55 research outputs found
Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium
<p>Abstract</p> <p>Background</p> <p><it>Msx1 </it>and <it>Msx2</it>, which belong to the highly conserved <it>Nk </it>family of homeobox genes, display overlapping expression patterns and redundant functions in multiple tissues and organs during vertebrate development. <it>Msx1 </it>and <it>Msx2 </it>have well-documented roles in mediating epithelial-mesenchymal interactions during organogenesis. Given that both <it>Msx1 </it>and <it>Msx2 </it>are crucial downstream effectors of Bmp signaling, we investigated whether <it>Msx1 </it>and <it>Msx2 </it>are required for the Bmp-induced endothelial-mesenchymal transformation (EMT) during atrioventricular (AV) valve formation.</p> <p>Results</p> <p>While both <it>Msx1-/- </it>and <it>Msx2-/- </it>single homozygous mutant mice exhibited normal valve formation, we observed hypoplastic AV cushions and malformed AV valves in <it>Msx1-/-; Msx2-/- </it>mutants, indicating redundant functions of <it>Msx1 </it>and <it>Msx2 </it>during AV valve morphogenesis. In <it>Msx1/2 </it>null mutant AV cushions, we found decreased Bmp2/4 and <it>Notch1 </it>signaling as well as reduced expression of <it>Has2</it>, <it>NFATc1 </it>and <it>Notch1</it>, demonstrating impaired endocardial activation and EMT. Moreover, perturbed expression of chamber-specific genes <it>Anf</it>, <it>Tbx2</it>, <it>Hand1 </it>and <it>Hand2 </it>reveals mispatterning of the <it>Msx1/2 </it>double mutant myocardium and suggests functions of <it>Msx1 </it>and <it>Msx2 </it>in regulating myocardial signals required for remodelling AV valves and maintaining an undifferentiated state of the AV myocardium.</p> <p>Conclusion</p> <p>Our findings demonstrate redundant roles of <it>Msx1 </it>and <it>Msx2 </it>in regulating signals required for development of the AV myocardium and formation of the AV valves.</p
The Dopamine Transporter Gene, a Spectrum of Most Common Risky Behaviors, and the Legal Status of the Behaviors
This study tests the specific hypothesis that the 9R/9R genotype in the VNTR of the dopamine transporter gene (DAT1) exerts a general protective effect against a spectrum of risky behaviors in comparison to the 10R/9R and 10R/10R genotypes, drawing on three-time repeated measures of risky behaviors in adolescence and young adulthood on about 822 non-Hispanic white males from the Add Health study. Our data have established two empirical findings. The first is a protective main effect in the DAT1 gene against risky behaviors. The second finding is that the protective effect varies over age, with the effect prominent at ages when a behavior is illegal and the effect largely vanished at ages when the behavior becomes legal or more socially tolerated. Both the protective main effect and the gene-lifecourse interaction effect are replicated across a spectrum of most common risky behaviors: delinquency, variety of sexual partners, binge drinking, drinking quantity, smoking quantity, smoking frequency, marijuana use, cocaine use, other illegal drug use, and seatbelt non-wearing. We also compared individuals with the protective genotype and individuals without it in terms of age, physical maturity, verbal IQ, GPA, received popularity, sent popularity, church attendance, two biological parents, and parental education. These comparisons indicate that the protective effect of DAT1*9R/9R cannot be explained away by these background characteristics. Our work demonstrates how legal/social contexts can enhance or reduce a genetic effect on risky behaviors
Global Analysis of Extracytoplasmic Stress Signaling in Escherichia coli
The Bae, Cpx, Psp, Rcs, and σE pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response
Premature ovarian failure and ovarian autoimmunity
Premature ovarian failure (POF) is defined as a syndrome characterized by
menopause before the age of 40 yr. The patients suffer from anovulation
and hypoestrogenism. Approximately 1% of women will experience menopause
before the age of 40 yr. POF is a heterogeneous disorder with a
multicausal pathogenesis involving chromosomal, genetic, enzymatic,
infectious, and iatrogenic causes. There remains, however, a group of POF
patients without a known etiology, the so-called "idiopathic" form. An
autoimmune etiology is hypothesized for the POF cases with a concomitant
Addison's disease and/or oophoritis. It is concluded in this review that
POF in association with adrenal autoimmunity and/or Addison's disease
(2-10% of the idiopathic POF patients) is indeed an autoimmune disease.
The following evidence warrants this view: 1) The presence of
autoantibodies to steroid-producing cells in these patients; 2) The
characterization of shared autoantigens between adrenal and ovarian
steroid-producing cells; 3) The histological picture of the ovaries of
such cases (lymphoplasmacellular infiltrate around steroid-producing
cells); 4) The existence of various autoimmune animal models for this
syndrome, which underlines the autoimmune nature of the disease. There is
some circumstantial evidence for an autoimmune pathogenesis in idiopathic
POF patients in the absence of adrenal autoimmunity or Addison's disease.
Arguments in support of this are: 1) The presence of cellular immune
abnormalities in this POF patient group reminiscent of endocrine
autoimmune diseases such as IDDM, Graves' disease, and Addison's disease;
2) The more than normal association with IDDM and myasthenia gravis. Data
on the presence of various ovarian autoantibodies and anti-receptor
antibodies in these patients are, however, inconclusive and need further
evaluation. A strong argument against an autoimmune pathogenesis of POF in
these patients is the nearly absent histological confirmation (the
presence of an oophoritis) in these cases (< 3%). However, in animal
models using ZP immunization, similar follicular depletion and fibrosis
(as in the POF women) can be detected. Accepting the concept that POF is a
heterogenous disorder in which some of the idiopathic forms are based on
an abnormal self-recognition by th
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