A nhaD Na+/H+ antiporter and a pcd homologues are among the Rhodothermus marinus complex I genes

The NADH:menaquinone oxidoreductase (Nqo) is one of the enzymes present in the respiratory chain of the thermohalophilic bacterium Rhodothermus marinus. The genes coding for the R. marinus Nqo subunits were isolated and sequenced, clustering in two operons [nqo1 to nqo7 (nqoA) and nqo10 to nqo14 (nqoB)] and two independent genes (nqo8 and nqo9). Unexpectedly, two genes encoding homologues of a NhaD Na+/H+ antiporter (NhaD) and of a pterin-4alpha-carbinolamine dehydratase (PCD) were identified within nqoB, flanked by nqo13 and nqo14. Eight conserved motives to harbour iron-sulphur centres are identified in the deduced primary structures, as well as two consensus sequences to bind nucleotides, in this case NADH and FMN. Moreover, the open-reading-frames of the putative NhaD and PCD were shown to be co-transcribed with the other complex I genes encoded by nqoB. The possible role of these two genes in R. marinus complex I is discussed.     

L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy

Iron is essential in the retina because the heme-containing enzyme guanylate cyclase modulates phototransduction in rods and cones. Transferrin endocytosis is the classical pathway for obtaining iron from the blood circulation in the retina. However, the iron storage protein ferritin has been also recently proposed as an iron carrier. In this study, the presence of Scara5 and its binding to L-ferritin was investigated in the retina. Our results showed that Scara5, the specific receptor for L-ferritin, was expressed in mouse and human retinas in many cell types, including endothelial cells. Furthermore, we showed that intravenously injected ferritin crossed the blood retinal barrier through L-ferritin binding to Scara5 in endothelial cells. Thus, suggesting the existence of a new pathway for iron delivery and trafficking in the retina. In a murine model of photoreceptor degeneration, Scara5 was downregulated, pointing out this receptor as a potential player implicated in retinopathy and also as a possible therapeutic target.     

Barrels X-meeting announcement

Abstract

A cerebrovascular accident, otherwise known as stroke, has the potential to damage multiple areas within the brain affecting descending motor control via a multitude of pathways resulting in a wide variety of movement problems. The cortico-reticulospinal system, one of the largest motor systems, is frequently affected, compromising its output, resulting in postural control deficits. The identification of clinically relevant instruments and scales to document and evaluate recovery in post-stroke patients is vital. However, the availability of such measures and scales which take into consideration the role of postural control as an integral component of functional movement performance are scarce. This paper will critically discuss the importance of integrating current neuroscience and motor control knowledge in order to better understand and describe the clinical presentation of persons post-stroke such that the effectiveness of stroke rehabilitation can be appropriately measured.     

Portuguese Family Physicians’ Awareness of Diagnostic and Laboratory Test Costs: A Cross-Sectional Study

Background

Physicians’ ability to make cost-effective decisions has been shown to be affected by their knowledge of health care costs. This study assessed whether Portuguese family physicians are aware of the costs of the most frequently prescribed diagnostic and laboratory tests.

Methods

A cross-sectional study was conducted in a representative sample of Portuguese family physicians, using computer-assisted telephone interviews for data collection. A Likert scale was used to assess physician’s level of agreement with four statements about health care costs. Family physicians were also asked to estimate the costs of diagnostic and laboratory tests. Each physician’s cost estimate was compared with the true cost and the absolute error was calculated.

Results

One-quarter (24%; 95% confidence interval: 23%–25%) of all cost estimates were accurate to within 25% of the true cost, with 55% (95% IC: 53–56) overestimating and 21% (95% IC: 20–22) underestimating the true actual cost. The majority (76%) of family physicians thought they did not have or were uncertain as to whether they had adequate knowledge of diagnostic and laboratory test costs, and only 7% reported receiving adequate education. The majority of the family physicians (82%) said that they had adequate access to information about the diagnostic and laboratory test costs. Thirty-three percent thought that costs did not influence their decision to order tests, while 27% were uncertain.

Conclusions

Portuguese family physicians have limited awareness of diagnostic and laboratory test costs, and our results demonstrate a need for improved education in this area. Further research should focus on identifying whether interventions in cost knowledge actually change ordering behavior, in identifying optimal methods to disseminate cost information, and on improving the cost-effectiveness of care.     

Inequality of Experience of Dental Caries between Different Ethnic Groups of Brazilians Aged 15 to 19 Years

Introduction

The aim of this study was to assess inequality of experience of dental caries, based on race/ethnicity, among Brazilian adolescents aged 15 to 19 years in 2010 and test whether socioeconomic indicators fully explain ethnic differences in dental caries.

Methods

Data from a National Oral Health Survey conducted in Brazil in 2010 was analysed. Race/ethnicity was self-assigned and modified to White, African descents, East Asian descents, Mixed Race and Indigenous descents. The prevalence of caries experience by race/ethnic group in 2010(n = 5,367) was calculated. Further analysis included conceptual hierarchical modelling and mediation analysis.

Results

Caries experience was 76.9% in 15 to 19 year old Brazilians in 2010. While African descents were 32% more likely to have caries experience than Whites, Mixed Race were 69% more likely to have caries experience than Whites. Hierarchical conceptual modelling analysis confirmed the highly significant association between caries and race/ethnicity. Mixed Race and East Asian descents were 1.44 (95% CI 1.24–1.67) and 1.81 (95% CI 1.02–3.20) times more likely to experience caries than Whites after adjusting for age, sex, education and income. The difference in the likelihood of experiencing caries between Whites and African descents was not statistically significant after adjusting for years of education and family income. The results of mediation analysis confirmed that inequality of caries experience between Whites and Mixed Race and East Asian descents was mediated through education and income. The likelihood that Mixed Race and East Asian descents would experience caries compared to Whites was attenuated, by 14.8% and by 9.5% respectively, after adjusting for years of education and income.

Conclusions

Data analysis demonstrated that Whites have benefited more from the significant reduction in dental caries experience in 15 to 19 year old Brazilians, as compared to African descents and Mixed Race. Education and income fully explained ethnic inequalities in experience of dental caries between Whites and African descents, and largely explained inequalities between Whites and Mixed Race.     

Phosphorylation of silk fibroins improves the cytocompatibility of silk fibroin derived materials: A platform for the production of tuneable material

Silk fibroin demonstrates great biocompatibility and is suitable for many biomedical applications, including tissue engineering and regenerative medicine. Current research focuses on manipulating the physico‐chemical properties of fibroin, and examining the effect of this manipulation on firobin's biocompatibility. Regenerated silk fibroin was modified by in vitro enzymatic phosphorylation and cast into films. Films were produced by blending, at several ratios, the phosphorylated and un‐phosphorylated fibroin solutions. Fourier transform infra‐red spectroscopy was used to determine the specific P–OH vibration peak, confirming the phosphorylation of the regenerated silk fibroin solution. Differential scanning calorimetry showed that phosphorylation altered the intra‐ and inter‐molecular interactions. Further experiments demonstrated that phosphorylation can be used to tailor the hydrophylicity/hydrophobicity ratio as well as the crystalinity of silk fibroin films. Release profiling of a model drug was highly dependent on silk modification level. Cytotoxicity assays showed that exposure to lixiviates of phosphorylated films only slightly affected cellular metabolism and proliferation, although direct contact resulted in a strong direct correlation between phosphorylation level and cell proliferation. This new method for tuning silk biomaterials to obtain specific structural and biochemical features can be adapted for a wide range of applications. Phosphorylation of silk fibroins may be applied to improve the cytocompatibility of any silk‐based device that is considered to be in contact with live animals or human tissues.     

Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass

Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of β cell maintenance and provide a rational strategy to inhibit this protease?for the expansion of functional pancreatic β cell mass.     

Quantitative proteomics (2-D DIGE) reveals molecular strategies employed by Burkholderia cenocepacia to adapt to the airways of cystic fibrosis patients under antimicrobial therapy

Chronic respiratory infections caused by Burkholderia cenocepacia in patients with cystic fibrosis (CF) are characterized by low responsiveness to antibiotic therapy and, in general, to a more rapid decline of lung function. To get clues into the molecular mechanisms underlying the adaptive strategies employed to deal with the stressing conditions of the CF lung including antibiotic therapy, quantitative proteomics (2-D DIGE) was used to compare the expression programs of two clonal isolates retrieved from a chronically infected CF patient. Isolate IST439 was the first bacterium recovered while the clonal variant IST4113 was obtained after 3 years of persistent infection and intravenous therapy with ceftazidime/gentamicin. This isolate exhibits higher resistance levels towards different classes of antimicrobials. Proteins of the functional categories Energy metabolism, Translation, Nucleotide synthesis, Protein folding and stabilization are more abundant in IST4113, compared with IST439, suggesting an increased protein synthesis, DNA repair and stress resistance in IST4113. The level of proteins involved in peptidoglycan, membrane lipids and lipopolysaccharide synthesis is also altered and proteins involved in iron binding and transport are more abundant in IST4113. The quantitative comparison of the two proteomes suggests a genetic adaptation leading to increased antimicrobial resistance and bacterial persistence in the CF airways.