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Article
Open AccessThe single-cell opioid responses in the context of HIV (SCORCH) consortium
Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of th...
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Article
Redox regulation of m6A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes
Type 1 diabetes (T1D) is characterized by the destruction of pancreatic β-cells. Several observations have renewed the interest in β-cell RNA sensors and editors. Here, we report that N6-methyladenosine (m6A) is ...
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Article
Open AccessHIV reprograms host m6Am RNA methylome by viral Vpr protein-mediated degradation of PCIF1
N6,2′-O-dimethyladenosine (m6Am) is an abundant RNA modification located adjacent to the 5′-end of the mRNA 7-methylguanosine (m7G) cap structure. m6A methylation on 2′-O-methylated A at the 5′-ends of mRNAs is c...
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Article
Cellular diversity of human cerebral organoids revealed by single cell RNA-seq
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Article
Open AccessGlial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids
Methamphetamine (METH) is a potent stimulant that induces a euphoric state but also causes cognitive impairment, neurotoxicity and neurodevelopmental deficits. Yet, the molecular mechanisms by which METH cause...
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Article
Open AccessOptimizing sequencing protocols for leaderboard metagenomics by combining long and short reads
As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewe...
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Protocol
Profiling of N6-Methyladenosine in Zika Virus RNA and Host Cellular mRNA
N6-Methylation of adenosine (m6A) in viral RNA was first identified in Rous sarcoma virus, influenza virus, and SV40 virus several decades ago. More recently, human immunodeficiency virus-1, hepatitis C virus, an...
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Article
Open AccessLipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply
Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) ...
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Protocol
Next-Generation Sequencing of Genome-Wide CRISPR Screens
Genome-wide functional genomic screens utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system have proven to be a powerful tool for systematic genomic perturbation in mamm...
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Article
Open AccessPolycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity
The polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6...
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Article
Dynamics of the human and viral m6A RNA methylomes during HIV-1 infection of T cells
N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA. Very little is known of the function of m6A in the immune system or its role in host–pathogen interactions. Here, we invest...
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Protocol
Enhancing Induced Pluripotent Stem Cell Generation by MicroRNA
Somatic reprogramming to generate induced pluripotent stem cells, or iPSC, is a powerful tool in developmental biology, disease modeling, and regenerative medicine. microRNAs have been shown to regulate many k...
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Article
Therapeutic targeting of microRNAs: current status and future challenges
MicroRNAs (miRNAs) have important roles in many aspects of human diseases, and their targeted inhibition may have substantial therapeutic impact.
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Article
Open AccessStaged miRNA re-regulation patterns during reprogramming
MiRNAs often operate in feedback loops with transcription factors and represent a key mechanism for fine-tuning gene expression. In transcription factor-induced reprogramming, miRNAs play a critical role; howe...
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Chapter
Dysregulation of Long Non-coding RNAs in Human Disease
The mammalian genome is composed of thousands of long non-coding RNAs (lncRNAs). Accumulating evidence suggests that lncRNAs play diverse biological roles through a variety of molecular mechanisms including ep...
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Article
Open AccessA kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation
Somatic cells can be reprogrammed to form embryonic stem cell-like induced pluripotent stem cells (iPSCs), but the process suffers from low efficiency and the underlying molecular mechanisms that control repro...
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Chapter
Structure and Gene-Silencing Mechanisms of Small Noncoding RNAs
Small (19–31-nucleotides) noncoding RNAs were identified in the past 10 years for their distinct function in gene silencing. The best known gene-silencing phenomenon, RNA interference (RNAi), is triggered in a...
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Article
Small-molecule inhibition of HIV-1 Vif
The HIV-1 protein Vif, which promotes degradation of the host cell's antiviral APOBEC3 proteins, has yet to be targeted for therapeutic intervention. Nathans et al. use a high-throughput fluorescence screen to id...
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Article
Illuminating the silence: understanding the structure and function of small RNAs
RNA interference (RNAi) is an ancient and evolutionarily conserved gene-silencing mechanism that is triggered by double-stranded (ds)RNA. dsRNA, which is produ...
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Article
Target accessibility dictates the potency of human RISC
In this report, we examined the effect of increased target site access on activated human RNA-induced silencing complex (RISC*) catalysis. Kinetic studies revealed that siRNA-programmed RISC* cleaved target RNA w...
