Department of Bioscience & Bioengineering

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Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22-23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation. Copyright © 2008 Society for Neuroscience.

World University root node

Journal of Neuroscience

Large-scale reorganization in the somatosensory cortex and thalamus after sensory loss in macaque monkeys

The reaction of Cu(ClO4)2·6H2O with t-BuP(O)(OH)2 and 3,5-(CF3)2PzH in the presence of triethylamine afforded the dodecanuclear cage {[Et 3NH]2[Cu12(μ-3,5-(CF3) 2Pz)6(μ3-OH)6(μ-OH) 3(μ3-t-BuPO3)2(μ6- t-BuPO3)3][t-BuPO2OH]-[C6H 5CH3]2} (2). The molecular structure of this cage revealed that it possesses a barrel-shaped architechture. The cage structure is built by the cumulative coordination action of phosphonate, hydroxide, and pyrazolyl ligands. A similar reaction involving Cu(NO 3)2·3H2O, t-BuP(O)(OH)2, 3,5-dimethylpyrazole, and triethylamine afforded another dodecanuclear cage [Cu12(μ-DMPz)8(η1-DMPzH) 2(μ4-O)2(μ3-OH) 4(μ3-t-BuPO3)4]·3MeOH (3). The latter is crown-shaped and is built by the coordination of pyrazole, pyrazolyl, phosphonate, hydroxide, oxide, and methanol ligands. Both of the dodecanuclear cages are efficient nucleases in the presence of magnesium monoperoxyphthalate. © 2008 American Chemical Society.

Inorganic Chemistry

Barrel- and crown-shaped dodecanuclear copper(II) cages built from phosphonate, pyrazole, and hydroxide ligands

This study describes the use of peptide vesicular platforms for the templated growth of fibrillar structures to craft hybrids that retain the gross morphological features of two discreet self-assembled peptides. A synthetic triskelion peptide, which results in the rapid emergence of self-assembled spherical structures, was employed as a template. Addition of either one of two different peptides, both of which form long filamentous structures when co-incubated with the triskelion solution, affords hybrids that retain the gross morphology of both the spherical and filamentous structures. It is surmised that this process is aided by hydrogen bonding and the interdigitation of aromatic residues, which leads to the growth of hybrid structures. We believe that observations concerning the surface-assisted growth of peptide fibrils and tubular structures from vesicular platforms may have ramifications for the design and development of peptide-based hybrid materials with controlled hierarchical structures. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Chemistry - A European Journal

Templated growth of hybrid structures at the peptide-peptide interface

Laccase from basidiomycete fungus Cyathus bulleri was evaluated for its ability to decolorize a number of reactive and acidic dyes in the presence of natural and synthetic mediators. The extent of decolorization was monitored at different mediator/dye concentrations and incubation time. Among the synthetic mediators, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) was effective at low mediator/dye ratios and resulted in 80-95% decolorization at rates that varied from 226∈±∈4 nmol min-1 mg -1 for Reactive Orange 1 to 1,333∈±∈15 nmol min -1 mg-1 for Reactive Red 198. Other synthetic mediators like 1-hydroxybenzotriazole and violuric acid showed both concentration- and time-dependent increases in percent decolorization. Natural mediators like vanillin, on the other hand, were found to be less effective on all the dyes except Reactive Orange 1. Computed rates of decolorization were about twofold lower than that with ABTS. The laccase-ABTS system also led to nearly 80% decolorization for the simulated dye mixture. No clear correlation between laccase activity on the mediator and its ability to decolorize dyes was found, but pH had a significant effect: Optimum pH for decolorization coincided with the optimum pH for mediator oxidation. The treated samples were also evaluated for toxicity in model microbial systems. The laccase-mediator system appears promising for treatment of textile wastewaters. © 2008 Humana Press.

Applied Biochemistry and Biotechnology

Mediator-assisted decolorization and detoxification of textile dyes/dye mixture by cyathus bulleri laccase

Cytokines mediate many immune and inflammatory responses contributing to tumorigenesis. The present study evaluated polymorphisms of IL4, IL6, and TNF (previously TNFA) genes influencing risk in development of transitional cell carcinoma of bladder and recurrence after bacillus Calmette-Guérin (BCG) immunotherapy. The study included 136 unrelated histopathologically confirmed cases and 200 population-based controls. Genomic DNA was extracted from peripheral leukocytes and genotyped for polymorphism in IL4 intron 3, with point mutations identified by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in IL6-174 G/C and by PCR-restriction fragment length polymorphism analysis in TNF-308 G/A. The IL6 variant C/C exhibited significant association with bladder cancer risk (odds ratio OR = 2.811, P = 0.004), but IL4 and TNF genetic variants did not. Significant association was observed for IL4 (B1/B2+B2/B2) with high-grade or late-stage tumor for TaG3+T1 and T2+ (OR = 5.950, and 6.342 respectively) and with smoking (P = 0.004, OR = 4.202). Low recurrence risk was observed in BCG-treated patients carrying C/C genotype of IL6 (hazard ratio = 0.298, P = 0.03), and also higher recurrence-free survival (log rank P = 0.021). TNF and IL4 demonstrated no association of bladder cancer risk and BCG therapy. The low-producing variant C/C of IL6 may be a risk factor for bladder cancer, whereas high-producing genotypes of IL4 (B1/B2+B2/B2) may predispose to higher risk in patients with high-grade or late-stage tumor and smoking habits. The low-producing C/C IL6 genotype, which favors Th1 response, may be a beneficial prognostic indicator for treatment and survival of BCG-treated patients. © 2008 Elsevier Inc. All rights reserved.

Cancer genetics and cytogenetics

{Anti-and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade and bacillus Calmette-Gu{\'{e}}rin immunotherapy in {\ldots}}

The cellular alterations that give rise to cancer initiate changes in cytokine expression. Though IL-6 is known to play a major role in proliferation of tumor cells, IL-4 upregulates androgen receptors and prostate-specific antigen (PSA). The present study was undertaken to evaluate the association of IL-4 and IL-6 gene polymorphisms for the susceptibility to prostate cancer (PCa) risk. Our study included 200 controls and 200 histologically confirmed cases of PCa. Polymorphisms in IL-4 (intron 3, by VNTR analysis) and IL-6 (-174 G/C, by amplification refractory mutation system, i.e., ARMS-PCR) were genotyped in all the subjects. There was no significant association of IL-4 and IL-6 gene polymorphisms with the risk of PCa. Nevertheless, twofold risk with progression to bone metastasis (odds ratio = 2.09; 95% confidence interval = 1.16-3.75; p = 0.014) in PCa patients was observed. No association with other confounding factors such as PSA level, Gleason score, and lifestyle-associated risk factors like tobacco chewing and cigarette smoking was seen. Our study suggests that an IL-6 gene variant may be associated with prostate progression and bone metastasis. © Copyright 2008, Mary Ann Liebert, Inc.

DNA and cell biology

Association between −174 G/C Promoter Polymorphism of the Interleukin-6 Gene and Progression of Prostate Cancer in North Indian Population

XRCC1 protein plays crucial role in base excision repair (BER) by acting as a scaffold for other BER enzymes. Variants in XRCC1 gene might alter protein structure/function or create alternatively spliced protein influencing BER efficiency and affect individual susceptibility/recurrence to urinary bladder cancer (BC). We tested whether polymorphisms in XRCC1 gene were associated with BC risk and further to substantiate risk of recurrence after Bacillus Calmette-Guerin (BCG) immunotherapy. Genotyping for three polymorphic sites of XRCC1 gene at codon Arg194Trp (PvuII), Arg280His (RsaI) and Arg399Gln (MspI) in 140 BC cases and 190 controls by PCR-RFLP method was done. We observed significant association in heterozygous genotype (GA) of codon 280 and 399 with BC risk (OR = 1.96, p = 0.021 and OR = 1.81, p = 0.021, respectively), however no association was seen for variant AA genotype. A trend of increased risk with high stage and grade in patients with codon 194 variant genotypes (CT + TT) was observed. Haplotype analysis showed that individuals with haplotype 194C-280G-399A were at >3-fold higher risk for BC (OR = 3.48, p = 0.01). The A/A genotype of codon 399 was associated with high risk for recurrence in BCG treated patients (HR = 5.05, p = 0.01) thus, showing reduced recurrence free survival (AA/GG = 12/60 months; log rank p = 0.004). The study suggested no association of variant genotypes with the susceptibility to BC. Haplotype analysis however, revealed that XRCC1 399 A allele may have a major role as patients with haplotype 194C-280G-399A carrying variant allele of 399 were at higher risk. ©2008 Landes Bioscience.

Cancer biology \& therapy

XRCC1 codon 399 mutant allele: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy

Sequencing of the human and chimpanzee genomes has revealed ∼99% similarity in the coding sequence between both the species, which in no way parallels the observable phenotypic differences. Contribution of the non-coding sequences which comprise a bulk of the genome, in functional divergence between human and chimpanzee, is largely understudied. In this context, we have compared extents of divergence in the non-coding repetitive DNA in a data set of well-classified neuronal and housekeeping genes between human and chimpanzee. The coding regions of these genes have earlier been extensively compared between the two species. It was revealed that the neurodevelopmental genes show accelerated evolution compared to neurophysiology and housekeeping genes in human. In this study, comparative analysis in terms of repeat spectrum, divergence in dinucleotide content density, JC divergence and its partitioning in repeats versus unique regions and transcription factor binding sites indicate different extents of functional constraints associated with the non-coding repeat regions. The constraints are also different when the upstream and downstream genic regions are compared across the functional categories. The neurodevelopmental genes seem to diverge more in the genic regions, whereas the neurophysiology genes show higher divergence in the upstream 2 kb region. Most of the divergence observed in the housekeeping genes is contributed by repeats. We also observe an accumulation of function-specific transcription factor profiles in the human lineage. Interestingly, a major fraction of the regulatory sites in these regions is differently partitioned in the repetitive sequences which in turn is dependant upon the relative distribution of the repeats across the functional categories. Thus, differential distribution of repeats across the various functional categories could have substantial effects on genome wide regulation and structure. The insights obtained from this study further add a new facet to the contribution of non-coding factors especially repeats in divergence of human and chimpanzee. © 2007 Springer-Verlag.

Molecular Genetics and Genomics

Non-random genomic divergence in repetitive sequences of human and chimpanzee in genes of different functional categories

This report describes formation of soft vesicular structures by a tetrapeptide and its disruption triggered by potassium ions. © The Royal Society of Chemistry.

Fulltext

Chemical Communications

Self-assembly and potassium ion triggered disruption of peptide-based soft structures

Biological molecules serve as convenient scaffolds for the construction of nanoscopic architectures which can effectively interact with small molecules and metal complexes to extend their scope for nano(bio)technological applications. Metalloproteins possess natural metal ion binding motifs and the possibility of using these sequences to generate metalated peptide conjugates with defined metal ion coordination offers a facile entry into metalated supramolecular aggregates. This report describes the formation of metalated fibers from Cu-binding octarepeat motifs of the prion protein. Conjugate 1 effectively binds copper, silver, and manganese, leading to persistent length and thermally stable peptide fibers, which could be applied for molecular bioelectronic applications. © 2007 Elsevier Ltd. All rights reserved.