Translation-dependent mRNA localization to Caenorhabditis elegans adherens junctions

mRNA localization is an evolutionarily widespread phenomenon that can facilitate subcellular protein targeting. Extensive work has focused on mRNA targeting through 'zip-codes' within untranslated regions (UTRs), whereas much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5' or 3' UTRs. We suggest a model in which dlg-1 transcripts are co-translationally localized with the nascent protein: first the translating complex goes to the cell membrane using sequences located at the C-terminal/3' end, and then apically using N-terminal/5' sequences. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting

Recent advances in non-surgical management of cancer in the elderly [version 1; referees: 2 approved]

This article summarizes the seminal publications from mid-2016 through 2017 in the area of medical care for older adults with cancer. Areas addressed include chemotherapy tolerance and efficacy in the aged, geriatric fitness assessments, and advancements in palliative and supportive care. The practice-changing finding from this past year’s publications is that antipsychotics should not be used in the management of terminal delirium in older adults receiving palliative care. The other trials demonstrated an improved understanding of the utility of geriatric assessments in patients with cancer, developed the body of information about which chemotherapy agents are safe and effective in older adults (and which are not), and expanded our understanding of good palliative and supportive care

Determination of absolute neutrino masses from Z-bursts

Ultrahigh energy neutrinos (UHE\nu) scatter on relic neutrinos (R\nu) producing Z bosons, which can decay hadronically producing protons (Z-burst). We compare the predicted proton spectrum with the observed ultrahigh energy cosmic ray (UHECR) spectrum and determine the mass of the heaviest R\nu via a maximum likelihood analysis. Our prediction depends on the origin of the power-like part of the UHECR spectrum: m_\nu=2.75^{+1.28}_{-0.97} eV for Galactic halo and 0.26^{+0.20}_{-0.14} eV for extragalactic (EG) origin. The necessary UHE\nu flux should be detected in the near future.Comment: slight rewording, revised neutrino fluxes, conclusions unchanged, version to appear in Phys. Rev. Let

Relic neutrino masses and the highest energy cosmic rays

We consider the possibility that a large fraction of the ultrahigh energy cosmic rays are decay products of Z bosons which were produced in the scattering of ultrahigh energy cosmic neutrinos on cosmological relic neutrinos. We compare the observed ultrahigh energy cosmic ray spectrum with the one predicted in the above Z-burst scenario and determine the required mass of the heaviest relic neutrino as well as the necessary ultrahigh energy cosmic neutrino flux via a maximum likelihood analysis. We show that the value of the neutrino mass obtained in this way is fairly robust against variations in presently unknown quantities, like the amount of neutrino clustering, the universal radio background, and the extragalactic magnetic field, within their anticipated uncertainties. Much stronger systematics arises from different possible assumptions about the diffuse background of ordinary cosmic rays from unresolved astrophysical sources. In the most plausible case that these ordinary cosmic rays are protons of extragalactic origin, one is lead to a required neutrino mass in the range 0.08 eV - 1.3 eV at the 68 % confidence level. This range narrows down considerably if a particular universal radio background is assumed, e.g. to 0.08 eV - 0.40 eV for a large one. The required flux of ultrahigh energy cosmic neutrinos near the resonant energy should be detected in the near future by AMANDA, RICE, and the Pierre Auger Observatory, otherwise the Z-burst scenario will be ruled out.Comment: 19 pages, 22 figures, REVTeX

Geriatric assessment predicts hospitalization frequency and long-term care use in older adult cancer survivors

PURPOSE The association between geriatric assessment (GA)–identified impairments and long-term health care use in older cancer survivors remains unknown. Our objective was to evaluate whether a GA performed at cancer diagnosis was predictive of hospitalizations and long-term care (LTC) use in older adult cancer survivors. METHODS Older adults with GA performed between 3 months before through 6 months after diagnosis were included (N = 125). Patients with Medicare Parts A and B coverage and no managed care were identified. Hospitalizations and LTC use (skilled nursing or assisted living) were assessed up to 5 years postdiagnosis. GA risk measures were evaluated in separate Poisson models estimating the relative risk (RR) for hospital and LTC visits, adjusting for age and Charlson comorbidity score. RESULTS The mean age of patients was 74 years, and the majority were female (80%) and white (90%). Breast cancer (64%) and early-stage disease (stages 0 to III, 77%) were common. Prefrail/frail status (RR, 2.5; P, .001), instrumental activities of daily living impairment (RR, 5.47; P, .001), and limitations in climbing stairs (RR, 2.94; P, .001) were associated with increased hospitalizations. Prefrail/frail status (RR, 1.86; P, .007), instrumental activities of daily living impairment (RR, 4.58; P, .001), presence of falls (RR, 6.73; P, .001), prolonged Timed Up and Go (RR, 5.45; P, .001), and limitations in climbing stairs (RR, 1.89; P, .005) were associated with LTC use. CONCLUSION GA-identified impairments were associated with increased hospitalizations and LTC use among older adults with cancer. GA-focused interventions should be targeted toward high-risk patients to reduce long-term adverse health care use in this vulnerable population

Tibio-femoral joint constraints for bone pose estimation during movement using multi-body optimization

The financial support of the Universita'Italo-Francese (Call Vinci) and of the Department of Human Movement and Sport Sciences of the University of Rome ''Foro Italico'' is gratefully acknowledged. The authors wish to acknowledge Dr. Sophie Lacoste for her technical support and John McCamley for his contribution to the refinement of the manuscriptWhen using skin markers and stereophotogrammetry for movement analysis, bone pose estimation may be performed using multi-body optimization with the intent of reducing the effect of soft tissue artefacts. When the joint of interest is the knee, improvement of this approach requires defining subject-specific relevant kinematic constraints. The aim of this work was to provide these constraints in the form of plausible values for the distances between origin and insertion of the main ligaments (ligament lengths), during loaded healthy knee flexion, taking into account the indeterminacies associated with landmark identification during anatomical calibration. Ligament attachment sites were identified through virtual palpation on digital bone templates. Attachments sites were estimated for six knee specimens by matching the femur and tibia templates to low-dose stereoradiography images. Movement data were obtained using stereophotogrammetry and pin markers. Relevant ligament lengths for the anterior and posterior cruciate, lateral collateral, and deep and superficial bundles of the medial collateral ligaments (ACL, PCL, LCL, MCLdeep, MCLsup) were calculated. The effect of landmark identification variability was evaluated performing a Monte Carlo simulation on the coordinates of the origin-insertion centroids. The ACL and LCL lengths were found to decrease, and the MCLdeep length to increase significantly during flexion, while variations in PCL and MCLsup length was concealed by the experimental indeterminacy. An analytical model is given that provides subject-specific plausible ligament length variations as functions of the knee flexion angle and that can be incorporated in a multi-body optimization procedure

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

The Fluorescence Detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics Research Section