April E. Williams
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View article: Targeting CyclinD1-CDK6 to Mitigate Senescence-Driven Inflammation and Age-Associated Functional Decline
Targeting CyclinD1-CDK6 to Mitigate Senescence-Driven Inflammation and Age-Associated Functional Decline Open
Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the Senescence Associated Secretory Phenotype (SASP) and interferon-stimulated genes (ISGs). Cyclin D1 (CCND1), a key cell cycle regu…
View article: Med14 phosphorylation shapes genomic response to GLP-1 Agonist
Med14 phosphorylation shapes genomic response to GLP-1 Agonist Open
Under feeding conditions, release of glucagon-like peptide (GLP-1) from intestinal L cells promotes insulin secretion and pancreatic beta cell viability. Binding of GLP-1 to its cognate receptor on the beta cell surface results in inductio…
View article: A retinoic acid:YAP1 signaling axis controls atrial lineage commitment
A retinoic acid:YAP1 signaling axis controls atrial lineage commitment Open
In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is no…
View article: A single valine to leucine switch disrupts <i>Plasmodium falciparum</i> AP2-G DNA binding and reveals GDV1’s role in <i>ap2-g</i> activation
A single valine to leucine switch disrupts <i>Plasmodium falciparum</i> AP2-G DNA binding and reveals GDV1’s role in <i>ap2-g</i> activation Open
Sexual commitment in Plasmodium parasites is essential for malaria transmission, yet much remains unknown about the underlying signaling events initiating sexual conversion in a subpopulation of parasites. We discovered a single valine (V …
View article: Lateral habenula astroglia modulate the potentiating antidepressant-like effects of bright light stimulation in intractable depression
Lateral habenula astroglia modulate the potentiating antidepressant-like effects of bright light stimulation in intractable depression Open
Background Beside image vision, light plays a pivotal role in regulating diverse non-visual functions, including affective behaviors. Recently, bright light stimulation (BLS) was revealed to be beneficial for treating non-seasonal depressi…
View article: Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer
Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer Open
Age is a major risk factor for liver cancer, as is the case for most adult human cancers. However, the underlying mechanisms are not well defined. A better understanding of the role of aging in liver and other cancers can facilitate approa…
View article: PCBS: an R package for fast and accurate analysis of bisulfite sequencing data
PCBS: an R package for fast and accurate analysis of bisulfite sequencing data Open
Motivation Whole-genome bisulfite sequencing is a powerful tool for analyzing chromatin methylation genome-wide, but analysis of whole-genome bisulfite data is slow, inflexible, and often inaccurate. Results We developed PCBS (Principal Co…
View article: Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer
Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer Open
Age is a major risk factor for liver cancer, as is the case for most adult human cancers. However, the underlying mechanisms are not well defined. A better understanding of the role of aging in liver and other cancers can facilitate approa…
View article: A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment
A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment Open
Vitamin A/Retinoic Acid (Vit A/RA) signaling is essential for heart development. In cardiac progenitor cells (CPCs), RA signaling induces the expression of atrial lineage genes while repressing ventricular genes, thereby promoting the acqu…
View article: PCBS: an R package for fast and accurate analysis of bisulfite sequencing data
PCBS: an R package for fast and accurate analysis of bisulfite sequencing data Open
Motivation Whole-genome bisulfite sequencing is a powerful tool for analyzing chromatin methylation genome-wide, but analysis of whole-genome bisulfite data is hampered by slow, inaccurate, and inflexible pipelines. Results We developed PC…
View article: NGLY1 mutations cause protein aggregation in human neurons
NGLY1 mutations cause protein aggregation in human neurons Open
Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1's activity in human …
View article: Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC Open
Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK fa…
View article: Supplementary Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Supplementary Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC Open
Supplemental Data
View article: Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC Open
Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK fa…
View article: Supplementary Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Supplementary Data from The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC Open
Supplemental Data
View article: Age-dependent roles of cardiac remodeling in sepsis defense and pathogenesis
Age-dependent roles of cardiac remodeling in sepsis defense and pathogenesis Open
Summary Disease tolerance is a defense strategy essential for survival of infections, limiting physiological damage without killing the pathogen. The disease course and pathology a pathogen may cause can change over the lifespan of a host …
View article: Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis
Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis Open
Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis—an autophagy-dependent program th…
View article: Atlas-Guided Discovery of Transcription Factors for T Cell Programming
Atlas-Guided Discovery of Transcription Factors for T Cell Programming Open
CD8 + T cells differentiate into diverse states that shape immune outcomes in cancer and chronic infection 1–4 . To systematically define the transcription factors (TFs) driving these states, we built a comprehensive atlas integrating tran…
View article: Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals Open
Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of feeding and fasting. In both animals and humans, TRF has pleiotropic health benefits that arise from multiple organ systems, yet …
View article: Time–restricted eating alters the 24‐hour profile of adipose tissue transcriptome in men with obesity
Time–restricted eating alters the 24‐hour profile of adipose tissue transcriptome in men with obesity Open
Objective Time‐restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24‐hour profiles of plasma metabolites, …
View article: Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies
Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies Open
Sprague Dawley ( SD ) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at explor…
View article: Astroglia in lateral habenula is essential for antidepressant efficacy of light
Astroglia in lateral habenula is essential for antidepressant efficacy of light Open
Successful antidepressant (AD) treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate here, using a new mous…
View article: Polymorphic SNPs, short tandem repeats and structural variants are responsible for differential gene expression across C57BL/6 and C57BL/10 substrains
Polymorphic SNPs, short tandem repeats and structural variants are responsible for differential gene expression across C57BL/6 and C57BL/10 substrains Open
Summary Mouse substrains are an invaluable model for understanding disease. We compared C57BL/6J, which is the most commonly used inbred mouse strain, with 8 C57BL/6 and 5 C57BL/10 closely related inbred substrains. Whole genome sequencing…
View article: Clinical reconciliation of patient social context and implementation of preventive care guidelines
Clinical reconciliation of patient social context and implementation of preventive care guidelines Open
Background Preventive care practice guidelines are disseminated regularly through federal and scientific groups as a way of promoting best practices and evidence-based health promotion. Yet rates of their implementation are historically lo…
View article: The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC Open
Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK fa…