RESUMEN
Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.
Asunto(s)
COVID-19 , Dengue , Complejo IV de Transporte de Electrones , Infección por el Virus Zika , Humanos , Alelos , COVID-19/genética , ADN Mitocondrial/metabolismo , Complejo IV de Transporte de Electrones/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Células Madre Pluripotentes Inducidas/metabolismo , Interferón Tipo I/metabolismo , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Virus Zika , Infección por el Virus Zika/genética , Dengue/genéticaRESUMEN
Three hundred and seventy-four rhizobacteria were isolated from the rhizosphere soil (RS) or rhizoplane (RP) of Echinochloa crus-galli, Carex leiorhyncha, Commelina communis, Persicaria lapathifolia, Carex kobomugi, and Equisetum arvense, grown in contaminated soil with petroleum and heavy metals. The isolates were screened for plant growth-promoting potential (PGPP), including indole acetic acid (IAA) productivity, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and siderophore(s) synthesis ability. IAA production was detected in 86 isolates (23.0%), ACC deaminase activity in 168 isolates (44.9%), and siderophore(s) synthesis in 213 isolates (57.0%). Among the rhizobateria showing PGPP, 162 rhizobacteria had multiple traits showing more than two types of PGPP. The PGPP-having rhizobateria were more abundant in the RP (82%) samples than the RS (75%). There was a negative correlation (-0.656, p < 0.05) between the IAA-producers and the ACC deaminase producers. Clustering analysis by principal component analysis showed that RP was the most important factor influencing ecological distribution and physiological characterization of PGPP-possesing rhizobateria.
Asunto(s)
Liasas de Carbono-Carbono/metabolismo , Ácidos Indolacéticos/metabolismo , Rhizobium/metabolismo , Sideróforos/biosíntesis , Microbiología del Suelo , Contaminantes del Suelo/aislamiento & purificación , Liasas de Carbono-Carbono/análisis , Ácidos Indolacéticos/análisis , Análisis de Componente Principal , Sideróforos/análisis , Contaminantes del Suelo/químicaRESUMEN
The role of plant growth-promoting rhizobacteria (PGPR) in the phytoremediation of heavy-metal-contaminated soils is important in overcoming its limitations for field application. A plant growth-promoting rhizobacterium, Serratia sp. SY5, was isolated from the rhizoplane of barnyard grass (Echinochloa crus-galli) grown in petroleum and heavy-metal-contaminated soil. This isolate has shown capacities for indole acetic acid production and siderophores synthesis. Compared with a non-inoculated control, the radicular root growth of Zea mays seedlings inoculated with SY5 can be increased by 27- or 15.4-fold in the presence of 15 mg-Cd/l or 15 mg-Cu/l, respectively. The results from hydroponic cultures showed that inoculation of Serratia sp. SY5 had a favorable influence on the initial shoot growth and biomass of Zea mays under noncontaminated conditions. However, under Cd-contaminated conditions, the inoculation of SY5 significantly increased the root biomass of Zea mays. These results indicate that Serratia sp. SY5 can serve as a promising microbial inoculant for increased plant growth in heavy-metal-contaminated soils to improve the phytoremediation efficiency.
Asunto(s)
Serratia , Zea mays , Biodegradación Ambiental , Biomasa , Cadmio/química , Cadmio/metabolismo , Echinochloa/microbiología , Hidroponía , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/microbiología , Serratia/aislamiento & purificación , Serratia/fisiología , Sideróforos/biosíntesis , Microbiología del Suelo , Contaminantes del Suelo/química , Zea mays/crecimiento & desarrollo , Zea mays/microbiologíaRESUMEN
Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine formation both in vitro and in vivo. However, whether Fyn's regulation of dendritic spine formation is brain-region specific and age-dependent is unknown. In the present study, we systematically examined whether Fyn altered dendritic spine density and morphology in the cortex and hippocampus and if these effects were age-dependent. We found that Fyn knockout mice trended toward a decrease in dendritic spine density in cortical layers II/III, but not in the hippocampus, at 1 month of age. Additionally, Fyn knockout mice had significantly decreased dendritic spine density in both the cortex and hippocampus at 3 months and 1 year, and Fyn's effect on dendritic spine density was age-dependent in the hippocampus. Moreover, Fyn knockout mice had wider spines at the three time points (1 month, 3 months, 1 year) in the cortex. These findings suggest that Fyn regulates dendritic spine number and morphology over time and provide further support for Fyn's role in maintaining proper synaptic function in vivo.