83 research outputs found
Presynaptic Translation: Stepping Out of the Postsynaptic Shadow
The ability of the nervous system to convert transient experiences into long-lasting structural changes at the synapse relies upon protein synthesis. It has become increasingly clear that a critical subset of this synthesis occurs within the synaptic compartment. While this process has been extensively characterized in the postsynaptic compartment, the contribution of local translation to presynaptic function remains largely unexplored. However, recent evidence highlights the potential importance of translation within the presynaptic compartment. Work in cultured neurons has shown that presynaptic translation occurs specifically at synapses undergoing long-term plasticity and may contribute to the maintenance of nascent synapses. Studies from our laboratory have demonstrated that Fragile X proteins, which regulate mRNA localization and translation, are expressed at the presynaptic apparatus. Further, mRNAs encoding presynaptic proteins traffic into axons. Here we discuss recent advances in the study of presynaptic translation as well as the challenges confronting the field. Understanding the regulation of presynaptic function by local protein synthesis promises to shed new light on activity-dependent modification of synaptic architecture
UTILIZATION OF THE LINE-INTERCEPT METHOD TO ESTIMATE THE COVERAGE, DENSITY, AND AVERAGE LENGTH OF ROW SKIPS IN COTTON AND OTHER ROW CROPS
In row crops, a skip is a length of row within the drill where the crop has failed to establish. If the number of skips and their mean length per acre becomes too high, then considerable losses in crop yield occur. Frequently, farmers are faced with the decision to replant a crop which has row skips. To make the best decision, reliable estimates of the stand loss due to skips must be available. In making this decision, three parameters are useful: the percent of the area per acre that is skipped, the number of individual skips (that is, density) per acre, and the mean row length per skip. The line-intercept method for the sampling of two-dimensional objects (particles) can be used to obtain estimates of these parameters. The method is illustrated with an example from a cotton field
EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons
RNA-binding proteins (RBPs) function in higher-order assemblages such as RNA granules to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of neuronal Fragile X granules that associate with axonal mRNA and ribosomes in the intact brain. However, the FXR2P domains important for assemblage formation in a cellular system are unknown. Here we used an EGFP insertional mutagenesis approach to probe for FXR2P intrinsic features that influence its structural states. We tested 18 different in-frame FXR2P(EGFP) fusions in neurons and found that the majority did not impact assemblage formation. However, EGFP insertion within a 23 amino acid region of the low complexity (LC) domain induced FXR2P(EGFP) assembly into two distinct fibril states that were observed in isolation or in highly-ordered bundles. FXR2P(EGFP) fibrils exhibited different developmental timelines, ultrastructures and ribosome associations. Formation of both fibril types was dependent on an intact RNA-binding domain. These results suggest that restricted regions of the LC domain, together with the RNA-binding domain, may be important for FXR2P structural state organization in neurons
TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve
Background: The TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) trial (NCT01700439) evaluated the performance of the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis.
Methods: TRANSFORM was a prospective, nonrandomized, multicenter (n 1�4 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon- expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year.
Results: Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 26.9 minutes and 69.2 34.7 minutes, respectively, and for minimally invasive surgical 63.1 25.4 minutes and 84.6 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons data- base comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively (P<.001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; throm- boembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively
COSMOS-Web: Intrinsically Luminous z10 Galaxy Candidates Test Early Stellar Mass Assembly
We report the discovery of 15 exceptionally luminous
candidate galaxies discovered in the first 0.28 deg of JWST/NIRCam imaging
from the COSMOS-Web Survey. These sources span rest-frame UV magnitudes of
, and thus constitute the most intrinsically luminous
candidates identified by JWST to-date. Selected via NIRCam imaging
with Hubble ACS/F814W, deep ground-based observations corroborate their
detection and help significantly constrain their photometric redshifts. We
analyze their spectral energy distributions using multiple open-source codes
and evaluate the probability of low-redshift solutions; we conclude that 12/15
(80%) are likely genuine sources and 3/15 (20%) likely
low-redshift contaminants. Three of our candidates push the limits of
early stellar mass assembly: they have estimated stellar masses
, implying an effective stellar baryon fraction of
, where . The assembly of such stellar reservoirs is made
possible due to rapid, burst-driven star formation on timescales 100\,Myr
where the star-formation rate may far outpace the growth of the underlying dark
matter halos. This is supported by the similar volume densities inferred for
galaxies relative to
-- both about Mpc -- implying they live in halos of comparable
mass. At such high redshifts, the duty cycle for starbursts would be of order
unity, which could cause the observed change in the shape of the UVLF from a
double powerlaw to Schechter at . Spectroscopic redshift
confirmation and ensuing constraints of their masses will be critical to
understanding how, and if, such early massive galaxies push the limits of
galaxy formation in CDM.Comment: 30 pages, 9 figures; ApJ submitte
The Web Epoch of Reionization Lyman- Survey (WERLS) I. MOSFIRE Spectroscopy of Lyman- Emitters
We present the first results from the Web Epoch of Reionization
Lyman- Survey (WERLS), a spectroscopic survey of Lyman-
emission using Keck I/MOSFIRE and LRIS. WERLS targets bright () galaxy
candidates with photometric redshifts of selected
from pre-JWST imaging embedded in the Epoch of Reionization (EoR) within three
JWST deep fields: CEERS, PRIMER, and COSMOS-Web. Here, we report 11
Lyman- emitters (LAEs; 3 secure and 8 tentative candidates) detected in
the first five nights of WERLS MOSFIRE data. We estimate our observed LAE yield
is %, broadly consistent with expectations assuming some loss from
redshift uncertainty, contamination from sky OH lines, and that the Universe is
approximately half-ionized at this epoch, whereby observable Lyman-
emission is unlikely for galaxies embedded in a neutral intergalactic medium.
Our targets are selected to be UV-bright, and span a range of absolute UV
magnitudes with . With two LAEs detected at
, we also consider the possibility of an ionized bubble at this
redshift. Future synergistic Keck+JWST efforts will provide a powerful tool for
pinpointing beacons of reionization and mapping the large scale distribution of
mass relative to the ionization state of the Universe.Comment: 27 pages, 8 figures; ApJ submitte
Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo
Background: A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings: We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion: Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies
Using global remote camera data of a solitary species complex to evaluate the drivers of group formation
We would like to thank Megan Whatton, Belden Giman, Hongliang Bu, Dajun Wang, Fang Wang, Roland Kays, Jillian Kilborn, and New Hampshire Fish and Game for their roles in contributing data that was used in this analysis. Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the US Government.Peer reviewe
Unveiling the distant Universe: Characterizing Galaxies in the first epoch of COSMOS-Web
We report the identification of 15 galaxy candidates at using the
initial COSMOS-Web JWST observations over 77 arcmin through four NIRCam
filters (F115W, F150W, F277W, F444W) with an overlap with MIRI (F770W) of 8.7
arcmin. We fit the sample using several publicly-available SED fitting and
photometric redshift codes and determine their redshifts between and
(), UV-magnitudes between M =
21.2 and 19.5 (with M) and rest-frame
UV slopes (). These galaxies are, on average, more
luminous than most candidates discovered by JWST so far in the
literature, while exhibiting similar blue colors in their rest-frame UV. The
rest-frame UV slopes derived from SED-fitting are blue ([2.0,
2.7]) without reaching extremely blue values as reported in other recent
studies at these redshifts. The blue color is consistent with models that
suggest the underlying stellar population is not yet fully enriched in metals
like similarly luminous galaxies in the lower redshift Universe. The derived
stellar masses with MM are not in tension with the standard
CDM model and our measurement of the volume density of such UV
luminous galaxies aligns well with previously measured values presented in the
literature at . Our sample of galaxies, although compact, are
significantly resolved.Comment: Submitted to Ap
Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks
Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host
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