Novel Insights Regarding the Operational Characteristics and Teleological Purpose of the Renal Na+-K+-Cl2 Cotransporter (NKCC2s) Splice Variants

The absorptive Na+-K+-Cl− cotransporter (NKCC2) is a polytopic protein that forms homooligomeric complexes in the apical membrane of the thick ascending loop of Henle (TAL). It occurs in at least four splice variants (called B, A, F, and AF) that are identical to one another except for a short region in the membrane-associated domain. Although each of these variants exhibits unique functional properties and distributions along the TAL, their teleological purpose and structural organization remain poorly defined. In the current work, we provide additional insight in these regards by showing in mouse that the administration of either furosemide or an H2O-rich diet, which are predicted to alter NKCC2 expression in the TAL, exerts differential effects on mRNA levels for the variants, increasing those of A (furosemide) but decreasing those of F and AF (furosemide or H2O). Based on a yeast two-hybrid mapping analysis, we also show that the formation of homooligomeric complexes is mediated by two self-interacting domains in the COOH terminus (residues 671 to 816 and 910 to 1098), and that these complexes could probably include more than one type of variant. Taken together, the data reported here suggest that A, F, and AF each play unique roles that are adapted to specific physiological needs, and that the accomplishment of such roles is coordinated through the splicing machinery as well as complex NKCC2–NKCC2 interactions

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation

Edge Detection in Landing Budgerigars (Melopsittacus undulatus)

Background: While considerable scientific effort has been devoted to studying how birds navigate over long distances, relatively little is known about how targets are detected, obstacles are avoided and smooth landings are orchestrated. Here we examine how visual features in the environment, such as contrasting edges, determine where a bird will land. Methodology/Principal Findings: Landing in budgerigars (Melopsittacus undulatus) was investigated by training them to fly from a perch to a feeder, and video-filming their landings. The feeder was placed on a grey disc that produced a contrasting edge against a uniformly blue background. We found that the birds tended to land primarily at the edge of the disc and walk to the feeder, even though the feeder was in the middle of the disc. This suggests that the birds were using the visual contrast at the boundary of the disc to target their landings. When the grey level of the disc was varied systematically, whilst keeping the blue background constant, there was one intermediate grey level at which the budgerigar's preference for the disc boundary disappeared. The budgerigars then landed randomly all over the test surface. Even though this disc is (for humans) clearly distinguishable from the blue background, it offers very little contrast against the background, in the red and green regions of the spectrum. Conclusions: We conclude that budgerigars use visual edges to target and guide landings. Calculations of photoreceptor excitation reveal that edge detection in landing budgerigars is performed by a color-blind luminance channel that sums the signals from the red and green photoreceptors, or, alternatively, receives input from the red double-cones. This finding has close parallels to vision in honeybees and primates, where edge detection and motion perception are also largely color-blind

Study of Zγ events and limits on anomalous ZZγ and Zγγ couplings in pp̄ collisions at s=1.96TeV

We present a measurement of the Zγ production cross section and limits on anomalous ZZγ and Zγγ couplings for form-factor scales of Λ=750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eeγ (μμγ) final state using 320(290)pb-1 of pp̄ collisions at s=1.96TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are |h10,30Z|<0.23, |h20,40Z|<0.020, |h10,30γ|<0.23, and |h20,40γ|<0.019 for Λ=1000GeV. © 2005 The American Physical Society

Search for R-parity violating supersymmetry via the LLE couplings lambda_{121}, lambda_{122} or lambda_{133} in ppbar collisions at sqrt(s)=1.96 TeV

A search for gaugino pair production with a trilepton signature in the framework of R-parity violating supersymmetry via the couplings lambda_121, lambda_122, or lambda_133 is presented. The data, corresponding to an integrated luminosity of L~360/pb, were collected from April 2002 to August 2004 with the D0 detector at the Fermilab Tevatron Collider, at a center-of-mass energy of sqrt(s)=1.96 TeV. This analysis considers final states with three charged leptons with the flavor combinations eel, mumul, and eetau (l=e or mu). No evidence for supersymmetry is found and limits at the 95% confidence level are set on the gaugino pair production cross section and lower bounds on the masses of the lightest neutralino and chargino are derived in two supersymmetric models.Comment: 9 pages, 4 figures (fig2 includes 3 subfigures

Measurement of the Bs0B^{0}_{s} Lifetime Using Semileptonic Decays

We report a measurement of the $B^0_{s}$ lifetime in the semileptonic decay channel $B^0_{s}\to D^-_s \mu^{+}\nu X$ (and its charge conjugate), using approximately 0.4 fb$^{-1}$ of data collected with the D0 detector during 2002 -- 2004. We have reconstructed 5176 $D^-_s \mu^{+}$ signal events, where the $D_s^-$ is identified via the decay $D_s^-\to \phi\pi^-$, followed by $\phi\to K^+ K^-$. Using these events, we have measured the $B^0_s$ lifetime to be $\tau(B^0_{s}) = 1.398 \pm 0.044$ $({stat}) ^{+0.028}_{-0.025}$ $({syst}) {ps}$. This is the most precise measurement of the $B_s^0$ lifetime to date.Comment: To appear in Phys. Rev. Lett., 7 pages, 2 figure

Measurement of the Lifetime Difference in the B_s^0 System

We present a study of the decay B_s^0 -> J/psi phi We obtain the CP-odd fraction in the final state at time zero, R_perp = 0.16 +/- 0.10 (stat) +/- 0.02 (syst), the average lifetime of the (B_s, B_sbar) system, tau (B_s^0) =1.39^{+0.13}_{-0.16} (stat) ^{+0.01}_{-0.02} (syst) ps, and the relative width difference between the heavy and light mass eigenstates, Delta Gamma/Gamma = (Gamma_L - Gamma_H)/Gamma =0.24^{+0.28}_{-0.38} (stat) ^{+0.03}_{-0.04} (syst). With the additional constraint from the world average of the B_s^0$lifetime measurements using semileptonic decays, we find tau (B_s^0)= 1.39 +/- 0.06 ~ps and Delta Gamma/\Gamma = 0.25^{+0.14}_{-0.15}. For the ratio of the B_s^0 and B^0 lifetimes we obtain tau(B_s^0)/tau(B^0)} = 0.91 +/- 0.09 (stat) +/- 0.003 (syst).Comment: submitted to Phys. Rev. Lett. FERMILAB-PUB-05-324-

Measurement of Semileptonic Branching Fractions of B Mesons to Narrow D** States

Using the data accumulated in 2002-2004 with the DO detector in proton-antiproton collisions at the Fermilab Tevatron collider with centre-of-mass energy 1.96 TeV, the branching fractions of the decays B -> \bar{D}_1^0(2420) \mu^+ \nu_\mu X and B -> \bar{D}_2^{*0}(2460) \mu^+ \nu_\mu X and their ratio have been measured: BR(\bar{b}->B) \cdot BR(B-> \bar{D}_1^0 \mu^+ \nu_\mu X) \cdot BR(\bar{D}_1^0 -> D*- pi+) = (0.087+-0.007(stat)+-0.014(syst))%; BR(\bar{b}->B)\cdot BR(B->D_2^{*0} \mu^+ \nu_\mu X) \cdot BR(\bar{D}_2^{*0} -> D*- \pi^+) = (0.035+-0.007(stat)+-0.008(syst))%; and (BR(B -> \bar{D}_2^{*0} \mu^+ \nu_\mu X)BR(D2*0->D*- pi+)) / (BR(B -> \bar{D}_1^{0} \mu^+ \nu_\mu X)\cdot BR(\bar{D}_1^{0}->D*- \pi^+)) = 0.39+-0.09(stat)+-0.12(syst), where the charge conjugated states are always implied.Comment: submitted to Phys. Rev. Let

Measurement of the ppbar to ttbar production cross section at sqrt(s)=1.96 TeV in the fully hadronic decay channel

A measurement of the top quark pair production cross section in proton anti-proton collisions at an interaction energy of sqrt(s)=1.96 TeV is presented. This analysis uses 405 pb-1 of data collected with the D0 detector at the Fermilab Tevatron Collider. Fully hadronic ttbar decays with final states of six or more jets are separated from the multijet background using secondary vertex tagging and a neural network. The ttbar cross section is measured as sigma(ttbar)=4.5 -1.9 +2.0 (stat) -1.1 +1.4 (syst) +/- 0.3 (lumi) pb for a top quark mass of m(t) = 175 GeV/c^2.Comment: 10 pages, 10 figures, submitted to Phys. Rev.

Search for Neutral Higgs Bosons Decaying to Tau Pairs in p-pbar Collisions at sqrt(s) = 1.96 TeV

A search for the production of neutral Higgs bosons Phi decaying into tau^+tau^- final states in p-pbar collisions at a center-of-mass energy of 1.96 TeV is presented. The data, corresponding to an integrated luminosity of up to 348 pb^-1, were collected by the D0 experiment at the Fermilab Tevatron Collider. Since no excess compared to the expectation from standard model processes is found, limits on the production cross section times branching ratio are set. The results are combined with those obtained from the D0 search for Phi b(b) to b-bbar-b(bbar) and are interpreted in the minimal supersymmetric standard model.Comment: Version accpeted by Phys. Rev. Lett. (minor changes