Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

High transverse momentum eta meson production in p+p, d+Au and Au+Au collisions at sqrt(s_NN) = 200 GeV

Inclusive transverse momentum spectra of eta mesons in the range p_T~2-12 GeV/c have been measured at mid-rapidity (|\eta| < 0,35) by the PHENIX experiment at RHIC in p+p, d+Au and Au+Au collisions at sqrt(s_NN) = 200 GeV. The eta mesons are reconstructed through their eta--> \gamma\gamma channel for the three colliding systems as well as through the eta-->pi^0 pi+ pi- decay mode in p+p and d+Au collisions. The nuclear modification factor in d+Au collisions, R_dAu(p_T~1.0-1.1, suggests at most only modest p_T broadening ("Cronin enhancement"). In central Au+Au reactions, the eta yields are significantly suppressed, with R_AuAu(pT)~0.2. The ratio of eta to pi^0 yields is approximately constant as a function of p_T for the three colliding systems in agreement with the high-p_T world average of R_eta/pi^0 \approx 0.5 in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions for a wide range of center-of-mass energies [sqrt(s_NN)~3-1800 GeV] as well as, for high scaled momentum x_p, in e+e- annihilations at sqrt(s)=91.2 GeV. These results are consistent with a scenario where high-p_T eta production in nuclear collisions at RHIC is largely unaffected by initial-state effects, but where light-quark mesons (pi^0;eta) are equally suppressed due to final-state interactions of the parent partons in the dense medium produced in Au+Au reactions.Comment: 391 authors, NN pages text, RevTeX4, figures, tables. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms

Long-term associative learning predicts verbal short-term memory performance

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Managing caries:the need to close the gap between the evidence base and current practice

Underpinned by a changing knowledge of the aetiology of caries and its sequelae, and assisted by established and advancing dental materials, there is growing evidence supporting less invasive management of dental caries based on the principles of minimal intervention dentistry. This narrative review assesses both the evidence and the adoption of less invasive caries management strategies and describes ways in which the gap between evidence and practice might be overcome. While there is increasing data supporting less invasive management of carious lesions, these are not standard in most dental practices worldwide. Usually, clinical studies focused on efficacy as outcome, and did not take into consideration the views and priorities of other stakeholders, such as primary care dentists, educators, patients and those financing services. Involving these stakeholders into study design and demonstrating the broader advantages of new management strategies might improve translation of research into practice. In theory, clinical dentists can rely on a growing evidence in cariology regarding less invasive management options. In practice, further factors seem to impede adoption of these strategies. Future research should address these factors by involving major stakeholders and investigating their prioritised outcomes to narrow or close the evidence gap.</p

Pathological replication in cells lacking RecG DNA translocase

Little is known about what happens when forks meet to complete DNA replication in any organism. In this study we present data suggesting that the collision of replication forks is a potential threat to genomic stability. We demonstrate that Escherichia coli cells lacking RecG helicase suffer major defects in chromosome replication following UV irradiation, and that this is associated with high levels of DNA synthesis initiated independently of the initiator protein DnaA. This UV-induced stable DNA replication is dependent on PriA helicase and continues long after UV-induced lesions have been excised. We suggest UV irradiation triggers the assembly of new replication forks, leading to multiple fork collisions outside the terminus area. Such collisions may generate branched DNAs that serve to establish further new forks, resulting in uncontrolled DNA amplification. We propose that RecG reduces the likelihood of this pathological cascade being set in motion by reducing initiation of replication at D- and R-loops, and other structures generated as a result of fork collisions. Our results shed light on why replication initiation in bacteria is limited to a single origin and why termination is carefully orchestrated to a single event within a restricted area each cell cycle

Bifunctional Anti-Huntingtin Proteasome-Directed Intrabodies Mediate Efficient Degradation of Mutant Huntingtin Exon 1 Protein Fragments

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide (CAG)n repeat expansion in the coding sequence of the huntingtin gene, and an expanded polyglutamine (>37Q) tract in the protein. This results in misfolding and accumulation of huntingtin protein (htt), formation of neuronal intranuclear and cytoplasmic inclusions, and neuronal dysfunction/degeneration. Single-chain Fv antibodies (scFvs), expressed as intrabodies that bind htt and prevent aggregation, show promise as immunotherapeutics for HD. Intrastriatal delivery of anti-N-terminal htt scFv-C4 using an adeno-associated virus vector (AAV2/1) significantly reduces the size and number of aggregates in HDR6/1 transgenic mice; however, this protective effect diminishes with age and time after injection. We therefore explored enhancing intrabody efficacy via fusions to heterologous functional domains. Proteins containing a PEST motif are often targeted for proteasomal degradation and generally have a short half life. In ST14A cells, fusion of the C-terminal PEST region of mouse ornithine decarboxylase (mODC) to scFv-C4 reduces htt exon 1 protein fragments with 72 glutamine repeats (httex1-72Q) by ∼80–90% when compared to scFv-C4 alone. Proteasomal targeting was verified by either scrambling the mODC-PEST motif, or via proteasomal inhibition with epoxomicin. For these constructs, the proteasomal degradation of the scFv intrabody proteins themselves was reduced<25% by the addition of the mODC-PEST motif, with or without antigens. The remaining intrabody levels were amply sufficient to target N-terminal httex1-72Q protein fragment turnover. Critically, scFv-C4-PEST prevents aggregation and toxicity of httex1-72Q fragments at significantly lower doses than scFv-C4. Fusion of the mODC-PEST motif to intrabodies is a valuable general approach to specifically target toxic antigens to the proteasome for degradation

Replication fork collisions cause pathological chromosomal amplification in cells lacking RecG DNA translocase

Duplication and transmission of chromosomes require precise control of chromosome replication and segregation. Here we present evidence that RecG is a major factor influencing these processes in bacteria. We show that the extensive DnaA-independent stable DNA replication observed without RecG can lead to replication of any area of the chromosome. This replication is further elevated following irradiation with UV light and appears to be perpetuated by secondary events that continue long after the elimination of UV lesions. The resulting pathological cascade is associated with an increased number of replication forks traversing the chromosome, sometimes with extensive regional amplification of the chromosome, and with the accumulation of highly branched DNA intermediates containing few Holliday junctions. We propose that the cascade is triggered by replication fork collisions that generate 3′ single-strand DNA flaps, providing sites for PriA to initiate re-replication of the DNA and thus to generate linear duplexes that provoke recombination, allowing priming of even further replication. Our results shed light on why termination of replication in bacteria is normally limited to a single encounter of two forks and carefully orchestrated within a restricted area, and explain how a system of multiple forks and random termination can operate in eukaryotes