Supporting Cells Remove and Replace Sensory Receptor Hair Cells in a Balance Organ of Adult Mice

Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreER(T2)-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreER(T2)-expressing supporting cells or by Atoh1-CreER(TM)-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury

More Elevated Fastballs Associated with Placement on the Injured List Due to Shoulder Injury

Purpose To evaluate whether impending shoulder injury was associated with changes in pitch location or velocity immediately preceding injury. Methods Pitchers placed on the injured list (IL) due to a shoulder injury between 2015 and 2020 were identified in the Major League Baseball transactions database. Four-seam fastball velocity and frequency of pitch location for each pitch type was collected for each player in the season before placement on the IL and within 1 month of placement on the IL with a minimum of 55 pitches thrown of 1 type. Pitch locations were collected as identified by Baseball Savant’s Game-Day Zones. Game-Day Zones were consolidated into high (above the strike zone midpoint) versus low, arm side (closer to the pitcher’s arm side of the plate) versus opposite side, and within the strike zone versus out of zone. Repeated measures analysis of variance determined differences in four-seam velocity and the location distribution of 4-seam fastballs, change-ups, and breaking balls among each group. Results In total, 267 pitchers were placed on the IL for a shoulder injury with the majority diagnosed with inflammation (89/267) followed by strain or sprain (69/267). Four-seam fastball locations significantly increased above the mid-point of the zone (45.9% vs 42.4%, P = .008) and out of the strike zone (48.5% vs 46.5%, P = .011) within a month before IL placement. There was no significant change in 4-seam fastball velocity immediately before IL placement. Conclusions Pitchers threw more elevated 4-seam fastballs and out-of-zone 4-seam fastballs in the month before IL placement for shoulder injury. These findings suggest that a loss of 4-seam fastball command decreases with impending shoulder injury. Level of Evidence IV, prognostic case series

The LEECH Exoplanet Imaging Survey: Limits on Planet Occurrence Rates Under Conservative Assumptions

We present the results of the largest $L^{\prime}$ ($3.8~\mu$m) direct imaging survey for exoplanets to date, the Large Binocular Telescope Interferometer (LBTI) Exozodi Exoplanet Common Hunt (LEECH). We observed 98 stars with spectral types from B to M. Cool planets emit a larger share of their flux in $L^{\prime}$ compared to shorter wavelengths, affording LEECH an advantage in detecting low-mass, old, and cold-start giant planets. We emphasize proximity over youth in our target selection, probing physical separations smaller than other direct imaging surveys. For FGK stars, LEECH outperforms many previous studies, placing tighter constraints on the hot-start planet occurrence frequency interior to $\sim20$ au. For less luminous, cold-start planets, LEECH provides the best constraints on giant-planet frequency interior to $\sim20$ au around FGK stars. Direct imaging survey results depend sensitively on both the choice of evolutionary model (e.g., hot- or cold-start) and assumptions (explicit or implicit) about the shape of the underlying planet distribution, in particular its radial extent. Artificially low limits on the planet occurrence frequency can be derived when the shape of the planet distribution is assumed to extend to very large separations, well beyond typical protoplanetary dust-disk radii ($\lesssim50$ au), and when hot-start models are used exclusively. We place a conservative upper limit on the planet occurrence frequency using cold-start models and planetary population distributions that do not extend beyond typical protoplanetary dust-disk radii. We find that $\lesssim90\%$ of FGK systems can host a 7 to 10 $M_{\mathrm{Jup}}$ planet from 5 to 50 au. This limit leaves open the possibility that planets in this range are common.Comment: 31 pages, 13 figures, accepted to A

Personality dimensions of people who suffer from visual stress

Personality dimensions of participants who suffer from visual stress were compared with those of normal participants using the Eysenck Personality Inventory. Extraversion-Introversion scores showed no significant differences between the participants who suffered visual stress and those who were classified as normal. By contrast, significant differences were found between the normal participants and those with visual stress in respect of Neuroticism-Stability. These differences accord with Eysenck's personality theory which states that those who score highly on the neuroticism scale do so because they have a neurological system with a low threshold such that their neurological system is easily activated by external stimuli. The findings also relate directly to the theory of visual stress proposed by Wilkins which postulates that visual stress results from an excess of neural activity. The data may indicate that the excess activity is likely to be localised at particular neurological regions or neural processes

Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model

Background: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. Methodology/Principal Findings: We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change

First detection of two superoutbursts during rebrightening phase of a WZ Sge-type Dwarf Nova : TCP J21040470+4631129

We report on photometric and spectroscopic observations and analysis of the 2019 superoutburst of TCP J21040470+4631129. This object showed a 9 mag superoutburst with early superhumps and ordinary superhumps, which are the features of WZ Sge-type dwarf novae. Five rebrightenings were observed after the main superoutburst. The spectra during the post-superoutburst stage showed Balmer, He I, and possible sodium doublet features. The mass ratio is derived as 0.0880(9) from the period of the superhump. During the third and fifth rebrightenings, growing superhumps and superoutbursts were observed, which have never been detected during a rebrightening phase among WZ Sge-type dwarf novae with multiple rebrightenings. To induce a superoutburst during the brightening phase, the accretion disk needs to have expanded beyond the 3 : 1 resonance radius of the system again after the main superoutburst. These peculiar phenomena can be explained by the enhanced viscosity and large radius of the accretion disk suggested by the higher luminosity and the presence of late-stage superhumps during the post-superoutburst stage, plus by more mass supply from the cool mass reservoir and/or from the secondary because of the enhanced mass transfer than those of other WZ Sge-type dwarf novae.peer-reviewe

First Detection of Two Superoutbursts during Rebrightening Phase of a WZ Sge-type Dwarf Nova: TCP J21040470+4631129

We report photometric and spectroscopic observations and analysis of the 2019 superoutburst of TCP J21040470+4631129. This object showed a 9-mag superoutburst with early superhumps and ordinary superhumps, which are the features of WZ Sge-type dwarf novae. Five rebrightenings were observed after the main superoutburst. The spectra during the post-superoutburst stage showed the Balmer, He I and possible sodium doublet features. The mass ratio is derived as 0.0880(9) from the period of the superhump. During the third and fifth rebrightenings, growing superhumps and superoutbursts were observed, which have never been detected during a rebrightening phase among WZ Sge-type dwarf novae with multiple rebrightenings. To induce a superoutburst during the brightening phase, the accretion disk was needed to expand beyond the 3:1 resonance radius of the system again after the main superoutburst. These peculiar phenomena can be explained by the enhanced viscosity and large radius of the disk suggested by the higher luminosity and the presence of late-stage superhumps during the post-superoutburst stage, plus by more mass supply from the cool mass reservoir and/or from the secondary because of the enhanced mass transfer than those of other WZ Sge-type dwarf novae.Comment: 13 pages, 10 figures, accepted for publication in PAS

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD