Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 Ϯ 3% of the glucan phosphate and 20 Ϯ 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of glucan by intestinal epithelial cells was not Dectindependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of glucan. Oral glucan increased systemic levels of interleukin (IL)-12 (151 Ϯ 15%) in mice. Oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.

Background: Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factoralpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-α in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKA y .

Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other's spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses. Viral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.

BackgroundHair cortisol concentration (HCC), as a novel promising method to retrospectively measure hypothalamic-pituitary-adrenal (HPA) axis activation, is being increasingly studied. We tested the relationships between HCC and a range of possible confounding variables in a Spanish sample of healthy adults and pregnant women.MethodsThe number of healthy adults who participated in the study was 529, being 270 males and 259 females, with a combined mean age of 37.88 years (SD = 15.66). Additionally, a separate sample of 62 pregnant women was also recruited with a mean age of 32.95 (SD = 3.67), and in the first trimester of pregnancy. Each participant was interviewed before the study to obtain sociodemographic and lifestyle variables, and a hair sample was taken from the posterior vertex of the head, cut as close to the scalp as possible. Assuming the average growth rate of head hair is 1 cm per month, a 3-cm segment was analysed, in order to measure the cortisol concentrations from a three-month period. For the pregnant women, hair samples for each trimester of pregnancy were analysed.ResultsThe mean hair cortisol concentration was 127.91 (111.52) pg/mg for the general sample. The variables of age, education, employment status, use of hair dyes, use of oral contraceptives, and physical exercise had a significant relation to HCC. When adjusted for further variables, only education and physical exercise remained statistically significant. When including the use of oral contraceptives and only with respect to females, only physical exercise remains statistically significant. For the subsample of pregnant woman, the mean hair cortisol concentration was 334.51 (409.77) pg/mg for the first trimester, 302.18 (270.24) pg/mg for the second trimester, and 331.31 (295.46) pg/mg for the third trimester of pregnancy. None of the assessed confounding variables (age, body mass index, previous miscarriages, employment status, hair dyes, dependent children and physical exercise), except education level, was related to HCC.ConclusionsIn this sample of healthy Spaniards, results suggested an association between HCC and physical exercise and educational level. In pregnant women, the prevalence of HCC was higher than in non-pregnant woman, and was related to educational level. This study emphasises the need to determine the relationship between HCC and confounders such as sociodemographic and lifestyle variables in the general population and specific groups formed by individuals such as pregnant women.

The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.

Respiratory viruses from diverse families cocirculate in human populations and are frequently detected within the same host. Although clinical studies suggest that infection by multiple different respiratory viruses may alter disease severity, animal models in which we can control the doses, timing, and strains of coinfecting viruses are critical to understanding how coinfection affects disease severity.

word count: 247 12 Text word count: 5,657 Abstract 15 Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory 16 viral infections in human populations and are detected as co-pathogens within hosts. Clinical and 17 epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce 18disease severity and that they may also interfere with each other's spread within a host population. 19To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, 20 we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted 21 influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced 22 pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was 23 associated with an early inflammatory response in the lungs and enhanced clearance of PR8. 24However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit 25 replication of PR8 within respiratory epithelia or in vitro. Inflammation in co-infected mice 26

Understanding susceptibility of seabirds to fisheries bycatch requires quantifying overlap of seabird at-sea habitat with fisheries’ distribution and effort. Pink-footed Shearwaters (Ardenna creatopus) are vulnerable seabirds that breed only in Chile. Recently, high rates of Pink-footed Shearwater bycatch (i.e. >1,500 observed mortalities 2015–2017) were documented by observers in central Chilean purse-seine fisheries. We present analysis of Pink-footed Shearwater at-sea movements and overlap with central Chilean purse-seine fleets targeting common sardine (Strangomera bentincki), Peruvian anchoveta (Engraulis ringens), and Chilean jack mackerel (Trachurus murphyi). To determine overlap during 2015–2017, we paired locations from 49 Pink-footed Shearwaters rearing nestlings at Isla Mocha, Chile, with locations and number of observed purse-seine sets in central Chile. Pink-footed Shearwaters typically visited waters ≤30 km offshore throughout central Chile. Foraging trip durations varied interannually, with longer trips in 2016, but all years revealed persistent foraging hotspots near Valdivia, the Gulf of Arauco, and Isla Mocha, Chile. Greatest overlap between Pink-footed Shearwaters and fisheries occurred with the sardine/anchoveta fleet near Valdivia (artisanal and industrial) and the Gulf of Arauco (artisanal); overlap with the jack mackerel fleet was minimal. Given Pink-footed Shearwater bycatch documented in these fisheries, this overlap may indicate risk of bycatch for these birds, although we did not directly quantify shearwater–fisheries interaction. Our results can inform further fishery monitoring efforts, as well as collaboration among scientists, managers, and fishers to identify, quantify, and reduce fisheries bycatch of Pink-footed Shearwaters within Chile and internationally.