Cosmological structure formation from soft topological defects

Some models have extremely low-mass pseudo-Goldstone bosons that can lead to vacuum phase transitions at late times, after the decoupling of the microwave background.. This can generate structure formation at redshifts z greater than or approx 10 on mass scales as large as M approx 10 to the 18th solar masses. Such low energy transitions can lead to large but phenomenologically acceptable density inhomogeneities in soft topological defects (e.g., domain walls) with minimal variations in the microwave anisotropy, as small as delta Y/T less than or approx 10 to the minus 6 power. This mechanism is independent of the existence of hot, cold, or baryonic dark matter. It is a novel alternative to both cosmic string and to inflationary quantum fluctuations as the origin of structure in the Universe

Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor

Parasympathetic nerve-mediated contractions of detrusor smooth muscle are generated by ATP and acetylcholine (ACh) release from efferent nerve terminals. In humans, ACh is responsible for detrusor contractions in normal human bladders, whereas ATP has an additional role in overactive bladder pathologies. The ATP metabolite, adenosine, relaxes nerve-mediated contractions, with a potential action via presynaptic adenosine A1 receptor activation and subsequent suppression of neuronal ATP release. We investigated the effect of A1 receptor activation and downstream cAMP-dependent pathways on nerve-mediated ATP and ACh release, and detrusor contraction in mouse detrusor. Bladders from male C57BL/6 mice (12 wk) were used for in vitro experiments. Upon electrical field stimulation of intact preparations (detrusor and mucosal layers), ATP or ACh release was measured simultaneously with tension recordings. Activation of A1 receptors by adenosine or exogenous agonists reduced the lower frequency component of nerve-mediated contractions and neuronal ATP release. The A1 receptor antagonist abolished these effects. A1 receptor activation inhibits adenylyl cyclase (AC) activity and cAMP generation. The effect of A1 receptor activation was mimicked by a PKA antagonist but not by modulators of exchange proteins activated by cAMP, demonstrating that modulation of nerve-mediated ATP release is via PKA. Adenosine had no effect on ACh release or the higher frequency component of nerve-mediated contractions. Differential regulation of neurotransmitter release is possible at the detrusor nerve-muscle junction, as demonstrated by A1 receptor activation, and downstream inhibition of AC, cAMP generation, and PKA. The ability to specifically attenuate ATP release offers a potential to target purinergic motor pathways enhanced in overactive bladder pathologies

A Cytochrome-b Perspective on Passerina Bunting Relationships

We sequenced the complete mitochondrial cytochrome-b gene (1,143 nucleotides) for representatives of each species in the cardinalid genera Passerina (6 species), Guiraca (1 species), and Cyanocompsa (3 species), and used a variety of phylogenetic methods to address relationships within and among genera. We determined that Passerina, as presently recognized, is paraphyletic. Lazuli Bunting (P. amoena) is sister to the much larger Blue Grosbeak (Guiraca caerulea). Indigo Bunting (P. cyanea) and Lazuli Bunting are not sister taxa as generally thought. In all weighted parsimony trees and for the gamma-corrected HKY tree, Indigo Bunting is the sister of two sister groups, a “blue” (Lazuli Bunting and Blue Grosbeak) and a “painted” (Rosita\u27s Bunting [P. rositae], Orange-breasted Bunting [P. leclancherii], Varied Bunting [P. versicolor], and Painted Bunting [P. ciris]) clade. The latter two species form a highly supported sister pair of relatively more recent origin. Uncorrected (p) distances for ingroup (Passerina and Guiraca) taxa range from 3.0% (P. versicolor–P. ciris) to 7.6% (P. cyanea–P. leclancherii) and average 6.5% overall. Assuming a molecular clock, a bunting “radiation” between 4.1 and 7.3 Mya yielded four lineages. This timing is consistent with fossil evidence and coincides with a late-Miocene cooling during which a variety of western grassland habitats evolved. A reduction in size at that time may have allowed buntings to exploit that new food resource (grass seeds). We speculate that the Blue Grosbeak subsequently gained large size and widespread distribution as a result of ecological character displacement

Financial sector reforms and stochastic policy simulations: A flow of funds model for India

We apply stochastic simulation methods to a system-wide flow of funds model for India for 1951-94. We address two issues; first, the impact of financial reforms on interest rates and loanable funds, and second, the robustness of policy where there is uncertainty about the true model. We find considerable variation in policy risk depending on the policy instrument and the policy regime. Interest rate risks are greater in the controlled regime; quantity risks are greater in the decontrolled regime. Outcomes also depend on controls on intermediaries: more heavily controlled banks respond differently from other less heavily controlled financial intermediaries

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation

Geodatabase Development to Support Hyperspectral Imagery Exploitation

Geodatabase development for coastal studies conducted by the Naval Research Laboratory (NRL) is essential to support the exploitation of hyperspectral imagery (HSI). NRL has found that the remote sensing and mapping science community benefits from coastal classifications that group coastal types based on similar features. Selected features in project geodatabases relate to significant biological and physical forces that shape the coast. The project geodatabases help researchers understand factors that are necessary for imagery post processing, especially those features having a high degree of temporal and spatial variability. NRL project geodatabases include a hierarchy of environmental factors that extend from shallow water bottom types and beach composition to inland soil and vegetation characteristics. These geodatabases developed by NRL allow researchers to compare features among coast types. The project geodatabases may also be used to enhance littoral data archives that are sparse. This paper highlights geodatabase development for recent remote sensing experiments in barrier island, coral, and mangrove coast types

Computational Design and Elaboration of a De Novo Heterotetrameric α-Helical Protein that Selectively Binds an Emissive Abiological (Porphinato)zinc Chromophore

The first example of a computationally de novo designed protein that binds an emissive abiological chromophore is presented, in which a sophisticated level of cofactor discrimination is pre-engineered. This heterotetrameric, C(2)-symmetric bundle, A(His):B(Thr), uniquely binds (5,15-di[(4-carboxymethyleneoxy)phenyl]porphinato)zinc [(DPP)Zn] via histidine coordination and complementary noncovalent interactions. The A(2)B(2) heterotetrameric protein reflects ligand-directed elements of both positive and negative design, including hydrogen bonds to second-shell ligands. Experimental support for the appropriate formulation of [(DPP)Zn:A(His):B(Thr)](2) is provided by UV/visible and circular dichroism spectroscopies, size exclusion chromatography, and analytical ultracentrifugation. Time-resolved transient absorption and fluorescence spectroscopic data reveal classic excited-state singlet and triplet PZn photophysics for the A(His):B(Thr):(DPP)Zn protein (k(fluorescence) = 4 x 10(8) s(-1); tau(triplet) = 5 ms). The A(2)B(2) apoprotein has immeasurably low binding affinities for related [porphinato]metal chromophores that include a (DPP)Fe(III) cofactor and the zinc metal ion hemin derivative [(PPIX)Zn], underscoring the exquisite active-site binding discrimination realized in this computationally designed protein. Importantly, elements of design in the A(His):B(Thr) protein ensure that interactions within the tetra-alpha-helical bundle are such that only the heterotetramer is stable in solution; corresponding homomeric bundles present unfavorable ligand-binding environments and thus preclude protein structural rearrangements that could lead to binding of (porphinato)iron cofactors

N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs

Post-transcriptional regulation of mRNA during oxygen deprivation, or hypoxia, can affect the survivability of cells. Hypoxia has been shown to increase stability of a subset of ischemia-related mRNAs, including VEGF. RNA binding proteins and miRNAs have been identified as important for post-transcriptional regulation of individual mRNAs, but corresponding mechanisms that regulate global stability are not well understood. Recently, mRNA modification by N6-methyladenosine (m6A) has been shown to be involved in post-transcriptional regulation processes including mRNA stability and promotion of translation, but the role of m6A in the hypoxia response is unknown. In this study, we investigate the effect of hypoxia on RNA modifications including m6A. Our results show hypoxia increases m6A content of poly(A)+ messenger RNA (mRNA), but not in total or ribosomal RNA in HEK293T cells. Using m6A mRNA immunoprecipitation, we identify specific hypoxia-modified mRNAs, including glucose transporter 1 (Glut1) and c-Myc, which show increased m6A levels under hypoxic conditions. Many of these mRNAs also exhibit increased stability, which was blocked by knockdown of m6A-specific methyltransferases METTL3/14. However, the increase in mRNA stability did not correlate with a change in translational efficiency or the steady-state amount of their proteins. Knockdown of METTL3/14 did reveal that m6A is involved in recovery of translational efficiency after hypoxic stress. Therefore, our results suggest that an increase in m6A mRNA during hypoxic exposure leads to post-transcriptional stabilization of specific mRNAs and contributes to the recovery of translational efficiency after hypoxic stress

Tip-Leakage Vortex Inception on a Ducted Rotor

The tip-leakage vortex occurring on a ducted rotor was examined using both three component Laser Doppler Velocimetry (LDV) and planar Particle Imaging Velocimetry (PIV). The vortex strength and core size were examined for different vortex cross sections downstream of the blade trailing edge. The variability of these quantities are observed with PIV and the average quantities are compared between LDV and PIV. Developed cavitation is also examined for the leakage vortex. The implication of vortex variability on cavitation inception is discussed

Characterisation of nerve‐mediated ATP release from bladder detrusor muscle and its pathological implications

Background and Purpose. To characterise the molecular mechanisms that determine variability of atropine‐resistance of nerve‐mediated contractions in human and guinea‐pig detrusor smooth muscle Experimental Approach. Atropine‐resistance of nerve‐mediated contractions, and the role of P2X1 receptors, was measured in isolated preparations from guinea‐pigs and also humans with or without overactive bladder syndrome, from which the mucosa was removed. Nerve‐mediated ATP release was measured directly with amperometric ATP‐sensitive electrodes. Ecto‐ATPase activity of guinea‐pig and human detrusor samples was measured in vitro by measuring the concentration‐dependent rate of ATP breakdown. The transcription of ecto‐ATPase subtypes in human samples was measured by qPCR. Key Results Atropine resistance was greatest in guinea‐pig detrusor, absent in human tissue from normally‐functioning bladders and intermediate in human overactive bladder. Greater atropine resistance correlated with reduction of contractions by the ATP‐diphospho‐hydrolase apyrase, directly implicating ATP in their generation. E‐NTPDase‐1 was the most abundantly transcribed ecto‐ATPase of those tested and transcription was reduced in tissue from human overactive, compared to normal, bladders. E‐NTPDase‐1 enzymatic activity was inversely related to the magnitude of atropine resistance. Nerve‐mediated ATP release was continually measured and varied with stimulation frequency over the range 1‐16 Hz. Conclusion and Implications Atropine‐resistance in nerve‐mediated detrusor contractions is due to ATP release and its magnitude is inversely related to E‐NTPDase‐1 activity. ATP is released under different stimulation conditions compared to acetylcholine that implies different routes for their release</p