Activation of PKR by a short-hairpin RNA.

Recognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54's potential to activate PKR, a key player in the immune response to dsRNA.

Induction of Viral Mimicry Upon Loss of DHX9 and ADAR1 in Breast Cancer Cells.

Unlabelled: Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The IFN-inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for adenosine deaminase acting on RNA 1 (ADAR1) in many cancers, including breast.

Assessment of Ground Contact Time in the Field: Evaluation of Validity and Reliability.

Weber, JA, Hart, NH, Rantalainen, T, Connick, M, and Newton, RU. Assessment of ground contact time in the field: evaluation of validity and reliability. J Strength Cond Res 38(1): e34-e39, 2024-The capacity to measure the kinetic and kinematic components of running has been extensively investigated in laboratory settings.

Induction of viral mimicry upon loss of DHX9 and ADAR1 in breast cancer cells.

Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The interferon inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for ADAR1 in many cancers, including breast.

8-azaadenosine and 8-chloroadenosine are not selective inhibitors of ADAR.

The RNA editing enzyme ADAR, is an attractive therapeutic target for multiple cancers. Through its deaminase activity, ADAR edits adenosine to inosine in dsRNAs. Loss of ADAR in some cancer cell lines causes activation of the type I interferon pathway and the PKR translational repressor, leading to inhibition of proliferation and stimulation of cell death.

It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.

Anti-tumorigenic mechanisms mediated by the tumor suppressor p53, upon oncogenic stresses, are our bodies' greatest weapons to battle against cancer onset and development. Consequently, factors that possess significant p53-regulating activities have been subjects of serious interest from the cancer research community. Among them, MDM2 and ARF are considered the most influential p53 regulators due to their abilities to inhibit and activate p53 functions, respectively.

Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer.

Importance: To our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American and non-Hispanic White women with triple-negative breast cancer (TNBC). Little is known about whether racial disparities vary by sociodemographic, clinical, and neighborhood factors.

Objective: To examine the differences in clinical treatment and outcomes between African American and White women in a nationally representative cohort of patients with TNBC and further examine the contributions of sociodemographic, clinical, and neighborhood factors to TNBC outcome disparities.

Upregulation of 5'-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor.

Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown.

Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of endogenous double-stranded RNAs.

Relationship Between Mechanical Effectiveness in Sprint Running and Force-Velocity Characteristics of a Countermovement Jump in Australian Rules Football Athletes.

Morris, CG, Weber, JA, and Netto, KJ. Relationship between mechanical effectiveness in sprint running and force-velocity characteristics of a countermovement jump in Australian rules football athletes. J Strength Cond Res 36(3): e59-e65, 2022-This study evaluated the mechanical determinants of 40-m sprint performance in elite Australian Rules Football (ARF) athletes and identified variables of countermovement jumps (CMJs) that related to the sprint.

Associations of race and ethnicity with risk of developing invasive breast cancer after lobular carcinoma in situ.

Background: Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS.

Methods: We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015.

DHX33 Interacts with AP-2β To Regulate Gene Expression and Promote Cancer Cell Survival.

The RNA helicase DHX33 has been found to be overexpressed in human cancers, where it promotes cancer development. Previous reports have shown that DHX33 deficiency caused cancer cell apoptosis, but the underlying mechanism remains unknown. In this study, we discovered that DHX33 regulates Bcl-2 family protein expression.

Race and risk of subsequent aggressive breast cancer following ductal carcinoma in situ.

Background: General populations of black women have a higher risk of developing breast cancer negative for both estrogen receptor (ER) and progesterone receptor (PR) in comparison with white counterparts. Racial differences remain unknown in the risk of developing aggressive invasive breast cancer (IBC) that is characterized by negativity for both ER and PR (ER-PR-) or higher 21-gene recurrence scores after ductal carcinoma in situ (DCIS).

Methods: This study identified 163,892 women (10.

Assessment of a Novel Algorithm to Determine Change-of-Direction Angles While Running Using Inertial Sensors.

Balloch, AS, Meghji, M, Newton, RU, Hart, NH, Weber, JA, Ahmad, I, and Habibi, D. Assessment of a novel algorithm to determine change-of-direction angles while running using inertial sensors. J Strength Cond Res 34(1): 134-144, 2020-The ability to detect and quantify change-of-direction (COD) movement may offer a unique approach to load-monitoring practice.

Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation.

Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion.

The Role of RNA Editing in Cancer Development and Metabolic Disorders.

Numerous human diseases arise from alterations of genetic information, most notably DNA mutations. Thought to be merely the intermediate between DNA and protein, changes in RNA sequence were an afterthought until the discovery of RNA editing 30 years ago. RNA editing alters RNA sequence without altering the sequence or integrity of genomic DNA.

Functional Basis of Asymmetrical Lower-Body Skeletal Morphology in Professional Australian Rules Footballers.

Hart, NH, Newton, RU, Weber, J, Spiteri, T, Rantalainen, T, Dobbin, M, Chivers, P, and Nimphius, S. Functional basis of asymmetrical lower-body skeletal morphology in elite Australian footballers. J Strength Cond Res 34(3): 791-799, 2020-Bone strength is a product of its material and structural properties and is highly responsive to mechanical load.

Sabotaging of the oxidative stress response by an oncogenic noncoding RNA.

Overexpression of the multiple myeloma set domain (MMSET) Wolf-Hirschhorn syndrome candidate 1 gene, which contains an orphan box H/ACA class small nucleolar RNA, ACA11, in an intron, is associated with several cancer types, including multiple myeloma (MM). ACA11 and MMSET are overexpressed cotranscriptionally as a result of the t(4;14) chromosomal translocation in a subset of patients with MM. RNA sequencing of CD138 tumor cells from t(4;14)-positive and -negative MM patient bone marrow samples revealed an enhanced oxidative phosphorylation mRNA signature.

DHX33 Transcriptionally Controls Genes Involved in the Cell Cycle.

The RNA helicase DHX33 has been shown to be a critical regulator of cell proliferation and growth. However, the underlying mechanisms behind DHX33 function remain incompletely understood. We present original evidence in multiple cell lines that DHX33 transcriptionally controls the expression of genes involved in the cell cycle, notably cyclin, E2F1, cell division cycle (CDC), and minichromosome maintenance (MCM) genes.