Lung mediated auditory contrast enhancement improves the Signal-to-noise ratio for communication in frogs

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Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19

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Identification of a functional proprotein convertase cleavage site in microfibril-associated glycoprotein 2

Microfibril-associated glycoprotein 2 (MAGP2) is a secreted protein associated with multiple cellular activities including the organization of elastic fibers in the extracellular matrix (ECM), angiogenesis, as well as regulating Notch and integrin signaling. Importantly, increases in MAGP2 positively correlate with poor prognosis for some ovarian cancers. It has been assumed that full-length MAGP2 is responsible for all reported effects; however, here we show MAGP2 is a substrate for the proprotein convertase (PC) family of endoproteases. Proteolytic processing of MAGP2 by PC cleavage could serve to regulate secretion and thus, activity and function as reported for other extracellular and cell-surface proteins. In support of this idea, MAGP2 contains an evolutionarily conserved PC consensus cleavage site, and amino acid sequencing of a newly identified MAGP2 C-terminal cleavage product confirmed functional PC cleavage. Additionally, mutagenesis of the MAGP2 PC consensus cleavage site or treatment with PC inhibitors prevented MAGP2 proteolytic processing. Finally, both cleaved and uncleaved MAGP2 were detected extracellularly and MAGP2 secretion appeared independent of PC cleavage, suggesting that PC processing occurs mainly outside the cell. Our characterization of alternative forms of MAGP2 present in the extracellular space not only enhances diversity of this ECM protein but also provides a previously unrecognized molecular mechanism for regulation of MAGP2 biological activity.     

Mental Health Following Acquisition of Disability in Adulthood—The Impact of Wealth

BackgroundAcquisition of a disability in adulthood has been associated with a reduction in mental health. We tested the hypothesis that low wealth prior to disability acquisition is associated with a greater deterioration in mental health than for people with high wealth.MethodsWe assess whether level of wealth prior to disability acquisition modifies this association using 12 waves of data (2001–2012) from the Household, Income and Labour Dynamics in Australia survey–a population-based cohort study of working-age Australians. Eligible participants reported at least two consecutive waves of disability preceded by at least two consecutive waves without disability (1977 participants, 13,518 observations). Fixed-effects linear regression was conducted with a product term between wealth prior to disability (in tertiles) and disability acquisition with the mental health component score of the SF–36 as the outcome.ResultsIn models adjusted for time-varying confounders, there was evidence of negative effect measure modification by prior wealth of the association between disability acquisition and mental health (interaction term for lowest wealth tertile: -2.2 points, 95% CI -3.1 points, -1.2, p<0.001); low wealth was associated with a greater decline in mental health following disability acquisition (-3.3 points, 95% CI -4.0, -2.5) than high wealth (-1.1 points, 95% CI -1.7, -0.5).ConclusionThe findings suggest that low wealth prior to disability acquisition in adulthood results in a greater deterioration in mental health than among those with high wealth.     

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples

The ubiquitin-proteasome system has recently been implicated in various pathologies including neurodegenerative diseases and cancer. In light of this, techniques for studying the regulatory mechanism of this system are essential to elucidating the cellular and molecular processes of the aforementioned diseases. The use of hemagglutinin derived ubiquitin probes outlined in this paper serves as a valuable tool for the study of this system. This paper details a method that enables the user to perform assays that give a direct visualization of deubiquitinating enzyme activity. Deubiquitinating enzymes control proteasomal degradation and share functional homology at their active sites, which allows the user to investigate the activity of multiple enzymes in one assay. Lysates are obtained through gentle mechanical cell disruption and incubated with active site directed probes. Functional enzymes are tagged with the probes while inactive enzymes remain unbound. By running this assay, the user obtains information on both the activity and potential expression of multiple deubiquitinating enzymes in a fast and easy manner. The current method is significantly more efficient than using individual antibodies for the predicted one hundred deubiquitinating enzymes in the human cell.     

Limnological regime shifts caused by climate warming and Lesser Snow Goose population expansion in the western Hudson Bay Lowlands (Manitoba,Canada)

Shallow lakes are dominant features in subarctic and Arctic landscapes and are responsive to multiple stressors, which can lead to rapid changes in limnological regimes with consequences for aquatic resources. We address this theme in the coastal tundra region of Wapusk National Park, western Hudson Bay Lowlands (Canada), where climate has warmed during the past century and the Lesser Snow Goose (LSG; Chen caerulescens caerulescens) population has grown rapidly during the past ~40 years. Integration of limnological and paleolimnological analyses documents profound responses of productivity, nutrient cycling, and aquatic habitat to warming at three ponds (“WAP 12”, “WAP 20”, and “WAP 21″), and to LSG disturbance at the two ponds located in an active nesting area (WAP 20, WAP 21). Based on multiparameter analysis of ²¹⁰Pb‐dated sediment records from all three ponds, a regime shift occurred between 1875 and 1900 CE marked by a transition from low productivity, turbid, and nutrient‐poor conditions of the Little Ice Age to conditions of higher productivity, lower nitrogen availability, and the development of benthic biofilm habitat as a result of climate warming. Beginning in the mid‐1970s, sediment records from WAP 20 and WAP 21 reveal a second regime shift characterized by accelerated productivity and increased nitrogen availability. Coupled with 3 years of limnological data, results suggest that increased productivity at WAP 20 and WAP 21 led to atmospheric CO₂ invasion to meet algal photosynthetic demand. This limnological regime shift is attributed to an increase in the supply of catchment‐derived nutrients from the arrival of LSG and their subsequent disturbance to the landscape. Collectively, findings discriminate the consequences of warming and LSG disturbance on tundra ponds from which we identify a suite of sensitive limnological and paleolimnological measures that can be utilized to inform aquatic ecosystem monitoring.     

Sixty Hertz Neurostimulation Amplifies Subthalamic Neural Synchrony in Parkinson’s Disease

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson’s disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony. Here we demonstrate for the first time that during intra-operative 60 Hz STN DBS, one or more bands of resting state neural synchrony were amplified in the STN in PD. We recorded intra-operative STN resting state local field potentials (LFPs) from twenty-eight STNs in seventeen PD subjects after placement of the DBS lead (model 3389, Medtronic, Inc.) before and during three randomized neurostimulation sets (130 Hz/1.35V, 130 Hz/2V, 60 Hz/2V). During 130 Hz/2V DBS, baseline (no DBS) STN alpha (8 – 12 Hz) and beta (13 – 35 Hz) band power decreased (N=14, P < 0.001 for both), whereas during 60 Hz/2V DBS, alpha band and peak frequency power increased (P = 0.012, P = 0.007, respectively). The effect of 60 Hz/2V DBS opposed that of power-equivalent (130 Hz/1.35V) DBS (alpha: P < 0.001, beta: P = 0.006). These results show that intra-operative 60 Hz STN DBS amplified whereas 130 Hz STN DBS attenuated resting state neural synchrony in PD; the effects were frequency-specific. We demonstrate that neurostimulation may be useful as a tool to selectively modulate resting state resonant bands of neural synchrony and to investigate its influence on motor and non-motor behaviors in PD and other neuropsychiatric diseases.     

Quality Improvement in Surgery Combining Lean Improvement Methods with Teamwork Training: A Controlled Before-After Study

Background

To investigate the effectiveness of combining teamwork training and lean process improvement, two distinct approaches to improving surgical safety. We conducted a controlled interrupted time series study in a specialist UK Orthopaedic hospital incorporating a plastic surgery team (which received the intervention) and an Orthopaedic theatre team acting as a control.

Study Design

We used a 3 month intervention with 3 months data collection period before and after it. A combined teamwork training and lean process improvement intervention was delivered by an experienced specialist team. Before and after the intervention we evaluated team non-technical skills using NOTECHS II, technical performance using the glitch rate and WHO checklist compliance using a simple 3 point scale. We recorded complication rate, readmission rate and length of hospital stay data for 6 months before and after the intervention.

Results

In the active group, but not the control group, full compliance with WHO Time Out (T/O) increased from 14 to 71% (p = 0.032), Sign Out attempt rate (S/O) increased from 0% to 50% (p<0.001) and Oxford NOTECHS II scores increased after the intervention (P = 0.058). Glitch rate decreased in the active group and increased in the control group (p = 0.001). Complications and length of stay appeared to rise in the control group and fall in the active group.

Conclusions

Combining teamwork training and systems improvement enhanced both technical and non-technical operating team process measures, and were associated with a trend to better safety outcome measures in a controlled study comparison. We suggest that approaches which address both system and culture dimensions of safety may prove valuable in reducing risks to patients.