609 research outputs found
Retraction Notice of the Article: The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles
Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation
Exon skipping in the RET Gene encodes novel isoforms that differentially regulate RET Protein signal transduction
Rearranged during transfection (RET), a receptor tyrosine kinase that is activated by the glial cell line-derived neurotrophic factor family ligands (GFLs), plays a crucial role in the development and function of the nervous system and additionally is required for kidney development and spermatogenesis. RET encodes a transmembrane receptor that is 20 exons long and produces two known protein isoforms differing in C-terminal amino acid composition, referred to as RET9 and RET51. Studies of human pheochromocytomas identified two additional novel transcripts involving the skipping of exon 3 or exons 3, 4, and 5 and are referred to as RETÎE3 and RETÎE345, respectively. Here we report the presence of RetÎE3 and RetÎE345 in zebrafish, mice, and rats and show that these transcripts are dynamically expressed throughout development of the CNS, peripheral nervous system, and kidneys. We further explore the biochemical properties of these isoforms, demonstrating that, like full-length RET, RETÎE3 and RETÎE345 are trafficked to the cell surface, interact with all four GFRÎą co-receptors, and have the ability to heterodimerize with full-length RET. Signaling experiments indicate that RETÎE3 is phosphorylated in a similar manner to full-length RET. RETÎE345, in contrast, displays higher baseline autophosphorylation, specifically on the catalytic tyrosine, Tyr905, and also on one of the most important signaling residues, Tyr1062. These data provide the first evidence for a physiologic role of these isoforms in RET pathway function
Discovery of sultam-containing small-molecule disruptors of the huntingtinâcalmodulin proteinâprotein interaction
The aberrant proteinâprotein interaction between calmodulin and mutant huntingtin protein in Huntingtonâs disease patients has been found to contribute to Huntingtonâs disease progression. A high-throughput screen for small molecules capable of disrupting this interaction revealed a sultam series as potent small-molecule disruptors. Diversification of the sultam scaffold afforded a set of 24 analogs or further evaluation. Several structureâactivity trends within the analog set were found, most notably a negligible effect of absolute stereochemistry and a strong beneficial correlation with electron-withdrawing aromatic substituents. The most promising analogs were profiled for off-target effects at relevant kinases and, ultimately, one candidate molecule was evaluated for neuroprotection in a neuronal cell model of Huntingtonâs disease
The calibration of the Sudbury Neutrino Observatory using uniformly distributed radioactive sources
The production and analysis of distributed sources of 24Na and 222Rn in the
Sudbury Neutrino Observatory (SNO) are described. These unique sources provided
accurate calibrations of the response to neutrons, produced through
photodisintegration of the deuterons in the heavy water target, and to low
energy betas and gammas. The application of these sources in determining the
neutron detection efficiency and response of the 3He proportional counter
array, and the characteristics of background Cherenkov light from trace amounts
of natural radioactivity is described.Comment: 24 pages, 13 figure
Is cosmology consistent?
We perform a detailed analysis of the latest CMB measurements (including
BOOMERaNG, DASI, Maxima and CBI), both alone and jointly with other
cosmological data sets involving, e.g., galaxy clustering and the Lyman Alpha
Forest. We first address the question of whether the CMB data are internally
consistent once calibration and beam uncertainties are taken into account,
performing a series of statistical tests. With a few minor caveats, our answer
is yes, and we compress all data into a single set of 24 bandpowers with
associated covariance matrix and window functions. We then compute joint
constraints on the 11 parameters of the ``standard'' adiabatic inflationary
cosmological model. Out best fit model passes a series of physical consistency
checks and agrees with essentially all currently available cosmological data.
In addition to sharp constraints on the cosmic matter budget in good agreement
with those of the BOOMERaNG, DASI and Maxima teams, we obtain a heaviest
neutrino mass range 0.04-4.2 eV and the sharpest constraints to date on gravity
waves which (together with preference for a slight red-tilt) favors
``small-field'' inflation models.Comment: Replaced to match accepted PRD version. 14 pages, 12 figs. Tiny
changes due to smaller DASI & Maxima calibration errors. Expanded neutrino
and tensor discussion, added refs, typos fixed. Combined CMB data, window and
covariance matrix at http://www.hep.upenn.edu/~max/consistent.html or from
[email protected]
Acceptability of multipurpose human papillomavirus vaccines among providers and mothers of adolescent girls: A mixed-methods study in five countries
Introduction Multipurpose vaccines (MPVs) could be formulated to prevent multiple sexually transmitted infections simultaneously. Little is known about acceptability of MPVs among vaccine health care providers (HCPs) or mothers of adolescent girls. Methods 151 adolescent vaccine providers and 118 mothers of adolescent girls aged 9â14 were recruited from five geographically-diverse countries: Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providersâ preferences for single-purpose human papillomavirus (HPV) vaccine versus MPVs (including HPV+herpes simplex virus (HSV)â2, HPV+HIV, or HPV+HSV-2+HIV) via quantitative surveys. Maternal MPV attitudes were assessed in four focus group discussions (FGDs) in each country. Results Most providers preferred MPVs over single-purpose HPV vaccination, with preference ranging from 61% in Malaysia to 96% in South Africa. HPV+HSV-2+HIV was the most preferred MPV formulation (56â82%). Overall, 53% of the mothers preferred MPVs over single-purpose HPV vaccines, with strongest support in South Africa (90%) and lowest support in South Korea (29%). Convenience and trust in the health care system were commonly-cited reasons for MPV acceptability. Safety and efficacy concerns were common barriers to accepting MPVs, though specific concerns differed by country. Across FGDs, additional safety and efficacy information on MPVs were requested, particularly from trusted sources like HCPs. Conclusions Though maternal acceptability of MPVs varied by country, MPV acceptability would be enhanced by having HCPs provide parents with additional MPV vaccine safety and efficacy information. While most providers preferred MPVs, future health behavior research should identify acceptability barriers, and targeted provider interventions should equip providers to improve vaccination discussions with parents
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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