Biology subjects

Guo, B.

Publications and source records attributed to Guo, B..

7 recordsLinked to original sources

bioRxiv2018

Preliminary Study of the Potential Mechanism of CTSD in the Aging Process of Sepiella japonica: Fundamental Function Analysis

Cathepsin D, a kind of endopeptidase, can degrade peptides and proteins in lysosomes, which are involved in cell apoptosis. Previous transcriptome analysis of optic glands of Sepiella japonica across four growth stages, expression of a cathepsin D-like segment was found to be significantly different. Based on the complete cDNA sequence of S. japonica, the CTSD gene (also called sjCTSD, GenBank accession no. KY745896.1) was cloned using RACE amplification; this gene is 1389 bp in length and encodes proteins composed of 393 amino acids. Spatio-temporal expression profiles of the sjCTSD gene were determined using qPCR assays, which showed that the expression levels of sjCTSD constantly increased across four growth stages in 9 of 11 tissues that were investigated. In the optic glands, as well as pancreas and liver cells, sjCTSD expression levels sharply increased during the post-spawning phase. To investigate the potential role of the sjCTSD gene in aging progress, we constructed the prokaryotic expression vector of pET28a/sjCTSD. After induced by IPTG, the recombinant protein sjCTSD was obtained in the form of inclusion bodies, with a molecular size of approximately 40.3 kDa, the inclusion body of sjCTSD can be converted to soluble protein through the denaturation and renaturation. The results of functional experiments showed that sjCTSD could degrade bovine hemoglobin under acidic conditions, and inhibit the growth of Escherichia coli and Vibrio alginolyticus, which was speculated that the increased expression of sjCTSD may help inhibit the invasion of pathogenic bacteria with the immune function of cuttlefish declines during the aging process. To a certain extent, these results indicated the potential functional role of the sjCTSD gene in the aging process of S. japonica. This study provides insights to further understand the roles of lysosomal proteins on anti-aging effects in S. japonica and other cephalopoda species.

genetics↗

bioRxiv2018

Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis

Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) was previously identified as a negative regulator of osteogenic lineage activity. Here we demonstrated that PLEKHO1 was highly expressed in osteoblasts of articular specimens from RA patients and inflammatory arthritis mice. Genetic deletion of osteoblastic Plekho1 ameliorated joint inflammation in mice with collagen-induced arthritis (CIA) and K/BxN serum-transfer arthritis (STA), whereas overexpressing Plekho1 only within osteoblasts in CIA and STA mice demonstrated exacerbated local inflammation. Further in vitro studies indicated that PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-kB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition improved joint inflammation and attenuated bone formation reduction in CIA mice and non-human primate arthritis model. These data strongly suggest that highly expressed PLEKHO1 in osteoblast mediates joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.

cell biology↗

bioRxiv2018

Principal component based adaptive association test of multiple traits using GWAS summary statistics

Genetics hold great promise to precision medicine by tailoring treatment to the individual patient based on their genetic profiles. Toward this goal, many large-scale genome-wide association studies (GWAS) have been performed in the last decade to identify genetic variants associated with various traits and diseases. They have successfully identified tens of thousands of disease-related variants. However they have explained only a small proportion of the overall trait heritability for most traits and are of very limited clinical use. This is partly owing to the small effect sizes of most genetic variants, and the common practice of \"testing association between one trait and one genetic variant at a time\" in most GWAS, even when multiple related traits are often measured for each individual. Increasing evidence suggests that many genetic variants can influence multiple traits simultaneously, and we can gain more power by testing association of multiple traits simultaneously. It is appealing to develop novel multi-trait association test methods that need only GWAS summary data, since it is generally very hard to access the individual-level GWAS phenotype and genotype data.\n\nMost existing GWAS summary data based association test methods have relied on ad hoc approach or crude Monte Carlo approximation. In this paper we develop rigorous statistical methods for efficient and powerful multi-trait association test. We develop robust and efficient methods to accurately estimate the marginal trait correlation matrix using only GWAS summary data. We construct the principal component (PC) based association test from the summary statistics. PC based test has optimal power when the underlying multi-trait signal can be captured by the first PC, and otherwise it will have suboptimal performance. We develop an adaptive test by optimally weighting the PC based test and the omnibus chi-square test to achieve robust performance under various scenarios. We develop efficient numerical algorithms to compute the analytical p-values for all the proposed tests without the need of Monte Carlo sampling. We illustrate the utility of proposed methods through application to the GWAS meta-analysis summary data for multiple lipids and glycemic traits. We identify multiple novel loci that were missed by individual trait based association test.\n\nAll the proposed methods are implemented in an R package available at http://www.github.com/baolinwu/MTAR. The developed R programs are extremely efficient: it takes less than two minutes to compute the list of genome-wide significant SNPs for all proposed multi-trait tests for the lipids GWAS summary data with 2.5 million SNPs on a single Linux desktop.

bioinformatics↗

bioRxiv2017

Is the HIV epidemic over? Investigating population dynamics using Bayesian methodology to estimate epidemiological parameters for a system of stochastic differential equations

Current estimates of the HIV epidemic indicate a decrease in the incidence of the disease in the undiagnosed subpopulation over the past 10 years. However, a lack of access to care has not been considered when modeling the population. Populations at high risk for contracting HIV are twice as likely to lack access to reliable medical care. In this paper, we consider three contributors to the HIV population dynamics: susceptible pool exhaustion, lack of access to care, and usage of anti-retroviral therapy (ART) by diagnosed individuals. We consider the change in the proportion of undiagnosed individuals as the parameter in a simple Markov model. We obtain conservative estimates for the proportional change of the infected subpopulations using hierarchical Bayesian statistics. The estimated proportional change is used to derive epidemic parameter estimates for a system of stochastic differential equations (SDEs). Epidemic parameters are modified to capture the dynamics of each of the three contributors, as well as all their possible combinations. Model fit is quantified to determine the best explanation for the observed dynamics in the infected subpopulations.\n\nAuthor summaryUsing a combination of statistics and mathematical modeling, we look at some possible reasons for the reported decrease in the number of undiagnosed people living with HIV. One possibility is that the population of people at significant risk to contract HIV is being depleted (susceptibles). This might happen if significant risk for HIV infection occurs in small percentages of the overall population. Another possibility is that infected individuals lack access to care in some regions due to poverty or other cause. In this case we have to question the accuracy of the estimated size of that population. Finally, most diagnosed individuals report being on medication that reduces their viral load. This greatly reduces their chance to transmit HIV to susceptible individuals. We also combine these possibilities and look at the best explanation for the infected population size.

epidemiology↗

bioRxiv2017

A negative feedback mechanism in the insulin-regulated glucose homeostasis in Japanese flounder Paralichthys olivaceus by two ways of glucose administration

The present study comparatively analyzed the blood glucose and insulin concentration, the temporal and spatial expression of brain-gut peptides and the key enzymes of glycolysis and gluconeogenesis in Japanese flounder by intraperitoneal (IP) injection and oral (OR) administration of glucose. Samples were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48h after IP and OR, respectively. Results showed that the hyperglycemia lasted 5 hours and 21 hours in OR and IP group, respectively. The serum insulin concentration significantly decreased (1.58{+/-}0.21mIU/L) at 3h after IP glucose. However, it significantly increased at 3h (3.37{+/-}0.34mIU/L) after OR glucose. The gene expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and orexin precursor in the brain showed different profiles between the OR and IP group. The OR not IP administration of glucose had significant effects on the gene expressions of preprovasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and gastrin in the intestine. When the blood glucose concentration peaked in both IP and OR group, the glucokinase expression in liver was stimulated, but the expression of fructose-1,6-bisphosphatase was depressed. In conclusion, brain-gut peptides were confirmed in the present study. And the serum insulin and the brain-gut peptides have different responses between the IP and OR administration of glucose. A negative feedback mechanism in the insulin-regulated glucose homeostasis was suggested in Japanese flounder. Furthermore, this regulation could be conducted by activating PI3k-Akt, and then lead to the pathway downstream changes in glycolysis and gluconeogenesis.

biochemistry↗

bioRxiv2017

Dynamic interhemispheric coordination in face processing

Our conscious experience of the world is normally unified. The brain coordinates different processes from the left and right hemispheres into one experience. However, the neural mechanisms underlying interhemispheric coordination remain poorly understood. A mechanistic approach to understanding interhemispheric coordination is \"communication through coherence\" (Fries, 2005; 2015). Using a recently developed time-resolved psychophysics (Fiebelkorn, Saalmann, & Kastner, 2013; Landau & Fries, 2012; Song, Meng, Chen, Zhou, & Luo, 2014), combined with fMRI decoding method, we investigated the interhemispheric coordination through coherence, by focusing on a quintessential case of hemispheric lateralized brain function: face processing in the left and right fusiform face area (FFA). We observed coherent oscillatory fMRI multi-voxel patterns in the left and right FFA when two stimuli presented successively cross visual fields, either initiating coordination from the left hemisphere or right hemisphere. When interhemispheric coordination started from the dominant right hemisphere, a coherent 44{degrees} phase difference between the left and right FFA in 3-4 Hz was observed; whereas when interhemispheric coordination started from the non-dominant left hemisphere, a coherent -17{degrees} phase difference between the left and right FFA in 5.5-6.5 Hz was observed. These results suggest that different phase coherence might mediate the interhemispheric coordination of face perception, depending on whether the initiating hemisphere is dominant or non-dominant. Our findings provide compelling fMRI evidence for interhemispheric coordination through coherence. The time-resolved fMRI decoding approach would be a useful starting point for a more promising approach for future investigation in interhemispheric dynamic coordination with fine-grained spatial and temporal resolution.

neuroscience↗

bioRxiv2017

Fluctuations of fMRI activation patterns reveal theta-band dynamics of visual object priming

The brain dynamically creates predictions about upcoming stimuli to guide perception efficiently. Recent behavioral results suggest theta-band oscillations contribute to this prediction process, however litter is known about the underlying neural mechanism. Here, we combine fMRI and a time-resolved psychophysical paradigm to access fine temporal-scale profiles of the fluctuations of brain activation patterns corresponding to visual object priming. Specifically, multi-voxel activity patterns in the fusiform face area (FFA) and the parahippocampal place area (PPA) show temporal fluctuations at a theta-band (~5 Hz) rhythm. Importantly, the theta-band power in the FFA negatively correlates with reaction time, further indicating the critical role of the observed cortical theta oscillations. Moreover, alpha-band (~10 Hz) shows a dissociated spatial distribution, mainly linked to the occipital cortex. These findings, to our knowledge, are the first fMRI study that indicates temporal fluctuations of multi-voxel activity patterns and that demonstrates theta and alpha rhythms in relevant brain areas.

neuroscience↗