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

Sagittal Subtalar and Talocrural Joint Assessment During Ambulation With Controlled Ankle Movement (CAM) Boots

Background: The purpose of the current study was to determine sagittal plane talocrural and subtalar kinematic differences between barefoot and controlled ankle movement (CAM) boot walking. This study used fluoroscopic images to determine talar motion relative to tibia and calcaneal motion relative to talus. Methods: Fourteen male subjects (mean age 24.1 ± 3.5 years) screened for normal gait were tested. A fluoroscopy unit was used to collect images at 200 Hz during stance. Sagittal motion of the talocrural and subtalar joints were analyzed barefoot and within short and tall CAM boots. Results: Barefoot talocrural mean maximum plantar and dorsiflexion were 9.2 ± 5.4 degrees and −7.5 ± 7.4 degrees, respectively; short CAM boot mean maximum plantar and dorsiflexion were 3.2 ± 4.0 degrees and −4.8 ± 10.2 degrees, respectively; and tall CAM boot mean maximum plantar and dorsiflexion were −0.2 ± 3.5 degrees and −2.4 ± 5.1 degrees, respectively. Talocrural mean range of motion (ROM) decreased from barefoot (16.7 ± 5.1 degrees) to short CAM boot (8.0 ± 4.9 degrees) to tall CAM boot (2.2 ± 2.5 degrees). Subtalar mean maximum plantarflexion angles were 5.3 ± 5.6 degrees for barefoot walking, 4.1 ± 5.9 degrees for short CAM boot walking, and 3.0 ± 4.7 degrees for tall CAM boot walking. Mean minimum subtalar plantarflexion angles were 0.7 ± 3.2 degrees for barefoot walking, 0.7 ± 2.9 degrees for short CAM boot walking, and 0.1 ± 4.8 degrees for tall CAM boot walking. Subtalar mean ROM decreased from barefoot (4.6 ± 3.9 degrees) to short CAM boot (3.4 ± 3.8 degrees) to tall CAM boot (2.9 ± 2.6 degrees). Conclusion: Tall and short CAM boot intervention was shown to limit both talocrural and subtalar motion in the sagittal plane during ambulation. The greatest reductions were seen with the tall CAM boot, which limited talocrural motion by 86.8% and subtalar motion by 37.0% compared to barefoot. Short CAM boot intervention reduced talocrural motion by 52.1% and subtalar motion by 26.1% compared to barefoot. Clinical Relevance: Both short and tall CAM boots reduced talocrural and subtalar motion during gait. The short CAM boot was more convenient to use, whereas the tall CAM boot more effectively reduced motion. In treatments requiring greater immobilization of the talocrural and subtalar joints, the tall CAM boot should be considered

RUNNING TO THE BEAT: DOES LISTENING TO MUSIC AFFECT RUNNING CADENCE AND LOWER EXTREMITY BIOMECHANICS?

This aimed to determine if music with specific target beats per minute (bpm) could be used for treadmill running cadence training to alter lower extremity biomechanics and, thus, reduce injury risk. Motion analysis and a synchronized triaxial accelerometer collected data from eighteen runners during treadmill running. Participants ran at a self-selected speed (SS) to determine their baseline cadence. They also ran to music where the bpm of the songs was increased by 5% and 10% over SS cadence. Post hoc tests showed significant differences in heart rate from SS. There were no significant differences between cadence or peak acceleration. In the current study, music was not shown to be a viable method for cadence training in runners. Our findings led to methodology recommendations for future work in using music to effectively improve running cadence

Using Mock Interviews to Evaluate an Interprofessional Education (IPE) Curriculum

The aim of this study was to evaluate the influence of targeted team care training in our institution’s interprofessional practice and education (IPE) program on medical and pharmacy students\u27 expression of knowledge and attitudes about team care as measured in a mock interview. Medical and Pharmacy students were recruited to participate in a 20-minute mock interview for an advanced placement position

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

Preparing for and managing change: Climate adaptation for biodiversity and ecosystems

The emerging field of climate-change adaptation has experienced a dramatic increase in attention as the impacts of climate change on biodiversity and ecosystems have become more evident. Preparing for and addressing these changes are now prominent themes in conservation and natural resource policy and practice. Adaptation increasingly is viewed as a way of managing change, rather than just maintaining existing conditions. There is also increasing recognition of the need not only to adjust management strategies in light of climate shifts, but to reassess and, as needed, modify underlying conservation goals. Major advances in the development of climate-adaptation principles, strategies, and planning processes have occurred over the past few years, although implementation of adaptation plans continues to lag. With ecosystems expected to undergo continuing climate-mediated changes for years to come, adaptation can best be thought of as an ongoing process, rather than as a fixed endpoint. © The Ecological Society of America

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

Validation of an algorithm using inpatient electronic health records to determine the presence and severity of cirrhosis in patients with hepatocellular carcinoma in England: an observational study.

OBJECTIVES:Outcomes in hepatocellular carcinoma (HCC) are determined by both cancer characteristics and liver disease severity. This study aims to validate the use of inpatient electronic health records to determine liver disease severity from treatment and procedure codes. DESIGN:Retrospective observational study. SETTING:Two National Health Service (NHS) cancer centres in England. PARTICIPANTS:339 patients with a new diagnosis of HCC between 2007 and 2016. MAIN OUTCOME:Using inpatient electronic health records, we have developed an optimised algorithm to identify cirrhosis and determine liver disease severity in a population with HCC. The diagnostic accuracy of the algorithm was optimised using clinical records from one NHS Trust and it was externally validated using anonymised data from another centre. RESULTS:The optimised algorithm has a positive predictive value (PPV) of 99% for identifying cirrhosis in the derivation cohort, with a sensitivity of 86% (95% CI 82% to 90%) and a specificity of 98% (95% CI 96% to 100%). The sensitivity for detecting advanced stage cirrhosis is 80% (95% CI 75% to 87%) and specificity is 98% (95% CI 96% to 100%), with a PPV of 89%. CONCLUSIONS:Our optimised algorithm, based on inpatient electronic health records, reliably identifies and stages cirrhosis in patients with HCC. This highlights the potential of routine health data in population studies to stratify patients with HCC according to liver disease severity