Sound synchronization of bubble trains in a viscous fluid : Experiment and modeling

Acknowledgements: We thank the São Paulo State Agency FAPESP and the Federal Brazilian Agency CNPq for the financial support. M.S.B. acknowledges EPSRC Grant No. EP/IO32606/1.Peer reviewedPublisher PD

A Novel Role of Cdk9/CyclinT2 complexes in skeletal muscle and Rhabdomyosarcoma cells

Cyclin dependent kinase 9 (Cdk9) is a member of the cyclin dependent kinase family. The regulatory units of Cdk9 are the T family Cyclins (T1, T2) and Cyclin K1. Cyclin T2 has two forms termed CycT2a and CycT2b that arise by an alternative splicing of the primary transcript. Previous studies underscored a crucial role for Cdk9 in association of Cyclin T2 during skeletal myogenesis. Upon induction of muscle differentiation, MyoD recruits Cdk9/CycT2 on musclespecific gene promoter sequences. This complex is able to phosphorylate the C-terminal domain of RNA polymerase II, enhancing Myod function and promoting myogenic differentiation. Rhabdomyosarcoma (RMS), one of the most common childhood solid tumor, arises from muscle precursor cells and fails to complete both the differentiation program both the irreversibly cell cycle exit, resulting in uncontrolled proliferation and incomplete myogenesis. In RMS, Cdk9 fails to phosphorylate MyoD and the ability of MyoD to arrest cell proliferation and to activate the myogenic program is repressed. The result of this study confirmed the involvement of Cdk9/ CyclinT2 complexes during the myogenesis. Both isoforms of Cyclin T2 are able to activate the myogenic program at different stages of differentiation but CycT2b have a predominant role of in particular during the latest stages. Moreover we demonstred that EZH2 is probably responsible to inhibition of Cdk9 in RMS cells and her overexpression contribuite to inhibition of myogenesis

Dripping Faucet Dynamics Clarified by an Improved Mass-Spring Model

An improved mass-spring model for a dripping faucet is presented. The model is constructed based on the numerical results which we recently obtained from fluid dynamical calculations. Both the fluid dynamical calculations and the present mass-spring model exhibit a variety of complex behavior including transition to chaos in good agreement with experiments. Further, the mass-spring model reveals fundamental dynamics inherent in the dripping faucet system.Comment: 17 pages, 17 figure

The EEE Project

The new experiment ``Extreme Energy Events'' (EEE) to detect extensive air showers through muon detection is starting in Italy. The use of particle detectors based on Multigap Resistive Plate Chambers (MRPC) will allow to determine with a very high accuracy the direction of the axis of cosmic ray showers initiated by primaries of ultra-high energy, together with a high temporal resolution. The installation of many of such 'telescopes' in numerous High Schools scattered all over the Italian territory will also allow to investigate coincidences between multiple primaries producing distant showers. Here we present the experimental apparatus and its tasks.Comment: 4 pages, 29th ICRC 2005, Pune, Indi

Tailoring Targeted Therapy to Individual Patients: Lessons to be Learnt from the Development of Mitomycin C

The modern era of targeted therapeutics offers the potential to tailor therapy to individual patients whose tumours express a specific target. Previous attempts to forecast tumour response to conventional chemotherapeutics based on similar principles have however been disappointing. Mitomycin C (MMC), for example, is a bioreductive drug that requires metabolic activation by cellular reductases for activity. The enzyme NAD(P)H:Quinone oxidoreductase-1 (NQO1) can reduce MMC to DNA damaging species but attempts to establish the relationship between tumour response to MMC and NQO1 expression have generated conflicting reports of good and poor correlations. Several other reductases are known to activate MMC. This, in conjunction with the fact that various physiological and biochemical factors influence therapeutic response, suggests that the mechanism of action of MMC is too complex to allow tumour response to be predicted on the basis of a single enzyme. Alternative approaches using more complex biological and pharmacological systems that reflect the spectrum of reductases present within the tumour have been developed and it remains to be seen whether or not the predictive value of these approaches is enhanced. With regards to targeted therapeutics, the experience with MMC suggests that prediction of tumour response based on analysis of a single target may be too simplistic. Multiple mechanisms of action and the influence of tumour microenvironment on cell biology and drug delivery are likely to influence the final outcome of therapy. The challenge for the future progression of this field is to develop assays that reflect the overall biological and pharmacological processes involved in drug activation whilst retaining the simplicity and robustness required for routine chemosensitivity testing in a clinical setting

Regulation of skeletal muscle development and homeostasis by gene imprinting, histone acetylation and microRNA

Epigenetics is defined as heritable information other that the DNA sequence itself. The concept implies that the regulation of gene expression is highly complex and epigenetics can control from fine tuning to permanent gene activation/deactivation. Skeletal muscle is the main tissue for locomotion and energy metabolism in the body, and represent at least 40% of the body mass. Body mass and function vary according to age but also quickly adapt to physiological as well as pathological cues. Besides transcriptional mechanisms that control muscle differentiation, postnatal growth and remodeling, there are numerous epigenetic mechanisms of regulation that modulate muscle gene expression. In this review, we describe and discuss only some of the mechanisms of epigenetic regulation - such as DNA methylation, histone modifications, and microRNAs - that have been characterized in detail and that we believe are crucial for skeletal muscle development and disease