum concentrations of CRP and ESR. In contrast, in the HLA B27- patients concentrations of ESR were significantly associated with disease activity, but not the concentrations of CRP. Conclusion: These results indicates that the known difference between HLA B27 positive and HLA B27 negative AS and suggest that the different pathogenic mechanisms involve in the two forms of AS, and the geographic regions and also the age at which the illness begins is one of the important predictors for the functional and clinical status in the disease course in Indian population.

Respiratory infection with Francisella tularensis (Ft) is characterized by a muted, acute host response, followed by sepsis-like syndrome that results in death. Infection with Ft establishes a principally anti-inflammatory environment that subverts host-cell death programs to facilitate pathogen replication. Although the role of cytokines has been explored extensively, the role of eicosanoids in tularemia pathogenesis is not fully understood. Given that lipoxin A4 (LXA4) has anti-inflammatory properties, we investigated whether this lipid mediator affects host responses manifested early during infection. The addition of exogenous LXA4 inhibits PGE2 release by Ft-infected murine monocytes in vitro and diminishes apoptotic cell death. Tularemia pathogenesis was characterized in 5-lipoxygenase-deficient (Alox5−/−) mice that are incapable of generating LXA4. Increased release of proinflammatory cytokines and chemokines, as well as increased apoptosis, was observed in Alox5−/− mice as compared with their wild-type counterparts. Alox5−/− mice also exhibited elevated recruitment of neutrophils during the early phase of infection and increased resistance to lethal challenge. Conversely, administration of exogenous LXA4 to Alox5−/− mice made them more susceptible to infection thus mimicking wild-type animals. Taken together, our results suggest that 5-LO activity is a critical regulator of immunopathology observed during the acute phase of respiratory tularemia, regulating bacterial burden and neutrophil recruitment and production of proinflammatory modulators and increasing morbidity and mortality. These studies identify a detrimental role for the 5-LO–derived lipid mediator LXA4 in Ft-induced immunopathology. Targeting this pathway may have therapeutic benefit as an adjunct to treatment with antibiotics and conventional antimicrobial peptides, which often have limited efficacy against intracellular bacteria.

Chalcones possess various biological properties, for example, antimicrobial, anti-inflammatory, analgesic, antimalarial, anticancer, antiprotozoal and antitubercular activity. In this study, naphthylchalcone derivatives were synthesized and characterized using 1H NMR 13C NMR, Fourier transform infrared and mass techniques. Yields for all derivatives were found to be >90%. Protein–drug interactions influence the absorption, distribution, metabolism and excretion (ADME) properties of a drug. Therefore, to establish whether the synthesized naphthylchalcone derivatives can be used as drugs, their binding interaction toward a serum protein (bovine serum albumin) was investigated using fluorescence, circular dichroism and molecular docking techniques under physiological conditions. Fluorescence quenching of the protein in the presence of naphthylchalcone derivatives, and other derived parameters such as association constants, number of binding sites and static quenching involving confirmed non-covalent binding interactions in the protein–ligand complex were observed. Circular dichroism clearly showed changes in the secondary structure of the protein in the presence of naphthylchalcones, indicating binding between the derivatives and the serum protein. Molecular modelling further confirmed the binding mode of naphthylchalcone derivatives in bovine serum albumin. A site-specific molecular docking study of naphthylchalcone derivatives with serum albumin showed that binding took place primarily in the aromatic low helix and then in subdomain II. The dominance of hydrophobic, hydrophilic and hydrogen bonding was clearly visible and was responsible for stabilization of the complex.

Structural polymorphism is an extremely significant phenomenon of nucleic acids, in which DNA and RNA oligonucleotide sequences are able to adapt various canonical, alternative and multistranded structures. These alternative forms of DNA and RNA have an enormous potential of participating in various cellular processes by recognizing ligands such as proteins, drugs and metal ions in a sequence and structure-specific manner. Such DNA-ligand interactions prove to be highly beneficial when exploited for therapeutic purposes. Many of these DNA/ RNA structures recognizing drugs have already proved their potential as anticancer, antibacterial, anthelmintic and antiviral properties. Over the last 2-3 decades, many mechanisms of DNA-drug interactions have been documented, but still many other new mechanisms are being explored. Designing new drugs with improved efficacy and specificity is of prime concern for all researchers which not only deals with the experiments related to synthesizing drugs, but also takes care of searching novel routes or agents for administration or delivery of these therapeutic agents by increasing their nuclear and cellular uptake. This review aims at explaining the structural polymorphs/ multistranded DNA structures and their interactions with pharmaceutical drugs in a structure-specific manner, along with their modes of interactions and biological relevance. This detailed overview of multistranded DNA structures and interacting drugs might further facilitate our understanding about molecular targets and drug development in a more precise manner for the larger benefit of mankind.

Development of micronutrient enriched staple foods is an important breeding goal in view of the extensive problem of ‘hidden hunger’ caused by micronutrient malnutrition. In the present study, kernel iron (Fe) and zinc (Zn) concentrations were evaluated in a set of 31 diverse maize inbred lines in three trials at two locations – Delhi (Kharif 2007 & 2008) and Hyderabad (Rabi 2007–08). The ranges of kernel Fe and Zn concentrations were 13.95–39.31 mg/kg and 21.85–40.91 mg/kg, respectively, across the three environments. Pooled analysis revealed significant genotype × environment (G × E) interaction in the expression of both the micronutrient traits, although kernel Fe was found to be more sensitive to G × E as compared to kernel Zn. Seven inbred lines, viz., BAJIM-06-03, DQPM-6, CM212, BAJIM-06-12, DQPM-7, DQPM-2 and CM129, were found to be the most stable and promising inbred lines for kernel Zn concentration, while for kernel Fe concentration, no promising and stable genotypes could be identified. Analysis of molecular diversity in 24 selected inbred lines with phenotypic contrast for the two kernel micronutrient traits, using 50 SSR markers covering the maize genome, revealed high levels of polymorphisms (214 SSR alleles; mean PIC value = 0.62). The phenotypically contrasting and genetically diverse maize inbred lines identified in this study could be potentially utilized in further studies on QTL analysis of kernel micronutrient traits in maize, and the stable and most promising kernel micronutrient-rich maize genotypes provide a good foundation for developing micronutrient-enriched maize varieties suitable for the Indian context.

CD14 is a glycosylphosphatidylinositol-anchored protein expressed primarily on myeloid cells (eg, neutrophils, macrophages, and dendritic cells). CD14(-/-) mice infected with Borrelia burgdorferi, the causative agent of Lyme disease, produce more proinflammatory cytokines and present with greater disease and bacterial burden in infected tissues. Recently, we uncovered a novel mechanism whereby CD14(-/-) macrophages mount a hyperinflammatory response, resulting from their inability to be tolerized by B. burgdorferi. Paradoxically, CD14 deficiency is associated with greater bacterial burden despite the presence of highly activated neutrophils and macrophages and elevated levels of cytokines with potent antimicrobial activities. Killing and clearance of Borrelia, especially in the joints, depend on the recruitment of neutrophils. Neutrophils can migrate in response to chemotactic gradients established through the action of gelatinases (eg, matrix metalloproteinase 9), which degrade collagen components of the extracellular matrix to generate tripeptide fragments of proline-glycine-proline. Using a mouse model of Lyme arthritis, we demonstrate that CD14 deficiency leads to decreased activation of matrix metalloproteinase 9, reduced degradation of collagen, and diminished recruitment of neutrophils. This reduction in neutrophil numbers is associated with greater numbers of Borrelia in infected tissues. Variation in the efficiency of neutrophil-mediated clearance of B. burgdorferi may underlie differences in the severity of Lyme arthritis observed in the patient population and suggests avenues for development of adjunctive therapy designed to augment host immunity.