CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10

The effect that multiple percutaneous exposures to Schistosoma larvae has on the development of early CD4+ lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) of Schistosoma mansoni cercariae, compared to a single dose (1×), results in CD4+ T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+ cell proliferation and cytokine production. FoxP3+ CD4+ regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+ cell population from 4× mice was slight, as proliferation was only partly circumvented through the in vitro addition of exogenous interleukin-2 (IL-2), and the in vivo blockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+ cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+ cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+ T cell hyporesponsiveness after repeated parasite exposure involving CD4+ cell apoptosis

Electric Versus Manual Tooth Brushing among Neuroscience ICU Patients: Is it Safe?

Poor oral hygiene has been associated with ventilator-acquired pneumonia. Yet providing oral care for intubated patients is problematic. Furthermore, concerns that oral care could raise intracranial pressure (ICP) may cause nurses to use foam swabs to provide oral hygiene rather than tooth brushing as recommended by the American Association of Critical-Care Nurses. Evidence is needed to support the safety of toothbrushing during oral care. We therefore evaluated ICP and cerebral perfusion pressure (CPP) during oral care with a manual or electric toothbrush in intubated patients in a neuroscience intensive care unit (ICU). As part of a larger 2-year, prospective, randomized clinical trial, 47 adult neuroscience ICU patients with an ICP monitor received oral care with a manual or electric toothbrush. ICP and CPP were recorded before, during, and after oral care over the first 72 h of admission. Groups did not differ significantly in age, gender, or severity of injury. Of 807 ICP and CPP measurements obtained before, during, and after oral care, there were no significant differences in ICP (P = 0.72) or CPP (P = 0.68) between toothbrush methods. Analysis of pooled data from both groups revealed a significant difference across the three time points (Wilks' lambda, 12.56; P < 0.001; partial eta(2), 0.36). ICP increased significantly (mean difference, 1.7 mm Hg) from before to during oral care (P = 0.001) and decreased significantly (mean difference, 2.1 mm Hg) from during to after oral care (P < 0.001). In the absence of preexisting intracranial hypertension during oral care, tooth brushing, regardless of method, was safely performed in intubated neuroscience ICU patients

Direct and Simultaneous Observation of Ultrafast Electron and Hole Dynamics in Germanium

Understanding excited carrier dynamics in semiconductors is crucial for the development of photovoltaics and efficient photonic devices. However, overlapping spectral features in optical/NIR pump-probe spectroscopy often render assignments of separate electron and hole carrier dynamics ambiguous. Here, ultrafast electron and hole dynamics in germanium nanocrystalline thin films are directly and simultaneously observed by attosecond transient absorption spectroscopy (ATAS) in the extreme ultraviolet at the germanium M_{4,5}-edge (~30 eV). We decompose the ATAS spectra into contributions of electronic state blocking and photo-induced band shifts at a carrier density of 8*10^{20}cm^{-3}. Separate electron and hole relaxation times are observed as a function of hot carrier energies. A first order electron and hole decay of ~1 ps suggests a Shockley-Read-Hall recombination mechanism. The simultaneous observation of electrons and holes with ATAS paves the way for investigating few to sub-femtosecond dynamics of both holes and electrons in complex semiconductor materials and across junctions.Comment: Includes Supplementary Informatio

Wildfire impact : natural experiment reveals differential short-term changes in soil microbial communities

A wildfire which overran a sensor network site provided an opportunity (a natural experiment) to monitor short-term post-fire impacts (immediate and up to three months post-fire) in remnant eucalypt woodland and managed pasture plots. The magnitude of fire-induced changes in soil properties and soil microbial communities was determined by comparing (1) variation in fire-adapted eucalypt woodland vs. pasture grassland at the burnt site; (2) variation at the burnt woodland-pasture sites with variation at two unburnt woodland-pasture sites in the same locality; and (3) temporal variation pre- and post-fire. In the eucalypt woodland, soil ammonium, pH and ROC content increased post-fire, while in the pasture soil, soil nitrate increased post-fire and became the dominant soluble N pool. However, apart from distinct changes in N pools, the magnitude of change in most soil properties was small when compared to the unburnt sites. At the burnt site, bacterial and fungal community structure showed significant temporal shifts between pre- and post-fire periods which were associated with changes in soil nutrients, especially N pools. In contrast, microbial communities at the unburnt sites showed little temporal change over the same period. Bacterial community composition at the burnt site also changed dramatically post-fire in terms of abundance and diversity, with positive impacts on abundance of phyla such as Actinobacteria, Proteobacteria and Firmicutes. Large and rapid changes in soil bacterial community composition occurred in the fire-adapted woodland plot compared to the pasture soil, which may be a reflection of differences in vegetation composition and fuel loading. Given the rapid yet differential response in contrasting land uses, identification of key soil bacterial groups may be useful in assessing recovery of fire-adapted ecosystems, especially as wildfire frequency is predicted to increase with global climate change

An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the “price” of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions These results indicate that increasing the “price” of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy