The roles of Smads and Pitx2 in cardiac development

The heart is the first organ to form in vertebrates during embryogenesis, and its circulatory function is essential to embryonic survival. Cardiac morphogenesis comprises a complex series of interactions involving cells from several embryonic origins. These cell-cell interactions are regulated temporally and spatially by programs of inductive signaling events, including BMP signaling transduced by Smads and left-right asymmetry signaling mediated by Pitx2. Disruptions of BMP signaling and left-right asymmetry signaling result in abnormal cardiac morphogenesis that causes congenital heart disease in humans. In this study, conventional and conditional gene targeting approaches were employed to dissect the functions of Smad8 and Smad1, intracellular BMP signaling transducers, and Pitx2, a direct target of left-right signaling, in cardiac development. We generated the Smad8mt mutant allele and the Smad8lacZ knock-in allele. Smad8 homozygous mutant mice were viable and fertile without obvious abnormalities. The Smad8lacZ knock-in allele showed that Smad8 was expressed in the myocardium of cardiac outflow tract and atrioventricular cushions. We did not find defects in these Smad8-expressing cardiac regions in Smad8mt/mt and Smad8lacZ/lacZ mutants, indicating that Smad8 is dispensable for cardiac development. Conditional knockout of Smad1 using the Nkx2.5Cre allele in cardiac mesoderm resulted in partial inactivation of Smad1 in the myocardium and complete deletion of Smad1 in the epicardium, and caused ventricular hypoplasia featured with a thinner compact zone, suggesting that Smad1 signaling in the epicardium is required for myocardial morphogenesis in ventricles. Previous data have shown that Pitx2 null mutants exhibit defects in the cardiac outflow tract, a region populated with cells from the cardiac mesoderm and the cardiac neural crest. We found that the cardiac neural crest normally populated into the outflow tract in Pitx2 null mutant. Moreover, specific deletion of Pitx2 in the neural crest resulted in normal heart formation. Deletion of Pitx2 in the cardiac mesoderm caused defective outflow tract, revealing that the function of Pitx2 in the cardiac outflow tract resides in splanchnic and branchial arch mesoderm, and is independent of cardiac neural crest cells. ^

What Makes Small-City Downtowns Viable?

The paper examines the experience of Connecticut's urban centers over the past century with an eye toward informing public policy. An in-depth qualitative discussion describes the rise and characteristics of urbanism, and then its unraveling. Linear regression analysis then quantifies the impact of various contributory factors on urban economic health in Connecticut cities since 1980. The findings suggest that local policymakers are largely unable to influence economic conditions in their cities.

Identifying and removing barriers to cycling as a viable means of transportation in Houston, Texas

The citizens of Houston, Texas, spend much time commuting. It has repeatedly been named among the “Fattest Cities” by Men’s Fitness Magazine (The fittest and fattest cities in America – Men’s Fitness. ). Obesity is one of its major public health problems as Houstonians often do not engage in enough physical activity to help them maintain their ideal weights. The use of bicycles provides a healthy and ecological alternative to commuting by driving. However, because urban cyclists must often share the roads with motorized vehicles, cyclists are often exposed to high levels of emissions. As vulnerable users of the roadways, urban cyclists also face the threat of injury. Nevertheless, there are some programs that encourage the use of bicycles. Laws and ordinances not only reveal public policy relating to bicycling but are a means to develop policy which can encourage bicycling. ^

A simple mathematical model that describes the growth of the area and the number of total and viable cells in yeast colonies

We propose a model, based on the Gompertz equation, to describe the growth of yeasts colonies on agar medium. This model presents several advantages: (i) one equation describes the colony growth, which previously needed two separate ones (linear increase of radius and of the squared radius); (ii) a similar equation can be applied to total and viable cells, colony area or colony radius, because the number of total cells in mature colonies is proportional to their area; and (iii) its parameters estimate the cell yield, the cell concentration that triggers growth limitation and the effect of this limitation on the specific growth rate. To elaborate the model, area, total and viable cells of 600 colonies of Saccharomyces cerevisiae, Debaryomyces fabryi, Zygosaccharomyces rouxii and Rhodotorula glutinis have been measured. With low inocula, viable cells showed an initial short exponential phase when colonies were not visible. This phase was shortened with higher inocula. In visible or mature colonies, cell growth displayed Gompertz-type kinetics. It was concluded that the cells growth in colonies is similar to liquid cultures only during the first hours, the rest of the time they grow, with near-zero specific growth rates, at least for 3 weeks.

Targeted overexpression of protein kinase C β2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the β isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCβ isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCβ2 isoform in the myocardium. These mice overexpressed the PKCβ2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCβ-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCβ2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved.

RXR gamma null mice are apparently normal and compound RXR alpha +/-/RXR beta -/-/RXR gamma -/- mutant mice are viable.

The RXR gamma (RXR, retinoid X receptor) gene was disrupted in the mouse. Homozygous mutant mice developed normally and were indistinguishable from their RXR gamma +/- or wild-type littermates with respect to growth, fertility, viability, and apparent behavior in the animal facility. Moreover, RXR alpha -/-/RXR gamma -/- and RXR beta -/-/RXR gamma -/- mutant phenotypes were indistinguishable from those of RXR alpha -/- and RXR beta -/- mutants, respectively. Strikingly, RXR alpha +/-/RXR beta -/-/RXR gamma -/- triple mutants were viable. Thus, it appears that RXR gamma does not exert any essential function that cannot be performed by RXR alpha or RXR beta, and one copy of RXR alpha is sufficient to perform most of the functions of the RXRs.

Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism.

RNA editing in the nucleus of higher eukaryotes results in subtle changes to the RNA sequence, with the ability to effect dramatic changes in biological function. The first example to be described and among the best characterized, is the cytidine-to-uridine editing of apolipoprotein B (apo-B) RNA. The editing of apo-B RNA is mediated by a novel cytidine deaminase, apobec-1, which has acquired the ability to bind RNA. The stop translation codon generated by the editing of apo-B RNA truncates the full-length apo-B100 to form apo-B48. The recent observations of tumor formation in Apobec-1 transgenic animals, together with the fact that Apobec-1 is expressed in numerous tissues lacking apo-B, raises the issue of whether this enzyme is essential for a variety of posttranscriptional editing events. To directly test this, mice were created with a null mutation in Apobec-1 using homologous recombination in embryonic stem cells. Mice, homozygous for this mutation, were viable and made apo-B100 but not apo-B48. The null animals were fertile, and a variety of histological, behavioral, and morphological analyses revealed no phenotype other than abnormalities in lipoprotein metabolism, which included an increased low density lipoprotein fraction and a reduction in high density lipoprotein cholesterol. These studies demonstrate that neither apobec-1 nor apo-B48 is essential for viability and suggest that the major role of apobec-1 may be confined to the modulation of lipid transport.

Agouti regulation of intracellular calcium: role in the insulin resistance of viable yellow mice.

Several dominant mutations at the agouti locus in the mouse cause a syndrome of marked obesity, hyperinsulinemia, and insulin resistance. Although it is known that the agouti gene is expressed in an ectopic manner in these mutants, the precise mechanism by which the agouti gene product mediates these effects is unclear. Since intracellular Ca2+ is believed to play a role in mediating insulin action and dysregulation of Ca2+ flux is observed in diabetic animals and humans, we examined the status of intracellular Ca2+ in mice carrying the dominant agouti allele, viable yellow (Avy). We show here that in mice carrying this mutation, the intracellular free calcium concentration ([Ca2+]i) is elevated in skeletal muscle, and the degree of elevation is closely correlated with the degree to which the mutant traits are expressed in individual animals. Moreover, we demonstrate that the agouti gene product is capable of inducing increased [Ca2+]i in cultured and freshly isolated skeletal muscle myocytes from wild-type mice. Based on these findings, we present a model in which we propose that the agouti polypeptide promotes insulin resistance in mutant animals through its ability to increase [Ca2+]i.

¿Es viable un fondo de cohesión social iberoamericano?

Al margen de razones puramente solidarias, la cohesión social y las políticas orientadas a alcanzarla se justifican por los réditos recíprocos derivados de las relaciones económicas internacionales. Bajo determinadas circunstancias, estos réditos pueden aumentar gracias a las políticas de cohesión, tanto para los receptores como para los donantes netos de fondos. En primer lugar, porque se aprovechan en mayor medida las ventajas que proporciona la especialización productiva. En segundo lugar, porque aumentan los incentivos para reducir las barreras al movimiento de mercancías y factores de producción. En tercer lugar, porque pueden fortalecer las capacidades institucionales de los distintos países. Finalmente, porque, junto a estas razones de índole económico, existen también importantes beneficios de corte sociopolítico.

Una revisión de los condicionantes de la profesión periodística desde la perspectiva sociológica de McNair. ¿Es viable un periodismo profesional de calidad?

La actividad periodística se ha visto sometida en los últimos años a una transformación radical fundamentada, principalmente, aunque no sólo, en la revolución tecnológica que ha incrementado exponencialmente las posibilidades de unos medios además siguen lidiando con los condicionamientos procedentes de los entornos políticos, económicos, profesionales y sociales. Ante este nuevo escenario, se plantea una pregunta inmediata: ¿sigue resultando viable un periodismo profesional y de calidad con los condicionantes actuales? Este artículo trata de dar respuesta a la pregunta de investigación desde una revisión actualizada de la perspectiva sociológica sobre la que McNair analiza los factores que condicionan la profesión.

A Viable Alternative to Basel III Prudential Capital Rules. CEPS Policy Brief No. 291, May 2013

Stefano Micossi argues in this paper that the Basel framework for bank prudential requirements is deeply flawed and that the Basel III revision has failed to correct these flaws, making the system even more complicated, opaque and open to manipulation. In practice, he finds that the present system does not offer regulators and financial markets a reliable capital standard for banks and its divergent implementation in the main jurisdictions of the European Union and the United States has broken the market into special fiefdoms governed by national regulators in response to untoward special interests. The time is ripe to stop tinkering with minor adjustment and revisions in order to rescue the system, because the system cannot be rescued. In response to the current situation, Micossi calls for abandoning reference to risk-weighted assets calculated by banks with their internal risk management models for the determination of banks’ prudential capital, together with the preoccupation with the asset side of banks in correcting for risk exposure. He suggests that the alternative may be provided by a combination of a straight capital ratio and a properly designed deposit insurance system. It is a logical, complete and much less distortive alternative; it would serve better the cause of financial stability as well as the interest of the banks in clear, transparent and level playing field.

Analysis of airborne viable bacteria at solid waste processing facilities /

Mode of access: Internet.

¿Es viable el feto que nace con un hidroraquis ó espina bífida?... [Manuscrito] : memoria leída en la Academia ... /

Tít. entresacado del texto.

The design of an economically viable large-scale computer based education system /

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