bioRxiv ScienceSearch

Biology subjects

Liu, N.

Publications and source records attributed to Liu, N..

9 recordsLinked to original sources

Heart Rate n-Variability (HRnV): A Novel Representation of Beat-to-Beat Variation in Electrocardiography

Heart rate variability (HRV) is a widely adopted tool for evaluating changes in cardiac autonomic regulation. The majority of efforts have focused on developing methods to assess HRV by deriving sophisticated parameters with linear and nonlinear techniques and adopting advanced signal processing tools for efficient noise removal and accurate QRS detection. In this paper, we propose a novel representation of beat-to-beat variation in an electrocardiogram (ECG), called heart rate n-variability (HRnV), as an alternative to conventional HRV measures. We derived two novel HRnV measures based on non-overlapped and overlapped RR intervals. We also conducted a simulation study by using an ECG record from the MIT-BIH Normal Sinus Rhythm Database to demonstrate the feasibility of calculating HRnV parameters. Among the time domain parameters, we observed that the values were generally incremental with the increase in n. We observed the same trend of changes for the frequency domain parameters. In the nonlinear analysis, the differences between HRV and HRnV from Poincare plot measures were obvious, while those from entropy and detrended fluctuation analysis metrics were not. HRnV measures enable us to augment conventional HRV measures with additional parameters. Although issues remain to be addressed regarding HRnV, we hope to stimulate a new stream of research on this new representation of HRV. HRnV is an important addition to HRV and will contribute to extending the landscape of current studies on HRV.

bioengineering

Microfluidic study of effects of flow velocity and nutrient concentration on biofilm accumulation and adhesive strength in microchannels

AbstractBiofilm accumulation in the porous media can cause plugging and change many physical properties of porous media. Up to now, applications of desired biofilm growth and its subsequent bioplugging have been attempted for various practices. A deeper understanding of the relative influences of hydrodynamic conditions including flow velocity and nutrient concentration, on biofilm growth and detachment is necessary to plan and analyze bioplugging experiments and field trials. The experimental results by means of microscopic imaging over a T-shape microchannel show that flow velocity and nutrient concentrations can have significant impacts on biofilm accumulation and adhesive strength in both flowing and stagnant microchannels. Increase in fluid velocity could facilitate biofilm growth, but that above a velocity threshold, biofilm detachment and inhibition of biofilm formation due to high shear stress were observed. High nutrient concentration prompts the biofilm growth, but was accompanied by a relatively weak adhesive strength. This research provides an overview of biofilm development in a hydrodynamic environment for better predicting and modelling the bioplugging associated with porous system in petroleum industry, hydrogeology, and water purification.\n\nIMPORTANCEIn the recent decade, the use of bacteria has become more and more important in many applications. Bioplugging caused by bacteria growth in porous media has been explored as a viable technique for some applications, such as bioremediation, water purification and microbial enhanced oil recovery (MEOR). In order to control biofilms/biomasses selectively/directionally plugging in desirable places, the role of hydrodynamic conditions on biofilm growth and detachment is essential to investigate. Herein, a T-shape microchannel was prepared to study effects of flow velocity and nutrient concentration on biofilm accumulation and adhesive strength at pore scale. Our results suggest that flow velocity and nutrient concentration could control biofilm accumulation in microchannels. The finding helps explain and predict the engineering bioplugging in porous media, especially for the selective plugging strategy of a MEOR field trial.

bioengineering

Metabolic Reaction Network-based Recursive Metabolite Identification for Untargeted Metabolomics

Metabolite identification is a long-standing challenge in untargeted metabolomics and a major hurdle for functional metabolomics studies. Here, we developed a metabolic reaction network-based recursive algorithm and webserver called MetDNA for the large-scale and unambiguous identification of metabolites (available at http://metdna.zhulab.cn). We showcased the versatility of our workflow using different instrument platforms, data acquisition methods, and biological sample types and demonstrated that over 2,000 metabolites could be identified from one experiment.

bioinformatics

Enabling the hypothesis-driven prioritization of ligand candidates in big databases: Screenlamp and its application to GPCR inhibitor discovery for invasive species control

While the advantage of screening vast databases of molecules to cover greater molecular diversity is often mentioned, in reality, only a few studies have been published demonstrating inhibitor discovery by screening more than a million compounds for features that mimic a known three-dimensional ligand. Two factors contribute: the general difficulty of discovering potent inhibitors, and the lack of free, user-friendly software to incorporate project-specific knowledge and user hypotheses into 3D ligand-based screening. The Screenlamp modular toolkit presented here was developed with these needs in mind. We show Screenlamps ability to screen more than 12 million commercially available molecules and identify potent in vivo inhibitors of a G protein-coupled bile acid receptor within the first year of a discovery project. This pheromone receptor governs sea lamprey reproductive behavior, and to our knowledge, this project is the first to establish the efficacy of computational screening in discovering lead compounds for aquatic invasive species control. Significant enhancement in activity came from selecting compounds based on one of the hypotheses: that matching two distal oxygen groups in the three-dimensional structure of the pheromone is crucial for activity. Six of the 15 most active compounds met these criteria. A second hypothesis - that presence of an alkyl sulfate side chain results in high activity - identified another 6 compounds in the top 10, demonstrating the significant benefits of hypothesis-driven screening.

bioinformatics

Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity

Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging is unclear. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. Moreover, we show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis by gene mutation diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 defines a new aging mechanism and that stimulation of glycolysis promotes metabolic health and longevity.

molecular biology

Peripheral, intrareceptor inhibition in mosquito olfaction

How chemical signals are integrated at the peripheral sensory system of insects is still an enigma. Here we show that when coexpressed with Orco in Xenopus oocytes, an odorant receptor from the southern house mosquito, CquiOR32, generated inward (regular) currents when challenged with cyclohexanone and methyl salicylate, whereas eucalyptol and fenchone elicited inhibitory (upward) currents. Responses of CquiOR32-CquiOrco-expressing oocytes to odorants were reduced in a dose-dependent fashion by coapplication of inhibitors. This intrareceptor inhibition was also manifested in vivo in fruit flies expressing the mosquito receptor CquiOR32, as well in neurons on the antennae of the southern house mosquito. Likewise, an orthologue from the yellow fever mosquito, AaegOR71, showed intrareceptor inhibition in the Xenopus oocyte recording system and corresponding inhibition in antennal neurons. Intrareceptor inhibition was also manifested in mosquito behavior. Blood-seeking females were repelled by methyl salicylate, but repellence was significantly reduced when methyl salicylate was coapplied with eucalyptol.\n\nOne Sentence SummaryIntrareceptor inhibition was observed in mosquito odorant receptors expressed in heterologous systems, in vivo, and manifested in behavioral responses.

neuroscience

Mechanochemical Coupling and Bi-Phasic Force-Velocity Dependence in the Ultra-Fast Ring ATPase SpoIIIE

Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motors mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore, we find that SpolIIEs velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.

biochemistry

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

Incidental identification of maternal malignancies in two Asian women underwent noninvasive prenatal test

Noninvasive prenatal test (NIPT) has been widely used as a screening test for trisomy 13, 18 and 21 worldwide. Recently, coexistence of maternal malignancy and pregnancy has drawn increasing attention in NIPT studies. Malignancy in pregnant women potentially affected NIPT results, which may cause false positive results or failed tests. However, no such case has ever been reported in Asian population. In this study, for the first time, we reported a stage III dysgerminoma and advanced gastric cancer during pregnancy accidentally identified during NIPT tests. These two women showed aberrant chromosome aneuploidies in NIPT results and concordant pattern of genome disruption found in tumor samples. The findings in this study further validate the effect of maternal malignancy on NIPT results and strengthen the possibility of detecting malignant tumors through NIPT in the future.

cancer biology