Biology subjects

Li, P.

Publications and source records attributed to Li, P..

At least 325 records · Page 18Linked to original sources

bioRxiv2019

Structural changes in the gut microbiome of short-term and long-term medical workers compared to normal controls

ObjectiveHospital environment has been implicated in enrichment and exchange of pathogens and antibiotic resistances, but its potential in shaping the symbiotic microbial community of the hospital staff is unclear. This study was designed to evaluate the alteration of gut microbiome in medical workers compared to non-medical controls.\n\nDesignProspective cross-sectional cohort study.\n\nSettingIntensive care unit (ICU) and other departments from a center in northeast China.\n\nSubjects175 healthy medical workers (1-3 months short-term workers, n = 80; >1 year long-term workers, n = 95) and 80 healthy normal controls.\n\nInterventionsNone.\n\nMeasurements and Main ResultsFecal samples of all subjects were analyzed using the 16S rRNA gene sequencing. Medical workers exhibited remarkable deviation in gut microbial within-sample diversity and enterotypes stratification, and shift in overall microbial structure. Short-term workers were significantly more abundant in taxa including Lactobacillus, Butyrivibrio, Clostridiaceae_Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter and Desulfovibrio, and with lower abundances of Bacteroides and Blautia compared with the controls. While long-term workers were enriched in taxa including Dialister, Veillonella, Clostridiaceae_Clostridium, Bilophila, Desulfovibrio, Pseudomonas and Akkermansia, with lower abundances of Bacteroides and Coprococcus compared with the controls. In addition, medical workers working years (short-term vs. long-term), hospital department (resident doctor vs. nursing staff) and work position (ICU vs. not-ICU) revealed considerable effects on their gut microbiome. Moreover, by analyzing the environmental samples (n = 9) around the inpatient wards and the hospital, we showed that the gut microbiota of medical workers was closer to environmental microbiota than that of the normal controls, probably in correlation to lasting exposure to the pathogenic taxa (e.g. Pseudomonas) in health workers.\n\nConclusionsOur findings demonstrated structural changes in the gut microbial community of the medical workers. Further studies are proposed for investigating the potentially physiological influence of the altered gut microbiome in medical participants.\n\nIMPORTANCEIn this study, we for the first time focused on the influence of hospital environmental factors on gut microbiota of medical workers. The significance of our study is not limited to revealing the remodeling effect of the hospital environment on the gut microbiota of medical workers. Based on these, we also propose targeted and operational recommendations that can promote the health of hospital staff.

microbiology↗

bioRxiv2019

P16 methylation increases the sensitivity of cancer cells to the CDK4/6 inhibitor palbociclib

The P16 (CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment. P16 is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells with P16 deletion are more sensitive to palbociclib than those without. However, whether P16 methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n=522) was positively correlated with both the P16 expression level and P16 gene copy number. Our experimental results further showed that cancer cell lines with P16 methylation were more sensitive to palbociclib than those without. To determine whether P16 methylation directly increased the sensitivity of cancer cells to palbociclib, we induced P16 methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineered P16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 M). Notably, palbociclib treatment also selectively inhibited the proliferation of the P16-methylated subpopulation of P16-Dnmt cells, further indicating that P16 methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of the P16 gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.

pharmacology and toxicology↗

bioRxiv2019

Transmural and rate-dependent profiling of drug-induced arrhythmogenic risks through in silico simulations of multichannel pharmacology

BackgroundIn vitro hERG blockade assays alone provide insufficient information to accurately discriminate \"safe\" from \"dangerous\" drugs. Recent studies have suggested that the integration of multiple ion channel inhibition data can improve the prediction of drug-induced arrhythmogenic risks. In this study, using a family of cardiac cell models representing electrophysiological heterogeneities across the ventricular wall, we quantitatively evaluated transmural and rate-dependent properties of drug-induced arrhythmogenicity through computer simulations of multichannel pharmacology.\n\nMethods and ResultsRate-dependent drug effects of multiple ion channel inhibition on cardiac electrophysiology at their effective free therapeutic plasma concentrations (EFTPCs) were investigated using a group of in silico cell models (Purkinje (P) cells, endocardial (Endo) cells, mid-myocardial (M) cells and epicardial (Epi) cells). We found that (1) M cells are much more sensitive than the other cell types to drug-induced arrhythmias and can develop early afterdepolarization (EAD) in response to bepridil, dofetilide, sotalol, terfenadine, cisapride or ranolazine. (2) Most drug-induced adverse effects, such as pronounced action potential prolongations or EADs, occur at slower pacing rates. (3) Although most drug-induced EADs occur in M cells, the application of quinidine at its EFTPC can cause EADs in all four cell types. (4) The underlying ionic mechanism of drug-induced EADs differs across different cell types; while INaL is the major depolarizing current during the generation of EAD in P cells, ICaL is mostly predominant in other cell types. (5) Drug-induced AP alternans with larger beat-to-beat variations occur at high pacing rates in mostly P cells, while the application of bepridil can cause alternating EAD patterns at slower pacing rates in M cells.\n\nConclusionsIn silico analysis of transmural and rate-dependent properties using multichannel inhibition data can be useful to accurately predict drug-induced arrhythmogenic risks and can also provide mechanistic insights into drug-induced adverse events related to cardiac arrhythmias.\n\nAuthor summaryIn vitro hERG blockade assays alone provide insufficient information to accurately discriminate \"safe\" from \"dangerous\" drugs, and computer simulation of ventricular action potential using multichannel inhibition data could be a useful tool to evaluate drug-induced arrhythmogenic risks. Our study suggested that the profiling of drug-induced transmural heterogeneities in cellular electrophysiology at all physiological pacing frequencies can be essential for the comprehensive evaluation of drug safety, and for the quantitative investigation into ionic mechanisms underlying drug-specific arrhythmogenic events. These in silico models and approaches may contribute to the ongoing construction of a comprehensive paradigm for the evaluation of drug-induced arrhythmogenic risks, potentially increase the success rate and accelerate the process of novel drug development.

pharmacology and toxicology↗

bioRxiv2019

Using Machine Learning and Gene Nonhomology Features to Predict Gene Ontology

Advances in genome sequencing and annotation have eased the difficulty of identifying new gene sequences. Predicting the functions of these newly identified genes remains challenging. Genes descended from a common ancestral sequence are likely to have common functions. As a result homology is widely used for gene function prediction. This means functional annotation errors also propagate from one species to another. Several approaches based on machine learning classification algorithms were evaluated for their ability to accurately predict gene function from non-homology gene features. Among the eight supervised classification algorithms evaluated, random forest-based prediction consistently provided the most accurate gene function prediction. Non-homology-based functional annotation provides complementary strengths to homology-based annotation, with higher average performance in Biological Process GO terms, the domain where homology-based functional annotation performs the worst, and weaker performance in Molecular Function GO terms, the domain where the accuracy of homology-based functional annotation is highest. Non-homology-based functional annotation based on machine learning may ultimately prove useful both as a method to assign predicted functions to orphan genes which lack functionally characterized homologs, and to identify and correct functional annotation errors which were propagated through homology-based functional annotations.

bioinformatics↗

bioRxiv2019

E-cadherin binds glycosylated sodium-taurocholate cotransporting polypeptide to facilitate hepatitis B virus entry

Hepatitis B virus (HBV) continues to pose a serious public health risk and is one of the major causes of chronic liver disease and hepatocellular carcinoma. Current antiviral therapy does not effectively eradicate HBV and, thus, further investigation into the mechanisms employed by HBV to allow for invasion of host cells, is critical for the development of novel therapeutic agents. Sodium-taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for HBV. However, the specific mechanism by which HBV and NTCP interact remains unclear. Herein we show that the expression of E-cadherin was upregulated in cells expressing HBV, while knockdown of E-cadherin in HepG2-NTCP cells, HepaRG cells and primary human hepatocytes served to significantly inhibit infection by HBV and HBV pseudotyped particles. Alternatively, exogenous E-cadherin expression was found to significantly enhance HBV uptake by HepaRG cells. Further, mechanistic studies identified glycosylated NTCP localized to the cell membrane via E-cadherin binding, which subsequently allowed for more efficient binding between NTCP and the preS1 of the large HBV surface proteins. E-cadherin was also found to play a key role in establishing and maintaining hepatocyte polarity, which is essential for efficient HBV infection. These observations suggest that E-cadherin facilitates HBV entry through regulation of NTCP distribution and hepatocyte polarity.\n\nAuthor SummaryHepatitis B Virus (HBV) still seriously endangers public health. It is very important to understand the mechanism of HBV invading host cells for developing new therapy target. Sodium-taurocholate cotransporting polypeptide (NTCP) is the key receptor mediating HBV invasion, while other molecules also exhibit important roles in ensuring efficient and productive HBV infection. This study reports that E-cadherin facilitates HBV entry by directly interacting with glycosylated NTCP to mediate its distribution on the hepatocyte membrane and also affects the efficacy of HBV invasion by influncing hepatocyte polarity.

microbiology↗

bioRxiv2019

Experimental study of lumbar ligamentum flavum hypertrophy induced in bipedal mice

Lumbar spinal stenosis (LSS) is a common degenerative disease among the elderly. The role that mechanical stress-induced hypertrophic ligamentum flavum (HLF) plays in patients with LSS remains unclear. Here, we used a finite element analysis to investigate the stress characteristics on the ligamentum flavum (LF) and evaluate the feasibility of a mouse model of HLF. First, we induced a bipedal posture in mice by taking advantage of their hydrophobia. A micro-CT scan was performed to examine their spinal change during bipedal posture. A finite element analysis showed that the stress and strain on the upright posture were significantly increased compared with those on the sprawling posture. Tissue staining showed that the degeneration degree of the LF in bipedal standing group gradually increased over the modeling period. The amount of elastic fibers decreased under HLF, whereas the amount of collagen fibers, the number of the LF cells, and the expression of fibrosis-related factors increased. Compared with aged group, LF degeneration was more severe in the bipedal standing group. Our findings demonstrate that the increased stress caused by a posture change causes HLF and that a bipedal mouse model can be used to study HLF in vivo.

biophysics↗

bioRxiv2019

The YdiU Domain Modulates Bacterial Stress Signaling through UMPylation

Sensing stressful conditions and adjusting cellular metabolism to adapt to the environment is essential for bacteria to survive in variable situations. Here, we describe a new stress-related protein YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine 5-monophosphate to a protein tyrosine/histidine residue--a novel modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+-binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. The detailed mechanism is proposed based on Apo-YdiU, YdiU-ATP, YdiU-AMP crystal structures and molecular dynamics simulation models of YdiU-UTP and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation. HighlightsO_LIYdiU involves in stress-resistance of Salmonella. C_LIO_LIYdiU mediates protein UMPylation in a Mn2+-dependent manner. C_LIO_LIStructural insights into YdiU-mediated UMPylation. C_LIO_LIUMPylation of chaperones by YdiU modulates their function. C_LI

biochemistry↗

bioRxiv2019

Transcriptional Differences of Peanut (Arachis hypogaea L.) Seeds in the Fresh-harvest, After-ripened and Just-germinated States: insights into regulatory networks of seed dormancy-release and germination

Seed dormancy and germination are the two important traits related to plant survival and reproduction, and crop yield. To understand their regulation mechanism, it is crucial to clarify which genes or which pathways participate in the regulation of these processes. However, little information is available during the procedure of seed dormancy and germination in peanut. In this study, the seeds of the variety Luhua No.14 with non-deep dormancy were selected and its transcriptional changes at three developmental stages: the fresh-harvest (FS), the after-ripened (DS) and the just-germinated seeds (GS), were investigated by comparative transcriptomics analysis. The results showed that genes with increased transcription in DS vs FS comparison were overrepresented for oxidative phosphorylation, glycolysis pathway and tricarboxylic acid cycle (TCA), suggesting that after a period of drying storage, the intermediates stored in dry seeds were rapidly mobilized by glycolysis, TCA cycle, glyoxylate cycle, etc.; the electron transport chain accompanying with respiration has been reactivated to provide ATP for mobilization of other reserves and seed germination. In GS vs DS pairwise, dozens of the up-regulated genes were related to plant hormone biosynthesis and signal transduction, including the majority of components in auxin signal pathway, and brassinosteroid biosynthesis and signal transduction, and some GA and ABA signal transduction genes. During seeds germination, the expression of some EXPANSIN and XYLOGLUCAN ENDOTRANSGLYCOSYLASE was also significantly enhanced. To investigate the effect of different hormone during the procedure of seed germination, the contents and the differential distribution of ABA, GA, BR and IAA in cotyledon, hypocotyl and radicle, and plumule of three seed sections at different developmental stages were also detected. Combining with previous data in other species, a model of regulatory network related to peanut seed germination was developed. This model will helpful to gain further understanding of the mechanisms controlling seed dormancy and germination.

plant biology↗

bioRxiv2019

Computational fluid dynamics simulation of changes in the morphology and airflow dynamics of the upper airways in OSAHS patients after treatment with oral appliances

ObjectivesTo explore the changes of morphology and internal airflow in upper airways (UA) after the use of oral appliances (OAs) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS), and investigate the mechanisms by which OAs function as a therapy for OSAHS.\n\nMethodsEight OSAHS patients (all male, aged 37-58, mean age 46.25) underwent CT scans before and after OA use. Then, computational fluid dynamics(CFD) models were built on the base of the CT scans using Mimics and ANSYS ICEM CFD software. The internal airflow of the upper airways was simulated using ANSYS-FLUENT and the results were analyzed using ANSYS-CFD-Post. The data were analyzed to identify the most important changes of biomechanical properties between patients with and without OA intervention. Upper airway morphology and the internal airflow changes were compared using t-tests and Spearman correlation coefficient analysis.\n\nResultsThe narrowest area of upper airways was found to be located in the lower bound of velopharynx, where the volume and pressure were statistically significantly increased (P<0.05) and the air velocity was statistically significantly decreased (P<0.05) in the presence of the OA(P<0.05). After wearing OA, pharyngeal resistance was significantly decreased (P<0.05), from 290.63 to 186.25Pa/L, and the airflow resistance of the pharynx has reduced by 35.9%.\n\nConclusionThe enlargement of the upper airway after wearing the OA changed its airflow dynamics, which decreased the negative pressure and resistance in narrow areas of the upper airways. Thus, the collapsibility of the upper airways was reduced and patency was sustained.

biophysics↗

bioRxiv2019

Vascularized human cortical organoids model cortical development in vivo

Modelling the neuronal progenitor proliferation and organization processes that produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. To provide a vascularized and functional model of brain organoids, we demonstrated a new paradigm to generate vascularized organoids that consist of typical human cortical cell types and recapitulate the lamination of the neocortex with a vascular structure formation for over 200 days. In addition, the observation of the sEPSCs (spontaneous Excitatory Postsynaptic Potential) and sIPSCs (spontaneous Inhibitory Postsynaptic Potential) and the bidirectional electrical transmission indicated the presence of chemical and electrical synapses in the vOrganoids. More importantly, the single-cell RNA-seq analysis illustrated that the vOrganoids exhibited microenvironments to promote neurogenesis and neuronal maturation that resembled in vivo processes. The transplantation of the vOrganoids to the mouse S1 cortex showed human-mouse co-constructed functional blood vessels in the grafts that could promote the survival and integration of the transplanted cells to the host. This vOrganoid culture method could not only serve as a model to study human cortical development and to explore brain disease pathology but could also provide potential prospects for new cell therapies for neural system disorders and injury.

neuroscience↗

bioRxiv2019

Decomposing Retrosynthesis into Reactive Center Prediction and Molecule Generation

Chemical retrosynthesis has been a crucial and challenging task in organic chemistry for several decades. In early years, retrosynthesis is accomplished by the disconnection approach which is labor-intensive and requires expert knowledge. Afterward, rule-based methods have dominated in retrosynthesis for years. In this study, we revisit the disconnection approach by leveraging deep learning (DL) to boost its performance and increase the explainability of DL. Concretely, we propose a novel graph-based deep-learning framework, named DeRetro, to predict the set of reactants for a target product by executing the process of disconnection and reactant generation orderly. Experimental results report that DeRetro achieves new state-of-the-art performance in predicting the reactants. In-depth analyses also demonstrate that even without the reaction type as input, DeRetro retains its retrosynthesis performance while other methods show a significant decrease, resulting in a large margin of 19% between DeRetro and previous state-of-the-art rule-based method. These results have established DeRetro as a powerful and useful computational tool in solving the challenging problem of retrosynthetic analysis.

bioengineering↗

bioRxiv2019

Serotonin Neurons in the Dorsal and Medial Raphe Nuclei: from Single-Cell Transcriptomes to Whole-Brain Projections

Serotonin neurons of the dorsal and medial raphe nuclei (DR and MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.

neuroscience↗

bioRxiv2019

lncRNAKB: A comprehensive knowledgebase of long non-coding RNAs

We have assembled a comprehensive long non-coding RNA knowledgebase (lncRNAKB) of 77,199 annotated human lncRNAs (224,286 transcripts) by methodically integrating widely used lncRNAs resources. To facilitate functional characterization of lncRNAs, we employed Genotype-Tissue Expression (GTEx) project to provide tissue-specific gene expression profiles of lncRNAs in 31 solid organ tissues. Additional information includes network analysis to identify co-expressed gene modules to potentially delineate lncRNA function. Tissue-specificity, phylogenetic conservation scores and coding potential for lncRNAs are included. Finally, using whole genome sequencing data from GTEx, expression quantitative trait loci (cis-eQTL) regulated lncRNAs were calculated in all tissues. lncRNAKB is available at http://www.lncrnakb.org.

bioinformatics↗

bioRxiv2019

Microstructural plasticity in the bilingual brain

The human brain has been uniquely equipped with the remarkable ability to acquire more than one language, as in bilingual individuals. Previous neuroimaging studies have indicated that learning a second language (L2) induced neuroplasticity at the macrostructural level. In this study, using the quantitative MRI (qMRI) combined with functional MRI (fMRI) techniques, we quantified the microstructural properties and tested whether second language learning modulates the microstructure in the bilingual brain. We found significant microstructural variations related to age of acquisition of second language in the left inferior frontal region and the left fusiform gyrus that are crucial for resolving lexical competition of bilinguals two languages. Early second language acquisition contributes to enhance cortical development at the microstructural level.\n\nSignificant statementThe ability to communicate in two languages is becoming more and more important in the increasingly global community. Does learning a second language (L2) affect the human brain development? At the macrostructural level, there has been neuroimaging evidence revealing neuroplasticity induced by the acquisition of L2. Here, we employed the quantitative MRI technique to investigate the microstructural variations related to L2 learning, and found that age of acquisition of L2, but not its proficiency, is associated with cortical proliferation. Early second language acquisition seems to enhance cortical development at the microstructural level.

neuroscience↗

bioRxiv2019

Tissue-specific Hi-C analyses of rice, foxtail millet and maize suggest non-canonical function of plant chromatin domains

Chromatins are not randomly packaged in the nucleus and their organization plays important roles in transcription regulation. Using in situ Hi-C, we have compared the 3D chromatin architectures of rice mesophyll and endosperm, foxtail millet bundle sheath and mesophyll, and maize bundle sheath, mesophyll and endosperm tissues. We have also profiled their DNA methylation, open chromatin, histone modification and gene expression to investigate whether chromatin structural dynamics are associated with epigenome features changes. We found that plant global A/B compartment partitions are stable across tissues, while local A/B compartment has tissue-specific dynamic that is associated with differential gene expression. Plant domains are largely stable across tissues, while rare domain border changes are often associated with gene activation. Genes inside plant domains are not conserved across species, and lack significant co-expression behavior unlike those in mammalian cells. When comparing synteny gene pairs, we found those maize genes involved in gene island chromatin loops have shorter genomic distances in smaller genomes without gene island loops such as rice and foxtail millet, suggesting that they have conserved functions. Our study revealed that the 3D configuration of the plant chromatin is also complex and dynamic with unique features that need to be further examined.

genomics↗

bioRxiv2019

Dissection and validation of minor quantitative trait loci (QTLs) conferring grain size and weight in rice

Grain size and weight contribute greatly to the grain yield of rice. In order to identify minor QTLs conferring grain size and weight, an F2 population derived from a cross between two indica rice lines showing small difference on grain size, Guangzhan 63-4S (GZ63-4S) and Dodda, and its derived F2:3 population were developed and used for QTL analysis. Totally, 36 QTLs for grain size and weight were detected, and 7 were repeatedly detected, of which the number of beneficial alleles was contributed roughly equally by the two parents. In order to further validate effects of QTLs detected, a BC1F2 population derived from a backcross of a mixture of F2 lines with GZ63-4S was developed and subjected to QTL selection. Heterozygous regions of 3 QTLs, qGS3, qTGW6.2 and qGT7 were identified, and corresponding near-isogenic lines (NILs) of each QTL were constructed with three rounds of self-crosses. In the background of NILs, qGS3 was responsible for GL, LWR, GT and TGW, qTGW6.2 was for GL and TGW, and qGT7 was for GT and TGW. These results have laid the foundation of further fine mapping and cloning of underlying genes, and could be of great use in breeding and improvement of rice lines with desirable size and yield.

genetics↗

bioRxiv2018

Measurements of Subthreshold and Fast Population Neuronal Activity with Genetically Encoded Calcium Indicator GCaMP-6f

GCaMP-6f is among the best calcium indicators and has been widely used for monitoring neuronal activity in the brain. Applications are at cellular level (calcium transients of action potentials) or population activity (fluorimetry) during network events. Two important issues remain less explored: 1) Is GCaMP-6f signal sensitive enough for detecting subthreshold activity, similar to the sensitivity of local field potential (LFP)? 2) Is the GCaMP-6f signal fast enough for detecting network oscillations seen in LFP? Here the two issues are explored in a number of network events including hippocampus sharp waves (SWs), carbachol induced theta oscillations, interictal-like spikes and neuronal response evoked by high frequency stimuli. SWs are a typical network event with the majority of neurons receiving subthreshold excitatory or inhibitory synaptic input without firing action potentials. The excitatory/inhibitory post synaptic potentials (EPSP/IPSP) in the neuropil become detectable in local field potential (LFP) signals. We compare simultaneously recorded LFP and optical recording of GCaMP-6f fluorescent signals in Thy1-GCaMP-6f mice hippocampal slices. We found that the occurrence of SWs produces a clear population GCaMP-6f signal of 0.3% dF/F. This population GCaMP-6f signal correlated well with the LFP, albeit a delay of ~50 ms was observed. The population GCaMP-6f signal follows well with the 20 Hz population activity evoked by electric stimuli, while activity up to 40 Hz was detected with reduced amplitude. GCaMP-6f and LFP signals showed a large amplitude discrepancy. The amplitude of GCaMP increased ~1000 times from SW to carbachol induced theta burst, while the LFP changed less than 10 times. Our results suggested that population GCaMP-6f signals may become a sensitive tool for detecting network activity, especially for that with low LFP amplitude during elevated spiking rate but asynchronized events. GCaMP signal is fast enough for monitoring theta and beta oscillations (<25Hz) in the neuronal population. Faster calcium indicators (e.g., GCaMP-7) may improve the frequency response property for detecting gamma band oscillations. In addition, population GCaMP recordings are non-contact and free from stimulation artifacts. These features may be useful for high throughput recordings and applications sensitive to stimulus artifact, e.g., monitoring response during continuous stimulations.

neuroscience↗

bioRxiv2018

QTL mapping of leaf angle on eight nodes in maize enable the optimize canopy by differential operating of leaf angle at different levels of plant

Leaf angle (LA) is one of the most important canopy architecture related traits of maize (Zea mays L.). Currently, there is an urgent need to elucidate the genetic mechanism of LA at canopy-wide levels for optimizing dense-planting canopy architecture. In present study, one RIL population derived from two parent lines which show distinct plant architecture was used to perform QTL mapping for LA at eight leaves below the tassel under three environments. Dozens of QTL for LA at eight leaves were identified, which were mapped on all maize chromosomes except for the tenth chromosome. Among them, there were nine common QTL as they were identified for LA more than 1 leaves or in two or three environments. And individual QTL could explain 1.29% - 20.14% of the phenotypic variation and affect LA of 1-8 leaves, including qLA5.1 affected LA of all eight leaves, qLA3.1 affected LA of the upper leaves (1stLA to 4thLA), and qLA9.1 could affect LA of the lower leaves (5thLA to 8thLA). Furthermore, the results indicated that the genetic architecture of LA at eight leaves was different. Specifically, 8thLA was mainly affected by major and minor QTL; 1stLA, 4thLA and 5thLA were affected by epistatic interactions beside major and minor QTL; while the other four LAs were simultaneously affected by major QTL, minor QTL, epistatic interactions and environments. These results provide a comprehensive understanding of genetic basis of LA at canopy-wide levels, which will be beneficial to design ideal plant architecture under dense planting in maize. Author contribution statementJ. L. and D. T. designed and supervised the study, D. T., Z.C., J.N., Q.J., P.L., L.W., J.Z., C.L. performed the phenotypic data collection. D. T. analyzed the data and drafted the manuscript, D. T. and Z.C. revised and finalized the manuscript. All the authors read and approved the manuscript. Key messageDozens of QTL for leaf angle of eight consecutive leaves were identified in the RIL population across three environments, providing the information that optimization of canopy architecture at various canopy levels.

plant biology↗