Granulocyte-targeted therapies for airway diseases

The average respiration rate for an adult is 12–20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common feature – airway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs

Dye-sensitized solar cell with a titanium-oxide-modified carbon nanotube transparent electrode

Cataloged from PDF version of article.Transparent and conductive carbon-based materials are promising for window electrodes in solid-state optoelectronic devices. However, the catalytic activity to redox reaction limits their application as a working electrode in a liquid-type dye-sensitized solar cell (DSSC). In this letter, we propose and demonstrate a transparent carbon nanotubes (CNTs) film as the working electrode in a DSSC containing iodide/triiodide redox couples. This implementation is realized by inhibiting the charge-transfer kinetics at CNT/redox solution interface with an aid of thin titanium oxide film that facilitates the unidirectional flow of electrons in the cell without sacrificing the electrical and optical properties of CNT. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3610488

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumin-induced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine–proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma

Cultivation of Human Corneal Endothelial Cells Isolated from Paired Donor Corneas

Consistent expansion of human corneal endothelial cells (hCECs) is critical in the development of tissue engineered endothelial constructs. However, a wide range of complex culture media, developed from different basal media have been reported in the propagation of hCECs, some with more success than others. These results are further confounded by donor-to-donor variability. The aim of this study is to evaluate four culture media in the isolation and propagation of hCECs isolated from a series of paired donor corneas in order to negate donor variability

Effect of seasonal changes on fertility parameters of Holstein dairy cows in subtropical climate of Taiwan

Objective: The purpose of this retrospective study was to investigate the relationship between temperature-humidity index (THI), season, and conception rate (CR) of Holstein cows in central Taiwan. Methods: The mean performance and number of observations were statistically evaluated for various parameters, including age at first service, number of days open, gestation length, CR, and calving interval for different parities. Results: The results indicate that the mean age at first service was 493.2 days; the gestation length was similar across all cows of different parities, ranging from 275.1 to 280.7 days. The overall CR of all inseminations was significantly lower in multiparous cows (47.26%±0.22%) than in heifers (57.14%±0.11%) (p72 and during the hot season (from June to November), CRs for multiparous cows were significantly reduced compared to that for heifers, while the ratio remained unchanged among heifers for all seasons. Conclusion: To achieve a high CR, lactating cows should be bred in winter and spring (from December to May) from the start of the seasonal breeding program, whereas the heifer should be allowed to breed in summer and fall under the subtropical climate in Taiwan

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

10.1242/dev.131573Development (Cambridge, England)1436950-961GUSTO (Growing up towards Healthy Outcomes

Impacts of Habitat Degradation on Tropical Montane Biodiversity and Ecosystem Services: A Systematic Map for Identifying Future Research Priorities

Tropical montane forests (TMFs) are major centers of evolutionary change and harbor many endemic species with small geographic ranges. In this systematic map, we focus on the impacts of anthropogenic habitat degradation on TMFs globally. We first determine how TMF research is distributed across geographic regions, degradation type (i.e., deforestation, land-use conversion, habitat fragmentation, ecological level (i.e., ecosystem, community, population, genetic) and taxonomic group. Secondly, we summarize the impacts of habitat degradation on biodiversity and ecosystem services, and identify deficiencies in current knowledge. We show that habitat degradation in TMFs impacts biodiversity at all ecological levels and will be compounded by climate change. However, despite montane species being perceived as more extinction-prone due to their restricted geographic ranges, there are some indications of biotic resilience if the impacts to TMFs are less severe. Species richness and key species interactions can be maintained in mildly degraded sites, and gene flow can persist between TMF fragments. As such, minimally degraded areas such as secondary forests and restored areas could play a crucial role in maintaining the meta-community and ecosystem services of TMFs—either via resource provision or by linking patches of pristine forest. Research deficiencies highlighted include poor research representation in Asian and African TMFs, few assessments of population and genetic-level responses to fragmentation, and little assessment of the impacts of habitat fragmentation at all ecological levels. To address these concerns, we present a list of the top research priorities to urgently address the growing threat of habitat degradation in TMF

Impacts of Habitat Degradation on Tropical Montane Biodiversity and Ecosystem Services: A Systematic Map for Identifying Future Research Priorities

Tropical montane forests (TMFs) are major centers of evolutionary change and harbor many endemic species with small geographic ranges. In this systematic map, we focus on the impacts of anthropogenic habitat degradation on TMFs globally. We first determine how TMF research is distributed across geographic regions, degradation type (i.e., deforestation, land-use conversion, habitat fragmentation, ecological level (i.e., ecosystem, community, population, genetic) and taxonomic group. Secondly, we summarize the impacts of habitat degradation on biodiversity and ecosystem services, and identify deficiencies in current knowledge. We show that habitat degradation in TMFs impacts biodiversity at all ecological levels and will be compounded by climate change. However, despite montane species being perceived as more extinction-prone due to their restricted geographic ranges, there are some indications of biotic resilience if the impacts to TMFs are less severe. Species richness and key species interactions can be maintained in mildly degraded sites, and gene flow can persist between TMF fragments. As such, minimally degraded areas such as secondary forests and restored areas could play a crucial role in maintaining the meta-community and ecosystem services of TMFs—either via resource provision or by linking patches of pristine forest. Research deficiencies highlighted include poor research representation in Asian and African TMFs, few assessments of population and genetic-level responses to fragmentation, and little assessment of the impacts of habitat fragmentation at all ecological levels. To address these concerns, we present a list of the top research priorities to urgently address the growing threat of habitat degradation in TMF

Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion

A self-controlled case series study to measure the risk of SARS-CoV-2 infection associated with attendance at sporting and cultural events: the UK Events Research Programme events.

BACKGROUND: In 2021, whilst societies were emerging from major social restrictions during the SARS-CoV-2 pandemic, the UK government instigated an Events Research Programme to examine the risk of COVID-19 transmission from attendance at cultural events and explore ways to enable people to attend a range of events whilst minimising risk of transmission. We aimed to measure any impact on risk of COVID-19 transmission from attendance at events held at or close to commercially viable capacity using routinely collected data. METHODS: Data were obtained on attendees at Phase 3 Events Research Programme events, for which some infection risk mitigation measures were in place (i.e. evidence of vaccination or a negative lateral flow test). Attendance data were linked with COVID-19 test result data from the UK Test and Trace system. Using a self-controlled case series design, we measured the within person incidence rate ratio for testing positive for COVID-19, comparing the rate in days 3 to 9 following event attendance (high risk period) with days 1 and 2 and 10-16 (baseline period). Rate ratios were adjusted for estimates of underlying regional COVID-19 prevalence to account for population level fluctuations in infection risk, and events were grouped into broadly similar types. RESULTS: From attendance data available for 188,851 attendees, 3357 people tested positive for COVID-19 during the observation period. After accounting for total testing trends over the period, incidence rate ratios and 95% confidence intervals for positive tests were 1.16 (0.53-2.57) for indoor seated events, 1.12 (0.95-1.30) for mainly outdoor seated events, 0.65 (0.51-0.83) for mainly outdoor partially seated events, and 1.70 (1.52-1.89) for mainly outdoor unseated multi-day events. CONCLUSIONS: For the majority of event types studied in the third phase of the UK Events Research Programme, we found no evidence of an increased risk of COVID-19 transmission associated with event attendance. However, we found a 70% increased risk of infection associated with attendance at mainly outdoor unseated multi-day events. We have also demonstrated a novel use for self-controlled case series methodology in monitoring infection risk associated with event attendance