Self-regulatory problems mediate the association of contextual stressors and unprotected intercourse among rural, African American, young adult men.

In this brief report, the hypothesis that self-regulatory problems would mediate the association between contextual stressors and unprotected intercourse among rural African American young adult men was investigated. Family support and religiosity were hypothesized to ameliorate the influence of contextual stressors on self-regulatory problems. Hypotheses were tested on 79 sexually active men from a sample recruited with Respondent Driven Sampling; episodes of unprotected intercourse constituted the criterion variable.

Linking parenting and informal mentor processes to depressive symptoms among rural African American young adult men.

Little is known about the rates of depressive symptoms among rural African American men during young adulthood or the processes that predict those rates. Many rural African American men in the deep South confront difficult environments that provide minimal resources and diminishing social support to help them embark on beneficial life paths. A model of protective processes hypothesized to deter depression among this population was tested that included autonomy-promoting parenting, informal mentoring, and protective self-regulatory processes.

p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal.

The p53 tumor suppressor limits proliferation in response to cellular stress through several mechanisms. Here, we test whether the recently described ability of p53 to limit stem cell self-renewal suppresses tumorigenesis in acute myeloid leukemia (AML), an aggressive cancer in which p53 mutations are associated with drug resistance and adverse outcome. Our approach combined mosaic mouse models, Cre-lox technology, and in vivo RNAi to disable p53 and simultaneously activate endogenous Kras(G12D)-a common AML lesion that promotes proliferation but not self-renewal.

A cascade model connecting life stress to risk behavior among rural African American emerging adults.

A three-wave cascade model linking life stress to increases in risk behavior was tested with 347 African American emerging adults living in the rural South. Data analyses using structural equation modeling and latent growth curve modeling demonstrated that life stress was linked to increases in risk behavior as African Americans transitioned out of secondary school. The cascade model indicated that life stress fostered increases in negative emotions.

Long-term effects of the strong African American families program on youths' alcohol use.

Objective: This report extends earlier accounts by addressing the effects of the Strong African American Families (SAAF) program across 65 months. Two hypotheses were tested: (a) Rural African American youths randomly assigned to participate in SAAF would demonstrate lower rates of alcohol use than would control youths more than 5 years later, and (b) SAAF's effects on deterring the onset of alcohol use in early adolescence would carry forward to mediate the program's long-term effects.

Method: African American youths in rural Georgia (mean age at pretest = 10.

Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies.

Monosomy 7 and del(7q) are associated with adverse features in myeloid malignancies. A 2.5-Mb commonly deleted segment (CDS) of chromosome band 7q22 is implicated as harboring a myeloid tumor suppressor gene (TSG); however, molecular analysis of candidate TSGs has not uncovered loss of function.

Mutant Ikzf1, KrasG12D, and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents.

Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in Mx1-Cre, Kras(G12D) mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within Ikzf1 is an early event in leukemogenesis that precedes Kras(G12D) expression and later acquisition of somatic Notch1 mutations.

Depressive symptomatology mediates the effect of socioeconomic disadvantage on HbA(1c) among rural African Americans with type 2 diabetes.

Objective: Rural African Americans with diabetes mellitus type 2 (T2D) represent a disadvantaged and understudied group who experience difficulties with maintaining glycemic control. Although mounting evidence has linked socioeconomic disadvantage to chronic disease morbidity, few studies have examined the mediating mechanisms that account for this effect. We hypothesized that rural African Americans' financial distress, community disadvantage, and educational attainment would predict glycemic control, indirectly, via effects on depressive symptoms.

Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras.

The cascade comprising Raf, mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) is a therapeutic target in human cancers with deregulated Ras signalling, which includes tumours that have inactivated the Nf1 tumour suppressor. Nf1 encodes neurofibromin, a GTPase-activating protein that terminates Ras signalling by stimulating hydrolysis of Ras-GTP. We compared the effects of inhibitors of MEK in a myeloproliferative disorder (MPD) initiated by inactivating Nf1 in mouse bone marrow and in acute myeloid leukaemias (AMLs) in which cooperating mutations were induced by retroviral insertional mutagenesis.

Participation in a family-centered prevention program decreases genetic risk for adolescents' risky behaviors.

Objective: The present research addressed the following important question in pediatric medicine: can participation in an efficacious preventive intervention ameliorate the risk that a genetic vulnerability factor is hypothesized to confer on increases in risk behaviors across preadolescence?

Methods: As part of the Strong African American Families preventive intervention study, data were collected from 641 black families in rural Georgia, assigned randomly to the prevention or control condition. The prevention condition consisted of 7 consecutive meetings at community facilities, with separate parent and youth skill-building curricula and a family curriculum. Each meeting included separate, concurrent sessions for parents and youths, followed by a joint parent-youth session in which families practiced skills they learned in the separate sessions.

Mouse models of human AML accurately predict chemotherapy response.

The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience.

Change in caregiver depression in response to parent training: genetic moderation of intervention effects.

A previous report in the Journal of Family Psychology (S. R. H.

Curing APL: differentiation or destruction?

In a recent issue of Nature Medicine, Nasr et al. show that the effectiveness of all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia is independent of their ability to cause differentiation. Targeted destruction of the PML-RARalpha oncoprotein appears key to eliminating the cells from which relapse can arise.

Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family.

Individual members of the retinoblastoma (Rb) tumor suppressor gene family serve critical roles in the control of cellular proliferation and differentiation, but the extent of their contributions is masked by redundant and compensatory mechanisms. Here we employed a conditional knockout strategy to simultaneously inactivate all three members, Rb, p107, and p130, in adult hematopoietic stem cells (HSCs). Rb family triple knockout (TKO) mice develop a cell-intrinsic myeloproliferation that originates from hyperproliferative early hematopoietic progenitors and is accompanied by increased apoptosis in lymphoid progenitor populations.

Long-term effects of the strong African American families program on youths' conduct problems.

Purpose: The Strong African American Families program, a universal intervention to deter alcohol use among rural African American preadolescents, was evaluated to determine whether it also prevented conduct problems across the 29 months separating the pretest and long-term follow-up assessments. The program is based on a contextual model in which intervention effects on parental behavior and youth protective factors are hypothesized to lead to behavior changes.

Methods: African American 11-year-olds (N = 667) and their primary caregivers were randomly selected from public school lists of fifth-grade students and randomly assigned to an intervention (n = 369) or control (n = 298) condition.

The Influence of Role Status on Risky Sexual Behavior Among African Americans During the Transition to Adulthood.

Little research has examined the links between role status changes during the transition to adulthood and sexual behaviors that place African Americans at risk for sexually transmitted infections. Moreover, the mediating processes that explain these links, or protective factors that may buffer young adults from risky sexual behavior, are unknown. African American young adults who had either completed or dropped out of high school (ages 18 to 21, N = 186) provided information regarding their sexual behavior, role status, substance use, peer affiliations, religiosity, and receipt of protective family processes.

mTORC1 promotes survival through translational control of Mcl-1.

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a frequent occurrence in human cancers and a major promoter of chemotherapeutic resistance. Inhibition of one downstream target in this pathway, mTORC1, has shown potential to improve chemosensitivity. However, the mechanisms and genetic modifications that confer sensitivity to mTORC1 inhibitors remain unclear.

Epigenetic nucleosomes: Alu sequences and CG as nucleosome positioning element.

Alu sequences carry periodical pattern with CG dinucleotides (CpG) repeating every 31-32 bases. Similar distances are observed in distribution of DNA curvature in crystallized nucleosomes, at positions +/-1.5 and +/-4.

Integrins in prostate cancer progression.

Integrins, which are transmembrane receptors for extracellular matrix proteins, play a key role in cell survival, proliferation, migration, gene expression, and activation of growth factor receptors. Their functions and expression are deregulated in several types of cancer, including prostate cancer. In this article, we review the role of integrins in prostate cancer progression and their potential as therapeutic targets.

Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure.

O(6)-methylguanine DNA methyltransferase (MGMT) deficiency is associated with an increased susceptibility to alkylating agent toxicity. To understand the contribution of MGMT in protecting against cyclophosphamide (CP)-induced toxicity, mutagenesis and tumorigenesis, we compared the biological effects of this agent in transgenic Mgmt knockout and wild-type mice. In addition, neurofibromin (Nf1)+/- background was used to increase the likelihood of CP-induced tumorigenesis.

The protective effect of KCNMB1 E65K against hypertension is restricted to blood pressure treatment with beta-blockade.

Genetic polymorphisms that influence smooth muscle cell contraction and relaxation may affect the response to anti-hypertensive therapy. Our finding of lower blood pressure (BP) in the setting of treatment for hypertension, particularly with beta-blockade, in Caucasian --carriers in two community cohorts has implications for personalization of therapy in hypertension.

Change in caregiver depression as a function of the Strong African American Families Program.

A randomized prevention trial contrasted families who participated in the Strong African American Families Program (SAAF), a preventive intervention for rural African American parents and their 11-year-olds, with control families. This article focuses on the program's effect on primary caregivers' depressive symptoms. Among the 167 caregivers with elevated scores on the Center for Epidemiologic Studies-Depression Scale, SAAF participation was associated with reduced depressive symptoms, enhanced parenting, and perceived improvements in youth behavior.

Psychological functioning, support for self-management, and glycemic control among rural African American adults with diabetes mellitus type 2.

Objective: To test a contextual-ecological model of factors relevant for glycemic control in an understudied and vulnerable population of persons with diabetes mellitus Type 2.

Design: Rural African American adults (40-65 years old, n = 200) with Type 2 diabetes and 200 adult support persons whom the adults with diabetes nominated were interviewed in their homes. Adults with diabetes and support persons reported their own psychological functioning, which included depressive symptoms, self-esteem levels, and optimism levels as well as the quality of their relationship with one another.

BCL-2 and mutant NRAS interact physically and functionally in a mouse model of progressive myelodysplasia.

Myelodysplastic syndromes (MDS) are clonal stem cell hematologic disorders that evolve to acute myeloid leukemia (AML) and thus model multistep leukemogenesis. Activating RAS mutations and overexpression of BCL-2 are prognostic features of MDS/AML transformation. Using NRASD12 and BCL-2, we created two distinct models of MDS and AML, where human (h)BCL-2 is conditionally or constitutively expressed.