Quick minds slowed down: effects of rotation and stimulus category on the attentional blink

Background

Most people show a remarkable deficit to report the second of two targets when presented in close temporal succession, reflecting an attentional restriction known as the ‘attentional blink’ (AB). However, there are large individual differences in the magnitude of the effect, with some people showing no such attentional restrictions.

Methodology/Principal Findings

Here we present behavioral and electrophysiological evidence suggesting that these ‘non-blinkers’ can use alphanumeric category information to select targets at an early processing stage. When such information was unavailable and target selection could only be based on information that is processed relatively late (rotation), even non-blinkers show a substantial AB. Electrophysiologically, in non-blinkers this resulted in enhanced distractor-related prefrontal brain activity, as well as delayed target-related occipito-parietal activity (P3).

Conclusion/Significance

These findings shed new light on possible strategic mechanisms that may underlie individual differences in AB magnitude and provide intriguing clues as to how temporal restrictions as reflected in the AB can be overcome.     

Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability

Intracellular signaling mechanisms in red blood cells (RBCs) involve various protein kinases and phosphatases and enable rapid adaptive responses to hypoxia, metabolic requirements, oxidative stress, or shear stress by regulating the physiological properties of the cell. Protein phosphorylation is a ubiquitous mechanism for intracellular signal transduction, volume regulation, and cytoskeletal organization in RBCs. Spectrin-based cytoskeleton connects integral membrane proteins, band 3 and glycophorin C to junctional proteins, ankyrin and Protein 4.1. Phosphorylation leads to a conformational change in the protein structure, weakening the interactions between proteins in the cytoskeletal network that confers a more flexible nature for the RBC membrane. The structural organization of the membrane and the cytoskeleton determines RBC deformability that allows cells to change their ability to deform under shear stress to pass through narrow capillaries. The shear stress sensing mechanisms and oxygenation-deoxygenation transitions regulate cell volume and mechanical properties of the membrane through the activation of ion transporters and specific phosphorylation events mediated by signal transduction. In this review, we summarize the roles of Protein kinase C, cAMP-Protein kinase A, cGMP-nitric oxide, RhoGTPase, and MAP/ERK pathways in the modulation of RBC deformability in both healthy and disease states. We emphasize that targeting signaling elements may be a therapeutic strategy for the treatment of hemoglobinopathies or channelopathies. We expect the present review will provide additional insights into RBC responses to shear stress and hypoxia via signaling mechanisms and shed light on the current and novel treatment options for pathophysiological conditions.     

The morphology of the dorsal and ventral skin of Triturus karelinii (Caudata: Salamandridae)

In this study, for the first time, the morphology of the dorsal and ventral skin of Triturus karelinii using light microscopy through histochemical methods was described. The skin exhibited basic morphological characteristics of the other urodeles: the epidermis composed of keratinized stratified epithelium with numerous conical protrusions and the dermis subdivided into spongy and compact layers. In the spongious dermis, three distinct types of glands were observed, namely serous, mucous and mixed glands. These glands were alveolar and occurred in both males and females. The morphologies of all three skin glands differed from anurans and other urodeles, having peculiar characteristics. Serous glands exhibited three different appearances. An unusual finding in mucous glands was the different appearance of their granules, showing diverse density after staining with PAS and AB. The histochemical analysis clearly demonstrated the presence of neutral, acid and sulfated mucins in the adenocytes of mucous glands. Mixed glands formed by mucous and serous glands exhibited the same morphological traits of both types of glands. Light microscopic observations revealed that the dorsal and ventral skin showed structural similarities with some minor differences, possibly resulting from their functions.     

Plasma expander viscosity effects on red cell-free layer thickness after moderate hemodilution

The objective of the study was to investigate the effects of plasma viscosity after hemodilution on the thickness of the erythrocyte cell free layer (CFL) and on the interface between the flowing column of erythrocytes and the vascular endothelium. The erythrocyte CFL thickness was measured in the rat cremaster muscle preparation. Plasma viscosity was modified in an isovolemic hemodilution, in which the systemic hematocrit (Hctsys) was lowered to 30%. The plasma expanders (PE) of similar nature and different viscosities were generated by glutaraldehyde polymerization of human serum albumin (HSA) at various molar ratios glutaraldehyde to HSA: (i) unpolymerized HSA; (ii) PolyHSA24:1, molar ratio = 24 and (iii) PolyHSA60:1, molar ratio = 60. The HSA viscosities determined at 200 s(-1) were 1.1, 4.2 and 6.0 dyn x cm(-2), respectively. CFL thickness, vessel diameter and blood flow velocity were measured, while volumetric flow, shear rate and stress were calculated. Hemodilution with PolyHSA60:1 increased plasma viscosity and the blood showed marked shear thinning behavior. CFL thickness decreased as plasma viscosity increased after hemodilution; thus the CFL thickness with HSA and PolyHSA24:1 increased compared to baseline. Conversely, the CFL thickness of PolyHSA60:1 was not different from baseline. Blood flow increased with both PolyHSA's compared to baseline. Wall shear rate and shear stress increased for PolyHSA60:1 compared to HSA and PolyHSA24:1, respectively. In conclusion, PE viscosity determined plasma viscosity after hemodilution and affected erythrocyte column hydrodynamics, changing the velocity profile, CFL thickness, and wall shear stress. This study relates the perfusion caused by PolyHSA60:1 to hemodynamic changes induced by the rheological properties of blood diluted with PolyHSA60:1.     

Effects of ascorbic acid and ��-carotene on HepG2 human hepatocellular carcinoma cell line

Recent studies have demonstrated that vegetable rich diets have protective effects on the occurrence and prognosis of various cancers. In addition to dietary intakes, ascorbic acid and β-carotene are also taken as supplements. The aim of this study was to assess effects of ascorbic acid, β-carotene and their combinations on human hepatocellular carcinoma cell line HepG2. Ascorbic acid and β-carotene were applied to cells as plasma peak concentrations (70 and 8 μM, respectively) and their half concentrations (35 and 4 μM, respectively) for 24 and 48 h. Genotoxic and cytotoxic effects of ascorbic acid and β-carotene were evaluated by alkali single cell gel electrophoresis (SCGE), acridine orange/ethidium bromide staining patterns of cells (apoptosis and necrosis) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS). Results of the SCGE demonstrated that both ascorbic acid and β-carotene caused DNA damage on HepG2 which were also concordant to increased apoptosis and necrosis of cells. Increased TBARS values also demonstrated increased lipid peroxidation in these cells. Results of the present study demonstrates that when dietary intakes of ascorbic acid and β-carotene and their relevant achievable plasma level concentrations were considered, both ascorbic acid and β-carotene induce genotoxic and cytotoxic damage on HepG2 together with increased oxidative damage in contrast to their protective effect on healthy cells. This may be correlated to oxidative status and balance of ROS in hepatocellular carcinoma cells.     

The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease

This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the oxidative stress that occurs in an experimental mouse model of Parkinson’s disease (PD). An experimental model of PD was created by four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 × 20 mg/kg, at 12 h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36 mg/kg/day). The motor activity of the mice was evaluated via the pole test, and the dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant enzymes in the brain were determined by spectrophotometric assays and the concentration of thiobarbituric acid-reactive substances (TBARS) were measured as an index of oxidative damage. The number of apoptotic dopaminergic cells significantly increased in MPTP-treated mice compared to controls. Although DHA significantly diminished the number of cell deaths in MPTP-treated mice, it did not improve the decreased motor activity observed in the experimental PD model. Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP + DHA group as compared to the MPTP group. TBARS levels in the brain were significantly increased following MPTP treatment. Glutathione peroxidase (GPx) and catalase (CAT) activities of brain were unaltered in all groups. The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group, but DHA treatment did not have an effect on SOD activity in the MPTP + DHA group. Our current data show that DHA treatment exerts neuroprotective actions on an experimental mouse model of PD. There was a decrease tendency in brain lipid oxidation of MPTP mice but it did not significantly.     

Vitamin D and the regulation of placental inflammation

The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas -/- for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated -/- placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated -/- placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1(-/-) versus Cyp27b1(+/+) placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1(-/-) placentas. Similar results for IL-6 expression were observed with placentas -/- for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D(3), suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.     

Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans

The gastric peptide ghrelin promotes energy storage, appetite, and food intake. Nutrient intake strongly suppresses circulating ghrelin via molecular mechanisms possibly involving insulin and gastrointestinal hormones. On the basis of the growing evidence that glucose-dependent insulinotropic polypeptide (GIP) is involved in the control of fuel metabolism, we hypothesized that GIP and/or insulin, directly or via changes in plasma metabolites, might affect circulating ghrelin. Fourteen obese subjects were infused with GIP (2.0 pmol·kg(-1)·min(-1)) or placebo in the fasting state during either euglycemic hyperinsulinemic (EC) or hyperglycemic hyperinsulinemic clamps (HC). Apart from analysis of plasma ghrelin and insulin levels, GC-TOF/MS analysis was applied to create a hormone-metabolite network for each experiment. The GIP and insulin effects on circulating ghrelin were analyzed within the framework of those networks. In the HC, ghrelin levels decreased in the absence (19.2% vs. baseline, P = 0.028) as well as in the presence of GIP (33.8%, P = 0.018). Ghrelin levels were significantly lower during HC with GIP than with placebo, despite insulin levels not differing significantly. In the GIP network combining data on GIP-infusion, EC+GIP and HC+GIP experiments, ghrelin was integrated into hormone-metabolite networks through a connection to a group of long-chain fatty acids. In contrast, ghrelin was excluded from the network of experiments without GIP. GIP decreased circulating ghrelin and might have affected the ghrelin system via modification of long-chain fatty acid pools. These observations were independent of insulin and offer potential mechanistic underpinnings for the involvement of GIP in systemic control of energy metabolism.     

Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty‐four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20 mg/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20 mg/kg MTX, i.p, single dose+40 mg/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24 hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony‐stimulating factor (G‐CSF), osteopontin (OPN), and heat shock protein‐70 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G‐CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.