Huang Y et al. (2020) Microorganisms "Genetic Variation in Caenorhabditis elegans Responses to Pathogenic Microbiota."

Huang Y, Kammenga JE

[Microorganisms, 2020]

The bacterivorous nematode <i>Caenorhabditis elegans</i> is an important model species for understanding genetic variation of complex traits. So far, most studies involve axenic laboratory settings using <i>Escherichia coli</i> as the sole bacterial species. Over the past decade, however, investigations into the genetic variation of responses to pathogenic microbiota have increasingly received attention. Quantitative genetic analyses have revealed detailed insight into loci, genetic variants, and pathways in <i>C. elegans</i> underlying interactions with bacteria, microsporidia, and viruses. As various quantitative genetic platforms and resources like <i>C. elegans</i> Natural Diversity Resource (CeNDR) and Worm Quantitative Trait Loci (WormQTL) have been developed, we anticipate that expanding <i>C. elegans</i> research along the lines of genetic variation will be a treasure trove for opening up new insights into genetic pathways and gene functionality of microbiota interactions.

Huang Y et al. (2007) BMC Genomics "A bootstrap based analysis pipeline for efficient classification of phylogenetically related animal miRNAs."

Gu X, Huang Y

[BMC Genomics, 2007]

ABSTRACT: BACKGROUND: Phylogenetically related miRNAs (miRNA families) convey important information of the function and evolution of miRNAs. Due to the special sequence features of miRNAs, pair-wise sequence identity between miRNA precursors alone is often inadequate for unequivocally judging the phylogenetic relationships between miRNAs. Most of the current methods for miRNA classification rely heavily on manual inspection and lack measurements of the reliability of the results. RESULTS: In this study, we designed an analysis pipeline (the Phylogeny-Bootstrap-Cluster (PBC) pipeline) to identify miRNA families based on branch stability in the bootstrap trees derived from overlapping genome-wide miRNA sequence sets. We tested the PBC analysis pipeline with the miRNAs from six animal species, H. sapiens, M. musculus, G. gallus, D. rerio, D. melanogaster, and C. elegans. The resulting classification was compared with the miRNA families defined in miRBase. The two classifications were largely consistent. CONCLUSIONS: The PBC analysis pipeline is an efficient method for classifying large numbers of heterogeneous miRNA sequences. It requires minimum human involvement and provides measurements of the reliability of the classification results.

Huang Y et al. (2021) Genes (Basel) "Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection."

Sterken MG, van Zwet K, Pijlman GP, Kammenga JE, van Sluijs L, Huang Y

[Genes (Basel), 2021]

The nematode Caenorhabditis elegans has been a versatile model for understanding the molecular responses to abiotic stress and pathogens. In particular, the response to heat stress and virus infection has been studied in detail. The Orsay virus (OrV) is a natural virus of C. elegans and infection leads to intracellular infection and proteostatic stress, which activates the intracellular pathogen response (IPR). IPR related gene expression is regulated by the genes pals-22 and pals-25, which also control thermotolerance and immunity against other natural pathogens. So far, we have a limited understanding of the molecular responses upon the combined exposure to heat stress and virus infection. We test the hypothesis that the response of C. elegans to OrV infection and heat stress are co-regulated and may affect each other. We conducted a combined heat-stress-virus infection assay and found that after applying heat stress, the susceptibility of C. elegans to OrV was decreased. This difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with heat stress and OrV infection. Subsequent mutant screens suggest that pals-22 provides a link between viral response and heat stress, leading to enhanced OrV tolerance of C. elegans after heat stress.

Huang Y et al. (2014) Int J Clin Exp Med "Immunoregulation effect of crude extract of C. elegans on allergic asthma."

Zhang Y, Guo W, Li C, Huang Y, Jiang Y, Guo M, Gong W, He L

[Int J Clin Exp Med, 2014]

UNLABELLED: To explore effects of natural crude extract of C. elegans on treatment of asthma. METHOD: Obtain crude extract of C. elegans from synchronically incubated C. elegans via centrifugation, washing and ultrasonic emulsification, etc.; measure C. elegans's protein molecular weight via SDS-polyacrylamide gel electrophoresis (SDS-PAG electrophoresis); construct animal models of asthma with 6-8-week-old BALB/c female mice sensitized by chicken ovalbumin (OVA); conduct immunotherapy on animals with asthma with different doses of mixture of C. elegans and OVA (COM) respectively; take PBS buffer group and OVA group as control groups; conduct inspection of cell factors and differential count of cells in serum IgE, IgG1 and IgG2a antibodies and bronchoalveolar lavage fluid (BALF) via enzyme linked immunosorbent assay (ELISA); and incise lung tissue for pathology observation. RESULT: C. elegans's protein molecular weight is about 50 kd. In bronchoalveolar lavage fluid (BALF) of OVA group, cell factors IL-5 and IL-13 are more than those in PBS buffer group, but IL-2 and IFN- are less than those in PBS buffer group; these differences are of statistical significance (P&lt;0.05). Total cellular score and number of eosinophile granulocyte in BALF of OVA group are more than those in PBS buffer group (P&lt;0.05), and the difference in serum IgE, IgG1 and IgG2a between these two groups is of statistical significance (P&lt;0.05). For groups treatment by different doses of COM, cell factors IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) are less than those in OVA group, but IL-2 and IFN- are more than those in OVA group; these differences are of statistical significance (P&lt;0.05). Total cellular score and number of eosinophile granulocyte in BALF of COM treatment groups are less than those in OVA group (P&lt;0.05); serum IgE and IgG1 less than those in OVA group, but IgG2a is more than that in OVA group; these differences are of statistical significance (P&lt;0.05). CONCLUSION: The natural crude extract of C. elegans has immunoregulation to animals with asthma.

Huang Y-J et al. (1994) Worm Breeder's Gazette "From Ascaris to C. elegans: A Way to Study Gene Structure and Function"

Tobler H, Huang Y-J, Mueller F

[Worm Breeder's Gazette, 1994]

FROM ASCARIS TO C. ELEGANS: A WAY TO STUDY GENE STRUCTURE AND FUNCTION Huang Y-J., Tobler H. and Muller F., Institute of Zoology, University of Pribourg, Perolles, CH-1700 Fribourg, Switzerland

Huang Y et al. (2023) Aging Dis "Longevity-Associated Transcription Factor ATF7 Promotes Healthspan by Suppressing Cellular Senescence and Systematic Inflammation."

Yu Q, Xiao FH, Li YH, Li J, Yang LQ, Ge MX, Li JL, He Y, Ao HS, Kong QP, Huang Y

[Aging Dis, 2023]

Aging is characterized by persistent low-grade systematic inflammation, which is largely responsible for the occurrence of various age-associated diseases. We and others have previously reported that long-lived people (such as centenarians) can delay the onset of or even escape certain major age-related diseases. Here, by screening blood transcriptome and inflammatory profiles, we found that long-lived individuals had a relatively lower inflammation level (IL6, TNF&#x3b1;), accompanied by up-regulation of activating transcription factor 7 (ATF7). Interestingly, ATF7 expression was gradually reduced during cellular senescence. Loss of ATF7 induced cellular senescence, while overexpression delayed senescence progress and senescence-associated secretory phenotype (SASP) secretion. We showed that the anti-senescence effects of ATF7 were achieved by inhibiting nuclear factor kappa B (NF-&#x3ba;B) signaling and increasing histone H3K9 dimethylation (H3K9me2). In Caenorhabditis elegans, ATF7 overexpression significantly suppressed aging biomarkers and extended lifespan. Our findings suggest that ATF7 is a longevity-promoting factor that lowers cellular senescence and inflammation in long-lived individuals.

Huang Y et al. (2022) Hum Mol Genet "Mutant D620N and VPS35 induces motor dysfunction and impairs DAT-mediated dopamine recycling pathway."

Pei Z, Chen X, Li J, Zeng Y, Huang Y, Ross CA, Guo W, Zeng J, Liang F, Tan EK, Smith W, Low BC, He X, Huang H, Zhou L, Thomas J

[Hum Mol Genet, 2022]

The D620N mutation in vacuolar protein sorting protein 35 (VPS35) gene has been identified to be linked to late onset familial Parkinson disease (PD). However, the pathophysiological roles of VPS35-D620N in PD remain unclear. Here, we generated the transgenic C. elegans overexpressing either human wild type or PD-linked mutant VPS35-D620N in neurons. C. elegans expressing VPS35-D620N, compared with non-transgenic controls, showed movement disorders and dopaminergic neuron loss. VPS35-D620N worms displayed more swimming induced paralysis but showed no defects in BSR assays, thus indicating the disruption of dopamine (DA) recycling back inside neurons. Moreover, VPS35 formed a protein interaction complex with DA transporter (DAT), RAB5, RAB11, and FAM21. In contrast, the VPS35-D620N mutant destabilized these interactions, thus disrupting DAT transport from early endosomes to recycling endosomes, and decreasing DAT at the cell suffice. These effects together increased DA in synaptic clefts, and led to dopaminergic neuron degeneration and motor dysfunction. Treatment with reserpine significantly decreased the swimming induced paralysis in VPS35-D620N worms, as compared with vehicle treated VPS35-D620N worms. Our studies not only provide novel insight into the mechanisms of VPS35-D620N-induced dopaminergic neuron degeneration and motor dysfunction via disruption of DAT function and the DA signaling pathway, but also indicate a potential strategy to treat VPS35-D620N related PD and other disorders.

Huang Y et al. (2024) Heliyon "Research on the anti-oxidant and anti-aging effects of Polygonatum kingianum saponins in Caenorhabditis elegans."

Huang Y, Tan N, Cheng S, He J, Wang Y, Qiu J, Deng J, Gao S, Song Z, Yang T

[Heliyon, 2024]

Oxidative stress and its impact on aging are critical areas of research. Natural anti-oxidants, such as saponins found in <i>Polygonatum sibiricum</i>, hold promise as potential clinical interventions against aging. In this study, we utilized the nematode model organism, <i>Caenorhabditis elegans</i>, to investigate the pharmacological effects of <i>Polygonatum sibiricum</i> saponins (PKS) on antioxidation and anti-aging. The results demonstrated a significant anti-aging biological activity associated with PKS. Through experiments involving lifespan and stress, lipofuscin, q-PCR, and ROS measurement, we found that PKS effectively mitigated aging-related processes. Furthermore, the mechanism underlying these anti-aging effects was linked to the SKN-1 signaling pathway. PKS increased the nuclear localization of the SKN-1 transcription factor, leading to the up-regulation of downstream anti-oxidant genes, such as gst-4 and sod-3, and a substantial reduction in intracellular ROS levels within the nematode. In conclusion, our study sheds light on the anti-oxidant and anti-aging properties of PKS in <i>C. elegans</i>. This research not only contributes to understanding the biological mechanisms involved but also highlights the potential therapeutic applications of these natural compounds in combating aging-related processes.

Huang Y et al. (2017) Front Microbiol "Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus."

Zhang H, Du A, Zheng X, Chen X, Ding H, Guo X, Yang Y, Huang Y, Zhou Q

[Front Microbiol, 2017]

Haemonchus contortus (H. contortus) is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans (C. elegans) has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22. In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi) experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant (ok693) from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22. Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

Huang X-Y (1994) Computer Applications in the Biosciences "On global sequence alignment."

Huang X-Y

[Computer Applications in the Biosciences, 1994]

We present a dynamic programming algorithm for computing a best global alignment of two sequences. The proposed algorithm is robust in identifying any of several global relationships between two sequences. The algorithm delivers a best alignment of two sequences in linear space and quadratic time. We also describe a multiple alignment algorithm based on the pairwise algorithm. Both algorithms have been implemented as portable C programs. Experimental results indicate that for a commonly used set of gap penalties, the new programs produce more satisfactory alignments on sequences of various lengths than some existing pairwise and multiple programs based on the dynamic programming algorithm of Needleman and Wunsch.