2,220 research outputs found
Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export
Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export
Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies
We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD
On the possibility of magneto-structural correlations: detailed studies of di-nickel carboxylate complexes
A series of water-bridged dinickel complexes of the general formula [Ni<sub>2</sub>(μ<sub>2</sub>-OH<sub>2</sub>)(μ2-
O<sub>2</sub>C<sup>t</sup>Bu)<sub>2</sub>(O<sub>2</sub>C<sup>t</sup>Bu)2(L)(L0)] (L = HO<sub>2</sub>C<sup>t</sup>Bu, L0 = HO<sub>2</sub>C<sup>t</sup>Bu (1), pyridine (2),
3-methylpyridine (4); L = L0 = pyridine (3), 3-methylpyridine (5)) has been synthesized
and structurally characterized by X-ray crystallography. The magnetic properties
have been probed by magnetometry and EPR spectroscopy, and detailed measurements
show that the axial zero-field splitting, D, of the nickel(ii) ions is on the same order as
the isotropic exchange interaction, J, between the nickel sites. The isotropic exchange
interaction can be related to the angle between the nickel centers and the bridging
water molecule, while the magnitude of D can be related to the coordination sphere at
the nickel sites
First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)
The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated
observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec
spectrograph. The MINERVA mission is to discover super-Earths in the habitable
zones of nearby stars. This can be accomplished with MINERVA's unique
combination of high precision and high cadence over long time periods. In this
work, we detail changes to the MINERVA facility that have occurred since our
previous paper. We then describe MINERVA's robotic control software, the
process by which we perform 1D spectral extraction, and our forward modeling
Doppler pipeline. In the process of improving our forward modeling procedure,
we found that our spectrograph's intrinsic instrumental profile is stable for
at least nine months. Because of that, we characterized our instrumental
profile with a time-independent, cubic spline function based on the profile in
the cross dispersion direction, with which we achieved a radial velocity
precision similar to using a conventional "sum-of-Gaussians" instrumental
profile: 1.8 m s over 1.5 months on the RV standard star HD 122064.
Therefore, we conclude that the instrumental profile need not be perfectly
accurate as long as it is stable. In addition, we observed 51 Peg and our
results are consistent with the literature, confirming our spectrograph and
Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte
Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps
Peer reviewedPublisher PD
Does electronic clinical microbiology results reporting influence medical decision making: a pre- and post-interview study of medical specialists
Background: Clinicians view the accuracy of test results and the turnaround time as the two most important service aspects of the clinical microbiology laboratory. Because of the time needed for the culturing of infectious agents, final hardcopy culture results will often be available too late to have a significant impact on early antimicrobial therapy decisions, vital in infectious disease management. The clinical microbiologist therefore reports to the clinician clinically relevant preliminary results at any moment during the diagnostic process, mostly by telephone. Telephone reporting is error prone, however. Electronic reporting of culture results instead of reporting on paper may shorten the turnaround time and may ensure correct communication of results. The purpose of this study was to assess the impact of the implementation of electronic reporting of final microbiology results on medical decision making. Methods. In a pre- and post-interview study using a semi-structured design we asked medical specialists in our hospital about their use and appreciation of clinical microbiology results reporting before and after the implementation of an electronic reporting system. Results: Electronic reporting was highly appreciated by all interviewed clinicians. Major advantages were reduction of hardcopy handling and the possibility to review results in relation to other patient data. Use and meaning of microbiology reports differ significantly between medical specialties. Most clinicians need preliminary results for therapy decisions quickly. Therefore, after the implementation of electronic reporting, telephone consultation between clinician and microbiologist remained the key means of communication. Conclusions: Overall, electronic reporting increased the workflow efficiency of the medical specialists, but did not have an impact on their decision-making
Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays
A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%
Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−
The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
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