Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders

Introduction

Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD.

Methods

In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3–15) with ASD is investigated. Given well documented differences in parent and trained examiners ratings of symptom severity, we employed a standardized parent`s questionnaire (Nisonger Child Behavior Rating Form) as well as a direct examiner`s rating (Autism diagnostic observation schedule) for assessment of hyperactivity symptoms.

Results

Although it was found there was no significant association between actual plasmatic testosterone levels and hyperactivity symptoms, the number of CAG triplets was significantly negatively correlated with hyperactivity symptoms (R² = 0.118, p = 0.007) in the sample, indicating increased androgen receptor sensitivity in association with hyperactivity symptoms. Direct trained examiner´s assessment appeared to be a relevant method for evaluating of behavioral problems in the investigation of biological underpinnings of these problems in our study.

Conclusions

A potential ASD subtype characterized by increased rates of hyperactivity symptoms might have distinct etiopathogenesis and require a specific behavioral and pharmacological approach. We propose an increase of androgen receptor sensitivity as a biomarker for a specific ASD subtype accompanied with hyperactivity symptoms. Findings are discussed in terms of their implications for practice and future research.     

Digalactosyl-diacylglycerol deficiency impairs the capacity for photosynthetic intersystem electron transport and state transitions in Arabidopsis thaliana due to photosystem I acceptor-side limitations

Compared with wild type, the dgd1 mutant of Arabidopsis thaliana exhibited a lower amount of PSI-related Chl-protein complexes and lower abundance of the PSI-associated polypeptides, PsaA, PsaB, PsaC, PsaL and PsaH, with no changes in the levels of Lhca1-4. Functionally, the dgd1 mutant exhibited a significantly lower light-dependent, steady-state oxidation level of P700 (P700(+)) in vivo, a higher intersystem electron pool size, restricted linear electron transport and a higher rate of reduction of P700(+) in the dark, indicating an increased capacity for PSI cyclic electron transfer compared with the wild type. Concomitantly, the dgd1 mutant exhibited a higher sensitivity to and incomplete recovery of photoinhibition of PSI. Furthermore, dgd1 exhibited a lower capacity to undergo state transitions compared with the wild type, which was associated with a higher reduction state of the plastoquinone (PQ) pool. We conclude that digalactosyl-diacylglycerol (DGDG) deficiency results in PSI acceptor-side limitations that alter the flux of electrons through the photosynthetic electron chain and impair the regulation of distribution of excitation energy between the photosystems. These results are discussed in terms of thylakoid membrane domain reorganization in response to DGDG deficiency in A. thaliana.     

Mitochondrial Porin Por1 and Its Homolog Por2 Contribute to the Positive Control of Snf1 Protein Kinase in Saccharomyces cerevisiae

Saccharomyces cerevisiae Snf1 is a member of the conserved Snf1/AMP-activated protein kinase (Snf1/AMPK) family involved in regulating responses to energy limitation, which is detected by mechanisms that include sensing adenine nucleotides. Mitochondrial voltage-dependent anion channel (VDAC) proteins, also known as mitochondrial porins, are conserved in eukaryotes from yeast to humans and play key roles in mediating mitochondrial outer membrane permeability to small metabolites, including ATP, ADP, and AMP. We previously recovered the yeast mitochondrial porin Por1 (yVDAC1) from a two-hybrid screen for Snf1-interacting proteins. Here, we present evidence that Snf1 interacts with Por1 and its homolog Por2 (yVDAC2). Cells lacking Por1 and Por2, but not respiratory-deficient rho⁰ cells lacking the mitochondrial genome, exhibit reduced Snf1 activation loop phosphorylation in response to glucose limitation. Thus, Por1 and Por2 contribute to the positive control of Snf1 protein kinase. Physical proximity to the VDAC proteins and mitochondrial surface could facilitate Snf1''s ability to sense energy limitation.     

Temperature-induced greening of<Emphasis Type="Italic"> Chlorella vulgaris</Emphasis>. The role of the cellular energy balance and zeaxanthin-dependent nonphotochemical quenching

When cells of the green alga Chlorella vulgaris Beij. are transferred from growth at 5 degrees C and an irradiance of 150 micromol photons m(-2) s(-1) to 27 degrees C and the same irradiance, they undergo what is normally considered a high-light to low-light phenotypic change. This involves a 3-fold increase in cellular chlorophyll content with a concomitant increase in light-harvesting complex polypeptide levels. This process appears to occur in response to the cellular capacity to utilize the products of photosynthesis, with the redox state of the plastoquinone pool sensing the cellular energy balance. The phenotypic adjustment can be enhanced or blocked using chemical inhibitors that modulate the redox state of the plastoquinone pool. The functional changes in the photosynthetic apparatus that occurred during the high-light to low-light acclimation were examined with special consideration paid to the paradox that 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-treated cells, with non-functional photosystem II (PSII), accumulate light-harvesting polypeptides. At the structural and basic functional levels, the light-harvesting complex of the cells treated with DCMU was indistinguishable from that of the untreated, control cells. To examine how PSII was protected in the DCMU-treated cells, we measured the content of xanthophyll-cycle pigments. It appeared that a zeaxanthin-dependent nonphotochemical quenching process was involved in PSII protection during greening in the presence of DCMU. Metabolic inhibitors of mitochondrial respiration were used to examine how the change in cellular energy balance regulates the greening process. Apparently, the mitochondrion acts to supply energy to the chloroplast during greening, and inhibition of mitochondrial respiration diminishes chlorophyll accumulation apparently through an increase in the redox state of the plastoquinone pool.     

Urban Sheep Keeping in West Africa: Can Socioeconomic Household Profiles Explain Management and Productivity?

Rapid urbanization in Africa leads to a spatial concentration of people with different cultural origins and socioeconomic backgrounds resulting in a great diversity of life styles and livelihood strategies. One common strategy in Maroua/Cameroon and Bobo-Dioulasso/Burkina Faso is urban sheep keeping. Cluster analyses identified distinct socioeconomic groups with similarities between the towns: traditional livestock keepers, households headed by well educated government employees or traders, and more vulnerable groups formed of households headed by females, retired people or people with limited formal education. The household types in Bobo varied in their perception of the importance and the development of urban sheep keeping and their future plans. Those in Maroua differed in management intensity and in the potential to adapt their practices to the urban environment. Development interventions to reduce environmental pollution and risks for human health associated with urban sheep keeping need to account for these differences in the target group.     

Co-expression of human ABCG5 and ABCG8 in insect cells generates an androstan stimulated membrane ATPase activity

Mutations in the ATP-binding cassette (ABC) proteins ABCG5 or ABCG8 cause sitosterolemia, a condition with increased accumulation of plant sterols. Upon high level expression of the ABCG5 and ABCG8 proteins in baculovirus-Sf9 cell expression system we found a distinct, vanadate sensitive ATPase activity in isolated membrane preparations only when the two proteins were co-expressed. This ATPase activity was significantly stimulated by the addition of certain androgen hormones and analogs, and was effectively inhibited by progesterone. Our results provide a new aspect of biochemical and functional characterization of the ABCG5/ABCG8 proteins and their possible involvement in steroid hormone transport or regulation.     

A cold-adapted esterase from psychrotrophic <Emphasis Type="Italic">Pseudoalteromas</Emphasis> sp. strain 643A

A psychrotrophic bacterium producing a cold-adapted esterase upon growth at low temperatures was isolated from the alimentary tract of Antarctic krill Euphasia superba Dana, and classified as Pseudoalteromonas sp. strain 643A. A genomic DNA library of strain 643A was introduced into Escherichia coli TOP10F', and screening on tributyrin-containing agar plates led to the isolation of esterase gene. The esterase gene (estA, 621 bp) encoded a protein (EstA) of 207 amino acid residues with molecular mass of 23,036 Da. Analysis of the amino acid sequence of EstA suggests that it is a member of the GDSL-lipolytic enzymes family. The purification and characterization of native EstA esterase were performed. The enzyme displayed 20-50% of maximum activity at 0-20 degrees C. The optimal temperature for EstA was 35 degrees C. EstA was stable between pH 9 and 11.5. The enzyme showed activity for esters of short- to medium-chain (C(4) and C(10)) fatty acids, and exhibited no activity for long-chain fatty acid esters like that of palmitate and stearate. EstA was strongly inhibited by phenylmethylsulfonyl fluoride, 2-mercaptoethanol, dithiothreitol and glutathione. Addition of selected divalent ions e.g. Mg(2+), Co(2+) and Cu(2+) led to the reduction of enzymatic activity and the enzyme was slightly activated ( approximately 30%) by Ca(2+) ions.     

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.     

The pheromonal gland of Lymantria dispar: Morphology and evidence for its innervation

The morphological features of the glandular epithelium that secretes pheromone in the polyphagous pest gypsy moth Lymantria dispar are described by light and electron microscopy. The monolayered gland cells are covered by the folded cuticle of the intersegmental membrane between the 8th and 9th abdominal segments showing neither sites of discontinuity nor distinct openings on its external surface. The cells bear a large, often irregularly shaped nucleus, and contain granules of variable amount and electron‐density. These granules are mostly located in the basal compartment of the cytoplasm, in a labyrinthine zone laying on a basement membrane. The apical membrane of the gland cells bear microvilli and cell–cell contact is established by different junctional structures. Nerve fibers enwrapped in glia are found beneath the basement membrane, in close contact with the secretory cells. This latter finding represents the first evidence of the innervation of the pheromonal gland in L. dispar. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.     

An MTA phosphorylase gene discovered in the metagenomic library derived from Antarctic top soil during screening for lipolytic active clones confers strong pink fluorescence in the presence of rhodamine B

Eubacteria encode proteins that are required for nucleoid organization and for regulation of DNA-dependent processes. Of these histone-like proteins (Hlps), Escherichia coli HU has been shown to associate with the nucleoid and to regulate processes such as DNA repair and recombination. In contrast, the divergent HU homologs encoded by mycobacteria have been variously identified as involved in the physiology of dormancy, in the response to cold shock, or as laminin-binding proteins associated with the cell envelope. We show here, contrary to previous reports that the HU-related Hlp from Mycobacterium smegmatis associates with the nucleoid in vivo . Using indirect fluorescent antibody microscopy we show that cold shock causes Hlp to accumulate in the cytoplasm of M. smegmatis . No evidence of surface-associated Hlp was found in M. smegmatis cells treated for cell wall permeabilization. Quantitative Western blots indicate that exponentially growing cells contain c . 120 molecules per cell, with upregulation of Hlp after cold shock estimated to be c . 10-fold. That Hlp associates with the nucleoid in vivo suggests functions in DNA metabolism, perhaps in adaptation to environmental stress.