1,047 research outputs found

    What Happens on Myspace Stays on Myspace: Authentication and Griffin v. State

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    The conduction pathway of potassium channels is water free under physiological conditions.

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    Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism

    GluR1 links structural and functional plasticity at excitatory synapses

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    Long-term potentiation (LTP), a cellular model of learning and memory, produces both an enhancement of synaptic function and an increase in the size of the associated dendritic spine. Synaptic insertion of AMPA receptors is known to play an important role in mediating the increase in synaptic strength during LTP, whereas the role of AMPA receptor trafficking in structural changes remains unexplored. Here, we examine how the cell maintains the correlation between spine size and synapse strength during LTP. We found that cells exploit an elegant solution by linking both processes to a single molecule: the AMPA-type glutamate receptor subunit 1 (GluR1). Synaptic insertion of GluR1 is required to permit a stable increase in spine size, both in hippocampal slice cultures and in vivo. Synaptic insertion of GluR1 is not sufficient to drive structural plasticity. Although crucial to the expression of LTP, the ion channel function of GluR1 is not required for the LTP-driven spine size enhancement. Remarkably, a recombinant cytosolic C-terminal fragment (C-tail) of GluR1 is driven to the postsynaptic density after an LTP stimulus, and the synaptic incorporation of this isolated GluR1 C-tail is sufficient to permit spine enlargement even when postsynaptic exocytosis of endogenous GluR1 is blocked. We conclude that during plasticity, synaptic insertion of GluR1 has two functions: the established role of increasing synaptic strength via its ligand-gated ion channel, and a novel role through the structurally stabilizing effect of its C terminus that permits an increase in spine size

    Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation

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    The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pH-sensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content

    The Effect of Walking an Unfamiliar Versus Companion Dog on Mood, Exercise Enjoyment, and Heart Rate: A Pilot Field Study

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    Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 3, 2021. Background: Walking unfamiliar dogs, such as therapy dogs, has been shown to improve physiological exercise responses and exercise adherence, but whether walking a companion dog results in superior benefits is currently unknown. The purpose of the current pilot field study was to elucidate preliminary evidence of how walking an unfamiliar or companion dog influences mood, exercise enjoyment, and heart rate during a 1.5-mile walk. Methods: Participants (n=8) walked 1.5-miles at their own pace with an unfamiliar or companion dog while mood, exercise enjoyment, and heart rate were measured. Point of application #1: Walking an unfamiliar dog resulted in improved pre- to post- exercise mood changes compared to walking their own companion dog. Point of application #2: Enjoyment of exercise was higher while walking the unfamiliar dog compared to the companion dog. Point of application #3: Mean exercise heart rate was significantly higher while walking the unfamiliar versus companion dog although time to completion of the 1.5-miles was unaffected

    James B Beard: The Father of Contemporary Turfgrass Science

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    James B Beard (24 Sept 1935 to 8 May 2018) can rightly be considered the “Father” of contemporary turfgrass science. During his career, he was known for setting a standard that provided the foundation for turfgrass science through his thorough approach to research, teaching, mentoring and communications. The books he published outlined a vision for an evolving scientific discipline. He trained and mentored \u3e45 domestic and international doctoral and master students and numerous post-doctoral trainees, who in turn continued to raise the quality of contemporary turfgrass science in the USA and internationally. He led the effort to change the name of Division C- 5 of the Crop Science Society of America (CSSA) from Turfgrass to Turfgrass Science, making C-5 an important and a vital part of the society. His subsequent rigorous education and mentoring of others continued to strengthen the division. He recognized the importance of quality, peer-reviewed science and the need for C-5 to be represented on the Crop Science Journal (CSJ) Editorial Board to expedite this goal. His leadership and encouragement led to the creation of a C-5 Technical Editor position on the CSJ Editorial Board in 2002. Beard provided the vision and worked with other leaders worldwide to develop the International Turfgrass Society (ITS) and the ITS Research Journal. The ITS and its leaders and members have been instrumental in enhancing turfgrass science internationally. Beard’s leadership, along with others in turfgrass academia and industry, resulted in the USGA Turfgrass and Environmental Research Program that provides a competitive grant-fund source for turfgrass research. Beard appreciated and vigorously studied history and contributions to turfgrass science by those who went before us. He leaves behind a legacy in science that deserves recognition and respect. It is our hope that this synopsis of Beard’s career accomplishments will inspire present and future turfgrass scientists to follow in his footsteps

    Lateral orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases

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    Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected sequential effects, including increased willingness to take risks following risky wins, and spatial ‘win-stay/lose-shift’ biases. Recordings from lateral orbitofrontal cortex (lOFC) revealed encoding of reward history and receipt, and optogenetic inhibition of lOFC eliminated rats’ increased preference for risk following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and the lOFC’s role in adaptive behavior promotes learning of more abstract biases (here, biases for the risky option), but not spatial ones

    A robust automated method to analyze rodent motion during fear conditioning

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    A central question in the study of LTP has been to determine what role it plays in memory formation and storage. One valuable form of learning for addressing this issue is associative fear conditioning. In this paradigm an animal learns to associate a tone and shock, such that subsequent presentation of a tone evokes a fear response (freezing behavior). Recent studies indicate that overlapping cellular processes underlie fear conditioning and LTP. The fear response has generally been scored manually which is both labor-intensive and subject to potential artifacts such as inconsistent or biased results. Here we describe a simple automated method that provides unbiased and rapid analysis of animal motion. We show that measured motion, in units termed significant motion pixels (SMPs), is both linear and robust over a wide range of animal speeds and detection thresholds and scores freezing in a quantitatively similar manner to trained human observers. By comparing the frequency distribution of motion during baseline periods and to the response to fox urine (which causes unconditioned fear), we suggest that freezing and non-freezing are distinct behaviors. Finally, we show how this algorithm can be applied to a fear conditioning paradigm yielding information on long and short-term associative memory as well as habituation. This automated analysis of fear conditioning will permit a more rapid and accurate assessment of the role of LTP in memory

    Coastal Ice-Core Record of Recent Northwest Greenland Temperature and Sea-Ice Concentration

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    Coastal ice cores provide an opportunity to investigate regional climate and sea-ice variability in the past to complement hemispheric-scale climate reconstructions from ice-sheet-interior ice cores. Here we describe robust proxies of Baffin Bay temperature and sea-ice concentration from the coastal 2Barrel ice core collected in the Thule region of northwest Greenland. Over the 1990–2010 record, 2Barrel annually averaged methanesulfonic acid (MSA) concentrations are significantly correlated with May–June Baffin Bay sea-ice concentrations and summer temperatures. Higher MSA is observed during warmer years with less sea ice, indicative of enhanced primary productivity in Baffin Bay. Similarly, 2Barrel annually averaged deuterium excess (d-excess) values are significantly correlated with annual Baffin Bay sea-ice concentrations and summer and annual temperatures. Warm (cool) years with anomalously low (high) sea-ice concentration are associated with proportionally more (less) low-d-excess Baffin Bay moisture at the ice-core site. Multilinear regression models incorporating 2Barrel MSA, d-excess and snow accumulation account for 38–51% of the Baffin Bay sea-ice and temperature variance. The annual temperature model is significantly correlated with temperatures throughout most of Greenland and eastern Arctic Canada due to the strong influence of the North Atlantic Oscillation and Atlantic Multidecadal Oscillation

    Uncertainty Analysis in Population-Based Disease Microsimulation Models

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    Objective. Uncertainty analysis (UA) is an important part of simulation model validation. However, literature is imprecise as to how UA should be performed in the context of population-based microsimulation (PMS) models. In this expository paper, we discuss a practical approach to UA for such models. Methods. By adapting common concepts from published UA guidelines, we developed a comprehensive, step-by-step approach to UA in PMS models, including sample size calculation to reduce the computational time. As an illustration, we performed UA for POHEM-OA, a microsimulation model of osteoarthritis (OA) in Canada. Results. The resulting sample size of the simulated population was 500,000 and the number of Monte Carlo (MC) runs was 785 for 12-hour computational time. The estimated 95% uncertainty intervals for the prevalence of OA in Canada in 2021 were 0.09 to 0.18 for men and 0.15 to 0.23 for women. The uncertainty surrounding the sex-specific prevalence of OA increased over time. Conclusion. The proposed approach to UA considers the challenges specific to PMS models, such as selection of parameters and calculation of MC runs and population size to reduce computational burden. Our example of UA shows that the proposed approach is feasible. Estimation of uncertainty intervals should become a standard practice in the reporting of results from PMS models
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