Strong evidence for a novel schizophrenia risk locus on chromosome 1p31.1 in homogeneous pedigrees from Tamil Nadu, India

OBJECTIVE: The study of ethnically homogeneous populations may help to identify schizophrenia risk loci. The authors conducted a genomewide linkage scan for schizophrenia in an Indian population. METHOD: Participants were 441 individuals (262 affected probands and siblings) who were recruited primarily from one ethnically homogeneous group, the Tamil Brahmin caste, although individuals from other geographically proximal castes also participated. Genotyping of 124 affected sibling pair pedigrees was performed with 402 short tandem repeat polymorphisms. Linkage analyses were conducted using nonparametric exponential LOD (logarithm of the odds ratio for linkage) scores and parametric heterogeneity LOD scores. Parametric heterogeneity scores were calculated using simple dominant and recessive models, correcting for multiple statistics. The data were examined for evidence of consanguinity. Genomewide significance levels were determined using 10,000 gene dropping simulations. RESULTS: These findings revealed genomewide significant linkage to chromosome 1p31.1, through the use of both exponential and heterogeneity LOD scores, incorporating correction for multiple statistics and mild consanguinity. The estimated sibling recurrence risk associated with this putative locus was 1.95. Analysis for heterogeneity LOD scores also detected suggestive linkage to chromosomes 13q22.1 and 16q12.2. Using 117 tag single nucleotide polymorphisms (SNPs), family-based association analyses of phosphodiesterase 4B (PDE4B), the closest schizophrenia candidate gene, detected no convincing evidence of association, suggesting that the chromosome 1 peak represents a novel risk locus. CONCLUSIONS: This is the first study-to the authors' knowledge-to report significant linkage of schizophrenia to chromosome 1p31.1. Further investigation of this chromosome region in diverse populations is warranted to identify underlying sequence variants.

Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of flight tandem mass spectrometry and a case-control approach

Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.

Tributyltin chloride-sodium cyanoborohydride mediated tandem radical cyclisation-reductive demethoxylation sequence

Reaction of the bromoketals 3, 7a-g and 11 with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of AIBN furnished the ethers 5, 8a-g and 13 via a tandem sequence comprising of a radical cyclisation reaction and tri-n-butylhalostannane and sodium cyanoborohydride mediated reductive demethoxylation of the resulting cyclic ketals.

Convenient Synthesis of Ferrocene Conjugates Mediated by Benzyltriethylammonium Tetrathiomolybdate in a Multi-Step Tandem Process

The synthesis of a wide range of ferrocene-derived sulfur-linked mono- and disubstituted Michael adducts and conjugates mediated by benzyltriethylammonium tetrathiomolybdate (1) in a tandem process is reported. New route to access acryloylferrocene (4) and 1,1'-diacryloylferrocene (5) is discussed. Conjugation of amino acids to ferrocene is established via their N and C termini and also via side chains employing conjugate addition as key step to furnish mono-and divalent conjugates. This methodology has also been extended to access several ferrocene-carbohydrate conjugates. The electrochemical behavior of some selected ferrocene conjugates was studied by cyclic voltammetry.

An algorithm to find similar internal sequence repeats

In recent years, identification of sequence patterns has been given immense importance to understand better their significance with respect to genomic organization and evolutionary processes. To this end, an algorithm has been derived to identify all similar sequence repeats present in a protein sequence. The proposed algorithm is useful to correlate the three-dimensional structure of various similar sequence repeats available in the Protein Data Bank against the same sequence repeats present in other databases like SWISS-PROT, PIR and Genome databases.

Synthesis based on cyclohexadienes. Part 34. A tandem cationic rearrangement-ene cyclisation route to 2-pupukeanone

A new strategy for the construction of the isotwistane skeleton is reported from easily available cyclohexadienes, which involves a one-pot cationic skeletal rearrangement and ene cyclisation of a bicyclo[2.2.2]octenone derivative and a cationic rearrangement of a tricyclo[5.3.0.0(4,8)]decane to a [4.3.1.0(3,7)]decane skeleton as the key steps in the synthesis of 2-pupukeanone.

An algorithm to find distant repeats in a pair of protein sequences

Distant repeats between a pair of protein sequences can be exploited to study the various aspects of proteins such as structure-function relationship, disorders due to protein malfunction, evolutionary analysis, etc. An in-depth analysis of the distant repeats would facilitate to establish a stable evolutionary relation of the repeats with respect to their three-dimensional structure. To this effect, an algorithm has been devised to identify the distant repeats in a pair of protein sequences by essentially using the scores of PAM (Percent Accepted Mutation) matrices. The proposed algorithm will be of much use to researchers involved in the comparative study of various organisms based on the amino-acid repeats in protein sequences. (C) 2010 Elsevier B.V. All rights reserved.

Tandem Michael reaction. Synthesis of bridged diketones

Addition of NaOMe, NaOEt, or NaOPr(i) to dispironaphthalenone 1 resulted in the formation of diketones 4a-c and 5a-c. The structure assigned to 4a was confirmed by conversion to the known hemiacetal 3. Similar addition of carbon nucleophiles like diethyl malonate, dimethyl malonate, methyl cyanoacetate, and ethyl cyanoacetate afforded diketones 4d-g. Formation of these compounds has been rationalized.

Tandem 5-exo-trig allyl and 3-exo-trig radical cyclisation and rearrangement to copa and ylanga type sesquiterpene skeleton

A novel tandem 5-exo-trig allyl and 3-exo-trig radical cyclisation and rearrangement to copa and ylanga type sesquiterpene skeleton is reported.

RPS: Repeats in Protein Sequences

Repeats are two or more contiguous segments of amino acid residues that are believed to have arisen as a result of intragenic duplication, recombination and mutation events. These repeats can be utilized for protein structure prediction and can provide insights into the protein evolution and phylogenetic relationship. Therefore, to aid structural biologists and phylogeneticists in their research, a computing resource (a web server and a database), Repeats in Protein Sequences (RPS), has been created. Using RPS, users can obtain useful information regarding identical, similar and distant repeats (of varying lengths) in protein sequences. In addition, users can check the frequency of occurrence of the repeats in sequence databases such as the Genome Database, PIR and SWISS-PROT and among the protein sequences available in the Protein Data Bank archive. Furthermore, users can view the three-dimensional structure of the repeats using the Java visualization plug-in Jmol. The proposed computing resource can be accessed over the World Wide Web at http://bioserver1.physics.iisc.ernet.in/rps/.

Enantiospecific synthesis of functionalised bicyclo[3.3.1] nonanes from 10-bromocarvones via tandem intermolecular alkylation-intramolecular Michael addition sequence

A simple and convenient tandem methodology for the enantiospecific generation of functionalised bicyclo[3.3.1] nonanes 9,14-18, via intermolecular alkylation of Michael donors with 10-bromocarvones 7, 10 and 11, followed by intramolcular Michael addition, is achieved. An unsuccessful attempt for the extension of the methodology for a possible short enantiospecific approach to AB-ring system 22 of taxanes via the allyl bromide 21, is also described.

Structure of tandem and its implication for bifunctional intercalation into dna

Quinoxaline antibiotics (Fig. 1a, b) form a useful group of compounds for the study of drug–nucleic acid interactions1,2. They consist of a cross-bridged cyclic octadepsipeptide, variously modified, bearing two quinoxaline chromophores. These antibiotics intercalate bifunctionally into DNA2,3 probably via the narrow groove, forming a complex in which, most probably, two base pairs are sandwiched between the chromophores4,5. Depending on the nature of their sulphur-containing cross-bridge and modifications to their amino acid side chains, they display characteristic patterns of nucleotide sequence selectivity when binding to DNAs of different base composition and to synthetic polydeoxynucleotides4,6,7. This specificity has been tentatively ascribed to specific hydrogen-bonding interactions between functional groups in the DNA and complementary moieties on the peptide ring2,4,5. Variations in selectivity have been attributed both to changes in the conformation of the peptide backbone6 and no modifications of the cross-bridge7. These suggestions were made, however, in the absence of firm knowledge about the three-dimensional structure and conformation of the antibiotic molecules. We now report the X-ray structure analysis of the synthetic analogue of the antibiotic triostin A, TANDEM (des-N-tetramethyl triostin A) (Fig. 1c), which binds preferentially to alternating adenine-thymine sequences7. The X-ray structure provides a starting point for exploring the origin of this specificity and suggests possible models for the binding of other members of the quinoxaline series.

Features of a unique intronless cluster of class I small heat shock protein genes in tandem with box C/D snoRNA genes on chromosome 6 in tomato (Solanum lycopersicum)

Physical clustering of genes has been shown in plants; however, little is known about gene clusters that have different functions, particularly those expressed in the tomato fruit. A class I 17.6 small heat shock protein (Sl17.6 shsp) gene was cloned and used as a probe to screen a tomato (Solanum lycopersicum) genomic library. An 8.3-kb genomic fragment was isolated and its DNA sequence determined. Analysis of the genomic fragment identified intronless open reading frames of three class I shsp genes (Sl17.6, Sl20.0, and Sl20.1), the Sl17.6 gene flanked by Sl20.1 and Sl20.0, with complete 5' and 3' UTRs. Upstream of the Sl20.0 shsp, and within the shsp gene cluster, resides a box C/D snoRNA cluster made of SlsnoR12.1 and SlU24a. Characteristic C and D, and C' and D', boxes are conserved in SlsnoR12.1 and SlU24a while the upstream flanking region of SlsnoR12.1 carries TATA box 1, homol-E and homol-D box-like cis sequences, TM6 promoter, and an uncharacterized tomato EST. Molecular phylogenetic analysis revealed that this particular arrangement of shsps is conserved in tomato genome but is distinct from other species. The intronless genomic sequence is decorated with cis elements previously shown to be responsive to cues from plant hormones, dehydration, cold, heat, and MYC/MYB and WRKY71 transcription factors. Chromosomal mapping localized the tomato genomic sequence on the short arm of chromosome 6 in the introgression line (IL) 6-3. Quantitative polymerase chain reaction analysis of gene cluster members revealed differential expression during ripening of tomato fruit, and relatively different abundances in other plant parts.