STRP Screening Sets for the human genome at 5 cM density

Background  

Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density.     

Functional organization of adult motor cortex is dependent upon continued protein synthesis

The functional organization of adult cerebral cortex is characterized by the presence of highly ordered sensory and motor maps. Despite their archetypical organization, the maps maintain the capacity to rapidly reorganize, suggesting that the neural circuitry underlying cortical representations is inherently plastic. Here we show that the circuitry supporting motor maps is dependent upon continued protein synthesis. Injections of two different protein synthesis inhibitors into adult rat forelimb motor cortex caused an immediate and enduring loss of movement representations. The disappearance of the motor map was accompanied by a significant reduction in synapse number, synapse size, and cortical field potentials and caused skilled forelimb movement impairments. Further, motor skill training led to a reappearance of movement representations. We propose that the circuitry of adult motor cortex is perpetually labile and requires continued protein synthesis in order to maintain its functional organization.     

A novel heparan sulphate with high degree of N-sulphation and high heparin cofactor-II activity from the brine shrimp Artemia franciscana

With the aid of heparinase and heparitinases from Flavobacterium heparinum and 13C and IH NMR spectroscopy it was shown that the heparan sulphate isolated from the brine shrimp Artemia franciscana exhibits structural features intermediate between those of mammalian heparins and heparan sulphates. These include an unusually high degree of N-sulphation (with corresponding very low degree of N-acetylation), a relatively high content of iduronic acid residues (both unsulphated and 2-O-sulphated) and a relatively low degree of 6-O-sulphation of the glucosamine residues. The major sequences (glucuronic acid-->N-sulphated glucosamine and glucuronic acid-->N, 6-disulphated glucosamine) are most probably arranged in blocks. Although exhibiting negligible anticlotting activity in the APTT and anti-factor Xa assays the A. franciscana heparan sulphate has a high heparin cofactor-II activity (about 1/3 that of heparin).     

Autocrine secretion of TGF-β1 and TGF-β2 by pre-adipocytes and adipocytes: A potent negative regulator of adipocyte differentiation and proliferation of mammary carcinoma cells

Summary We have developed an in vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma, SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly stimulates proliferation of SP1 cells. We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which inhibit DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells, but not DR27 mutant epithelial cells which lack TGF-β type II receptor. Inhibitory activity of CMs was partially abrogated by neutralizing anti-TGF-β1 and anti-TGF-β2 antibodies, and was removed following ultrafiltration through membranes of 10 000 M_r but not 30 000 M_r pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-β1-like and TGF-β2-like molecules. In addition, acid-treated CM as well as purified TGF-β inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that pre-adipocytes spontaneously activate their own secreted TGF-β, whereas mature adipocytes do not, and suggest that activation of TGF-β has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-β may be an important modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment.     

Growth of Tomato Plants in Soil Contaminated with Kuwait Crude Oil

This laboratory study measured growth of one plant species, Lycopersicon esculentum Big Girl (tomato), that is sensitive to the presence of soil contamination, in Kuwait soil amended with crude-oil-contaminated soil. Germinated tomato seeds were placed in containers with soil containing 0, 0.12, 0.24, 0.36, 0.48, 0.60, 1.2, and 2.4% crude oil and were grown in an indoor growth chamber. Plants grew in Kuwait soil containing up to 0.36% crude oil; however, growth and fruit production were compromised at crude oil concentrations greater than 0.12% when compared with control plants. Plants did not grow in Kuwait soil amended with 0.48% crude oil or higher.     

Serum Biomarkers in Patients with Relapsing Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)

Introduction

Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly- diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) with highly active disease. The role of these biomarkers in relapsing disease is unclear.

Methods

Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients). Epidemiological, clinical and laboratory data were available for all visits.

Results

At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.

Conclusions

Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.     

Impact of Sn/F Pre-Treatments on the Durability of Protective Coatings against Dentine Erosion/Abrasion

For preventing erosive wear in dentine, coating with adhesives has been suggested as an alternative to fluoridation. However, clinical studies have revealed limited efficacy. As there is first evidence that Sn²⁺ increases bond strength of the adhesive Clearfil SE (Kuraray), the aim of the present study was to investigate whether pre-treatment with different Sn²⁺/F⁻ solutions improves the durability of Clearfil SE coatings. Dentine samples (eight groups, n=16/group) were freed of smear layer (0.5% citric acid, 10 s), treated (15 s) either with no solution (control), aminefluoride (AmF, 500 ppm F⁻, pH 4.5), SnCl₂ (800/1600 ppm Sn²⁺; pH 1.5), SnCl₂/AmF (500 ppm F⁻, 800 ppm Sn²⁺, pH 1.5/3.0/4.5), or Elmex Erosion Protection Rinse (EP, 500 ppm F⁻, 800 ppm Sn²⁺, pH 4.5; GABA International), then rinsed with water (15 s) and individually covered with Clearfil SE. Subsequently the specimens were subjected to an erosion/abrasion protocol consisting of 1320 cycles of immersion in 0.5% citric acid (5°C/55°C; 2 min) and automated brushing (15 s, 200 g, NaF-toothpaste, RDA 80). As the coatings proved stable up to 1320 cycles, 60 modified cycles (brushing time 30 min/cycle) were added. Wear was measured profilometrically. After SnCl₂/AmF, pH 4.5 or EP pre-treatment all except one coating survived. In the other groups, almost all coatings were lost and there was no significant difference to the control group. Pre-treatment with a Sn²⁺/F⁻ solution at pH 4.5 seems able to improve the durability of adhesive coatings, rendering these an attractive option in preventing erosive wear in dentine.     

Latent Autoimmune Diabetes in Adults in the United Arab Emirates: Clinical Features and Factors Related to Insulin-Requirement

Aims

To describe and to characterize clinical features of latent autoimmune diabetes in adults (LADA) compared to type 1 and type 2 diabetes in the UAE.

Methods

In this cross-sectional study a dataset including 18,101 subjects with adult-onset (>30 years) diabetes was accessed. 17,072 subjects fulfilled the inclusion/exclusion criteria. Data about anthropometrics, demographics, autoantibodies to Glutamic Acid Decarboxylase (GADA) and to Islet Antigen 2 (anti-IA2), HbA1c, cholesterol and blood pressure were extracted. LADA was diagnosed according to GADA and/or anti-IA2 positivity and time to insulin therapy.

Results

437 (2.6%) patients were identified as LADA and 34 (0.2%) as classical type 1 diabetes in adults. Mean age at diagnosis, BMI, waist circumference, systolic blood pressure and HbA1c significantly differed between, LADA, type 2 and type 1 diabetes, LADA showing halfway features between type 2 and type 1 diabetes. A decreasing trend for age at diagnosis and waist circumference was found among LADA subjects when subdivided by positivity for anti-IA2, GADA or for both antibodies (p=0.013 and p=0.011 for trend, respectively). There was a gradual downward trend in autoantibody titre in LADA subjects requiring insulin within the first year from diagnosis to subjects not requiring insulin after 10 years of follow-up (p<0.001).

Conclusions

This is the first study describing the clinical features of LADA in the UAE, which appear to be different from both type 1 and type 2 diabetes. Furthermore, we showed that the clinical phenotype of LADA is dependent on different patterns of antibody positivity, influencing the time to insulin requirement.     

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of “autism”. The second aim was to compare cognitive profiles obtained on the third edition versus 4^th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger’s Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.