Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 955 records · Page 53Linked to original sources

bioRxiv2019

A unified neurocognitive model of the anterior temporal lobe contributions to semantics, language, social behaviour & face recognition

AbstractThe anterior temporal lobes (ATL) have become a key brain region of interest in cognitive and clinical neuroscience. Contemporary explorations are founded upon neuropsychological investigations of semantic dementia (SD) that describe the patients selective semantic impairment and the variations in their language, behavioural and face recognition abilities. The purpose of this investigation was to generate a single unified model which captures the known cognitive-behavioural variations in SD, and integrates with the considerable database on healthy semantic function and other patient groups. A new analytical approach was able to capture the graded neuropsychological differences and map these to the patients distribution of frontotemporal atrophy. Multiple regression and principal component analyses confirmed that the degree of generalised semantic impairment was related to the patients total, bilateral ATL atrophy. Verbal production and word-finding abilities were related to total ATL atrophy as well as to the balance of left>right ATL atrophy. Behavioural apathy was found to relate positively to the degree of orbitofrontal atrophy and negatively to total temporal volumes. Disinhibited behaviour was related to right ATL and orbitofrontal atrophy and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.

neuroscience↗

bioRxiv2019

JMJD6 Cleaves MePCE to Release P-TEFb

More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II-CTD by positive transcription elongation factor (P-TEFb) is a necessary precursor event that enables productive transcription elongation. The exact mechanism on how the sequestered P-TEFb is released from the 7SK snRNP complex and recruited to Pol II-CTD remains unknown. In this report, we reveal methylphosphate capping enzyme (MePCE), a core component of the 7SK snRNP complex, as the cognate substrate for Jumonji domain-containing 6 (JMJD6)s novel proteolytic function. Our evidences consist of a crystal structure of JMJD6 bound to methyl-arginine, enzymatic assays of JMJD6 cleaving MePCE in vivo and in vitro, binding assays, and downstream effects of Jmjd6 knockout and overexpression on Pol II-CTD phosphorylation. We propose that JMJD6 assists bromodomain containing 4 (BRD4) to recruit P-TEFb to Pol II-CTD by disrupting the 7SK snRNP complex.

biochemistry↗

bioRxiv2019

Population genomics and pathotypic evaluation of the bacterial leaf blight pathogen of rice

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight disease, which reduces crop yield by up to 50% in rice production. Despite its substantial threat on food production worldwide, knowledge about its population structure, virulence diversity and the relationship between them is limited. We used whole-genome sequencing to explore the diversity and evolution of Xoo during the past 30 years in the main rice-planting areas of China. Six separate lineages were revealed by phylogenomic analysis, with CX-5 and CX-6 predominating in the population for decades. The recent sporadic outbreaks were respectively caused by Xoo derived from these lineages especially the two major ones. The lineage and sub-lineage distribution of isolates strongly correlated to their geographical origin, which was found to be mainly determined by the planting of the two major rice subspecies, indica and japonica. Large-scale virulence testing was conducted to evaluate the diversity of pathogenicity for Xoo. We found rapid virulence dynamics against rice, and its determinant factors including genetic background of Xoo, rice resistance genes and the planting environment of rice. Genetic background was investigated deeply by comparative genomics, which indicates that transposition events contributing the most to evolution of the Xoo genome and the rapid diversification of virulence. This study provided a good model to understand the evolution and dynamics of plant pathogens in the context of interaction with their hosts which are influenced by both geographical conditions and farming practices.

genomics↗

bioRxiv2019

Quantitative intravital imaging of Plasmodium falciparum sporozoites: A novel platform to test malaria intervention strategies

Malaria infection starts with the injection of motile Plasmodium sporozoites into the hosts skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functional in vivo assays with human malaria parasites are lacking. Here, we present the first characterization of P. falciparum sporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influences P. falciparum sporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier for Plasmodium. We observe that P. falciparum sporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targeting P. falciparum sporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoites in vivo. Screening of intervention strategies for in vivo efficacy against Pf sporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.

microbiology↗

bioRxiv2019

The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy

Picornaviruses, comprising important and widespread pathogens of humans and animals, have evolved to control apoptosis and autophagy for their replication and spread. However, the underlying mechanism of the association between apoptosis/autophage and viral pathogenicity remains unclear. In the present study, VP3 of picornaviruses was demonstrated to induce apoptosis and autophagy. Foot-and-mouth disease virus (FMDV), which served as a research model here, can strongly induce both apoptosis and autophagy in the skin lesions. By directly interacting with p53, FMDV-VP3 facilitates its phosphorylation and translocation, resulting in Bcl-2 family-mediated apoptosis and LC3-dependent autophagy. The single residue Gly129 of FMDV-VP3 plays a crucial role in apoptosis and autophagy induction and the interaction with p53. Consistently, the comparison of rescued FMDV with mutated Gly129 and parental virus showed that the Gly129 is indispensable for viral replication and pathogenicity. More importantly, the Gly129 locates at a bend region of random coil structure, the mutation of Gly to Ala remarkably shrunk the volume of viral cavity. Coincidentally, the Gly is conserved in the similarly location of other picornaviruses, including poliovirus (PV), enterovirus 71 (EV71), coxsackievirus (CV) and seneca valley virus (SVA). This study demonstrates that picornaviruses induce apoptosis and autophagy to facilitate its pathogenicity and the Gly is functional site, providing novel insights into picornavirus biology.

microbiology↗

bioRxiv2019

Inhibiting Mycobacterium tuberculosis ClpP1P2 by addressing the equatorial handle domain of ClpP1 subunit

Unlike other bacterial ClpP systems, mycobacterial ClpP1P2 complex is essential for mycobacterial survival. The functional details of Mycobacterium tuberculosis (Mtb) ClpP1P2 remains largely elusive and selectively targeting ClpP of different species is a big challenge. In this work, cediranib was demonstrated to significantly decrease the activity of MtbClpP1P2. By solving the crystal structure of cediranib-bound MtbClpP1P2, we found that cediranib dysregulates MtbClpP1P2 by interfering with handle domain of the equatorial region of MtbClpP1, indicating that the inter-ring dynamics are crucial for its function. This finding provides direct evidence for the notion that a conformational switch in the equatorial handle domain is essential for ClpP activity. We also present biochemical data to interpret the distinct interaction pattern and inhibitory properties of cediranib toward MtbClpP1P2. These results suggest that the variable handle domain region is responsible for the species-selectivity of cediranib, which suggests the equatorial handle domain as a potential region for screening pathogen-specific ClpP inhibitors.

biochemistry↗

bioRxiv2019

An updated analysis of opioids increasing the risk of fractures

ObjectiveTo assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies.\n\nMethodsThe included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate.\n\nResultsIn total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53 - 2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed.\n\nConclusionsThe meta-analysis showed that the use of opioids significantly increased the risk of fracture.

pharmacology and toxicology↗

bioRxiv2019

Use of extracellular polymer substances as additives for improving biogas yield and digestion performance

To understand how extracellular polymer substances (EPS) as additives promotes methanogenesis, batch tests of methane production potential in anaerobic reactors with the addition of EPS or not were conducted. Research showed that EPS increased remarkably methane production during anaerobic digestion (36.5% increase compared with the control). EPS enriched functional microorganisms such as Firmicutes, Actinobacteria, Synergistetes, and Chloroflexi. Among them, 8.86% OTUs from the important hydrolysis and acidification phyla, which may be an important reason for the enhanced methanogenic capacity of anaerobic granular sludge. Additionally, EPS also improved the abundance of cytochrome c (c-Cyts), accelerating the direct interspecies electron transfer (DIET) between syntrophic bacteria and methanogens, thus enhancing the methane production. Interestingly, the average particle size, volatile suspended solids/total suspended solids (VSS/TSS) and EPS content of anaerobic granular sludge (AnGS) in the EPS reactor were approximately equal to that of the control reactor during the anaerobic digestion, illustrating that EPS could not affect the physicochemical properties of AnGS. Therefore, these results suggested that EPS mainly played a role in the form of conductive materials in the anaerobic digestion process. Compared with conductive materials, EPS as biomass conductive materials was not only environmentally friendly and economical but also no secondary pollution.\n\nImportanceCompared with the reported conductive materials, EPS has the potential of biodegradation, electron transfer and no significant secondary pollution. Besides, there are few studies on the utilization of EPS resources, especially the effect of EPS as an additive on anaerobic digestion performance. To clarify whether EPS as conductive materials or carbon source promotes methanogenesis. Therefore, in this study, we investigated the influence of EPS as an additive on the methanogenic capacity, physical-chemical properties, microbial community structure and metabolic function of anaerobic granular sludge (AnGS), and preliminarily expatiate the influence mechanism of EPS as an additive on methanogenesis. At the meantime, the research is expected to provide new solutions for the improvement of anaerobic digestion performance and disposal of waste mud.

biochemistry↗

bioRxiv2019

Cell growth kinetics and accumulation of secondary metabolite of Bletilla striata Rchb.f. using cell suspension culture

Bletilla striata (Orchidaceae) is a well-recognized endangered medicinal plant due to inadequate natural reproduction with high market worth. To evaluate the cell growth kinetics and accumulation of secondary metabolites (SMs), the cell suspension culture is proved to be a valuable approach for acquiring the high yield of medicinal parts. An effective cell suspension culture for obtaining B. striata cell growth and its SMs was in vitro induction of callus from B. striata seeds. The cell growth kinetics and accumulation of SMs were analyzed using the mathematical model. Results cell growth kinetic model revealed that the growth curve of B. striata suspension cells was curved as sigmoid shape, indicating the changes of the growth curve of suspension cells. Improved Murashige and Skoog cell growth medium was the utmost favorable medium for B. striata callus formation with the highest cell growth during the stationary phase of cultivation period, the cell growth acceleration was started after 7 days and thereafter gradually decrease at 24 day and then reached to highest at 36 day of cultivation period in both dry weight and fresh weight. The coelonin concentration was peak during exponential growth stage and decreased afterward at the stationary phase in the cell suspension culture. The maximum content of coelonin (about 0.3323 mg/g cell dry weight) was observed on the 18th day of the cultivation cycle while the dactylorhin A and militarine reached highest at 24 day, and p-hydroxybenzyl alcohol at 39 day. This investigation also laid a foundation for multi-mathematical model to better describe the accumulation variation of SMs. The production of SMs had shown great specificity during cells growth and development. This research provided a well-organized way to more accumulation and production of SMs, on scale-up biosynthesis in B. striata cell suspension culture.

plant biology↗

bioRxiv2019

Evidence for mutation-order speciation between convergent ecotypes

Natural selection shapes how new species arise, yet the mechanisms that generate reproductive barriers remain debated. Although ecological divergence in contrasting environments and mutation-order processes in similar environments are often viewed as distinct speciation mechanisms, we show they act together as part of a continuum we call parallel mosaic speciation. In the Senecio lautus species complex, Dune and Headland ecotypes have evolved repeatedly along the Australian coastline. Through crossing experiments and field studies, we find that divergent natural selection promotes strong reproductive isolation between the Dune and Headland ecotypes. While uniform selection maintains reproductive compatibility among ecologically similar Dune populations, Headland populations have evolved reproductive barriers despite their convergent prostrate phenotypes, likely driven by adaptation to heterogeneous environments. To understand how habitat heterogeneity contributes to patterns of reproductive isolation, we extend previous theoretical work on the accumulation of hybrid incompatibilities to account for environmental gradients and polygenic adaptation. We show that the probability of reproductive isolation depends on three factors: how similar the environments are, how complex the genetic architecture is, and how selection coefficients are distributed among beneficial mutations. These theoretical findings explain how reproductive isolation arises in systems like Senecio, where multiple forms of selection jointly drive parallel speciation.

evolutionary biology↗

bioRxiv2019

Model reconstruction from Small angle X-ray Scattering data using deep learning methods

We present an algorithm based on a deep learning method for model reconstruction from small angle X-ray scattering (SAXS) data. An auto-encoder for protein 3D models was trained to compress 3D shape information into vectors of a 200-dimensional latent space, and the vectors are optimized using genetic algorithms to build 3D models that are consistent with the scattering data. The algorithm was implemented using Python with the TensorFlow framework and tested with experimental data, demonstrating capacity and robustness of accurate model reconstruction even without using prior model size information.\n\nSynopsisA deep learning method based on the auto-encoder framework for model reconstruction from small angle scattering data

bioinformatics↗

bioRxiv2019

Phylogenomics provides new insights into gains and losses of selenoproteins among Archaeplastida

Selenoproteins that contain selenocysteine (Sec) are found in all kingdoms of life. Although they constitute a small proportion of the proteome, selenoproteins play essential roles in many organisms. In photosynthetic eukaryotes, selenoproteins have been found in algae but are missing in land plants (embryophytes). In this study, we explored the evolutionary dynamics of Sec incorporation by conveying a genomic search for the Sec machinery and selenoproteins across Archaeplastida. We identified a complete Sec machinery and variable sizes of selenoproteomes in the main algal lineages. However, the entire Sec machinery was missing in the BV clade (Bangiophyceae-Florideophyceae) of Rhodoplantae (red algae) and only partial machinery was found in three species of Archaeplastida, indicating parallel loss of Sec incorporation in different groups of algae. Further analysis of genome and transcriptome data suggests that all major lineages of streptophyte algae display a complete Sec machinery, although the number of selenoproteins is low in this group, especially in subaerial taxa. We conclude that selenoproteins tend to be lost in Archaeplastida upon adaptation to a subaerial or acidic environment. The high number of redox-active selenoproteins found in some bloom-forming marine microalgae may be related to defense against viral infections. Some of the selenoproteins in these organisms may have been gained by horizontal gene transfer from bacteria.

molecular biology↗

bioRxiv2019

Combining statistical and neural network approaches to derive energy functions for completely flexible protein backbone design

A designable protein backbone is one for which amino acid sequences that stably fold into it exist. To design such backbones, a general method is much needed for continuous sampling and optimization in the backbone conformational space without specific amino acid sequence information. The energy functions driving such sampling and optimization must faithfully recapitulate the characteristically coupled distributions of multiplexes of local and non-local conformational variables in designable backbones. It is also desired that the energy surfaces are continuous and smooth, with easily computable gradients. We combine statistical and neural network (NN) approaches to derive a model named SCUBA, standing for Side-Chain-Unspecialized-Backbone-Arrangement. In this approach, high-dimensional statistical energy surfaces learned from known protein structures are analytically represented as NNs. SCUBA is composed as a sum of NN terms describing local and non-local conformational energies, each NN term derived by first estimating the statistical energies in the corresponding multi-variable space via neighbor-counting (NC) with adaptive cutoffs, and then training the NN with the NC-estimated energies. To determine the relative weights of different energy terms, SCUBA-driven stochastic dynamics (SD) simulations of natural proteins are considered. As initial computational tests of SCUBA, we apply SD simulated annealing to automatically optimize artificially constructed polypeptide backbones of different fold classes. For a majority of the resulting backbones, structurally matching native backbones can be found with Dali Z-scores above 6 and less than 2 [A] displacements of main chain atoms in aligned secondary structures. The results suggest that SCUBA-driven sampling and optimization can be a general tool for protein backbone design with complete conformational flexibility. In addition, the NC-NN approach can be generally applied to develop continuous, noise-filtered multi-variable statistical models from structural data.\n\nLinux executables to setup and run SCUBA SD simulations are publicly available (http://biocomp.ustc.edu.cn/servers/download_scuba.php). Interested readers may contact the authors for source code availability.

bioinformatics↗

bioRxiv2019

Chromosome level draft genomes of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), an alien invasive pest in China

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) is a severely destructive pest native to the Americas, but has now become an alien invasive pest in China, and causes significant economic loss. Therefore, in order to make effective management strategies, it is highly essential to understand genomic architecture and its genetic background. In this study, we assembled two chromosome scale genomes of the fall armyworm, representing one male and one female individual procured from Yunnan province of China. The genome sizes were identified as 542.42 Mb with N50 of 14.16 Mb, and 530.77 Mb with N50 of 14.89 Mb for the male and female FAW, respectively. We predicted about 22,201 genes in the male genome. We found the expansion of cytochrome P450 and glutathione s-transferase gene families, which are functionally related to the intensified detoxification and pesticides tolerance. Further population analyses of corn strain (C strain) and rice strain (R strain) revealed that the Chinese fall armyworm was most likely invaded from Africa. These strain information, genome features and possible invasion source described in this study will be extremely important for making effective strategies to manage the fall armyworms.

genomics↗

bioRxiv2019

An improved pig reference genome sequence to enable pig genetics and genomics research

The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limited its utility. We present two annotated highly contiguous chromosome-level genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

genomics↗

bioRxiv2019

A Novel Antenna Protein Complex in the Life Cycle of Cyanobacterial Photosystem II

In oxygenic photosynthetic organisms, photosystem II (PSII) is a unique membrane protein complex that catalyzes light-driven oxidation of water. PSII undergoes frequent damage due to its demanding photochemistry. However, many facets of its repair and reassembly following photodamage remain unknown. We have discovered a novel PSII subcomplex that lacks five key PSII core reaction center polypeptides: D1, D2, PsbE, PsbF, and PsbI. This pigment-protein complex does contain the PSII core antenna proteins CP47 and CP43, as well as most of their associated low-molecular-mass subunits, and the assembly factor Psb27. Immunoblotting analysis, multiple mass spectrometry techniques, and ultrafast spectroscopic results supported the absence of a functional reaction center in this chlorophyll-protein complex. We therefore refer to it as the no reaction center complex (NRC). Additionally, genetic deletion of PsbO on the PSII lumenal side resulted in an increased NRC population, indicative of a faulty PSII repair scheme at the cellular level. Analytical ultracentrifugation studies and clear native acrylamide gel analysis showed that the NRC complex is a stable pigment-protein complex and not a mixture of free CP47 and CP43 proteins. Our finding challenges the current model of the PSII repair cycle and implies an alternative PSII repair strategy. We propose that formation of this pigment-protein complex maximizes PSII repair economy by preserving an intact PSII core antenna shell in a single complex that is available for PSII reassembly, thus minimizing the risk of randomly diluting multiple recycling components in the thylakoid membrane following a photodamage event at the RC.\n\nSignificance statementPhotosystem II (PSII) converts sunlight into chemical energy, powering nearly all life on Earth. The efficiency of this process is maximized under various environmental conditions by a frequent repair and reassembly cycle that follows inevitable PSII damage even during normal oxygenic photosynthesis. We have isolated a novel pigment protein PSII subcomplex in which, surprisingly, the reaction center (RC) components of PSII are absent. Formation of this stable chlorophyll-protein complex suggests a protective mechanism whereby longer-lived PSII subunits are unplugged from the damaged RC to prevent harmful, aberrant photochemistry during RC repair. This finding provides intriguing new insight into how PSII is assembled and rebuilt to optimize its performance to optimally catalyze one of the most challenging reactions in biology.

plant biology↗

bioRxiv2019

Comparative analyses of 3654 chloroplast genomes unraveled new insights into the evolutionary mechanism of green plants

BackgroundChloroplast are believed to arise from a cyanobacterium through endosymbiosis and they played vital roles in photosynthesis, oxygen release and metabolites synthesis for the plant. With the advent of next-generation sequencing technologies, until December 2018, about 3,654 complete chloroplast genome sequences have been made available. It is possible to compare the chloroplast genome structure to elucidate the evolutionary history of the green plants.\n\nResultsWe compared the 3654 chloroplast genomes of the green plants and found extreme conservation of gene orders and gene blocks in the green plant such as ATP synthase cluster, Phytosystem, Cytochrome cluster, and Ribosomal cluster. For the chloroplast-based phylogenomics, we used three different data sets to recover the relationships within green plants which accounted for biased GC content and could mitigate the bias in molecular data sets by increasing taxon sampling. The main topology results include: I) Chlorokybales + Mesostigmatales as the earliest-branching lineage and a clade comprising Zygnematales+ Desmidiales formed a grade as the sister group to the land plants, II) Based on matrix AA data, Bryophytes was strongly supported as monophyletic but for matrix nt123 data, hornworts, mosses and liverworts were placed as successive sister lineages of Tracheophytes with strong support, III) Magnoliids were placed in the outside of Monocots using the matrix nt123 data and the matrix AA data, IV) Ceratophyllales + Chloranthales as sister to the Eudicots using matrix nt123 data, but when using matrix nt12 data and AA data, only Ceratophyllales sister to the Eudicots.\n\nConclusionWe present the first of its kind large scale comparative analyses of the chloroplast coding gene constitution for 3654 green plants. Some important genes likely showed co-occurrence and formed gene cluster and gene blocks in Streptophyta. We found a clear expansion of IRs (Inverted Repeats) among seed plants. The comprehensive taxon sampling and different data sets recovered a strong relationship for green plants.

plant biology↗

bioRxiv2019

Accelerating iterative deconvolution and multiview fusion by orders of magnitude

We describe theoretical and practical advances in algorithm and software design, resulting in ten to several thousand-fold faster deconvolution and multiview fusion than previous methods. First, we adapt methods from medical imaging, showing that an unmatched back projector accelerates Richardson-Lucy deconvolution by at least 10-fold, in most cases requiring only a single iteration. Second, we show that improvements in 3D image-based registration with GPU processing result in speedups of 10-100-fold over CPU processing. Third, we show that deep learning can provide further accelerations, particularly for deconvolution with a spatially varying point spread function. We illustrate the power of our methods from the subcellular to millimeter spatial scale, on diverse samples including single cells, nematode and zebrafish embryos, and cleared mouse tissue. Finally, we show that our methods facilitate the use of new microscopes that improve spatial resolution, including dual-view cleared tissue light-sheet microscopy and reflective lattice light-sheet microscopy.

bioengineering↗