Biology subjects

Wang, X.-H.

Publications and source records attributed to Wang, X.-H..

5 recordsLinked to original sources

bioRxiv2025

A Mechanosensitive GPCR at vestibular kinocilium is required for normal balance

Intracellular calcium increase and neurotransmitter release in vestibular hair cells (VHCs) play central roles in equilibrioception, which is one of the basic senses essential for daily life activities and movement in mammals. Independent of mechano-electrical transduction (MET), whether Gq protein-coupled receptor (GqPCR) signaling participate in the regulation of intracellular calcium dynamics and induce neuronal transmitter release in hair cells remains unknown. We screened mechanosensitive GqPCRs in VHCs and found that a Class C GPCR, metabotropic glutamate receptor 2 (mGlu2), is expressed in kinocilia and is essential for normal balance. Notably, the dispensable role of mGlu2 in normal hearing is consistent with absent of mature kinocilia in cochlea hair cells. Different from the conventional mGlu2-Gi signaling, the sensing of mechanical signals by mGlu2 activates the Gq-PLCD4 pathway, increases intracellular calcium concentration and promotes neurotransmitter release in VHCs. Hair cell-specific deficiency of either Grm2 or Gnaq, or knockdown of Plcd4 expression, but not deficiency of another GqPCR Gpr68, causes significant balance deficits. Reintroduction of mGlu2 into the VHCs of Pou4f3-CreER+/- Grm2fl/fl mice restore vestibular functions. Our study reveals a previously uncharacterized role of GPCR signaling in equilibrioception and provides important insight into kinocilia signaling in VHCs, which are absent in mature cochlear hair cells.

cell biology↗

bioRxiv2023

Russula subgen. Cremeoochraceae subgen. nov.: a very small and ancient lineage sharing with Multifurca (Russulaceae) an identical, largely circum-Pacific distribution pattern

The application of DNA data on a worldwide sampling has revolutionized the infrageneric classification of the highly diverse ectomycorrhizal genus Russula. Based on collections made in New Zealand, East Asia and North America, this study describes the new subgenus Cremeoochraceae, the ninth subgenus in Russula. Even though BLASTn of the ITS sequences suggested affinities with species of subgenera Russula and Heterophyllidiae, the phylogenetic analysis based on a five-locus DNA dataset placed the target samples in an independent major clade that is systematically equivalent to subgenus. The new subgenus shares with subgen. Brevipedum subsect. Pallidosporinae the general field habit, the unequal lamellae and the relatively small spores with inamyloid suprahilar spot and similar spore ornamentation. It differs from the latter subsection principally in the poor contents of all types of cystidioid cells and the often areolate-scurfy pileus surface composed of slender, undulating hyphal terminations with frequent subcapitate apices. Biogeographically, subgen. Cremeoochraceae shares with Multifurca, the sister genus of Lactarius, a circum-Pacific distribution pattern with the exception of South America. Both lineages lack representatives in Europe and Africa. The hypothesis proposing an African origin for the genus is considered unlikely.

molecular biology↗

bioRxiv2021

Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone (IMC) expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but both reduced the virus burden, and V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 abolished these effector activities and abrogated virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity.

immunology↗

bioRxiv2020

SMRT sequencing yields the chromosome-scale reference genome of tea tree, Camellia sinensis var. sinensis

Tea is the oldest and most popular nonalcoholic beverage consumed in the world. It provides abundant secondary metabolites that account for its diverse flavors and health benefits. Here we present the first high-quality chromosome-length reference genome of C. sinensis var. sinensis using long read single-molecule real time (SMRT) sequencing and Hi-C technologies to anchor the [~]2.85-Gb genome assembly into 15 pseudo-chromosomes with a scaffold N50 length of [~]195.68 Mb. We annotated at least 2.17 Gb ([~]74.13%) of repetitive sequences and high-confidence prediction of 40,812 protein-coding genes in the [~]2.92-Gb genome assembly. This accurately assembled genome allows us to comprehensively annotate functionally important gene families such as those involved in the biosynthesis of catechins, theanine and caffeine. The contiguous genome assembly provides the first view of the repetitive landscape allowing us to accurately characterize retrotransposon diversity. The large tea tree genome is dominated by a handful of Ty3-gypsy long terminal repeat (LTR) retrotransposon families that recently expanded to high copy numbers. We uncover the latest bursts of numerous non-autonomous LTR retrotransposons that may interfere with the propagation of autonomous retroelements. This reference genome sequence will largely facilitate the improvement of agronomically important traits relevant to the tea quality and production.

genomics↗

bioRxiv2018

Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

The positive correlation of high levels of plasma anti-V2 antibodies (Abs) with protective immunity in the Phase III anti-HIV RV144 vaccine trial generated interest in the induction of these Abs for HIV vaccine development. We analyzed plasma samples from 79 chronically infected Cameroonian individuals for Ab reactivity against three V1V2 fusion proteins and five cyclic V2 peptides and found that HIV-1 infection induces different levels of anti-V2 Abs. While the majority of plasma samples reacted strongly with one or more V2 antigens, 10% (8) of the samples were nonreactive. Deficiency of anti-V2 Abs was consistently found in longitudinal plasma samples tested over 8 to 54 months of HIV infection. There was a strong correlation between binding activities of plasma anti-V2 Abs and anti-gp120 and anti-gp41 Abs, suggesting that deficiency of V2 Abs could be related, in part, to a limited ability to elicit strong Ab responses. Analysis of gp120 sequences revealed that the V2 region of viruses from donors with V2-deficient versus V2-reactive Abs displayed a tendency toward longer length, more glycans, and lower isoelectric point and charge. No differences between these two patient groups were noted in the same parameters measured in the V1 region. These data suggest that immunogens containing a shorter V2 region with fewer glycosylation sites and higher electrostatic charges would be beneficial for induction of anti-V2 Abs, but the ability to mount a strong general Ab response to HIV-1 appears to be a dominant factor.\n\nIMPORTANCEThe results of the RV144 vaccine clinical trial showed a correlation between plasma Abs against a V1V2 fusion protein and a decreased risk of acquiring HIV-1 infection. This turned the focus of some HIV vaccine design to the induction of elevated levels of anti-V2 Abs to increase vaccine efficacy. In plasma samples from Cameroonian individuals infected with HIV-1, we observed broad variations in levels of anti-V2 Abs, and 8 of the 79 plasma samples tested displayed substantial deficiency of V2 Abs. Sequence analysis of the V2 region from plasma viruses and multivariate analyses of V2 characteristics showed a significant difference in several features between V2-deficient and V2-reactive plasma Abs. These results suggest that HIV vaccine immunogens containing a V2 region with shorter length, fewer glycosylation sites, and higher electrostatic charges may be beneficial for induction of a higher level of anti-V2 Abs and thus contribute to HIV vaccine efficacy.

immunology↗