Biology subjects

Liu, K.

Publications and source records attributed to Liu, K..

312 records · Page 18Linked to original sources

bioRxiv2018

Using molecular ecological network analysis to explore the effects of chemotherapy on intestinal microbial communities of colorectal cancer patients

Intestinal microbiota is now widely known to be key roles in the nutrition uptake, metabolism, and the regulation of human immune responses. However, we do not know how changes the intestinal microbiota in response to the chemotherapy. In this study, we used network-based analytical approaches to explore the effects of five stages of chemotherapy on the intestinal microbiota of colorectal cancer patients. The results showed that chemotherapy greatly reduced the alpha diversity and changed the specie-specie interaction networks of intestinal microbiota, proved by the network size, network connectivity and modularity. The OTU167 and OTU8 from the genus Fusobacterium and Bacteroides were identified as keystone taxa by molecular ecological networks in the first two stages of chemotherapy, and were significantly correlated with tumor makers (P < 0.05). Five stages of chemotherapy did not make the intestinal micro-ecosystem regain a steady state, because of the lower alpha diversity and more complicated ecological networks compared to the healthy individuals. Furthermore, combing the changes of ecological networks with the tumor markers, the intestinal microbiota was closely linked with clinical chemotherapeutic effects.\n\nImportanceA deeply understanding of the role of intestinal microbiota contributes to help us find path forward for improving the prognosis of colorectal cancer patients. In addition, diet or probiotics interventions will be a possible attempt to improve the clinical chemotherapeutic effects for colorectal cancer patients.

microbiology↗

bioRxiv2018

The Roles of Neighborhood Composition and Autism Prevalence on Vaccination Exemption Pockets: A Population-wide Study

The number of children entering schools without mandated vaccinations has increased in high-income countries due to the rise of nonmedical exemptions from school vaccination requirements. Herd immunity is threatened when unvaccinated children are concentrated in spatial pockets. It is often assumed that these exemption clusters are merely the result of population composition. On the other hand, despite the role of vaccine-autism controversy to the current wave of anti-vaccine movement, we do not know if exemption clusters are associated with local autism rates. Our spatial analysis of California shows that while racial/ethnic composition is associated with the locations of large exemption pockets, other sociodemographic factors and access to health care resources have limited geographical span. We decouple the race/ethnicity effect from that of unobserved socioeconomic status by examining families in poverty. Using unique address-level data on the locations of the majority of children with an autism diagnosis, we show that the prevalence of autism is not associated with the locations of large pockets of vaccination exemptions. In addition, we find charter schools in most exemption clusters; potential spillovers from charter schools to neighboring public schools are evaluated. Exemption pockets are not merely the result of population composition and community-level interventions are needed to maintain herd immunity.\n\nHighlightsO_LIAutism prevalence rates are not associated with the locations of large exemption pockets.\nC_LIO_LIThe average exemption rate in charter schools (7.5%) was higher than private schools.\nC_LIO_LIProportion non-Hispanic white has the strongest association with large exemption clusters.\nC_LIO_LIPopulation composition cannot fully explain the exemption clusters.\nC_LI

epidemiology↗

bioRxiv2018

Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

A central goal of HIV-1-vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion-stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryo-electron microscopy structures of these antibodies revealed fusion peptide-conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses suggesting translatability. The N terminus of the HIV-1-fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

immunology↗

bioRxiv2017

A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery

We performed a high time-resolution, longitudinal study of normal pregnancy development by measuring cell-free RNA (cfRNA) in blood from women during each week of pregnancy. Analysis of tissue-specific transcripts in these samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific responses of the maternal immune system to pregnancy. We established a \"clock\" for normal pregnancy development and enabled a direct molecular approach to determine expected delivery dates with comparable accuracy to ultrasound, creating the basis for a portable, inexpensive fetal dating method. We also identified a related gene set that accurately discriminated women at risk for spontaneous preterm delivery up to two months in advance of labor, forming the basis of a potential screening test for risk of preterm delivery.

bioengineering↗

bioRxiv2017

Phosphate starvation induces replacement of phospholipids with the betaine lipid diacylglycerol-N,N,N-trimethylhomoserine in the human fungal pathogen Candida albicans

We have previously demonstrated that phosphate starvation induces replacement of phosphatidylcholine with the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) in fungi. In Neurospora crassa, the BTA1 gene encodes the betaine lipid synthase, which is necessary and sufficient for DGTS synthesis. BTA1 expression and DGTS accumulation are part of the fungal phosphorus (Pi) deprivation (PHO) regulon, mediated by the NUC-1/Pho4p transcription factor. We now demonstrate that the human pathogen Candida albicans encodes a BTA1 ortholog (CaBTA1), which is activated during Pi scarcity. The CaBTA1 gene is also induced under certain biofilm-promoting conditions independent of Pi starvation. RNA-seq and qRT-PCR showed a significant increase in CaBTA1 expression in response to Pi limitation. Thin-layer chromatography and LC-ESI-MS/MS confirmed the replacement of PC with DGTS in wild-type under low Pi and showed the absence of DGTS in the bta1{Delta}{Delta} mutant.\n\nPi limitation in the gut of critically ill patients also triggers the switching of C. albicans into an invasive filamentous form. To assess the role of BTA1 and DGTS in the pathogenicity of C. albicans in vitro, we compared the growth and morphology of bta1{Delta}{Delta} and wild type in hyphaeinducing media and observed defects in biofilm formation and invasive growth in the bta1{Delta}{Delta} mutant. This observation is complemented by RNA-seq data demonstrating that Pi starvation in planktonic C. albicans cells induces the expression of virulence-associated cell surface proteins. Taken together, these results show novel functional interactions between lipid metabolism and remodeling, biofilm formation, and the phosphate starvation response of C. albicans.

microbiology↗

bioRxiv2017

Post-transcriptional regulation of adult CNS axonal regeneration by Cpeb1

Adult mammalian CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we study the transcriptome and proteome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naive spinal cords identify a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were downregulated in the total RNA-fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovers a global conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

neuroscience↗