Performance of protein stability predictors.

Stability is a fundamental property affecting function, activity, and regulation of biomolecules. Stability changes are often found for mutated proteins involved in diseases. Stability predictors computationally predict protein-stability changes caused by mutations.

Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA/DNA hybrid.

We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mitochondrial DNA replication intermediates are essentially duplex throughout their length but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mitochondrial DNA replication involving RNA incorporation throughout the lagging strand.

Structural and functional characteristics of xenavidin, the first frog avidin from Xenopus tropicalis.

Background: Avidins are proteins with extraordinarily high ligand-binding affinity, a property which is used in a wide array of life science applications. Even though useful for biotechnology and nanotechnology, the biological function of avidins is not fully understood. Here we structurally and functionally characterise a novel avidin named xenavidin, which is to our knowledge the first reported avidin from a frog.

Phenotypic suppression of the Drosophila mitochondrial disease-like mutant tko(25t) by duplication of the mutant gene in its natural chromosomal context.

A mutation in the Drosophila gene technical knockout (tko(25t)), encoding mitoribosomal protein S12, phenocopies human mitochondrial disease. We isolated three spontaneous X-dominant suppressors of tko(25t) (designated Weeble), exhibiting almost wild-type phenotype and containing overlapping segmental duplications including the mutant allele, plus a second mitoribosomal protein gene, mRpL14. Ectopic, expressed copies of tko(25t) and mRpL14 conferred no phenotypic suppression.

Variation in use and costs of primary health and social services in mental health or drinking problems.

Background: Psychiatric inpatient hospital care was cut dramatically in Finland in recent last decades, and patients were assigned to care in the community. Consequently, the burden of care shifted from hospital districts to municipalities, which have considerable autonomy in organizing health and social services. These changes probably created locally differing service patterns in mental health care.

Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up.

Objective: To evaluate whether hematocrit (HCT) is associated with coronary heart disease (CHD) mortality in men over 55 years of age in Finland.

Methods: Health survey data were recorded in 1980 from 670 men, aged 55 years. The causes of deaths during a 28-year follow-up were obtained from official records.

Pathogenic or not? And if so, then how? Studying the effects of missense mutations using bioinformatics methods.

Many gene defects are relatively easy to identify experimentally, but obtaining information about the effects of sequence variations and elucidation of the detailed molecular mechanisms of genetic diseases will be among the next major efforts in mutation research. Amino acid substitutions may have diverse effects on protein structure and function; thus, a detailed analysis of the mutations is essential. Experimental study of the molecular effects of mutations is laborious, whereas useful and reliable information about the effects of amino acid substitutions can readily be obtained by theoretical methods.

Phylogeny of Tec family kinases identification of a premetazoan origin of Btk, Bmx, Itk, Tec, Txk, and the Btk regulator SH3BP5.

It is generally considered mammals and birds have five Tec family kinases (TFKs): Btk, Bmx (also known as Etk), Itk, Tec, and Txk (also known as Rlk). Here, we discuss the domains and their functions and regulation in TFKs. Over the last few years, a large number of genomes from various phyla have been sequenced making it possible to study evolutionary relationships at the molecular and sequence level.

Immunome knowledge base (IKB): an integrated service for immunome research.

Background: Functioning of the immune system requires the coordinated expression and action of many genes and proteins. With the emergence of high-throughput technologies, a great amount of molecular data is available for the genes and proteins of the immune system. However, these data are scattered into several databases and literature and therefore integration is needed.

Identification of candidate disease genes by integrating Gene Ontologies and protein-interaction networks: case study of primary immunodeficiencies.

Disease gene identification is still a challenge despite modern high-throughput methods. Many diseases are very rare or lethal and thus cannot be investigated with traditional methods. Several in silico methods have been developed but they have some limitations.

Androgen regulation of the androgen receptor coregulators.

Background: The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer.

Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.

Machine learning method for knowledge discovery experimented with otoneurological data.

We have been interested in developing an otoneurological decision support system that supports diagnostics of vertigo diseases. In this study, we concentrate on testing its inference mechanism and knowledge discovery method. Knowledge is presented as patterns of classes.

Bradavidin II from Bradyrhizobium japonicum: a new avidin-like biotin-binding protein.

A gene encoding an avidin-like protein was discovered in the genome of B. japonicum. The gene was cloned to an expression vector and a protein, named bradavidin II, was produced in E.

Efficiency of the immunome protein interaction network increases during evolution.

Background: Details of the mechanisms and selection pressures that shape the emergence and development of complex biological systems, such as the human immune system, are poorly understood. A recent definition of a reference set of proteins essential for the human immunome, combined with information about protein interaction networks for these proteins, facilitates evolutionary study of this biological machinery.

Results: Here, we present a detailed study of the development of the immunome protein interaction network during eight evolutionary steps from Bilateria ancestors to human.

Cancer screening: evidence and practice in Europe 2008.

We examine the theoretical basis of screening, followed by an evaluation of screening initiatives from a population health perspective and a discussion of the organisation of mass screening programmes. Evidence for the effectiveness of screening by primary site from both randomised trials and evaluation of service screening is summarised and the existing cancer screening programmes in the European Union are described. Sufficient evidence from several randomised trials to demonstrate mortality reduction exists for breast cancer and colorectal cancer screening.

Physicochemical feature-based classification of amino acid mutations.

A huge quantity of gene and protein sequences have become available during the post-genomic era, and information about genetic variations, including amino acid substitutions and SNPs, is accumulating rapidly. To understand the effects of these changes, it is often essential to apply bioinformatics tools. Where there is a lack of homologous sequences or a three-dimensional structure, it becomes essential to predict the effects of mutations based solely on protein sequence information.

Identification of differentially expressed genes after PPM1D silencing in breast cancer.

Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent 1 delta) has been observed in various cancer cell lines and primary tumors and has also been associated with cancers of poor prognosis. In addition to the negative feedback regulation of p38-p53 signaling, PPM1D inhibits other tumor suppressor activities and is involved in the control of DNA damage and repair pathways. To elucidate the functional significance of PPM1D in breast cancer, we employed RNA interference to downregulate PPM1D expression in BT-474, MCF7, and ZR-75-1 breast cancer cell lines and then investigated the effects of PPM1D silencing on global gene expression patterns and signaling pathways using oligonucleotide microarrays.

Spectrum of disease-causing mutations in protein secondary structures.

Background: Most genetic disorders are linked to missense mutations as even minor changes in the size or properties of an amino acid can alter or prevent the function of the protein. Further, the effect of a mutation is also dependent on the sequence and structure context of the alteration.

Results: We investigated the spectrum of disease-causing missense mutations in secondary structure elements in proteins with numerous known mutations and for which an experimentally defined three-dimensional structure is available.

Coronary reactivity, homocysteine and methylenetetrahydrofolate reductase gene variation in young men during pravastatin therapy.

High plasma homocysteine (Hcy) has been linked to impaired endothelial function. We investigated whether treatment with pravastatin affects the Hcy levels. Moreover, we studied whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism affects coronary vasomotion at baseline and during the treatment with pravastatin.

Angiosarcoma after radiotherapy: a cohort study of 332,163 Finnish cancer patients.

We evaluated the risk of angiosarcoma after radiotherapy among all patients with cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, or rectum, and lymphoma diagnosed in Finland during 1953-2003, identified from the Finnish Cancer Registry. Only angiosarcomas of the trunk were considered, this being the target of radiotherapy for the first cancer. In the follow-up of 1.

Immunome: a reference set of genes and proteins for systems biology of the human immune system.

The function of the immune system requires coordinated expression and action of many genes and proteins. With the emergence of high throughput technologies it has become possible to target human immunity from a systems biology point of view. To perform systems biology studies with comparable results we need not just a reference gene and protein set but also useful and descriptive reference categories for the immunity related genes.

IDR knowledge base for primary immunodeficiencies.

Background: The ImmunoDeficiency Resource (IDR) is a knowledge base for the integration of the clinical, biochemical, genetic, genomic, proteomic, structural, and computational data of primary immunodeficiencies. The need for the IDR arises from the lack of structured and systematic information about primary immunodeficiencies on the Internet, and from the lack of a common platform which enables doctors, researchers, students, nurses and patients to find out validated information about these diseases.

Description: The IDR knowledge base, first released in 1999, has grown substantially.

ImmTree: database of evolutionary relationships of genes and proteins in the human immune system.

Background: The immune system, which is a complex machinery, is based on the highly coordinated expression of a wide array of genes and proteins. The evolutionary history of the human immune system is not well characterised. Although several studies related to the development and evolution of immunological processes have been published, a full-scale genome-based analysis is still missing.

The role of job satisfaction, job dissatisfaction and demographic factors on physicians' intentions to switch work sector from public to private.

This study is based on a unique data set for the years 1988-2003 and uses structural equation models to examine the impact of job satisfaction and job dissatisfaction on physicians' intention to switch from public- to private-sector work. In Finland, physicians who work primarily in a public-hospital or health-centre setting can also run a private practice. Therefore, we also analysed the impact of having a private practice on a physician's intention to change sector.