Biology subjects

Ma, X.

Publications and source records attributed to Ma, X..

32 records · Page 2Linked to original sources

bioRxiv2018

Dynamics of the sex ratio in Tetrahymena thermophila

Sex is often hailed as one of the major successes in evolution, and in sexual organisms the maintenance of proper sex ratio is crucial. As a large unicellular eukaryotic lineage, ciliates exhibit tremendous variation in mating systems, especially the number of sexes and the mechanism of sex determination (SD), and yet how the populations maintain proper sex ratio is poorly understood. Here Tetrahymena thermophila, a ciliate with seven mating types (sexes) and probabilistic SD mechanism, is analyzed from the standpoint of population genetics. It is found based on a newly developed population genetics model that there are plenty of opportunities for both the co-existence of all seven sexes and the fixation of a single sex, pending on several factors, including the strength of natural selection. To test the validity of predictions, five experimental populations of T. thermophila were maintained in the laboratory so that the factors that can influence the dynamics of sex ratio could be controlled and measured. Furthermore, whole-genome sequencing was employed to examine the impact of newly arisen mutations. Overall, it is found that the experimental observations highly support theoretical predictions. It is expected that the newly established theoretical framework is applicable in principle to other multi-sex organisms to bring more insight into the understanding of the maintenance of multiple sexes in a natural population.

evolutionary biology↗

bioRxiv2018

Transposable element insertions shape gene regulation and melanin production in a fungal pathogen

Background\n\nVariation in gene expression contributes to phenotypic diversity within species and adaptation. However, very few cases of adaptive regulatory changes have been reported and the mechanisms underlying variation in gene expression remain largely unexplored. Fungal pathogen genomes are highly plastic and harbour numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work we elucidated how transposable elements contribute to variation of melanin accumulation, a quantitative adaptive trait of fungal pathogens that is involved in survival under stress conditions.\n\nResults\n\nWe demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogen Zymoseptoria tritici. We show that differences in melanin levels between two strains of Z. tritici are due to two levels of transcriptional regulation: 1) variation in the promoter sequence of Zmr1, and 2) an insertion of transposable elements upstream of the Zmr1 promoter. Remarkably, independent insertions of transposable elements upstream of Zmr1 occurred in 9% of Z. tritici strains from around the world and negatively regulated Zmr1 expression, contributing to melanin accumulation variation.\n\nConclusions\n\nOur studies demonstrate that different layers of transcriptional control fine-tune the synthesis of melanin. These regulatory mechanisms potentially evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.

molecular biology↗

bioRxiv2018

Epidemiology, Microbiology and Therapeutic Consequences of Chronic Osteomyelitis in Northern China: A Retrospective Analysis of 255 Patients

The study aimed to explore the epidemiology and clinical characteristics of chronic osteomyelitis observed in a northern China hospital. Clinical data of 255 patients with chronic osteomyelitis from January 2007 to January 2014 were collected and analyzed, including general information, disease data, treatment and follow-up data. Chronic osteomyelitis is more common in males and in the age group from 41-50 years of age. Common infection sites are the femur, tibiofibular, and hip joint. More g+ than g- bacterial infections were observed, with S. aureus the most commonly observed pathogenic organism. The positive detection rate from debridement bacterial culture is 75.6%. The detection rate when five samples are sent for bacterial culture is 90.6%, with pathogenic bacteria identified in 82.8% of cases. The two-stage debridement method (87.0%) has higher first curative rate than the one-stage debridement method (71.2%). To improve detection rate using bacterial culture, at least five samples are recommended. Treatment of chronic osteomyelitis with two-stage debridement, plus antibiotic-loaded polymethylmethacrylate (PMMA) beads provided good clinical results in this study and is therefore recommended.

microbiology↗

bioRxiv2018

Oxytocin enhancement of emotional empathy: generalization across cultures and effects on amygdala activity

Accumulating evidence suggests that the neuropeptide oxytocin can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of oxytocin would specifically enhance emotional empathy via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task (MET) to determine whether oxytocins facilitation of emotional empathy can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). Oxytocin enhanced emotional empathy across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level oxytocin enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of oxytocin on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of oxytocin in facilitating emotional empathy and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.

neuroscience↗

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↗

bioRxiv2018

Bacillus licheniformis global nitrogen homeostatic regulator TnrA is a direct repressor of pgsBCAA transcription in Poly-γ-glutamic acid synthesis

Poly-{gamma}-glutamic acid ({gamma}-PGA) is a multifunctional and naturally occurring biopolymer made from D- and L-glutamate as monomers, which is mainly produced by Bacillus. Few reports have been focused on the regulation network of {gamma}-PGA synthesis in recent years. In this study, we have demonstrated that Bacillus licheniformis global nitrogen homeostatic regulator TnrA is a direct repressor of {gamma}-PGA synthase PgsBCAA in {gamma}-PGA synthesis. First, our results confirmed that TnrA repressed {gamma}-PGA synthesis, deficiency of tnrA led to a 22.03% increase of {gamma}-PGA production, and the {gamma}-PGA yield was decreased by 19.02% in the TnrA overexpression strain. Transcriptional level assay illustrated that the {gamma}-PGA synthase gene cluster pgsBCAA transcriptional level were increased in the tnrA deficient strain WX{Delta}tnrA, indicating that {gamma}-PGA synthase PgsBCAA was negatively regulated by TnrA. Furthermore, electrophoretic mobility shift assay (EMSA) and enzyme expression assays confirmed that TnrA directly repressed pgsBCAA expression by binding to pgsBCAA promoter, and the TnrA-binding site \"CGTCGTCTTCTGTTACA\" in the pgsBCAA promoter was identified by sequence and software analysis. Finally, computer analysis confirmed that the transcription regulations of {gamma}-PGA synthase PgsBCAA by TnrA were highly conserved in other well-studied Bacillus species (B. licheniformis, Bacillus subtilis and Bacillus amyloliquefaciens). Collectively, our results implied that TnrA was a direct repressor for pgsBCAA expression in {gamma}-PGA synthesis, and this research provided a novel regulatory mechanism underlying {gamma}-PGA synthesis, and a new approach that deficiency of tnrA increases {gamma}-PGA production.\n\nImportance{gamma}-PGA is an important biopolymer with many applications, which is mainly produced by Bacillus species. Glutamic acid is the precursor for {gamma}-PGA synthesis, which is catalyzed by the {gamma}-PGA synthase PgsBCAA. Previously, the expression of PgsBCAA was reported to be regulated by ComA-ComP and DegS-DegU, DegQ and SwrA systems, however, few researches were focused on the regulation network of {gamma}-PGA synthesis in recent years. In our research, the {gamma}-PGA synthase PgsBCAA was confirmed to be negatively regulated by the nitrogen metabolism regulator TnrA, and the TnrA binding site in the pgsBCAA promoter was identified in B. licheniformis WX-02. Furthermore, computer analysis implied that TnrA-mediated regulation effect on pgsBCAA expression was highly conserved in Bacillus. Collectively, our research provided a novel regulatory mechanism underlying {gamma}-PGA synthesis, and a new approach that deficiency of tnrA increases {gamma}-PGA production.

microbiology↗

bioRxiv2018

Sex- and Context-dependent Effects of Oxytocin on Social Reward Processing

We interact socially and form bonds with others because such experiences are rewarding. However, an insecure attachment style or social anxiety can reduce these rewarding effects. The neuropeptide oxytocin (OXT) may facilitate social interactions either by increasing their rewarding experience or by attenuating anxiety, although effects can be sex- and attachment-style dependent. In this study, 64 pairs of same-sex friends completed a social sharing paradigm in a double-blind, placebo-controlled, between-subject design with one friend inside an MRI scanner and the other in a remote behavioral testing room. In this way we could examine whether intranasal-OXT differentially modulated the emotional impact of social sharing and associated neural processing. Additionally, we investigated if OXT effects were modulated by sex and attachment style. Results showed that in women, but not men, OXT increased ratings for sharing stimuli with their friend but not with a stranger, particularly in the friend in the scanner. Corresponding neuroimaging results showed that OXT decreased both amygdala and insula activity as well as their functional connectivity in women when they shared with friends but had the opposite effect in men. On the other hand, OXT did not enhance responses in brain reward circuitry. In the PLC treated group amygdala responses in women when they shared pictures with their friend were positively associated with attachment anxiety and OXT uncoupled this. Our findings demonstrate that OXT facilitates the impact of sharing positive experiences with others in women, but not men, and that this is associated with differential effects on the amygdala and insula and their functional connections. Furthermore, OXT particularly reduced increased amygdala responses during sharing in individuals with higher attachment anxiety. Thus, OXT effects in this context may be due more to reduced anxiety when sharing with a friend than to enhanced social reward.

neuroscience↗

bioRxiv2017

A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)

The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.

genomics↗

bioRxiv2017

Rice TSV3 Encoding Obg-like GTPase Protein is Essential for Chloroplast Development during the Early Leaf Stage under Cold Stress

The Spo0B-associated GTP-binding (Obg) proteins occupy a wide variety of roles in the viability of nearly all bacteria. Its detailed roles in higher plants have not yet been elucidated. A novel rice thermo-sensitive virescent mutant tsv3 was identified in this study that displayed albino phenotype at 20{degrees}C before the 3-leaf stage while being normal green at 32{degrees}C or even at 20{degrees}C after the 4-leaf stage. The mutant phenotype was aligned with altered chlorophyll (Chl) content and chloroplast development. Map-based cloning and complementation test showed that TSV3 encoded a kind of small GTP binding protein. Subcellular localization revealed that TSV3 was in chloroplast. TSV3 transcripts were highly expressed in leaves and weak or undetectable in other tissues, suggesting the tissue-specific expression. In tsv3 mutant, the transcriptional levels of certain genes associated with biogenesis of chloroplast ribosomes 50S subunit were severely decreased at the 3-leaf-stage under cold stress, but could be recovered to normal levels at a higher temperature (32{degrees}C). The observations from this study indicated that the rice nuclear-encoded TSV3 plays important roles in chloroplast development at early leaf stage under cold stress.

plant biology↗

bioRxiv2017

Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions

We present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Childrens Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, miRNA sequencing and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including novel gene fusions and focal MBNL1, ZEB2, and ELF1 deletions, were disproportionately prevalent in young as compared to adult patients. Conversely, DNMT3A and TP53 mutations, common in adults, are conspicuously absent from virtually all pediatric cases. Novel GATA2, FLT3, and CBL mutations, recurrent MYC-ITD, NRAS, KRAS, and WT1 mutations are frequent in pediatric AML. Deletions, mutations, and promoter DNA hypermethylation convergently impact Wnt signaling, Polycomb repression, innate immune cell interactions, and a cluster of zinc finger genes associated with KMT2A rearrangements. These results highlight the need for, and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.

cancer biology↗

bioRxiv2017

VCF2CNA: A tool for efficiently detecting copy-number alteration in VCF genotype data

VCF2CNA is a web interface tool for copy-number alteration (CNA) analysis of VCF and other variant file formats. We applied it to 46 adult glioblastoma and 146 pediatric neuroblastoma samples sequenced by Illumina and Complete Genomics (CGI) platforms respectively. VCF2CNA was highly consistent with a state-of-the-art algorithm using raw sequencing data (mean F1-score=0.994) in high-quality glioblastoma samples and was robust to uneven coverage introduced by library artifacts. In the neuroblastoma set, VCF2CNA identified MYCN high-level amplifications in 31 of 32 clinically validated samples compared to 15 found by CGIs HMM-based CNA model. The findings suggest that VCF2CNA is an accurate, efficient and platform-independent tool for CNA analyses without accessing raw sequence data.

genomics↗

bioRxiv2017

Genome-wide Segregation of Single Nucleotide and Structural Variants into Single Leukemia Cells

We present a new approach for determining comprehensive variant profiles of single cells using a microfluidic amplicon-based strategy. This method can be used to reconstruct the clonal architecture and mutational history of a malignancy using all classes and sizes of single nucleotide and structural variants, providing insights into the temporal changes in mutational classes and processes that led to the development of a cancer. Using this approach, we interrogated single cells from a patient with leukemia, determining that processes producing structural variation preceded single nucleotides changes in the development of that malignancy.

cancer biology↗

bioRxiv2017

Mutation of a palmitoyltransferase ZDHHC18-like gene is responsible for the minute wing mutation in the silkworm (Bombyx mori)

Pulpal- and adult-stage minute wing (mw) mutants of the silkworm Bombyx mori have much smaller wings than those of the wild type. Herein, we report the genetic and molecular mechanisms underling the formation of the minute wing. Fine mapping and positional cloning revealed that a palmitoyltransferase ZDHHC18-like gene (BmAPP)was responsible for the mw mutation. CRISPR/Cas9 screening of the BmAPP gene in wild-type embryos revealed that a significant proportion of adults had the mw mutation. In an mw mutant strain, u11, a 10-bp insertion in the promoter of a novel gene resulted in low-level translation of a protein belonging to the DHHC family. A PiggyBac-based transgenic analysis showed that the promoter induced the expression of aBmAPP gene promoter in the wild type but not the mw mutant. These findings indicate that functional deletion of this gene promoter accounts for the mw mutation in silkworm. The possibility that BmAPP gene is involved in Hippo signalling pathway, an evolutionarily conserved signaling pathway that controls organ size, is discussed.

molecular biology↗

bioRxiv2017

Evaluation of Oxford Nanopore MinION Sequencing for 16S rRNA Microbiome Characterization

In this manuscript we evaluate the potential for microbiome characterization by sequencing of near-full length 16S rRNA gene region fragments using the Oxford Nanopore MinION (hereafter Nanopore) sequencing platform. We analyzed pure-culture E. coli and P. fluorescens, as well as a low-diversity mixed community sample from hydraulic fracturing produced water. Both closed and open reference operational taxonomic unit (OTU) picking failed, necessitating the direct use of sequences without OTU picking. The Ribosomal Database Project classifier against the Green Genes database was found to be the optimal annotation approach, with average pure-culture annotation accuracies of 93.8% and 82.0% at the phyla and genus levels, respectively. Comparative analysis of an environmental sample using Nanopore and Illumina MiSeq sequencing identified high taxonomic similarity when using a weighted metric (Bray-Curtis), and significantly reduced similarity when using an unweighted metric (Jaccard). These results highlight the great potential of Nanopore sequencing to analyze broad microbial community trends, and the challenge of applying Nanopore sequencing to discern rare taxa in mixed microbial communities. Finally, we observed that between-run carryover following washes on the same flowcell accounted for >10% of sequence reads, necessitating future development to either prevent carryover or filter sequences of interest (e.g. barcoding).

microbiology↗