Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. © 2013 European Molecular Biology Organization

Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

Quantum phase transition in a single-molecule quantum dot

Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many-particle physical system is forced to evolve continuously between two distinct, competing ground states. This phenomenon, often related to a zero-temperature magnetic phase transition, can be observed in several strongly correlated materials such as heavy fermion compounds or possibly high-temperature superconductors, and is believed to govern many of their fascinating, yet still unexplained properties. In contrast to these bulk materials with very complex electronic structure, artificial nanoscale devices could offer a new and simpler vista to the comprehension of quantum phase transitions. This long-sought possibility is demonstrated by our work in a fullerene molecular junction, where gate voltage induces a crossing of singlet and triplet spin states at zero magnetic field. Electronic tunneling from metallic contacts into the $\rm{C_{60}}$ quantum dot provides here the necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure

Shape-Based Tracking Allows Functional Discrimination of Two Immune Cell Subsets Expressing the Same Fluorescent Tag in Mouse Lung Explant

Dendritic Cells (DC) represent a key lung immune cell population, which play a critical role in the antigen presenting process and initiation of the adaptive immune response. The study of DCs has largely benefited from the joint development of fluorescence microscopy and knock-in technology, leading to several mouse strains with constitutively labeled DC subsets. However, in the lung most transgenic mice do express fluorescent protein not only in DCs, but also in closely related cell lineages such as monocytes and macrophages. As an example, in the lungs of CX3CR1+/gfp mice the green fluorescent protein is expressed mostly by both CD11b conventional DCs and resident monocytes. Despite this non-specific staining, we show that a shape criterion can discriminate these two particular subsets. Implemented in a cell tracking code, this quantified criterion allows us to analyze the specific behavior of DCs under inflammatory conditions mediated by lipopolysaccharide on lung explants. Compared to monocytes, we show that DCs move slower and are more confined, while both populations do not have any chemotactism-associated movement. We could generalize from these results that DCs can be automatically discriminated from other round-shaped cells expressing the same fluorescent protein in various lung inflammation models

Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees

The spread of infectious diseases crucially depends on the pattern of contacts among individuals. Knowledge of these patterns is thus essential to inform models and computational efforts. Few empirical studies are however available that provide estimates of the number and duration of contacts among social groups. Moreover, their space and time resolution are limited, so that data is not explicit at the person-to-person level, and the dynamical aspect of the contacts is disregarded. Here, we want to assess the role of data-driven dynamic contact patterns among individuals, and in particular of their temporal aspects, in shaping the spread of a simulated epidemic in the population. We consider high resolution data of face-to-face interactions between the attendees of a conference, obtained from the deployment of an infrastructure based on Radio Frequency Identification (RFID) devices that assess mutual face-to-face proximity. The spread of epidemics along these interactions is simulated through an SEIR model, using both the dynamical network of contacts defined by the collected data, and two aggregated versions of such network, in order to assess the role of the data temporal aspects. We show that, on the timescales considered, an aggregated network taking into account the daily duration of contacts is a good approximation to the full resolution network, whereas a homogeneous representation which retains only the topology of the contact network fails in reproducing the size of the epidemic. These results have important implications in understanding the level of detail needed to correctly inform computational models for the study and management of real epidemics

Predicting mental imagery based BCI performance from personality, cognitive profile and neurophysiological patterns

Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy— EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants’ BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants’ performance with a mean error of less than 3 points. This study determined how users’ profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user

Psychophysiological effects of massage-myofascial release after exercise: a randomized sham-control study

This is a copy of an article published in the Journal of Alternative and Complementary Medicine © 2008 Mary Ann Liebert, Inc.; Journal of Alternative and Complementary Medicine is available online at: http://online.liebertpub.com.Objective: The aim of this study was to evaluate the effect of massage on neuromuscular recruitment, mood state, and mechanical nociceptive threshold (MNT) after high-intensity exercise. Design: This was a prospective randomized clinical trial using between-groups design. Setting: The study was conducted at a university-based sports medicine clinic. Participants: Sixty-two (62) healthy active students age 18–26 participated. Interventions: Participants, randomized into two groups, performed three 30-second Wingate tests and immediately received whole-body massage-myofascial induction or placebo (sham ultrasound/magnetotherapy) treatment. The duration (40 minutes), position, and therapist were the same for both treatments. Main outcome measures: Dependent variables were surface electromyography (sEMG) of quadriceps, profile of mood states (POMS) and mechanical nociceptive threshold (MNT) of trapezius and masseter muscles. These data were assessed at baseline and after exercise and recovery periods. Results: Generalized estimating equations models were performed on dependent variables to assess differences between groups. Significant differences were found in effects of treatment on sEMG of Vastus Medialis (VM) (p 0.02) and vigor subscale (p 0.04). After the recovery period, there was a significant decrease in electromyographic (EMG) activity of VM (p 0.02) in the myofascial-release group versus a nonsignificant increase in the placebo group (p 0.32), and a decrease in vigor (p 0.01) in the massage group versus no change in the placebo group (p 0.86). Conclusions: Massage reduces EMG amplitude and vigor when applied as a passive recovery technique after a high-intensity exercise protocol. Massage may induce a transient loss of muscle strength or a change in the muscle fiber tension–length relationship, influenced by alterations of muscle function and a psychological state of relaxation.The trial was funded by a research project grant (11/UPB10/06) from the Spanish Higher Sports Council

Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

<p/> <p>Background</p> <p>Hypersentivity Syndrome (HS) may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature.</p> <p>Case presentation</p> <p>A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months.</p> <p>Conclusion</p> <p>Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.</p

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio