C. elegans mutant identification with a one-step whole-genome-sequencing and SNP mapping strategy.

Whole-genome sequencing (WGS) is becoming a fast and cost-effective method to pinpoint molecular lesions in mutagenized genetic model systems, such as Caenorhabditis elegans. As mutagenized strains contain a significant mutational load, it is often still necessary to map mutations to a chromosomal interval to elucidate which of the WGS-identified sequence variants is the phenotype-causing one. We describe here our experience in setting up and testing a simple strategy that incorporates a rapid SNP-based mapping step into the WGS procedure. In this strategy, a mutant retrieved from a genetic screen is crossed with a polymorphic C. elegans strain, individual F2 progeny from this cross is selected for the mutant phenotype, the progeny of these F2 animals are pooled and then whole-genome-sequenced. The density of polymorphic SNP markers is decreased in the region of the phenotype-causing sequence variant and therefore enables its identification in the WGS data. As a proof of principle, we use this strategy to identify the molecular lesion in a mutant strain that produces an excess of dopaminergic neurons. We find that the molecular lesion resides in the Pax-6/Eyeless ortholog vab-3. The strategy described here will further reduce the time between mutant isolation and identification of the molecular lesion

Forbidden Transitions in a Magneto-Optical Trap

We report the first observation of a non-dipole transition in an ultra-cold atomic vapor. We excite the 3P-4P electric quadrupole (E2) transition in $^{23}$Na confined in a Magneto-Optical Trap(MOT), and demonstrate its application to high-resolution spectroscopy by making the first measurement of the hyperfine structure of the 4P$_{1/2}$ level and extracting the magnetic dipole constant A $=$ 30.6 $\pm$ 0.1 MHz. We use cw OODR (Optical-Optical Double Resonance) accompanied by photoinization to probe the transition

Is arrhythmogenicity related to the speed of reperfusion during thrombolysis for myocardial infarction?

The objective of this study was to relate the number of ventricular arrhythmias (VA) to the normalization time of the ST segment during thrombolysis for acute myocardial infarction. The 24 h Holter recordings, begun on start of intravenous thrombolytic therapy, and the 12-lead electrocardiograms of 41 patients with a patent infarct-related artery according to coronary angiography were analysed. The mean time from onset of chest pain to angiography was 30.5±3.1 h, ≥24 h in 59%. The normalization time of the ST segment, assessed by the time of decrease of ST segment elevation from start of Holter recording to normal or steady state was ≥60 min in 13 patients (group 1), 60 to 180 min in 15 patients (group 2) and > 180 min in 13 patients (group 3). The incidence of VA was similar in all groups, except for ventricular tachycardias (VT) >15 beats (group 1:69%, group 2:13%, group 3:15%, P=0.002) The frequency of accelerated idioventricular rhythms (AIVR), early AIVR (≤6 h) and of VT was significantly higher in group 1 than in group 3 with a 8-, 30- and 6- fold increase, respectively (back transformed mean). We conclude that the number of V As is related to the normalization time of the ST segment during reperfusion. This may suggest that faster reflow is more arrhythmogeni

Summertime cooling of the shallow continental shelf

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C07015, doi:10.1029/2010JC006744.In summer on the shallow New England continental shelf, near the coast the water temperature is much cooler than the observed surface heat flux suggests. Using depth-integrated heat budgets in 12 and 27 m water depth calculated from observed surface heat flux, water temperature, and velocity, we demonstrate that on time scales of weeks to months the water is persistently cooled due to a mean upwelling circulation. Because the mean wind is weak, that mean circulation is likely not wind driven; it is partly a tidal residual circulation. A feedback exists between the cross-shelf and surface heat fluxes: the two fluxes remain nearly in balance for months, so the water temperature is nearly constant in spite of strong surface heating (the heat budget is two-dimensional). A conceptual model explains the feedback mechanism: the short flushing time of the shallow shelf produces a near steady state heat balance, regardless of the exact form of the circulation, and the feedback is via the influence of surface heating on temperature stratification. Along-shelf heat flux divergence is apparently small compared to the surface and cross-shelf heat flux divergences on time scales of weeks to months. Heat transport due to Stokes drift from surface gravity waves is substantial, warms the shallow shelf in summer, and was previously ignored. In winter, the surface heat flux dominates and the observed water temperature is close to the temperature predicted from surface cooling (the heat budget is one-dimensional); weak winter stratification makes the cross-shelf heat flux small even during strong cross-shelf circulation.This research was funded by National Aeronautics and Space Administration Headquarters grant NNG04GL03G and Earth System Science Fellowship Grant NNG04GQ14H; Woods Hole Oceanographic Institution through Academic Programs Fellowship Funds and MVCO; National Science Foundation grants OCE‐0241292, OCE‐0548961, and OCE‐0337892; the Jewett/ EDUC/Harrison Foundation; and Office of Naval Research contracts N00014‐01‐1‐0029 and N00014‐05‐10090 for the Low‐Wind Component of the Coupled Boundary Layers Air‐Sea Transfer Experiment

Moving toward a prevention strategy for osteoporosis by giving a voice to a silent disease

Abstract A major unmet challenge in developing preventative treatment programs for osteoporosis is that the optimal timing of treatment remains unknown. In this commentary we make the argument that the menopausal transition (MT) is a critical period in a woman’s life for bone health, and that efforts aimed at reducing fracture risk later in life may benefit greatly from strategies that treat women earlier with the intent of keeping bones strong as long as possible. Bone strength is an important parameter to monitor during the MT because engineering principles can be applied to differentiate those women that maintain bone strength from those women that lose bone strength and are in need of early treatment. It is critical to understand the underlying mechanistic causes for reduced strength to inform treatment strategies. Combining measures of strength with data on how bone structure changes during the MT may help differentiate whether a woman is losing strength because of excessive bone resorption, insufficient compensatory bone formation, trabeculae loss, or some combination of these factors. Each of these biomechanical mechanisms may require a different treatment strategy to keep bones strong. The technologies that enable physicians to differentially diagnose and treat women in a preventive manner, however, have lagged behind the development of prophylactic treatments for osteoporosis. To take advantage of these treatment options, advances in preventive treatment strategies for osteoporosis may require developing new technologies with imaging resolutions that match the pace by which bone changes during the MT and supplementing a woman's bone mineral density (BMD)-status with information from engineering-based analyses that reveal the structural and material changes responsible for the decline in bone strength during the menopausal transition.http://deepblue.lib.umich.edu/bitstream/2027.42/134529/1/40695_2016_Article_16.pd

Temporal trends in cardiogenic shock complicating acute myocardial infarction

BACKGROUND: Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997. METHODS: We conducted an observational study of 9076 residents of metropolitan Worcester, Massachusetts, who were hospitalized with confirmed acute myocardial infarction in all local hospitals during 11 one-year periods between 1975 and 1997. Our study included periods before and after the advent of reperfusion therapy. RESULTS: The incidence of cardiogenic shock remained relatively stable over time, averaging 7.1 percent among patients with acute myocardial infarction. The results of a multivariable regression analysis indicated that the patients hospitalized during recent study years were not at a substantially lower risk for shock than patients hospitalized in the mid-to-late 1970s. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (71.7 percent) than those who did not have cardiogenic shock (12.0 percent, P\u3c0.001). A significant trend toward an increase in in-hospital survival among patients with cardiogenic shock in the mid-to-late 1990s was found in crude and adjusted analyses. CONCLUSIONS: Our findings indicate no significant change in the incidence of cardiogenic shock complicating acute myocardial infarction over a 23-year period. However, the short-term survival rate has increased in recent years at the same time as the use of coronary reperfusion strategies has increased

Spin Excitations in a Fermi Gas of Atoms

We have experimentally investigated a spin excitation in a quantum degenerate Fermi gas of atoms. In the hydrodynamic regime the damping time of the collective excitation is used to probe the quantum behavior of the gas. At temperatures below the Fermi temperature we measure up to a factor of 2 reduction in the excitation damping time. In addition we observe a strong excitation energy dependence for this quantum statistical effect.Comment: 4 pages, 3 figure

ESI, a new Keck Observatory echellette spectrograph and imager

The Echellette Spectrograph and Imager (ESI) is a multipurpose instrument which has been delivered by the Instrument Development Laboratory of Lick Observatory for use at the Cassegrain focus of the Keck II telescope. ESI saw first light on August 29, 1999. ESI is a multi-mode instrument that enables the observer to seamlessly switch between three modes during an observation. The three modes of ESI are: An R=13,000-echellette mode; Low-dispersion prismatic mode; Direct imaging mode. ESI contains a unique flexure compensation system which reduces the small instrument flexure to negligible proportions. Long-exposure images on the sky show FWHM spot diameters of 34 microns (0.34") averaged over the entire field of view. These are the best non-AO images taken in the visible at Keck Observatory to date. Maximum efficiencies are measured to be 28% for the echellette mode and greater than 41% for low-dispersion prismatic mode including atmospheric, telescope and detector losses. In this paper we describe the instrument and its development. We also discuss the performance-testing and some observational results.Comment: 10 pages, 14 figures, 8tables, accepted for publication in PASP, 15 April 200