The electric dipole response of 76^{76}Se above 4 MeV

The dipole response of $^{76}_{34}$Se in the energy range 4 to 9 MeV has been analyzed using a $(\vec\gamma,{\gamma}')$ polarized photon scattering technique, performed at the High Intensity $\gamma$-Ray Source facility, to complement previous work performed using unpolarized photons. The results of this work offer both an enhanced sensitivity scan of the dipole response and an unambiguous determination of the parities of the observed J=1 states. The dipole response is found to be dominated by $E1$ excitations, and can reasonably be attributed to a pygmy dipole resonance. Evidence is presented to suggest that a significant amount of directly unobserved excitation strength is present in the region, due to unobserved branching transitions in the decays of resonantly excited states. The dipole response of the region is underestimated when considering only ground state decay branches. We investigate the electric dipole response theoretically, performing calculations in a 3D cartesian-basis time-dependent Skyrme-Hartree-Fock framework.Comment: 20 pages, 18 figures, to be submitted to PR

Patients’ Perceptions of Memory Functioning Before and After Surgical Intervention to Treat Medically Refractory Epilepsy.

Purpose:One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery. Methods: Objective memory (Wechsler Memory Scale–Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients ∼6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory–2nd Edition) was used to control variance attributable to emotional distress. Results: Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery. Conclusions: In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>FKBP10 </it>gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found <it>FKBP10 </it>mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis.</p> <p>Methods</p> <p>The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures.</p> <p>Results</p> <p>Homozygosity mapping identified <it>FKBP10 </it>as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene.</p> <p>Conclusions</p> <p>Our study demonstrates that <it>FKBP10 </it>mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with <it>FKBP10 </it>mutations.</p

Comparing biological networks via graph compression

<p>Abstract</p> <p>Background</p> <p>Comparison of various kinds of biological data is one of the main problems in bioinformatics and systems biology. Data compression methods have been applied to comparison of large sequence data and protein structure data. Since it is still difficult to compare global structures of large biological networks, it is reasonable to try to apply data compression methods to comparison of biological networks. In existing compression methods, the uniqueness of compression results is not guaranteed because there is some ambiguity in selection of overlapping edges.</p> <p>Results</p> <p>This paper proposes novel efficient methods, CompressEdge and CompressVertices, for comparing large biological networks. In the proposed methods, an original network structure is compressed by iteratively contracting identical edges and sets of connected edges. Then, the similarity of two networks is measured by a compression ratio of the concatenated networks. The proposed methods are applied to comparison of metabolic networks of several organisms, <it>H. sapiens, M. musculus, A. thaliana, D. melanogaster, C. elegans, E. coli, S. cerevisiae,</it> and <it>B. subtilis,</it> and are compared with an existing method. These results suggest that our methods can efficiently measure the similarities between metabolic networks.</p> <p>Conclusions</p> <p>Our proposed algorithms, which compress node-labeled networks, are useful for measuring the similarity of large biological networks.</p

Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen

Autoregulation of the Drosophila Noncoding roX1 RNA Gene

Most genes along the male single X chromosome in Drosophila are hypertranscribed about two-fold relative to each of the two female X chromosomes. This is accomplished by the MSL (male-specific lethal) complex that acetylates histone H4 at lysine 16. The MSL complex contains two large noncoding RNAs, roX1 (RNA on X) and roX2, that help target chromatin modifying enzymes to the X. The roX RNAs are functionally redundant but differ in size, sequence, and transcriptional control. We wanted to find out how roX1 production is regulated. Ectopic DC can be induced in wild-type (roX1+ roX2+) females if we provide a heterologous source of MSL2. However, in the absence of roX2, we found that roX1 expression failed to come on reliably. Using an in situ hybridization probe that is specific only to endogenous roX1, we found that expression was restored if we introduced either roX2 or a truncated but functional version of roX1. This shows that pre-existing roX RNA is required to positively autoregulate roX1 expression. We also observed massive cis spreading of the MSL complex from the site of roX1 transcription at its endogenous location on the X chromosome. We propose that retention of newly assembled MSL complex around the roX gene is needed to drive sustained transcription and that spreading into flanking chromatin contributes to the X chromosome targeting specificity. Finally, we found that the gene encoding the key male-limited protein subunit, msl2, is transcribed predominantly during DNA replication. This suggests that new MSL complex is made as the chromatin template doubles. We offer a model describing how the production of roX1 and msl2, two key components of the MSL complex, are coordinated to meet the dosage compensation demands of the male cell

Protein Complex Evolution Does Not Involve Extensive Network Rewiring

The formation of proteins into stable protein complexes plays a fundamental role in the operation of the cell. The study of the degree of evolutionary conservation of protein complexes between species and the evolution of protein-protein interactions has been hampered by lack of comprehensive coverage of the high-throughput (HTP) technologies that measure the interactome. We show that new high-throughput datasets on protein co-purification in yeast have a substantially lower false negative rate than previous datasets when compared to known complexes. These datasets are therefore more suitable to estimate the conservation of protein complex membership than hitherto possible. We perform comparative genomics between curated protein complexes from human and the HTP data in Saccharomyces cerevisiae to study the evolution of co-complex memberships. This analysis revealed that out of the 5,960 protein pairs that are part of the same complex in human, 2,216 are absent because both proteins lack an ortholog in S. cerevisiae, while for 1,828 the co-complex membership is disrupted because one of the two proteins lacks an ortholog. For the remaining 1,916 protein pairs, only 10% were never co-purified in the large-scale experiments. This implies a conservation level of co-complex membership of 90% when the genes coding for the protein pairs that participate in the same protein complex are also conserved. We conclude that the evolutionary dynamics of protein complexes are, by and large, not the result of network rewiring (i.e. acquisition or loss of co-complex memberships), but mainly due to genomic acquisition or loss of genes coding for subunits. We thus reveal evidence for the tight interrelation of genomic and network evolution