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1.
Front Microbiol ; 12: 792556, 2021.
Article in English | MEDLINE | ID: mdl-35250904

ABSTRACT

Microbiome mediates early life immune deviation in asthma development. Recurrent wheeze (RW) in pre-school years is a risk factor for asthma diagnosis in school-age children. Dysbiosis exists in asthmatic airways, while its origin in pre-school years and relationship to RW is not clearly defined. This study investigated metagenomics of nasopharyngeal microbiome in pre-school children with RW. We applied whole-genome shotgun sequencing and human rhinovirus (HRV) detection on nasopharyngeal samples collected from three groups of pre-school children: (i) RW group: 16 children at-risk for asthma who were hospitalized for RW, (ii) inpatient control (IC): 18 subjects admitted for upper respiratory infection, and (iii) community control (CC): 36 children without respiratory syndromes. Sequence reads were analyzed by MetaPhlAn2 and HUMAnN2 algorithm for taxonomic and functional identification. Linear discriminant analysis effect size (LEfSe) analysis was used to identify discriminative features. We identified that Moraxella catarrhalis and Dolosigranulum pigrum were predominant species in nasopharynx. RW had lower alpha diversity (Shannon diversity index) than CC (0.48 vs. 1.07; P adj = 0.039), characterized by predominant Proteobacteria. LEfSe analysis revealed D. pigrum was the only discriminative species across groups (LDA = 5.57, P = 0.002), with its relative abundance in RW, IC, and CC being 9.6, 14.2, and 37.3%, respectively (P < 0.05). LEfSe identified five (ribo)nucleotides biosynthesis pathways to be group discriminating. Adjusting for HRV status, pre-school children with RW have lower nasopharyngeal biodiversity, which is associated with Proteobacteria predominance and lower abundance of D. pigrum. Along with discriminative pathways found in RW and CC, these microbial biomarkers help to understand RW pathogenesis.

2.
Biochem J ; 459(1): 181-91, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24444330

ABSTRACT

SRPKs (serine/arginine protein kinases) are highly specific kinases that recognize and phosphorylate RS (Arg-Ser) dipeptide repeats. It has been shown previously that SRPK1 phosphorylates the RS domain of SRSF1 (serine/arginine splicing factor 1) at multiple sites using a directional and processive mechanism. Such ability to processively phosphorylate substrates is proposed to be an inherent characteristic of SRPKs. SRPK2 is highly related to SRPK1 in sequence and in vitro properties, yet it has been shown to have distinct substrate specificity and physiological function in vivo. To study the molecular basis for substrate specificity of SRPK2, we investigated the roles of the non-kinase regions and a conserved docking groove of SRPK2 in the recognition and phosphorylation of different substrates: SRSF1 and acinusS. Our results reveal that a conserved electronegative docking groove in SRPK2, but not its non-kinase regions, is responsible for substrate binding regardless of their identities. Although SRPK2 phosphorylates SRSF1 in a processive manner as predicted, an electronegative region on acinusS restricts SRPK2 phosphorylation to a single specific site despite the presence of multiple RS dipeptides. These results suggest that primary structural elements on the substrates serve as key regulatory roles in determining the phosphorylation mechanism of SRPK2.


Subject(s)
Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Protein Serine-Threonine Kinases/chemistry , Protein Serine-Threonine Kinases/genetics , Amino Acid Sequence , Cell Line, Tumor , Conserved Sequence , Humans , Molecular Sequence Data , Phosphorylation/physiology , Protein Binding/physiology , Substrate Specificity
3.
PLoS One ; 6(6): e21602, 2011.
Article in English | MEDLINE | ID: mdl-21738728

ABSTRACT

Nucleosome assembly proteins play important roles in chromatin remodeling, which determines gene expression, cell proliferation and terminal differentiation. Testis specific protein, Y-encoded-like 2 (TSPYL2) is a nucleosome assembly protein expressed in neuronal precursors and mature neurons. Previous studies have shown that TSPYL2 binds cyclin B and inhibits cell proliferation in cultured cells suggesting a role in cell cycle regulation. To investigate the physiological significance of TSPYL2 in the control of cell cycle, we generated mice with targeted disruption of Tspyl2. These mutant mice appear grossly normal, have normal life span and do not exhibit increased tumor incidence. To define the role of TSPYL2 in DNA repair, checkpoint arrest and apoptosis, primary embryonic fibroblasts and thymocytes from Tspyl2 deficient mice were isolated and examined under unperturbed and stressed conditions. We show that mutant fibroblasts are impaired in G1 arrest under the situation of DNA damage induced by gamma irradiation. This is mainly attributed to the defective activation of p21 transcription despite proper p53 protein accumulation, suggesting that TSPYL2 is additionally required for p21 induction. TSPYL2 serves a biological role in maintaining the G1 checkpoint under stress condition.


Subject(s)
Cell Cycle Proteins/metabolism , Animals , Apoptosis/genetics , Apoptosis/physiology , Blotting, Northern , Blotting, Western , Cell Cycle/genetics , Cell Cycle/physiology , Cell Cycle Proteins/genetics , Cells, Cultured , DNA Damage/genetics , DNA Damage/physiology , Flow Cytometry , G1 Phase/genetics , G1 Phase/physiology , Immunohistochemistry , Mice , Mice, Knockout
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