A formal goodness-of-fit test for spatial binary Markov random field models.

Binary spatial observations arise in environmental and ecological studies, where Markov random field (MRF) models are often applied. Despite the prevalence and the long history of MRF models for spatial binary data, appropriate model diagnostics have remained an unresolved issue in practice. A complicating factor is that such models involve neighborhood specifications, which are difficult to assess for binary data.

A cell-based fluorescent system and statistical framework to detect meiosis-like induction in plants.

Genetic gains made by plant breeders are limited by generational cycling rates and flowering time. Several efforts have been made to reduce the time to switch from vegetative to reproductive stages in plants, but these solutions are usually species-specific and require flowering. The concept of nurseries is that somatic plant cells can be induced to form haploid cells that have undergone recombination (creating artificial gametes), which can then be used for cell fusion to enable breeding in a Petri dish.

Assessing data analysis techniques in a high-throughput meiosis-like induction detection system.

Background: Strategies to understand meiotic processes have relied on cytogenetic and mutant analysis. However, thus far in vitro meiosis induction is a bottleneck to laboratory-based plant breeding as factor(s) that switch cells in crops species from mitotic to meiotic divisions are unknown. A high-throughput system that allows researchers to screen multiple candidates for their meiotic induction role using low-cost microfluidic devices has the potential to facilitate the identification of factors with the ability to induce haploid cells that have undergone recombination (artificial gametes) in cell cultures.

Overcoming roadblocks for nurseries in plants: induction of meiosis.

Efforts to increase genetic gains in breeding programs of flowering plants depend on making genetic crosses. Time to flowering, which can take months to decades depending on the species, can be a limiting factor in such breeding programs. It has been proposed that the rate of genetic gain can be increased by reducing the time between generations by circumventing flowering through the induction of meiosis.

Echocardiographic Assessment of Valvular Involvement in Chronic Rheumatic Heart Disease in BSMMU, Bangladesh.

Rheumatic heart disease (RHD) is a disease of poverty, is almost entirely preventable, and is the most common cardiovascular disease worldwide in those under 25 years especially in the developing county like Bangladesh. RHD is caused by acute rheumatic fever (ARF) which typically results in cumulative valvular lesions that may present clinically after a number of years of sub-clinical disease. It has a progressive course and patients usually may require valve repair/replacement in future.

Feasibility and Safety of Distal Transradial Access in the Anatomical Snuffbox for Coronary Angiography and Intervention.

Distal transradial access in the anatomical snuffbox has advantages over standard proximal access in terms of patient and operator comfort levels and risk of ischemia. Radial artery preservation could be a relevant issue in patients requiring multiple radial artery procedures and coronary bypass with the use of a radial graft or construction of Arterio-Venous fistula in patient of chronic kidney disease. One relevant drawback is the challenging puncture of a small and weak artery, with a steeper learning curve.

Visceral Adiposity Index Score is the Better Predictor of Clinical and Coronary Angiographic Severity Assessment than Other Adiposity Indices in Patients with Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is one of the leading causes of death throughout the world and obesity especially visceral adiposity is one of the important concerns globally due to its huge impact on coronary artery disease particularly on ACS. There are several traditional methods like BMI, WC, WHR, WHtR etc. but none of these can measure visceral fat accurately.

Teaching Cardiopulmonary Resuscitation to Young Children (<12 Years Old).

Out-of-hospital cardiac arrest is a major public health concern. Research has shown that initiation of cardiopulmonary resuscitation (CPR) by lay bystanders increases survival rates. Evidence also shows that CPR training, delivered in various ways, is successful in a wide age range of children.

LC-MS/MS assay for quantitation of enalapril and enalaprilat in plasma for bioequivalence study in Indian subjects.

Background: Enalapril (EPL) is an angiotensin-converting enzyme inhibitor for the treatment of hypertension and chronic heart failure. Enalaprilat (EPLT) is an active metabolite that contributes to the overall activity of EPL.

Aim: To quantitate EPL along with its metabolite EPLT using LC-MS/MS, a bioanalytical method was developed and validated with tolbutamide in human plasma using a protein precipitation technique.

Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method.

A comparative pharmacokinetic study of a fixed dose combination for essential hypertensive patients: a randomized crossover study in healthy human volunteers.

Background: This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects.

Methods: The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days.

Mechanisms of DNA binding and regulation of Bacillus anthracis DNA primase.

DNA primases are pivotal enzymes in chromosomal DNA replication in all organisms. In this article, we report unique mechanistic characteristics of recombinant DNA primase from Bacillus anthracis. The mechanism of action of B.

Discovery, characterization and comparison of inhibitors of Bacillus anthracis and Staphylococcus aureus replicative DNA helicases.

Antibacterial compounds with new mechanisms of action are needed for effective therapy against drug-resistant pathogens in the clinic and in biodefense. Screens for inhibitors of the essential replicative helicases of Bacillus anthracis and Staphylococcus aureus yielded 18 confirmed hits (IC(50)25 microM). Several (5 of 18) of the inhibitors were also shown to inhibit DNA replication in permeabilized polA-deficient B.

An essential DnaB helicase of Bacillus anthracis: identification, characterization, and mechanism of action.

We have described a novel essential replicative DNA helicase from Bacillus anthracis, the identification of its gene, and the elucidation of its enzymatic characteristics. Anthrax DnaB helicase (DnaB(BA)) is a 453-amino-acid, 50-kDa polypeptide with ATPase and DNA helicase activities. DnaB(BA) displayed distinct enzymatic and kinetic properties.

Subunit interactions in the assembly of Saccharomyces cerevisiae DNA polymerase alpha.

Eukaryotic DNA polymerase (pol) alpha is a complex of four subunits. The subunits in the yeast Saccharomyces cerevisiae are: 167, 79, 62 and 48 kDa polypeptides. The p79 subunit has no known enzymatic functions, but it is essential for growth and chromosomal DNA replication.

Conformational dynamics of DnaB helicase upon DNA and nucleotide binding: analysis by intrinsic tryptophan fluorescence quenching.

DnaB helicase of E. coli unwinds duplex DNA in the replication fork using the energy of ATP hydrolysis. We have analyzed structural and conformational changes in the DnaB protein in various nucleotides and DNA bound intermediate states by fluorescence quenching analysis of intrinsic fluorescence of native tryptophan (Trp) residues in DnaB.

Affinity and sequence specificity of DNA binding and site selection for primer synthesis by Escherichia coli primase.

Primase is an essential DNA replication enzyme in Escherichia coli and responsible for primer synthesis during lagging strand DNA replication. Although the interaction of primase with single-stranded DNA plays an important role in primer RNA and Okazaki fragment synthesis, the mechanism of DNA binding and site selection for primer synthesis remains unknown. We have analyzed the energetics of DNA binding and the mechanism of site selection for the initiation of primer RNA synthesis on the lagging strand of the replication fork.

Modulation of enzymatic activities of Escherichia coli DnaB helicase by single-stranded DNA-binding proteins.

The modulation of enzymatic activities of Escherichia coli DnaB helicase by homologous and heterologous single-stranded DNA-binding proteins (SSBs) and its DNA substrates were analyzed. Although DnaB helicase can unwind a variety of DNA substrates possessing different fork-like structures, the rate of DNA unwinding was significantly diminished with substrates lacking a 3' fork. A 5 nt fork appeared to be adequate to attain the maximum rate of DNA unwinding.

Cell cycle specific plasmid DNA replication in the nuclear extract of Saccharomyces cerevisiae: modulation by replication protein A and proliferating cell nuclear antigen.

Plasmid DNA replication in nuclear extracts of Saccharomyces cerevisiae in vitro has been shown to be S-phase specific, similar to that observed in vivo. We report here a reconstituted in vitro system with partially purified replication proteins, purified replication protein A (RPA), and recombinant proliferating cell nuclear antigen (PCNA). Nuclear extracts from S-phase, G(1)-phase, and unsynchronized yeast cells were fractionated by phosphocellulose chromatography.

Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration.

The retina-specific human ABC transporter (ABCR) functions in the retinal transport system and has been implicated in several inherited visual diseases, including Stargardt disease, fundus flavimaculatus, cone-rod dystrophy, and age-related macular degeneration. We have previously described a general ribonucleotidase activity of the first nucleotide binding domain (NBD1) of human ABCR (Biswas, E. E.

Nucleotide binding domain 1 of the human retinal ABC transporter functions as a general ribonucleotidase.

Members of the ATP binding cassette (ABC) superfamily are transmembrane proteins that are found in a variety of tissues which transport substances across cell membranes in an energy-dependent manner. The retina-specific ABC protein (ABCR) has been linked through genetic studies to a number of inherited visual disorders, including Stargardt macular degeneration and age-related macular degeneration (ARMD). Like other ABC transporters, ABCR is characterized by two nucleotide binding domains and two transmembrane domains.

A novel human hexameric DNA helicase: expression, purification and characterization.

We have cloned, expressed and purified a hexameric human DNA helicase (hHcsA) from HeLa cells. Sequence analysis demonstrated that the hHcsA has strong sequence homology with DNA helicase genes from Saccharomyces cerevisiae and Caenorhabditis elegans, indicating that this gene appears to be well conserved from yeast to human. The hHcsA gene was cloned and expressed in Escherichia coli and purified to homogeneity.

The C-terminal nucleotide binding domain of the human retinal ABCR protein is an adenosine triphosphatase.

The rod outer segment ATP binding cassette (ABC) transporter protein (ABCR) plays an important role in retinal rod cells presumably transporting retinal. Genetic studies in humans have linked mutations in the ABCR gene to a number of inherited retinal diseases particularly Stargardt macular degeneration and age-related macular degeneration (ARMD). The ABCR protein is characterized by two nucleotide binding domains and two transmembrane domains, each consisting of six membrane-spanning helices.

Mechanism of DNA binding by the DnaB helicase of Escherichia coli: analysis of the roles of domain gamma in DNA binding.

We have analyzed the mechanism of single-stranded DNA (ssDNA) binding mediated by the C-terminal domain gamma of the DnaB helicase of Escherichia coli. Sequence analysis of this domain indicated a specific basic region, "RSRARR", and a leucine zipper motif that are likely involved in ssDNA binding. We have carried out deletion as well as in vitro mutagenesis of specific amino acid residues in this region in order to determine their function(s) in DNA binding.

Mechanism of DnaB helicase of Escherichia coli: structural domains involved in ATP hydrolysis, DNA binding, and oligomerization.

We describe the delineation of three distinct structural domains of the DnaB helicase of Escherichia coli: domain alpha, amino acid residues (aa) 1-156; domain beta, aa 157-302; and domain gamma, aa 303-471. Using mutants with deletion in these domains, we have examined their role(s) in hexamer formation, DNA-dependent ATPase, and DNA helicase activities. The mutant DnaBbetagamma protein, in which domain alpha was deleted, formed a hexamer; whereas the mutant DnaBalphabeta, in which domain gamma was deleted, could form only dimers.