Casting Light on Dark Matter

The prospects for detecting a candidate supersymmetric dark matter particle at the LHC are reviewed, and compared with the prospects for direct and indirect searches for astrophysical dark matter. The discussion is based on a frequentist analysis of the preferred regions of the Minimal supersymmetric extension of the Standard Model with universal soft supersymmetry breaking (the CMSSM). LHC searches may have good chances to observe supersymmetry in the near future - and so may direct searches for astrophysical dark matter particles, whereas indirect searches may require greater sensitivity, at least within the CMSSM.Comment: 16 pages, 13 figures, contribution to the proceedings of the LEAP 2011 Conferenc

PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse.

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMVPACAP) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with Adcyap1fl/fl mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction in female mice

Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse.

The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release

Tachykinin signaling is required for the induction of the preovulatory LH surge and normal LH pulses.

Tachykinins (NKA, NKB and Substance P) are important components of the neuroendocrine control of reproduction by directly stimulating Kiss1 neurons to control GnRH pulsatility, essential for reproduction. Despite this role of tachykinins for successful reproduction, knockout mice for Tac1 (NKA/SP) and Tac2 (NKB) genes are fertile, resembling the phenotype of human patients bearing NKB signaling mutations, who often reverse their hypogonadal phenotype. This suggests the existence of compensatory mechanisms among the different tachykinin ligand-receptor systems, to maintain reproduction in the absence of one of them. In order to test this hypothesis, we generated complete tachykinin deficient mice (Tac1/Tac2KO). Male mice displayed delayed puberty onset and decreased LH pulsatility (frequency and amplitude of LH pulses) but preserved fertility. However, females did not show signs of puberty onset (first estrus) within 45 days after vaginal opening, displayed low frequency (but normal amplitude) of LH pulses and 80% of them remained infertile. Further evaluation identified a complete absence of the preovulatory LH surge in Tac1/Tac2KO females as well as in WT females treated with NKB or SP receptor antagonists. These data confirmed a fundamental role for tachykinins in the timing of puberty onset and LH pulsatility and uncovered a role of tachykinin signaling in the facilitation of the preovulatory LH surge. Overall, these findings indicate that tachykinin signaling plays a dominant role in the control of ovulation, with potential implications as pathogenic mechanism and therapeutic target to improve reproductive outcomes in women with ovulation impairments

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Effective Dark Matter Model: Relic density, CDMS II, Fermi LAT and LHC

The Cryogenic Dark Matter Search recently announced the observation of two signal events with a 77% confidence level. Although statistically inconclusive, it is nevertheless suggestive. In this work we present a model-independent analysis on the implication of a positive signal in dark matter scattering off nuclei. Assuming the interaction between (scalar, fermion or vector) dark matter and the standard model induced by unknown new physics at the scale $\Lambda$, we examine various dimension-6 tree-level induced operators and constrain them using the current experimental data, e.g. the WMAP data of the relic abundance, CDMS II direct detection of the spin-independent scattering, and indirect detection data (Fermi LAT cosmic gamma-ray), etc. Finally, the LHC reach is also explored

Reproductive Hormone-Dependent and -Independent Contributions to Developmental Changes in Kisspeptin in GnRH-Deficient Hypogonadal Mice

Kisspeptin is a potent activator of GnRH-induced gonadotropin secretion and is a proposed central regulator of pubertal onset. In mice, there is a neuroanatomical separation of two discrete kisspeptin neuronal populations, which are sexually dimorphic and are believed to make distinct contributions to reproductive physiology. Within these kisspeptin neuron populations, Kiss1 expression is directly regulated by sex hormones, thereby confounding the roles of sex differences and early activational events that drive the establishment of kisspeptin neurons. In order to better understand sex steroid hormone-dependent and -independent effects on the maturation of kisspeptin neurons, hypogonadal (hpg) mice deficient in GnRH and its downstream effectors were used to determine changes in the developmental kisspeptin expression. In hpg mice, sex differences in Kiss1 mRNA levels and kisspeptin immunoreactivity, typically present at 30 days of age, were absent in the anteroventral periventricular nucleus (AVPV). Although immunoreactive kisspeptin increased from 10 to 30 days of age to levels intermediate between wild type (WT) females and males, corresponding increases in Kiss1 mRNA were not detected. In contrast, the hpg arcuate nucleus (ARC) demonstrated a 10-fold increase in Kiss1 mRNA between 10 and 30 days in both females and males, suggesting that the ARC is a significant center for sex steroid-independent pubertal kisspeptin expression. Interestingly, the normal positive feedback response of AVPV kisspeptin neurons to estrogen observed in WT mice was lost in hpg females, suggesting that exposure to reproductive hormones during development may contribute to the establishment of the ovulatory gonadotropin surge mechanism. Overall, these studies suggest that the onset of pubertal kisspeptin expression is not dependent on reproductive hormones, but that gonadal sex steroids critically shape the hypothalamic kisspeptin neuronal subpopulations to make distinct contributions to the activation and control of the reproductive hormone cascade at the time of puberty

The R-Process Alliance: Fourth Data Release from the Search for R-process-enhanced Stars in the Galactic Halo

This compilation is the fourth data release from the R-Process Alliance (RPA) search for r-process-enhanced stars and the second release based on "snapshot" high-resolution (R ~ 30,000) spectra collected with the du Pont 2.5 m Telescope. In this data release, we propose a new delineation between the r-I and r-II stellar classes at $[\mathrm{Eu}/\mathrm{Fe}]=+0.7$, instead of the empirically chosen $[\mathrm{Eu}/\mathrm{Fe}]=+1.0$ level previously in use, based on statistical tests of the complete set of RPA data released to date. We also statistically justify the minimum level of [Eu/Fe] for definition of the r-I stars, [Eu/Fe] > +0.3. Redefining the separation between r-I and r-II stars will aid in the analysis of the possible progenitors of these two classes of stars and determine whether these signatures arise from separate astrophysical sources at all. Applying this redefinition to previous RPA data, the number of identified r-II and r-I stars changes to 51 and 121, respectively, from the initial set of data releases published thus far. In this data release, we identify 21 new r-II, 111 new r-I (plus 3 re-identified), and 7 new (plus 1 re-identified) limited-r stars out of a total of 232 target stars, resulting in a total sample of 72 new r-II stars, 232 new r-I stars, and 42 new limited-r stars identified by the RPA to date