Spermatogenesis and sertoli cell activity in mice lacking Sertoli cell receptors for follicle stimulating hormone and androgen

Spermatogenesis in the adult male depends on the action of FSH and androgen. Ablation of either hormone has deleterious effects on Sertoli cell function and the progression of germ cells through spermatogenesis. In this study we generated mice lacking both FSH receptors (FSHRKO) and androgen receptors on the Sertoli cell (SCARKO) to examine how FSH and androgen combine to regulate Sertoli cell function and spermatogenesis. Sertoli cell number in FSHRKO-SCARKO mice was reduced by about 50% but was not significantly different from FSHRKO mice. In contrast, total germ cell number in FSHRKO-SCARKO mice was reduced to 2% of control mice (and 20% of SCARKO mice) due to a failure to progress beyond early meiosis. Measurement of Sertoli cell-specific transcript levels showed that about a third were independent of hormonal action on the Sertoli cell, whereas others were predominantly androgen dependent or showed redundant control by FSH and androgen. Results show that FSH and androgen act through redundant, additive, and synergistic regulation of spermatogenesis and Sertoli cell activity. In addition, the Sertoli cell retains a significant capacity for activity, which is independent of direct hormonal regulation

Intrinsic selection biases of ground-based gravitational wave searches for high-mass BH-BH mergers

The next generation of ground-based gravitational wave detectors may detect a few mergers of comparable-mass M\simeq 100-1000 Msun ("intermediate-mass'', or IMBH) spinning black holes. Black hole spin is known to have a significant impact on the orbit, merger signal, and post-merger ringdown of any binary with non-negligible spin. In particular, the detection volume for spinning binaries depends significantly on the component black hole spins. We provide a fit to the single-detector and isotropic-network detection volume versus (total) mass and arbitrary spin for equal-mass binaries. Our analysis assumes matched filtering to all significant available waveform power (up to l=6 available for fitting, but only l<= 4 significant) estimated by an array of 64 numerical simulations with component spins as large as S_{1,2}/M^2 <= 0.8. We provide a spin-dependent estimate of our uncertainty, up to S_{1,2}/M^2 <= 1. For the initial (advanced) LIGO detector, our fits are reliable for $M\in[100,500]M_\odot$ ($M\in[100,1600]M_\odot$). In the online version of this article, we also provide fits assuming incomplete information, such as the neglect of higher-order harmonics. We briefly discuss how a strong selection bias towards aligned spins influences the interpretation of future gravitational wave detections of IMBH-IMBH mergers.Comment: 18 pages, 15 figures, accepted by PRD. v2 is version accepted for publication, including minor changes in response to referee feedback and updated citation

Short Gamma-Ray Bursts and Binary Mergers in Spiral and Elliptical Galaxies: Redshift Distribution and Hosts

To test whether the short GRB rates, redshift distribution and host galaxies are consistent with current theoretical predictions, we use avery large database of population synthesis calculations to examine BH-NS and NS-NS merger rates in the universe, factoring in (i) the star formation history of the universe, (ii) a heterogeneous population of star-forming galaxies, including spirals and ellipticals, and (iii) a simple flux-limited selection model for short GRB detection. When we require our models reproduce the known short GRB rates and redshift measurements (and, for NS-NS, the merger rates extrapolated from binary pulsars in the Galaxy), a small fraction of models reproduce all observations, both when we assume a NS-NS and a BH-NS origin for bursts. Most commonly models produce mergers preferentially in spiral galaxies if short GRBs arise from NS-NS mergers alone. Model universes where present-day binary mergers occur preferentially in elliptical galaxies necessarily include a significant fraction of binaries with long delay times between birth and merger (often $O(10{\rm Gyr})$). Though long delays occur, almost all of our models predict that a higher proportion of short GRBs should occur at moderate to high redshift (e.g., $z>1$) than has presently been observed, in agreement with recent observations which suggest a selection bias towards successful follow-up of low-redshift short GRBs. Finally, if only a fraction of BH-NS mergers have the right combination of masses and spins to make GRBs, then at best only a small fraction of BH-NS models could be consistent with all {\em current} available data. (Abridged)Comment: 14 figures, using bitmapped fonts (via eps2eps) to fit in archive space restrictions; better resolution figures are available from the author. Accepted for publication in ApJ. v3 updates reference

Constraining population synthesis models via the binary neutron star population

The observed sample of double neutron-star (NS-NS) binaries presents a challenge to population-synthesis models of compact object formation: the parameters entering into these models must be carefully chosen so as to match (i) the observed star formation rate and (ii) the formation rate of NS-NS binaries, which can be estimated from the observed sample and the selection effects related to the discoveries with radio-pulsar surveys. In this paper, we select from an extremely broad family of possible population synthesis models those few (2%) which are consistent with the observed sample of NS-NS binaries. To further sharpen the constraints the observed NS-NS population places upon our understanding of compact-object formation processes, we separate the observed NS-NS population into two channels: (i) merging NS-NS binaries, which will inspiral and merge through the action of gravitational waves within $10$ Gyr, and (ii) wide NS-NS binaries, consisting of all the rest. With the subset of astrophysically consistent models, we explore the implications for the rates at which double black hole (BH-BH), black hole-neutron star (BH-NS), and NS-NS binaries will merge through the emission of gravitational waves.Comment: (v1) Submitted to ApJ. Uses emulateapj.cls. 8 pages, 7 figures. (v2) Minor textual changes in response to referee queries. Substantial additions in appendicies, including a detailed discussion of sample multidimensional population synthesis fit

Comparing compact binary parameter distributions I: Methods

Being able to measure each merger's sky location, distance, component masses, and conceivably spins, ground-based gravitational-wave detectors will provide a extensive and detailed sample of coalescing compact binaries (CCBs) in the local and, with third-generation detectors, distant universe. These measurements will distinguish between competing progenitor formation models. In this paper we develop practical tools to characterize the amount of experimentally accessible information available, to distinguish between two a priori progenitor models. Using a simple time-independent model, we demonstrate the information content scales strongly with the number of observations. The exact scaling depends on how significantly mass distributions change between similar models. We develop phenomenological diagnostics to estimate how many models can be distinguished, using first-generation and future instruments. Finally, we emphasize that multi-observable distributions can be fully exploited only with very precisely calibrated detectors, search pipelines, parameter estimation, and Bayesian model inference

Evolution of the Hemifused Intermediate on the Pathway to Membrane Fusion

AbstractThe pathway to membrane fusion in synthetic and biological systems is thought to pass through hemifusion, in which the outer leaflets are fused while the inner leaflets engage in a hemifusion diaphragm (HD). Fusion has been proposed to be completed by lysis of the expanded HD that matures from a localized stalklike initial connection. However, the process that establishes the expanded HD is poorly understood. Here we mathematically modeled hemifusion of synthetic vesicles, where hemifusion and fusion are most commonly driven by calcium and membrane tension. The model shows that evolution of the hemifused state is driven by these agents and resisted by interleaflet frictional and tensile stresses. Predicted HD growth rates depend on tension and salt concentration, and agree quantitatively with experimental measurements. For typical conditions, we predict that HDs expand at ∼30 μm2/s, reaching a final equilibrium area ∼7% of the vesicle area. Key model outputs are the evolving HD tension and area during the growth transient, properties that may determine whether HD lysis occurs. Applying the model to numerous published experimental studies that reported fusion, our results are consistent with a final fusion step in which the HD ruptures due to super-lysis HD membrane tensions

Waves of Arrivance

In this essay, we conduct an ancestral genealogy of the term “arrivant” through Kumina ceremony. A spiritual and ceremonial practice based in Jamaica, Kumina is, as Kamau Brathwaite describes, a living  fragmentation of an African religion which arrived in the Caribbean through the Middle Passage. On arrival, Kumina retained its ancestral remembrance and its Central African Indigeneity. The tidal intimacies of Kumina have a relation to Imogene “Queenie” Kennedy, known by Kamau Brathwaite, in the title-inspired epigraph to The Arrivants: A New World Trilogy (1973), as Kumina Queen. Originally based in St. Thomas and later Kingston, Jamaica, Kennedy’s role in her community as a Kumina Queen exemplifies the intimacies and relationalities among African and Taíno Indigeneities. Through her life and her Word, this paper will consider how “arrivant” continues to be an honorific for CentralAfrican ancestors who arrived in Jamaica as liminally enslaved and indentured

The connexin mimetic peptide Gap27 and Cx43-Knockdown reveal differential roles for Connexin43 in wound closure events in skin model systems

In the epidermis, remodelling of Connexin43 is a key event in wound closure. However, controversy between the role of connexin channel and non-channel functions exist. We compared the impact of SiRNA targeted to Connexin43 and the connexin mimetic peptide Gap27 on scrape wound closure rates and hemichannel signalling in adult keratinocytes (AK) and fibroblasts sourced from juvenile foreskin (JFF), human neonatal fibroblasts (HNDF) and adult dermal tissue (ADF). The impact of these agents, following 24 h exposure, on (encoding Connexin43), and gene expression, and Connexin43 and pSmad3 protein expression levels, were examined by qPCR and Western Blot respectively. In all cell types Gap27 (100-100 μM) attenuated hemichannel activity. In AK and JFF cells, Gap27 (100 nM-100 μM) enhanced scrape wound closure rates by ~50% but did not influence movement in HNDF or ADF cells. In both JF and AK cells, exposure to Gap27 for 24 h reduced the level of Cx43 protein expression but did not affect the level in ADF and HNDF cells. Connexin43-SiRNA enhanced scrape wound closure in all the cell types under investigation. In HDNF and ADF, Connexin43-SiRNA enhanced cell proliferation rates, with enhanced proliferation also observed following exposure of HDNF to Gap27. By contrast, in JFF and AK cells no changes in proliferation occurred. In JFF cells, Connexin43-SiRNA enhanced levels and in JFF and ADF cells both Connexin43-SiRNA and Gap27 enhanced pSmad3 protein expression levels. We conclude that Connexin43 signalling plays an important role in cell migration in keratinocytes and foreskin derived fibroblasts, however, different pathways are evoked and in dermal derived adult and neonatal fibroblasts, inhibition of Connexin43 signalling plays a more significant role in regulating cell proliferation than cell migration

Dynamical Interactions and the Black Hole Merger Rate of the Universe

Binary black holes can form efficiently in dense young stellar clusters, such as the progenitors of globular clusters, via a combination of gravitational segregation and cluster evaporation. We use simple analytic arguments supported by detailed N-body simulations to determine how frequently black holes born in a single stellar cluster should form binaries, be ejected from the cluster, and merge through the emission of gravitational radiation. We then convolve this ``transfer function'' relating cluster formation to black hole mergers with (i) the distribution of observed cluster masses and (ii) the star formation history of the universe, assuming that a significant fraction gcl of star formation occurs in clusters and that a significant fraction gcand of clusters undergo this segregation and evaporation process. We predict future ground--based gravitational wave (GW) detectors could observe ~500 (gcl/0.5) (gcand/0.1) double black hole mergers per year, and the presently operating LIGO interferometer would have a chance (50%) at detecting a merger during its first full year of science data. More realistically, advanced LIGO and similar next-generation gravitational wave observatories provide unique opportunities to constrain otherwise inaccessible properties of clusters formed in the early universe.Comment: 4 pages, 2 figures. To appear in PRD Rapid Communication