Development and Morphology of the Ventricular Outflow Tracts.

It is customary, at the current time, to consider many, if not most, of the lesions involving the ventricular outflow tract in terms of conotruncal malformations. This reflects the introduction, in the early 1940s, of the terms conus and truncus to describe the components of the developing outflow tract. The definitive outflow tracts in the postnatal heart, however, possess three, rather than two, components. These are the intrapericardial arterial trunks, the arterial roots, and the subvalvar ventricular outflow tracts. Congenital lesions afflicting the arterial roots, however, are not currently considered to be conotruncal malformations. This suggests a lack of logic in the description of cardiac development and its use as a means of categorizing congenital malformations. It is our belief that the developing outflow tract, like the postnatal outflow tracts, can readily be described in tripartite fashion, with its distal, intermediate, and proximal components forming the primordiums of the postnatal parts. In this review, we present evidence obtained from developing mice and human hearts to substantiate this notion. We show that the outflow tract, initially with a common lumen, is divided into its aortic and pulmonary components by a combination of an aortopulmonary septum derived from the dorsal wall of the aortic sac and outflow tract cushions that spiral through its intermediate and proximal components. These embryonic septal structures, however, subsequently lose their septal functions as the outflow tracts develop their own discrete walls. We then compare the developmental findings with the anatomic arrangements seen postnatally in the normal human heart. We show how correlations with the embryologic findings permit logical analysis of the congenital lesions involving the outflow tracts

Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children

The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.Keywords: Homocysteine; Epilepsy; Folic acid; Vitamin B12; Anti-epileptic dru

Semantic dementia: a complex and culturally influenced presentation.

The variants of frontotemporal dementia (FTD) require careful differentiation from primary psychiatric disorders as the neuropsychiatric manifestations can overshadow the unique cognitive deficits. The language variants of FTD are less readily recognised by trainees despite making up around 43% of cases. This educational article presents an anonymised case of one of the language variants: semantic dementia. The cognitive deficits and neuropsychiatric manifestations (delusions and hyperreligiosity) are explored in terms of aetiology and management. By the end of the article, readers should be able to differentiate FTD from Alzheimer's disease, understand the principles of management and associated risks, and develop a multifaceted approach to hyperreligiosity in dementia

Power spectra of solar brightness variations at different inclinations

Magnetic features on the surfaces of cool stars cause variations of their brightness. Such variations have been extensively studied for the Sun. Recent planet-hunting space telescopes allowed measuring brightness variations in hundred thousands of other stars. The new data posed the question of how typical is the Sun as a variable star. Putting solar variability into the stellar context suffers, however, from the bias of solar observations being made from its near-equatorial plane, whereas stars are observed at all possible inclinations. We model solar brightness variations at timescales from days to years as they would be observed at different inclinations. In particular, we consider the effect of the inclination on the power spectrum of solar brightness variations. The variations are calculated in several passbands routinely used for stellar measurements. We employ the Surface Flux Transport Model (SFTM) to simulate the time-dependent spatial distribution of magnetic features on both near- and far-sides of the Sun. This distribution is then used to calculate solar brightness variations following the SATIRE (Spectral And Total Irradiance REconstruction) approach. We have quantified the effect of the inclination on solar brightness variability at timescales down to a day. Thus, our results allow making solar brightness records directly comparable to those obtained by the planet-hunting space telescopes. Furthermore, we decompose solar brightness variations into the components originating from the solar rotation and from the evolution of magnetic features

Instantons on ALE spaces and Super Liouville Conformal Field Theories

We provide evidence that the conformal blocks of N=1 super Liouville conformal field theory are described in terms of the SU(2) Nekrasov partition function on the ALE space O_{P^1}(-2).Comment: 10 page

Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc-mediated response to hyperosmolarity

Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified. The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes. Based on microarray studies we chose two tyrosine-kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc phosphorylation and generated single and double knock-out mutants to them. Transcriptional regulation of STATc and STATc dependent genes was disturbed in pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2 resulted in diminished or completely abolished increased transcription of STATc dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ. Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-) cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced phosphorylation was mirrored by a significant delay in nuclear translocation of GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747. Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo. Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an, as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and hence its inhibition, and that Pyk3 is involved in the regulation of STATc by either directly or indirectly activating it. Our results add further complexities to the regulation of STATc, which presumably ensure its optimal activation in response to different environmental cues

Biochemical Properties of Highly Neuroinvasive Prion Strains

Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrPSc. Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrPSc over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrPSc over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS

The combined impact of sauerkraut with Leuconostoc mesenteroides to enhance immunomodulatory activity in Escherichia coli-infected mice

This study investigated the combined impact of sauerkraut and Leuconostoc mesenteroides culture on immunomodulatory activity in experimental animal. The in vivo immunomodulatory activity of Escherichia coli-infected Balb-C mice was ascertained in fermented sauerkrauts [test vs. control]. Both sauerkrauts enhanced the adaptive immune response [evidenced by an increase in CD4+ CD8+ IFN-γ, TNFα] and innate immune response [represented by a decrease of CD68-IL-6]. Nev- ertheless, the in vivo immunomodulatory activity of sauerkraut combined with L. mesenteroides was higher than that shown in sauerkraut control solely