Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme

Heterochromatin is a specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. Despite its globally repressive role, heterochromatin must also be dynamic, allowing for its repair and replication. In budding yeast, heterochromatin formation requires silent information regulators (Sirs) Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating-type loci. Previously, we found that the SWI/SNF chromatin remodeling enzyme can catalyze the ATP-dependent eviction of Sir3p from recombinant nucleosomal arrays, and this activity enhances early steps of recombinational repair in vitro. Here, we show that the ATPase subunit of SWI/SNF, Swi2p/Snf2p, interacts with the heterochromatin structural protein Sir3p. Two interaction surfaces are defined, including an interaction between the ATPase domain of Swi2p and the nucleosome binding, Bromo-Adjacent-Homology domain of Sir3p. A SWI/SNF complex harboring a Swi2p subunit that lacks this Sir3p interaction surface is unable to evict Sir3p from nucleosomes, even though its ATPase and remodeling activities are intact. In addition, we find that the interaction between Swi2p and Sir3p is key for SWI/SNF to promote resistance to replication stress in vivo and for establishment of heterochromatin at telomeres

Groundwater Sensitivity to Climate Variations Across Australia

Groundwater response to climate variations is often pivotal to managing groundwater sustainably. However, this relationship is rarely explicitly examined because of the complexity of surface to subsurface processes and the diverse impacts of multiple drivers, such as groundwater pumping and land use changes. In this paper, we address this challenge by proposing methods to quantify the sensitivity of groundwater level and recharge to temporal climate variability across Australia. Using the HydroSight groundwater hydrograph toolbox we first identify 1,143 out of a total of 4,350 bores as climate-driven, where historically, head was primarily driven by climate variations. Streamflow elasticity measures are then adapted to groundwater to quantify the long-term head and recharge sensitivity. We find that the national median sensitivity of head and recharge to precipitation change are 42 and 0.43 mm mm$^{−1}$, respectively (interquartiles: 20–77 and 0.30–0.55 mm mm$^{−1}$); both of which are ∼8 times that of potential evapotranspiration. Nationally, the results are spatially correlated, suggestive of large-scale effects. The responses of head and recharge appear to be primarily related to climate type and hydrogeology. The more arid the climate, the higher the head sensitivity but the lower the recharge sensitivity. Porous media generally show higher head sensitivity than fractured media due to smaller aquifer specific yield, and again contrarily for that of recharge. These findings contribute to understanding the long-term impact of climate change on groundwater and thus provide valuable insights for sustainable groundwater management

The relationship between ventilatory threshold and repeated-sprint ability in competitive male ice hockey players

Background/objective The relationship between ventilatory threshold (VT1, VT2) and repeated-sprint ability (RSA) in competitive male ice hockey players was investigated. Methods Forty-three male ice hockey players aged 18–23 years competing in NCAA Division I, NCAA Division III, and Junior A level participated. Participants performed an incremental graded exercise test on a skate treadmill to determine V˙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eV˙O2peak, VT1, and VT2 using MedGraphics Breezesuit™ software (v-slope). Participants performed an on-ice repeated shift (RSA) test consisting of 8-maximal skating bouts, lasting approximately 25 s and interspersed with 90 s of passive recovery, to determine first gate, second gate, and total sprint decrement (%dec). Pearson product-moment correlations and multiple regressions were used to assess relationships between ventilatory threshold variables (VT1, VT2, Stage at VT1, and Stage at VT2) and RSA (first gate, second gate, and total course decrement). Results Stage at VT2 was the only variable substantially correlated with first gate (r = −0.35; P \u3c 0.05), second gate (r = −0.58; P \u3c 0.001) and total course decrement (r = −0.42; P \u3c 0.05). Conclusion The results of this study demonstrated that VT is substantially associated with RSA, and VT2 is more strongly correlated with RSA than V˙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eV˙O2peak. This study suggests that longer duration high-intensity interval training at intensities that increase workrate at VT2 may lead to possible improvements in RSA

Short-term emission line and continuum variations in Mrk110

We present results of a variability campaign of Mrk110 performed with the 9.2-m Hobby-Eberly Telescope (HET) at McDonald Observatory. The high S/N spectra cover most of the optical range. They were taken from 1999 November through 2000 May. The average interval between the observations was 7.3 days and the median interval was only 3.0 days. Mrk110 is a narrow-line Seyfert 1 galaxy. During our campaign the continuum flux was in a historically low stage. Considering the delays of the emission lines with respect to the continuum variations we could verify an ionization stratification of the BLR. We derived virial masses of the central black hole from the radial distances of the different emission lines and from their widths. The calculated central masses agree within 20%. Furthermore, we identified optical HeI singlet emission lines emitted in the broad-line region. The observed line fluxes agree with theoretical predictions. We show that a broad wing on the red side of the [OIII]5007 line is caused by the HeI singlet line at 5016A.Comment: 11 pages, 16 figures, A&A Latex. Accepted for publication in A&A Main Journa

Going their own way-male recreational runners and running-related injuries : a qualitative thematic analysis

Objective Recreational running is one of the most common physical leisure activities worldwide and is associated with high rates of running related injury (RRI). Little is known of the perceptions of male recreational runners regarding the aetiology and management of RRI. Design Utilising an interpretive phenomenological analysis framework, qualitative data was gathered from participants via interview, and reflexive thematic analysis was used to develop insights into the experiences and perceptions of the participants in relation to RRI. Materials and methods Two focus groups with a total of six (mean age 37.8 ± 9.5 years, 16.5 ± 13.1 years running experience) male recreational runners were used to obtain data regarding their understanding of RRI causation, prevention and management. Interviews were evaluated using a sixphase reflexive thematic analysis approach to generate and interpret themes within the data. Results Three themes (Mind, Body and Education) were identified by the analysis as critical to RRI avoidance. Mind refers to the self-understanding and self-management of personal limits required for RRI prevention. Body reflects a degree of physical conditioning necessary for injury free running, while Education indicates an understanding of how to correctly structure a running program. When viewed together these themes can be seen to form an 'internal locus of injury' model which highlights the runners' beliefs that RRI are related to their decisions regarding training and running, and that avoidance of injury lies within their personal control. Conclusion Recreational runners rely on self-management, in preference to professional advice, to manage training loads, fitness and RRI. Health care professionals involved with this population may consider the use of online resources, a preferred option of runners, to assist runners to build their knowledge base and support their development to experienced runners

Protected Health Information filter (Philter): accurately and securely de-identifying free-text clinical notes.

There is a great and growing need to ascertain what exactly is the state of a patient, in terms of disease progression, actual care practices, pathology, adverse events, and much more, beyond the paucity of data available in structured medical record data. Ascertaining these harder-to-reach data elements is now critical for the accurate phenotyping of complex traits, detection of adverse outcomes, efficacy of off-label drug use, and longitudinal patient surveillance. Clinical notes often contain the most detailed and relevant digital information about individual patients, the nuances of their diseases, the treatment strategies selected by physicians, and the resulting outcomes. However, notes remain largely unused for research because they contain Protected Health Information (PHI), which is synonymous with individually identifying data. Previous clinical note de-identification approaches have been rigid and still too inaccurate to see any substantial real-world use, primarily because they have been trained with too small medical text corpora. To build a new de-identification tool, we created the largest manually annotated clinical note corpus for PHI and develop a customizable open-source de-identification software called Philter ("Protected Health Information filter"). Here we describe the design and evaluation of Philter, and show how it offers substantial real-world improvements over prior methods

Cutaneous microvascular reactivity in Charcot neuroarthropathy : a systematic review and meta-analysis

Background: To systematically evaluate the literature investigating the relationship between cutaneous microvascular reactivity in the foot of adults with diabetes-related Charcot neuroarthropathy compared to a non-Charcot adult control group. Methods: A systematic search was conducted to June 2021 using the biomedical databases EBSCO Megafile Ultimate, Cochrane Library and EMBASE. Original research conducting comparative investigation of cutaneous microvascular reactivity in the foot of adults with diabetes and any pattern of acute or chronic Charcot neuroarthropathy and any non-Charcot adult control groups were included. A modified Critical Appraisal Skills Programme tool was used for quality appraisal. Cutaneous microvascular reactivity in diabetes-related Charcot neuroarthropathy data were synthesised and meta-analysis conducted where possible. Results: The search strategy identified 1,684 articles, with seven eligible for inclusion. Included studies used various methodologies and equipment to assess cutaneous microvascular reactivity in 553 participants (162 with Charcot neuroarthropathy). Cutaneous microvascular reactivity in Charcot neuroarthropathy groups was impaired compared to uncomplicated diabetes groups. Meta-analysis investigating the difference in response to thermal hyperaemia demonstrated a significant difference in cutaneous microvascular reactivity between Charcot neuroarthropathy and peripheral neuropathy with a large, pooled effect size (SMD 1.46 95% CI: 0.89– 2.02) and low heterogeneity (I 2 = 4%, T 2 = 0.01) indicating that the cutaneous microvascular response is more impaired in peripheral neuropathy than in Charcot neuroarthropathy. Conclusions: Charcot neuroarthropathy is associated with greater cutaneous microvascular reactivity in the periphery relative to diabetes cohorts with diabetes-related peripheral neuropathy alone. It is unknown if this occurs prior to, or as a result of, Charcot neuroarthropathy

Multi-Player Quantum Games

Recently the concept of quantum information has been introduced into game theory. Here we present the first study of quantum games with more than two players. We discover that such games can possess a new form of equilibrium strategy, one which has no analogue either in traditional games or even in two-player quantum games. In these `pure' coherent equilibria, entanglement shared among multiple players enables new kinds of cooperative behavior: indeed it can act as a contract, in the sense that it prevents players from successfully betraying one-another.Comment: 5 pages, 2 figs. Substantial revisons inc. new result

Buoyancy Instabilities in Galaxy Clusters: Convection Due to Adiabatic Cosmic Rays and Anisotropic Thermal Conduction

Using a linear stability analysis and two and three-dimensional nonlinear simulations, we study the physics of buoyancy instabilities in a combined thermal and relativistic (cosmic ray) plasma, motivated by the application to clusters of galaxies. We argue that cosmic ray diffusion is likely to be slow compared to the buoyancy time on large length scales, so that cosmic rays are effectively adiabatic. If the cosmic ray pressure $p_{cr}$ is $\gtrsim 25$ of the thermal pressure, and the cosmic ray entropy ($p_{\rm cr}/\rho^{4/3}$; $\rho$ is the thermal plasma density) decreases outwards, cosmic rays drive an adiabatic convective instability analogous to Schwarzschild convection in stars. Global simulations of galaxy cluster cores show that this instability saturates by reducing the cosmic ray entropy gradient and driving efficient convection and turbulent mixing. At larger radii in cluster cores, the thermal plasma is unstable to the heat flux-driven buoyancy instability (HBI), a convective instability generated by anisotropic thermal conduction and a background conductive heat flux. Cosmic-ray driven convection and the HBI may contribute to redistributing metals produced by Type 1a supernovae in clusters. Our calculations demonstrate that adiabatic simulations of galaxy clusters can artificially suppress the mixing of thermal and relativistic plasma; anisotropic thermal conduction allows more efficient mixing, which may contribute to cosmic rays being distributed throughout the cluster volume.Comment: submitted to ApJ; 15 pages and 12 figures; abstract shortened to < 24 lines; for high resolution movies see http://astro.berkeley.edu/~psharma/clustermovie.htm