Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism

Multi-leptons with High Transverse Momentum at HERA

Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb-1. The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e+p collision data with a scalar sum of the lepton transverse momenta above 100GeV while 1.94 ± 0.17 events are expected. Such events are not observed in e-p collisions for which 1.19 ± 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions. © SISSA 2009

Events with an Isolated Lepton and Missing Transverse Momentum and Measurement of W Production at HERA

A search for events containing an isolated electron or muon and missing transverse momentum produced in e±p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb-1. The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e+p data, at large hadronic transverse momentum PTX \u3c 25GeV, a total of 23 events are observed compared to a prediction of 14.0 ±1.9. The total single W boson production cross section is measured as 1.06 ± 0.16 (stat.) ± 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 ± 0.19 pb

Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement.

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism

The effects of seasons and weather on sleep patterns measured through longitudinal multimodal sensing

Funding Information: This research is based on work supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), via IARPA Contract No. 2017-17042800007. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of ODNI, Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Previous studies of seasonal effects on sleep have yielded unclear results, likely due to methodological differences and limitations in data size and/or quality. We measured the sleep habits of 216 individuals across the U.S. over four seasons for slightly over a year using objective, continuous, and unobtrusive measures of sleep and local weather. In addition, we controlled for demographics and trait-like constructs previously identified to correlate with sleep behavior. We investigated seasonal and weather effects of sleep duration, bedtime, and wake time. We found several small but statistically significant effects of seasonal and weather effects on sleep patterns. We observe the strongest seasonal effects for wake time and sleep duration, especially during the spring season: wake times are earlier, and sleep duration decreases (compared to the reference season winter). Sleep duration also modestly decreases when day lengths get longer (between the winter and summer solstice). Bedtimes and wake times tend to be slightly later as outdoor temperature increases.Peer reviewe

The effects of seasons and weather on sleep patterns measured through longitudinal multimodal sensing.

Previous studies of seasonal effects on sleep have yielded unclear results, likely due to methodological differences and limitations in data size and/or quality. We measured the sleep habits of 216 individuals across the U.S. over four seasons for slightly over a year using objective, continuous, and unobtrusive measures of sleep and local weather. In addition, we controlled for demographics and trait-like constructs previously identified to correlate with sleep behavior. We investigated seasonal and weather effects of sleep duration, bedtime, and wake time. We found several small but statistically significant effects of seasonal and weather effects on sleep patterns. We observe the strongest seasonal effects for wake time and sleep duration, especially during the spring season: wake times are earlier, and sleep duration decreases (compared to the reference season winter). Sleep duration also modestly decreases when day lengths get longer (between the winter and summer solstice). Bedtimes and wake times tend to be slightly later as outdoor temperature increases

Alignment between Heart Rate Variability from Fitness Trackers and Perceived Stress: Perspectives from a Large-Scale in Situ Longitudinal Study of Information Workers

Funding Information: This paper is based upon work supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (2017-17042800007), the National Science Foundation (SES 2030599 and SES 1928612), and the National Institute of Health (R21NR018972). The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the Office of the Director of National Intelligence, Intelligence Advanced Research Projects Activity, or the US government. The US government is authorized to reproduce and distribute reprints for governmental purposes notwithstanding any copyright annotation therein. Publisher Copyright: ©Gonzalo J Martinez, Ted Grover, Stephen M Mattingly, Gloria Mark, Sidney D’Mello, Talayeh Aledavood, Fatema Akbar, Pablo Robles-Granda, Aaron Striegel.Background: Stress can have adverse effects on health and well-being. Informed by laboratory findings that heart rate variability (HRV) decreases in response to an induced stress response, recent efforts to monitor perceived stress in the wild have focused on HRV measured using wearable devices. However, it is not clear that the well-established association between perceived stress and HRV replicates in naturalistic settings without explicit stress inductions and research-grade sensors. Objective: This study aims to quantify the strength of the associations between HRV and perceived daily stress using wearable devices in real-world settings. Methods: In the main study, 657 participants wore a fitness tracker and completed 14,695 ecological momentary assessments (EMAs) assessing perceived stress, anxiety, positive affect, and negative affect across 8 weeks. In the follow-up study, approximately a year later, 49.8% (327/657) of the same participants wore the same fitness tracker and completed 1373 EMAs assessing perceived stress at the most stressful time of the day over a 1-week period. We used mixed-effects generalized linear models to predict EMA responses from HRV features calculated over varying time windows from 5 minutes to 24 hours. Results: Across all time windows, the models explained an average of 1% (SD 0.5%; marginal R2) of the variance. Models using HRV features computed from an 8 AM to 6 PM time window (namely work hours) outperformed other time windows using HRV features calculated closer to the survey response time but still explained a small amount (2.2%) of the variance. HRV features that were associated with perceived stress were the low frequency to high frequency ratio, very low frequency power, triangular index, and SD of the averages of normal-to-normal intervals. In addition, we found that although HRV was also predictive of other related measures, namely, anxiety, negative affect, and positive affect, it was a significant predictor of stress after controlling for these other constructs. Inthe follow-up study, calculating HRV when participants reported their most stressful time of the day was less predictive and provided a worse fit (R2=0.022) than the work hours time window (R2=0.032). Conclusions: A significant but small relationship between perceived stress and HRV was found. Thus, although HRV is associated with perceived stress in laboratory settings, the strength of that association diminishes in real-life settings. HRV might be more reflective of perceived stress in the presence of specific and isolated stressors and research-grade sensing. Relying on wearable-derived HRV alone might not be sufficient to detect stress in naturalistic settings and should not be considered a proxy for perceived stress but rather a component of a complex phenomenon.Peer reviewe