β-Catenin is a pH sensor with decreased stability at higher intracellular pH.

β-Catenin functions as an adherens junction protein for cell-cell adhesion and as a signaling protein. β-catenin function is dependent on its stability, which is regulated by protein-protein interactions that stabilize β-catenin or target it for proteasome-mediated degradation. In this study, we show that β-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster β-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase β-TrCP. While β-catenin phosphorylation was pH independent, higher pHi induced increased β-TrCP binding and decreased β-catenin stability. An evolutionarily conserved histidine in β-catenin (found in the β-TrCP DSGIHS destruction motif) is required for pH-dependent binding to β-TrCP. Expressing a cancer-associated H36R-β-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic β-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of β-catenin stability, functioning in coincidence with phosphorylation

The Underestimation Of Egocentric Distance: Evidence From Frontal Matching Tasks

There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1α), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically

Sensitivity of super-kamiokande with gadolinium to low energy antineutrinos from pre-supernova emission

Supernova detection is a major objective of the Super-Kamiokande (SK) experiment. In the next stage of SK (SK-Gd), gadolinium (Gd) sulfate will be added to the detector, which will improve the ability of the detector to identify neutrons. A core-collapse supernova (CCSN) will be preceded by an increasing flux of neutrinos and antineutrinos, from thermal and weak nuclear processes in the star, over a timescale of hours; some of which may be detected at SK-Gd. This could provide an early warning of an imminent CCSN, hours earlier than the detection of the neutrinos from core collapse. Electron antineutrino detection will rely on inverse beta decay events below the usual analysis energy threshold of SK, so Gd loading is vital to reduce backgrounds while maximizing detection efficiency. Assuming normal neutrino mass ordering, more than 200 events could be detected in the final 12 hr before core collapse for a 15–25 solar mass star at around 200 pc, which is representative of the nearest red supergiant to Earth, α-Ori (Betelgeuse). At a statistical false alarm rate of 1 per century, detection could be up to 10 hr before core collapse, and a pre-supernova star could be detected by SK-Gd up to 600 pc away. A pre-supernova alert could be provided to the astrophysics community following gadolinium loading

Search for neutrinos in coincidence with gravitational wave events from the LIGO–Virgo O3a observing run with the Super-Kamiokande detector

The Super-Kamiokande detector can be used to search for neutrinos in time coincidence with gravitational waves detected by the LIGO–Virgo Collaboration (LVC). Both low-energy (7–100 MeV) and high-energy (0.1–105 GeV) samples were analyzed in order to cover a very wide neutrino spectrum. Follow-ups of 36 (out of 39) gravitational waves reported in the GWTC-2 catalog were examined; no significant excess above the background was observed, with 10 (24) observed neutrinos compared with 4.8 (25.0) expected events in the high-energy (low-energy) samples. A statistical approach was used to compute the significance of potential coincidences. For each observation, p-values were estimated using neutrino direction and LVC sky map; the most significant event (GW190602_175927) is associated with a post-trial p-value of 7.8% (1.4σ). Additionally, flux limits were computed independently for each sample and by combining the samples. The energy emitted as neutrinos by the identified gravitational wave sources was constrained, both for given flavors and for all flavors assuming equipartition between the different flavors, independently for each trigger and by combining sources of the same nature

Efficacy of regular professional brushing by a dental nurse for 3 months in nursing home residents-A randomized, controlled clinical trial

Objectives The oral health of nursing home residents is poor for various reasons. Many require help for oral hygiene. Regular professional brushing by a dental nurse should improve oral hygiene. This study aimed to determine the efficacy of regular tooth brushing by a dental nurse on the oral health of nursing home residents. Methods This controlled trial randomized participants (n = 50; mean age 83 +/- 8 years) to brushing by a dental nurse every 2 weeks for 3 months (n = 25; test group) or oral hygiene procedures performed/controlled by nursing home staff (n = 25; control group). Personal, general and oral health, as well as various oral hygiene parameters-plaque index (PI), gingivitis index (GI), papilla bleeding index (PBI), oral hygiene index (OHI) and Volpe-Manhold Index (VMI)-were evaluated at baseline, after initial professional dental cleaning and before last brushing. Results At baseline, oral health was impaired according to investigated indices in both groups. After professional brushing for 3 months, there were improvements in PI, GI and PBI, with significant increases compared with the control group in OHI and VMI (P = 0.017 and P < 0.001, respectively). Among the control group, the number of teeth decreased while the root caries index increased (P = 0.002 between groups). Conclusions Regular professional brushing every 2 weeks by a dental nurse can be recommended for nursing homes residents to improve oral health parameters and to help reduce root caries incidence as a basis to preserve the number of teeth. Such oral hygiene procedures will maintain and improve the oral health of nursing home residents