A novel haplotype within C-reactive protein gene influences CRP levels and coronary heart disease risk in Northwest Indians

According to several epidemiological and clinical studies, the concentration of C-reactive protein (CRP) in blood is associated with the risk of coronary heart disease (CHD). However, these studies are limited in high incidence and prevalence area of North-West India. The present case control study investigated the contribution of three relevant CRP single nucleotide polymorphisms: ?717A>G located in the promoter region (rs2794521), +1059G>C on exon2 (rs1800947) and +1444C>T in the 3′ UTR (rs1130864) in 180 angiographically verified CHD cases and 175 control subjects. Minor allele frequencies (G, C and T) of rs2794521, rs1800947 and rs1130864 are observed to be 21.1, 11.7, 29.4 and 11.4, 10.0, 19.7 % in CHD cases and controls respectively. AA genotype of ?717A>G and TT genotype of +1444C>T were significantly associated (P = 0.02 & 0.03 respectively) with the risk of CHD whereas, +1059G and +1444T were found to be strongly related (P = 0.023 & P = 0.008 respectively) with multivariable adjusted CRP levels. AGT Haplotype was significantly associated with the adjusted CRP levels (P < 0.05). Disease association analysis revealed that haplotype AGT influences CHD risk (OR 2.4, 95 % CI 1.23–4.84, P = 0.006) which exacerbates after correcting the confounding effects of risk variables (OR 2.5, 95 % CI 1.27–4.99, P = 0.004). With the global index of Akaike information criterion, it has been observed that the carrying each single unit of this susceptibility haplotype increases CHD risk by a value of 2.41 ± 0.439 (β ± SE) in the recessive mode.     

Genome‐wide analyses of rice root development QTLs and development of an online resource, Rootbrowse

Genetic control of root development in rice is complex and the underlying mechanisms (constitutive and adaptive) are poorly understood. Lowland and upland varieties of indica and japonica rice with contrasting root development characteristics have been crossed, mapping populations developed and a number of QTLs in different chromosomes were identified. As these studies have used different sets of markers and many of the QTLs identified are long, it is difficult to exploit the varietal difference for improved root traits by marker assisted selection and for identification of concerned alleles. Intensive data mining of literature resulted in the identification 861 root development QTLs and associated microsatellite markers located on different chromosomes. The QTL and marker data generated and the genome sequence of rice were used for construction of a relational database, Rootbrowse, using MySQL relational database management system and Bio::DB::GFF schema. The data is viewed using GBrowse visualization tool. It graphically displays a section of the genome and all features annotated on it including the QTLs. The QTLs can be displayed along with SSR markers, protein coding genes and/or known root development genes for prediction of probable candidate genes.     

Genetic insight of schizophrenia: past and future perspectives

Schizophrenia (SCZ) has a heritability of about 80%, and the search for the genetic basis of this disease has been frustrating. Because schizophrenia has no distinguishing pathology or diagnostic criteria, it is difficult to relate gene changes to discrete physiological or biochemical changes associated with the disease. Schizophrenia fits the profile of a complex disorder in which multiple genes interact along with environmental influences to produce a range of phenotypes. There is accumulating evidence that both common genetic variants with small effects and rare genetic lesions with large effects determine risk of SCZ. As recently shown, thousands of common single nucleotide polymorphisms (SNPs), each with small effect, cumulatively could explain about 30% of the underlying genetic risk of SCZ. The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that genetic research is poised to deliver crucial insights into the nature of schizophrenia. In this review, we outline a general theoretical background of genetic mechanisms involved in SCZ.     

Structure modeling and dynamics driven mutation and phosphorylation analysis of Beta-amyloid peptides

The most common characteristics of diverse age-related neurodegenerative diseases are aggregation and accumulation of the misfolded protein in the brain. Alzheimer׳s disease (AD) is one of these protein conformational diseases. Extracellular accumulation of amyloid β (Aβ) is one the neuropathological hallmarks of Alzheimer disease. Various studies have shown that mutation in specific hydrophobic region of Aβ protein inhibit the formation of β sheet, thus aggregation of this protein is stalled. The identification of such mutation in Aβ protein can help us in elucidating the etiology of sporadic Aβ. In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker). The effects of the substitutions were analysed using molecular dynamics simulation studies. The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.     

Evaluation of change in implant abutment after teeth surface modifications

The surface modifications in teeth increase the retentive strength of cemented castings by providing micro as well as macro retentive ridge and groove patterns. Restoring the dental implants with cement-retained prosthesis is well known. Therefore, it is of interest to compare retentive property of implant abutments with and without circumferential grooves. Hence, 20 straight shoulder type titanium abutments were with abutment screws as well as prefabricated plastic copings and corresponding 12 mm-long stainless steel laboratory implant analogs were used. The abutments were divided into two subgroups of 10 abutments each: without grooves and with grooves. After thermocycling and storing the cemented abutments in water at 37°C water for 6 days they were assembled in the Universal testing machine and subjected to a pullout test (retention) at a crosshead speed of 5.0mm/min to record forces in Newton. Data suggest that the addition of grooves increased the retention. The mean retentive forces of standard machined abutments (plain) cemented with Resin modified GIC showed 339.34 N. Retention increased by 667.39N after addition of circumferential grooves. The surface modification of an implant abutment by means of circumferential grooves is an effective method of improving the retention of cast crowns cemented with resin modified GIC especially in short abutments.     

Construction of multiple herbicide resistant ammonia excreting strains of cyanobacteriumNostoc muscorum

Summary Machete resistant (Mat ^r), basalin resistant (Bas ^r), 3(3,4 dichlorophenyl)-1,1-dimethyl urea resistant (DCMU ^r), atrazine resistant (Atr ^r) and propanil resistant (Prp ^r) phenotypes ofGloeocapsa sp. were cotransformed toNostoc muscorum at high frequency. Spontaneously occurring mutants of the multiple herbicide resistant transformant containing L-methionine-DL-sulfoximine resistant (Msx ^r), ethylene diamine resistant (Eda ^r), or phosphinothricin resistant (Ppt ^r) glutamine synthetase (GS) showed extracellular liberation of ammonia resulting from fixation of N₂ under photosynthetic conditions. Results suggest a definite role of GS activity in regulation of extracellular ammonia.     

Genetic control of heterocyst formation in the blue-Green algae Nostoc muscorum and nostoc linckia

Non-heterocystous, non-nitrogenfixing (het ^- nif^-), heterocystous, non-nitrogenfixing (het ⁺ nif^-) and multiple heterocystous, nitrogen-fixing (M-het ⁺ nif⁺) mutants of heterocystous, nitrogen-fixing (het ⁺ nif⁺) wild-type Nostoc muscorum and Nostoc linckia were isolated and characterized with respect to (a) nitrogenfixing activity, (b) reversion frequency, (c) ammonium repressibility of heterocyst formation, (d) heterocyst spacing pattern, and (e) action of L-methionine-DL-sulphoximine (MSO), an inhibitor of glutamine synthetase (GS), on heterocyst regulation. The mutant and revertant results suggest: (i) either involvement of a common genetic determinant in the formation of heterocyst and nitrogenase or the organization of het genes and nif genes in a single operon prone to complete inactivation by a single polar mutation, (ii) non-participation of active nitrogenase in regulation of heterocyst spacing; (iii) involvement of genetic factor(s) in the control of heterocyst spacing pattern in N. linckia, and (iv) apparently different nature of the mechanism of heterocyst inhibition by proheterocyst from that of heterocyst inhibition by NO ₃ ^- or NH ₄ ⁺ . L-Methionine-DL-sulphoximine inhibits growth and causes heterocyst formation in chains in N. linckia growing in nitrogen-free, NO ₃ ^- , NO ₂ ^- or NH ₄ ⁺ medium, thus indicating a close physiological linkage between heterocyst and inorganic nitrogen metabolism regulation.     

Limited Invasive Protocol: Optimizing Diagnostic Modalities in Corticotropin Mediated Cushing Syndrome

BackgroundTo limit the role of bilateral inferior petrosal sinus sampling (BIPSS) in distinguishing between Cushing disease (CD) and ectopic Cushing syndrome (ECS), recent reports have proposed a noninvasive approach based on a combination of biochemical testing and radiological imaging as an alternative to the conventional invasive strategy (CIS). However, this strategy requires further validation. The current study aimed to evaluate 2 limited invasive protocols (LIP-1 and LIP-2) in limiting the role of BIPSS while maintaining a diagnostic accuracy similar to that of CIS.MethodsThis was a single-center study conducted on individuals with corticotropin-dependent Cushing syndrome. The LIPs were based on performing high-dose dexamethasone suppression (>50% cut-off in first [LIP-1] and >80% in second [LIP-2]) and magnetic resonance imaging of the sella in all individuals and selective use of computed tomography of the chest and abdomen before BIPSS. These LIPs were evaluated for limiting the use of BIPSS, their accuracy, and cost in comparison to CIS.ResultsOf the 206 individuals, 114 (97 of CD and 21 of ECS) were eligible for the current study. Using LIP-1, LIP-2, and CIS, BIPSS could have been avoided in 62.3%, 35.9%, and 25.4% of individuals, respectively. The positive predictive value for CD using LIP-1 and LIP-2 was 98.9% and 100%, respectively. The cost per patient evaluated using LIP-1, LIP-2, and CIS was $602.21, $966.81, and $1107.78, respectively.ConclusionLIPs represent an equally accurate, less invasive, and more cost-effective alternative to the CIS for distinguishing between CD and ECS.