Relationship between Expression of Cellular Receptor-27.8kDa and Lymphocystis Disease Virus (LCDV) Infection

The 27.8kDa membrane protein from flounder (Paralichthys olivaceus) gill (FG) cells was previously identified as a putative cellular receptor involved in lymphocystis disease virus (LCDV) infection. In this paper, the expression of receptor-27.8kDa (27.8R) and LCDV loads in FG cells and hirame natural embryo (HINAE) cells were investigated upon LCDV infection and anti-27.8R monoclonal antibody (MAb) treatment. The results showed the 27.8R was expressed and co-localized with LCDV in both FG and HINAE cell surface. After LCDV infection, the expression of 27.8R exhibited a dose-dependent up-regulation with the increasing of LCDV titers, and demonstrated a tendency to increase firstly and then decrease during a time course up to 9 days; LCDV copies showed a similar variation trend to the 27.8R expression, however, it reached the highest level later than did the 27.8R expression. Additionally, the 27.8R expression and LCDV copies in FG cells were higher than those in HINAE cells. In the presence of increasing concentration of the anti-27.8R MAbs, the up-regulation of 27.8R expression and the copy numbers of LCDV significantly declined post LCDV infection, and the cytopathic effect induced by LCDV in the two cell lines was accordingly reduced, indicating anti-27.8R MAbs pre-incubation could inhibit the up-regulation of 27.8R expression and LCDV infection. These results suggested that LCDV infection could induce up-regulation of 27.8R expression, which in turn increased susceptibility and availability of FG and HINAE cells for LCDV entry, providing important new insights into the LCDV replication cycle and the interaction between this virus and the host cells.     

Immune response of Japanese flounder Paralichthys olivaceus to outer membrane protein of Edwardsiella tarda

The humoral and cellular immune responses of Japanese flounder, Paralichthys olivaceus, were investigated following intraperitioneal injection with outer membrane protein (OMP) of Edwardsiella tarda in Freund's incomplete adjuvant (FIA). The specific serum antibody titre against OMP of E. tarda were measured using ELISA for 14 weeks, and the total serum antibody concentrations were also determined according to the sandwich ELISA standard model constructed using purified IgM. Both of the specific and total antibodies had an increase and reached their peaks 4 weeks after immunization. Simultaneously, the percentages of sIg + lymphocytes in blood, spleen, pronephros and mesonephros were detected by flow cytometry. It was shown that the percentages of sIg + lymphocytes in all lymphoid organs reached their peak levels 4 weeks after immunization, and then decreased gradually. To investigate the protection against infection, three challenges were performed in the same way at day 14, 30 and 100 after immunization, fish challenged at day 30 showed a higher relative percentage survival (RPS) of 71 compared to the 14-day group (30) and 100-day group (53), which indicated a positive correlation between the survival and the levels of the antibody.     

Cox Regression in Nested Case–Control Studies with Auxiliary Covariates

Summary Nested case–control (NCC) design is a popular sampling method in large epidemiological studies for its cost effectiveness to investigate the temporal relationship of diseases with environmental exposures or biological precursors. Thomas' maximum partial likelihood estimator is commonly used to estimate the regression parameters in Cox's model for NCC data. In this article, we consider a situation in which failure/censoring information and some crude covariates are available for the entire cohort in addition to NCC data and propose an improved estimator that is asymptotically more efficient than Thomas' estimator. We adopt a projection approach that, heretofore, has only been employed in situations of random validation sampling and show that it can be well adapted to NCC designs where the sampling scheme is a dynamic process and is not independent for controls. Under certain conditions, consistency and asymptotic normality of the proposed estimator are established and a consistent variance estimator is also developed. Furthermore, a simplified approximate estimator is proposed when the disease is rare. Extensive simulations are conducted to evaluate the finite sample performance of our proposed estimators and to compare the efficiency with Thomas' estimator and other competing estimators. Moreover, sensitivity analyses are conducted to demonstrate the behavior of the proposed estimator when model assumptions are violated, and we find that the biases are reasonably small in realistic situations. We further demonstrate the proposed method with data from studies on Wilms' tumor.     

Developmental regulation of group I metabotropic glutamate receptors in the premature brain and their protective role in a rodent model of periventricular leukomalacia

Cerebral white matter injury in premature infants, known as periventricular leukomalacia (PVL), is common after hypoxia-ischemia (HI). While ionotropic glutamate receptors (iGluRs) can mediate immature white matter injury, we have previously shown that excitotoxic injury to premyelinating oligodendrocytes (preOLs) in vitro can be attenuated by group I metabotropic glutamate receptor (mGluR) agonists. Thus, we evaluated mGluR expression in developing white matter in rat and human brain, and tested the protective efficacy of a central nervous system (CNS)-penetrating mGluR agonist on injury to developing oligodendrocytes (OLs) in vivo. Group I mGluRs (mGluR1 and mGluR5) were strongly expressed on OLs in neonatal rodent cerebral white matter throughout normal development, with highest expression early in development on preOLs. Specifically at P6, mGluR1 and mGLuR5 were most highly expressed on GalC-positive OLs compared to neurons, axons, astrocytes and microglia. Systemic administration of (1S,3R) 1-aminocyclopentane-trans-1,3,-dicarboxylic acid (ACPD) significantly attenuated the loss of myelin basic protein in the white matter following HI in P6 rats. Assessment of postmortem human tissue showed both mGluR1 and mGluR5 localized on immature OLs in white matter throughout development, with mGluR5 highest in the preterm period. These data indicate group I mGluRs are highly expressed on OLs during the peak period of vulnerability to HI and modulation of mGluRs is protective in a rodent model of PVL. Group I mGluRs may represent important therapeutic targets for protection from HI-mediated white matter injury.     

Revealing the community and metabolic potential of active methanotrophs by targeted metagenomics in the Zoige wetland of the Tibetan Plateau

The Zoige wetland of the Tibetan Plateau is one of the largest alpine wetlands in the world and a major emission source of methane. Methane oxidation by methanotrophs can counteract the global warming effect of methane released in the wetlands. Understanding methanotroph activity, diversity and metabolism at the molecular level can guide the isolation of the uncultured microorganisms and inform strategy-making decisions and policies to counteract global warming in this unique ecosystem. Here we applied DNA stable isotope probing using ¹³C-labelled methane to label the genomes of active methanotrophs, examine the methane oxidation potential and recover metagenome-assembled genomes (MAGs) of active methanotrophs. We found that gammaproteobacteria of type I methanotrophs are responsible for methane oxidation in the wetland. We recovered two phylogenetically novel methanotroph MAGs distantly related to extant Methylobacter and Methylovulum. They belong to type I methanotrophs of gammaproteobacteria, contain both mxaF and xoxF types of methanol dehydrogenase coding genes, and participate in methane oxidation via H₄MPT and RuMP pathways. Overall, the community structure of active methanotrophs and their methanotrophic pathways revealed by DNA-SIP metagenomics and retrieved methanotroph MAGs highlight the importance of methanotrophs in suppressing methane emission in the wetland under the scenario of global warming.     

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.     

Construction of Ordered Atomic Donor–Acceptor Architectures in bcc IrGa Intermetallic Compounds toward Highly Electroactive and Stable Overall Water Splitting

Benefiting from ordered atomic structures and strong d-orbital interactions, intermetallic compounds (IMCs) are promising electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, the body-centered cubic IrGa IMCs with atomic donor–acceptor architectures are synthesized and anchored on the nitrogen-doped reduced graphene oxide (i.e., IrGa/N-rGO). Structural characterizations and theoretical calculations reveal that the electron-rich Ir sites are atomically dispersed in IrGa/N-rGO, facilitating the electron transfer between Ir atoms and adsorbed species, which can efficiently decrease the energy barriers of the potential determining step for both HER and OER. Impressively, the IrGa/N-rGO||IrGa/N-rGO exhibits excellent performance for overall water splitting in alkaline medium, requiring a low cell voltage of 1.51 V to achieve 10 mA cm⁻², meanwhile, exhibiting no significant degradation for 100 h. This work demonstrates that the rational design of noble metal electrocatalysts with donor–acceptor architectures is beneficial for catalytic reactions in energy conversion applications.