Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

<p>Abstract</p> <p>Background</p> <p>Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4.</p> <p>Results</p> <p>Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC). While mutational inactivation of the histone acetyltransferase (HAT) gene <it>HAT1 </it>alone does not compromise origin firing or initiation of DNA replication, a deletion in <it>HAT1 </it>(or <it>HAT2</it>) exacerbates the growth defects of conditional <it>orc-ts </it>mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork.</p> <p>Conclusion</p> <p>We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p). The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.</p

RESERVATION MODEL FOR REAL-TIME BIDDING BASED ADVERTISING SYSTEM

An advertisement management system can enable an advertiser to switch between realtime bidding and reservation delivery modes. A request is received to transition a campaign from a real-time bidding mode to a reservation mode. A reservation engine determines proposed terms for a reservation contract. An acceptance of the proposed terms is received from the advertiser. The campaign is transitioned from the real-time bidding mode to the reservation mode and a reservation contract is established between the advertisement management system and the advertiser, with campaign parameters made immutable for the duration of the contract

Magnetism, superconductivity and coupling in cuprate heterostructures probed by low-energy muon-spin rotation

We present a low-energy muon-spin-rotation study of the magnetic and superconducting properties of YBa2Cu3O7/PrBa2Cu3O7 trilayer and bilayer heterostructures. By determining the magnetic-field profiles throughout these structures we show that a finite superfluid density can be induced in otherwise semiconducting PrBa2Cu3O7 layers when juxtaposed to YBa2Cu3O7 "electrodes" while the intrinsic antiferromagnetic order is unaffected.Comment: 10 pages, 9 figures; figure 9 corrected in version

Dimensionality Control of Electronic Phase Transitions in Nickel-Oxide Superlattices

The competition between collective quantum phases in materials with strongly correlated electrons depends sensitively on the dimensionality of the electron system, which is difficult to control by standard solid-state chemistry. We have fabricated superlattices of the paramagnetic metal LaNiO3 and the wide-gap insulator LaAlO3 with atomically precise layer sequences. Using optical ellipsometry and low-energy muon spin rotation, superlattices with LaNiO3 as thin as two unit cells are shown to undergo a sequence of collective metalinsulator and antiferromagnetic transitions as a function of decreasing temperature, whereas samples with thicker LaNiO3 layers remain metallic and paramagnetic at all temperatures. Metal-oxide superlattices thus allow control of the dimensionality and collective phase behavior of correlated-electron systems

Controlling the near-surface superfluid density in underdoped YBa₂Cu₃O_6+<i>x</i> by photo-illumination

The interaction with light weakens the superconducting ground state in classical superconductors. The situation in cuprate superconductors is more complicated: illumination increases the charge carrier density, a photo-induced effect that persists below room temperature. Furthermore, systematic investigations in underdoped YBa₂Cu₃O6+x (YBCO) have shown an enhanced critical temperature Tc. Until now, studies of photo-persistent conductivity (PPC) have been limited to investigations of structural and transport properties, as well as the onset of superconductivity. Here we show how changes in the magnetic screening profile of YBCO in the Meissner state due to PPC can be determined on a nanometer scale utilizing low-energy muons. The data obtained reveal a strongly increased superfluid density within the first few tens of nanometers from the sample surface. Our findings suggest a non-trivial modification of the near-surface band structure and give direct evidence that the superfluid density of YBCO can be controlled by light illumination

SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling

Patients with Charcot-Marie-Tooth neuropathy and gene targeting in mice revealed an essential role for the SH3TC2 gene in peripheral nerve myelination. SH3TC2 expression is restricted to Schwann cells in the peripheral nervous system, and the gene product, SH3TC2, localizes to the perinuclear recycling compartment. Here, we show that SH3TC2 interacts with the small guanosine triphosphatase Rab11, which is known to regulate the recycling of internalized membranes and receptors back to the cell surface. Results of protein binding studies and transferrin receptor trafficking are in line with a role of SH3TC2 as a Rab11 effector molecule. Consistent with a function of Rab11 in Schwann cell myelination, SH3TC2 mutations that cause neuropathy disrupt the SH3TC2/Rab11 interaction, and forced expression of dominant negative Rab11 strongly impairs myelin formation in vitro. Our data indicate that the SH3TC2/Rab11 interaction is relevant for peripheral nerve pathophysiology and place endosomal recycling on the list of cellular mechanisms involved in Schwann cell myelinatio

QiSampler: evaluation of scoring schemes for high-throughput datasets using a repetitive sampling strategy on gold standards

<p>Abstract</p> <p>Background</p> <p>High-throughput biological experiments can produce a large amount of data showing little overlap with current knowledge. This may be a problem when evaluating alternative scoring mechanisms for such data according to a gold standard dataset because standard statistical tests may not be appropriate.</p> <p>Findings</p> <p>To address this problem we have implemented the QiSampler tool that uses a repetitive sampling strategy to evaluate several scoring schemes or experimental parameters for any type of high-throughput data given a gold standard. We provide two example applications of the tool: selection of the best scoring scheme for a high-throughput protein-protein interaction dataset by comparison to a dataset derived from the literature, and evaluation of functional enrichment in a set of tumour-related differentially expressed genes from a thyroid microarray dataset.</p> <p>Conclusions</p> <p>QiSampler is implemented as an open source R script and a web server, which can be accessed at <url>http://cbdm.mdc-berlin.de/tools/sampler/</url>.</p

Improvement of antibiotic prescription in outpatient care: a cluster-randomized intervention study using a sentinel surveillance network of physicians

Objectives To assess the effectiveness of implementing guidelines, coupled with individual feedback, on antibiotic prescribing behaviour of primary care physicians in Switzerland. Methods One hundred and forty general practices from a representative Swiss sentinel network of primary care physicians participated in this cluster-randomized prospective intervention study. The intervention consisted of providing guidelines on treatment of respiratory tract infections (RTIs) and uncomplicated lower urinary tract infections (UTIs), coupled with sustained, regular feedback on individual antibiotic prescription behaviour during 2 years. The main aims were: (i) to increase the percentage of prescriptions of penicillins for all RTIs treated with antibiotics; (ii) to increase the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics; (iii) to decrease the percentage of quinolone prescriptions for all cases of exacerbated COPD (eCOPD) treated with antibiotics; and (iv) to decrease the proportion of sinusitis and other upper RTIs treated with antibiotics. The study was registered at ClinicalTrials.gov (NCT01358916). Results While the percentage of antibiotics prescribed for sinusitis or other upper RTIs and the percentage of quinolones prescribed for eCOPD did not differ between the intervention group and the control group, there was a significant increase in the percentage of prescriptions of penicillins for all RTIs treated with antibiotics [57% versus 49%, OR = 1.42 (95% CI 1.08-1.89), P = 0.01] and in the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics [35% versus 19%, OR = 2.16 (95% CI 1.19-3.91), P = 0.01] in the intervention group. Conclusions In our setting, implementing guidelines, coupled with sustained individual feedback, was not able to reduce the proportion of sinusitis and other upper RTIs treated with antibiotics, but increased the use of recommended antibiotics for RTIs and UTIs, as defined by the guideline