Photic resetting in night-shift work: impact on nurses' sleep

The objective of this study was to quantify daytime sleep in night-shift workers with and without an intervention designed to recover the normal relationship between the endogenous circadian pacemaker and the sleep/wake cycle. Workers of the treatment group received intermittent exposure to full-spectrum bright light during night shifts and wore dark goggles during the morning commute home. All workers maintained stable 8-h daytime sleep/darkness schedules. The authors found that workers of the treatment group had daytime sleep episodes that lasted 7.1 ± .1 h (mean?±?SEM) versus 6.6 ± .2 h for workers in the control group (p =?.04). The increase in total sleep time co-occurred with a larger proportion of the melatonin secretory episode during daytime sleep in workers of the treatment group. The results of this study showed reestablishment of a phase angle that is comparable to that observed on a day-oriented schedule favors longer daytime sleep episodes in night-shift workers. (Author correspondence: diane.boivin@douglas.mcgill.ca ).     

Voltage-dependent-anion-channels (VDACs) in Arabidopsis have a dual localization in the cell but show a distinct role in mitochondria

In mammals, the Voltage-dependent anion channels (VDACs) are predominant proteins of the outer mitochondrial membrane (OMM) where they contribute to the exchange of small metabolites essential for respiration. They were shown to be as well associated with the plasma membrane (PM) and act as redox enzyme or are involved in ATP release for example. In Arabidopsis, we show that four out of six genomic sequences encode AtVDAC proteins. All four AtVDACs are ubiquitously expressed in the plant but each of them displays a specific expression pattern in root cell types. Using two complementary approaches, we demonstrate conclusively that the four expressed AtVDACs are targeted to both mitochondria and plasma membrane but in differential abundance, AtVDAC3 being the most abundant in PM, and conversely, AtVDAC4 almost exclusively associated with mitochondria. These are the first plant proteins to be shown to reside in both these two membranes. To investigate a putative function of AtVDACs, we analyzed T-DNA insertion lines in each of the corresponding genes. Knock-out mutants for AtVDAC1, AtVDAC2 and AtVDAC4 present slow growth, reduced fertility and yellow spots in leaves when atvdac3 does not show any visible difference compared to wildtype plants. Analyses of atvdac1 and atvdac4 reveal that yellow areas correspond to necrosis and the mitochondria are swollen in these two mutants. All these results suggest that, in spite of a localization in plasma membrane for three of them, AtVDAC1, AtVDAC2 and AtVDAC4 have a main function in mitochondria.     

Methyl Jasmonate Increases the Tropane Alkaloid Scopolamine and Reduces Natural Herbivory in Brugmansia suaveolens: Is Scopolamine Responsible for Plant Resistance?

The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10?days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause?Ceffect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.     

Using biofeedback while immersed in a stressful videogame increases the effectiveness of stress management skills in soldiers

This study assessed the efficacy of using visual and auditory biofeedback while immersed in a tridimensional videogame to practice a stress management skill (tactical breathing). All 41 participants were soldiers who had previously received basic stress management training and first aid training in combat. On the first day, they received a 15-minute refresher briefing and were randomly assigned to either: (a) no additional stress management training (SMT) for three days, or (b) 30-minute sessions (one per day for three days) of biofeedback-assisted SMT while immersed in a horror/first-person shooter game. The training was performed in a dark and enclosed environment using a 50-inch television with active stereoscopic display and loudspeakers. On the last day, all participants underwent a live simulated ambush with an improvised explosive device, where they had to provide first aid to a wounded soldier. Stress levels were measured with salivary cortisol collected when waking-up, before and after the live simulation. Stress was also measured with heart rate at baseline, during an apprehension phase, and during the live simulation. Repeated-measure ANOVAs and ANCOVAs confirmed that practicing SMT was effective in reducing stress. Results are discussed in terms of the advantages of the proposed program for military personnel and the need to practice SMT.     

Glutathione Depletion and Carbon Ion Radiation Potentiate Clustered DNA Lesions,Cell Death and Prevent Chromosomal Changes in Cancer Cells Progeny

Poor local control and tumor escape are of major concern in head-and-neck cancers treated by conventional radiotherapy or hadrontherapy. Reduced glutathione (GSH) is suspected of playing an important role in mechanisms leading to radioresistance, and its depletion should enable oxidative stress insult, thereby modifying the nature of DNA lesions and the subsequent chromosomal changes that potentially lead to tumor escape.This study aimed to highlight the impact of a GSH-depletion strategy (dimethylfumarate, and l-buthionine sulfoximine association) combined with carbon ion or X-ray irradiation on types of DNA lesions (sparse or clustered) and the subsequent transmission of chromosomal changes to the progeny in a radioresistant cell line (SQ20B) expressing a high endogenous GSH content. Results are compared with those of a radiosensitive cell line (SCC61) displaying a low endogenous GSH level.DNA damage measurements (γH2AX/comet assay) demonstrated that a transient GSH depletion in resistant SQ20B cells potentiated the effects of irradiation by initially increasing sparse DNA breaks and oxidative lesions after X-ray irradiation, while carbon ion irradiation enhanced the complexity of clustered oxidative damage. Moreover, residual DNA double-strand breaks were measured whatever the radiation qualities. The nature of the initial DNA lesions and amount of residual DNA damage were similar to those observed in sensitive SCC61 cells after both types of irradiation. Misrepaired or unrepaired lesions may lead to chromosomal changes, estimated in cell progeny by the cytome assay. Both types of irradiation induced aberrations in nondepleted resistant SQ20B and sensitive SCC61 cells. The GSH-depletion strategy prevented the transmission of aberrations (complex rearrangements and chromosome break or loss) in radioresistant SQ20B only when associated with carbon ion irradiation. A GSH-depleting strategy combined with hadrontherapy may thus have considerable advantage in the care of patients, by minimizing genomic instability and improving the local control.     

Exceptional amyloid beta peptide hydrolyzing activity of nonphysiological immunoglobulin variable domain scaffolds

Nucleophilic sites in the paired variable domains of the light and heavy chains (VL and VH domains) of Ig can catalyze peptide bond hydrolysis. Amyloid beta (Abeta)-binding Igs are under consideration for immunotherapy of Alzheimer disease. We searched for Abeta-hydrolyzing human IgV domains (IgVs) in a library containing a majority of single chain Fv clones mimicking physiological VL-VH-combining sites and minority IgV populations with nonphysiological structures generated by cloning errors. Random screening and covalent selection of phage-displayed IgVs with an electrophilic Abeta analog identified rare IgVs that hydrolyzed Abeta mainly at His14-Gln15. Inhibition of IgV catalysis and irreversible binding by an electrophilic hapten suggested a nucleophilic catalytic mechanism. Structural analysis indicated that the catalytic IgVs are nonphysiological structures, a two domain heterodimeric VL (IgVL2-t) and single domain VL clones with aberrant polypeptide tags (IgVL-t'). The IgVs hydrolyzed Abeta at rates superior to naturally occurring Igs by 3-4 orders of magnitude. Forced pairing of the single domain VL with VH or VL domains resulted in reduced Abeta hydrolysis, suggesting catalysis by the unpaired VL domain.Angstrom level amino acid displacements evident in molecular models of the two domain and unpaired VL domain clones explain alterations of catalytic activity. In view of their superior catalytic activity, the VL domain IgVs may help attain clearance of medically important antigens more efficiently than natural Igs.     

Mechanical properties of coronary stents determined by using finite element analysis.

The mechanical function of a stent deployed in a damaged artery is to provide a metallic tubular mesh structure. The purpose of this study was to determine the exact mechanical characteristics of stents. In order to achieve this, we have used finite-element analysis to model two different type of stents: tubular stents (TS) and coil stents (CS). The two stents chosen for this modeling present the most extreme mechanical characteristics of the respective types. Seven mechanical properties were studied by mathematical modeling with determination of: (1) stent deployment pressure, (2) the intrinsic elastic recoil of the material used, (3) the resistance of the stent to external compressive forces, (4) the stent foreshortening, (5) the stent coverage area, (6) the stent flexibility, and (7) the stress maps. The pressure required for deployment of CS was significantly lower than that required for TS, over 2.8 times greater pressure was required for the tubular model. The elastic recoil of TS is higher than CS (5.4% and 2.6%, respectively). TS could be deformed by 10% at compressive pressures of between 0.7 and 1.3 atm whereas CS was only deformed at 0.2 and 0.7 atm. The degree of shortening observed increases with deployment diameter for TS. CS lengthen during deployment. The metal coverage area is two times greater for TS than for CS. The ratio between the stiffness of TS and that of CS varies from 2060 to 2858 depending on the direction in which the force is applied. TS are very rigid and CS are significantly more flexible. Stress mapping shows stress to be localized at link nodes. This series of finite-element analyses illustrates and quantifies the main mechanical characteristics of two different commonly used stents. In interventional cardiology, we need to understand their mechanisms of implantation and action.     

Discrimination between precancerous and cancerous lesions of the uterine cervix by DNA measurements on tissue sections

Morphologically typical uterine cervical biopsies were separated into normal cervices, condylomas and cervical intraepithelial neoplasias (CIN) grades I, II and III. At least 100 nuclei per lesion were measured on 4 micron Feulgen-stained sections using a Zeiss microspectrophotometer, with a variant of the plug method used to compute the nuclear DNA content. DNA distribution histograms were then decomposed into subsets of diploid, tetraploid, octoploid and aneuploid cells. The decomposition, which assumed a log-normal model of polydiploidy distribution, led to the identification of six indices: (1) the percentage of diploid cells, (2) the percentage of tetraploid cells, (3) the percentage of octoploid cells, (4) the percentage of aneuploid cells with DNA contents less than tetraploidy, (5) the percentage of aneuploid cells with DNA contents between tetraploidy and octaploidy and (6) the percentage of aneuploid cells with DNA contents greater than octoploidy. These indices, along with the mean nuclear radius, the 5c exceeding rate and the 2c deviation index, generated a nine-dimensional space. Two methods of discriminant analysis on this space showed discriminating powers of 78.22% and 87.13%, respectively, as compared to the original diagnoses. The most discriminating variable in both analyses appeared to be the percentage of octoploid cells.     

Phosphofructokinase isozymes from human organs and blood cells.

Phosphofructokinase (PFK) isozymes of blood cells and some human tissues were studied by starch gel electrophoresis and immunoprecipitation by anti-muscle and anti-erythrocyte PFK sera. PFK from muscle, heart, brain and placenta were totally precipitated by both antisera. PFK from blood cells (erythrocytes, lymphocytes, granulocytes, platelets) were precipitated more strongly by anti-erythrocyte PFK serum than by anti-muscle PFK serum. Liver, kidney and monoblast PFK were slightly precipitated by both antisera. From the electrophoretic patterns and the immunoprecipitation curves we may conclude that muscle contains the homotetrameric M4 forms; platelet, liver and kidney the homotetrameric E4 form, and blood cells the M-E hybrids. Monoblasts probably contain a E4 type PFK precursor, and heart, placenta and brain, a modified M4 type PFK. Other isozymes, unrelated with muscle and erythrocyte, were revealed in liver and kidney.