Correlation Between Photosensitivity and Downwelling Irradiance in Mesopelagic Crustaceans

The current study determined behavioral and electrophysiological photosensitivities for three species of mesopelagic crustaceans: Pasiphaea multidentata Esmark, 1866 (Decapoda: Pasiphaeidae), Sergestes arcticus Kröyer, 1855 (Decapoda: Sergestidae), and Meganyctiphanes norvegica M. Sars, 1857 (Euphausiacea: Euphausiidae). In addition, in situ quantifications of the species’ vertical distributions in relation to downwelling irradiances were also determined in two locations in the northwest Atlantic Ocean, Wilkinson Basin (WB) and Oceanographer Canyon (OC). Data are from six 2-week cruises between June and September from 1995 to 2001. P. multidentata and M. norvegica were the most abundant large crustaceans in WB, and S. arcticus and M. norvegica were the most abundant large crustaceans in OC. The behavioral light sensitivity thresholds of P. multidentata and M. norvegica from WB were both 107 photons cm−2 s−1 and those of S. arcticus and M. norvegica from OC were both 108 photons cm−2 s−1. Electrophysiologically, P. multidentata was significantly more sensitive than M. norvegica from either location, S. arcticus was significantly more sensitive than M. norvegica from OC, and M. norvegica from WB was significantly more sensitive than M. norvegica from OC. A correlation was found between electrophysiologically measured photosensitivity and downwelling irradiance, with the most sensitive species, P. multidentata and S. arcticus, associated with the lowest irradiance at daytime depths. The photosensitivities of M. norvegicacollected from the clearer waters of OC were significantly lower than those of individuals collected from the more turbid WB waters. These results indicate that downwelling irradiance has a significant impact on interspecies and intraspecies vertical distribution patterns in the mesopelagic realm

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization

&lt;p&gt;Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.&lt;/p&gt;</p

Automated evaluation of probe-based confocal laser endomicroscopy in the lung

Rationale Probe-based confocal endomicroscopy provides real time videos of autoflourescent elastin structures within the alveoli. With it, multiple changes in the elastin structure due to different diffuse parenchymal lung diseases have previously been described. However, these evaluations have mainly relied on qualitative evaluation by the examiner and manually selected parts post-examination. Objectives: To develop a fully automatic method for quantifying structural properties of the imaged alveoli elastin and to perform a preliminary assessment of their diagnostic potential. Methods 46 patients underwent probe-based confocal endomicroscopy, of which 38 were divided into 4 groups categorizing different diffuse parenchymal lung diseases. 8 patients were imaged in representative healthy lung areas and used as control group. Alveolar elastin structures were automatically segmented with a trained machine learning algorithm and subsequently evaluated with two methods developed for quantifying the local thickness and structural connectivity. Measurements and main results The automatic segmentation algorithm performed generally well and all 4 patient groups showed statistically significant differences with median elastin thickness, standard deviation of thickness and connectivity compared to the control group. Conclusion Alveoli elastin structures can be quantified based on their structural connectivity and thickness statistics with a fully-automated algorithm and initial results highlight its potential for distinguishing parenchymal lung diseases from normal alveoli

Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection

Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6–infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, “fused” liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6–infected mice generated type 1 liver kidney microsomal–like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6–infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases

Muscle Expression of Mutant Androgen Receptor Accounts for Systemic and Motor Neuron Disease Phenotypes in Spinal and Bulbar Muscular Atrophy

SummaryX-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene. Pathological findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a role for muscle in disease pathogenesis. To determine the contribution of muscle, we developed a BAC mouse model featuring a floxed first exon to permit cell-type-specific excision of human AR121Q. BAC fxAR121 mice develop systemic and neuromuscular phenotypes, including shortened survival. After validating termination of AR121 expression and full rescue with ubiquitous Cre, we crossed BAC fxAR121 mice with Human Skeletal Actin-Cre mice. Muscle-specific excision prevented weight loss, motor phenotypes, muscle pathology, and motor neuronopathy and dramatically extended survival. Our results reveal a crucial role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective treatments

Measuring and improving respiratory outcomes in cystic fibrosis lung disease: Opportunities and challenges to therapy

Cystic fibrosis (CF) is a life-shortening disease with significant morbidity. Despite overall improvements in survival, patients with CF experience frequent pulmonary exacerbations and declining lung function, which often accelerates during adolescence. New treatments target steps in the pathogenesis of lung disease, such as the basic defect in CF (CF Transmembrane Conductance Regulator [CFTR]), pulmonary infections, inflammation, and mucociliary clearance. These treatments offer hope but also present challenges to patients, clinicians, and researchers. Comprehensive assessment of efficacy is critical to identify potentially beneficial treatments. Lung function and pulmonary exacerbation are the most commonly used outcome measures in CF clinical research. Other outcome measures under investigation include measures of CFTR function; biomarkers of infection, inflammation, lung injury and repair; and patient-reported outcomes. Molecular diagnostics may help elucidate the complex CF airway microbiome. As new treatments are developed for patients with CF, efforts should be made to balance treatment burden with quality of life. This review highlights emerging treatments, obstacles to optimizing outcomes, and key future directions for research

A continental analysis of ecosystem vulnerability to atmospheric nitrogen deposition

Atmospheric nitrogen (N) deposition has been shown to decrease plant species richness along regional deposition gradients in Europe and in experimental manipulations. However, the general response of species richness to N deposition across different vegetation types, soil conditions, and climates remains largely unknown even though responses may be contingent on these environmental factors. We assessed the effect of N deposition on herbaceous richness for15,136 forest, woodland, shrubland, and grassland sites across the continental United States, to address how edaphic and climatic conditions altered vulnerability to this stressor. In our dataset, with N deposition ranging from 1 to 19 kg N·ha−1·y−1, we found a unimodal relationship; richness increased at low deposition levels and decreased above 8.7 and 13.4 kg N·ha−1·y−1 in open and closed-canopy vegetation, respectively. N deposition exceeded critical loads for loss of plant species richness in 24% of 15,136 sites examined nationwide. There were negative relationships between species richness and N deposition in 36% of 44 community gradients. Vulnerability to N deposition was consistently higher in more acidic soils whereas the moderating roles of temperature and precipitation varied across scales. We demonstrate here that negative relationships between N deposition and species richness are common, albeit not universal, and that fine-scale processes can moderate vegetation responses to N deposition. Our results highlight the importance of contingent factors when estimating ecosystem vulnerability to N deposition and suggest that N deposition is affecting species richness in forested and nonforested systems across much of the continental United States

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees