Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation

Mutations in the coding region of the angiotensin II type 2 receptor gene (AGTR2) were recently identified to cause X-linked recessive mental retardation. We report a mutation screening of the AGTR2 gene in 57 Finnish male patients with non-syndromic mental retardation. We identified two mutations, a 62GT transversion, which leads to a substitution of glycine for valine (G21V) and a 157AT transversion, which causes a substitution of isoleucine for phenylalanine (I53F). The patients with AGTR2 sequence variants had severe/profound mental retardation, epileptic seizures, restlessness, hyperactivity, and disturbed development of speech.     

The role of MatP,ZapA and ZapB in chromosomal organization and dynamics in Escherichia coli

Despite extensive research over several decades, a comprehensive view of how the Escherichia coli chromosome is organized within the nucleoid, and how two daughter chromosomes segregate has yet to emerge. Here we investigate the role of the MatP, ZapA and ZapB proteins in organizing the replication terminus (Ter) region and in the chromosomal segregation process. Quantitative image analysis of the fluorescently labeled Ter region shows that the replication terminus attaches to the divisome in a single segment along the perimeter of the cell in a MatP, ZapA and ZapB-dependent manner. The attachment does not significantly affect the bulk chromosome segregation in slow growth conditions. With or without the attachment, two chromosomal masses separate from each other at a speed comparable to the cell growth. The separation starts even before the replication terminus region positions itself at the center of the nucleoid. Modeling of the segregation based on conformational entropy correctly predicts the positioning of the replication terminus region within the nucleoid. However, the model produces a distinctly different chromosomal density distribution than the experiment, indicating that the conformational entropy plays a limited role in segregating the chromosomes in the late stages of replication.     

Integral membrane protein P16 of bacteriophage PRD1 stabilizes the adsorption vertex structure

The icosahedral membrane-containing double-stranded DNA bacteriophage PRD1 has a labile receptor binding spike complex at the vertices. This complex, which is analogous to that of adenovirus, is formed of the penton protein P31, the spike protein P5, and the receptor binding protein P2. Upon infection, the internal phage membrane transforms into a tubular structure that protrudes through a vertex and penetrates the cell envelope for DNA injection. We describe here a new class of PRD1 mutants lacking virion-associated integral membrane protein P16. P16 links the spike complex to the viral membrane and is necessary for spike stability. We also show that the unique vertex used for DNA packaging is intact in the P16-deficient particle, indicating that the 11 adsorption vertices and the 1 portal vertex are functionally and structurally distinct.     

Work Disability among Employees with Diabetes: Latent Class Analysis of Risk Factors in Three Prospective Cohort Studies

Background

Studies of work disability in diabetes have examined diabetes as a homogeneous disease. We sought to identify subgroups among persons with diabetes based on potential risk factors for work disability.

Methods

Participants were 2,445 employees with diabetes from three prospective cohorts (the Finnish Public Sector study, the GAZEL study, and the Whitehall II study). Work disability was ascertained via linkage to registers of sickness absence and disability pensions during a follow-up of 4 years. Study-specific latent class analysis was used to identify subgroups according to prevalent comorbid disease and health-risk behaviours. Study-specific associations with work disability at follow-up were pooled using fixed-effects meta-analysis.

Results

Separate latent class analyses for men and women in each cohort supported a two-class solution with one subgroup (total n = 1,086; 44.4%) having high prevalence of chronic somatic diseases, psychological symptoms, obesity, physical inactivity and abstinence from alcohol and the other subgroup (total n = 1,359; 55.6%) low prevalence of these factors. In the adjusted meta-analyses, participants in the ‘high-risk’ group had more work disability days (pooled rate ratio = 1.66, 95% CI 1.38–1.99) and more work disability episodes (pooled rate ratio = 1.33, 95% CI 1.21–1.46). These associations were similar in men and women, younger and older participants, and across occupational groups.

Conclusions

Diabetes is not a homogeneous disease in terms of work disability risk. Approximately half of people with diabetes are assigned to a subgroup characterised by clustering of comorbid health conditions, obesity, physical inactivity, abstinence of alcohol, and associated high risk of work disability; the other half to a subgroup characterised by a more favourable risk profile.     

Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic PGE2

Two modes of cervical application of a gel containing PGE₂ have been compared in a total of 30 patients with indication for induction of labor and unripe cervix. Fifteen patients had gel injected endocervically; in 10 patients the gel contained 400μg PGE₂, in 5 controls the gel was inactive. Fifteen subjects had a 15 ml Foley catheter passed through the cervix and placed extra-amniotically; in 10 of them 3 ml gel with 400 or 800μg PGE₂ was injected, while 5 controls received inactive gel. Plasma levels of 13,14-dihydro-15-keto-PGF_2α (PGFM) were measured in blood samples drawn before and , 1, 2, 4, 6, and 8 hours after gel application. Neither the Foley catheter nor the application of inactive gel caused significant changes in the cervical scores or the PGFM levels. PGE₂ in the endocervix increased cervical scores without altering plasma PGFM levels. Extra-amniotic PGE₂ caused a more rapid increase of the cervical scores and a progressive rise in PGFM levels. The plasma (PGFM) levels were found to be related to the degree and to the rate of cervical dilatation. The correlation with cervical dilatation was highly significant. Labor began spontaneously or after artificial rupture of the membranes in 80% of the extra-amniotic, and 50% of the endocervical PGE₂-group, but in none of the controls. These data indicate that the increased uterine PGF_2α production is not necessary for the early stages of cervical ripening, whereas dilatation beyond 4 cm does not proceed without such increase.     

Phase and glass transition behaviour of concentrated barley starch-glycerol-water mixtures, a model for thermoplastic starch

The effects of glycerol and water content on the thermal transitions of plasticized barley starch were examined using differential scanning calorimetry. The glycerol contents studied were 14, 20, 29 and 39% and the water content, obtained by conditioning in different relative humidities, varied in the range 1–28%. On the basis of the observed calorimetric glass transition temperatures and corresponding heat capacity increments it was inferred that a single phase system occurred at low water and glycerol contents, while in other cases phase separation occurred and the system was composed of starch-rich and starch-poor phases. Dynamic mechanical thermal analysis on a phase-separated sample showed mechanical loss peaks corresponding to the glass transitions of both phases. Amylopectin crystallization did not occur within 1 week of storage in mixtures having less than 20% water, indicating that glycerol interacted with starch, inhibiting crystallization of amylopectin.     

Oscillating Ca2+-Induced Channel Activity Obtained in BLM with a Mitochondrial Membrane Component

Oscillations in ion fluxes and membrane potential may be observed in cells and in mitochondria as well. We obtained Ca²⁺-induced oscillations in channel activity in black-lipid membranes reconstituted with hydrophobic components extracted from mitochondria. Mitoplasts prepared from purified rat liver mitochondria were extracted with ethanol followed by Folch extraction and further partial purification by silicic acid chromatography. Channel activity was measured in lipid bilayers formed from bovine brain lipids and 10% cardiolipin with addition of the purified tractions. The conductance with 10 mM Ca²⁺ was 100 pS or its multiples. Ca²⁺ gradients of 4 : 1 induced oscillating channel activity for several hours, with initial open states of 40 s and closed states of 56 s; the open times gradually decreasing to 8.6 s. No channel activity was seen without added fractions. The channel activity was associated with a Ca²⁺-binding lipid, nonpolar, low-molecular-weight fraction that in gel electrophoresis was not stained with Coomassie Blue and did not contain carbohydrate-staining material. ¹H-Nuclear magnetic resonance spectra of the substance showed the presence of aliphatic chains and carbonyls, but the detailed structure remains to be elucidated.     

Dynamics of a Laterally Evolving Community of Ribozyme-Like Agents as Studied with a Rule-Based Computing System

The very early forms of life probably comprised ribozyme-like agents that were able to catalyze reactions and serve as templates for their own replication. The early evolution has also been suggested to occur mainly horizontally between proto-cells or inorganic compartments rather than vertically from parent cell to their dividing siblings. In order to study the evolutionary dynamics of such a community a rule-based computing system entitled as PrimordialEvo was developed. The system simulates a three dimensional matrix of compartments in which replicators, resource collectors and various other actors thrive. Horizontal movement between compartments may be due to genetically induced vesicle formation or random drift. Analysis of the simulation experiments suggests that active sharing of innovations between compartments is important for the overall reproductive success of life. The capability of natural selection to favor genes in the system was also tested, and, for example, the frequency of anti-parasites was observed to increase when parasites were allowed to emerge.