Biology subjects

Guo, B.

Publications and source records attributed to Guo, B..

At least 73 records · Page 4Linked to original sources

bioRxiv2020

A novel high-accuracy genome assembly method utilizing a high-throughput workflow

Across domains of biological research using genome sequence data, high-quality reference genome sequences are essential for characterizing genetic variation and understanding the genetic basis of phenotypes. However, the construction of genome assemblies for various species is often hampered by complexities of genome organization, especially repetitive and complex sequences, leading to mis-assembly and missing regions. Here, we describe a high-throughput gold standard genome assembly workflow using a large-scale bacterial artificial chromosome (BAC) library with a refined two-step pooling strategy and the Lamp assembler algorithm. This strategy minimizes the laborious processes of physical map construction and clone-by-clone sequencing, enabling inexpensive sequencing of several thousand BAC clones. By applying this strategy with a minimum tiling path BAC clone library for the short arm of chromosome 2D (2DS) of bread wheat, 98% of BAC sequences, covering 92.7% of the 2DS chromosome, were assembled correctly for this species with a highly complex and repetitive genome. We also identified 48 large mis-assemblies in the reference wheat genome assembly (IWGSC RefSeq v1.0) and corrected these large mis-assemblies in addition to filling 92.2% of the gaps in RefSeq v1.0. Our 2DS assembly represents a new benchmark for the assembly of complex genomes with both high accuracy and efficiency.

genomics↗

bioRxiv2020

Local brassinosteroid biosynthesis enables optimal root growth

Brassinosteroid hormones are indispensable for root growth and they control both cell division and cell elongation through the establishment of an increasing signaling gradient along the longitudinal root axis. Because of their limited mobility, the importance of brassinosteroid distribution for achieving the signaling maximum is largely overlooked. Expression pattern analysis of all known brassinosteroid biosynthetic enzymes revealed that not all cells in the Arabidopsis thaliana root possess full biosynthetic machinery and completion of biosynthesis relies on cell-to-cell movement of the hormone precursors. We demonstrate that brassinosteroid biosynthesis is largely restricted to the root elongation zone where it overlaps with brassinosteroid signaling maxima. Moreover, optimal root growth requires hormone concentrations, low in the meristem and high in the root elongation zone attributable to an increased biosynthesis. Our finding that spatiotemporal regulation of hormone synthesis results in a local hormone accumulation provides a paradigm for hormone-driven organ growth in the absence of long-distance hormone transport in plants.

plant biology↗

bioRxiv2020

Phytophthora sojae effector Avr1d functions as E2 competitor and inhibits ubiquitination activity of GmPUB13 to facilitate infection

Oomycete pathogens such as Phytophthora secrete a repertoire of effectors to host cells to manipulate host immunity and benefit infection. In this study, we found that an RxLR effector, Avr1d, promoted Phytophthora sojae infection in soybean hairy-roots. Using a yeast two-hybrid screen, we identified the soybean E3 ubiquitin ligase GmPUB13 as a host target for Avr1d. By co-immunoprecipitation, gel infiltration and ITC assays, we confirmed that Avr1d interacts with GmPUB13 both in vivo and in vitro. Furthermore, we found that Avr1d inhibits the E3 ligase activity of GmPUB13. The crystal structure of Avr1d in complex with GmPUB13 was solved and revealed that Avr1d occupies the binding site for E2 ubiquitin conjugating enzyme on GmPUB13. In line with this, Avr1d competed with E2 ubiquitin conjugating enzymes for GmPUB13 binding in vitro, thereby decreasing the E3 ligase activity of GmPUB13. Meanwhile, we found that inactivation of the ubiquitin ligase activity of GmPUB13 stabilized GmPUB13 by blocking GmPUB13 degradation. Silencing of GmPUB13 in soybean hairy-roots decreased P. sojae infection, suggesting that GmPUB13 acts as a susceptibility factor, negatively regulating soybean resistance against P. sojae. Altogether, this study highlights a novel virulence mechanism of Phytophthora effectors, by which Avr1d competes with E2 for GmPUB13 binding to repress the GmPUB13 E3 ligase activity and thereby stabilizing the susceptibility factor GmPUB13 to facilitate Phytophthora infection. This is the first study to unravel the structural basis for modulation of host targets by Phytophthora effectors and will be instrumental for boosting plant resistance breeding. Significance StatementUbiquitination acts as a crucial regulator in plant immunity. Accordingly, microbial pathogens secrete effectors to hijak host ubiquitination system. However, the molecular mechanisms by which microbial effectors modulate host ubiquitination system are not yet clear. Here, we found that the Phytophthora sojae effector Avr1d physically binds to the U-box type E3 ligase GmPUB13, a susceptibility factor in soybean. The crystal structure of Avr1d in complex with GmPUB13 revealed that Avr1d occupies the binding site in GmPUB13 for the E2 ubiquitin conjugating enzyme and competes with E2 for physical binding to GmPUB13. Avr1d stabilized GmPUB13 by suppressing the self-ubiquitination activity of GmPUB13 and thereby promoting Phytophthora infection. This study provides structural basis for modulation of host targets by Phytophthora effectors.

microbiology↗

bioRxiv2020

DReSS: A difference measurement based on reachability between state spaces of Boolean networks

Researches on dynamical features of biological systems are mostly based on fixed network structure. However, both biological factors and data factors can cause structural perturbations to biological regulatory networks. There are researches focus on the influence of such structural perturbations to the systems dynamical features. Reachability is one of the most important dynamical features, which describe whether a state can automatically evolve into another state. However, there is still no method can quantitively describe the reachability differences of two state spaces caused by structural perturbations. DReSS, Difference based on Reachability between State Spaces, is proposed in this research to solve this problem. First, basic properties of DReSS such as non-negativity, symmetry and subadditivity are proved based on the definition. And two more indexes, diagDReSS and iDReSS are proposed based on the definition of DReSS. Second, typical examples like DReSS = 0 or 1 are shown to explain the meaning of DReSS family, and the differences between DReSS and traditional graph distance are shown based on the calculation steps of DReSS. Finally, differences of DReSS distribution between real biological regulatory network and random networks are compared. Multiple interaction positions in real biological regulatory network show significant different DReSS value with those in random networks while none of them show significant different diagDReSS value, which illustrates that the structural perturbations tend to affect reachability inside and between attractor basins rather than to affect attractor set itself. Author summaryBoolean network is a kind of networks which is widely used to model biological regulatory systems. There are structural perturbations in biological systems based on both biological factors and data-related factors. We propose a measurement called DReSS to describe the difference between state spaces of Boolean networks, which can be used to evaluate the influence of specific structural perturbations of a network to its state space quantitively. We can use DReSS to detect the sensitive interactions in a regulatory network, where structural perturbations can influence its state space significantly. We proved properties of DReSS including non-negativity, symmetry and subadditivity, and gave examples to explain the meaning of some special DReSS values. Finally, we present an example of using DReSS to detect sensitive vertexes in yeast cell cycle regulatory network. DReSS can provide a new perspective on how different interactions affect the state space of a specific regulatory network differently.

bioinformatics↗

bioRxiv2020

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice (GMP) requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), our findings suggest that IMRCs are ready for clinical trials on lung disorders.

cell biology↗

bioRxiv2020

Hybrid origin of Populus tomentosa Carr. identified through genome sequencing and phylogenomic analysis

Populus tomentosa is widely distributed and cultivated in the Northern and Central China, where it is of great economic and ecological importance. However, the origin of P. tomentosa remains controversial. Here, we used a PacBio+Hi-C+Illumina strategy to sequence and assemble its 740.2 Mb (2n) genome. The assembly accounts for greater than 92.1% of the 800-megabase genome, comprises 38 chromosomes, and contains 59,124 annotated protein-coding genes. Phylogenomic analyses elucidated dynamic genome evolution events among its closely related white poplars, and revealed that tomentosa is comprised of two subgenomes, which we deomonstrate is likely to have resulted from hybridization between Populus adenopoda as the female, and Populus alba var. pyramidalis as the male, around 3.93 Mya. We also detected structural variations and allele-indels across genome. Our study presents a high quality and well assembled genome, unveils the origin of the widely distributed and planted P. tomentosa, and provides a powerful resource for comparative plant biology, breeding, and biotechnology.

genomics↗

bioRxiv2020

Convergent genetic architecture underlies parallel pelvic reduction in genetically highly structured stickleback species

Repeated and independent adaptation to specific environmental conditions from standing genetic variation is common. However, if genetic variation is limited, the evolution of similar locally adapted traits may be restricted to genetically different and potentially less optimal solutions or prevented from happening altogether. Using a quantitative trait locus (QTL) mapping approach, we identified the genomic regions responsible for the repeated pelvic reduction (PR) in three crosses between nine-spined stickleback populations expressing full and reduced pelvic structures. In one cross, PR mapped to linkage group 7 (LG7) containing the gene Pitx1, known to control pelvic reduction also in the three-spined stickleback. In the two other crosses, PR was polygenic and attributed to ten novel QTL, of which 90% were unique to specific crosses. When screening the genomes from 27 different populations for deletions in the Pitx1 regulatory element, these were only found in the population in which PR mapped to LG7, even though the morphological data indicated large effect QTL for PR in several other populations as well. Consistent with the available theory and simulations parameterised on empirical data, we hypothesise that the observed variability in genetic architecture of PR is due to heterogeneity in the spatial distribution of standing genetic variation caused by >2x stronger population structuring among freshwater populations and >10x stronger genetic isolation by distance in the sea in nine-spined sticklebacks as compared to three-spined sticklebacks.

evolutionary biology↗

bioRxiv2020

Varying co-factor requirements for MAML1-dependent transcription at different Notch-responsive target genes

Mastermind proteins are required for transcription of Notch target genes, yet the molecular basis for mastermind function remains incompletely understood. Previous work has shown that Notch can induce transcriptional responses by binding to promoters, but more often by binding to enhancers, with HES4 and DTX1 as representative mammalian examples of promoter and enhancer responsiveness, respectively. Here, we show that mastermind dependence of the Notch response at these loci is differentially encoded in Jurkat T-ALL cells. Knockout of Mastermind-like1 (MAML1) eliminates Notch responsive activation of both these genes, and reduced target gene expression is accompanied by a decrease in H3K27 acetylation, consistent with the importance of MAML1 for p300 activity. Add-back of defined MAML1 constructs in knockout cells identifies residues 151-350 of MAML1 as essential for expression of either Notch-responsive gene. Fusion of the Notch-binding region of MAML1 to the HAT domain of p300 rescues expression of HES4 but not DTX1, suggesting that an additional activity of MAML1 is needed for gene induction at a distance. Together, these studies establish the functional importance of the MAML1151-350 region for Notch-dependent transcriptional induction, and reveal differential requirements for MAML1-dependent recruitment activities at different Notch responsive loci, highlighting the molecular complexity of NTC-stimulated transcription.

molecular biology↗

bioRxiv2019

Viral manipulation of functionally distinct neurons from mice to humans

Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two that are selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across species, from mice to humans. Finally, we demonstrate that our selection method is generalizable to other genes and characterize four additional PV-specific enhancers with exquisite specificity for distinct regions of the brain. Altogether, these viral tools can be used for cell-type specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

neuroscience↗

bioRxiv2019

Genome sequencing of the nine-spined stickleback (Pungitius pungitius) provides insights into chromosome evolution.

The Gasterostidae fish family hosts several species that are important models for eco-evolutionary, genetic and genomic research. In particular, a wealth of genetic and genomic data have been generated for the three-spined stickleback (Gasterosteus aculeatus), the ecologys supermodel, while the genomic resources for the nine-spined stickleback (Pungitius pungitius) have remained relatively scarce. Here, we report a high-quality chromosome-level genome assembly of P. pungitius consisting of 5,303 contigs (N50 = 1.2 Mbp) with a total size of 521 Mbp. These contigs were mapped to 21 linkage groups using a high-density linkage map, yielding a final assembly with 98.5% BUSCO completeness. A total of 25,062 protein-coding genes were annotated, and ca. 23% of the assembly was found to consist of repetitive elements. A comprehensive analysis of repetitive elements uncovered centromeric-specific tandem repeats and provided insights into the evolution of retrotransposons. A multigene phylogenetic analysis inferred a divergence time of about 26 million years (MYA) between nine- and three-spined sticklebacks, which is far older than the commonly assumed estimate of 13 MYA. Compared to the three-spined stickleback, we identified an additional duplication of several genes in the hemoglobin cluster. Sequencing data from populations adapted to different environments indicated potential copy number variations in hemoglobin genes. Furthermore, genome-wide synteny comparisons between three- and nine-spined sticklebacks identified chromosomal rearrangements underlying the karyotypic differences between the two species. The high-quality chromosome-scale assembly of the nine-spined stickleback genome obtained with long-read sequencing technology provides a crucial resource for comparative and population genomic investigations of stickleback fishes and teleosts.

genomics↗

bioRxiv2019

Native protein delivery into rice callus using ionic complexes of protein and cell-penetrating peptides

Direct protein delivery into intact plants remains a challenge for the agricultural and plant science fields. Cell-penetrating peptide (CPP)-mediated protein delivery requires the binding of CPPs to a protein to carry the protein into the cell through the cell wall and lipid bilayer. Thus, we prepared ionic complexes of a CPP-containing carrier peptide and a cargo protein, namely, Citrine yellow fluorescent protein, and subsequently studied their physicochemical properties. Two types of carrier peptides, BP100(KH)9 and BP100CH7, were investigated for delivery efficiency into rice callus. Both BP100(KH)9 and BP100CH7 successfully introduced Citrine protein into rice callus cells under pressure and vacuum treatment. Moreover, delivery efficiency varied at different growth stages of rice callus; 5-day rice callus was a more efficient recipient for Citrine than 21-day callus.

plant biology↗

bioRxiv2019

Carbohydrate, glutathione, and polyamine metabolism are central to Aspergillus flavus oxidative stress responses over time

The primary and secondary metabolites of fungi are critical for adaptation to environmental stresses, host pathogenicity, competition with other microbes, and reproductive fitness. Drought-derived reactive oxygen species (ROS) have been shown to stimulate aflatoxin production and regulate development in Aspergillus flavus, and may function in signaling with host plants. Here, we have performed global, untargeted metabolomics to better understand the role of aflatoxin production in oxidative stress responses, and also explore isolate-specific oxidative stress responses over time. Two field isolates of A. flavus, AF13 and NRRL3357, possessing high and moderate aflatoxin production, respectively, were cultured in medium with and without supplementation with 15mM H2O2, and mycelia were collected following 4 and 7 days in culture for global metabolomics. Overall, 389 compounds were described in the analysis which were examined for differential accumulation. Significant differences were observed in both isolates in response to oxidative stress and when comparing sampling time points. The moderate aflatoxin-producing isolate, NRRL3357, showed extensive stimulation of antioxidant mechanisms and pathways including polyamines metabolism, glutathione metabolism, TCA cycle, and lipid metabolism while the highly aflatoxigenic isolate, AF13, showed a less vigorous response to stress. Carbohydrate pathway levels also imply that carbohydrate repression and starvation may influence metabolite accumulation at the later timepoint. Higher conidial oxidative stress tolerance and antioxidant capacity in AF13 compared to NRRL3357, inferred from their metabolomic profiles and growth curves over time, may be connected to aflatoxin production capability and aflatoxin-related antioxidant accumulation. The coincidence of several of the detected metabolites in H2O2-stressed A. flavus and drought-stressed hosts suggests their potential role in the interaction between these organisms and their use as markers/targets to enhance host resistance through biomarker selection or genetic engineering.\n\nAuthor SummaryAspergillus flavus is a fungal pathogen of several important crops including maize and peanut. This pathogen produces carcinogenic mycotoxins known as aflatoxins during infection of plant materials, and is particularly severe under drought stress conditions. This results in significant losses in crop value and poses a threat to food safety and security globally. To combat this, understanding how this fungus responds to environmental stresses related to drought can allow us to identify novel methods of mitigating aflatoxin contamination. Here, we analyzed the accumulation of a broad series of metabolites over time in two isolates of A. flavus with differing stress tolerance and aflatoxin production capabilities in response to drought-related oxidative stress. We identified several metabolites and mechanisms in A. flavus which allow it to cope with environmental oxidative stress and may influence aflatoxin production and fungal growth. These may serve as potential targets for selection in breeding programs for the development of new cultivars, or for alteration using genetic engineering approaches to mitigate excessive aflatoxin contamination under drought stress.

microbiology↗

bioRxiv2018

Powerful statistical method to detect disease associated genes using publicly available GWAS summary data

Genome-wide association studies (GWAS) have thus far achieved substantial success. In the last decade a large number of common variants underlying complex diseases have been identified through GWAS. In most existing GWAS, the identified common variants are obtained by single marker based tests, that is, testing one single nucleotide polymorphisms (SNP) at a time. Generally the basic functional unit of inheritance is a gene, rather than a SNP. Thus, results from gene level association test can be more readily integrated with downstream functional and pathogenic investigation. In this paper, we propose a general gene-based p-value adaptive combination approach (GPA) which can integrate association evidence of multiple genetic variants using only GWAS summary statistics (either p-value or other test statistics). The proposed method could be used to test both continuous and binary traits through not only a single but also multiple studies, which helps overcome the limitation of existing methods that only can be applied to specific type of data. We conducted thorough simulation studies to verify that the proposed method controls type I errors well, and performs favorably compared to single-marker analysis and other existing methods. We demonstrated the utility of our proposed method through analysis of GWAS meta-analysis results for fasting glucose and lipids from the international MAGIC consortium and Global Lipids Consortium, respectively. The proposed method identified some novel traits associated genes which can improve our understanding of the mechanisms involved in {beta}-cell function, glucose homeostasis and lipids traits.

genetics↗

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↗