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PLOS Biology: New Articles

  • <i>Mdga2</i> deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice

    by Dongdong Zhao, Yuanhui Huo, Naizhen Zheng, Xiang Zhu, Dingting Yang, Yunqiang Zhou, Shengya Wang, Yiru Jiang, Yili Wu, Yun-wu Zhang

    Memprin/A5/mu (MAM) domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) is an excitatory synaptic suppressor and its mutations have been associated with autism spectrum disorder (ASD). However, the detailed physiological function of MDGA2 and the mechanism underlying MDGA2 deficiency-caused ASD has yet to be elucidated. Herein, we not only confirm that Mdga2 +/− mice exhibit increased excitatory synapse transmission and ASD-like behaviors, but also identify aberrant brain-derived neurotrophic factor/tyrosine kinase B (BDNF/TrkB) signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its memprin/A5/mu domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signaling activity. Importantly, we demonstrate that inhibiting the BDNF/TrkB signaling by both small molecular compound and MDGA2-derived peptide can attenuate the increase of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitatory synaptic activity and social deficits in MDGA2-deficient mice. These results highlight a novel MDGA2-BDNF/TrkB-dependent mechanism underlying the synaptic function regulation, which may become a therapeutic target for ASD.

  • An agricultural triazole induces genomic instability and haploid cell formation in the human fungal pathogen <i>Candida tropicalis</i>

    by Tianren Hu, Qiushi Zheng, Chengjun Cao, Shuaihu Li, Yanfeng Huang, Zhangyue Guan, Lingyu Ji, Jian Bing, Han Du, Austin M. Perry, Clarissa J. Nobile, Bing Li, Haiqing Chu, Guanghua Huang

    The human fungal pathogen Candida tropicalis is widely distributed in clinical and natural environments. It is known to be an obligate diploid organism with an incomplete and atypical sexual cycle. Azole-resistant C. tropicalis isolates have been observed with increasing prevalence in many countries in recent years. Here, we report that tebuconazole (TBZ), a triazole fungicide widely used in agriculture, can induce ploidy plasticity and the formation of haploid cells in C. tropicalis. The evolved C. tropicalis strains with ploidy variations exhibit a cross-resistance between TBZ and standard azoles used in clinical settings (such as fluconazole and voriconazole). Similar to its diploid cells, these newly discovered C. tropicalis haploid cells are capable of undergoing filamentation, white-opaque switching, and mating. However, compared to its diploid cells, these haploid C. tropicalis cells grow more slowly under in vitro culture conditions and are less virulent in a mouse model of systemic infection. Interestingly, flow cytometry analysis of a clinical strain with extremely low genome heterozygosity indicates the existence of natural C. tropicalis haploids. Discovery of this C. tropicalis haploid state sheds new light into the biology and genetic plasticity of C. tropicalis and could provide the framework for the development of new genetic tools in the field.

  • Diatom heterotrophy on brown algal polysaccharides emerged through horizontal gene transfer, gene duplication, and neofunctionalization

    by Zeng Hao Lim, Peng Zheng, Christopher Quek, Minou Nowrousian, Finn L. Aachmann, Gregory Jedd

    A major goal of evolutionary biology is to identify the genetic basis for the emergence of complex adaptive traits. Diatoms are ancestrally photosynthetic microalgae. However, in the genus Nitzschia, loss of photosynthesis led to a group of free-living secondary heterotrophs whose manner of acquiring chemical energy is unclear. Here, we sequence the genome of the non-photosynthetic diatom Nitzschia sing1 and identify the genetic basis for its catabolism of the brown algal cell wall polysaccharide alginate. N. sing1 obtained an endolytic alginate lyase enzyme by horizontal gene transfer (HGT) from a marine bacterium. Subsequent gene duplication through unequal crossing over and transposition led to 91 genes in three distinct gene families. One family retains the ancestral endolytic enzyme function. By contrast, the two others underwent domain duplication, gain, loss, rearrangement, and mutation to encode novel functions that can account for oligosaccharide import through the endomembrane system and the exolytic production of alginate monosaccharides. Together, our results show how a single HGT event followed by substantial gene duplication and neofunctionalization led to alginate catabolism and access to a new ecological niche.

  • A hypermobile prophage in the genome of a key human gut bacterium

    by Andrey N. Shkoporov, Colin Hill

    Phages infecting anaerobic bacteria are highly abundant in the mammalian gut, but their biology and ecological impact are poorly understood. A new PLOS Biology study provides a glimpse into the disruptive biology of the Hankyphages, parasites of the ubiquitous Bacteroidaceae.

  • The multiscale brain structural re-organization that occurs from childhood to adolescence correlates with cortical morphology maturation and functional specialization

    by Yirong He, Debin Zeng, Qiongling Li, Lei Chu, Xiaoxi Dong, Xinyuan Liang, Lianglong Sun, Xuhong Liao, Tengda Zhao, Xiaodan Chen, Tianyuan Lei, Weiwei Men, Yanpei Wang, Daoyang Wang, Mingming Hu, Zhiying Pan, Haibo Zhang, Ningyu Liu, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He, Shuyu Li

    From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synapses to macroscale white matter pathways. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, using two independent multimodal imaging developmental datasets aged 6–14 years, we investigated developmental process of multiscale cortical organization by constructing an in vivo multiscale structural connectome model incorporating white matter tractography, cortico–cortical proximity, and microstructural similarity. By employing the gradient mapping method, the principal gradient derived from the multiscale structural connectome effectively recapitulated the sensory-association axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, characterized by enhanced differentiation between primary sensory and higher-order transmodal regions along the principal gradient. This age-related differentiation paralleled regionally heterogeneous changes in cortical morphology. Furthermore, the developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. Notably, the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially underpinned by synaptic and hormone-related biological processes. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.