Biology subjects

Zhao, L.

Publications and source records attributed to Zhao, L..

At least 361 records · Page 20Linked to original sources

bioRxiv2020

The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

microbiology↗

bioRxiv2020

A single-cell RNAseq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding

Schistosomiasis is an ancient and chronic neglected tropical disease that infects over 240 million people and kills over 200,000 of the worlds poorest people every year1, 2. There are no vaccines and because there is only one drug available, the need for new therapeutics is great. The causative agents of this disease are flatworm parasites that dwell inside the hosts circulation, often for decades, where they feed on blood and lay eggs which are primarily responsible for disease pathology. As metazoans comprised of multiple tissue types, understanding the schistosomes tissues on a molecular level and their functions during what can be decades of successful parasitism could suggest novel therapeutic strategies. Here, we employ single-cell RNAseq to characterize 43,642 cells from the pathogenic (adult) stage of the schistosome lifecycle. From these data, we characterize 68 molecularly distinct cell populations that comprise nearly all tissues described morphologically, including the nervous and reproductive systems. We further uncover a lineage of somatic stem cells responsible for producing and maintaining the parasites gut - the primary tissue responsible for digestion of host blood. Finally, we show that a homologue of hepatocyte nuclear factor 4 (hnf4) is expressed in this gut lineage and required for gut maintenance, blood feeding and inducing egg-associated pathology in vivo. Together, the data highlight the utility of this single-cell RNAseq atlas to understand schistosome biology and identify potential therapeutic interventions.

microbiology↗

bioRxiv2020

Cross-feeding between Thauera aminoaromatica and Rhodococcus pyridinivorans drove quinoline biodegradation in a denitrifying bioreactor

The complex bacterial community is predominated by several taxa, such as Thauera and Rhodococcus, in a quinoline-degrading denitrifying bioreactor. Yet it remains unclear about how the interactions between the different bacteria mediate the quinoline metabolism in denitrifying condition. In this study, we designed a sequence-specific amplification to guide the isolation of the most predominant bacteria and obtained four strains of Thauera aminoaromatica, the representative of one key member in the bioreactor. Test on these isolates demonstrated that all of them were unable to strive on quinoline but could efficiently degrade 2-hydroxyquinoline, the hypothesized primary intermediate of quinoline catabolism, under nitrate-reducing condition. However, another isolate, Rhodococcus pyridinivorans YF3, corresponding to the second abundant taxon in the same bioreactor, was found to degrade quinoline via 2-hydroxyquinoline. The end products and removal rate of quinoline by isolate YF3 were largely varied with the quantity of available oxygen. Specifically, quinoline could only be converted into 2-hydroxyquinoline without further transformation under the condition with insufficient oxygen, e.g. less than 0.5% initial oxygen in the vials. However, if were aerobically pre-cultured in the medium with quinoline the resting cells of YF3 could anaerobically convert quinoline into 2-hydroxyquinoline. A two-strain consortium constructed with isolates from Thauera (R2) and Rhodococcus (YF3) demonstrated an efficient denitrifying degradation of quinoline. Thus, we experimentally proved that the metabolism interaction based on the 2-hydroxyquinoline cross-feeding between two predominant bacteria constituted the mainstream of quinoline degradation. This work sheds light on the understanding of mechanism of quinoline removal in the denitrifying bioreactor. ImportanceWe experimentally verified the most predominant Thauera sp. was indeed active degrader for the intermediate metabolites and the second abundant taxon Rhodococcus exerted, however, key function for opening the food box for a complex quinoline-degrading community. An ecological guild composed of two isolates was assembled, revealing the different roles of keystone organisms in the microbial community. This study, to our best knowledge, is the first report on the cross feeding between the initial attacker with unprofitable catalysis of reluctant heterocyclic compounds and the second bacterium which then completely degrade the compound transformed by the first bacterium. These results could be a significant step forward towards elucidation of microbial mechanism for quinoline denitrifying degradation.

microbiology↗

bioRxiv2020

Cardiomyocyte-specific ACSL1 Deficiency Prevents Cardiac Lipotoxicity and Alleviates Heart Dysfunction in the ob/ob Model of Obesity

Cardiac lipotoxicity is associated with structural remodeling and functional changes that are features of obesity-related cardiomyopathy. Both high fat diet and the ob/ob mutation lead to increased fatty acid (FA) uptake, elevated triacylglycerol (TAG) content, hypertrophy, and systolic and diastolic dysfunction in murine hearts. Cardiomyocyte-specific long-chain acyl-CoA synthetase 1 (ACSL1) deficiency (Acsl1H-/-) results in a 90% reduction in FA activation, suggesting that Acsl1 ablation might alleviate obesity-associated myocardial dysfunction. Double knockout ob-Acsl1H-/- and ob-Acsl1flox/flox control mice were treated with tamoxifen at 20 weeks of age; heart function, TAG content, and relevant gene expression were assessed immediately before and 2 and 5 weeks after treatment. Heart weights initially increased in lean and obese Acsl1H-/- mice, but normalized in ob-Acsl1H-/- mice by 5 weeks. Ventricular TAG content was decreased by 51% and 61% in ob-Acsl1H-/- mice 2 and 5 weeks after Acsl1 knockout induction, respectively. Moreover, ACSL1 knockout resulted in increased survival of ob/ob mice, suggesting that lack of ACSL1 protected obese hearts subjected to stress. Our results indicate that partial knockdown of cardiac ACSL1 is sufficient to reverse cardiac TAG accumulation and to ameliorate heart dysfunction even in the context of established obesity-related cardiomyopathy.

physiology↗

bioRxiv2020

Compressive Big Data Analytics: An Ensemble Meta-Algorithm for High-dimensional Multisource Datasets

Health advances are contingent on continuous development of new methods and approaches to foster data driven discovery in the biomedical and clinical health sciences. Open-science offers hope for tackling some of the challenges associated with Big Data and team-based scientific discovery. Domain-independent reproducibility, area-specific replicability, curation, analysis, organization, management and sharing of health-related digital objects are critical components. This study expands the functionality and utility of an ensemble semi-supervised machine learning technique called Compressive Big Data Analytics (CBDA). Applied to high-dimensional data, CBDA identifies salient features and key biomarkers for reliable and reproducible forecasting of binary or multinomial outcomes. The method relies on iterative subsampling, combines function optimization and statistical inference, and generates ensemble predictions of observed univariate outcomes. In this manuscript, we extend the CBDA technique by (1) efficiently handling extremely large datasets, (2) generalizing the internal and external validation steps, (3) expanding the set of base-learners for joint ensemble prediction, (4) introduce an automated selection of CBDA specifications, and (5) provide mechanisms to assess CBDA convergence, evaluate the prediction accuracy, and measure result consistency. We validated the CBDA 2.0 technique using synthetic datasets as well as a population-wide census-like study, which grounds the mathematical models and the computational algorithm into translational health research settings. Specifically, we empirically validated the CBDA technique on a large-scale clinical study (UK Biobank), which includes imaging, cognitive, and clinical assessment data. The UK Biobank archive presents several difficult challenges related to the aggregation, harmonization, modeling, and interrogation of the information. These problems are related to the complex longitudinal structure, feature heterogeneity, multicollinearity, incongruency, and missingness, as well as violations of classical parametric assumptions that require novel health analytical approaches. Our results showcase the scalability, efficiency and potential of CBDA to compress complex data into structural information leading to derived knowledge and translational action. The results of the real case-study suggest new and exciting avenues of research in the context of identifying, tracking, and treating mental health and aging-related disorders. Following open-science principles, we share the entire end-to-end protocol, source-code, and results. This facilitates independent validation, result reproducibility, and team-based collaborative discovery.

bioinformatics↗

bioRxiv2020

Myosin X interaction with KIF13B, a crucial pathway for Netrin-1-induced axonal development

Myosin X (Myo X) transports cargos to the tip of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of Myo X cargos essential for Netrin-1-regulated axon pathfinding. Myo Xs function in axon development in vivo and the underlying mechanisms remain poorly understood. Here, we provide evidence for Myo Xs function in Netrin-1-DCC regulated axon development in mouse neocortex. Knocking-out (KO) or knocking-down (KD) Myo X in embryonic cortical neurons impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Myo X interacts with KIF13B (a kinesin family motor protein), which is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in KIF13B dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. These results suggest Myo X-KIF13B as a critical pathway for Netrin-1 promoted axon initiation and branching/targeting.

developmental biology↗

bioRxiv2019

Choroid-resident macrophages maintain local vasculature and RPE integrity and spontaneously regenerate following depletion

The choroid of the eye provides necessary vascular supply to the outer retina across the retinal pigment epithelial (RPE) layer and is a locus of progressive degenerative change in aging and age-related macular degeneration (AMD). Cellular mechanisms that maintain or compromise choroidal vasculature homeostasis are not well understood, complicating therapeutic efforts. We discover here that pharmacological ablation of macrophages normally resident in the adult mouse choroid via blockade of the CSF1 receptor resulted in progressive thinning of the choroid layer and atrophy of the choriocapillaris. Concurrently, choroidal macrophage ablation also induced structural disorganization of the RPE cell layer, downregulation of RPE visual cycle genes, and altered RPE angiogenic factor expression. Suspension of CSF1R blockade following ablation conversely enabled spontaneous regeneration of the choroidal macrophage population, restoring original macrophage distribution and morphological features. Macrophage repopulation significantly ameliorated the ablation-induced changes in RPE structure and angiogenic factor expression and arrested choroidal vascular atrophy. These findings reveal a previously unsuspected trophic function of resident choroidal macrophages in the maintenance of choroidal vasculature and the RPE layer, suggesting that insufficiency of macrophage function may contribute to age- and AMD-associated pathology. Modulating choroidal macrophage support function can constitute a strategy for therapeutic preservation of the choroid and RPE in AMD prevention and treatment. Significance StatementChoroidal atrophy is associated with normal aging and progression in age-related macular degeneration (AMD), a leading cause of blindness. Herein, we identify the choroidal macrophage as a critical player in the homeostatic maintenance of choroid-RPE complex of the eye. Depletion of choroidal macrophages resulted in progressive vascular atrophy, altered structure of retinal pigment epithelial (RPE) cells, and dysregulated RPE expression of visual cycle protein and angiogenic factors, VEGF and PEDF. We discovered that choroidal macrophages can regenerate and repopulate the choroid following depletion, ameliorating RPE alterations and arresting vascular atrophy. Our results suggest that insufficiency of macrophage function may contribute to age- and AMD-associated pathology, and modulation of macrophage support functions may be therapeutically useful in AMD prevention and treatment.

immunology↗

bioRxiv2019

Cytokines and schizophrenia revisited: a two-sample multi-marker Mendelian randomization approach

BackgroundSchizophrenia is a complex mental disorder with recent evidence suggesting a critical immune component underpinning its pathophysiology. Two-sample Mendelian randomization (MR) provided an opportunity to probe the immune changes in schizophrenia by harnessing the increasing availability of summary-level data from large GWAS consortia. ObjectiveTo map the extensive immune response of schizophrenia in terms of cytokines/chemokines and to explore the effect of cytokines induced by schizophrenia (SCZ-induced cytokines) on the brain structure and function Sources and methodsUsing the summary-level data generated from GWAS of schizophrenia, cytokines in the peripheral blood and imaging-derived phenotypes (IDPs), we performed two rounds of two-sample MR analysis; the identified cytokines from first round of analysis (schizophrenia => cytokines) were modeled for its underlying structure and subsequent clustering analysis further grouped SCZ-induced cytokines based on their genetic similarities. The multi-phenotype summary statistics of each cytokine module were then used as instrumental variables (IVs) for the second round of MR analysis to detect their effect on brain structure and function. ResultsThe first round of MR analysis identified nine cytokines, the highlight of which includes IL18 (OR = 1.292, P = 8.37 x 10-42) and TNFa (OR = 0.721, P = 7.33 x 10-6), to be causally associated with schizophrenia. These SCZ-induced cytokines could be clustered into three modules. The second round of MR analysis (cytokine module => IDPs) indicated that module B (SCGFb-IP10-CTACK-IL6) significantly increased the level of IDPs including IDP_T1_SIENAX_peripheral_grey_normalised_volume ({beta} = 0.0453, P = 4.40x1010), IDP_dMRI_TBSS_MD_Posterior_corona_radiata_R ({beta}= 0.0584, P = 8.89x 10-16) and IDP_dMRI_TBSS_MD_Cingulum_hippocampus_R ({beta} = 0.0563, P = 9.88x 10-15), with module C (IL18-GROa-TNFa) increasing the level of IDP_dMRI_TBSS_L2_Posterior_thalamic_radiation_R ({beta}= 0.0341, P = 2.67x 10-6). ConclusionOur study, for the first time, mapped the causal link from schizophrenia to the comprehensive immune responses, and the findings suggest immune networks play a role in pathophysiology of schizophrenia by mediating the deviations of total gray matter volume and white matter fibers possibly in the mesolimbic system.

bioinformatics↗

bioRxiv2019

Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform.

Alexander disease results from gain of function mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed in astrocytes. At least eight GFAP isoforms have been described, however, the predominant alpha isoform accounts for approximately 90% of GFAP protein in the central nervous system. Here we describe exonic variants identified in three unrelated families with Type II Alexander disease that alter the splicing of GFAP pre-mRNA and result in upregulation of a previously uncharacterized GFAP lambda isoform (NM 001363846.1). Affected members of Family 1 and Family 2 shared the same missense variant, NM 001363846.1:c.1289G>A;p.(Arg430His) while in Family 3 we identified a synonymous variant in the adjacent nucleotide, NM 001363846.1:c.1290C>A;p.(Arg430Arg). Using RNA and protein analysis of brain autopsy samples, and a mini-gene splicing reporter assay, we demonstrate both variants result in upregulation of the lambda isoform. We assessed other GFAP variants in the ClinVar database for predicted aberrant splicing and using the same assay demonstrated significant changes to splicing for two selected variants. Our approach demonstrates the importance of characterizing the effect of GFAP variants on mRNA splicing in order to inform future pathophysiologic and therapeutic study for Alexander disease.

genetics↗

bioRxiv2019

qKW9 encodes a pentatricopeptide repeat protein affecting photosynthesis and grain filling in maize

Kernel weight is an important yield component in maize that was selected during domestication. Many kernel weight genes have been identified through mutant analysis, and are mostly involved in the biogenesis and functional maintenance of organelles or other fundamental cellular activities. However, only a limited number of loci underlying quantitative variation in kernel weight have been cloned. Here we characterize a maize kernel weight QTL, qKW9 and find that it encodes a DYW motif pentatricopeptide repeat protein involved in C-to-U editing of NdhB, a subunit of the chloroplast NADH dehydrogenase-like complex. In a null qKW9 background, C-to-U editing of NdhB was abolished, and photosynthesis was reduced, suggesting that qKW9 regulates kernel weight by controling the maternal source of photosynthate for grain filling. Characterization of qKW9 highlights the importance of optimizing photosynthesis on maize grain yield production.

plant biology↗

bioRxiv2019

A novel antiviral lncRNA EDAL shields a T309 O-GlcNAcylation site to promote EZH2 degradation

The central nervous system (CNS) is vulnerable for viral infection, yet few host factors in the CNS are known to defend invasion by neurotropic viruses. We report here that multiple neurotropic viruses, including rabies virus (RABV), vesicular stomatitis virus (VSV), Semliki Forest virus (SFV) and herpes simplex virus 1 (HSV-1), elicit the neuronal expression of a host-encoded lncRNA EDAL. EDAL inhibits the replication of these neurotropic viruses in neuronal cells and RABV infection in mouse brains. EDAL binds to the conserved histone methyltransferase enhancer of zest homolog 2 (EZH2) and specifically causes EZH2 degradation via lysosomes, reducing the cellular H3K27me3 level. The antiviral function of EDAL resides in a 56-nt antiviral substructure through which its 18-nt helix-loop intimately contacts multiple EZH2 sites surrounding T309, a known O-GlcNAcylation site. EDAL positively regulate the transcription of Pcp4l1 encoding a 10 kDa peptide, which inhibits the replication of mutiple neurotropic viruses. Our findings proposed a model in which a neuronal lncRNA can exert an effective antiviral function via blocking a specific O-GlcNAcylation that determines EZH2 lysosomal degradation.

microbiology↗

bioRxiv2019

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Germ cell 1 spermatogonial (GC-1spg) cells are multipotent progenitor cells. We previously confirmed that bone morphogenetic protein (BMP) 9 is among the most osteogenic BMPs. However, whether GC-1spg cells are driven toward osteogenic differentiation under proper stimuli is uncertain. Additionally, the molecular mechanism of BMP9 remains unclear. In the present study, we aimed to determine whether BMP9 can induce osteogenic differentiation of GC-1spg cells. Recombinant adenoviruses were generated by the AdEasy system to regulate the BMP9 expression in GC-1spg cells. We identified osteogenic markers by real-time PCR and staining techniques in vitro. Ectopic ossification assays and histological analysis were also performed to verify the in vivo activity of BMP9. Finally, potential signaling pathways of BMP9 were assessed by transcriptome sequencing and KEGG enrichment analysis. Using recombinant adenoviruses, we demonstrate that BMP9 upregulates osteogenic markers including Runx2, osteocalcin, osteopontin, and Sox9. BMP9 also activates alkaline phosphatase activity and calcium deposition in GC-1spg cells. In vivo results show that BMP9 overexpression in GC-1spg cells promotes ectopic bone formation and chondrogenesis. In addition, RNA-sequencing and KEGG pathway analysis demonstrate that several signaling pathways are involved in BMP9-mediated osteogenesis. GC-1spg cells not only maintain spermatogenesis but also retain the ability to form bone tissue. Therefore, BMP9 activity in GC-1spg cells may help identify signaling pathways implicated in bone formation and could be of use in regenerative medicine.

cell biology↗

bioRxiv2019

Zonation-dependent single-endothelial cell transcriptomic changes in the aged brain

With advances in single-cell genomics, molecular signatures of cells comprising the brain vasculature are revealed in unprecedented detail1,2, yet the ageing-associated cell subtype transcriptomic changes which may contribute to neurovascular dysfunction in neurodegenerative diseases3-7 remain elusive. Here, we performed single-cell transcriptomic profiling of brain endothelial cells (EC) in young adult and aged mice to characterize their ageing-associated genome-wide expression changes. We identified zonation-dependent transcriptomic changes in aged brain EC subtypes, with capillary ECs exhibiting the most transcriptomic alterations. Pathway enrichment analysis revealed altered immune/cytokine signaling in ECs of all vascular segments, while functional changes impacting the blood-brain barrier (BBB) and glucose/energy metabolism were most prominently implicated in ECs of the capillary bed - the primary site where ECs and other neurovascular unit (NVU) cell types closely interact and coordinate to regulate BBB and cerebral blood flow in health and diseased conditions8-17. Furthermore, an overrepresentation of Alzheimers disease (AD)-associated genes identified from GWAS studies was evident among the human orthologs of differentially expressed genes of aged capillary ECs but not other EC subtypes. Importantly, for numerous EC-enriched differentially expressed genes with important functional roles at the BBB and/or association with AD, we found concordant expression changes in human aged or AD brains. Finally, we demonstrated that treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, strongly reverses transcriptomic changes in ECs and largely reduces BBB leakage in the aged brain. Thus, our study provides insights into detailed transcriptomic alterations underlying brain EC ageing that are complex with subtype specificity yet amenable to pharmacological interventions.

neuroscience↗

bioRxiv2019

Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus

Nearly all motile cilia contain a central apparatus (CA) composed of two connected singlet-microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown. Here, we integrated biochemical and genetic approaches with cryo-electron tomography to compare the CA of wild type Chlamydomonas with CA mutants. We identified a large (>2 MDa) complex, the C1a-e-c supercomplex, that requires the PF16 protein for assembly and contains the CA components FAP76, FAP81, FAP92, and FAP216. We localized these subunits within the supercomplex using nanogold-labeling and show that loss of any one of them results in impaired ciliary motility. These data provide insight into the subunit organization and three-dimensional (3D) structure of the CA, which is a prerequisite for understanding the molecular mechanisms by which the CA regulates ciliary beating.\n\nSummaryFu et al. use a wild-type vs. mutant comparison and cryo-electron tomography of Chlamydomonas flagella to identify central apparatus (CA) subunits and visualize their location in the native 3D CA structure. The study provides a better understanding of the CA and how it regulates ciliary motility.

cell biology↗

bioRxiv2019

Establishing RPTE-derived cell lines expressing hTERT for studying BK polyomavirus

We previously established an infection model for BKPyV in primary human renal proximal tubule epithelial (RPTE) cells. Use of these cells is limited by their inability to be passaged extensively. We describe RPTE cells immortalized with hTERT, which can serve as a model system for acute or persistent BKPyV infection.

microbiology↗

bioRxiv2019

Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

bioinformatics↗

bioRxiv2019

Systematical analysis reveals the novel function of Cyp2c29 in liver injury

As a severe lethal cancer, hepatocellular carcinoma (HCC) usually originates from chronic liver injury and inflammation, in which the discovery of key genes is important for HCC prevention. Here, we analyzed the time serial (from 0 week to 30 weeks) transcriptome data of liver injury samples in diethylnitrosamine (DEN)-induced HCC mouse model. Through expression and function analyses, we identified that Cyp2c29 was a key gene continuously downregulated during liver injury. Overexpression of Cyp2c29 suppressed the NF-{kappa}B activation, proinflammatory cytokine production and hepatocyte proliferation by increasing its production 14,15-epoxyeicosatrienoic acid (14,15-EET). Furthermore, in vivo Cyp2c29 protected against liver inflammation in liver injury mice models by reversing the expression on functions of cell proliferation, metabolism and inflammation including suppressing NF-{kappa}B pathway and compensatory proliferation. CYP2C8 and CYP2C9, two human homologs of mouse Cyp2c29, were decreased in human HCC progression and positively correlated with HCC patient survival. Therefore, through systematical analysis and verification, we identified that Cyp2c29 is a novel gene in liver injury and inflammation, which may be a potential biomarker for HCC prevention and prognosis.

bioinformatics↗

bioRxiv2019

A new variance ratio metric to detect the timescale of compensatory dynamics

Understanding the mechanisms governing ecological stability - why a property such as primary productivity is stable in some communities and variable in others - has long been a focus of ecology. Compensatory dynamics, in which anti-synchronous fluctuations between populations buffer against fluctuations at the community level, is a key theoretical mechanism of stability. Classically, compensatory dynamics have been quantified using a \"variance ratio\" approach that compares the ratio between community variance and aggregate population variance, such that a lower ratio indicates compensation and a higher ratio indicates synchrony among species fluctuations. However, population dynamics may be influenced by different drivers that operate on different timescales, and evidence from aquatic systems indicates that communities can be compensatory on some timescales and synchronous on others. The variance ratio and related metrics cannot reflect this timescale-specificity, yet have remained popular, especially in terrestrial systems. Here, we develop a timescale-specific variance ratio approach that formally decomposes the classical variance ratio according to the timescales of distinct contributions. The approach is implemented in a new R package, called tsvr, that accompanies this paper. We apply our approach to a long-term, multi-site grassland community dataset. Our approach demonstrates that the degree of compensation versus synchrony in community dynamics can vary by timescale. Across sites, population variability was typically greater over longer compared to shorter timescales. At some sites, minimal timescale-specificity in compensatory dynamics translated this pattern of population variability into a similar pattern of greater community variability on longer compared to shorter timescales. But at other sites, differentially stronger compensatory dynamics at longer compared to shorter timescales produced lower-than-expected community variability on longer timescales. Within every site there were plots that exhibited shifts in the strength of compensation between timescales. Our results highlight that compensatory versus synchronous dynamics are intrinsically timescale-dependent concepts, and our timescale-specific variance ratio provides a metric to quantify timescale-specificity and relate it back to the classic variance ratio.

ecology↗