The rockefeller university

Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the hypothalamic paraventricular nucleus (PVN), an area central to the stress response. The physiological function of relaxin-3 is unknown but previous work suggests a role in appetite control, stimulation of the hypothalamic-pituitary-gonadal axis and stress. Central administration of relaxin-3 induces c-fos expression in the PVN and increases plasma ACTH levels in rats. The aim of this study was to investigate the effect of central administration of human relaxin-3 (H3) on the hypothalamic-pituitary-adrenal (HPA) axis in male rodents in vivo and in vitro. Intracerebroventricular (i.c.v) administration of H3 (5 nmol) significantly increased plasma corticosterone at 30 min following injection compared with vehicle. Intra-PVN administration of H3 (1.8-1620 pmol) significantly increased plasma ACTH at 1620 pmol H3 and corticosterone at 180-1620 pmol H3 at 30 min following injection compared with vehicle. The stress hormone prolactin was also significantly raised at 15 min post-injection compared with vehicle. Treatment of hypothalamic explants with H3 (10-1000 nM) stimulated the release of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), but H3 had no effect on the release of ACTH from in vitro pituitary fragments. These results suggest that relaxin-3 may regulate the HPA axis, via hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central signal linking nutritional status, reproductive function and stress.

Transit-amplifying cells (TACs) are an early intermediate in tissue regeneration. Here, using hair follicles (HFs) as a paradigm, we show that emerging TACs constitute a signaling center that orchestrates tissue growth. Whereas primed stem cells (SCs) generate TACs, quiescent SCs only proliferate after TACs form and begin expressing Sonic Hedgehog (SHH). TAC generation is independent of autocrine SHH, but the TAC pool wanes if they can't produce SHH. We trace this paradox to two direct actions of SHH: promoting quiescent-SC proliferation and regulating dermal factors that stoke TAC expansion. Ingrained within quiescent SCs' special sensitivity to SHH signaling is their high expression of GAS1. Without sufficient input from quiescent SCs, replenishment of primed SCs for the next hair cycle is compromised, delaying regeneration and eventually leading to regeneration failure. Our findings unveil TACs as transient but indispensable integrators of SC niche components and reveal an intriguing interdependency of primed and quiescent SC populations on tissue regeneration.

Spin correlations and polarization in the top quark-antiquark system are measured using dilepton final states produced in pp collisions at the LHC at root s = 7 TeV. The data correspond to an integrated luminosity of 5.0 fb(-1) collected with the CMS detector. The measurements are performed using events with two oppositely charged leptons (electrons or muons), a significant imbalance in transverse momentum, and two or more jets, where at least one of the jets is identified as originating from a b quark. The spin correlations and polarization are measured through asymmetries in angular distributions of the two selected leptons, unfolded to the parton level. All measurements are found to be in agreement with predictions of the standard model.

A measurement of total and fiducial inclusive W and Z boson production cross sections in pp collisions at root s = 8 TeV is presented. Electron and muon final states are analyzed in a data sample collected with the CMS detector corresponding to an integrated luminosity of 18.2 +/- 0.5 pb(-1). The measured total inclusive cross sections times branching fractions are sigma(pp -> WX) x B(W -> l upsilon) = 12.21 +/- 0.03(stat) +/- 0.24(syst) +/- 0.32(lum) nb and sigma(pp -> ZX) x B(Z -> l(+)l(-)) = 1.15 +/- 0.01(stat) +/- 0.02(syst) +/- 0.03(lum) nb for the dilepton mass in the range of 60-120 GeV. The measured values agree with next-to-next-to-leading-order QCD cross section calculations. Ratios of cross sections are reported with a precision of 2%. This is the first measurement of inclusive W and Z boson production in proton-proton collisions at root s = 8 TeV.

Results are presented from a search for the production of a heavy gauge boson W' decaying into a top and a bottom quark, using a data set collected by the CMS experiment at root s = 8 TeV and corresponding to an integrated luminosity of 19.5 fb(-1). Various models of W'-boson production are studied by allowing for an arbitrary combination of left-and right-handed couplings. The analysis is based on the detection of events with a lepton (e, mu), jets, and missing transverse energy in the final state. No evidence for W'-boson production is found and 95% confidence level upper limits on the production cross section times branching fraction are obtained. For W' bosons with purely right-handed couplings, and for those with left-handed couplings assuming no interference effects, the observed 95% confidence level limit is M(W') > 2.05TeV. For W' bosons with purely left-handed couplings, including interference effects, the observed 95% confidence level limit is M(W') > 1.84 TeV. The results presented in this paper are the most stringent limits published to date.

Taylor's power law of fluctuation scaling (TL) states that for population density, population abundance, biomass density, biomass abundance, cell mass, protein copy number, or any other nonnegative-valued random variable in which the mean and the variance are positive, variance = a(mean)(b), a > 0, or equivalently log variance = log a + b x log mean. Many empirical examples and practical applications of TL are known, but understanding of TL's origins and interpretations remains incomplete. We show here that, as time becomes large, TL arises from multiplicative population growth in which successive random factors are chosen by a Markov chain. We give exact formulas for a and b in terms of the Markov transition matrix and the values of the successive multiplicative factors. In this model, the mean and variance asymptotically increase exponentially if and only if b > 2 and asymptotically decrease exponentially if and only if b < 2. (c) 2014 Elsevier Inc. All rights reserved.

Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with critical roles in both adaptive immunity and tolerance to self. Skin DCs carry antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In mice, Langerin-CD11b - dermal DCs are a low-frequency, heterogeneous, migratory DC subset that traffics to LNs (Langerin-CD11b - migDCs). Here, we build on the observation that Langerin-CD11b - migDCs are Fms-like tyrosine kinase 3 ligand (Flt3L) dependent and strongly Flt3L responsive, which may relate them to classical DCs. Examination of DC capture of FITC from painted skin, DC isolation from skin explant culture, and from the skin of CCR7 knockout mice, which accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin-CD11b - Flt3L-responsive DCs are largely CD24(+) and CX(3)CR1(low) and can be depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b - migDCs present antigen with equal efficiency to other DC subsets ex vivo, including classical CD8 alpha cDCs and Langerin +CD103+ dermal DCs. Finally, transcriptome analysis suggests a close relationship with other skin DCs, and a lineage relationship with other classical DCs. This work demonstrates that Langerin-CD11b - dermal DCs, a previously overlooked cell subset, may be an important contributor to the cutaneous immune environment.

Tawny crazy ants are spreading across the southern U.S., replacing one of the most notorious invasive pests, the red imported fire ant. A crucial factor in this process is that tawny crazy ants are able to efficiently detoxify fire ant venom.

Reversible thiol oxidation of cysteine residues occurs in many intracellular catalytic and signaling processes. Here we describe an optimized protocol, which can be completed in similar to 5 d, to unambiguously identify specific cysteine residues that are transiently and reversibly oxidized by comparing two complex biological samples obtained from yeast cell cultures at the proteome level. After ` freezing' the in vivo thiol stage of cysteine residues by medium acidification, we first block reduced thiols in extracts with iodoacetamide (IAM), and then we sequentially reduce and label reversible oxidized thiols with the biotin-based heavy or light IAM derivatives, which are known as isotope-coded affinity tag (ICAT) reagents, so that the two samples can be compared at once after combination of the labeled extracts, trypsin digestion, streptavidin-affinity purification of peptides containing oxidized cysteines, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. For the same protein extracts, before cysteine-containing peptide enrichment, individual relative protein concentrations are obtained by stable-isotope dimethyl labeling.

A search for flavor-changing neutral currents in top-quark decays t -> Zq is performed in events produced from the decay chain (tt) over bar -> Zq + Wb, where both vector bosons decay leptonically, producing a final state with three leptons (electrons or muons). A data set collected with the CMS detector at the LHC is used, corresponding to an integrated luminosity of 19.7 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV. No excess is seen in the observed number of events relative to the standard model prediction; thus, no evidence for flavor-changing neutral currents in top-quark decays is found. A combination with a previous search at 7 TeV excludes a t. Zq branching fraction greater than 0.05% at the 95% confidence level.