Neural Bases for Individual Differences in the Subjective Experience of Short Durations (Less than 2 Seconds)

The current research was designed to establish whether individual differences in timing performance predict neural activation in the areas that subserve the perception of short durations ranging between 400 and 1600 milliseconds. Seventeen participants completed both a temporal bisection task and a control task, in a mixed fMRI design. In keeping with previous research, there was increased activation in a network of regions typically active during time perception including the right supplementary motor area (SMA) and right pre-SMA and basal ganglia (including the putamen and right pallidum). Furthermore, correlations between neural activity in the right inferior frontal gyrus and SMA and timing performance corroborate the results of a recent meta-analysis and are further evidence that the SMA forms part of a neural clock that is responsible for the accumulation of temporal information. Specifically, subjective lengthening of the perceived duration were associated with increased activation in both the right SMA (and right pre-SMA) and right inferior frontal gyrus.     

Differences in the expression of LPS-receptors are not responsible for the sex-specific immune response after trauma and hemorrhagic shock

Several studies demonstrated a sex-specific cytokine secretion by macrophages following trauma-hemorrhage (T-H) and incubation with lipopolysaccharide A (LPS). Although LPS is known to act via the receptors CD14 and TLR4 on macrophages, it remains unknown whether differences in LPS receptor expression in males and females may be responsible for the gender-specific LPS induced cytokine response following (T-H). To study this, male and proestrus female mice (C3H/HeN) were subjected to trauma (laparotomy) followed by hemorrhage or sham operation. At 2 h thereafter, SMphi and PMphi were harvested and cultured for 2 h. The expression of CD14 and TLR4 was measured by flow cytometry on unstimulated SMphi and PMphi as well as after LPS stimulation. The results indicate that the expression of CD14 and TLR4 on SMphi and PMphi from female and male mice was similar in sham-operated animals and after (T-H). Incubation of macrophages with LPS did not alter CD14 and TLR4 expression in the study groups. Thus, the sex specific LPS induced cytokine secretion after (T-H) is not caused by differences in LPS receptor expression on Mphi of male and female mice.     

Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult.

Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These factors act via receptor complexes involving gp130 and LIFR-beta and ligand binding leads to activation of various signaling pathways, including phosphorylation of Stat3. The role of Stat3 in neuronal survival was investigated in mice by Cre-mediated gene ablation in motoneurons. Cre is expressed under the neurofilament light chain (NF-L) promoter, starting around E12 when these neurons become dependent on neurotrophic support. Loss of motoneurons during the embryonic period of naturally occurring cell death is not enhanced in NF-L-Cre; Stat3(flox/KO) mice although motoneurons isolated from these mice need higher concentrations of CNTF for maximal survival in culture. In contrast, motoneuron survival is significantly reduced after facial nerve lesion in the adult. These neurons, however, can be rescued by the addition of neurotrophic factors, including CNTF. Stat3 is essential for upregulation of Reg-2 and Bcl-xl expression in lesioned motoneurons. Our data show that Stat3 activation plays an essential role for motoneuron survival after nerve lesion in postnatal life but not during embryonic development, indicating that signaling requirements for motoneuron survival change during maturation.     

Assigned Versus Random,Countermeasure-Like Responses in the P300 Based Complex Trial Protocol for Detection of Deception: Task Demand Effects

We recently introduced an accurate and countermeasure resistant P300-based deception detection test called the complex trial protocol (Rosenfeld et al. in Psychophysiology 45(6):906–919, 2008). When subjects use countermeasures to all irrelevant items in the test, the probe P300 is increased rather than reduced (as it was in previous P300-based deception protocols), allowing detection of countermeasure users. The current experiment examines the role of task demand on the complex trial protocol by forcing the subject to make countermeasure-like response to stimuli. Subjects made either a simple random button response to both probe and irrelevant stimuli (experiment 1) or a more complex, assigned, button response to probe and irrelevant stimuli (experiment 2). We found that an increase in task demand reduced the effectiveness of the test. Using random responses we found a simple guilty hit rate of 11/12 with no false positives, but only a 4/11 hit rate for countermeasure-users. Using assigned responses we found a simple guilty hit rate of 8/15 with no false positives, and a 7/16 hit rate for countermeasure-users. We herein suggest that the high level of task demand associated with these countermeasure-like responses causes reduced hit rates.     

Oxidative Damage Markers Are Significantly Associated with the Carotid Artery Intima-Media Thickness after Controlling for Conventional Risk Factors of Atherosclerosis in Men

Background

This study aimed to assess the association between oxidative damage markers and carotid artery intima-media thickness (CIMT) after controlling for conventional risk factors of atherosclerosis in multiple logistic regression models.

Methods and Findings

Fifty-one case male participants (CIMT ≥ 0.9 mm) were enrolled during their visits to Korean Genomic Rural Cohort Study of Wonju centers between May 1 and August 31, 2011, along with 51 control participants (CIMT < 0.9 mm) selected using frequency matching by age group. The levels of oxidative damage markers, 8-hydroxy-2′-deoxyquuanosine (8-OHdG), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (Isoprostane), were measured. Conditional logistic regression models were used to evaluate relative relationships between the oxidative damage markers and the risk of high CIMT.

Results

The markers of oxidative lipid (Isoprostane and MDA) and DNA (8-OHdG) damage were associated with CIMT after controlling for the conventional risk factors, including age, low density lipoprotein, body mass index, smoking history, alcohol consumption, and metabolic syndrome (ORs [95% CI] for Isoprostane: 3^rd tertile, 8.47 [2.59-27.67]; for MDA: 3^rd tertile, 8.47 [2.59-27.67]; for 8-OHdG: 3^rd tertile, 5.58 [1.79-17.33]). When all the oxidative damage markers were incorporated in the same logistic regression model, only Isoprostanewas significantly related to CIMT (OR [95% CI]: 4.22 [1.31-13.53] in 2^nd tertile and 14.21 [3.34-60.56] in 3^rd tertile).

Conclusions

In this nested case-control study, the oxidative damage markers of lipid and DNA were associated with CIMT even after controlling for the conventional risk factors of cardiovascular diseases.     

Stable and Efficient Genetic Modification of Cells in the Adult Mouse V-SVZ for the Analysis of Neural Stem Cell Autonomous and Non-autonomous Effects

Relatively quiescent somatic stem cells support life-long cell renewal in most adult tissues. Neural stem cells in the adult mammalian brain are restricted to two specific neurogenic niches: the subgranular zone of the dentate gyrus in the hippocampus and the ventricular-subventricular zone (V-SVZ; also called subependymal zone or SEZ) in the walls of the lateral ventricles. The development of in vivo gene transfer strategies for adult stem cell populations (i.e. those of the mammalian brain) resulting in long-term expression of desired transgenes in the stem cells and their derived progeny is a crucial tool in current biomedical and biotechnological research. Here, a direct in vivo method is presented for the stable genetic modification of adult mouse V-SVZ cells that takes advantage of the cell cycle-independent infection by LVs and the highly specialized cytoarchitecture of the V-SVZ niche. Specifically, the current protocol involves the injection of empty LVs (control) or LVs encoding specific transgene expression cassettes into either the V-SVZ itself, for the in vivo targeting of all types of cells in the niche, or into the lateral ventricle lumen, for the targeting of ependymal cells only. Expression cassettes are then integrated into the genome of the transduced cells and fluorescent proteins, also encoded by the LVs, allow the detection of the transduced cells for the analysis of cell autonomous and non-autonomous, niche-dependent effects in the labeled cells and their progeny.     

Effects of 3,5,3'-triiodo-L-thyronine on the enzymes responsible for the metabolism of xenobiotics in the rat after increase in the dietary supply of cholesterol

A cholesterol rich diet fed to rats was found to increase the cytochrome P 450 content in hepatic microsomes. Furthermore, the variations of the same parameters promoted by 3,5,3'-triiodo-L-thyronine were strongly reduced in cholesterol supplemented rats. Cholesterol prevented the inducing effects of phenobarbital but did not oppose its decreasing effect on maximal fluorescence of ANS and PNA introduced into the microsome suspensions.