Lateral mobility of L-type calcium channels in synaptic terminals of retinal bipolar cells.

PURPOSE: Efficient and precise release of glutamate from retinal bipolar cells is ensured by the positioning of L-type Ca(2+) channels close to release sites at the base of the synaptic ribbon. We investigated whether Ca(2+) channels at bipolar cell ribbon synapses are fixed in position or capable of moving in the membrane. METHODS: We tracked the movements of individual L-type Ca(2+) channels in bipolar cell terminals after labeling channels with quantum dots (QDs) attached to α(2)δ(4) accessory Ca(2+) channel subunits via intermediary antibodies. RESULTS: We found that individual Ca(2+) channels moved within a confined domain of 0.13-0.15 μm(2) in bipolar cell terminals, similar to ultrastructural estimates of the surface area of the active zone beneath the ribbon. Disruption of actin expanded the confinement domain indicating that cytoskeletal interactions help to confine channels at the synapse, but the relatively large diffusion coefficients of 0.3-0.45 μm(2)/s suggest that channels are not directly anchored to actin. Unlike photoreceptor synapses, removing membrane cholesterol did not change domain size, indicating that lipid rafts are not required to confine Ca(2+) channels at bipolar cell ribbon synapses. CONCLUSIONS: The ability of Ca(2+) channels to move within the presynaptic active zone suggests that regulating channel mobility may affect release from bipolar cell terminals

Symptoms of Overtraining in Resistance Exercise: International Cross-Sectional Survey

Purpose: To provide details on the nature and symptomatic profile of training maladaptation in competitive resistance-based athletes to examine whether there are symptoms that may be used as prognostic indicators of overtraining. Identifying prognostic tools to assess for training maladaptation is essential for avoiding severe overtraining conditions. Methods: A Web-based survey was distributed to a cross-sectional convenience sample of competitive athletes involved in sports with a significant resistance-training component. The 46-item anonymous survey was distributed via industry experts and social media from July to August 2019. Results: The final sample included 605 responses (completion rate: 84%). About 71% of the respondents indicated that they had previously experienced an unexplained decrease in performance. Among those, the majority reported a performance decrement lasting 1 wk to 1 mo (43.8%). General feelings of fatigue were the most frequent self-reported symptom of maladaptation. Acute training maladaptation, lasting 4 mo) were training to muscle failure. Conclusion: The results from this study support the multifactorial nature of training maladaptation. The multidimensional nature of fatigue and individual variability in symptomatic responses precludes definitive prognostic symptoms or differential diagnostic factors of functional/nonfunctional overreaching or the overtraining syndrome in resistance exercise

A Search for Ultraviolet Emission from LINERs

We have obtained Hubble Space Telescope WFPC2 2200 A and optical V-band images of 20 low-luminosity active galactic nuclei, most of which are spectroscopically classified as LINERs, in order to search for a possible photoionizing continuum. Six (30%) of the galaxies are detected in the UV. Two of the detected galaxies (NGC 3642 and NGC 4203) have compact, unresolved nuclear UV sources, while the remaining four UV sources (in NGC 4569, NGC 5005, NGC 6500, and NGC 7743) are spatially extended. Combining our sample with that of Maoz et al. (1995), we find that the probability of detection of a nuclear UV source is greatest for galaxies having low internal reddening and low inclination, and we conclude that dust obscuration is the dominant factor determining whether or not a UV source is detected. Large emission-line equivalent widths and the presence of broad-line emission also increase the likelihood of detection of nuclear UV emission. Our results suggest that the majority of LINERs harbor obscured nuclear UV sources, which may be either accretion-powered active nuclei or young star clusters. Under the assumption that the compact UV sources in NGC 3642 and NGC 4203 have nonstellar power-law spectra extending into the extreme ultraviolet, the extrapolated ionizing fluxes are sufficiently strong to photoionize the narrow-line regions of these objects. The V-band images of many galaxies in our sample reveal remarkably strong dust lanes which may be responsible for obscuring some UV sources.Comment: 25 pages, 4 figures, 3 tables, LaTeX, AASTeX v4.0 style file, accepted for publication in The Astrophysical Journal, additional figures available at http://astro.berkeley.edu/~barth/papers/u

A Study of the Direct-Fitting Method for Measurement of Galaxy Velocity Dispersions

We have measured the central stellar velocity dispersions of 33 nearby spiral and elliptical galaxies, using a straightforward template-fitting algorithm operating in the pixel domain. The spectra, obtained with the Double Spectrograph at Palomar Observatory, cover both the Ca triplet and the Mg b region, and we present a comparison of the velocity dispersion measurements from these two spectral regions. Model fits to the Ca triplet region generally yield good results with little sensitivity to the choice of template star. In contrast, the Mg b region is more sensitive to template mismatch and to details of the fitting procedure such as the order of a polynomial used to match the continuum shape of the template to the object. As a consequence of the correlation of the [Mg/Fe] ratio with velocity dispersion, it is difficult to obtain a satisfactory model fit to the Mg b lines and the surrounding Fe blends simultaneously, particularly for giant elliptical galaxies with large velocity dispersions. We demonstrate that if the metallicities of the galaxy and template star are not well matched, then direct template-fitting results are improved if the Mg b lines themselves are excluded from the fit and the velocity dispersion is determined from the surrounding weaker lines.Comment: 14 pages. To appear in A

The Broad-Line and Narrow-Line Regions of the LINER NGC 4579

We report the discovery of an extremely broad H-alpha emission line in the LINER nucleus of NGC 4579. From ground-based observations, the galaxy was previously known to contain a Type 1 nucleus with a broad H-alpha line of FWHM = 2300 km/s and FWZI ~ 5000 km/s. New spectra obtained with the Hubble Space Telescope and a 0.2 arcsec-wide slit reveal an H-alpha component with FWZI ~ 18,000 km/s. The line is not obviously double-peaked, but it does possess shoulders on the red and blue sides which resemble the H-alpha profiles of double-peaked emitters such as NGC 4203 and NGC 4450. This similarity suggests that the very broad H-alpha profile in NGC 4579 may represent emission from an accretion disk. Three such objects have been found recently in two HST programs which have targeted a total of 30 galaxies, demonstrating that double-peaked or extremely broad-line emission in LINERs must be much more common than would be inferred from ground-based surveys. The ratio of the narrow [S II] 6716, 6731 lines shows a pronounced gradient indicating a steep rise in density toward the nucleus. The direct detection of a density gradient within the inner arcsecond of the narrow-line region confirms expectations from previous observations of linewidth-critical density correlations in several LINERs.Comment: 8 pages, includes 3 figures. To appear in The Astrophysical Journa

Identifying reports of randomized controlled trials (RCTs) via a hybrid machine learning and crowdsourcing approach

OBJECTIVES: Identifying all published reports of randomized controlled trials (RCTs) is an important aim, but it requires extensive manual effort to separate RCTs from non-RCTs, even using current machine learning (ML) approaches. We aimed tomake this process more efficient via a hybrid approach using both crowdsourcing andML. METHODS: We trained a classifier to discriminate between citations that describe RCTs and those that do not. We then adopted a simple strategy of automatically excluding citations deemed very unlikely to be RCTs by the classifier and deferring to crowdworkers otherwise. RESULTS: Combining ML and crowdsourcing provid es a highly sensitive RCT identification strategy (our estimates suggest 95%-99% recall) with substantially less effort (we observed a reduction of around 60%-80%) than relying on manual screening alone. CONCLUSIONS: Hybrid crowd-ML strategies warrant further exploration for biomedical curation/annotation tasks

Isolation and Monitoring of Cleanroom-Associated Microbial Contaminates From Geological Collections

Microbial contamination is of particular interest to geological curation as many microorganisms can change mineral composition and produce compounds used as biosignatures used for the detection of life. Microbial cells can change the mineral composition of rocks through organic acid production and direct enzymatic oxidation/reduction of transition metals. Enzymatic oxidation of iron and manganese can occur at a rate several orders of magnitude faster than under abiotic conditions and produce highly reactive nanoparticle- sized oxides that can react and sorb other metals and organic compounds. Many fungi can also produce organic acids that dissolve and chelate mineral matrices chemically reducing and dissolving rock surfaces. Finally, several common soil-associated bacteria and fungi produce secondary metabolites that contain unusual amino acid analogs and non-ribosomal peptides containing both L- and D- chirality used in characterizing carbonaceous chondrites and the detection of extraterrestrial life

IgA as a potential candidate for enteric monoclonal antibody therapeutics with improved gastrointestinal stability

Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a panel of antibody candidates for enteric mAb-based therapeutics. Recombinant IgG1 was the least stable following SIF incubation, while the stability of IgA generally increased upon polymerization, with subtle differences between subclasses. Notably, patterns of variability within and between mAbs suggest that variable regions contribute to mAb stability and potentially mediate mAb susceptibility to proteases. Despite relatively rapid degradation in SIF, mAbs targeting Enterotoxigenic Escherichia coli (ETEC) displayed functional activity following SIF treatment, with SIgA1 showing improved function compared to SIgA2. The results of this study have implications for the design of enteric therapeutics and subsequent selection of lead candidates based upon in vitro intestinal stability assessments

Electrical stimulation enhances the acetylcholine receptors available for neuromuscular junction formation

Neuromuscular junctions (NMJ) are specialized synapses that link motor neurons with muscle fibers. These sites are fundamental to human muscle activity, controlling swallowing and breathing amongst many other vital functions. Study of this synapse formation is an essential area in neuroscience; the understanding of how neurons interact and control their targets during development and regeneration are fundamental questions. Existing data reveals that during initial stages of development neurons target and form synapses driven by biophysical and biochemical cues, and during later stages they require electrical activity to develop their functional interactions. The aim of this study was to investigate the effect of exogenous electrical stimulation (ES) electrodes directly in contact with cells, on the number and size of acetylcholine receptor (AChR) clusters available for NMJ formation. We used a novel in vitro model that utilizes a flexible electrical stimulation system and allows the systematic testing of several stimulation parameters simultaneously as well as the use of alternative electrode materials such as conductive polymers to deliver the stimulation. Functionality of NMJs under our co-culture conditions was demonstrated by monitoring changes in the responses of primary myoblasts to chemical stimulants that specifically target neuronal signaling. Our results suggest that biphasic electrical stimulation at 250 Hz, 100 ¿s pulse width and current density of 1 mA/cm2 for 8 h, applied via either gold-coated mylar or the conductive polymer PPy, significantly increased the number and size of AChRs clusters available for NMJ formation. This study supports the beneficial use of direct electrical stimulation as a strategic therapy for neuromuscular disorders

Relativistic three-particle scattering equations

We derive a set of relativistic three-particle scattering equations in the three-particle c.m. frame employing a relativistic three-particle propagator suggested long ago by Ahmadzadeh and Tjon in the c.m. frame of a two-particle subsystem. We make the coordinate transformation of this propagator from the c.m. frame of the two-particle subsystem to the three-particle c.m. frame. We also point out that some numerical applications of the Ahmadzadeh and Tjon propagator to the three-nucleon problem use unnecessary nonrelativistic approximations which do not simplify the computational task, but violate constraints of relativistic unitarity and/or covariance.Comment: 5pages, text and one ps figure (in revtex) include