Comparative metabolomics reveals the mechanism of avermectin production enhancement by <Emphasis Type="Italic">S</Emphasis>-adenosylmethionine

It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30–60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC–MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production.     

The Acoustic Habitat Hypothesis: An Ecoacoustics Perspective on Species Habitat Selection

Sound is an inherent component of the environment that provides conditions and information necessary for many animal activities. Soniferous species require specific acoustic and physical conditions suitable for their signals to be transmitted, received, and effectively interpreted to successfully identify and utilize resources in their environment and interact with conspecifics and other heterospecific organisms. We propose the Acoustic Habitat Hypothesis to explain how the acoustic environment influences habitat selection of sound-dependent species. We postulate that sound-dependent species select and occupy habitats with unique acoustic characteristics that are essential to their functional needs and conducive to the threshold of sound frequency they produce and detect. These acoustic habitats are based on the composition of biophony, geophony, and technophony in the soundscape and on the biosemiotics mechanisms described in the eco-field hypothesis. The Acoustic Habitat Hypothesis initiates questions of habitat selection that go beyond the physical attributes of the environment by applying ecoacoustics theory. We outline the theoretical basis of the Acoustic Habitat Hypothesis and provide examples from the literature to support its assumptions. The concept of acoustic habitats has been documented in the literature for many years but here, we accurately and extensively define acoustic habitat and we put this concept into a unified theory. We also include perspectives on how the Acoustic Habitat Hypothesis can stimulate a paradigm shift in conservation strategies for threatened and endangered species.     

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells

ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.     

Neuroprotective Effect of Chitosan Oligosaccharide on Hypoxic-Ischemic Brain Damage in Neonatal Rats

Neonatal hypoxic-ischemic brain damage (HIBD) is one of the leading causes of neonatal mortality and permanent neurological disability worldwide and the effective treatment strategies are not yet available. It has been demonstrated that Chitosan oligosaccharide (COS) exerts protective effect in vitro ischemic brain injury. However, no information is available on possible effects of COS on neonatal HIBD. To investigate the hypothesis of the potential neuroprotective effect of COS on the brain injury due to HIBD, 7-day-old Sprague–Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37?°C. After COS treatment, the cerebral damage was measured by behavior tasks, 2,3,5-triphenyltetrazolium chloride(TTC), Hematoxyline-Eosin(HE), Nissl and Fluoro-Jade B(FJB)staining. In addition, the oxidative stress were assayed with ipsilateral hemisphere homogenates. Immunofluorescence staining were used to examine the activation of the astrocyte and microglia. Expression of inflammatory-related proteins were analyzed by western-blot analysis. In this study we found that administration of COS ameliorated early neurological reflex behavior, significantly reduce brain infarct volume and attenuated neuronal cell injury and degeneration. Furthermore, COS markedly decreased the level of MDA, lactic acid and increased SOD, GSH-Px and T-AOC. COS attenuated hypoxic-ischemic induced up-regulation of expressions of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), meanwhile it dramatically increased the interleukin-10 (IL-10). These results suggest that COS exerts neuroprotection on hypoxic-ischemic brain damage in neonatal rats, it implies COS might be a potential therapeutic for the treatment of HIBD.     

Risk Factors and Outcomes of Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients

Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210 days, respectively. There was a trend toward fewer IFI and mold infections in the last several years. Both acute graft-versus-host disease (GVHD) (OR 1.83, p = 0.05) and corticosteroid duration (OR 1.0, p = 0.026) were significantly associated with increased risk of IFI, acute GVHD (OR 2.3, p = 0.027) emerged as the most important association with mold infections. Any IFI [HR 4.1 (2.79–6.07), p < 0.0001] and mold infections [HR 3.34 (2.1–5.1), p < 0.0001] were independently associated with non-relapse mortality (NRM). This association persisted in the setting of both acute and chronic GVHD. Corticosteroid treatment for >90 days was also significantly associated with higher NRM [HR 1.9 (1.3–2.6), p < 0.0001]. This study highlights the impact of IFI on NRM among HCT patients. The decrease in number of IFI and mold infections over the last several years may reflect the benefit of prophylaxis with mold-active antifungal agents.     

Leaf phenology mediates provenance differences in herbivore populations on valley oaks in a common garden

1. Plants from different populations often display a variation in herbivore resistance. However, it is rarely understood what plant traits mediate such differences. 2. It was tested how leaf phenology affects herbivore populations in a 15‐year‐old common garden of valley oaks (Quercus lobata Née) with different populations and maternal parents from throughout the Q. lobata range. 3. The abundance of leaf miners (Stigmella sp. Shrank) and leaf phenology of oaks in the common garden was measured. 4. Leaf miner abundance varied among provenance locations (population), but not among maternal parents within populations. Leaf phenology varied by provenance location and maternal parent, and trees that leafed out earlier accrued higher leaf‐miner abundance. Path analysis indicated that leaf phenology was the likely driver of provenance and parental differences in resistance to leaf miners. 5. Understanding population differences is particularly important when considering transport of genotypes for ornamental or restoration purposes. The present study suggests that similarity in leaf phenology may be one factor that could be used to find genotypes with a similar herbivore resistance to local genotypes.