Nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress

Influenza A virus infection is an ongoing clinical problem and thus, there is an urgent need to understand the mechanisms that regulate the lung inflammation in order to unravel novel generic pharmacological strategies. Evidence indicates that the Nox2-containing NADPH oxidase enzyme promotes influenza A virus-induced lung oxidative stress, inflammation and dysfunction via ROS generation. In addition, lung epithelial and endothelial cells express the Nox1 isoform of NADPH oxidase, placing this enzyme at key sites to regulate influenza A virus-induced lung inflammation. The aim of this study was to investigate whether Nox1 oxidase regulates the inflammatory response and the oxidative stress to influenza infection in vivo in mice. Male WT and Nox1-deficient (Nox1−/y) mice were infected with the moderately pathogenic HkX-31 (H3N2, 1×104 PFU) influenza A virus for analysis of bodyweight, airways inflammation, oxidative stress, viral titre, lung histopathology, and cytokine/chemokine expression at 3 and 7 days post infection. HkX-31 virus infection of Nox1−/y mice resulted in significantly greater: loss of bodyweight (Day 3); BALF neutrophilia, peri-bronchial, peri-vascular and alveolar inflammation; Nox2-dependent inflammatory cell ROS production and peri-bronchial, epithelial and endothelial oxidative stress. The expression of pro-inflammatory cytokines including CCL2, CCL3, CXCL2, IL-1β, IL-6, GM-CSF and TNF-α was higher in Nox1−/y lungs compared to WT mice at Day 3, however, the expression of CCL2, CCL3, CXCL2, IFN-γ and the anti-inflammatory cytokine IL-10 were lower in lungs of Nox1−/y mice vs. WT mice at Day 7. Lung viral titre, and airways infiltration of active CD8+ and CD4+ T lymphocytes, and of Tregs were similar between WT and Nox1−/y mice. In conclusion, Nox1 oxidase suppresses influenza A virus induced lung inflammation and oxidative stress in mice particularly at the early phases of the infection. Nox1 and Nox2 oxidases appear to have opposing roles in the regulation of inflammation caused by influenza A viruses

Benefits for public healthcare buildings towards Net Zero Energy Buildings (NZEBs): initial reviews

NZEBs concept has received incrementing attention especially since European Union Parliament are progressively moving towards regulation in which all new buildings to be “nearly Zero-Energy” Buildings by 2020. Even though this concept delivers promising benefits, previous studies found that the benefit of NZEB is still in vague to the Malaysian construction industry, mostly for healthcare buildings. The NZEBs concept implementation is critical in healthcare building as it seen as a key part of the needed transition towards sustainable development. This paper aims to define benefits of NZEBs practices through initial investigation among architects. Several existing energies works of literature and pilot studies by using semi-structured interviews were conducted. The findings divulge that, although the term ‘NZEBs design strategies’ is not being used largely across construction industry in Malaysia, some sustainable practices related to the design stage of construction has been implemented. The findings are also promising in growing awareness, practices and implementation of NZEBs design strategies by the practitioner in Malaysia. It is foreseen that the paper will provide a straightforward knowledge for future research in NZEBs design strategies practices for healthcare buildings construction in Malaysia

A Longitudinal Study of Streptococcus mutans Colonization in Infants after Tooth Eruption

We previously reported that, before tooth eruption, over one-half of infants aged 6 mos were already infected with Streptococcus mutans. The aim of this investigation was to determine the colonization of S. mutans after tooth eruption in the same cohort of 111 infants (35 pre-term, 76 full-term). Our results showed that S. mutans colonization increased with increasing age, so that by 24 mos of age, 84% harbored the bacteria (p 10(5) CFU/mL (p < 0.02). In contrast, non-colonization of S. mutans was associated with toothbrushing (p < 0.03) and multiple courses of antibiotics (p < 0.001). Analysis of our data establishes the timing of S. mutans colonization in children from birth to 24 mos of age

Longitudinal Current Dissipation in Bose-glass Superconductors

A scaling theory of vortex motion in Bose glass superconductors with currents parallel to the common direction of the magnetic field and columnar defects is presented. Above the Bose-glass transition the longitudinal DC resistivity $\rho_{||}(T)\sim (T-T_{BG})^{\nu' z'}$ vanishes much faster than the corresponding transverse resistivity $\rho_{\perp}(T)\sim (T-T_{BG})^{\nu' (z'-2)}$, thus {\it reversing} the usual anisotropy of electrical transport in the normal state of layered superconductors. In the presence of a current $\bf J$ at an angle $\theta_J$ with the common field and columnar defect axis, the electric field angle $\theta_E$ approaches $\pi/2$ as $T\rightarrow T_{BG}^+$. Scaling also predicts the behavior of penetration depths for the AC currents as $T\rightarrow T_{BG}^-$, and implies a {\it jump discontinuity} at $T_{BG}$ in the superfluid density describing transport parallel to the columns.Comment: 5 pages, revte

Genetic regulation of glucoraphanin accumulation in Beneforté® broccoli

Diets rich in broccoli (Brassica oleracea var italica) have been associated with maintenance of cardiovascular health and reduction in risk of cancer. These health benefits have been attributed to glucoraphanin that specifically accumulates in broccoli. The development of broccoli with enhanced concentrations of glucoraphanin may deliver greater health benefits. Three high-glucoraphanin F1 broccoli hybrids were developed in independent programmes through genome introgression from the wild species Brassica villosa. Glucoraphanin and other metabolites were quantified in experimental field trials. Global SNP analyses quantified the differential extent of B. villosa introgression The high-glucoraphanin broccoli hybrids contained 2.5–3 times the glucoraphanin content of standard hybrids due to enhanced sulphate assimilation and modifications in sulphur partitioning between sulphur-containing metabolites. All of the high-glucoraphanin hybrids possessed an introgressed B. villosa segment which contained a B. villosa Myb28 allele. Myb28 expression was increased in all of the high-glucoraphanin hybrids. Two high-glucoraphanin hybrids have been commercialised as Beneforte broccoli. The study illustrates the translation of research on glucosinolate genetics from Arabidopsis to broccoli, the use of wild Brassica species to develop cultivars with potential consumer benefits, and the development of cultivars with contrasting concentrations of glucoraphanin for use in blinded human intervention studie

Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma

Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22–q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1–4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13–111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes’ stage were found. LOH was observed in colorectal tumours of all Dukes’ stages, including Dukes’ stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes. © 2000 Cancer Research Campaig

Developmental Defects of Enamel in Primary Teeth and Association with Early Life Course Events: A Study of 6--36 Month old Children in Manyara, Tanzania.

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).Focusing 6--36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child's early illness episodes and mothers' perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.22 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania