How do sister DNAs become entrapped within cohesin rings?

Sister chromatid cohesion (cohesion) is a process that ensures accurate segregation of genetic material into daughter cells during mitosis in eukaryotic cells. Cohesion is mediated by a highly conserved ring-shaped protein complex called cohesin. Cohesion is thought to arise from the topological entrapment of replicated sister DNAs inside the cohesin ring. Although cohesin can load onto, and topologically entrap individual DNAs prior to DNA replication, cohesion is established during S-phase in concert with DNA replication. Analysis of small circular DNAs in yeast has revealed that cohesion establishment can occur by two pathways operating in parallel. Firstly, cohesin can load onto replicated sister DNAs de novo in a manner that is dependent on the cohesin loading protein Scc2. Secondly, there exists a ‘conversion’ pathway in which cohesin binds to unreplicated DNA during G1, and remains associated with DNA throughout S-phase during which it is converted into cohesive cohesin. This process is independent of Scc2 but requires a group of replisome-associated factors which include Ctf4. Whether this cohesin conversion pathway generates cohesion of yeast chromosomes, and the molecular mechanisms underlying conversion, remain largely unknown. It is thought that opening of cohesin’s Smc1-Smc3 hinge is crucial for entrapment of individual DNAs, but whether this is the case for entrapment of sister DNAs is currently unclear. I have developed a unique assay to measure cohesion generated solely by cohesin rings associated with DNA from G1. Using this assay, we show for the first time that conversion of non-cohesive cohesin to cohesive cohesin occurs on S. cerevisiae chromosomes during DNA replication, and that this process does not require opening of the Smc1-Smc3 hinge. Furthermore, the conversion observed was significantly reduced by deletion of Ctf4 but not significantly impacted by inactivation of the cohesin loader Scc2. These data provide crucial mechanistic insight into the process of cohesin conversion, and unequivocally demonstrate that while hinge opening is required for loading of cohesin rings onto DNA, it is not required for conversion of these rings into cohesive forms

Noise-induced synchronization and anti-resonance in excitable systems; Implications for information processing in Parkinson's Disease and Deep Brain Stimulation

We study the statistical physics of a surprising phenomenon arising in large networks of excitable elements in response to noise: while at low noise, solutions remain in the vicinity of the resting state and large-noise solutions show asynchronous activity, the network displays orderly, perfectly synchronized periodic responses at intermediate level of noise. We show that this phenomenon is fundamentally stochastic and collective in nature. Indeed, for noise and coupling within specific ranges, an asymmetry in the transition rates between a resting and an excited regime progressively builds up, leading to an increase in the fraction of excited neurons eventually triggering a chain reaction associated with a macroscopic synchronized excursion and a collective return to rest where this process starts afresh, thus yielding the observed periodic synchronized oscillations. We further uncover a novel anti-resonance phenomenon: noise-induced synchronized oscillations disappear when the system is driven by periodic stimulation with frequency within a specific range. In that anti-resonance regime, the system is optimal for measures of information capacity. This observation provides a new hypothesis accounting for the efficiency of Deep Brain Stimulation therapies in Parkinson's disease, a neurodegenerative disease characterized by an increased synchronization of brain motor circuits. We further discuss the universality of these phenomena in the class of stochastic networks of excitable elements with confining coupling, and illustrate this universality by analyzing various classical models of neuronal networks. Altogether, these results uncover some universal mechanisms supporting a regularizing impact of noise in excitable systems, reveal a novel anti-resonance phenomenon in these systems, and propose a new hypothesis for the efficiency of high-frequency stimulation in Parkinson's disease

Autoencoder-based Joint Communication and Sensing of Multiple Targets

We investigate the potential of autoencoders (AEs) for building a joint communication and sensing (JCAS) system that enables communication with one user while detecting multiple radar targets and estimating their positions. Foremost, we develop a suitable encoding scheme for the training of the AE and for targeting a fixed false alarm rate of the target detection during training. We compare this encoding with the classification approach using one-hot encoding for radar target detection. Furthermore, we propose a new training method that complies with possible ambiguities in the target locations. We consider different options for training the detection of multiple targets. We can show that our proposed approach based on permuting and sorting can enhance the angle estimation performance so that single snapshot estimations with a low standard deviation become possible. We outperform an ESPRIT benchmark for small numbers of measurement samples

A novel adenovirus vector for easy cloning in the E3 region downstream of the CMV promoter

The construction of expression vectors derived from the human adenovirus type 5 (Ad5), usually based on homologous recombination, is time consuming as a shuttle plasmid has to be selected before recombination with the viral genome. Here, we describe a method allowing direct cloning of a transgene in the E3 region of the Ad5 genome already containing the immediate early CMV promoter upstream of three unique restriction sites. This allowed the construction of recombinant adenoviral genomes in just one step, reducing considerably the time of selection and, of course, production of the corresponding vectors. Using this vector, we produced recombinant adenoviruses, each giving high-level expression of the transgene in the transduced cells

What is the place of complementary and alternative therapies in the management of inflammatory bowel disease?

Les patients atteints de maladies inflammatoires chroniques intestinales (MICI) sont classés parmi les plus grands consommateurs de thérapies complémentaires et alternatives. En effet, les MICI impactent fortement la qualité de vie des patients du fait de leur caractère chronique et de la limite des traitements et de la réticence des patients pour les médicaments actuellement disponibles. Les thérapies complémentaires et alternatives deviennent actuellement très populaires y compris dans les pays occidentaux. L'objectif de cette mise au point est de développer les principales thérapies complémentaires, leur mécanisme d'action ainsi que l'evidence-based-medicine disponibles pour chacune d'entre elles tout en ayant conscience de la nécessité de faire appel aux sciences humaines pour leur évaluation.Patients with inflammatory bowel disease (IBD) are among the largest consumers of complementary and alternative therapies. IBD have a strong impact on patients' quality of life because of their chronic nature and the limitations and the reluctance of patients for the drugs currently available. Complementary and alternative medicines (CAMs) are currently becoming very popular, including in Western countries. The aim of this review is to develop main CAMs, their mechanism of action as well as the evidence-based-medicine available for each of them

Pre-clinical development as microbicide of zinc tetra-ascorbo-camphorate, a novel terpenoid derivative: Potent in vitro inhibitory activity against both R5- and X4-tropic HIV-1 strains without significant in vivo mucosal toxicity

<p>Abstract</p> <p>Background</p> <p>Terpenoid derivatives originating from many plants species, are interesting compounds with numerous biological effects, such as anti-HIV-1 activity. The zinc tetra-ascorbo-camphorate complex (or "C14"), a new monoterpenoid derivative was evaluated in vitro for its anti-HIV-1 activity on both R5- and X4-HIV-1 infection of primary target cells (macrophages, dendritic cells and T cells) and on HIV-1 transfer from dendritic cells to T cells.</p> <p>Results</p> <p>The toxicity study was carried out in vitro and also with the New Zealand White rabbit vaginal irritation model. C14 was found to be no cytotoxic at high concentrations (CC50 > 10 μM) and showed to be a potential HIV-1 inhibitor of infection of all the primary cells tested (EC50 = 1 μM). No significant changes could be observed in cervicovaginal tissue of rabbit exposed during 10 consecutive days to formulations containing up to 20 μM of C14.</p> <p>Conclusion</p> <p>Overall, these preclinical studies suggest that zinc tetra-ascorbo-camphorate derivative is suitable for further testing as a candidate microbicide to prevent male-to-female heterosexual acquisition of HIV-1.</p

Elastin-Derived Peptides Are New Regulators of Thrombosis

International audienc

The Innate Immune Response in Eisenia Fetida to Microbial Challenges

The common earthworm, Eisenia fetida, exhibits a rudimentary immune system. The earthworm needs cellular and chemical responses against a constant microbial exposure from its natural environment. Some cellular and chemical responses are found in the coelomic fluid and have been shown to demonstrate anti-microbial characteristics. This project uses microscopy and modified staining techniques to differentiate and categorize the cellular components found in the coelomic fluid. Following a microbial challenge by Klebsiella pneumoniae, an inflammatory response was initiated. Six groups of earthworms were injected with 0.05 ml of 1.0 x 106 cfu /ml K. pneumoniae on day one and tested over a period of five days. A group of three worms was shocked each day for the next five days to cause the coelomic fluid and cells to pass through the body wall. The coelomic fluid was placed directly on glass slides, dried and stained with a modified Wright’s stain using a wash buffer solution with a pH of 6.3. The stained cells were differentiated into four categories. Total cell counts were determined. The data indicated a marked proliferation in total cell counts in comparison to the control worms. This trend of increasing total cell counts continued over the five days. The percent ages of the four types of coelomic cells from the differential remained constant. Cells were photographed and documented for comparisons. Additional studies are ongoing to determine how long the Eisenia fetida take to remove Klebsiella pneumoniae from the coelomic cavity