Biology subjects

Guo, Y.

Publications and source records attributed to Guo, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Systemic hypoxia drives glycogen-fueled progression of lung adenocarcinoma

In advanced stages, lung adenocarcinoma obstructs airways and disrupts ventilation-perfusion relationships in the lung, causing systemic hypoxemia and enabling a feed-forward loop that accelerates malignancy. Systemic hypoxemia is also experienced due to common respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), potentially accelerating malignancy. In a statewide electronic health record network, pre-existing COPD (598 matched pairs) or sleep apnea (235 matched pairs) independently predicted worse survival following incident lung cancer diagnosis. Since the mechanistic basis of the link between malignancy and hypoxia is not well understood, we created systemic hypoxia in KrasLSL-G12D/+;Trp53fl/fl (KP) mice by delivering low inspired oxygen concentrations (8% inspired oxygen; 8 h daily). Hypoxia nearly doubled tumor multiplicity and selectively remodeled cancer central carbon metabolism. Spatially resolved metabolomics revealed marked tumor-compartment glycogen accumulation, elevated tricarboxylic-acid cycle intermediates, and depleted glycolytic pools. Quantitative proteomics across cellular models and autochthonous tumors demonstrated that systemic hypoxia drives glycogen mobilization selectively through the lysosomal enzyme acid -glucosidase (GAA). Tumor-cell-autonomous deletion of GAA eliminated the hypoxia-driven growth advantage and disrupted downstream anabolic biosynthetic pathways. Thus, systemic hypoxia drives lung adenocarcinoma expansion by mobilizing lysosomal glycogen reserves through GAA to sustain proliferative growth.

cancer biology↗

bioRxiv2018

Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4

Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). The induction of human Sertoli cells from fibroblasts could provide cellular sources for fertility and transplantation treatments. Here, we report the in vitro reprogramming of human fibroblasts to Sertoli cells and characterize these human induced Sertoli cells (hiSCs). Initially, five transcriptional factors (NR5A1, GATA4, WT1, SOX9 and DMRT1) and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, i.e., NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles that are similar to those of primary human Sertoli cells. Consistent with the known cellular properties of Sertoli cells, hiSCs attract endothelial cells and exhibit high number of lipid droplets in the cytoplasm. More importantly, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. In addition, hiSCs suppress the production of IL-2 and proliferation of human T lymphocytes. When hiSCs were cotransplanted with human embryonic kidney cells, these xenotransplanted human cells survived longer in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli-only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.

developmental biology↗

bioRxiv2018

Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites

Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested whether F. prausnitzii and other gut abundant bacteria are capable of metabolizing tacrolimus. Incubation of F. prausnitzii with tacrolimus led to production of two compounds (the major one named M1), which was not observed upon tacrolimus incubation with hepatic microsomes. Isolation, purification, and structure elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy indicated that M1 is a C-9 keto-reduction product of tacrolimus. Pharmacological activity testing using human peripheral blood mononuclear cells demonstrated that M1 is 15-fold less potent than tacrolimus as an immunosuppressant. Screening of 22 gut bacteria species revealed that most Clostridiales bacteria are extensive tacrolimus metabolizers. Tacrolimus conversion to M1 was verified in fresh stool samples from two healthy adults. M1 was also detected in the stool samples from kidney transplant recipients who had been taking tacrolimus orally. Together, this study presents gut bacteria metabolism as a previously unrecognized elimination route of tacrolimus, potentially contributing to the low and variable tacrolimus exposure after oral dosing.

pharmacology and toxicology↗

bioRxiv2018

Phage Mediate Bacterial Self Recognition

Cells are social, and self-recognition is an important and conserved aspect of group behavior where cells assist kin and antagonize non-kin to conduct group behavior such as foraging for food and biofilm formation. However, the role of the common bacterial cohabitant, phage, in kin recognition, has not been explored. Here we find that a boundary (demarcation line) is formed between different swimming Escherichia coli strains but not between identical clones; hence, motile bacterial cells discriminate between self and non-self. The basis for this self-recognition is a novel, 49 kb, T1-type, lytic phage of the family siphoviridae (named here SW1) that controls formation of the demarcation line by utilizing one of the hosts cryptic prophage proteins, YfdM, to propagate. Critically, SW1 increases the fitness of E. coli K-12 compared to the identical strain that lacks the phage. Therefore, bacteria use phage to recognize kin.

molecular biology↗

bioRxiv2018

Changes in Microorganisms in the Rhizosphere of Mulberry Genotypes with Differing Resistance to Bacterial Wilt

A close relationship between soil-borne diseases, soil microbial community structure, and functional diversity has been described in the mulberry plant. In the present study, microbial abundance, community structure, and functional diversity in the soil rhizosphere were compared in resistant (Kangqing10) and susceptible (Guisang12) mulberry genotypes using the dilution plate method, micro-ecology technology, and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). The goal of this study was to develop better management methods for mulberry cultivation and preventing and controlling bacterial wilt. Rhizosphere soil microorganisms were more abundant in the resistant normal mulberry genotype than in the susceptible normal mulberry genotype. Carbon source utilization was better in the susceptible normal mulberry genotype. These properties were lower in the resistant sickly mulberry genotype than in the susceptible sickly mulberry genotype. PCR-DGGE indicated that the bacterial and fungal community structures of the resistant genotypes were more stable than those of the susceptible genotypes. Correlation regression analysis implicated mulberry bacterial wilt in the loss of soil nutrients, particularly organic matter and nitrogen, which can disrupt the balance of the soil microbial community. Loss of soil organic matter and nitrogen had a lower impact on resistant genotype plants than on susceptible genotype plants. Therefore, resistant genotype plants displayed some resistance to bacterial wilt. Further insights into the soil rhizosphere microbial diversities of resistant and susceptible genotypes will help in the control and prevention of mulberry bacterial wilt.

microbiology↗

bioRxiv2018

Modeling circRNAs expression pattern with integrated sequence and epigenetic features identifies H3K79me2 as regulators for circRNAs expression

Circular RNAs (circRNAs) are an abundant class of noncoding RNAs with widespread, cell/tissue specific pattern. Because of their involvement in the pathogenesis of multiple disease, they are receiving increasing attention. Previous work suggested that epigenetic features might be related to circRNA expression. However, current algorithms for circRNAs prediction neglect these features, leading to constant results across different cells.\n\nHere we built a machine learning framework named CIRCScan, to predict expression status and expression levels of circRNAs in various cell lines based on sequence and epigenetic features. Both expression status and expression levels can be accurately predicted by different groups of features. For expression status, the top features were similar in different cells. However, the top features for predicting expression levels were different in different cells. Noteworthy, the importance of H3K79me2 ranked high in predicting both circRNAs expression status and levels across different cells, indicating its important role in regulating circRNAs expression. Further validation experiment in K562 confirmed that knock down of H3K79me2 did result in reduction of circRNA production.\n\nOur study offers new insights into the regulation of circRNAs by incorporating epigenetic features in prediction models in different cellular contexts.

bioinformatics↗

bioRxiv2018

High resolution discovery of chromatin interactions

Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a method for the genome-wide de novo discovery of chromatin interactions. Existing computational methods typically fail to detect weak or dynamic interactions because they use a peak-calling step that ignores paired-end linkage information. We have developed a novel computational method called Chromatin Interaction Discovery (CID) to overcome this limitation with an unbiased clustering approach for interaction discovery. CID outperforms existing chromatin interaction detection methods with improved sensitivity, replicate consistency, and concordance with other chromatin interaction datasets. In addition, CID also outperforms other methods in discovering chromatin interactions from HiChIP data. We expect that the CID method will be valuable in characterizing 3D chromatin interactions and in understanding the functional consequences of disease-associated distal genetic variations.

bioinformatics↗

bioRxiv2018

Sensing Plant Physiology and Environmental Stress by Automatically Tracking Fj and Fi Features in PSII Chlorophyll Fluorescence Induction

Following a step excitation, chlorophyll fluorescence (ChlF) from photosystem II of a dark-adapted plant leaf exhibits the well-known OJIP pattern. The OJIP induction has been widely applied in plant science, agriculture engineering, and environmental engineering. While the J and I phases are related to transitions of photochemical reaction redox states, characteristic fluorescence intensities for the two phases (Fj and Fi) are often treated as fixed time points in routine measurement and thus do not account for variations in plant and experimental conditions, which (1) neglects the time differences, potentially useful information for characterizing plant status and environmental factors, and (2) leads to errors in measured Fj and Fi values. In this work, a method for consistent measurement of Fj and Fi was developed through polynomial fitting and curvature analysis. The method measures the curvatures in the OJIP curve and automatically tracks the characteristic transition points under variable sample and experimental conditions. Experiments were carried out to demonstrate the concept and classification capabilities of the developed method. This research established a new framework to analyze ChlF and enhanced the applications of ChlF.

plant biology↗

bioRxiv2018

Effect of Lactobacillus reuteri on intestinal microflora and immune parameters: involvement of sex differences

Probiotic candidate L. reuteri was screened out for in vivo experiments based on a relatively higher gastrointestinal tolerance and moderate adhesiveness. As results shown in in-vivo experiments, a significantly higher level of IL-12 at low-dose group was found both in females and males. Higher levels of T-lymphocytes were also observed in females compared to control group, however, males displayed a reduction expcept for CD8-positive cells in ileum. In comparison to the control group, the relative abundance of phylotypes in the phylum Bacteroidetes (genus of Bacteroides, Prevotella) and Firmicutes (genus of ClostridiumIV) exihibited a reserve shift between sexes after L. reuteri intervened. Meanwhile, the relative abundance of several taxa (Acetobacteroides, Lactobcaillus, bacillus) also differed markedly in sexes at low-dose group, together with microbiota diversity, as indicated by Shannon index.\n\nImportanceSexual dimorphism has triggered researchers attention. However, the relationship between immune parameters and gut microbiota caused by Lactobacillus at different dosage are not fully elucidated. In present research, the possible probiotic role of L. reuteri DMSZ 8533 on immunomodulation and effect on fecal microbiota composition were investigated. Our findings demonstrate the importance of L. reuteri DMSZ 8533 as a potential probiotic strain with an immunomodulatory effect, which also alters the microflora composition depending on the sex of the host.

microbiology↗

bioRxiv2018

Colistin resistance prevalence in Escherichia coli from domestic animals in intensive breeding farms of Jiangsu Province, China

The global dissemination of colistin resistance has received a great deal of attention. Recently, the plasmid-mediated colistin resistance encoded by mcr-1 and mcr-2 genes in Escherichia coli (E.coli) strains from animals, food, and patients in China have been reported continuously. To make clear the colisin resistance and mcr gene spread in domestic animals in Jiangsu Province, we collected fecael swabs from pigs, chicken and cattle at different age distributed in intensive feeding farms. The selected chromogenic agar and mcr-PCR were used to screen the colisin resistance and mcr gene carriage. Colistin resistant E.coli colonies were identified from 54.25 % (440/811) pig faecal swabs, from 35.96 % (443/1232) chicken faecal swabs, and 26.92 % (42/156) from cattle faecal swabs. Of all the colisin resistant E.coli colonies, the positive amplifications of mcr-1 were significantly higher than mcr-2. The mcr-1 prevalence was 68.86 % (303/440) in pigs, 87.58 % (388/443) in chicken, and 71.43 % (30/42), compared with 46.82 % (206/440) in pigs, 14.90 % (66/443) in chicken, and 19.05 % (8/42) in cattle of prevalence of mcr-2. Co-occurrence of mcr-1 and mcr-2 was identified in 20 % (88/440) in pigs, 7.22 % (32/443) in chickens, and in 9.52 % (4/42) cattle. These data indicate that mcr was the most important colistin resistance mechanism. Interventions and alternative options are necessary to minimise further dissemination of mcr between food-producing animals and human.\n\nIMPORTANCEColistin is recognized one of the last defence lines for the treatment of highly resistant bacteria, but the emergence of resistance that conferred by a transferable plasmid-mediated mcr genes to this vital antibiotic is extremely disturbing. Here, we used E. coli as an index to monitor drug resistance in domestic animals (pigs, chicken and cattle). It was found that the colistin resistance widely occurred at all ages of domestic animals and the mcr-dependent mechanism dominated in E.coli. We also found that the elder and adult animals were a reservoir of resistant strains, suggesting a potential food safety issue and greater public health problems.

epidemiology↗

bioRxiv2018

Increased H. pylori stool shedding and EPIYA-D cagA alleles are associated with gastric cancer in an East Asian hospital

BackgroundHelicobacter pylori infection induces chronic inflammation and tissue damage in the stomach, increasing risk for gastric cancer. Paradoxically, these tissue alterations may promote loss of H. pylori infection during cancer progression. H. pyloris role in cancer progression beyond initiation is unclear. Geographic variation in gastric cancer risk has been attributed to variation in carriage and type of the H. pylori oncogene cagA.\n\nMethodsTo investigate possible differences in H. pylori load in the stomach and shedding in stool, H. pylori load and cagA genotype were assessed using droplet digital PCR assays on gastric mucosa and stool samples from 49 urea breath test-positive individuals, including 25 gastric cancer and 24 non-cancer subjects at Henan Cancer Hospital, Henan, China.\n\nResultsQuantitation of H. pylori DNA indicated similar gastric loads among cancer and non-cancer cases, but the gastric cancer group had a median H. pylori load in the stool that was six times higher than that of the non-cancer subjects. While the cagA gene was uniformly present among study subjects, only 70% had the East Asian cagA allele, which was significantly associated with gastric cancer (Fishers Exact Test, p = 0.03).\n\nConclusionH. pylori persists in a subset of gastric cancer cases and thus may contribute to cancer progression. In this East Asian population with a high prevalence of the cagA gene, the East Asian allele could still provide a marker for gastric cancer risk.\n\nImpactThis study contributes to our understanding of H. pylori dynamics in the context of pathological changes.

microbiology↗

bioRxiv2017

Unconsciously Implanted Visuoauditory Memory in the Presence of Cholecystokinin Retrieved in Behavioral Contexts

We investigated whether visuoauditory association can be artificially implanted in rodents and then retrieved in a behaviorally relevant context. Rats were trained to approach the left or right hole of a behavioral apparatus to retrieve a reward depending on the side of electrical stimulation of the auditory cortex (EAC) they received and mice were fear-conditioned to EAC. Next, an irrelevant visual stimulus (VS) was repeatedly paired with EAC in the presence of cholecystokinin (CCK) or with activation of terminals of entorhinal CCK neurons in the auditory cortex. In subsequent behavioral testing with VS, rats approached the hole associated with reward availability and mice showed a freezing response to the VS. A CCK antagonist blocked the establishment of visuoauditory association, whereas a CCK agonist rescued the deficit of association. Our findings provide a scientific foundation for \"memory implantation\" and indicate that CCK is the switching chemical for formation of visuoauditory association.

neuroscience↗

bioRxiv2017

Scalable volumetric imaging for ultrahigh-speed brain mapping at synaptic resolution

We describe a new light-sheet microscopy method for fast, large-scale volumetric imaging. Combining synchronized scanning illumination and oblique imaging over cleared, thick tissue sections in smooth motion, our approach achieves high-speed 3D image acquisition of an entire mouse brain within 2 hours, at a resolution capable of resolving synaptic spines. It is compatible with immunofluorescence labeling, enabling flexible cell-type specific brain mapping, and is readily scalable for large biological samples such as primate brain.

neuroscience↗

bioRxiv2017

Natural Variation of OsLG3 Controls Drought Stress Tolerance in Rice by Inducing ROS Scavenging

BackgroundImproving performance of rice under drought stress has potential to significant impact on rice productivity. Previously we reported that OsLG3 positively control rice grain length and yield.\n\nResultsIn this study, we found that OsLG3 was more strongly expressed in upland rice compared to lowland rice under drought stress condition. Candidate gene association analysis showed that the natural variation in OsLG3 was associated with tolerance to water deficit stress in germinating rice seeds. Transgenic rice with enhanced OsLG3 expression exhibited improved tolerance to drought and that is most likely due to enhanced ROS scavenging efficiency. Phylogenetic analysis and pedigree records indicated that the tolerant allele of OsLG3 has potential to improve drought tolerance of japonica rice.\n\nConclusionsCollectively, our work revealed that the natural variation of OsLG3 contributes to rice drought tolerance and the elite allele of OsLG3 is a promising genetic resource for the development of drought-tolerant and high-yield rice varieties.

plant biology↗

bioRxiv2017

A set informative multiple autosomal markers for human identification: forensic research and population genetics analysis in a Chinese Xinjiang Hui group

In recent years, insertion/deletion (InDel) markers became a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 24 previously studied populations using varies methods such as forensic statistical parameter analysis, phylogenetic reconstruction, STRUCTURE analysis, multi-dimensional scaling, and principal component analysis. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD 92), 0.2222 (HLD 114) to 0.5000 (HLD 6), respectively. Besides, after Bonferroni correction, no deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in Xinjiang Hui group. The cumulative probability of exclusion and combined discrimination power were 0.988849 and 0.99999999999378, respectively, which indicated that the 30 loci could be used as complementary genetic markers for paternity test and be qualified for personal identification in forensic cases. In this study, we found that Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations, and all the results based on different genetic methods we used had a strong support for this finding. The 30 InDel loci has important significance in forensic identification research, in spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, molecular genetic genotyping at various genetic markers is necessary in future studies.\n\nSummary StatementWe report here, a promising Individual identification and population differentiation maker which could be used in forensic cases.

genetics↗

bioRxiv2017

Sleeping Beauty transposon integrates into non-TA dinucleotides via an alternative mechanism

Sleeping Beauty transposon (SB) is an important genetic tool for generating mutations in vertebrates. It is well known that SB exclusively integrates into TA dinucleotides. However, this \"TA law\" has never been strictly tested in large number of insertion sites after next generation sequencing was widely utilized. In this study, we analyzed 600 million pairs of Illumina sequence reads and identified 28 thousand SB insertions in non-TA sites. We recovered some non-TA sites using PCR and confirmed that at least parts of the insertions at non-TA sites are real integrations. The consensus sequence of these non-TA sites showed an asymmetric pattern distinct from the symmetric pattern of the canonical TA sites. The right side of the consensus sequence is exactly the same as the sequence of SB transposon ends, indicating interaction between the transposon DNA and the target DNA. Based on these results we suggested that SB has an alternative integration mechanism besides the canonical one to integrate its DNA into non-TA sites.\n\nHighlights[~] For the first time, we proved that Sleeping Beauty transposon can integrate into non-TA dinucleotides.\n\n [~]For the first time, we provided evidence that transposon DNA can directly interact with target DNA.\n\n [~]And for the first time, we found that a transposon can have two independent integration mechanisms.

molecular biology↗

bioRxiv2017

Gelsolin regulates proliferation, apoptosis and invasion in NK/T-cell lymphoma cells through the PI3K/Akt signaling pathway

The expression of gelsolin (GSN) is abnormal in many cancers, including extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). However, the biological function of GSN and its mechanism in NKTCL remain unclear. We found GSN overexpression significantly suppressed cell proliferation, colony formationand invasion and promoted apoptosis of YTS cells. Moreover, the upregulation of GSN significantly decreased the protein levels of PI3K and p-AKT. Interestingly, blocking the PI3K/AKT signaling pathway significantly inhibited cell proliferation and invasion and promoted apoptosis of YTS cells. In conclusion, our findings indicate that GSN can suppress cell proliferation and invasion and promote apoptosis of YTS cells, which is likely to be mediated at least partially through inhibition of the PI3K/AKT signaling pathway.

cancer biology↗

bioRxiv2017

A novel k-mer set memory (KSM) motif representation improves regulatory variant prediction

The representation and discovery of transcription factor (TF) sequence binding specificities is critical for understanding gene regulatory networks and interpreting the impact of disease-associated non-coding genetic variants. We present a novel TF binding motif representation, the K-mer Set Memory (KSM), which consists of a set of aligned k-mers that are over-represented at TF binding sites, and a new method called KMAC for de novo discovery of KSMs. We find that KSMs more accurately predict in vivo binding sites than position weight matrix models (PWMs) and other more complex motif models across a large set of ChIP-seq experiments. KMAC also identifies correct motifs in more experiments than four state-of-the-art motif discovery methods. In addition, KSM derived features outperform both PWM and deep learning model derived sequence features in predicting differential regulatory activities of expression quantitative trait loci (eQTL) alleles. Finally, we have applied KMAC to 1488 ENCODE TF ChIP-seq datasets and created a public resource of KSM and PWM motifs. We expect that the KSM representation and KMAC method will be valuable in characterizing TF binding specificities and in interpreting the effects of non-coding genetic variations.

genomics↗