Ring 2 chromosome associated with failure to thrive,microcephaly and dysmorphic facial features

We report here a child with a ring chromosome 2 [r(2)] associated with failure to thrive, microcephaly and dysmorphic features. The chromosomal aberration was defined by chromosome microarray analysis, revealing two small deletions of 2p25.3 (139 kb) and 2q37.3 (147 kb).     

Isolation and Characterization of S-Adenosylmethionine-requiring Mutants and Role of S-Adenosylmethionine in the Regulation of Methionine Biosynthesis in Corynebacterium glutamicum

Using a minimal medium containing a methionine analog together with a small amount of S-adenosylmethionine (SAM), many SAM requiring mutants which responded only to SAM and not to methionine, S-adenosylhomocysteine, or homocysteine were efficiently isolated from Corynebacterium glutamicum TLD-140 after mutagenesis. Among them, SAM-14 and SAM-19 selected from selenomethionine resistant mutants were subjected to further investigation. Both mutants were unable to grow in a minimal medium and had no detectable activity of SAM synthetase. Both mutants acquired higher resistance to methionine hydroxamate and ethionine as well as to selenomethionine than TLD-140 and produced l-methionine in a medium.

Homoserine-O-transacetylase in SAM-19 was subject to full repression by the addition of excess SAM to the growth medium and was not repressed under SAM limitation, whereas addition of excess l-methionine under SAM limitation caused a partial repression of the enzyme. SAM synthetase as well as l-methionine biosynthetic enzymes in a methionine auxotroph of C. glutamicum was repressed by the addition of l-methionine to the growth medium.

These results suggest that SAM is implicated in the repression of l-methionine synthesizing enzymes in C. glutamicum.     

Skiing efficiency versus performance in double-poling ergometry

This study is on how leg utilisation may affect skiing efficiency and performance in double-poling ergometry. Three experiments were conducted, each with a different style of the double-poling technique: traditional with small knee range-of-motion and fixed heels (TRAD); modern with large knee range-of-motion and fixed heels (MOD1) and modern with large knee range-of-motion and free heels (MOD2). For each style, motion data were extracted with automatic marker recognition of reflective markers and applied to a 3D full-body musculoskeletal simulation model. Skiing efficiency (skiing work divided by metabolic muscle work) and performance (forward impulse) were computed from the simulation output. Skiing efficiency was 4.5%, 4.1% and 4.1% for TRAD, MOD1 and MOD2, respectively. Performance was 111, 143 and 149 Ns for TRAD, MOD1 and MOD2, respectively. Thus, higher lower body utilisation increased the performance but decreased the skiing efficiency. These results demonstrate the potential of musculoskeletal simulations for skiing efficiency estimations.     

Structural equation modelling analysis of evolutionary and ecological patterns in Australian Banksia

Evolutionary history of species, their geographic ranges, ecological ranges, genetic diversity, and resistance to pathogen infection, have been viewed as being mutually linked through a complex network of interactions. Previous studies have described simple correlations between pairs of these factors, while rarely separated the direct effects among multiple interacting factors. This study was to separate the effect of multiple interacting factors, to reveal the strength of the interactions among these factors, and to explore the mechanisms underlying the ecological and evolutionary processes shaping the geographic range, genetic diversity and fitness of species. I assembled comparative data on evolutionary history, geographic range, ecological range, genetic diversity, and resistance to pathogen infection for thirteen Banksia species from Australia. I used structural equation modelling to test multivariate hypotheses involving evolutionary history, geographic range, genetic diversity and fitness. Key results are: (1) Species with longer evolutionary times tend to occupy larger geographic ranges; (2) higher genetic diversity is directly associated with longer flowering duration in Banksia; and (3) species with higher genotypic diversity have higher level of resistance to infection caused by the pathogen Phytophthora cinnamomi, whereas heterozygosity has the opposite relationship with capacity of resistance to the infections caused by this pathogen. These results revealed a mutually linked and complex network of interactions among gene, species, environment and pathogen in evolutionary and ecological scales. These findings also have great practical significance and help to provide preemptive management options in pathogen control.     

Semichronic Inhibition of Glutathione Reductase Promotes Oxidative Damage to Proteins and Induces both Transcription and Translation of Tyrosine Hydroxylase in the Nigrostriatal System

We have evaluated the effect of N,N-bis (2-chloroethyl)-N-nitrosourea (BCNU), an inhibitor of glutathione reductase (GR), on the oxidative status along with the integrity of the nigrostriatal dopaminergic system of the rat. The oxidative status was studied by the quantification of carbonyl groups coupled to protein homogenates. Moreover, the specific oxidations in glial fibrillary acidic protein (GFAP) and neurofilament-200 (NF-200) were also measured. The results show that oxidative damage in proteins in the nigrostriatal system is confined to the striatum. Specific carbonyl groups coupled to native NF-200 and GFAP were also increased. These changes were accompanied by reactive astrocytosis in striatum but not in substantia nigra. In substantia nigra, decreased levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were observed following BCNU treatment. In contrast, DA levels were increased in the striatum along with an overall decrease in the ratios of DA metabolites to DA. We also studied the mRNA levels for tyrosine hydroxylase (TH) and the dopamine transporter (DAT) by in situ hybridization. TH mRNA but not DAT mRNA was significantly induced in substantia nigra following BCNU treatment, which was consistent with significant elevations in TH enzyme amount and activity and unchanged DA uptake in striatum. All these results support the DA free radical hypothesis and the key role of the striatal glutathione system in protecting the striatal system against oxidative stress.     

Oxidative Stress in Erythrocytes from Premature and Full-term Infants During their First 72 h of Life

Objective : The aim of this study was to evaluate the extent of lipid peroxidation and the response of the enzymatic and non-enzymatic antioxidant defence system in erythrocytes from full-term and premature infants at birth, after 3 and after 72 h of life. Study design: Twenty infants were selected and divided in two groups according to their gestational age. Blood samples were taken at birth, at 3 and at 72 h of life, erythrocytes were isolated and the following parameters were measured: fatty-acid profile, coenzyme Q, &#102 -tocopherol, hydroperoxides and the activity of the antioxidant enzymes catalase, superoxide dismutase (SOD) and cytosolic glutathione peroxidase (cGPx). Results: For the three studied periods, several differences between full-term and premature infants were found. Premature children showed a higher concentration of hydroperoxides, a lower level of &#102 -tocopherol and lower SOD and cGPx activity (except for cGPx at birth). Moreover, n-3 polyunsaturated fatty-acids percentages (essential for good neonatal development) were higher in full term children throughout all the study. Conclusion: Results suggest a strong imbalance between oxidants and antioxidants in premature infants during their first 72 h of life, a situation which could lead to several pathologies. Therefore, further research is needed, including possible nutritional intervention (with antioxidant therapy, supplementation of essential fatty acids and other dietary constituents) before and after birth.     

Two-intermediate model to characterize the structure of fast-folding proteins

This paper introduces a new model that enables researchers to conduct protein folding simulations. A two-step in silico process is used in the course of structural analysis of a set of fast-folding proteins. The model assumes an early stage (ES) that depends solely on the backbone conformation, as described by its geometrical properties—specifically, by the V-angle between two sequential peptide bond planes (which determines the radius of curvature, also called R-radius, according to a second-degree polynomial form). The agreement between the structure under consideration and the assumed model is measured in terms of the magnitude of dispersion of both parameters with respect to idealized values. The second step, called late-stage folding (LS), is based on the “fuzzy oil drop” model, which involves an external hydrophobic force field described by a three-dimensional Gauss function. The degree of conformance between the structure under consideration and its idealized model is expressed quantitatively by means of the Kullback-Leibler entropy, which is a measure of disparity between the observed and expected hydrophobicity distributions. A set of proteins, representative of the fast-folding group - specifically, cold shock proteins - is shown to agree with the proposed model.     

Relationship between progesterone, oestrone sulphate and cortisol and the components of renin angiotensin aldosterone system in Spanish purebred broodmares during pregnancy

The coordinated interaction of the components of the renin angiotensin aldosterone system (RAAS) with reproductive hormones such as progesterone, oestrogens and cortisol during pregnancy has been widely reported to play a vital role in foetal and placental development in various species, significantly influencing the proper achievement of pregnancy and foetal viability at birth. These interactions have not yet been clarified in mares. Thus, the purpose of the present research was to analyse the relationship between cortisol (CORT), progesterone (P4) and oestrone sulphate (OESTRONE), and the components of the RAAS, renin (REN), angiotensin II (ANG-II) and aldosterone (ALD) concentrations in Spanish broodmares during pregnancy.Venous blood samples were obtained monthly from a total of 31 Purebred Spanish broodmares aged between 5 and 15 years during the 11 months of pregnancy. Plasma and serum REN, ANG-II, ALD, P4, OESTRONE and CORT concentrations were analysed by competitive immunoassay. Pregnancy in Purebred Spanish broodmares is characterised by a progressive increase in REN and ALD, a decrease in CORT levels, variable fluctuations in P4 and OESTRONE and no variations in ANG-II concentrations (P < 0.05). Serum P4 was not correlated with either ALD or CORT. The OESTRONE and REN levels were not correlated, while OESTRONE and ALD showed a positive correlation (r = 0.16; P < 0.05). These results suggest that the sustained stimulation of the RAAS in normal pregnancy in Spanish broodmares is not totally dependent on the changes in P4 and CORT concentrations, despite the involvement of OESTRONE in the secretion of ALD. This brings into question the possible involvement of oestrogen in the secretion of ALD by a mechanism which is not exclusively dependent on REN. Consequently, at physiological levels, OESTRONE is not the only stimulus for REN synthesis, and the mineralocorticoids ALD and CORT do not show a competitive mechanism with P4 during pregnancy in mares. Other mechanisms which do not depend on these hormones should be considered in the modification of the RAAS during pregnancy in Spanish mares.