Measuring forces between protein fibers by microscopy

We propose a general scheme for measuring the attraction between mechanically frustrated semiflexible fibers by measuring their thermal fluctuations and shape. We apply this analysis to a system of sickle hemoglobin (HbS) fibers that laterally attract one another. These fibers appear to “zip” together before reaching mechanical equilibrium due to the existence of cross-links into a dilute fiber network. We are also able to estimate the rigidities of the fibers. These rigidities are found to be consistent with sickle hemoglobin “single” fibers 20 nm in diameter, despite recent experiments indicating that fiber bundling sometimes occurs. Our estimate of the magnitude of the interfiber attraction for HbS fibers is in the range 8 ± 7 kBT/μm, or 4 ± 3 kBT/μm if the fibers are assumed, a priori to be single fibers (such an assumption is fully consistent with the data). This value is sufficient to bind the fibers, overcoming entropic effects, although extremely chemically weak. Our results are compared to models for the interfiber attraction that include depletion and van der Waals forces. This technique should also facilitate a similar analysis of other filamentous protein assembles in the future, including β-amyloid, actin, and tubulin

Plasma 2020 - Intracluster Medium Plasmas

Galaxy clusters are the largest and most massive bound objects resulting from cosmic hierarchical structure formation. Baryons account for somewhat more than 10% of that mass, with roughly 90% of the baryonic matter distributed throughout the clusters as hot ($T>1$ keV), high-$\beta$, very weakly collisional plasma; the so-called "intracluster medium" (ICM). Cluster mergers, close gravitational encounters and accretion, along with violent feedback from galaxies and relativistic jets from active galactic nuclei, drive winds, gravity waves, turbulence and shocks within the ICM. Those dynamics, in turn, generate cluster-scale magnetic fields and accelerate and mediate the transport of high-energy charged particles. Kinetic-scale, collective plasma processes define the basic character and fundamental signatures of these ICM phenomena, which are observed primarily by X-ray and radio astronomers.Comment: 5 pages, 2 figures, submitted for the 2020 Decadal Assessment of Plasma Scienc

Asynchronous Amazon forest canopy phenology indicates adaptation to both water and light availability

Amazon forests represent nearly half of all tropical vegetation biomass and, through photosynthesis and respiration, annually process more than twice the amount of estimated carbon (CO2) from fossil fuel emissions. Yet the seasonality of Amazon canopy cover, and the extent to which seasonal fluctuations in water availability and photosynthetically available radiation influence these processes, is still poorly understood. Implementing six remotely sensed data sets spanning nine years (2003–2011), with reported field and flux tower data, we show that southern equatorial Amazon forests exhibit a distinctive seasonal signal. Seasonal timing of water availability, canopy biomass growth and net leaf flush are asynchronous in regions with short dry seasons and become more synchronous across a west-to-east longitudinal moisture gradient of increasing dry season. Forest cover is responsive to seasonal disparities in both water and solar radiation availability, temporally adjusting net leaf flush to maximize use of these generally abundant resources, while reducing drought susceptibility. An accurate characterization of this asynchronous behavior allows for improved understanding of canopy phenology across contiguous tropical forests and their sensitivity to climate variability and drought

Accuracy of methods for detecting an irregular pulse and suspected atrial fibrillation: a systematic review and meta-analysis

Background: Pulse palpation has been recommended as the first step of screening to detect atrial fibrillation. We aimed to determine and compare the accuracy of different methods for detecting pulse irregularities caused by atrial fibrillation. Methods: We systematically searched MEDLINE, EMBASE, CINAHL and LILACS until 16 March 2015. Two reviewers identified eligible studies, extracted data and appraised quality using the QUADAS-2 instrument. Meta-analysis, using the bivariate hierarchical random effects method, determined average operating points for sensitivities, specificities, positive and negative likelihood ratios (PLR, NLR); we constructed summary receiver operating characteristic plots. Results: Twenty-one studies investigated 39 interventions (n = 15,129 pulse assessments) for detecting atrial fibrillation. Compared to 12-lead electrocardiography (ECG) diagnosed atrial fibrillation, blood pressure monitors (BPMs; seven interventions) and non-12-lead ECGs (20 interventions) had the greatest accuracy for detecting pulse irregularities attributable to atrial fibrillation (BPM: sensitivity 0.98 (95% confidence interval (CI) 0.92–1.00), specificity 0.92 (95% CI 0.88–0.95), PLR 12.1 (95% CI 8.2–17.8) and NLR 0.02 (95% CI 0.00–0.09); non-12-lead ECG: sensitivity 0.91 (95% CI 0.86–0.94), specificity 0.95 (95% CI 0.92–0.97), PLR 20.1 (95% CI 12–33.7), NLR 0.09 (95% CI 0.06–0.14)). There were similar findings for smartphone applications (six interventions) although these studies were small in size. The sensitivity and specificity of pulse palpation (six interventions) were 0.92 (95% CI 0.85–0.96) and 0.82 (95% CI 0.76–0.88), respectively (PLR 5.2 (95% CI 3.8–7.2), NLR 0.1 (95% CI 0.05–0.18)). Conclusions: BPMs and non-12-lead ECG were most accurate for detecting pulse irregularities caused by atrial fibrillation; other technologies may therefore be pragmatic alternatives to pulse palpation for the first step of atrial fibrillation screening

Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Severity of Visual Field Loss at First Presentation to Glaucoma Clinics in England and Tanzania

Purpose: To compare severity of visual field (VF) loss at first presentation in glaucoma clinics in England and Tanzania. Methods: Large archives of VF records from automated perimetry were used to retrospectively examine vision loss at first presentation in glaucoma clinics in Tanzania (N = 1,502) and England (N = 9,264). Mean deviation (MD) of the worse eye at the first hospital visit was used as an estimate of detectable VF loss severity. Results: In Tanzania, 44.7% {CI95%: 42.2, 47.2} of patients presented with severe VF loss (< −20 dB), versus 4.6% {4.1, 5.0} in England. If we consider late presentation to also include cases of advanced loss (-12.01 dB to -20 dB), then the proportion of patients presenting late was 58.1% {55.6, 60.6} and 14.0% {13.3, 14.7}, respectively. The proportion of late presentations was greater in Tanzania at all ages, but the difference was particularly pronounced among working-age adults, with 50.3% {46.9, 53.7} of 18–65-year-olds presenting with advanced or severe VF loss, versus 10.2% {9.3, 11.3} in England. In both countries, men were more likely to present late than women. Conclusions: Late presentation of glaucoma is a problem in England, and an even greater challenge in Tanzania. Possible solutions are discussed, including increased community eye-care, and a more proactive approach to case finding through the use of disruptive new technologies, such as low-cost, portable diagnostic aids