Spotlight on New Therapeutic Opportunities for MYC-Driven Cancers.

MYC can be considered to be one of the most pressing and important targets for the development of novel anti-cancer therapies. This is due to its frequent dysregulation in tumors and due to the wide-ranging impact this dysregulation has on gene expression and cellular behavior. As a result, there have been numerous attempts to target MYC over the last few decades, both directly and indirectly, with mixed results.

Awareness of peers in recovery and of a campus collegiate recovery community at a university in the southeastern United States.

Little is known about the extent of student awareness about collegiate recovery communities (CRCs) and of peers in recovery. A convenience sample of 237 undergraduate students from a diverse major at a private university participated in an anonymous online survey in Fall 2019. Participants reported whether they knew about the local CRC, whether they knew a peer in recovery, sociodemographic characteristics, and other information.

Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells.

Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown.

The hepatic compensatory response to elevated systemic sulfide promotes diabetes.

Impaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production or sulfide donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range.

Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.

Infant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse.

Spatiofunctional Dynamics of NKX3.1 to Safeguard the Prostate from Cancer.

A novel role of NKX3.1 in the mitochondria regulating the transcription of the electron transport chain components is reported. Mechanistically, HSPA9 chaperones NKX3.

De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands.

The aberrant gain of DNA methylation at CpG islands is frequently observed in colorectal tumours and may silence the expression of tumour suppressors such as MLH1. Current models propose that these CpG islands are targeted by de novo DNA methyltransferases in a sequence-specific manner, but this has not been tested. Using ectopically integrated CpG islands, here we find that aberrantly methylated CpG islands are subject to low levels of de novo DNA methylation activity in colorectal cancer cells.

Recovery and Youth: An Integrative Review.

Although rates of alcohol and other substance use disorders in adolescents have been estimated for decades, little is known about the prevalence, pathways, and predictors of remission and long-term recovery among adolescents. This article provides an integrative review of the literature on youth recovery. A final selection of 39 relevant articles was grouped into five sections: treatment outcomes, special emphasis populations, recovery-oriented systems of care, families, and non-abstinence-based approaches.

The Biosynthesis of Enzymatically Oxidized Lipids.

Enzymatically oxidized lipids are a specific group of biomolecules that function as key signaling mediators and hormones, regulating various cellular and physiological processes from metabolism and cell death to inflammation and the immune response. They are broadly categorized as either polyunsaturated fatty acid (PUFA) containing (free acid oxygenated PUFA "oxylipins", endocannabinoids, oxidized phospholipids) or cholesterol derivatives (oxysterols, steroid hormones, and bile acids). Their biosynthesis is accomplished by families of enzymes that include lipoxygenases (LOX), cyclooxygenases (COX), cytochrome P450s (CYP), and aldo-keto reductases (AKR).

Recovery High School Attendance Effects on Student Delinquency and Substance Use: the Moderating Role of Social Problem Solving Styles.

Recovery high schools (RHSs) provide educational programming and therapeutic support services for young people in recovery from substance use disorders (SUDs). The objectives of this study were to examine whether students with SUDs who attended RHSs report less delinquency and substance use than students with SUDs who attended non-RHSs, and how students' social problem solving styles might moderate those associations. Participants were students from a longitudinal quasi-experimental study of adolescents who enrolled in high schools after receiving treatment for SUDs.

Net Benefits of Recovery High Schools: Higher Cost but Increased Sobriety and Educational Attainment.

Background: Recovery high schools (RHS) provide a supportive educational and therapeutic environment for students subsequent to treatment for substance use disorders (SUDs). Most students served by RHSs have concurrent mental health disorders and are at risk for school failure or dropout and substance use relapse.

Aims Of The Study: The central question addressed is whether RHSs are economically efficient alternatives to other high school settings for students in recovery.

Adolescent recovery capital and recovery high school attendance: An exploratory data mining approach.

Recovery high schools (RHSs) provide a recovery-supportive academic environment for adolescents in recovery from a substance use disorder and are located across the United States. However, only a small proportion of the 160,000 youth in recovery each year in the United States enroll in RHSs posttreatment, indicating that many youth do not access this relapse prevention resource despite its effectiveness. Thus, this study uses the adolescent-adapted recovery capital model (RCAM) to understand individual- and community-level predictors of attendance and identify disparities leading to barriers to accessing RHSs.

The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype.

Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21, p16, and p15 and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS.

Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence.

Cellular senescence is triggered by diverse stimuli and is characterized by long-term growth arrest and secretion of cytokines and chemokines (termed the SASP-senescence-associated secretory phenotype). Senescence can be organismally beneficial as it can prevent the propagation of damaged or mutated clones and stimulate their clearance by immune cells. However, it has recently become clear that senescence also contributes to the pathophysiology of aging through the accumulation of damaged cells within tissues.

The long non-coding RNA is a post transcriptional regulator of mitochondrial complex I catalytic activity.

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that , an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p.

Effects of Recovery High School Attendance on Students' Mental Health Symptoms.

Recovery high schools are one form of continuing care support for adolescents with substance use or other co-occurring disorders. Using a controlled quasi-experimental design, we compared mental health symptom outcomes at 6 months for adolescents who attended recovery high schools vs. non-recovery high schools (e.

ITPase deficiency causes a Martsolf-like syndrome with a lethal infantile dilated cardiomyopathy.

Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated "mutation negative" probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase). Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy.

Recovery schools for improving behavioral and academic outcomes among students in recovery from substance use disorders: a systematic review.

Unlabelled: This Campbell systematic review examines the effects of recovery schools on student behavioral and academic outcomes, compared to the effects of non-recovery schools. The review summarizes evidence from one quasi-experimental study (with a total of 194 participants) that had potential serious risk of bias due to confounding. Sizable portions of youth are in recovery from substance use disorders, and many youth will return to use after receiving substance use treatment.

Catapulting HSCs into action.

In this issue of , Umemoto et al. (https://doi.org/10.

Who attends recovery high schools after substance use treatment? A descriptive analysis of school aged youth.

Recovery high schools (RHSs) are an alternative high school option for adolescents with substance use disorders (SUDs), designed to provide a recovery-focused learning environment. The aims of this study were to examine the characteristics of youth who choose to attend RHSs, and to compare them with local and national comparison samples of youth in recovery from SUDs who were not enrolled in RHSs. We conducted secondary analysis of existing data to compare characteristics of youth in three samples: (1) adolescents with SUDs who enrolled in RHSs in Minnesota, Texas, and Wisconsin after discharge from treatment (RHSs; n = 171, 51% male, 86% White, 4% African American, 5% Hispanic); (2) a contemporaneously recruited local comparison sample of students with SUDs who did not enroll in RHSs (n = 123, 60% male, 77% White, 5% African American, 12% Hispanic); and (3) a national comparison sample of U.

'Pickle or a cucumber?' administrator and practitioner views of successful adolescent recovery.

Introduction: Adolescent substance use disorders often involve a recurring cycle of treatment and relapse. The academic and practical definition of for adults has been debated; yet, elements determining a successful adolescent recovery aside from abstinence have not been delineated. Thus, we sought to explore how practitioners and administrators define "success" in recovery and how they foster youth progress towards success.