Memory improves precision of cell sensing in fluctuating environments

Biological cells are often found to sense their chemical environment near the single-molecule detection limit. Surprisingly, this precision is higher than simple estimates of the fundamental physical limit, hinting towards active sensing strategies. In this work, we analyse the effect of cell memory, e.g. from slow biochemical processes, on the precision of sensing by cell-surface receptors. We derive analytical formulas, which show that memory significantly improves sensing in weakly fluctuating environments. However, surprisingly when memory is adjusted dynamically, the precision is always improved, even in strongly fluctuating environments. In support of this prediction we quantify the directional biases in chemotactic Dictyostelium discoideum cells in a flow chamber with alternating chemical gradients. The strong similarities between cell sensing and control engineering suggest universal problem-solving strategies of living matter

Impact of Stratospheric Ozone Zonal Asymmetries on the Tropospheric Circulation

The depletion and recovery of Antarctic ozone plays a major role in changes of Southern Hemisphere (SH) tropospheric climate. Recent studies indicate that the lack of polar ozone asymmetries in chemistry climate models (CCM) leads to a weaker and warmer Antarctic vortex, and smaller trends in the tropospheric mid-latitude jet and the surface pressure. However, the tropospheric response to ozone asymmetries is not well understood. In this study we report on a series of integrations of the Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) to further examine the effect of zonal asymmetries on the state of the stratosphere and troposphere. Integrations with the full, interactive stratospheric chemistry are compared against identical simulations using the same CCM except that (1) the monthly mean zonal mean stratospheric ozone from first simulation is prescribed and (2) ozone is relaxed to the monthly mean zonal mean ozone on a three day time scale. To analyze the tropospheric response to ozone asymmetries, we examine trends and quantify the differences in temperatures, zonal wind and surface pressure among the integrations

LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells

Melanoma cells steer out of tumours using self-generated lysophosphatidic acid (LPA) gradients. The cells break down LPA, which is present at high levels around the tumours, creating a dynamic gradient that is low in the tumour and high outside. They then also migrate up this gradient, creating a complex and evolving outward chemotactic stimulus. Here we introduce a new assay for self-generated chemotaxis, and show that raising LPA levels causes a delay in migration rather than loss of chemotactic efficiency. Knockdown of the lipid phosphatase LPP3 - but not its homologues LPP1 or LPP2 - diminishes the cell's ability to break down LPA. This is specific for chemotactically active LPAs, such as the 18:1 and 20:4 species. Inhibition of autotaxin-mediated LPA production does not diminish outward chemotaxis, but loss of LPP3-mediated LPA breakdown blocks it. Similarly, in both 2D and 3D invasion assays, knockdown of LPP3 diminishes melanoma cells' ability to invade. Our results demonstrate that LPP3 is the key enzyme in melanoma cells' breakdown of LPA, and confirm the importance of attractant breakdown in LPA-mediated cell steering

AKT and SGK kinases regulate cell migration by altering Scar/WAVE complex activation and Arp2/3 complex recruitment

Cell polarity and cell migration both depend on pseudopodia and lamellipodia formation. These are regulated by coordinated signaling acting through G-protein coupled receptors and kinases such as PKB/AKT and SGK, as well as the actin cytoskeletal machinery. Here we show that both Dictyostelium PKB and SGK kinases (encoded by pkbA and pkgB) are dispensable for chemotaxis towards folate. However, both are involved in the regulation of pseudopod formation and thus cell motility. Cells lacking pkbA and pkgB showed a substantial drop in cell speed. Actin polymerization is perturbed in pkbA- and reduced in pkgB- and pkbA-/pkgB- mutants. The Scar/WAVE complex, key catalyst of pseudopod formation, is recruited normally to the fronts of all mutant cells (pkbA-, pkgB- and pkbA-/pkgB-), but is unexpectedly unable to recruit the Arp2/3 complex in cells lacking SGK. Consequently, loss of SGK causes a near-complete loss of normal actin pseudopodia, though this can be rescued by overexpression of PKB. Hence both PKB and SGK are required for correct assembly of F-actin and recruitment of the Arp2/3 complex by the Scar/WAVE complex during pseudopodia formation

Competition between chemoattractants causes unexpected complexity and can explain negative chemotaxis

Negative chemotaxis, where eukaryotic cells migrate away from repellents, is important throughout biology, for example, in nervous system patterning and resolution of inflammation. However, the mechanisms by which molecules repel migrating cells are unknown. Here, we use predictive modeling and experiments with Dictyostelium cells to show that competition between different ligands that bind to the same receptor leads to effective chemorepulsion. 8-CPT-cAMP, widely described as a simple chemorepellent, is inactive on its own and only repels cells when it acts in combination with the attractant cAMP. If cells degrade either competing ligand, the pattern of migration becomes more complex; cells may be repelled in one part of a gradient but attracted elsewhere, leading to populations moving in different directions in the same assay or converging in an arbitrary place. More counterintuitively still, two chemicals that normally attract cells can become repellent when combined. Computational models of chemotaxis are now accurate enough to predict phenomena that have not been anticipated by experiments. We have used them to identify new mechanisms that drive reverse chemotaxis, which we have confirmed through experiments with real cells. These findings are important whenever multiple ligands compete for the same receptors

The impact of an assistive pole, seat configuration and strength in Paralympic seated throwing

Purpose: To quantify the influence of the assistive pole, seat configuration, and upper-body and trunk strength on seated-throwing performance in athletes with a spinal-cord injury (SCI). Methods: Ten Paralympic athletes competing in wheelchair rugby, basketball, or athletics (seated throws) participated in 2 randomized sessions: seated throwing and strength tests. Participants threw a club from a custom-built throwing chair, with and without a pole. 3D kinematic data were collected (150 Hz) for both conditions using standardized and self-selected seat configurations. Dominant and nondominant grip strength were measured using a dynamometer, and upper-body and trunk strength were measured using isometric contractions against a load cell. Results: Seated throwing with an assistive pole resulted in significantly higher hand speed at release than throwing without a pole (pole = 6.0 ± 1.5 m/s, no pole = 5.3 ± 1.5 m/s; P = .02). There was no significant difference in hand speed at release between standardized and self-selected seating configurations during seated throwing with or without an assistive pole. Grip strength (r = .59–.77), push/pull synergy (r = .81–.84), and trunk-flexion (r = .50–.58) strength measures showed large and significant correlations with hand speed at release during seated throwing with and without an assistive pole. Conclusions: This study has demonstrated the importance of the pole for SCI athletes in seated throwing and defined the relationship between strength and seated-throwing performance, allowing us to better understand the activity of seated throws and provide measures for assessing strength that may be valid for evidence-based classification

Impact of August 2017 British Columbia Pyrocumulonimbus Injection Events on Lower Stratospheric Composition

On August 12-13, 2017 large wildfires in the Cariboo region of British Columbia, Canada sparked a series of pyrocumulonimbus events lifting carbonaceous aerosol and other trace gases to the tropopause region (~10-11 km). Over the subsequent days, this plume of trace gas and aerosol species was observed from numerous NASA satellite instruments to rise to over 22 km due to the strong shortwave heating of the carbonaceous aerosol. We will show observations of CO and H2O from the Microwave Limb Sounder (MLS) instrument on Aura satellite demonstrating the clear rise and spread of the plume which can be coherently tracked for at least 2 months. Enhancements in HCN, CH3CN, and methanol (CH3OH) are also evident in MLS measurements with the former two having low vertical resolution. We have also detected a significantly lower concentration of O3 and HNO3 in the plume compared to the surrounding environment, which is consistent with a dynamical perturbation from the rapid diabatic rise of the heated plume from the tropopause through the lower stratosphere. In the weeks and months that followed this plume spread over much of the Northern Hemisphere and the aerosol was observed to be slowly removed by transport back into the troposphere. We will compare and contrast the Aug. 2017 event with the other large event in the MLS record, the Feb. 2009 Australian "Black Saturday" event, and use the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM) replayed to observed meteorology to understand the effect of the British Columbia event on trace gas species. GEOSCCM helps us to separate the relative roles of dynamics and chemistry on lower stratospheric trace gas composition changes, not only in the rising plume but also the impact of its eventual spread over the Northern Hemisphere during fall and winter of 2017-2018

Classifying motor coordination impairment in Para swimmers with brain injury

© 2018 Sports Medicine Australia Objectives: The International Paralympic Committee has mandated that International Sport Federations develop sport-specific classification systems that are evidence-based. This study examined the predictive and convergent validity of instrumented tapping tasks to classify motor coordination impairments in Para swimming. Design: Cross-sectional. Methods: Thirty non-disabled participants and twenty-one Para swimmers with brain injury completed several instrumented tapping tasks as an assessment of upper and lower limb motor coordination. Para swimmers also completed a maximal freestyle swim to obtain a performance measure. The predictive and convergent validity of instrumented tapping tasks was examined by establishing differences in test measures between participants with and without brain injury and defining the strength of association between test measures and maximal freestyle swim speed in Para swimmers, respectively. Results: Random forest successfully classified 96% of participants with and without brain injury using test measures derived from instrumented tapping tasks. Most test measures had moderate to high correlations (r = 0.54 to 0.72; p < 0.01) with maximal freestyle swim speed and collectively explained up to 72% of the variance in maximal freestyle swim performance in Para swimmers with brain injury. Conclusions: The results of this study evidence the predictive and convergent validity of instrumented tapping tasks to classify motor coordination impairments in Para swimmers with brain injury. These tests can be included in revised Para swimming classification to improve the objectivity and transparency in determining athlete eligibility and sport class for these Para athletes

Fam49/CYRI interacts with Rac1 and locally suppresses protrusions

Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion–retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. It thus behaves like a ‘local inhibitor’ as predicted in widely accepted mathematical models, but not previously identified in cells. CYRI therefore regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity and plasticity of protrusions