Collective dynamics of molecular motors pulling on fluid membranes

The collective dynamics of $N$ weakly coupled processive molecular motors are considered theoretically. We show, using a discrete lattice model, that the velocity-force curves strongly depend on the effective dynamic interactions between motors and differ significantly from a simple mean field prediction. They become essentially independent of $N$ if it is large enough. For strongly biased motors such as kinesin this occurs if $N\gtrsim 5$. The study of a two-state model shows that the existence of internal states can induce effective interactions.Comment: 5 pages, 5 figure

PCR Assay for Detection of Staphylococcus aureus in Fresh Lettuce (Lactuca sativa)

The growth in food demand and production growth of vegetables have led to the development of intensive production systems with the aim of having regular access to enough high‐quality food. The aim is to determine the incidence of Staphylococcus aureus in fresh lettuce by PCR in order to enhance the efficiency for detection and identification process. The Baird‐Parker method was used for isolating pathogens from 54 lettuce samples. Genomic DNA extraction was performed according the Mericon DNA Bacteria Plus Kit. The detection by PCR was performed using the pair of primers: coa gene (5′‐ATAGAGCTGATGGTACAGG‐3′ and 5′‐GCTTCCGATTGTTCGATGC‐3′). The phylogenetic tree was constructed by comparing conserved sequences from the adjacent 16S gene, using the F2C 5′‐AGAGTTTGATCATGGCTC‐3′ and C 5′‐ACGGGCGGTGTGTAC‐3′ primers. To test the antimicrobial effect, we used the disk diffusion method (Kirby‐Bauer) using Mueller‐Hinton agar and five antibiotics with different concentrations. The incidence of S. aureus was 1.7%. All the isolates were situated in the ATCC 11632 clade in accordance with other reported sequences belonging to this pathogen in the NCBI database. All the isolates seemed to be resistant to penicillin (10U). The molecular techniques used in this study are suitable for the identification of S. aureus isolated from lettuce, increasing our capability of detecting this pathogen by improving the process and increasing the efficiency contributing to the safety of this vegetable

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Primary Black Hole Spin in OJ 287 as Determined by the General Relativity Centenary Flare

OJ 287 is a quasi-periodic quasar with roughly 12 year optical cycles. It displays prominent outbursts that are predictable in a binary black hole model. The model predicted a major optical outburst in 2015 December. We found that the outburst did occur within the expected time range, peaking on 2015 December 5 at magnitude 12.9 in the optical R -band. Based on Swift /XRT satellite measurements and optical polarization data, we find that it included a major thermal component. Its timing provides an accurate estimate for the spin of the primary black hole, ##IMG## [http://ej.iop.org/images/2041-8205/819/2/L37/apjl523055ieqn1.gif] $i =0.313pm 0.01$ . The present outburst also confirms the established general relativistic properties of the system such as the loss of orbital energy to gravitational radiation at the 2% accuracy level, and it opens up the possibility of testing the black hole no-hair theorem with 10% accuracy during the present decade.Peer reviewe

A Search for QPOs in the Blazar OJ287: Preliminary Results from the 2015/2016 Observing Campaign

We analyse the light curve in the R band of the blazar OJ287, gathered during the 2015/2016 observing season. We did a search for quasi-periodic oscillations (QPOs) using several methods over a wide range of timescales. No statistically significant periods were found in the high-frequency domain both in the ground-based data and in Kepler observations. In the longer-period domain, the Lomb–Scargle periodogram revealed several peaks above the 99% significance level. The longest one—about 95 days—corresponds to the innermost stable circular orbit (ISCO) period of the more massive black hole. The 43-day period could be an alias, or it can be attributed to accretion in the form of a two-armed spiral wave.Peer reviewe

Authenticating the Presence of a Relativistic Massive Black Hole Binary in OJ 287 Using Its General Relativity Centenary Flare : Improved Orbital Parameters

Results from regular monitoring of relativistic compact binaries like PSR 1913+16 are consistent with the dominant (quadrupole) order emission of gravitational waves (GWs). We show that observations associated with the binary black hole (BBH) central engine of blazar OJ 287 demand the inclusion of gravitational radiation reaction effects beyond the quadrupolar order. It turns out that even the effects of certain hereditary contributions to GW emission are required to predict impact flare timings of OJ 287. We develop an approach that incorporates this effect into the BBH model for OJ 287. This allows us to demonstrate an excellent agreement between the observed impact flare timings and those predicted from ten orbital cycles of the BBH central engine model. The deduced rate of orbital period decay is nine orders of magnitude higher than the observed rate in PSR 1913+16, demonstrating again the relativistic nature of OJ 287's central engine. Finally, we argue that precise timing of the predicted 2019 impact flare should allow a test of the celebrated black hole "no-hair theorem" at the 10% level.Peer reviewe

Histone Deacetylase Inhibitors Globally Enhance H3/H4 Tail Acetylation Without Affecting H3 Lysine 56 Acetylation

Histone deacetylase inhibitors (HDACi) represent a promising avenue for cancer therapy. We applied mass spectrometry (MS) to determine the impact of clinically relevant HDACi on global levels of histone acetylation. Intact histone profiling revealed that the HDACi SAHA and MS-275 globally increased histone H3 and H4 acetylation in both normal diploid fibroblasts and transformed human cells. Histone H3 lysine 56 acetylation (H3K56ac) recently elicited much interest and controversy due to its potential as a diagnostic and prognostic marker for a broad diversity of cancers. Using quantitative MS, we demonstrate that H3K56ac is much less abundant than previously reported in human cells. Unexpectedly, in contrast to H3/H4 N-terminal tail acetylation, H3K56ac did not increase in response to inhibitors of each class of HDACs. In addition, we demonstrate that antibodies raised against H3K56ac peptides cross-react against H3 N-terminal tail acetylation sites that carry sequence similarity to residues flanking H3K56

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Dust environment and dynamical history of a sample of short-period comets: II. 81P/Wild 2 and 103P/Hartley 2

Aims. This paper is a continuation of the first paper in this series, where we presented an extended study of the dust environment of a sample of short-period comets and their dynamical history. On this occasion, we focus on comets 81P/Wild 2 and 103P/Hartley 2, which are of special interest as targets of the spacecraft missions Stardust and EPOXI. Methods. As in the previous study, we used two sets of observational data: a set of images, acquired at Sierra Nevada and Lulin observatories, and the Afρ data as a function of the heliocentric distance provided by the amateur astronomical association Cometas-Obs. The dust environment of comets (dust loss rate, ejection velocities, and size distribution of the particles) was derived from our Monte Carlo dust tail code. To determine their dynamical history we used the numerical integrator Mercury 6.2 to ascertain the time spent by these objects in the Jupiter family Comet region. Results. From the dust analysis, we conclude that both 81P/Wild 2 and 103P/Hartley 2 are dusty comets, with an annual dust production rate of 2.8 × 109 kg yr-1 and (0.4-1.5) × 109 kg yr-1, respectively. From the dynamical analysis, we determined their time spent in the Jupiter family Comet region as ~40 yr in the case of 81P/Wild 2 and ~1000 yr for comet 103P/Hartley 2. These results imply that 81P/Wild 2 is the youngest and the most active comet of the eleven short-period comets studied so far, which tends to favor the correlation between the time spent in JFCs region and the comet activity previously discussed

Targeting histone deacetyalses in the treatment of B- and T-cell malignancies

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin’s lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin’s lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have been approved in the US for the treatment of relapsed and refractory cutaneous T cell lymphomas (CTCL). Initially, these agents were developed with the idea that they affected transcriptional activation and thus gene expression, by modulating chromatin condensation and decondensation. It is now clear that their effects go beyond chromatin and by affecting the acetylation status of histones and other intra-cellular proteins, they modify gene expression and cellular function via multiple pathways. Gene expression profiles and functional genetic analysis has led to further understanding of the various molecular pathways that are affected by these agents including cell cycle regulation, pathways of cellular proliferation, apoptosis and angiogenesis all important in lymphomagenesis. There is also increasing data to support the effects of these agents on T cell receptor and immune function which may explain the high level of activity of these agents in T cell lymphomas and hodgkin’s lymphoma. There is ample evidence of epigenetic dysregulation in lymphomas which may underlie the mechanisms of action of these agents but how these agents work is still not clear. Current HDAC inhibitors can be divided into at least four classes based on their chemical structure. At present several of these HDAC inhibitors are in clinical trials both as single agents and in combination with chemotherapy or other biological agents. They are easy to administer and are generally well tolerated with minimal side effects. Different dosing levels and schedules and the use of isospecific HDAC inhibitors are some of the strategies that are being employed to increase the therapeutic effect of these agents in the treatment of lymphomas. There may also be class differences that translate into specific activity against different lymphoma. HDAC inhibitors will likely be incorporated into combinations of targeted therapies both in the upfront and relapsed setting for lymphomas