Understanding biochemistry: structure and function of nucleic acids.

Nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), carry genetic information which is read in cells to make the RNA and proteins by which living things function. The well-known structure of the DNA double helix allows this information to be copied and passed on to the next generation. In this article we summarise the structure and function of nucleic acids.

Long-Acting Injectable versus Oral Antipsychotics for Restoration of Competency to Stand Trial.

Treatment with antipsychotics is a mainstay of trial competency restoration, particularly given that most defendants deemed incompetent to stand trial have psychotic illnesses. We explored the association between competency restoration and antipsychotic type in a retrospective sample of defendants diagnosed with psychotic disorders and deemed incompetent to stand trial. Using regression models, we calculated the odds ratio of being competent to stand trial, adjusting for relevant confounders.

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Today, the development of analytic methods brings new scientific insights into the research on the mummification process used by embalmers in ancient Egypt. The application of these techniques of molecular analysis, elementary analysis, botanical analysis and bibliographic analysis of ancient texts allows us to know the composition of mummification balms and material involved in the conservation of the body. Such substances, which are mineral, animal or plant material, played a practical and a symbolic part in the composition of balms used for the preservation of mummified bodies and therefore in the passage to the eternal life after the death.

Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or 'ecstasy' and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices.

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.

Tobacco smoking in schizophrenia: investigating the role of incentive salience.

Background: Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations.

Activating transcription in bacteria.

Bacteria use a variety of mechanisms to direct RNA polymerase to specific promoters in order to activate transcription in response to growth signals or environmental cues. Activation can be due to factors that interact at specific promoters, thereby increasing transcription directed by these promoters. We examine the range of architectures found at activator-dependent promoters and outline the mechanisms by which input from different factors is integrated.

Analysis of mechanisms of activation and repression at bacterial promoters.

In bacteria, the expression of transcription units is controlled by regulatory regions, that contain one or more promoters and binding sites for regulatory proteins that activate or repress expression in response to different signals. In this chapter, we explain the diverse approaches that can be used to understand the mechanisms by which the different factors intervene, and how the effects are integrated. Bioinformatics, genetics and biochemistry must be combined to understand the organisation of regulatory regions and the mechanisms by which transcription initiation is controlled.

Development of the GENIPOL European flounder (Platichthys flesus) microarray and determination of temporal transcriptional responses to cadmium at low dose.

We have constructed a high density, 13 270-clone cDNA array for the sentinel fish species European flounder (Platichthys flesus), combining clones from suppressive subtractive hybridization and a liver cDNA library; DNA sequences of 5211 clones were determined. Fish were treated by single intraperitoneal injection with 50 micrograms cadmium chloride per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and 16 days postinjection in comparison to saline-treated controls. Gene expression responses were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR).

Identification of the CRP regulon using in vitro and in vivo transcriptional profiling.

The Escherichia coli cyclic AMP receptor protein (CRP) is a global regulator that controls transcription initiation from more than 100 promoters by binding to a specific DNA sequence within cognate promoters. Many genes in the CRP regulon have been predicted simply based on the presence of DNA-binding sites within gene promoters. In this study, we have exploited a newly developed technique, run-off transcription/microarray analysis (ROMA) to define CRP-regulated promoters.

A DNA expression array to detect toxic stress response in European flounder (Platichthys flesus).

As a first stage in developing a DNA array-based approach to investigating the effects of pollutants on an environmentally relevant European fish species, we have constructed a 160-gene custom microarray for European flounder. Degenerate primers were used to amplify 110 different fragments of stress-related and other genes from European flounder cDNA and genomic DNA. Additionally, 22 fragments were obtained by suppressive subtractive hybridisation (SSH).

Identification and analysis of 'extended -10' promoters in Escherichia coli.

We have compiled and aligned the DNA sequences of 554 promoter regions from Escherichia coli and analysed the alignment for sequence similarities. We have focused on the similarities and differences between promoters that either do or do not contain an extended -10 element. The distribution of -10 and -35 hexamer element sequences, the range of spacer lengths between these elements and the frequencies of occurrence of different nucleotides, dinucleotides and trinucleotides were investigated.

Identification of functional regulatory regions of the connexin32 gene promoter.

Connexin32 (Cx32) is the predominant gap junction protein expressed in adult rat hepatocytes. This study investigated transcriptional regulation of the rat Cx32 gene in MH(1)C(1) rat hepatoma cells using transient expression assays in conjunction with promoter mutagenesis and 5' nested deletion analysis. Site-directed mutagenesis of the -736 and -187 hepatocyte nuclear factor-1 (HNF-1) sites, the -196 and -116 Sp1 sites, and the -729 and -329 Yin Yang 1 (YY1) sites all significantly reduced promoter activity.

Substitutions in the Escherichia coli RNA polymerase sigma70 factor that affect recognition of extended -10 elements at promoters.

Previous work has shown that the base sequence of the DNA segment immediately upstream of the -10 hexamer at bacterial promoters (the extended -10 element) can make a significant contribution to promoter strength. Guided by recently published structural information, we used alanine scanning and suppression mutagenesis of Region 2.4 and Region 3.

Characterisation of the connexin32 promoter and changes in response element complexes in rat liver and hepatocytes during culture associated with oxidative stress.

Hepatic gap junctional intercellular communication (GJIC), mediated principally by connexin 32, provides a mechanism for regulating multicellular activities between neighbouring cells. The control of Cx32 gene expression at the transcriptional level has been investigated in rat liver tissue and in primary rat hepatocytes during culture. Several response elements have been identified and characterised using the electrophoretic mobility shift assay.

Positioning of region 4 of the Escherichia coli RNA polymerase sigma(70) subunit by a transcription activator.

A DNA cleavage reagent, specifically tethered to residue 581 of the Escherichia coli RNA polymerase sigma(70) subunit, has been used to investigate the location of sigma(70) region 4 in different complexes at the galp(1) promoter and the effect of the cyclic AMP receptor protein. The positions of DNA cleavage by the reagent are not affected by the cyclic AMP receptor protein. We conclude that transcription activation at the galp(1) promoter by the cyclic AMP receptor protein does not involve major conformation changes in or repositioning of sigma(70) region 4.

DNA sequence elements located immediately upstream of the -10 hexamer in Escherichia coli promoters: a systematic study.

We have made a systematic study of how the activity of an Escherichia coli promoter is affected by the base sequence immediately upstream of the -10 hexamer. Starting with an activator-independent promoter, with a 17 bp spacing between the -10 and -35 hexamer elements, we constructed derivatives with all possible combinations of bases at positions -15 and -14. Promoter activity is greatest when the 'non-template' strand carries T and G at positions -15 and -14, respectively.

Open complex formation during transcription initiation at the Escherichia coli galP1 promoter: the role of the RNA polymerase alpha subunit at promoters lacking an UP-element.

We have studied the role of the C-terminal domain of the alpha subunit (alphaCTD) of Escherichia coli RNA polymerase during transcription initiation at promoters lacking an UP-element. The temperature requirement for open complex formation was used as an indication of the kinetics of this process. We have previously shown that alphaCTD is required for transcription initiation at low temperature at the galP1 promoter, a promoter containing an UP-element.

Organization of open complexes at Escherichia coli promoters. Location of promoter DNA sites close to region 2.5 of the sigma70 subunit of RNA polymerase.

A cysteine-tethered DNA cleavage agent has been used to locate the position of region 2.5 of sigma70 in transcriptionally competent complexes between Escherichia coli RNA polymerase and promoters. In this study we have engineered sigma70 to introduce a unique cysteine residue at a number of positions in region 2.

Region 2.5 of the Escherichia coli RNA polymerase sigma70 subunit is responsible for the recognition of the 'extended-10' motif at promoters.

At some bacterial promoters, a 5'-TG-3' sequence element, located one base upstream of the -10 hexamer element, provides an essential motif necessary for transcription initiation. We have identified a mutant of the Escherichia coli RNA polymerase sigma70 subunit that has an altered preference for base sequences in this 'extended -10' region. We show that this mutant sigma70 subunit substantially increases transcription from promoters bearing 5'-TC-3' or 5'-TT-3' instead of a 5'-TG-3' motif, located one base upstream of the -10 hexamer.

Identification and characterization of inositol 1,4,5-trisphosphate receptors in rat testis.

PCR analysis and immunoblotting with isoform specific antibodies was used to identify the presence of type I, II and III inositol 1,4,5-trisphosphate receptors (InsP3Rs) in rat testis. PCR analysis also revealed that rat testis express both forms of the S1 splice variant (S1+ and S1-), but only the S2- from of the S2 splice variant of the type I InsP3 receptor. PCR analysis was also used to identify InsP3R isoform expression at a cellular level using myoid, Sertoli and germ cells derived from the testis of Wistar rats.

Temperature-dependence of open-complex formation at two Escherichia coli promoters with extended -10 sequences.

We have studied the formation of open complexes between purified RNA polymerase from Escherichia coli and DNA fragments carrying the galP1 promoter, a promoter with an extended -10 region. Unusually, these complexes are formed readily at low temperatures. This low-temperature opening is unaffected by deletions of either upstream or downstream promoter sequences.

Overexpression of human cardiac troponin-I and troponin-C in Escherichia coli and their purification and characterisation. Two point mutations allow high-level expression of troponin-I.

We have overexpressed human cardiac troponin-I in Escherichia coli. Initially, protein expression was not detected in the bacterial cell extracts. Systematic deletion of the N-terminal region of the protein generated a series of truncated mutants which were expressed at varying levels in the bacteria.

Thermal energy requirement for strand separation during transcription initiation: the effect of supercoiling and extended protein DNA contacts.

We have studied the role of extended protein DNA contacts and DNA topology on the ability of Escherichia coli RNA polymerase to form open complexes at several related promoters. The -35 region of several Escherichia coli promoters do not have homology with the consensus sequence, but still drive activator independent transcription initiation. This is due to the presence of a TG motif upstream from the -10 hexamer creating an 'extended -10' promoter.

Assaults by patients on psychiatric residents at three training sites.

Objective: This study attempted to determine how often psychiatric residents are exposed to violence, the types of violence they encounter, and what institutional changes might increase their safety.

Methods: Safety conditions at two private general hospitals and one state hospital that served as training sites for a psychiatric residency program were assessed through a survey of psychiatric residents and site visits to the hospitals. The survey asked residents to quantify violent incidents occurring in the emergency rooms, wards, and clinics at each site.