Biology subjects

Wei, C.

Publications and source records attributed to Wei, C..

79 records · Page 5Linked to original sources

bioRxiv2020

Great Expectations: A Critical Review of and Recommendations for the study of Reward Processing as a Cause and Predictor of Depression

Both human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Given the great promise of this research line, we scrutinize those findings and the theoretical claims that underlie them. To achieve this, we apply the framework provided by classical work on causality as well as contemporary approaches to prediction. We identify a number of conceptual, practical, and analytical challenges to this line of research, and use a pre-registered meta-analysis to quantify the longitudinal associations between reward processing aberrations and depression. We also investigate the impact of measurement error on reported data. We find that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the evidence thus far does not exclude their possible causal role in depression.

neuroscience↗

bioRxiv2020

p38delta genetic ablation protects female mice from anthracycline cardiotoxicity

BACKGROUNDThe efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative isoforms p38{gamma} and p38{delta}, remain uncharacterized. OBJECTIVESTo determine the potential cardioprotective effects of p38{gamma} and p38{delta} genetic deletion in mice subjected to acute DOX treatment. METHODSMale and female wild-type (WT), p38{gamma}-/-, p38{delta}-/- and p38{gamma}-/-{delta}-/- mice were injected with 30 mg/kg DOX and their survival was tracked for ten days. During this period cardiac function was assessed by echocardiography and electrocardiography and fibrosis by PicroSirius Red staining. Immunoblotting was performed to assess the expression of signaling proteins and markers linked to autophagy. RESULTSSignificantly improved survival was observed in p38{delta}-/- female mice post-DOX relative to WT females, but not in p38{gamma}-/- or p38{gamma}-/-{delta}-/- male or female mice. The improved survival in DOX-treated p38{delta}-/- females was associated with decreased fibrosis, increased cardiac output and LV diameter relative to DOX-treated WT females, and similar to saline-treated controls. Structural and echocardiographic parameters were either unchanged or worsened in all other groups. Increased autophagy, as evidenced by increased LC3-II level, and decreased mTOR activation was also observed in DOX-treated p38{delta}-/- females. CONCLUSIONSp38{delta} plays a crucial role in promoting DOX-induced cardiotoxicity in female mice by inhibiting autophagy. Therefore, p38{delta} targeting could be a potential cardioprotective strategy in anthracycline chemotherapy. NEW AND NOTEWORTHYThis study for the first time identifies the roles of the alternative p38{gamma} and p38{delta} MAPK isoforms in promoting DOX-cardiotoxicity in a sex-specific manner. While p38{gamma} systemic deletion did not affect DOX-cardiotoxicity, p38{delta} systemic deletion was cardioprotective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38{delta}-/- females and autophagy was increased.

physiology↗

bioRxiv2020

Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. ResultsWe surveyed the fecal and sputum (as a proxy for lung) microbiota in healthy controls and NSCLC patients of various stages, and found significant perturbations of gut- and sputum-microbiota in patients with NSCLC and DM. Machine-learning models combining both microbiota (mixed models) performed better than either dataset in patient stratification, with the highest area under the curve (AUC) value of 0.842. Sputum-microbiota contributed more than the gut in the mixed models; in addition, sputum-only models performed similarly to the mixed models in most cases. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers. ConclusionOur results indicate that alterations of sputum-microbiota have stronger relationships with NSCLC and distant metastasis than the gut, and strongly support the feasibility of metagenome-based non-invasive disease diagnosis and risk evaluation.

microbiology↗

bioRxiv2019

qKW9 encodes a pentatricopeptide repeat protein affecting photosynthesis and grain filling in maize

Kernel weight is an important yield component in maize that was selected during domestication. Many kernel weight genes have been identified through mutant analysis, and are mostly involved in the biogenesis and functional maintenance of organelles or other fundamental cellular activities. However, only a limited number of loci underlying quantitative variation in kernel weight have been cloned. Here we characterize a maize kernel weight QTL, qKW9 and find that it encodes a DYW motif pentatricopeptide repeat protein involved in C-to-U editing of NdhB, a subunit of the chloroplast NADH dehydrogenase-like complex. In a null qKW9 background, C-to-U editing of NdhB was abolished, and photosynthesis was reduced, suggesting that qKW9 regulates kernel weight by controling the maternal source of photosynthate for grain filling. Characterization of qKW9 highlights the importance of optimizing photosynthesis on maize grain yield production.

plant biology↗

bioRxiv2019

Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

The births of more than 8 million infants have been enabled globally through assisted reproductive technologies (ARTs), including conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with either fresh embryo transfer (ET) or frozen embryo transfer (FET). However, the potential for elevated risks of ART-related disorders persists in adult life, and the underlying epigenetic mechanisms are largely uncharacterized. Here, we recruited 100 nuclear families and profiled the DNA methylomes, genome-wide histone modifications and transcriptomes to clarify the inherent extra risks attributable to specific ART procedures. We discovered that IVF-ET seemed to introduce less disturbance into the infant epigenome than IVF-FET or ICSI-ET did. Furthermore, we noted approximately half of the DNA methylomic changes in ART-conceived offspring could be explained by parental background biases. Through removal of the parental effect, we confirmed that ART per se would introduce minor DNA methylation changes locally. More importantly, we found that ART-induced epigenomic alterations were highly enriched in the processes which might contribute to increased incidence of preeclampsia during pregnancy and metabolic syndrome in offspring. Overall, our study provides an epigenetic basis for the potential long-term health risks in ART-conceived offspring that reinforces the need to review all methods of human ART.

genetics↗

bioRxiv2018

Experimental infection characteristics of Bordetella pertussis via aerosol challenge on rhesus macaques

The effect of aerosol challenge of rhesus macaques with Bordetella pertussis and the feasibility of using rhesus monkeys as an animal model for pertussis infection were evaluated in this study. Four 1-year old rhesus macaques were aerosol challenged with B. pertussis at the concentration of 105 CFU/mL for 30 min (group 1) or 60 min (group 2). Rectal temperature was found slightly increased at days 3 and 5 and returned to baseline levels at day 21 after challenge. White blood cell counts peaked at day 7, with a 4.7~6.1-fold increase and returned to baseline levels at day 45. Bacteria colonization of nasopharyngeal swabs was observed, and the number of colonies was gradually increased and peaked at day 14, reaching 5.4-8.1 x 106/mL. The seroconversion rate of anti-pertussis toxin (PT), pertactin (PRN), and filamentous hemagglutinin(FHA) antibodies was 100%, with an increase in geometric mean titers after challenge. Analysis of cytokines revealed that the levels of cytokines including IL-2, IL-6, IL-8, IL-10, IL-17A, IL-13, IL-12, and IL-18 were significantly increased at days 5 to 14 in group 2. These results demonstrate that the characteristic of pertussis infection in infant rhesus macaque was similar as in human beings, which provide a clue to using infant rhesus macaque as a candidate model for pertussis infection in the future studies

microbiology↗

bioRxiv2018

Preliminary study on the application of PspA as carrier

The aim of the study is to research the feasibility of pneumococcal surface protein A (PspA) using as carrier protein. Three recombinant pneumococcal surface proteins A (come from family1 and family 2) were expressed by prokaryotic expression system and were conjugated to group A meningococcal polysaccharide (GAMP) to make three polysaccharide-protein conjugates. The conjugates, un-conjugated proteins, GAMP and GAMP-TT vaccine bulk (used as positive control) were immunized to mice and their immune effects were evaluated by the method of ELISA, FCM and SBA. The results showed that the polysaccharide-protein conjugates can produce higher levels of anti-GAMP IgG titers (P < 0.05), higher ratios of Th1/Th2 (P < 0.05) and higher levels of serum bactericidal activity (P < 0.05) compared with the un-conjugated GAMP. The conjugation of PspAs to GAMP also enhanced the anti-PspA responses compared with un-conjugated PspAs except PspA3. In conclusion, all the results indicated that three PspAs were suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the GAMP, and would protect against group A of epidemic cerebrospinal meningitis and also have the potential to provide broad protection from Streptococcus pneumonia.

immunology↗