Activation of Gastrin‐releasing Peptide Receptors in the Lumbosacral Spinal Cord is Required for Ejaculation in Male Rats

Introduction.  Ejaculation is a complex reflex mediated by a spinal ejaculation generator located in the lumbosacral spinal cord and consisting of a population of lumbar spinothalamic (LSt) neurons. LSt neurons and their intraspinal axonal projections contain several neuropeptides, including gastrin‐releasing peptide (GRP). Aim.  To test the hypothesis that GRP is critically involved in mediating ejaculation by acting in autonomic and motor areas of the lumbosacral spinal cord, utilizing a physiological paradigm to investigate ejaculatory reflexes in isolation of supraspinal inputs. Methods.  Dual immunohistochemistry for GRP and galanin was performed to investigate co‐expression of GRP in LSt cells of control male rats. Next, anesthetized, spinalized male rats received intrathecal infusions of either GRP antagonist RC‐3095 (0, 10, or 20 nmol/10 µL) or GRP (0, 0.2, 0.5 nmol/10 µL). Ejaculatory reflexes were induced by electrical stimulation of the dorsal penile nerve (DPN) which reliably triggers rhythmic increases in seminal vesicle pressure (SVP) and contractions of the bulbocavernosus muscle (BCM), indicative of the emission and expulsion phases of ejaculation, respectively. Main Outcome Measures.  GRP in LSt cells was expressed as percentages of co‐expression. SVP and electromyographic recording (EMG) of BCM activity following drug treatment and DPN stimulation were recorded and analyzed for numbers of SVP increases, BCM events and bursts. Results.  GRP was exclusively expressed in LSt cells and axons. Intrathecal infusion of RC‐3095, but not saline, blocked SVP increases and BCM bursting induced by DPN stimulation. Intrathecal infusions of GRP, but not saline, triggered SVP increases and BCM bursting in 43–66% of animals and facilitated SVP increases and BCM bursting induced by subthreshold DPN stimulation in all animals. Conclusion.  These data support a critical role for GRP for control of the emission and expulsion phases of ejaculation in male rats by acting in LSt target areas in the lumbosacral spinal cord. Kozyrev N, Lehman MN, and Coolen LM. Activation of gastrin‐releasing peptide receptors in the lumbosacral spinal cord is required for ejaculation in male rats. J Sex Med 2012;9:1303–1318.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91163/1/j.1743-6109.2012.02688.x.pd

Src phosphorylation converts Mdm2 from a ubiquitinating to a neddylating E3 ligase

Murine double minute-2 protein (Mdm2) is a multifaceted phosphorylated protein that plays a role in regulating numerous proteins including the tumor suppressor protein p53. Mdm2 binds to and is involved in conjugating either ubiquitin or Nedd8 (Neural precursor cell expressed, developmentally down-regulated 8) to p53. Although regulation of the E3 ubiquitin activity of Mdm2 has been investigated, regulation of the neddylating activity of Mdm2 remains to be defined. Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex. Mdm2-dependent Nedd8 conjugation of p53 results in transcriptionally inactive p53, a process that is reversed with a small molecule inhibitor to either Src or Ubc12. Thus, our studies reveal how Mdm2 may neutralize and elevate p53 in actively proliferating cells and also provides a rationale for using therapies that target the Nedd8 pathway in wild-type p53 tumors

Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep

Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive (‐ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30–90 or 60–90 resulted in increased numbers of VTA TH‐ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T‐treated ewes, which was primarily accounted for by greater numbers of TH‐ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T‐treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH‐ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH‐ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.We report a sex difference in ventral tegmental area (VTA) dopamine cells in the adult sheep with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive cells in males than females. Moreover, prenatal exposure to excess T during gestational days 30–90 or 60–90 caused increased numbers of VTA TH‐immunoreactive cells in adult ewes compared to control females. Sex differences were also demonstrated in the substantia nigra, but prenatal T had no effect on TH in this area. Results indicate that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels in the VTA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111123/1/ejn12871.pd

PEN: a low energy test of lepton universality

Allowed charged $\pi$ meson decays are characterized by simple dynamics, few available decay channels, mainly into leptons, and extremely well controlled radiative and loop corrections. In that sense, pion decays represent a veritable triumph of the standard model (SM) of elementary particles and interactions. This relative theoretical simplicity makes charged pion decays a sensitive means for testing the underlying symmetries and the universality of weak fermion couplings, as well as for studying pion structure and chiral dynamics. Even after considerable recent improvements, experimental precision is lagging far behind that of the theoretical description for pion decays. We review the current state of experimental study of the pion electronic decay $\pi^+ \to e^+\nu_e(\gamma)$, or $\pi_{e2(\gamma)}$, where the $(\gamma)$ indicates inclusion and explicit treatment of radiative decay events. We briefly review the limits on non-SM processes arising from the present level of experimental precision in $\pi_{e2(\gamma)}$ decays. Focusing on the PEN experiment at the Paul Scherrer Institute (PSI), Switzerland, we examine the prospects for further improvement in the near term.Comment: 11 pages, 5 figures; paper presented at the XIII International Conference on Heavy Quarks and Leptons, 22-27 May 2016, Blacksburg, Virginia, US

Assessing architectural evolution: A case study

This is the post-print version of the Article. The official published can be accessed from the link below - Copyright @ 2011 SpringerThis paper proposes to use a historical perspective on generic laws, principles, and guidelines, like Lehman’s software evolution laws and Martin’s design principles, in order to achieve a multi-faceted process and structural assessment of a system’s architectural evolution. We present a simple structural model with associated historical metrics and visualizations that could form part of an architect’s dashboard. We perform such an assessment for the Eclipse SDK, as a case study of a large, complex, and long-lived system for which sustained effective architectural evolution is paramount. The twofold aim of checking generic principles on a well-know system is, on the one hand, to see whether there are certain lessons that could be learned for best practice of architectural evolution, and on the other hand to get more insights about the applicability of such principles. We find that while the Eclipse SDK does follow several of the laws and principles, there are some deviations, and we discuss areas of architectural improvement and limitations of the assessment approach

Predator hunting mode and host plant quality shape attack-abatement patterns of predation risk in an insect herbivore

Group formation reduces individual predation risk when the proportion of prey taken per predator encounter declines faster than the increase in group encounter rate (a ack-abatement). Despite a ack-abatement being an important component of group formation ecology, several key aspects have not been empirically studied, that is, interactions with the hunting mode of the predator and how these relationships are modi ed by local habitat quality. In 79 cage trials, we examined individual egg predation risk in di erent-sized egg clutches from the blue willow beetle Phratora vulgatissima for two predators with di erent hunting modes (consumption of full group [Orthotylus marginalis] vs. part group [Anthocoris nemorum]). Because these predators also take nutrients from plant sap, we could examine how the quality of alternative food sources (high- vs. low-quality host plant sap) in uenced a ack-abatement pa erns in the presence of di erent hunting strategies. For the O. marginalis predator, individual egg predation risk was largely independent of group size. For A. nemorum, egg predation risk clearly declined with increasing group size. However, approximately one-third of the grouping bene t was lost to an increase in group detectability. There were clear di erences in a ack-abatement pa erns between plants with high- vs. low-quality sap. When O. marginalis was the predator, there was no clear change in a ack-abatement in relation to host plant quality. However, for A. nemorum there was a clear reduction in overall predation risk and a stronger a ack-abatement pa ern with increasing group size when plant sap quality increased. This implies that the relative bene ts of prey grouping behavior for any species might show diurnal or seasonal changes as other aspects of resource/habitat quality change for the focal predator. Modulation of a ack-abatement by bo om-up e ects such as plant-based food resources is yet to be incorporated into general theory, despite the ubiquity of omnivorous predators and with omnivory being important for shaping food webs, ecosystem functions, and in biological control. Thus, ongoing re nement of a ack- abatement theory by focusing on bo om-up vs. top-down processes could have signi cant impacts on many important contemporary elds of study

Collisional and thermal ionization of sodium Rydberg atoms I. Experiment for nS and nD atoms with n=8-20

Collisional and thermal ionization of sodium nS and nD Rydberg atoms with n=8-20 has been studied. The experiments were performed using a two-step pulsed laser excitation in an effusive atomic beam at atom density of about 2 10^{10} cm^{-3}. Molecular and atomic ions from associative, Penning, and thermal ionization processes were detected. It has been found that the atomic ions were created mainly due to photoionization of Rydberg atoms by photons of blackbody radiation at the ambient temperature of 300K. Blackbody ionization rates and effective lifetimes of Rydberg states of interest were determined. The molecular ions were found to be from associative ionization in Na(nL)+Na(3S) collisions. Rate constants of associative ionization have been measured using an original method based on relative measurements of Na_{2}^{+} and Na^{+} ion signals.Comment: 23 pages, 10 figure

OPTN/SRTR 2017 Annual Data Report: Heart

In 2017, 3273 heart transplants were performed in the United States. New listings continued to increase, and 3769 new adults were listed for heart transplant in 2017. Over the past decade, posttransplant mortality has declined. The number of new pediatric listings increased over the past decade, as did the number of pediatric heart transplants, although some fluctuation has occurred more recently. New listings for pediatric heart transplants increased from 481 in 2007 to 623 in 2017. The number of pediatric heart transplants performed each year increased from 330 in 2007 to 432 in 2017, slightly fewer than in 2016. Short‐term and long‐term mortality improved. Among pediatric patients who underwent transplant between 2015‐2016, 4.8% had died by 6 months and 6.2% by 1 year.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148229/1/ajt15278.pd