Gating NO Release from Nitric Oxide Synthase

We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV–vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for wt NOS and three mutants (H134S, I223V, H134S/I223V). We have confirmed that wt gsNOS has the lowest NO release rate of known NOS enzymes, whether bacterial or mammalian. We also have found that steric clashes at positions 223 and 134 hinder NO escape, as judged by enhanced rates in the single mutants. The empirical rate of NO release from the gsNOS double mutant (H134/I223V) is nearly as rapid as that of the fastest mammalian enzymes, demonstrating that both positions 223 and 134 function as gates for escape of the product diatomic molecule

Stem-Boring Caterpillars of Switchgrass in the Midwestern United States

Lepidopteran stem borers were collected from switchgrass, Panicum virgatum L., tillers showing symptoms of infestation at seven locations in Illinois and Iowa, with additional observations made on larval and adult activity. Blastobasis repartella (Dietz) (Coleophoridae), whose only known host is switchgrass, was common in plots grown for \u3e5 yr, whereas the polyphagous stalk borer, Papaipema nebris (Guenée) (Noctuidae), was abundant in newly established (i.e., first- and second year) switchgrass. Haimbachia albescens Capps (Crambidae) was collected from two locations in Illinois, making switchgrass the first known host for this species. Entry holes made by B. repartella and H. albescens were usually 1-2 cm above the soil surface, precluding discrimination between these species based on external appearance of damage. Although P. nebris often entered stems within 5 cm of the soil surface, they also seemed to move between stems and were the only species entering stems at heights \u3e15 cm. Adults of B. repartella were active on and above the switchgrass canopy by 2130 hours, with peak activity at ≈0230 hours. Activity of B. repartella adults seemed greatly reduced on one night with relatively cool temperatures and low wind speeds. Data from switchgrass and giant ragweed, Ambrosia trifida L., suggest P. nebris larvae move out of switchgrass during July in search of hosts with larger diameter stems, although by then hosts such as corn, Zea mays L., or Miscanthus spp. may have outgrown the potential for serious damage. However, switchgrass could contribute to greater adult populations of P. nebris if thick-stemmed hosts such as giant ragweed are not managed

Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation

Pathogenesis and treatment of chronic pulmonary disease

Covid-19 Vaccine Confidence, Concerns, and Uptake in Children Aged 5 and Older in Calgary, Alberta: a Longitudinal Cohort Study

OBJECTIVES: Beginning early in the pandemic, there was a worldwide effort to develop effective vaccines against the SARS-CoV-2 virus. Before and after the approval and implementation of vaccines, there were concerns about their need as well as their safety and rapid development. We explored child demographic characteristics and parental concerns to identify factors associated with the decision to vaccinate. METHODS: A cohort of 1035 children from Calgary was assembled in 2020 to participate in 5 visits every 6 months for survey completion and blood sampling for SARS-CoV-2 antibodies. Visits 1 to 2 occurred before approval of vaccines for children; Visits 3 to 5 occurred after vaccine approval for different age groups. We described vaccine concerns and utilized logistic regression to examine factors associated with the decision to vaccinate in children ≥5 years of age. RESULTS: Children ≥12 years of age, of non-white or non-black ethnicity, and who had received previous influenza vaccines had higher odds of being vaccinated against SARS-CoV-2. Children with previous SARS-CoV-2 infection had lower odds of being vaccinated. The most common concerns in early 2021 were about vaccine safety. By summer 2022, the most common concern was a belief that vaccines were not necessary. Through the study 88% of children were vaccinated. CONCLUSIONS: Age, ethnicity, previous infections, and vaccine attitudes were associated with parental decision to vaccinate against SARS-CoV-2. For children who remained unvaccinated, parents continued to have safety concerns and questioned the necessity of the vaccine. Complacency about the need for vaccination may be more challenging to address and overcome than concerns about safety alone

An update on oral cavity cancer:epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput ‘omics’ technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease. Keywords: Epidemiology, Oral Cancer, Survival, Risk Factors, Squamous Cell Carcinoma, Mouth Neoplasm

The Na 8200 Angstrom Doublet as an Age Indicator in Low-Mass Stars

We investigate the use of the gravity sensitive neutral sodium (NaI) doublet at 8183 Angstroms 8195 Angstroms (Na 8200 Angstrom doublet) as an age indicator for M dwarfs. We measured the Na doublet equivalent width (EW) in giants, old dwarfs, young dwarfs, and candidate members of the Beta Pic moving group using medium resolution spectra. Our Na 8200 Angstrom doublet EW analysis shows that the feature is useful as an approximate age indicator in M-type dwarfs with (V-K_s) >= 5.0, reliably distinguishing stars older and younger than 100 Myr. A simple derivation of the dependence of the Na EW on temperature and gravity supports the observational results. An analysis of the effects of metallicity show that this youth indicator is best used on samples with similar metallicity. The age estimation technique presented here becomes useful in a mass regime where traditional youth indicators are increasingly less reliable, is applicable to other alkali lines, and will help identify new-low mass members in other young clusters and associations.Comment: 26 pages, 8 figures, accepted to the Astronomical Journa

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer\u27s disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials

A Careful Look at Binding Site Reorganization in the even-skipped Enhancers of Drosophila and Sepsids

Organismic and Evolutionary Biolog

Metabolic disorders and the risk of head and neck cancer: a protocol for a systematic review and meta-analysis

Introduction Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer internationally. Established risk factors include smoking, alcohol and presence of human papillomavirus (HPV). The incidence rate of new disease continues to rise, despite falls in alcohol consumption and a reduction in smoking, the rising rates are unlikely to be solely attributed to HPV status alone. Obesity and its associated conditions such as type 2 diabetes (T2D) are implicated in the risk and progression of a variety of cancers, but there is paucity of evidence regarding its role in HNSCC. Methods and analysis A systematic review of cohort studies, reporting a risk of incident HNSCC, will be included. A systematic search strategy has been developed, multiple databases will be searched from January 1966 to November 2021, including Cochrane Library, OVID SP versions of Medline and EMBASE. The primary outcome will be incident HNSCC based on exposures of T2D, obesity, dyslipidaemia and hypertension as defined by the WHO. A combined risk effect across studies will be calculated using meta-analysis, although depending on the heterogeneity in study design, exposure and outcome reporting this may not be possible. Ethics and dissemination No ethical approval is required for this systematic review. The review will be published in a relevant peer-review journal and findings will be presented at scientific meetings in both poster and oral presentation form. PROSPERO registration number details This study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) with study registration number CRD42021250520. This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance statement