WASP restricts active Rac to maintain cells' front-rear polarization

YesEfficient motility requires polarized cells, with pseudopods at the front and a retracting rear. Polarization is maintained by restricting the pseudopod catalyst, active Rac, to the front. Here, we show that the actin nucleation-promoting factor Wiskott-Aldrich syndrome protein (WASP) contributes to maintenance of front-rear polarity by controlling localization and cellular levels of active Rac. Dictyostelium cells lacking WASP inappropriately activate Rac at the rear, which affects their polarity and speed. WASP’s Cdc42 and Rac interacting binding (“CRIB”) motif has been thought to be essential for its activation. However, we show that the CRIB motif’s biological role is unexpectedly complex. WASP CRIB mutants are no longer able to restrict Rac activity to the front, and cannot generate new pseudopods when SCAR/WAVE is absent. Overall levels of Rac activity also increase when WASP is unable to bind to Rac. However, WASP without a functional CRIB domain localizes normally at clathrin pits during endocytosis, and activates Arp2/3 complex. Similarly, chemical inhibition of Rac does not affect WASP localization or activation at sites of endocytosis. Thus, the interaction between small GTPases and WASP is more complex than previously thought—Rac regulates a subset of WASP functions, but WASP reciprocally restricts active Rac through its CRIB motif.Cancer Research UK grants A15672, A24450, and multidisciplinary grant A20017

The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

Purpose: Tracheal occlusion (TO)reverses pulmonary hypoplasia (PH)in congenital diaphragmatic hernia (CDH), but its mechanism of action remains poorly understood. Wnt signaling plays a critical role in lung development, but few studies exist. The purpose of our study was to a)confirm that our CDH rabbit model produced PH which was reversed by TO and b)determine the effects of CDH +/− TO on Wnt signaling. Methods: CDH was created in fetal rabbits at 23 days, TO at 28 days, and lung collection at 31 days. Lung body weight ratio (LBWR)and mean terminal bronchiole density (MTBD)were determined. mRNA and miRNA expression was determined in the left lower lobe using RT-qPCR. Results: Fifteen CDH, 15 CDH + TO, 6 sham CDH, and 15 controls survived and were included in the study. LBWR was low in CDH, while CDH + TO was similar to controls (p = 0.003). MTBD was higher in CDH fetuses and restored to control levels in CDH + TO (p \u3c 0.001). Reference genes TOP1, SDHA, and ACTB were consistently expressed within and between treatment groups. miR-33 and MKI67 were increased, and Lgl1 was decreased in CDH + TO. Conclusion: TO reversed pulmonary hypoplasia and stimulated early Wnt signaling in CDH fetal rabbits. Type of study: Basic science, prospective. Level of evidence: II

Surgical technique for developing a rabbit model of congenital diaphragmatic hernia and tracheal occlusion

The surgical model of congenital diaphragmatic hernia (CDH) has been utilized in exploring treatments and innovative therapies, such as tracheal occlusion (TO). The rabbit is an excellent surgical model compared to others due to lower cost, ease of care, short gestational period, and large litter size. This model is also ideal in studying lung hypoplasia of CDH because rabbit lung development is most similar to humans as alveolarization begins prior to birth and continues post-natally. However, the surgical technique in creating a rabbit model of CDH is quite difficult and information is lacking on how to establish this model. Therefore, the aim of this paper is to describe: • Surgical technique in establishing a rabbit model of CDH and TO • Perioperative care for pregnant rabbit doe

On the reheating stage after inflation

We point out that inflaton decay products acquire plasma masses during the reheating phase following inflation. The plasma masses may render inflaton decay kinematicaly forbidden, causing the temperature to remain frozen for a period at a plateau value. We show that the final reheating temperature may be uniquely determined by the inflaton mass, and may not depend on its coupling. Our findings have important implications for the thermal production of dangerous relics during reheating (e.g., gravitinos), for extracting bounds on particle physics models of inflation from Cosmic Microwave Background anisotropy data, for the production of massive dark matter candidates during reheating, and for models of baryogenesis or leptogensis where massive particles are produced during reheating.Comment: 8 pages, 2 figures. Submitted for publication in Phys. Rev.

Cosmic microwave background and large scale structure limits on the interaction between dark matter and baryons

We study the effect on the cosmic microwave background (CMB) anisotropy and large scale structure (LSS) power spectrum of a scattering interaction between cold dark matter and baryons. This scattering alters the CMB anisotropy and LSS spectrum through momentum transfer between the cold dark matter particles and the baryons. We find that current CMB observations can put an upper limit on the scattering cross section which is comparable with or slightly stronger than previous disk heating constraints at masses greater than 1 GeV, and much stronger at smaller masses. When large-scale structure constraints are added to the CMB limits, our constraint is more stringent than this previous limit at all masses. In particular, a dark matter-baryon scattering cross section comparable to the ``Spergel-Steinhardt'' cross section is ruled out for dark matter mass greater than 1 GeV.Comment: 8 pages, 2 figures, use RevTeX4, submitted to PRD replaced with revised versio

νd→μ−Δ++n\nu d \to \mu^- \Delta^{++} n Reaction and Axial Vector N−ΔN-\Delta Coupling

The reaction $\nu d \to \mu^- \Delta^{++} n$ is studied in the region of low $q^2$ to investigate the effect of deuteron structure and width of the $\Delta$ resonance on the differential cross section. The results are used to extract the axial vector $N-\Delta$ coupling $C^{A}_5$ from the experimental data on this reaction. The possibility to determine this coupling from electroweak interaction experiments with high intensity electron accelerators is discussed.Comment: 14 pages, REVTEX, 5 figure

Baryon number violation, baryogenesis and defects with extra dimensions

In generic models for grand unified theories(GUT), various types of baryon number violating processes are expected when quarks and leptons propagate in the background of GUT strings. On the other hand, in models with large extra dimensions, the baryon number violation in the background of a string is not trivial because it must depend on the mechanism of the proton stabilization. In this paper we argue that cosmic strings in models with extra dimensions can enhance the baryon number violation to a phenomenologically interesting level, if the proton decay is suppressed by the mechanism of localized wavefunctions. We also make some comments on baryogenesis mediated by cosmological defects. We show at least two scenarios will be successful in this direction. One is the scenario of leptogenesis where the required lepton number conversion is mediated by cosmic strings, and the other is the baryogenesis from the decaying cosmological domain wall. Both scenarios are new and have not been discussed in the past.Comment: 20pages, latex2e, comments and references added, to appear in PR

Cosmological bounds on large extra dimensions from non-thermal production of Kaluza-Klein modes

The existing cosmological constraints on theories with large extra dimensions rely on the thermal production of the Kaluza-Klein modes of gravitons and radions in the early Universe. Successful inflation and reheating, as well as baryogenesis, typically requires the existence of a TeV-scale field in the bulk, most notably the inflaton. The non-thermal production of KK modes with masses of order 100 GeV accompanying the inflaton decay sets the lower bounds on the fundamental scale M_*. For a 1 TeV inflaton, the late decay of these modes distort the successful predictions of Big Bang Nucleosynthesis unless M_*> 35, 13, 7, 5 and 3 TeV for 2, 3, 4, 5 and 6 extra dimensions, respectively. This improves the existing bounds from cosmology on M_* for 4, 5 and 6 extra dimensions. Even more stringent bounds are derived for a heavier inflaton.Comment: 17 pages, latex, 4 figure

Invisible Z-Boson Decays at e+e- Colliders

The measurement of the invisible Z-boson decay width at e+e- colliders can be done "indirectly", by subtracting the Z-boson visible partial widths from the Z-boson total width, or "directly", from the process e+e- -> \gamma \nu \bar{\nu}. Both procedures are sensitive to different types of new physics and provide information about the couplings of the neutrinos to the Z-boson. At present, measurements at LEP and CHARM II are capable of constraining the left-handed Z\nu\nu-coupling, 0.45 <~ g_L <~ 0.5, while the right-handed one is only mildly bounded, |g_R| <= 0.2. We show that measurements at a future e+e- linear collider at different center-of-mass energies, \sqrt{s} = MZ and \sqrt{s}s ~ 170 GeV, would translate into a markedly more precise measurement of the Z\nu\nu-couplings. A statistically significant deviation from Standard Model predictions will point toward different new physics mechanisms, depending on whether the discrepancy appears in the direct or the indirect measurement of the invisible Z-width. We discuss some scenarios which illustrate the ability of different invisible Z-boson decay measurements to constrain new physics beyond the Standard Model

Overfishing and habitat loss drive range contraction of iconic marine fishes to near extinction

Extinctions on land are often inferred from sparse sightings over time, but this technique is ill-suited for wide-ranging species. We develop a space-for-time approach to track the spatial contraction and drivers of decline of sawfishes. These iconic and endangered shark-like rays were once found in warm, coastal waters of 90 nations and are now presumed extinct in more than half (n = 46). Using dynamic geography theory, we predict that sawfishes are gone from at least nine additional nations. Overfishing and habitat loss have reduced spatial occupancy, leading to local extinctions in 55 of the 90 nations, which equates to 58.7% of their historical distribution. Retention bans and habitat protections are urgently necessary to secure a future for sawfishes and similar species