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View article: GCN2 enhances host survival and drives eIF2α phosphorylation during mouse adenovirus type 1 infection
GCN2 enhances host survival and drives eIF2α phosphorylation during mouse adenovirus type 1 infection Open
The integrated stress response (ISR) is a cellular signaling pathway that reduces protein synthesis in the face of cellular stress, including viral infection. Two eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and …
View article: Supplementary Figure S4 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Supplementary Figure S4 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
Supplementary Figure S4: (A) NCI-H358-RIT1M90I cells are resistant to divarasib single agent treatment and can be re-sensitized with divarasib and migoprotafib combination both in vitro and in vivo.
View article: Data from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Data from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
RIT1 is a RAS-family guanosine triphosphatase that is mutated in 2.4% and amplified in up to 14% of patients with lung adenocarcinoma. Yet the oncogenic potential of RIT1 in the lungs has not been fully established. Consequently, patients …
View article: Supplementary Figure S1 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Supplementary Figure S1 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
Supplementary Figure S1: RIT1 tumors have heterogenous pERK expression.
View article: Supplementary Table S1 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Supplementary Table S1 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
Supplementary Table S1: Assessment of immunohistochemistry staining intensity on lungs from RIT1 mice. Pathological findings are summarized for all tumors within each animal. Localization of CD3-positive T cells is described. IHC staining …
View article: Supplementary Figure S3 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Supplementary Figure S3 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
Supplementary Figure S3: Human RIT1 cell line, NCI-H2110, is sensitive to migoprotafib, belvarafenib, cobimetinib as single agent and in combination in vitro and in vivo.
View article: Supplementary Figure S2 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy
Supplementary Figure S2 from RIT1<sup>M90I</sup> Is a Driver of Lung Adenocarcinoma Tumorigenesis and Resistance to Targeted Therapy Open
Supplementary Figure S2: Ex vivo RIT1 cell lines have Trp53 genetic knockout and therapeutic vulnerabilities include MAPK/PI3K inhibitors and statins.
View article: Role of mouse adenovirus type 1 E4orf6-induced degradation of protein kinase R in pathogenesis
Role of mouse adenovirus type 1 E4orf6-induced degradation of protein kinase R in pathogenesis Open
Protein kinase R (PKR) is an interferon-induced antiviral protein activated by autophosphorylation in response to double strand DNA (dsRNA) and other stimuli. Activated PKR causes translation inhibition and apoptosis, and it contributes to…
View article: Modulation of <scp>OPC</scp> Mitochondrial Function by Inhibiting <scp>USP30</scp> Promotes Their Differentiation
Modulation of <span>OPC</span> Mitochondrial Function by Inhibiting <span>USP30</span> Promotes Their Differentiation Open
Multiple lines of evidence indicate that mitochondrial dysfunction occurs in demyelinating diseases, such as multiple sclerosis (MS). Failure of remyelination is thought to be caused in part by a block of oligodendrocyte progenitor cell (O…
View article: Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism
Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism Open
INTRODUCTION Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease‐modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to …
View article: Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer’s Disease and Multiple Sclerosis
Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer’s Disease and Multiple Sclerosis Open
Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist ant…
View article: RIT1M90I is a driver of lung adenocarcinoma tumorigenesis and resistance to targeted therapy
RIT1M90I is a driver of lung adenocarcinoma tumorigenesis and resistance to targeted therapy Open
RIT1 is a RAS-family GTPase that is mutated in 2.4% and amplified in up to 14% of lung adenocarcinoma patients. Yet, the oncogenic potential of RIT1 in the lungs is not completely understood. Many patients with RIT1 alterations are conside…
View article: CD2AP impacts Alzheimer’s disease through brain vascular function
CD2AP impacts Alzheimer’s disease through brain vascular function Open
Background Cerebrovascular impairment is a key aspect of Alzheimer’s Disease (AD) pathogenesis. Brain vascular defects appear early in the disease process and are associated with cognitive dysfunction. CD2‐associated protein (CD2AP), a sca…
View article: TMEM106B reduction does not rescue GRN deficiency in iPSC-derived human microglia and mouse models
TMEM106B reduction does not rescue GRN deficiency in iPSC-derived human microglia and mouse models Open
View article: Pkhd1cyli/cyli mice have altered renal Pkhd1 mRNA processing and hormonally sensitive liver disease
Pkhd1cyli/cyli mice have altered renal Pkhd1 mRNA processing and hormonally sensitive liver disease Open
Autosomal-recessive polycystic kidney disease (ARPKD; MIM #263200) is a severe, hereditary, hepato-renal fibrocystic disorder that causes early childhood morbidity and mortality. Mutations in the polycystic kidney and hepatic disease 1 ( P…
View article: TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice
TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice Open
Tumor progression locus 2 (TPL2) (MAP3K8) is a central signaling node in the inflammatory response of peripheral immune cells. We find that TPL2 kinase activity modulates microglial cytokine release and is required for microglia-mediated n…
View article: Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids
Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids Open
Loss-of-function mutations in Nav1.7, a voltage-gated sodium channel, cause congenital insensitivity to pain (CIP) in humans, demonstrating that Nav1.7 is essential for the perception of pain. However, the mechanism by which loss of Nav1.7…
View article: Author response: TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice
Author response: TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice Open
View article: Comment on “Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice”
Comment on “Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice” Open
We highlight potential issues with a Western blot assay using mouse anti–caspase-1 antibody to detect cleaved caspase-1 p20 subunit in mouse brain tissue lysates.
View article: Lipid nanoparticle delivery limits antisense oligonucleotide activity and cellular distribution in the brain after intracerebroventricular injection
Lipid nanoparticle delivery limits antisense oligonucleotide activity and cellular distribution in the brain after intracerebroventricular injection Open
Antisense oligonucleotide (ASO) therapeutics are being investigated for a broad range of neurological diseases. While ASOs have been effective in the clinic, improving productive ASO internalization into target cells remains a key area of …
View article: Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
Supplementary tables
View article: Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
With only a fraction of patients responding to cancer immunotherapy, a better understanding of the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart the fibroblastic landscape during pancreatic ductal ade…
View article: Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
With only a fraction of patients responding to cancer immunotherapy, a better understanding of the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart the fibroblastic landscape during pancreatic ductal ade…
View article: Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
Supplementary tables
View article: Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
Supplementary Figures
View article: Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Supplementary Data from Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15<sup>+</sup> Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy Open
Supplementary Figures
View article: Data from Transcriptional Subtypes Resolve Tumor Heterogeneity and Identify Vulnerabilities to MEK Inhibition in Lung Adenocarcinoma
Data from Transcriptional Subtypes Resolve Tumor Heterogeneity and Identify Vulnerabilities to MEK Inhibition in Lung Adenocarcinoma Open
Purpose:Lung adenocarcinomas comprise the largest fraction of non–small cell lung cancer, which is the leading cause of cancer-related deaths. Seventy-five percent of adenocarcinomas lack targeted therapies because of scarcity of druggable…
View article: Figure S4 from NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes
Figure S4 from NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes Open
Fig. S4, related to Fig. 4.
View article: Figure S1 from NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes
Figure S1 from NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes Open
Fig. S1, related to Figs 1 & 2. Tumor histology across genotypes at 8-16 weeks after Adeno-Cre infection.
View article: Figure S4 from Transcriptional Subtypes Resolve Tumor Heterogeneity and Identify Vulnerabilities to MEK Inhibition in Lung Adenocarcinoma
Figure S4 from Transcriptional Subtypes Resolve Tumor Heterogeneity and Identify Vulnerabilities to MEK Inhibition in Lung Adenocarcinoma Open
Supplemental Figure 4. Prognostic value of STK11 status relative to transcriptional subtype.