Folding and cytoplasm viscoelasticity contribute jointly to chromosome dynamics

The chromosome is a key player of cell physiology, and its dynamics provides valuable information about its physical organization. In both prokaryotes and eukaryotes, the short-time motion of chromosomal loci has been described as a Rouse model in a simple or viscoelastic medium. However, little emphasis has been put on the role played by the folded organization of chromosomes on the local dynamics. Clearly, stress-propagation, and thus dynamics, must be affected by such organization, but a theory allowing to extract such information from data, e.g.\ of two-point correlations, is lacking. Here, we describe a theoretical framework able to answer this general polymer dynamics question, and we provide a general scaling analysis of the stress-propagation time between two loci at a given arclength distance along the chromosomal coordinate. The results suggest a precise way to detect folding information from the dynamical coupling of chromosome segments. Additionally, we realize this framework in a specific theoretical model of a polymer with variable-range interactions in a viscoelastic medium characterized by a tunable scaling exponent, where we derive analytical estimates of the correlation functions.Comment: 14 pages including supplementary material

Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: Functional and therapeutic implications

This article is made available through the Brunel Open Access Publishing Fund. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear. Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5′-flanking region. Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members. MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU. Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects. The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results. Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference. Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU.SPARKS, The Neuroblastoma Society, a Wellcome Trust grant (to A. S.), and the Italian Association for Cancer Research

European Non-native Species in Aquaculture Risk Analysis Scheme - a summary of assessment protocols and decision support tools for use of alien species in aquaculture

The European Non-native Species in Aquaculture Risk Analysis Scheme (ENSARS) was developed in response to European 'Council Regulation No. 708/2007 of 11 June 2007 concerning use of alien and locally absent species in aquaculture' to provide protocols for identifying and evaluating the potential risks of using non-native species in aquaculture. ENSARS is modular in structure and adapted from non-native species risk assessment schemes developed by the European and Mediterranean Plant Protection Organisation and for the UK. Seven of the eight ENSARS modules contain protocols for evaluating the risks of escape, introduction to and establishment in open waters, of any non-native aquatic organism being used (or associated with those used) in aquaculture, that is, transport pathways, rearing facilities, infectious agents, and the potential organism, ecosystem and socio-economic impacts. A concluding module is designed to summarise the risks and consider management options. During the assessments, each question requires the assessor to provide a response and confidence ranking for that response based on expert opinion. Each module can also be used individually, and each requires a specific form of expertise. Therefore, a multidisciplinary assessment team is recommended for its completion

Sperm ultra-structure of <i>Odontosyllis ctenostoma</i> (Polychaeta: Syllidae) with inferences on syllid phylogeny and reproductive biology

The analysis of the complex reproductive patterns of Syllidae may drastically change the taxonomic hierarchy of the family. To further contribute to the knowledge of Syllidae we have described the sperm ultra-structure and some steps of spermiogenesis of Odontosyllis ctenostoma Claparède, 1868, the first non interstitial eusylline investigated. The mature sperm has a bell-shaped acrosome and contains electron-dense granular material and thin filaments. The barrel-shaped nucleus bears two depressions: one anterior facing the acrosome and the other posterior partially containing the distal centriole and up to six mitochondria. Odontosyllis ctenostoma spermatozoa can be ascribed to the ect-aquasperm type typical of species practising external fertilisation. This morphology is not in complete accordance either with the particular brood protection reported for the species or the egg size. The sperm is similar to those of the Syllinae species thus far investigated, but the acrosome resembles that of the exogonine spermatid. Some authors consider Odontosyllis to be phylogenetically closer to Syllinae, though it shares epigamy with Exogoninae. Others have hypothesised that the exogonine sperm could have been derived from sylline sperm by simplification. In our hypothesis this could have happened through a gradual passage from an Odontosyllis-like eusylline ancestor

Sperm ultra-structure and spermiogenesis in <i>Syllis krohni</i> (Polychaeta: Syllidae), with some observations on its reproductive biology

yllidae show a wide spectrum of both reproductive strategies and sperm types. Analysis of their reproductive patterns could drastically change the presently accepted taxonomic hierarchy of the group. To further contribute to the knowledge of Syllidae we have described the sperm ultra-structure and the spermiogenesis of Syllis krohni (Ehlers, 1864). Mature sperm has a cone-shaped acrosome whose distal end is notched by a trough that transversely encircles its anterior portion. During spermiogenesis, the acrosomal vesicle undergoes modifications leading to its final shape with a posterior opening. The nucleus appears flattened anteriorly and forms a cleft that surrounds the proximal centriole in its distal region. A 9+2 flagellar axoneme is observed. Up to five mitochondria surround the distal centriole. The spermatozoon of S. krohni can be ascribed to the ect-aquasperm type that is typical in species having external fertilisation and appears to be very similar in appearance to that of the congeneric species thus far investigated. The main difference is in the shape of the acrosome, which is more elongated and as long as the nucleus. Reproduction of syllids seems to be conservative within sub-families, and the sperm morphology can probably help in phylogenetic reconstruction. External fertilisation is a widespread strategy within the genus Syllis, probably leading to a substantial similarity in sperm morphology being maintained. It is hypothesised, however, that within the same sperm type linked to a particularly reproductive strategy, the acrosome ultra-structure can be indicative of phylogeny

Reply to comment by S. Peacock on “Glacial-interglacial circulation changes inferred from 231Pa/230Th sedimentary record in the North Atlantic region”

Peacock [2010, P10 hereafter] takes issue with several aspects of our recent article [Gherardi et al., 2009, G09hereafter]: (1) our description of the modern Atlantic meridional overturning circulation (AMOC), (2) apparent inconsistencies between modern circulation and our Holo-cene sedimentary 231Pa/230Th bathymetric profile, and (3) our use of cores for reconstructing AMOC from locations that do not lie beneath the Deep Western Boundary Current (DWBC). We welcome the comment as it affords us the opportunity to clarify important aspects of our approach to studying paleocirculation and to address any potential mis-understandings arising from the wording of our original text

How «personal» is the «personal Health Record»? Technology and patient empowerment in the care of Diabetes

This paper explores the role and meaning of medical information against the backdrop of new digital tools that allow for new forms of data management and sharing within the healthcare management network. The research investigates data management practices by parents of children with Type 1 diabetes as they are enabled by a Personal Health Record to become stewards of their own medical information. The underlying assumption of this and similar technologies is that they would support patient-provided collaboration and reduce the information gap between clinical encounters. Drawing on a qualitative research design, the authors analyze data management and sharing practices among patients and healthcare providers before and after the introduction of a digital logbook for diabetes management in the pediatric department of a hospital in northern Italy. The paper reveals how patients interpreted their new roles in terms of restricting access to their information, rather than facilitating its dissemination, to preserve their own competence and independent management of the information regarding their ≪PersonalGt; diseases

External gestation of Exogone naidina Öersted, 1845 (Polychaeta, Syllidae): Ventral attachment of eggs and embryos

The external gestation of sexually ripe females of the species Exogone naidina (Polychaeta, Syllidae) is described by means of SEM and TEM analysis. The eggs, embryos and juveniles are attached in close vicinity of each parapodial complex in a position immediately below each ventral cirrus and are connected to the female by a cup like structure. The formation of this adhesive disk is linked to secretory cells scattered between dermal cells of ripe female. This adhesive disk is present only in sexually mature animals and is considered as epitokous structure. The evolutive significance of ventral and dorsal attachment found within the Exogoninae is also discussed. © 2003 Elsevier Ltd. All rights reserved