Coronary Heart Disease and Cortical Thickness,Gray Matter and White Matter Lesion Volumes on MRI

Coronary heart disease (CHD) has been linked with cognitive decline and dementia in several studies. CHD is strongly associated with blood pressure, but it is not clear how blood pressure levels or changes in blood pressure over time affect the relation between CHD and dementia-related pathology. The aim of this study was to investigate relations between CHD and cortical thickness, gray matter volume and white matter lesion (WML) volume on MRI, considering CHD duration and blood pressure levels from midlife to three decades later. The study population included 69 elderly at risk of dementia who participated in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. CAIDE participants were examined in midlife, re-examined 21 years later, and then after additionally 7 years (in total up to 30 years follow-up). MRIs from the second re-examination were used to calculate cortical thickness, gray matter and WML volume. CHD diagnoses were obtained from the Finnish Hospital Discharge Register. Linear regression analyses were adjusted for age, sex, follow-up time and scanner type, and additionally total intracranial volume in GM volume analyses. Adding diabetes, cholesterol or smoking to the models did not influence the results. CHD was associated with lower thickness in multiple regions, and lower total gray matter volume, particularly in people with longer disease duration (>10 years). Associations between CHD, cortical thickness and gray matter volume were strongest in people with CHD and hypertension in midlife, and those with CHD and declining blood pressure after midlife. No association was found between CHD and WML volumes. Based on these results, long-term CHD seems to have detrimental effects on brain gray matter tissue, and these effects are influenced by blood pressure levels and their changes over time.     

Zinc and Copper Levels in Severe Heart Failure and the Effects of Atrial Fibrillation on the Zinc and Copper Status

Oxidative stress is involved in the pathogenesis of congestive heart failure (CHF). Some trace elements serve as antioxidant defenses. The purpose of this study was to analyze the effect of atrial fibrillation (AF) on zinc (Zn) and copper (Cu) levels in patients with advanced CHF. In this prospective study, serum Zn and Cu levels in 78 patients with clinically advanced CHF, i.e., New York Heart Association (NYHA) functional class III or IV (40 patients with AF and 38 in sinus rhythm) were measured using atomic absorption spectrophotometry. All patients also had a left ventricular ejection fraction (EF) of <35%. We recruited 40 volunteers with nearly the same age and weight as control. They had normal EF. There was no significant difference between patients with AF and those with sinus rhythm regarding serum Zn and Cu levels. However, both groups showed significant hypozincemia (p < 0.000) and a decreased Zn/Cu ratio (p < 0.03) compared with control group. Serum Cu levels were similar in the two groups and did not differ significantly from the control group. In patients with advanced CHF, irrespective of the rhythm, profound hypozincemia, and a decreased Zn/Cu ratio were present, which could be secondary to the activation of the renin–angiotensin–aldosterone system and CHF medications. The results suggest the need for more studies focusing on possible benefits with Zn nutriceutical replacement in patients with advanced CHF.     

Serum Zinc and Copper Levels in Ischemic Cardiomyopathy

Changes in the copper (Cu) and zinc (Zn) concentrations have been reported previously in ischemic cardiomyopathy (ISCMP). Due to controversial results, the aims of this study were to compare levels of Cu, Zn, and Zn/Cu ratio of ISCMP patients with healthy volunteers and also to investigate the possible relationship between trace elements status in ISCMP patients with the severity of clinical disease based on the New York Heart Association (NYHA) classification. The subjects of this study consisted of 30 ISCMP and 27 healthy volunteers. ISCMP was diagnosed with a history of previous myocardial infarction and also coronary artery disease was confirmed by coronary angiography. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with the SPSS 10 software using independent sample t test for comparing the levels of Cu and Zn between ISCMP and normal subjects. The mean Cu level of the ISCMP group (1.54 ± 0.52 mg/L) was significantly more than the Cu levels of the healthy volunteers (1.31 ± 0.24 mg/L; p = 0.048). The mean Zn levels of the ISCMP and healthy volunteers were 1.05 ± 0.28 and 1.12 ± 0.42, respectively, without any significant difference between groups. There was a trend for higher Cu level, lower Zn level, and lower Zn/Cu ratio in NYHA III patients in comparison with NYHA II group. Considering the results of this study, Cu may have a role in the development of ISCMP. Interventions such as administration of Cu chelators to relieve the symptoms or to decrease the progression of ISCMP is needed to be examined in large clinical trials. In this study, the Zn level of ISCMP patients was not significantly different in comparison with the healthy volunteers.     

Scopolamine administration modulates muscarinic, nicotinic and NMDA receptor systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration.C57BL/6J mice were used for the experiments and divided into four groups. Two groups were given scopolamine 1 mg/kg i.p. (the first group was trained and the second group untrained) in the multiple T-maze (MTM), a paradigm for evaluation of spatial memory. Likewise, vehicle-treated mice were trained or untrained thus serving as controls. Hippocampal levels of M1, nicotinic receptor alpha 4 (Nic4) and 7 (Nic7) and subunit NR1containing complexes were determined by immunoblotting on blue native gel electrophoresis.Vehicle-treated trained mice learned the task and showed memory retrieval on day 8, while scopolamine-treatment led to significant impairment of performance in the MTM. At the day of retrieval, hippocampal levels for M1, Nic7 and NR1 were higher in the scopolamine treated groups than in vehicle-treated groups.The concerted action, i.e. the pattern of four brain receptor complexes regulated by the anticholinergic compound scopolamine, is shown. Insight into probable action mechanisms of scopolamine at the brain receptor complex level in the hippocampus is provided. Scopolamine treatment is a standard approach to test cognitive enhancers and other psychoactive compounds in pharmacological studies and therefore knowledge on mechanisms is of pivotal interest.     

How Can Selection of Biologically Inspired Features Improve the Performance of a Robust Object Recognition Model?

Humans can effectively and swiftly recognize objects in complex natural scenes. This outstanding ability has motivated many computational object recognition models. Most of these models try to emulate the behavior of this remarkable system. The human visual system hierarchically recognizes objects in several processing stages. Along these stages a set of features with increasing complexity is extracted by different parts of visual system. Elementary features like bars and edges are processed in earlier levels of visual pathway and as far as one goes upper in this pathway more complex features will be spotted. It is an important interrogation in the field of visual processing to see which features of an object are selected and represented by the visual cortex. To address this issue, we extended a hierarchical model, which is motivated by biology, for different object recognition tasks. In this model, a set of object parts, named patches, extracted in the intermediate stages. These object parts are used for training procedure in the model and have an important role in object recognition. These patches are selected indiscriminately from different positions of an image and this can lead to the extraction of non-discriminating patches which eventually may reduce the performance. In the proposed model we used an evolutionary algorithm approach to select a set of informative patches. Our reported results indicate that these patches are more informative than usual random patches. We demonstrate the strength of the proposed model on a range of object recognition tasks. The proposed model outperforms the original model in diverse object recognition tasks. It can be seen from the experiments that selected features are generally particular parts of target images. Our results suggest that selected features which are parts of target objects provide an efficient set for robust object recognition.     

Cyclic AMP inhibits translation of cyclin D3 in T lymphocytes at the level of elongation by inducing eEF2-phosphorylation

The purpose of the present study was to understand the mechanism by which activated protein kinase A (PKA) leads to down-regulation of cyclin D3 in lymphocytes. By using Jurkat cells as a model system, we have been able to demonstrate that cyclin D3 is reduced at the level of translation by inhibition of elongation. One of the important factors involved in translational elongation is the eukaryotic elongation factor 2 (eEF2). eEF2 promotes translation in its unphosphorylated form, and we observed a rapid phosphorylation of the eEF2-protein upon forskolin treatment. When using specific inhibitors of the eEF2-kinase prior to forskolin treatment, we were able to inhibit the increased phosphorylation of eEF2. Furthermore, inhibition of eEF2-kinase prevented the forskolin-mediated down-regulation of cyclin D3. Taken together, it appears that activation of PKA in Jurkat cells reduces the expression of cyclin D3 at the level of translational elongation by increasing the phosphorylation of eEF2 and thereby inhibiting its activity.     

Radiation dose-dependent maintenance of G(2) arrest requires retinoblastoma protein

In response to ionizing radiation (IR), cell cycle checkpoints are activated to provide time for DNA repair. Several different checkpoint mechanisms have been elucidated. However, mechanisms that regulate the duration of cell cycle arrest are not understood. Previous studies have shown that the retinoblastoma tumor suppressor protein (RB) is required for radiation-induced G1 arrest. Working with primary fibroblasts derived from Rb+/+ and Rb-/- mouse embryos, we show that RB also regulates the duration of G2 arrest. The initial G2 checkpoint response is enhanced in Rb-/- cells due to a defect in G1 arrest. However, the permanent arrest in G2 induced by higher doses of IR does not occur in Rb-/- cells. Rb-/- cells either resumed proliferation or underwent apoptosis at IR doses that caused the majority of Rb+/+ cells to arrest permanently in G2. The prolongation of G2 arrest in Rb+/+ cells correlated with a gradual accumulation of hypophosphorylated RB. Thus, regulation of the RB function may be an important aspect in the maintenance of cell cycle checkpoints in DNA damage response.     

Contrasting Antioxidant and Cytotoxic Effects of Peroxiredoxin I and II in PC12 and NIH3T3 Cells

We examined the impact of peroxiredoxin-I (Prx-I) and peroxiredoxin-II (Prx-II) stable transduction on oxidative stress in PC12 neurons and NIH3T3 fibroblasts and found variability depending on cell type and Prx subtype. In PC12 neurons, Prx-II suppressed reactive oxygen species (ROS) generation by 36% (p < 0.01) relative to vector-infected control cells. However, in NIH3T3 fibroblasts, Prx-II overexpression resulted in a 97% (p < 0.01) increase in ROS generation. Prx-I transduction elevated ROS generation in PC12 cells. The effect of Prx-I on PC12 cells was potentiated in the presence of menadione, and suppressed by an inhibitor of nitric oxide synthetase. Prx-II transduction resulted in 25–35% lower levels of glutathione (GSH) in both cell types, while Prx-I transduction increased GSH levels in neurons and decreased GSH and caspase-3 activity in fibroblasts. Prx-I and Prx-II also had differing effects on cell viability. These results suggest that Prx-I and Prx-II can either increase or decrease intracellular oxidative stress depending on cell type or experimental conditions, particularly conditions affecting nitric oxide levels.Equivalent contributions were made by each author     

Plasmonic Near-Field Effect on Visible and Near-Infrared Emissions from Self-Assembled Gold Nanoparticle Films

Plasmonics - In this work, we have performed a systematic investigation of the plasmon near-field effect on photoluminescence (PL) behavior of the annealed self-assembled gold nanostructured films....