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Biology subjects

Pang, H.

Publications and source records attributed to Pang, H..

14 recordsLinked to original sources

Gn1a rice promotes symbiotic fish growth via reprogramming soil microbiome

Rice-fish symbiotic ecosystems significantly contribute to world food supply. Mutation in rice (Oryza sativa) quantitative trait locus Gn1a, encoding a cytokinin oxidase/dehydrogenase (OsCKX2), leads to cytokinin accumulation in plant, which promotes tillering and panicle branching to achieved higher yield and also shows a selective effect on soil microbial composition. Given that the growth of aquatic animals can be shaped by their surrounding microbial communities, we asked whether adjusting rice cytokinin levels might synergistically boosts both rice yield and fish growth. Herein, we co-cultured common carp (Cyprinus carpio) with ckx2 rice plants to determine the effect of cytokinins on fish. Surprisingly, compared to wild-type plants, the ckx2 plants enhanced nearly 10% fish growth and improved fish antibacterial capacity against Aeromonas hydrophila and Edwardsiella tarda. In fact, the growth-promoting effect on fish requires mediation by the soil microbiota. Mechanistically, ckx2 plants secreted more cytokinins into soil to reprogram the microbial composition, which subsequently translocated to fish gut and modulated the keystone microbes in gut to facilitate short-chain fatty acid production and carbohydrate degradation. These findings provide the first evidence that rice-derived cytokinins exert a cross-kingdom growth-promoting effect on fish, providing a boosting dual-production strategy for advancing rice-fish symbiotic ecosystem.

plant biology↗

LadybirdBase: a comprehensive biology, ecology and omics resource for ladybird beetles (Coccinellidae)

Ladybird beetles (Coleoptera: Coccinellidae) represent a highly diverse insect group comprising over 6000 species. Recently, an increasing amount of omics data on ladybirds has accumulated. To better understand their roles and adaptations in biological control, we developed LadybirdBase (http://www.ladybirdbase.com/), a comprehensive database that compiles both published and self-collected data on ladybird beetles. It contains five main modules that encompass: (1) the Biology Module summarizing information on over 6000 species, including their classification, morphology, diet, distribution, and omics data; (2) the Ecology Module offering diet and distribution records; (3) the Genomics Module integrating published and unpublished resources such as genomes, transcriptomes, mitogenomes, orthogroups, and variance; (4) the Microbiomics Module presenting 16S rRNA, ITS, and metagenome data; and (5) the Lab Test Module covering diet ranges, life histories under different treatments, and stress tolerance. Additionally, LadybirdBase offers analysis tools for species detection using morphology or barcodes, BLAST searches against the genome resources, differential gene expression analysis, and PCR primer search. LadybirdBase can greatly simplify species identification, enhance the efficiency of omics studies, and provide a theoretical foundation for the use of ladybirds in biological control.

bioinformatics↗

A tumor-secreted protein utilizes glucagon release to cause host wasting

Tumor-host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, however, is largely unknown. Using the conserved yki3SA-tumor model in Drosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to identify that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.

physiology↗

Circular DNA vcDNA-S7 derived from segmented-dsRNA virus BmCPV attenuated viral infection through RNase H1

Viral circDNA derived from insect positive-sense single-stranded RNA viruses plays a crucial role in regulating viral infections depending on the RNAi pathway. Our previous research has revealed that Bombyx mori cypovirus (BmCPV), a segmented-dsRNA virus, can generate viral circDNA vcDNA-S7, which can be transcribed to form RNA and further processed into small RNAs to defend against the virus through RNAi. However, whether vcDNA-S7 employs other mechanisms to resist the viruses. Presently, vcDNA-S7 has been found to resist BmCPV infection via a novel mechanism that depends on ribonuclease RNase H1 activity. It was found that the expression level of RNase H1 increased upon BmCPV infection (RNA virus) but not upon B. mori nucleopolyhedrovirus (BmNPV) (DNA virus) infection. RNase H1 has been shown to negatively regulate BmCPV infections. In addition, vcDNA-S7 was found to form a heteroduplex with the viral RNA and subsequently recruit RNase H1 to degrade the viral RNA within the heteroduplex, ultimately leading to the suppression of viral replication. Furthermore, the resistance of vcDNA-S7 to viruses was significantly reduced when cellular RNase H1 gene was silenced. These findings not only reveal a new antiviral mechanism involving circular DNA formed by reovirus but also offer intriguing insights into the antiviral function of RNase H1 in cells.

immunology↗

Human transmembrane protein 68 links triacylglycerol synthesis to membrane lipid homeostasis

Transmembrane protein 68 (TMEM68) is a recently identified mammalian triacylglycerol (TAG) synthase with high expression in the brain. How TMEM68 regulates cellular lipid metabolism in concert with other enzymatic pathways remains poorly understood. In this study, we assessed TMEM68 function in neuro- and gliablastoma cells by combining genetic gain- and loss-of-function approaches with lipidomics. We found that TMEM68 promotes TAG synthesis and lipid droplet formation independently of canonical acyl-CoA:diacylglycerol acyltransferase (DGAT) 1 and 2 enzymes and contributes a discrete fraction of basal cellular TAG storage. Notably, TMEM68 overexpression increased storage lipids at the expense of membrane lipids leading to a profound reduction of ether-linked glycerophospholipids (GPLs). Moreover, altered TMEM68 expression levels were associated with diminished prevalence of polyunsaturated GPLs. We conclude that TMEM68, besides its TAG synthesis function, acts as a multifaceted regulator of membrane lipid composition and polyunsaturated fatty acid homeostasis.

biochemistry↗

PhyloAln: a convenient reference-based tool to align sequences and high-throughput reads for phylogeny and evolution in the omic era

The current trend in phylogenetic and evolutionary analyses predominantly relies on omic data. However, traditional methods typically involve intricate and time-consuming procedures prior to core analyses. These procedures encompass assembly from high-throughput reads, decontamination, gene prediction, homology search, orthology assignment, multiple alignment, and matrix trimming. Such processes significantly impede the efficiency of research when dealing with extensive datasets. In this study, we present PhyloAln, a convenient reference-based tool capable of directly aligning high-throughput reads or complete sequences with existing alignments as reference for phylogenetic and evolutionary analyses. Through testing with both simulated and authentic datasets, PhyloAln demonstrates consistently robust performance in terms of alignment completeness and identity when compared to other reference-based tools. Additionally, we validate the tools adeptness in managing foreign and cross-contamination issues prevalent in sequencing data, which are often overlooked by other tools. Moreover, we showcase the broad applicability of PhyloAln by generating alignments and reconstructing phylogenies from transcriptomes of ladybird beetles, plastid genes of peppers, and ultraconserved elements of turtles. These results underscore the versatility of our tool. Leveraging these advantages, PhyloAln stands poised to expedite phylogenetic and evolutionary analyses in the omic era. The tool is accessible at https://github.com/huangyh45/PhyloAln.

bioinformatics↗

Ser149 is another potential 14-3-3 epsilon binding site of Cdc25B in the G2/M transition of mouse fertilized eggs

Cell cycle division 25B (CDC25B) belongs to the family of cell cycle regulatory proteins. It drives G2/M transition by activating cyclin-dependent protein kinases (CDK1), also known as CDC2, whose activity is directly related to its subcellular localization and phosphorylation state.14-3-3 (YHWA) regulates cell division cycle by binding to Cdc25B as a chaperone protein in mammals. Previously, we found that Cdc25B-Ser149 plays an important role in G2/M transition of mouse fertilized eggs, but the molecular mechanism of this transition remains unclear. In this study, we assessed the role of 14-3-3{varepsilon} (YHWAE) interaction with phosphorylated Cdc25B-Ser149 in G2/M transition of mouse fertilized eggs. Co-expression of Cdc25B-Ser149A and 14-3-3{varepsilon} could effectively activate maturation promoting factor (MPF) through direct dephosphorylation of Cdc2-Tyr15, and induce G2 fertilized eggs to enter mitosis rapidly. However, co-expression of the phosphomimic Cdc25B-Ser149D or Cdc25B-WT and 14-3-3{varepsilon} showed no significant difference in comparison with control groups. 14-3-3{varepsilon} binds to Cdc25B-WT, which is abolished when Ser149 is mutated to Ala. In addition, we found that 14-3-3{varepsilon} and Cdc25B were co-localized in the cytoplasm at the G1, S and early G2 phases. Cdc25B was translocated from the cytoplasm to the nucleus at the late G2 phase. However, when Ser149 is mutated to Ala, the cytoplasmic localization of Cdc25B is completely abolished. Our findings suggest that Cdc25B-Ser149 is another specific binding site for 14-3-3{varepsilon} in G2/M transition of one-cell fertilized mouse eggs, which plays essential roles in the regulation of early development of fertilized mouse eggs.

cell biology↗

Tight junction ZO proteins maintain tissue fluidity, ensuring efficient collective cell migration

Tight junctions are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. Albeit their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the tight junction proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward-bulged apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding-induced jamming and more small cells over time. Co-cultures comprising wildtype and dKD cells display phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.

biophysics↗

Extracellular vesicles mediate the intercellular exchange of nanoparticles

In order to exert their therapeutic effects, nanoparticles (NPs) often need to travel into the tissues composed of multilayered cells. Accumulative evidence has revealed the crucial role of transcellular transport route (entry into one cell, exocytosis, and re-entry into another) in this process. While NP endocytosis and subcellular transport have been intensively characterized, the exocytosis and re-entry steps are poorly understood, which becomes a barrier to improve NP delivery into complex tissues. Here, we termed the exocytosis and re-entry steps together as intercellular exchange. We developed a collagen-based 3D assay to specifically monitor and quantify the intercellular exchange events of NPs, and distinguish the contributions of several potential mechanisms. Our results showed that NPs can be exocytosed freely or enclosed inside extracellular vesicles (EVs) for re-entry, while direct cell-cell contact is hardly involved. EVs account for a significant fraction of NP intercellular exchange, and its importance in NP transport was demonstrated in vitro and in vivo. Intriguingly, while freely released NPs engage with the same cellular receptors for re-entry, EV-enclosed ones bypass this dependence. These studies provide an easy and precise system to investigate the intercellular exchange stage of NP delivery, and shed the first light in the importance of EVs in NP transport between cells and across complex tissues.

pharmacology and toxicology↗

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.

microbiology↗

Precision mapping of the mouse brain metabolome

Metabolism is physiologically fundamental to a biological system. Understanding brain metabolism is critical for our comprehensive knowledge of brain function in health and disease. Combining a microarray collection system with targeted metabolomics analysis, here we performed precision mapping of the metabolome in the mouse brain and created maps for 79 metabolites with a resolution of 0.125mm3 per pixel (i.e., brain subregion). The metabolome atlas provides researchers with a useful resource to interpret the vulnerability of specific brain regions to various disease-relevant metabolic perturbations.

neuroscience↗

Accumulation of an unprecedented 5'-deoxyadenos-4'-yl radical unmasks the kinetics of the radical-mediated C-C bond formation step in MoaA catalysis

Radical S-adenosyl-L-methionine (SAM) enzymes catalyze various free radical-mediated reactions. In these enzymes, the rate-determining SAM cleavage kinetically masks all the subsequent steps. Due to this kinetic masking, detailed mechanistic characterization of radical transformations catalyzed by these enzymes is very difficult. Here, we report a successful kinetic characterization of the radical C-C bond formation catalyzed by a MoaA radical SAM enzyme. MoaA catalyzes an unprecedented 3',8-cyclization of GTP into 3',8-cyclo-7,8-dihydro-GTP (3',8-cH2GTP) during the molybdenum cofactor (Moco) biosynthesis. Through a series of EPR and biochemical characterization, we found that MoaA accumulates a 5'-deoxyadenos-4'-yl radical (5'-dA-C4'*) under the turnover conditions, and forms (4'S)-5'-deoxyadenosine ((4'S)-5'-dA), which is a C-4' epimer of the naturally occurring (4'R)-5'-dA. Together with kinetic characterizations, these observations revealed the presence of a shunt pathway in which an on-pathway intermediate, GTP C-3' radical, abstracts H-4' atom from 5'-dA to transiently generate 5'-dA-C4'* that is subsequently reduced stereospecifically to yield (4'S)-5'-dA. Detailed kinetic characterization of the shunt and the main pathways provided the comprehensive view of MoaA kinetics, and determined the rate of the on-pathway 3',8-cyclization step as 2.7 {+/-} 0.7 s-1. Together with DFT calculations, this observation suggested that the 3',8-cyclization is accelerated by 6 [~] 9 orders of magnitude by MoaA. Potential contributions of the active-site amino acid residues, and their potential relationships with human Moco deficiency disease are discussed. This is the first determination of the magnitude of catalytic rate acceleration by a radical SAM enzyme, and provides the foundation for understanding how radical SAM enzymes achieve highly specific radical catalysis.

biochemistry↗

Genome analysis and Hi-C assisted assembly of Elaeagnus angustifolia L., a deciduous tree belonging to Elaeagnaceae

Elaeagnus angustifolia L. is a deciduous tree of the Elaeagnaceae family. It is widely used in the study of abiotic stress tolerance in plants and for the improvement of desertification-affected land due to its characteristics of drought resistance, salt tolerance, cold resistance, wind resistance, and other environmental adaptation. Here, we report the complete genome sequencing using the Pacific Biosciences (PacBio) platform and Hi-C assisted assembly of E. angustifolia. A total of 44.27 Gb raw PacBio sequel reads were obtained after filtering out low-quality data, with an average length of 8.64 Kb. And 39.56 Gb clean reads was obtained, with a sequencing coverage of 75x, and Q30 ratio > 95.46%. The 510.71 Mb genomic sequence was mapped to the chromosome, accounting for 96.94% of the total length of the sequence, and the corresponding number of sequences was 269, accounting for 45.83% of the total number of sequences. The genome sequence study of E. angustifolia can be a valuable source for the comparative genome analysis of the Elaeagnaceae family members, and can help to understand the evolutionary response mechanisms of the Elaeagnaceae to drought, salt, cold and wind resistance, and thereby provide effective theoretical support for the improvement of desertification-affected land.

genetics↗

Radiomics Analysis Using Stability Selection Supervised Principal Component Analysis for Right-censored Survival Data

Radiomics is a newly emerging field that involves the extraction of a large number of quantitative features from biomedical images through the use of data-characterization algorithms. Radiomics provides a noninvasive approach for personalized therapy decision by identifying distinctive imaging features for predicting prognosis and therapeutic response. So far, many of the published radiomics studies utilize existing out of the box algorithms to identify the prognostic markers from biomedical images that are not specific to radiomics data. T o better utilize biomedical image, we propose a novel machine learning approach, stability selection supervised principal component analysis (SSSuperPCA) that identify a set of stable features from radiomics big data coupled with dimension reduction for right censored survival outcomes. In this paper, we describe stability selection supervised principal component analysis for radiomics data with right-censored survival outcomes. The proposed approach allows us to identify a set of stable features that are highly associated with the survival outcomes, control the per-family error rate, and predict the survival in a simple yet meaningful manner. We evaluate the performance of SSSuperPCA using simulations and real data sets for non-small cell lung cancer and head and neck cancer, and compare it with other machine learning algorithms. The results demonstrate that our method has a competitive edge over other existing methods in identifying the prognostic markers from biomedical big imaging data for the prediction of right-censored survival outcomes. An R package SSSuperPCA is available at the website: http://web.hku.hk/[~]herbpang/SSSuperPCA.html

bioinformatics↗