Seedling Uptake and Fate of Soil-applied Capsaicin, a Potential Browse Deterrent

Seedling damage due to browse constitutes a major challenge to afforestation and reforestation efforts in the Central Hardwood Forest region of the USA. Many efforts have been made to deter herbivores, but the costs, implementation methods, and relative ineffectiveness of existing mitigation options often preclude operational implementation. An alternate means of deterring wildlife browse is capsaicin, a hot pepper concentrate, which has been reported to decrease herbivory of tree seedlings and is available in a controlled-release form designed to act systemically following application to the soil and subsequent plant uptake. However, the degree to which seedlings are capable of absorbing capsaicin from the soil solution and the location of absorbed capsaicin within the plant remain largely unexamined. A greenhouse experiment was conducted to determine the potential absorption of soil-applied capsaicin in post-transplant northern red oak (Quercus rubra L.) seedlings in conjunction with a growth chamber study investigating the fate of capsaicin in the soil. In the first experiment, each seedling received the recommended dose of 0.03g of soil-applied capsaicin, was separated into roots, leaves, and stems at three and five weeks after capsaicin application, and was analyzed using QQQ-LC/MS. No capsaicin or capsaicinoids were found in any of the tissues. Capsaicin was quantified in the soil, leachates, and ambient air using QQQ-LC/MS in a related experiment with the same growing conditions and capsaicin application rate. These results reflect observed efficacy of capsaicin in the field, and the implications of this study should be considered when evaluating animal browse mitigation measures

The Role of Alveolar Epithelial Cells in Initiating and Shaping Pulmonary Immune Responses: Communication between Innate and Adaptive Immune Systems

Macrophages and dendritic cells have been recognized as key players in the defense against mycobacterial infection. However, more recently, other cells in the lungs such as alveolar epithelial cells (AEC) have been found to play important roles in the defense and pathogenesis of infection. In the present study we first compared AEC with pulmonary macrophages (PuM) isolated from mice in their ability to internalize and control Bacillus Calmette-Guérin (BCG) growth and their capacity as APCs. AEC were able to internalize and control bacterial growth as well as present antigen to primed T cells. Secondly, we compared both cell types in their capacity to secrete cytokines and chemokines upon stimulation with various molecules including mycobacterial products. Activated PuM and AEC displayed different patterns of secretion. Finally, we analyzed the profile of response of AEC to diverse stimuli. AEC responded to both microbial and internal stimuli exemplified by TLR ligands and IFNs, respectively. The response included synthesis by AEC of several factors, known to have various effects in other cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP-1 plays a role in the recruitment of monocytes and macrophages to sites of infection and macrophages are the main producers of TNF, we speculate that both cell types can stimulate each other. Also, another cell-cell interaction was suggested when IFNs (produced mainly by lymphocytes) were able to induce expression of chemokines (IP-10 and RANTES) by AEC involved in the recruitment of circulating lymphocytes to areas of injury, inflammation, or viral infection. In the current paper we confirm previous data on the capacity of AEC regarding internalization of mycobacteria and their role as APC, and extend the knowledge of AEC as a multifunctional cell type by assessing the secretion of a broad array of factors in response to several different types of stimuli

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

An international comparative family medicine study of the Transition Project data from the Netherlands, Malta, Japan and Serbia. An analysis of diagnostic odds ratios aggregated across age bands, years of observation and individual practices

Item does not contain fulltextINTRODUCTION: This is a study of the process of diagnosis in family medicine (FM) in four practice populations from the Netherlands, Malta, Serbia and Japan. Diagnostic odds ratios (ORs) for common reasons for encounter (RfEs) and episode titles are used to study the process of diagnosis in international FM and to test the assumption that data can be aggregated across different age bands, practices and years of observation. METHODOLOGY: Participating family doctors (FDs) recorded details of all their patient contacts in an episode of care (EoC) structure using the International Classification of Primary Care (ICPC). RfEs presented by the patient and the diagnostic labels (EoC titles) recorded for each encounter were classified with ICPC. The relationships between RfEs and episode titles were expressed as ORs using Bayesian probability analysis to calculate the posterior (post-test) odds of an episode title given an RfE, at the start of a new EoC. RESULTS: The distributions of diagnostic ORs from the four population databases are tabled across age groups, years of observation and practices. CONCLUSIONS: There is a lot of congruence in diagnostic process and concepts between populations, across age groups, years of observation and FD practices, despite differences in the strength of such diagnostic associations. There is particularly little variability of diagnostic ORs across years of observation and between individual FD practices. Given our findings, it makes sense to aggregate diagnostic data from different FD practices and years of observation. Our findings support the existence of common core diagnostic concepts in international FM

An international comparative family medicine study of the Transition Project data from the Netherlands, Malta and Serbia. Is family medicine an international discipline? Comparing incidence and prevalence rates of reasons for encounter and diagnostic titles of episodes of care across populations

Item does not contain fulltextINTRODUCTION: This is a study of the epidemiology of family medicine (FM) in three practice populations from the Netherlands, Malta and Serbia. Incidence and prevalence rates, especially of reasons for encounter (RfEs) and episode labels, are compared. METHODOLOGY: Participating family doctors (FDs) recorded details of all their patient contacts in an episode of care (EoC) structure using electronic patient records based on the International Classification of Primary Care (ICPC), collecting data on all elements of the doctor-patient encounter. RfEs presented by the patient, all FD interventions and the diagnostic labels (EoCs labels) recorded for each encounter were classified with ICPC (ICPC-2-E in Malta and Serbia and ICPC-1 in the Netherlands). RESULTS: The content of family practice in the three population databases, incidence and prevalence rates of the common top 20 RfEs and EoCs in the three databases are given. CONCLUSIONS: Data that are collected with an episode-based model define incidence and prevalence rates much more precisely. Incidence and prevalence rates reflect the content of the doctor-patient encounter in FM but only from a superficial perspective. However, we found evidence of an international FM core content and a local FM content reflected by important similarities in such distributions. FM is a complex discipline, and the reduction of the content of a consultation into one or more medical diagnoses, ignoring the patient's RfE, is a coarse reduction, which lacks power to fully characterize a population's health care needs. In fact, RfE distributions seem to be more consistent between populations than distributions of EoCs are, in many respects

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population