Low prenatal vitamin D alters morphology, cell density and gene expression in adult rat brain: Correlations with schizophrenia

Statement of the study: Based on data from ecological and analytic epidemiological studies, we have proposed that low prenatal vitamin D is a candidate risk-modifying factor for schizophrenia. Previously, we demonstrated that low prenatal vitamin D adversely affected brain development in neonatal rats (Eyles et al, 2003). Here we examine the impact of both prenatal and early life hypovitaminosis D on various outcomes in the adult rat brain. Methods: Female Sprague-Dawley rats were made vitamin D deficient via the use of a special diet (Dyets CA) and lighting conditions that excluded UVB radiation. Animals were kept under these conditions for 6 weeks then mated with males kept under normal conditions. Vitamin deplete dams were kept under these conditions during pregnancy. Offspring from two test groups were examined. Offspring were either reared with dams repleted with vitamin D at birth or remained under deplete conditions till weaning. Both test groups were weaned under normal vitamin D conditions and remained so till testing at adulthood. We compared the brains of adult offspring kept under both test conditions with animals from control environments. Summary of results: We found a significant persistent dose-related increase in lateral ventricle volume and alterations in anterior cingulate and prefrontal cortical cell densities (consistent with the known prodifferentiation properties of this steroid). In both test groups we observed a reduced expression of NGF as well as a down-regulation of transcripts coding for GABAA alpha 4 receptor and two neuronal structural elements; MAP2 and Neurofilament L. Conclusion: These findings provide further evidence that vitamin D is involved in brain development. An increase in prefrontal cortical cell density, a reduction neuronal structural elements and persistent ventriculomegaly are all common anatomical findings in the brains of patients with schizophrenia. The specific reduction in transcripts for neuronal structural proteins but not GFAP is also in accordance with the proposal that frontal cortical architecture in schizophrenia reflects a reduction in connectivity rather than a reduction in glial processes(Goldman-Rakic and Selemon, 1997). These findings confirm the biological plausibility of early life hypovitaminosis D as a risk factor for schizophrenia.

Computational methods for prediction of T-cell epitopes - a framework for modelling, testing, and applications

Computational models complement laboratory experimentation for efficient identification of MHC-binding peptides and T-cell epitopes. Methods for prediction of MHC-binding peptides include binding motifs, quantitative matrices, artificial neural networks, hidden Markov models, and molecular modelling. Models derived by these methods have been successfully used for prediction of T-cell epitopes in cancer, autoimmunity, infectious disease, and allergy. For maximum benefit, the use of computer models must be treated as experiments analogous to standard laboratory procedures and performed according to strict standards. This requires careful selection of data for model building, and adequate testing and validation. A range of web-based databases and MHC-binding prediction programs are available. Although some available prediction programs for particular MHC alleles have reasonable accuracy, there is no guarantee that all models produce good quality predictions. In this article, we present and discuss a framework for modelling, testing, and applications of computational methods used in predictions of T-cell epitopes. (C) 2004 Elsevier Inc. All rights reserved.

Differential responses of antioxidant enzymes in pioneer and late-successional tropical tree species grown under sun and shade conditions

To investigate the ability of pioneer and late-successional species to adapt to a strong light environment in a reforestation area, we examined the activities of antioxidant enzymes in relation to photosystem chlorophyll a fluorescence and photosynthetic pigment concentration for eight tropical tree species grown under 100% (sun) and 10% (shade) sunlight irradiation. The pioneer (early-succession) species (PS) were Cecropia pachystachya, Croton urucurana, Croton floribundus and Schinus terebinthifolius. The non-pioneer (late succession) species (LS) were Hymenaea courbaril L var. stilbocarpa, Esenbeckia leiocarpa, Cariniana legalis and Tabebuia roseo-alba. We observed a greater decline in the ratio of variable to maximum chlorophyll a fluorescence (F(v)/F(m)) under full sunlight irradiation in the late-successional species than in the pioneer species. The LS species most sensitive to high irradiance were C. legalis and H. courbaril. In LS species, chlorophyll a, chlorophyll b and total chlorophyll concentrations were higher in the shade-grown plants than in plants that developed under full sunlight, but in the PS species C. floribundus and C. pachystachya, we did not observe significant changes in chlorophyll content when grown in the two contrasting environments. The carotenoids/total chlorophyll ratio increased significantly when plants developed under high-sunlight irradiation, but this response was not observed in the PS species S. terebinthifolius and C. pachystachya. The improved performance of the pioneer species in high sunlight was accompanied by an increase in superoxide dismutase (SOD. EC 1.15.1.1) activity, though no light-dependent increase in the activity of ascorbate peroxidase (APX. EC 1.11.1.11) was observed. The activity of catalase (CAT, EC 1.11.1.6) was reduced by high irradiation in both pioneer and late-successional species. Our results show that pioneer species perform better under high-sunlight irradiation than late-successional species, as indicated by increased SOD activity and a higher F IF,, ratio. C. legalis was the LS species most susceptible to photoinhibition under full sunlight conditions. These results suggest that pioneer plants have more potential tolerance to photo-oxidative damage than late-successional species associated with the higher SOD activity found in pioneer species. Reduced photoinhibition in pioneer species probably results from their higher photosynthetic capacities, as has been observed in a previous survey carried out by our group. (C) 2010 Elsevier B.V. All rights reserved.

Material influence on the stress corrosion cracking of rock bolts

Rock bolt stress corrosion cracking (SCC) has been investigated using the linearly increasing stress test (LIST). One series of experiments determined the threshold stress of various bolt metallurgies (900 MPa for 1355AXRC, and 800 MPa for MAC and MA840B steels). The high values of threshold stress suggest that SCC begins in rock bolts when they are sheared by moving rock strata. SCC only occurred for environmental conditions which produce hydrogen on the sample surface, leading to hydrogen embrittlement and SCC. Different threshold potentials were determined for a range of metallurgies. Cold work was shown to increase the resistance of the steel to SCC. Rock bolt rib geometry does not have a direct impact on the SCC resistance properties of the bolt, although the process by which the ribs are produced can introduce tensile stresses into the bolt which lower its resistance to SCC. (C) 2004 Elsevier Ltd. All rights reserved.

The 23rd October 2002 dust storm in eastern Australia: characteristics and meteorological conditions

The dust storm of 23 October 2002 covered most of eastern Australia and carried one of the largest recorded dust loads in Australia. In the 6 months leading up to the event, severe drought conditions in eastern Australia, plus above average maximum temperatures resulted in high potential evapo-transpiration rates, producing severe soil moisture deficits and reduced vegetation cover. Although increased wind speeds associated with a fast moving cold front were the meteorological driving force, these winds speeds were lower than those for the previously documented large dust storms. The dust storm was 2400 km long, up to 400 km across and 1.5-2.5 km in height. The plume area was estimated at 840,860 km 2 and the dust load at 0900 h was 3.35-4.85 million tones (Mt). These dust load estimates are highly sensitive to assumptions, regarding visibility-dust concentration relationships, vertical dust concentration profiles and dust ceilings. The event is examined using meteorological records, remote sensing and air quality monitoring. (C) 2004 Elsevier Ltd. All rights reserved.

Existence Results for Second Order Differential Equations with Nonlocal Conditions in Banach Spaces

This work is concerned with implicit second order abstract differential equations with nonlocal conditions. Assuming that the involved operators satisfy sonic compactness properties, we establish the existence of local mild solutions, the existence of global mild solutions and the existence of asymptotically almost periodic solutions.

Existence of solutions for a class of abstract differential equations with nonlocal conditions

We discuss the existence of mild, classical and strict solutions for a class of abstract differential equations with nonlocal conditions. Our technical approach allows the study of partial differential equations with nonlocal conditions involving partial derivatives or nonlinear expressions of the solution. Some concrete applications to partial differential equations are considered. (C) 2010 Elsevier Ltd. All rights reserved.

Choice of macroinvertebrate metrics to evaluate stream conditions in Atlantic Forest, Brazil

The development of biomonitoring programs based on the macroinvertebrate community requires the understanding of species distribution patterns, as well as of the responses of the community to anthropogenic stressors. In this study, 49 metrics were tested as potential means of assessing the condition of 29 first- and second-order streams located in areas of differing types of land use in So Paulo State, Brazil. Of the sampled streams, 15 were in well-preserved regions in the Atlantic Forest, 5 were among sugarcane cultivations, 5 were in areas of pasture, and 4 were among eucalyptus plantations. The metrics were assessed against the following criteria: (1) predictable response to the impact of human activity; (2) highest taxonomic resolution, and (3) operational and theoretical simplicity. We found that 18 metrics were correlated with the environmental and spatial predictors used, and seven of these satisfied the selection criteria and are thus candidates for inclusion in a multimetric system to assess low-order streams in So Paulo State. These metrics are family richness; Ephemeroptera, Plecoptera and Trichoptera (EPT) richness; proportion of Megaloptera and Hirudinea; proportion of EPT; Shannon diversity index for genus; and adapted Biological Monitoring Work Party biotic index.

Biomimetic in silico devices

We introduce biomimetic in silico devices, and means for validation along with methods for testing and refining them. The devices are constructed from adaptable software components designed to map logically to biological components at multiple levels of resolution. In this report we focus on the liver; the goal is to validate components that mimic features of the lobule (the hepatic primary functional unit) and dynamic aspects of liver behavior, structure, and function. An assembly of lobule-mimetic devices represents an in silico liver. We validate against outflow profiles for sucrose administered as a bolus to isolated, perfused rat livers. Acceptable in silico profiles are experimentally indistinguishable from those of the in situ referent. This new technology is intended to provide powerful Dew tools for challenging our understanding of how biological functional units function in vivo.

Trigeminal pain and quantitative sensory testing in painful peripheral diabetic neuropathy

Objective: To evaluate patients with Diabetes Mellitus type 2 and painful peripheral neuropathy in order to investigate oral complaints and facial somatosensory findings. Research design and methods: Case-control study; 29 patients (12 women, mean age 57.86 yo) with Diabetes Mellitus type 2 and 31 age-gender-matched controls were evaluated with a standardized protocol for general characteristics, orofacial pain, research diagnostic criteria for temporomandibular disorders, visual analogue scale and McGill Pain questionnaire, and a systematic protocol of quantitative sensory testing for bilateral facial sensitivity at the areas innervated by the trigeminal branches, which included the thermal detection by ThermoSensi 2, tactile evaluation with vonFrey filaments, and superficial pain thresholds with a superficial algometer (Micromar). Statistical analysis was performed with Wilcoxon, chi-square, confidence intervals and Spearman (p < 0.05). Results: Orofacial pain was reported by 55.2% of patients, and the most common descriptor was fatigue (50%); 17.2% had burning mouth. Myofascial temporomandibular disorders were diagnosed in 9(31%) patients. The study group showed higher sensory thresholds of pain at the right maxillary branch (p = 0.017) but sensorial differences were not associated with pain (p = 0.608). Glycemia and HbA(1c) were positively correlated with the quantitative sensory testing results of pain (p < 0.05) and cold (p = 0.044) perceptions. Higher pain thresholds were correlated with higher glycemia and glycated hemoglobin (p = 0.027 and p = 0.026). Conclusions: There was a high prevalence of orofacial pain and burning mouth was the most common complaint. The association of loss of pain sensation and higher glycemia and glycated hemoglobin can be of clinical use for the follow-up of DM complications. (C) 2010 Elsevier Ltd. All rights reserved.

Management of brachial plexus region tumours and tumour-like conditions: relevant diagnostic and surgical features in a consecutive series of eighteen patients

Tumours of the brachial plexus region are rare and most publications are case reports or studies with a small series of patients. The aim of this study is to present our experience in managing these lesions. We review 18 patients with tumours in the brachial plexus region submitted to surgical treatment in a 6 year period, including their clinical presentation, neuro-imaging data, surgical findings and outcome. The tumours comprised a heterogeneous group of lesions, including schwannomas, neurofibromas, malignant peripheral nerve sheath tumour (MPNST), sarcomas, metastases, desmoids and an aneurysmal bone cyst. The most common presentation was an expanding lump (83.33%). Eleven tumours were benign and 7 were malignant. Neurofibromatosis was present in only 2 patients (11.11%). Gross total resection was achieved in 14 patients and sub-total resection in the others. Only 3 patients presented with new post-operative motor deficits. The incidence of complications was low (16.5 %). The majority of tumours were benign and most of them could be excised with a low incidence of additional deficits. Some of the malignant tumours could be controlled by surgery plus adjuvant therapy, but this category is still associated with high morbidity and mortality rates.

A framework for specification-based testing

Test templates and a test template framework are introduced as useful concepts in specification-based testing. The framework can be defined using any model-based specification notation and used to derive tests from model-based specifications-in this paper, it is demonstrated using the Z notation. The framework formally defines test data sets and their relation to the operations in a specification and to other test data sets, providing structure to the testing process. Flexibility is preserved, so that many testing strategies can be used. Important application areas of the framework are discussed, including refinement of test data, regression testing, and test oracles.

Super-CHO - A cell line capable of autocrine growth under fully defined protein-free conditions

Chinese Hamster Ovary (CHO) cells are widely used for the large scale production of recombinant biopharmaceuticals. Growth of the CHO-K1 cell line has been demonstrated in serum-free medium containing insulin, transferrin and selenium. In an attempt to get autocrine growth in protein-free medium, DNA coding for insulin and transferrin production was transfected into CHO-K1 cells. Transferrin was expressed well, with clones secreting approximately 1000 ng/10(6)cells/24h. Insulin was poorly expressed, with rates peaking at 5 ng/10(6)cells/24h. Characterisation of the secreted insulin indicated that the CHO cells were incompletely processing the insulin molecule. Site-directed mutagenesis was used to introduce a furin (prohormone converting enzyme) recognition sequence into the insulin molecule, allowing the production of active insulin. However, the levels were still too low to support autocrine growth. Further investigations revealed insulin degrading activity (presumably due to the presence of insulin degrading enzymes) in the cytoplasm of CHO cells. To overcome these problems insulin-like growth factor I (instead of insulin) was transfected into the cells. IGF-1 was completely processed and expressed at rates greater than 500 ng/10(6)cells/24h. In this paper we report autonomous growth of the transfected CHO-K1 cell line expressing transferrin and IGF-1 in protein-free medium without the addition of exogenous growth factors. Growth rates and final cell densities of these cells were identical to that of the parent cell line CHO-K1 growing in insulin, transferrin, and selenium supplemented serum-free media.