Sex-specific meiotic recombination in the Prader—Willi/Angelman syndrome imprinted region

Meiotic recombination is a specifically timed and regulated process which does not occur randomly throughout the genome, but tends to be clustered in ‘hotspots'. There is extensive evidence that recombinatlon rate is influenced by chromatin conformation and that events are primarily initiated at gene promoter regions. In an effort to determine the pattern of chromatin condensation and recombinatlon at meiosis in an imprinted region, fine scale genetic mapping in the approximately 4 Mb Prader-Willi/Angelman syndrome deletion region was undertaken. The results Indicate that the male-female recombinatlon ratio can vary significantly over short regions. A male recombinatlon hotspot is localized to between the 3' end of GABRA5 and Dl 5S1 56, which Is adjacent to but outside the putative AS/PWS imprinted regions. In addition, a region of relatively high recombination In females is observed between Dl 5S1 28 and D15S97, which spans a domain of paternal allele-specific transcription implicated in the Prader-Willi syndrome. It is inferred that the Inactivation and relative condensation of this latter region on the maternal chromosome occurs as a post-meiotic modificatio

Threshold behavior in metastable dissociation of multi-photon ionized thymine and uracil

Microsecond-timescale HNCO loss has been observed from single-color multi-photon ionized pyrimidine nucleobases in the gas phase. Photon energy thresholds for the metastable channels have been measured at 5.55 ± 0.02 eV for thymine and 5.57 ± 0.02 eV for uracil. We argue that these results can be attributed to accessing the molecules’ S1 states with additional vibrational energy matching the threshold energy for HNCO loss from the radical cation. Combined with previous photoionization energies, this enables the S1 adiabatic energies to be deduced: 3.67 ± 0.07 eV for thymine and 3.77 ± 0.07 eV for uracil. These values are consistent with recent calculations

Efficient design and evaluation of countermeasures against fault attacks using formal verification

This paper presents a formal verification framework and tool that evaluates the robustness of software countermeasures against fault-injection attacks. By modeling reference assembly code and its protected variant as automata, the framework can generate a set of equations for an SMT solver, the solutions of which represent possible attack paths. Using the tool we developed, we evaluated the robustness of state-of-the-art countermeasures against fault injection attacks. Based on insights gathered from this evaluation, we analyze any remaining weaknesses and propose applications of these countermeasures that are more robust

Effect of age on the hemodynamic and sympathetic responses at the onset of isometric handgrip exercise.

Cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise. We tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained, despite a diminished cardiac function. Twelve young and twelve older (24 ± 3 and 63 ± 8 yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Mean arterial pressure (MAP) and cardiac output (Q) were assessed continuously by finger plethysmography and total peripheral resistance was calculated. MAP increased with the onset of handgrip; this increase was associated with handgrip intensity and was similar in both groups. Heart rate and Q increased with increasing handgrip intensity in both groups, but increases were greater in young vs. older individuals (age × handgrip intensity interaction, P \u3c 0.05). MSNA burst frequency increased (P \u3c 0.01), while MSNA burst incidence tended to increase (P = 0.06) with increasing handgrip intensity in both groups. The change in MSNA between baseline and handgrip, for both frequency and incidence, increased with increasing handgrip intensity for both groups. There was no effect of handgrip intensity or age on total peripheral resistance. The smaller heart rate and Q response during the first 20 s of handgrip exercise in older individuals was not accompanied by a greater sympathetic activation or vasoconstrictor response. However, increases in MAP were similar between groups, indicating that the pressor response at the onset of handgrip exercise is preserved with aging

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

A mutual reference shape based on information theory

International audienceIn this paper, we propose to consider the estimation of a refer-ence shape from a set of different segmentation results using both active contours and information theory. The reference shape is defined as the minimum of a criterion that benefits from both the mutual information and the joint entropy of the input segmentations and called a mutual shape. This energy criterion is here justified using similarities between informa-tion theory quantities and area measures, and presented in a continuous variational framework. This framework brings out some interesting evaluation measures such as the speci-ficity and sensitivity. In order to solve this shape optimization problem, shape derivatives are computed for each term of the criterion and interpreted as an evolution equation of an active contour. Some synthetical examples allow us to cast the light on the difference between our mutual shape and an average shape. Our framework has been considered for the estimation of a mutual shape for the evaluation of cardiac segmentation methods in MRI

Effects of 6 Months of Exercise-Based Cardiac Rehabilitation on Autonomic Function and Neuro-Cardiovascular Stress Reactivity in Coronary Artery Disease Patients

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P\u3c0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P\u3c0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P\u3c0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P\u3c0.01). Heart rate variability (all P\u3e0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P\u3e0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P\u3c0.05); yet, responses were reduced following CR (all P\u3c0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training

Stabilities of nanohydrated thymine radical cations: insights from multiphoton ionization experiments and ab initio calculations

Multi-photon ionization experiments have been carried out on thymine-water clusters in the gas phase. Metastable H2O loss from T+(H2O)n was observed at n ≥ 3 only. Ab initio quantum-chemical calculations of a large range of optimized T+(H2O)n conformers have been performed up to n = 4, enabling binding energies of water to be derived. These decrease smoothly with n, consistent with the general trend of increasing metastable H2O loss in the experimental data. The lowest-energy conformers of T+(H2O)3 and T+(H2O)4 feature intermolecular bonding via charge-dipole interactions, in contrast with the purely hydrogen-bonded neutrals. We found no evidence for a closed hydration shell at n = 4, also contrasting with studies of neutral clusters