Zhaobritt2009

e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are less then 1.The ability of Antarctic notothenioid fishes to mount a robust molecular response to hypoxia is largely unknown. The transcription factor, hypoxia-inducible factor-1 (HIF-1), a heterodimer of HIF-1α and HIF-1β subunits, is the master regulator of oxygen homeostasis in most metazoans. selleck chemicals We sought to determine if, in the hearts of Antarctic notothenioids, HIF-1 is activated and functional in response to either an acute heat stress or hypoxia. The red-blooded Notothenia coriiceps and the hemoglobinless icefish, Chaenocephalus aceratus, were exposed to their critical thermal maximum (CTMAX) or hypoxia (5.0 ± 0.3 mg of O2 L-1) for 2 h. Additionally, N. coriiceps was exposed to 2.3 ± 0.3 mg of O2 L-1 for 12 h, and red-blooded Gobionotothen gibberifrons was exposed to both levels of hypoxia. Levels of HIF-1α were quantified in nuclei isolated from heart ventricles using western blotting. Transcript levels of genes involved in anaerobic metabolism, and known to be regulated by HIF-1, were quantified by real-time PCR, and lactate levels were measured in heart ventricles. Protein levels of HIF-1α increase in nuclei of hearts of N. coriiceps and C. aceratus in response to exposure to CTMAX and in hearts of N. coriiceps exposed to severe hypoxia, yet mRNA levels of anaerobic metabolic genes do not increase in any species, nor do lactate levels increase, suggesting that HIF-1 does not stimulate metabolic remodeling in hearts of notothenioids under these conditions. Together, these data suggest that Antarctic notothenioids may be vulnerable to hypoxic events, which are likely to increase with climate warming.Wolbachia are intracellular bacteria that infect a wide range of invertebrates and have evolved various strategies to alter host reproduction for their own survival and dissemination. In small brown planthopper Laodelphax striatellus, Wolbachia-infected females lay more eggs than uninfected females. Our previous study has shown that Wolbachia are abundant in ovarian cells of L. striatellus and change the number of apoptotic nurse cells in a caspase-dependent manner to provide nutrition for oogenesis. The cellular and molecular bases of the Wolbachia-mediated alterations in L. striatellus oogenesis remain largely unknown. Here, we investigated whether germ cell mitosis, which has been implicated in determination of egg production rates, influences the interaction between fecundity and Wolbachia in L.striatellus. We used an anti-phospho-histone 3 (pH3) antibody to label and visualize mitotic cells. Microscopic observations indicated that the Wolbachia strain wStri increased the number of ovarioles that contained mitotic germ cells. The increased fecundity of Wolbachia-infected females was a result of mitosis of germ cells; the frequency of germ cell mitosis was much higher in infected females than in uninfected females. In addition, mitosis inhibition by Cdc20, CDK1, and CycB messenger RNA interference in Wolbachia-infected L. striatellus markedly decreased egg numbers. Live Wolbachia recolonization enhanced the egg production of uninfected L. striatellus by directly affecting mitosis regulators. Together, these data suggest that wStri might increase germ cell mitosis to enhance the fecundity of L. striatellus in a mitosis-regulating manner. Our findings establish a link between Wolbachia-induced mitosis and Wolbachia-mediated egg production effects.The sensitivity to volatile carbon dioxide (CO2) produced by humans and other animals is a critical component in the host preference behaviors of the malaria vector mosquito Anopheles coluzzii. The molecular receptors responsible for the ability to sense CO2 are encoded by three putative gustatory receptor (Gr) genes (Gr22,23,24) which are expressed in a distinctive array of sensory neurons housed in maxillary palp capitate peg sensilla of An. coluzzii. Despite the identification of these components and subsequent studies, there is a paucity of understanding regarding the respective roles of these three GRs in the mosquito's CO2 transduction process. To address this, we have used CRISPR/Cas9-based gene editing technique combined with in vivo electrophysiological recordings to directly examine the role of Gr22,23,24 in detecting CO2 in An. coluzzii. These studies reveal that both Gr23 and Gr24 are absolutely required to maintain in vivo CO2 sensitivity while, in contrast, Gr22 knock out mutants are still able to respond to CO2 stimuli albeit with significantly weaker sensitivity. Our data supports a model in which Gr22 plays a modulatory role to enhance the functionality of Gr23/24 complexes that are responsible for CO2 sensitivity of mosquitoes.

Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife.

Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6±3.4years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models.

Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, thete matter volume and/or worse white matter integrity.

Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

HIV-related neuroinflammation has been proposed as a catalyst for dopaminergic dysregulation in mesocortical pathways, which may contribute to the pathogenesis of depression. Abnormalities in dopaminergic neurotransmission and depression are common in people with HIV (PWH), however the link between dopamine (DA) and depression in PWH is poorly characterized. This study investigated CSF dopaminergic biomarkers, specifically DA and its metabolite, homovanillic acid (HVA), and examined their relationship with depressive symptoms and CSF neuroinflammatory markers in PWH and HIV-seronegative (HIV-) individuals.

Participants were 102 HIV- individuals and 123 PWH (mean age=42) who underwent neuropsychiatric evaluations and lumbar puncture. Current depression severity was classified using the Beck Depression Inventory-II (BDI-II). CSF was assayed for DA and HVA using high performance liquid chromatography and neuroinflammatory markers using immunoassays. Linear regressions modelled BDI-II scores as a function of HIV, dopaminergic biomarker z-scores, and their interaction, controlling for psychosocial factors.