Metal-directed columnar phase formation in tetrahedral zinc(II) and manganese(II) metallomesogens

New, non-discoid M(II) complexes [MCl2(L)] {M = Mn, Zn; L = 2,6-diformyl-4- methylphenolbis[3’,4’,5’-tris(hexadecyloxy)phenylimine]} have been prepared and shown to exhibit columnar mesophases, the nature of which was found to be metal-dependent. As analysed by DSC and small-angle X-ray diffraction experiments, the complex [ZnCl2(L)] exhibits a single mesophase with rectangular symmetry (Colr) between 46 and 145 °C, whereas the Mn(II) analogue [MnCl2(L)] displays a purely hexagonal mesophase (Colh) phase between 55 and 285 °C. By combining these results with those obtained from dilatometry, a model for the molecular organisation within the columnar mesophases is proposed. The single-crystal X-ray structure of the related complex [Zn(NO3)(L’)2]NO3.3MeOH {L’ = 2,6-diformyl-4-methylphenolbis[3’,4’,5’-tris(methoxy)phenylimine]} has been determined and supports the proposed mode of binding of the ligand to the metal via only one imine and a phenol

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

DODO: an efficient orthologous genes assignment tool based on domain architectures. Domain based ortholog detection

<p>Abstract</p> <p>Background</p> <p>Orthologs are genes derived from the same ancestor gene loci after speciation events. Orthologous proteins usually have similar sequences and perform comparable biological functions. Therefore, ortholog identification is useful in annotations of newly sequenced genomes. With rapidly increasing number of sequenced genomes, constructing or updating ortholog relationship between all genomes requires lots of effort and computation time. In addition, elucidating ortholog relationships between distantly related genomes is challenging because of the lower sequence similarity. Therefore, an efficient ortholog detection method that can deal with large number of distantly related genomes is desired.</p> <p>Results</p> <p>An efficient ortholog detection pipeline DODO (DOmain based Detection of Orthologs) is created on the basis of domain architectures in this study. Supported by domain composition, which usually directly related with protein function, DODO could facilitate orthologs detection across distantly related genomes. DODO works in two main steps. Starting from domain information, it first assigns protein groups according to their domain architectures and further identifies orthologs within those groups with much reduced complexity. Here DODO is shown to detect orthologs between two genomes in considerably shorter period of time than traditional methods of reciprocal best hits and it is more significant when analyzed a large number of genomes. The output results of DODO are highly comparable with other known ortholog databases.</p> <p>Conclusions</p> <p>DODO provides a new efficient pipeline for detection of orthologs in a large number of genomes. In addition, a database established with DODO is also easier to maintain and could be updated relatively effortlessly. The pipeline of DODO could be downloaded from <url>http://140.109.42.19:16080/dodo_web/home.htm</url></p

GHOSTM: A GPU-Accelerated Homology Search Tool for Metagenomics

A large number of sensitive homology searches are required for mapping DNA sequence fragments to known protein sequences in public and private databases during metagenomic analysis. BLAST is currently used for this purpose, but its calculation speed is insufficient, especially for analyzing the large quantities of sequence data obtained from a next-generation sequencer. However, faster search tools, such as BLAT, do not have sufficient search sensitivity for metagenomic analysis. Thus, a sensitive and efficient homology search tool is in high demand for this type of analysis.We developed a new, highly efficient homology search algorithm suitable for graphics processing unit (GPU) calculations that was implemented as a GPU system that we called GHOSTM. The system first searches for candidate alignment positions for a sequence from the database using pre-calculated indexes and then calculates local alignments around the candidate positions before calculating alignment scores. We implemented both of these processes on GPUs. The system achieved calculation speeds that were 130 and 407 times faster than BLAST with 1 GPU and 4 GPUs, respectively. The system also showed higher search sensitivity and had a calculation speed that was 4 and 15 times faster than BLAT with 1 GPU and 4 GPUs.We developed a GPU-optimized algorithm to perform sensitive sequence homology searches and implemented the system as GHOSTM. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We developed GHOSTM, which is a cost-efficient tool, and offer this tool as a potential solution to this problem

Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families

The microbes that inhabit particular environments must be able to perform molecular functions that provide them with a competitive advantage to thrive in those environments. As most molecular functions are performed by proteins and are conserved between related proteins, we can expect that organisms successful in a given environmental niche would contain protein families that are specific for functions that are important in that environment. For instance, the human gut is rich in polysaccharides from the diet or secreted by the host, and is dominated by Bacteroides, whose genomes contain highly expanded repertoire of protein families involved in carbohydrate metabolism. To identify other protein families that are specific to this environment, we investigated the distribution of protein families in the currently available human gut genomic and metagenomic data. Using an automated procedure, we identified a group of protein families strongly overrepresented in the human gut. These not only include many families described previously but also, interestingly, a large group of previously unrecognized protein families, which suggests that we still have much to discover about this environment. The identification and analysis of these families could provide us with new information about an environment critical to our health and well being

Searches for Gravitational Waves from Binary Neutron Stars: A Review

A new generation of observatories is looking for gravitational waves. These waves, emitted by highly relativistic systems, will open a new window for ob- servation of the cosmos when they are detected. Among the most promising sources of gravitational waves for these observatories are compact binaries in the final min- utes before coalescence. In this article, we review in brief interferometric searches for gravitational waves emitted by neutron star binaries, including the theory, instru- mentation and methods. No detections have been made to date. However, the best direct observational limits on coalescence rates have been set, and instrumentation and analysis methods continue to be refined toward the ultimate goal of defining the new field of gravitational wave astronomy.Comment: 30 pages, 5 Figures, to appear in "Short-Period Binary Stars: Observations, Analyses, and Results", Ed.s Eugene F. Milone, Denis A. Leahy, David W. Hobil

Gravitational Waves from Gravitational Collapse

Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins

<p>Abstract</p> <p>Background</p> <p>Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation.</p> <p>Results</p> <p>We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes.</p> <p>Conclusions</p> <p>Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.</p