Xiaohua He

Bio: Xiaohua He is an academic researcher from Wuhan University. The author has contributed to research in topics: Epilepsy & Viral replication. The author has an hindex of 23, co-authored 107 publications receiving 1961 citations. Previous affiliations of Xiaohua He include Centre national de la recherche scientifique.

The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods

Abstract: Representing a basal branch of arachnids, scorpions are known as 'living fossils' that maintain an ancient anatomy and are adapted to have survived extreme climate changes. Here we report the genome sequence of Mesobuthus martensii, containing 32,016 protein-coding genes, the most among sequenced arthropods. Although M. martensii appears to evolve conservatively, it has a greater gene family turnover than the insects that have undergone diverse morphological and physiological changes, suggesting the decoupling of the molecular and morphological evolution in scorpions. Underlying the long-term adaptation of scorpions is the expansion of the gene families enriched in basic metabolic pathways, signalling pathways, neurotoxins and cytochrome P450, and the different dynamics of expansion between the shared and the scorpion lineage-specific gene families. Genomic and transcriptomic analyses further illustrate the important genetic features associated with prey, nocturnal behaviour, feeding and detoxification. The M. martensii genome reveals a unique adaptation model of arthropods, offering new insights into the genetic bases of the living fossils.

DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson's disease.

Abstract: Selective degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease (PD) can be modeled by the administration of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+) ). Because abnormal mitochondrial dynamics are increasingly implicated in the pathogenesis of PD, in this study, we investigated the effect of MPP(+) on mitochondrial dynamics and assessed temporal and causal relationship with other toxic effects induced by MPP(+) in neuronal cells. In SH-SY5Y cells, MPP(+) causes a rapid increase in mitochondrial fragmentation followed by a second wave of increase in mitochondrial fragmentation, along with increased DLP1 expression and mitochondrial translocation. Genetic inactivation of DLP1 completely blocks MPP(+) -induced mitochondrial fragmentation. Notably, this approach partially rescues MPP(+) -induced decline in ATP levels and ATP/ADP ratio and increased [Ca(2+) ](i) and almost completely prevents increased reactive oxygen species production, loss of mitochondrial membrane potential, enhanced autophagy and cell death, suggesting that mitochondria fragmentation is an upstream event that mediates MPP(+) -induced toxicity. On the other hand, thiol antioxidant N-acetylcysteine or glutamate receptor antagonist D-AP5 also partially alleviates MPP(+) -induced mitochondrial fragmentation, suggesting a vicious spiral of events contributes to MPP(+) -induced toxicity. We further validated our findings in primary rat midbrain dopaminergic neurons that 0.5 μm MPP(+) induced mitochondrial fragmentation only in tyrosine hydroxylase (TH)-positive dopaminergic neurons in a similar pattern to that in SH-SY5Y cells but had no effects on these mitochondrial parameters in TH-negative neurons. Overall, these findings suggest that DLP1-dependent mitochondrial fragmentation plays a crucial role in mediating MPP(+) -induced mitochondria abnormalities and cellular dysfunction and may represent a novel therapeutic target for PD.

Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype.

Abstract: Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and axonal damage in the central nervous system. Cognitive deficits are recognized as one of the features of MS, and these deficits affect the patients’ quality of life. Increasing evidence from experimental autoimmune encephalomyelitis (EAE), the animal model of MS, has suggested that EAE mice exhibit hippocampal impairment and cognitive deficits. However, the underlying mechanisms are still unclear. The NLRP3 inflammasome is a key contributor to neuroinflammation and is involved in the development of MS and EAE. Activation of the NLRP3 inflammasome in microglia is fundamental for subsequent inflammatory events. Activated microglia can convert astrocytes to the neurotoxic A1 phenotype in a variety of neurological diseases. However, it remains unknown whether the NLRP3 inflammasome contributes to cognitive deficits and astrocyte phenotype alteration in EAE. In this study, we demonstrated that severe memory deficits occurred in the late phase of EAE, and cognitive deficits were ameliorated by treatment with MCC950, an inhibitor of the NLRP3 inflammasome. In addition, MCC950 alleviated hippocampal pathology and synapse loss. Astrocytes from EAE mice were converted to the neurotoxic A1 phenotype, and this conversion was prevented by MCC950 treatment. IL-18, which is the downstream of NLRP3 inflammasome, was sufficient to induce the conversion of astrocytes to the A1 phenotype through the NF-κB pathway. IL-18 induced A1 type reactive astrocytes impaired hippocampal neurons through the release of complement component 3 (C3). Altogether, our present data suggest that the NLRP3 inflammasome plays an important role in cognitive deficits in EAE, possibly via the alteration of astrocyte phenotypes. Our study provides a novel therapeutic strategy for hippocampal impairment in EAE and MS.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.