A General Strategy for Visible-Light Decaging Based on the Quinone Trimethyl Lock

Visible-light triggered quinone trimethyl locks are reported as a general design for long-wavelength photoremovable protecting groups for alcohols and amines. Intramolecular photoreduction unmasks a reactive phenol that undergoes fast lactonization to release alcohols and amines. Model substrates are released in quantitative yield along with well-defined, colorless hydroquinone byproducts. Substituent modifications of the quinone core allow absorption from 400 to 600 nm

A general strategy for visible-light decaging based on the quinone cis-alkenyl lock

Combining the fast thermal cyclization of o-coumaric acid derivatives with the intramolecular photoreduction of quinones gives new visible-light photoremovable protecting groups absorbing well above 450 nm

Quantitative nucleotide level analysis of regulation of translation in response to depolarization of cultured neural cells

Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence—notably upstream open reading frames and secondary structure in the 5′ untranslated region—both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome

A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site

To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta-19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence increased by (Delta-F/F) approximate to 10%, and the emission peak shifted to lower wavelengths, indicating a more hydrophobic environment for the fluorophore. The dose-response relations for Delta-F agreed well with those for epibatidine-induced currents, but were shifted approximate to 100-fold to the left of those for ACh-induced currents. Because (i) epibatidine binds more tightly to the alpha-gamma-binding site than to the alpha-delta site and (ii) ACh binds with reverse-site selectivity, these data suggest that Delta-F monitors an event linked to binding specifically at the alpha-delta-subunit interface. In experiments with flash-applied agonists, the earliest detectable Delta-F occurs within milliseconds, i.e., during activation. At low [ACh] (less than or equal to 10 muM), a phase of Delta-F occurs with the same time constant as desensitization, presumably monitoring an increased population of agonist-bound receptors. However, recovery from Delta-F is complete before the slowest phase of recovery from desensitization (time constant approximate to 250 s), showing that one or more desensitized states have fluorescence like that of the resting channel. That conformational transitions at the alpha-delta-binding site are not tightly coupled to channel activation suggests that sequential rather than fully concerted transitions occur during receptor gating. Thus, time-resolved fluorescence changes provide a powerful probe of nAChR conformational changes

Образовательное учреждение: проблемы правового регулирования организационно-правовой формы

The vertebrate stress response has been shown to suppress investment in reproductive and immune function and may also lead to a reduced investment in the production of secondary sexual traits. However, it has been difficult to model roles of stress in sexual selection due to the inconsistent results seen in empirical studies testing for the effect of stress on the expression of secondary sexual traits. We conducted a phylogenetically controlled meta-analysis of published associations between physiological correlates of stress and sexual signaling in vertebrates in order to identify any consistent patterns. Our analysis included signaling in both males and females, 4 stress measures, and 4 categories of sexually selected traits (vocalizations, traits that varied in size, traits that varied in coloration, and opposite-sex preference). Across 38 studies of 26 species, there was no significant relationship between physiological correlates of stress and the expression of sexual signals. Mean effect size, however, varied significantly across the 4 types of sexually selected trait. We propose development of a model that incorporates the nuanced effects of species ecology, trait type, ecological context, and the complex nature of the physiological stress response, on the expression of sexually selected traits

Electric Propulsion System Modeling for the Proposed Prometheus 1 Mission

The proposed Prometheus 1 spacecraft would utilize nuclear electric propulsion to propel the spacecraft to its ultimate destination where it would perform its primary mission. As part of the Prometheus 1 Phase A studies, system models were developed for each of the spacecraft subsystems that were integrated into one overarching system model. The Electric Propulsion System (EPS) model was developed using data from the Prometheus 1 electric propulsion technology development efforts. This EPS model was then used to provide both performance and mass information to the Prometheus 1 system model for total system trades. Development of the EPS model is described, detailing both the performance calculations as well as its evolution over the course of Phase A through three technical baselines. Model outputs are also presented, detailing the performance of the model and its direct relationship to the Prometheus 1 technology development efforts. These EP system model outputs are also analyzed chronologically showing the response of the model development to the four technical baselines during Prometheus 1 Phase A

A High Resolution Survey of the Galactic Plane at 408 MHz

The interstellar medium is a complex 'ecosystem' with gas constituents in the atomic, molecular, and ionized states, dust, magnetic fields, and relativistic particles. The Canadian Galactic Plane Survey has imaged these constituents with angular resolution of the order of arcminutes. This paper presents radio continuum data at 408 MHz over the area 52 degrees < longitude < 193 degrees, -6.5 degrees < latitude < 8.5 degrees, with an extension to latitude = 21 degrees in the range 97 degrees < longitude < 120 degrees, with angular resolution 2.8' x 2.8' cosec(declination). Observations were made with the Synthesis Telescope at the Dominion Radio Astrophysical Observatory as part of the Canadian Galactic Plane Survey. The calibration of the survey using existing radio source catalogs is described. The accuracy of 408-MHz flux densities from the data is 6%. Information on large structures has been incorporated into the data using the single-antenna survey of Haslam (1982). The paper presents the data, describes how it can be accessed electronically, and gives examples of applications of the data to ISM research.Comment: Accepted for publication in the Astronomical Journa

Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders

Recent advances have substantially increased the number of genes that are statistically associated with complex genetic disorders of the CNS such as autism and schizophrenia. It is now clear that there will likely be hundreds of distinct loci contributing to these disorders, underscoring a remarkable genetic heterogeneity. It is unclear whether this genetic heterogeneity indicates an equal heterogeneity of cellular mechanisms for these diseases. The commonality of symptoms across patients suggests there could be a functional convergence downstream of these loci upon a limited number of cell types or circuits that mediate the affected behaviors. One possible mechanism for this convergence would be the selective expression of at least a subset of these genes in the cell types that comprise these circuits. Using profiling data from mice and humans, we have developed and validated an approach, cell type-specific expression analysis, for identifying candidate cell populations likely to be disrupted across sets of patients with distinct genetic lesions. Using human genetics data and postmortem gene expression data, our approach can correctly identify the cell types for disorders of known cellular etiology, including narcolepsy and retinopathies. Applying this approach to autism, a disease where the cellular mechanism is unclear, indicates there may be multiple cellular routes to this disorder. Our approach may be useful for identifying common cellular mechanisms arising from distinct genetic lesions

The molecular basis of host specialization in bean pathovars of Pseudomonas syringae

Biotrophic phytopathogens are typically limited to their adapted host range. In recent decades, investigations have teased apart the general molecular basis of intraspecific variation for innate immunity of plants, typically involving receptor proteins that enable perception of pathogen-associated molecular patterns or avirulence elicitors from the pathogen as triggers for defense induction. However, general consensus concerning evolutionary and molecular factors that alter host range across closely related phytopathogen isolates has been more elusive. Here, through genome comparisons and genetic manipulations, we investigate the underlying mechanisms that structure host range across closely related strains of Pseudomonas syringae isolated from different legume hosts. Although type III secretionindependent virulence factors are conserved across these three strains, we find that the presence of two genes encoding type III effectors (hopC1 and hopM1) and the absence of another (avrB2) potentially contribute to host range differences between pathovars glycinea and phaseolicola. These findings reinforce the idea that a complex genetic basis underlies host range evolution in plant pathogens. This complexity is present even in host–microbe interactions featuring relatively little divergence among both hosts and their adapted pathogens