Kinesin-1 captures RNA cargo in its adaptable coils

The prototypic and ubiquitous microtubule motor, kinesin-1, uses a variety of adaptor proteins to facilitate the selective transport of diverse cargo within the cell. These cargo adaptors bind to the motor complex through interactions with the kinesin light or heavy chains (KLCs or KHCs). In this issue of Genes & Development, Dimitrova-Paternoga et al. (pp. 976–991) present the first structural characterization of a KHC–cargo adaptor interface. They describe an antiparallel heterotrimeric coiled-coil complex between the carboxy tail of KHC and Tm1-I/C (aTm1), the atypical tropomyosin that is important for oskar mRNA transport in Drosophila oocytes. This interaction enhances direct binding between KHC and RNA. Their findings demonstrate the structural plasticity of the KHC tail as a platform for protein–protein interactions and reveal how a cargo adaptor protein can modify a motor–RNA interface to promote transport

Ocean acidification in the surface waters of the Pacific-Arctic boundary regions

Author Posting. © The Oceanography Society, 2015. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 28, no. 2 (2015): 122-135, doi:10.5670/oceanog.2015.36.The continental shelves of the Pacific-Arctic Region (PAR) are especially vulnerable to the effects of ocean acidification (OA) because the intrusion of anthropogenic CO2 is not the only process that can reduce pH and carbonate mineral saturation states for aragonite (Ωarag). Enhanced sea ice melt, respiration of organic matter, upwelling, and riverine inputs have been shown to exacerbate CO2 -driven ocean acidification in high-latitude regions. Additionally, the indirect effect of changing sea ice coverage is providing a positive feedback to OA as more open water will allow for greater uptake of atmospheric CO2 . Here, we compare model-based outputs from the Community Earth System Model with a subset of recent ship-based observations, and take an initial look at future model projections of surface water Ωarag in the Bering, Chukchi, and Beaufort Seas. We then use the model outputs to define benchmark years when biological impacts are likely to result from reduced Ωarag. Each of the three continental shelf seas in the PAR will become undersaturated with respect to aragonite at approximately 30-year intervals, indicating that aragonite undersaturations gradually progress upstream along the flow path of the waters as they move north from the Pacific Ocean. However, naturally high variability in Ωarag may indicate higher resilience of the Bering Sea ecosystem to these low-Ωarag conditions than the ecosystems of the Chukchi and the Beaufort Seas. Based on our initial results, we have determined that the annual mean for Ωarag will pass below the current range of natural variability in 2025 for the Beaufort Sea and 2027 for the Chukchi Sea. Because of the higher range of natural variability, the annual mean for Ωarag for the Bering Sea does not pass out of the natural variability range until 2044. As Ωarag in these shelf seas slips below the present-day range of large seasonal variability by mid-century, the diverse ecosystems that support some of the largest commercial and subsistence fisheries in the world may be under tremendous pressure.This project was funded by the National Science Foundation (PLR- 1041102 and AGS-1048827)

Formation and transport of corrosive water in the Pacific Arctic region

This paper is not subject to U.S. copyright. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 152 (2018): 67-81, doi:10.1016/j.dsr2.2018.05.020.Ocean acidification (OA), driven by rising anthropogenic carbon dioxide (CO2), is rapidly advancing in the Pacific Arctic Region (PAR), producing conditions newly corrosive to biologically important carbonate minerals like aragonite. Naturally short linkages across the PAR food web mean that species-specific acidification stress can be rapidly transmitted across multiple trophic levels, resulting in widespread impacts. Therefore, it is critical to understand the formation, transport, and persistence of acidified conditions in the PAR in order to better understand and project potential impacts to this delicately balanced ecosystem. Here, we synthesize data from process studies across the PAR to show the formation of corrosive conditions in colder, denser winter-modified Pacific waters over shallow shelves, resulting from the combination of seasonal terrestrial and marine organic matter respiration with anthropogenic CO2. When these waters are subsequently transported off the shelf, they acidify the Pacific halocline. We estimate that Barrow Canyon outflow delivers ~2.24 Tg C yr-1 to the Arctic Ocean through corrosive winter water transport. This synthesis also allows the combination of spatial data with temporal data to show the persistence of these conditions in halocline waters. For example, one study in this synthesis indicated that 0.5–1.7 Tg C yr-1 may be returned to the atmosphere via air-sea gas exchange of CO2 during upwelling events along the Beaufort Sea shelf that bring Pacific halocline waters to the ocean surface. The loss of CO2 during these events is more than sufficient to eliminate corrosive conditions in the upwelled Pacific halocline waters. However, corresponding moored and discrete data records indicate that potentially corrosive Pacific waters are present in the Beaufort shelfbreak jet during 80% of the year, indicating that the persistence of acidified waters in the Pacific halocline far outweighs any seasonal mitigation from upwelling. Across the datasets in this large-scale synthesis, we estimate that the persistent corrosivity of the Pacific halocline is a recent phenomenon that appeared between 1975 and 1985. Over that short time, these potentially corrosive waters originating over the continental shelves have been observed as far as the entrances to Amundsen Gulf and M’Clure Strait in the Canadian Arctic Archipelago. The formation and transport of corrosive waters on the Pacific Arctic shelves may have widespread impact on the Arctic biogeochemical system and food web reaching all the way to the North Atlantic.National Science Foundation Grant PLR-1303617

Annual sea-air CO2fluxes in the Bering Sea: insights from new autumn and winter observations of a seasonally ice-covered continental shelf

High-resolution data collected from several programs have greatly increased the spatiotemporal resolution of pCO2(sw) data in the Bering Sea, and provided the first autumn and winter observations. Using data from 2008 to 2012, monthly climatologies of sea-air CO2 fluxes for the Bering Sea shelf area from April to December were calculated, and contributions of physical and biological processes to observed monthly sea-air pCO2 gradients (?pCO2) were investigated. Net efflux of CO2 was observed during November, December, and April, despite the impact of sea surface cooling on ?pCO2. Although the Bering Sea was believed to be a moderate to strong atmospheric CO2 sink, we found that autumn and winter CO2 effluxes balanced 65% of spring and summer CO2 uptake. Ice cover reduced sea-air CO2 fluxes in December, April, and May. Our estimate for ice-cover corrected fluxes suggests the mechanical inhibition of CO2 flux by sea-ice cover has only a small impact on the annual scale (<2%). An important data gap still exists for January to March, the period of peak ice cover and the highest expected retardation of the fluxes. By interpolating between December and April using assumptions of the described autumn and winter conditions, we estimate the Bering Sea shelf area is an annual CO2 sink of ?6.8 Tg C yr?1. With changing climate, we expect warming sea surface temperatures, reduced ice cover, and greater wind speeds with enhanced gas exchange to decrease the size of this CO2 sink by augmenting conditions favorable for greater wintertime outgassing

Ice nucleating particles carried from below a phytoplankton bloom to the arctic atmosphere

Author Posting. © American Geophysical Union, 2019. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 46(14), (2019): 8572-8581, doi: 10.1029/2019GL083039.As Arctic temperatures rise at twice the global rate, sea ice is diminishing more quickly than models can predict. Processes that dictate Arctic cloud formation and impacts on the atmospheric energy budget are poorly understood, yet crucial for evaluating the rapidly changing Arctic. In parallel, warmer temperatures afford conditions favorable for productivity of microorganisms that can effectively serve as ice nucleating particles (INPs). Yet the sources of marine biologically derived INPs remain largely unknown due to limited observations. Here we show, for the first time, how biologically derived INPs were likely transported hundreds of kilometers from deep Bering Strait waters and upwelled to the Arctic Ocean surface to become airborne, a process dependent upon a summertime phytoplankton bloom, bacterial respiration, ocean dynamics, and wind‐driven mixing. Given projected enhancement in marine productivity, combined oceanic and atmospheric transport mechanisms may play a crucial role in provision of INPs from blooms to the Arctic atmosphere.We sincerely thank the U.S. Coast Guard and crew of the Healy for assistance with equipment installation and guidance, operation of the underway and CTD systems, and general operation of the vessel during transit and at targeted sampling stations. We would also like to thank Allan Bertram, Meng Si, Victoria Irish, and Benjamin Murray for providing INP data from their previous studies. J. M. C., R. P., P. L., L. T., and E. B. were funded by the National Oceanic and Atmospheric Administration (NOAA)’s Arctic Research Program. J. C. was supported by the NOAA Experiential Research & Training Opportunities (NERTO) program. T. A. and N. C. were supported through the NOAA Earnest F. Hollings Scholarship program. A. P. was funded by the National Science Foundation under Grant PLR‐1303617. Russel C. Schnell and Michael Spall are acknowledged for insightful discussions during data analysis and interpretation. There are no financial conflicts of interest for any author. INP data are available in the supporting information, while remaining DBO‐NCIS data presented in the manuscript are available online (at https://www2.whoi.edu/site/dboncis/).2020-01-1

Molecular mechanism for kinesin-1 direct membrane recognition

The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1\u2013dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1\u2013mediated organelle transport

Differential sensing with arrays of de novo designed peptide assemblies

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings

Modeled Effect of Coastal Biogeochemical Processes, Climate Variability, and Ocean Acidification on Aragonite Saturation State in the Bering Sea

The Bering Sea is highly vulnerable to ocean acidification (OA) due to naturally cold, poorly buffered waters and ocean mixing processes. Harsh weather conditions within this rapidly changing, geographically remote environment have limited the quantity of carbon chemistry data, thereby hampering efforts to understand underlying spatial-temporal variability and detect long-term trends. We add carbonate chemistry to a regional biogeochemical model of the Bering Sea to explore the underlying mechanisms driving carbon dynamics over a decadal hindcast (2003–2012). The results illustrate that coastal processes generate considerable spatial variability in the biogeochemistry and vulnerability of Bering Sea shelf water to OA. Substantial seasonal biological productivity maintains high supersaturation of aragonite on the outer shelf, whereas riverine freshwater runoff loaded with allochthonous carbon decreases aragonite saturation states (ΩArag) to values below 1 on the inner shelf. Over the entire 2003–2012 model hindcast, annual surface ΩArag decreases by 0.025 – 0.04 units/year due to positive trends in the partial pressure of carbon dioxide (pCO2) in surface waters and dissolved inorganic carbon (DIC). Variability in this trend is driven by an increase in fall phytoplankton productivity and shelf carbon uptake, occurring during a transition from a relatively warm (2003–2005) to cold (2010–2012) temperature regime. Our results illustrate how local biogeochemical processes and climate variability can modify projected rates of OA within a coastal shelf system

Fracture Risk in Men With Congestive Heart Failure Risk Reduction With Spironolactone

ObjectivesThe purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF).BackgroundIn rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known.MethodsThe medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of having a fracture associated with spironolactone use were estimated using conditional logistic regression.ResultsWe identified 167 cases with a single-incident fracture and matched these by age and race to 668 control subjects without fractures. After adjustment for covariates, spironolactone use was inversely associated with total fracture (odds ratio: 0.575; 95% confidence interval: 0.346 to 0.955, p = 0.0324).ConclusionsThe use of spironolactone is inversely associated with fractures in men with CHF

Storm-induced upwelling of high pCO2 waters onto the continental shelf of the western Arctic Ocean and implications for carbonate mineral saturation states

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 39 (2012): L07606, doi:10.1029/2012GL051574.The carbon system of the western Arctic Ocean is undergoing a rapid transition as sea ice extent and thickness decline. These processes are dynamically forcing the region, with unknown consequences for CO2 fluxes and carbonate mineral saturation states, particularly in the coastal regions where sensitive ecosystems are already under threat from multiple stressors. In October 2011, persistent wind-driven upwelling occurred in open water along the continental shelf of the Beaufort Sea in the western Arctic Ocean. During this time, cold (32.4) halocline water—supersaturated with respect to atmospheric CO2 (pCO2 > 550 μatm) and undersaturated in aragonite (Ωaragonite < 1.0) was transported onto the Beaufort shelf. A single 10-day event led to the outgassing of 0.18–0.54 Tg-C and caused aragonite undersaturations throughout the water column over the shelf. If we assume a conservative estimate of four such upwelling events each year, then the annual flux to the atmosphere would be 0.72–2.16 Tg-C, which is approximately the total annual sink of CO2 in the Beaufort Sea from primary production. Although a natural process, these upwelling events have likely been exacerbated in recent years by declining sea ice cover and changing atmospheric conditions in the region, and could have significant impacts on regional carbon budgets. As sea ice retreat continues and storms increase in frequency and intensity, further outgassing events and the expansion of waters that are undersaturated in carbonate minerals over the shelf are probable.Funding for this work was provided by the National Science Foundation (ARC1041102 – JTM, OPP0856244-RSP, and ARC1040694- LWJ), the National Oceanic and Atmospheric Administration (CIFAR11021- RHB) and the West Coast & Polar Regions Undersea Research Center (POFP00983 – CLM and JM).2012-10-1