University of Naples Federico II

About: University of Naples Federico II is a education organization based out in Naples, Campania, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29291 authors who have published 68803 publications receiving 1920149 citations. The organization is also known as: Università degli Studi di Napoli Federico II & Naples University.

Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice.

Abstract: The serine-threonine kinase Akt seems to be central in mediating stimuli from different classes of receptors. In fact, both IGF-1 and IL6-like cytokines induce hypertrophic and antiapoptotic signals in cardiomyocytes through PI3K-dependent Akt activation. More recently, it was shown that Akt is involved also in the hypertrophic and antiapoptotic effects of β-adrenergic stimulation. Thus, to determine the effects of Akt on cardiac function in vivo, we generated a model of cardiac-specific Akt overexpression in mice. Transgenic mice were generated by using the E40K, constitutively active mutant of Akt linked to the rat α-myosin heavy chain promoter. The effects of cardiac-selective Akt overexpression were studied by echocardiography, cardiac catheterization, histological and biochemical techniques. We found that Akt overexpression produced cardiac hypertrophy at the molecular and histological levels, with a significant increase in cardiomyocyte cell size and concentric LV hypertrophy. Akt-transgenic mice also showed a remarkable increase in cardiac contractility compared with wild-type controls as demonstrated by the analysis of left ventricular (dP/dtmax) in an invasive hemodynamic study, although with graded dobutamine infusion, the maximum response was not different from that in controls. Diastolic function, evaluated by left ventricular dP/dtmin, was not affected at rest but was impaired during graded dobutamine infusion. Isoproterenol-induced cAMP levels, β-adrenergic receptor (β-AR) density, and β-AR affinity were not altered compared with control mice. Moreover, studies on signaling pathway activation from myocardial extracts demonstrated that glycogen synthase kinase3-β is phosphorylated, whereas p42/44 mitogen-activated protein kinases is not, indicating that Akt induces hypertrophy in vivo by activating the glycogen synthase kinase3-β/GATA 4 pathway. In summary, our results not only demonstrate that Akt regulates cardiomyocyte cell size in vivo, but, importantly, show that Akt modulates cardiac contractility in vivo without directly affecting β-AR signaling capacity.

Aerosol-type-dependent lidar ratios observed with Raman lidar

Abstract: [1] We summarize our Raman lidar observations which were carried out in Europe, Asia, and Africa during the past 10 years, with focus on particle extinction-to-backscatter ratios (lidar ratios) and Angstrom exponents. For the first time, we present statistics on lidar ratios for almost all climatically relevant aerosol types solely based on Raman lidar measurements. Sources of continental particles were in North America and Europe, the Sahara, and south and Southeast and east Asia. The North Atlantic Ocean, and the tropical and South Indian Ocean were the sources of marine particles. The statistics are complemented with lidar ratios describing aged forest fire smoke and pollution from polar regions (Arctic haze) after long-range transport. In addition, we present particle Angstrom exponents for the wavelength range from 355 to 532 nm and from 532 to 1064 nm. We compare our data set of lidar ratios to the recently published AERONET (Aerosol Robotic Network) lidar ratio climatology. That climatology is based on aerosol scattering modeling in which AERONET Sun photometer observations serve as input. Raman lidar measurements of extinction-to-backscatter ratios of Saharan dust and urban aerosols differ significantly from the numbers obtained with AERONET Sun photometers. There are also differences for some of the Angstrom exponents. Further comparison studies are needed to reveal the reason for the observed differences.

PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis

Abstract: Permanent congenital hypothyroidism (CH) is a common disease that occurs in 1 of 3,000–4,000 newborns. Except in rare cases due to hypothalamic or pituitary defects, CH is characterized by elevated levels of thyroid-stimulating hormone (TSH) resulting from reduced thyroid function. When thyroid hormone therapy is not initiated within the first two months of life, CH can cause severe neurological, mental and motor damage1,2. In 80–85% of cases, CH is associated with and presumably is a consequence of thyroid dysgenesis (TD). In these cases, the thyroid gland can be absent (agenesis, 35–40%), ectopically located (30–45%) and/or severely reduced in size (hypoplasia, 5%). Familial cases of TD are rare, even though ectopic or absent thyroid has been occasionally observed in siblings3. The pathogenesis of TD is still largely unknown. Although a genetic component has been suggested, mutations in the gene encoding the receptor for the thyroid-stimulating hormone (TSHR) have been identified in only two cases of TD with hypoplasia4,5. We report mutations in the coding region of PAX8 in two sporadic patients and one familial case of TD. All three point mutations are located in the paired domain of PAX8 and result in severe reduction of the DMA-binding activity of this transcription factor. These genetic alterations implicate PAX8 in the pathogenesis of TD and in normal thyroid development.