Molecular diversity in rice blast resistance gene Pi-ta makes it highly effective against dynamic population of Magnaporthe oryzae

Rice blast is one of the important diseases of rice which can be effectively managed by the deployment of resistance genes. Pi-ta is one of the major blast resistant genes effective against pathogen populations in different parts of India. We analysed allelic variants of Pi-ta from 48 rice lines selected after phenotyping of 529 rice landraces across three eco-geographical blast hot spot regions. Besides, Pi-ta orthologue sequences of 220 rice accessions belonging to wild and cultivated species of rice were also included in the study for a better evo–devo perspective of the diversity present in the gene and the selection pressures acting on this locus. We obtained high nucleotide variations (SNPs and insertion–deletions) in the intronic region. We also identified 64 haplotypes based on nucleotide polymorphism in these alleles. Pi-ta orthologues of Indian landraces were scattered in eight major haplotypes indicating its heterogenous nature. We identified a total of 47 different Pi-ta protein variants on the basis of deduced amino acid residues amongst the orthologues. Five unique and novel Pi-ta variants were identified for the first time in rice landraces exhibiting different reaction types against the Magnaporthe oryzae population. A high value of Pi_non/syn was observed only in the leucine-rich domain of the alleles cloned from Indian landraces, indicating strong selective forces acting on this region. The detailed molecular analysis of the Pi-ta orthologues provides insights to a high degree of inter- and intraspecific relationships amongst the Oryza species. We identified rice landraces possessing the effective alleles of this resistance gene which can be used in future blast resistance breeding programmes.     

Synthesis, absolute stereochemistry and molecular design of the new antifungal and antibacterial antibiotic produced by Streptomyces sp.201

The absolute stereochemistry of the new antifungal and antibacterial antibiotic produced by Streptomyces sp.201 has been established by achieving the total synthesis of the product. A series of analogues have also been synthesized by changing the side chain and their bioactivity assessed against different microbial strains. Among them, 1e (R = C8H17) was found to be the most potent with MIC of 8 microg/mL against Mycobacterium tuberculosis, 12 microg/mL against Escherichia coli and 16 microg/mL against Bacillus subtilis 6 microg/mL against Proteus vulgaris. This was followed by 1b (R = C5H11) with MIC of 10-20 microg/mL range and 1d (R = C7H15) with MIC of 14-24 g/mL, whereas 1a (R = C4H9) and 1f (R = C18H35) were found to be completely inactive. Besides, 1c (R = C6H13) showed certain extent of antibacterial activity in the range of 24-50 microg/mL. Mycobacterium tuberculosis was very sensitive to 1e (R = C8H17) with MIC of 8 microg/mL. Antifungal activity of analogues 1d (R = C7H15) and 1e, (R = C8H17) against Fusarium oxysporum and Rhizoctonia solani were found promising with MFCs in the 15-18 microg/mL range.     

Histological complexities of pancreatic lesions from transgenic mouse models are consistent with biological and morphological heterogeneity of human pancreatic cancer

Although pancreatic cancer is the fourth leading cause of cancer death, it has received much less attention compared to other malignancies. There are several transgenic animal models available for studies of pancreatic carcinogenesis, but most of them do not recapitulate, histologically, human pancreatic cancer. Here we review some detailed molecular complexity of human pancreatic cancer and their reflection in histomorphological complexities of pancreatic lesions developed in various transgenic mouse models with a special concern for studying the effects of chemotherapeutic and chemopreventive agents. These studies usually require a large number of animals that are at the same age and gender and should be either homozygote or heterozygote but not a mixture of both. Only single-transgene models can meet these special requirements, but many currently available models require a mouse to simultaneously bear several transgene alleles. Thus it is imperative to identify new gene promoters or enhancers that are specific for the ductal cells of the pancreas and are highly active in vivo so as to establish new single-transgene models that yield pancreatic ductal adenocarcinomas for chemotherapeutic and chemopreventive studies.     

Complexation thermodynamics and the structure of the binary and the ternary complexes of Am, Cm and Eu with IDA and EDTA + IDA

The stability and the associated thermodynamic parameters of the binary and the ternary complexes of trivalent Am, Cm, and Eu with IDA and with EDTA + IDA, were determined by using a solvent extraction technique for aqueous solutions of I = 6.60 m (NaClO₄) at temperatures of 0-60 °C. The endothermic enthalpy and the positive entropy reflect the significant effect of dehydration in the formation of these complexes at high ionic strength. TRLFS and NMR (¹H and ¹³C) data helped to establish the structure of the ternary complexes in solution. In the ternary complex M(EDTA)(IDA)³⁻, EDTA binds via four carboxylates and two nitrogens, and IDA via two carboxylates and one nitrogen to the central Eu³⁺.     

α-Lipoic Acid,an Organosulfur Biomolecule a Novel Therapeutic Agent for Neurodegenerative Disorders: An Mechanistic Perspective

Neurochemical Research - Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (C8H14O2S2) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic...     

BDNF-restricted knockout mice as an animal model for aggression

Mice with global deletion of one brain-derived neurotrophic factor (BDNF) allele or with forebrain-restricted deletion of both alleles show elevated aggression, but this phenotype is accompanied by other behavioral changes, including increases in anxiety and deficits in cognition. Here we performed behavioral characterization of conditional BDNF knockout mice generated using a Cre recombinase driver line, KA1-Cre, which expresses Cre in few areas of brain: highly at hippocampal area CA3 and moderately in dentate gyrus, cerebellum and facial nerve nucleus. The mutant animals exhibited elevated conspecific aggression and social dominance, but did not show changes in anxiety-like behaviors assessed using the elevated plus maze and open field test. There were no changes in depression-like behaviors tested in the forced swim test, but small increase in immobility in the tail suspension test. In cognitive tasks, mutants showed normal social recognition and normal spatial and fear memory, but exhibited a deficit in object recognition. Thus, this knockout can serve as a robust model for BDNF-dependent aggression and object recognition deficiency.     

Synthesis of novel peptide nucleic acid-peptide chimera for non-invasive imaging of cancer

A chelator-peptide-PNA-peptide chimera specific for KRAS has been prepared by continuous solid phase coupling with a C-terminal insulin-like growth factor 1 (IGF1) ligand, D(cys-ser-lys-cys), and N-terminal bis(S-benzoyl thioglycoloyl) diaminopropanoate chelator for radionuclide labeling. The probe was purified by RP-HPLC and characterized by MALDI-TOF mass spectroscopy. The probe was labeled with 99mTc and 64Cu. Both labeled probes accumulated in human pancreatic cancer xenografts in immunocompromised mice. Control experiments with mismatch chimeras and control xenografts will be necessary to determine the specificity of this molecular diagnostic strategy.     

The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Background  

a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed.