The 'Spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families

Recent studies have characterised a family of giant cytoskeletal crosslinkers encoded by the short stop gene in Drosophila and the dystonin/BPAG1 and MACF1 genes in mammals. We refer to the products of these genes as spectraplakins to highlight the fact that they share features with both the spectrin and plakin superfamilies. These genes produce a variety of large proteins, up to almost 9000 residues long, which can potentially extend 0.4 µm across a cell. Spectraplakins can interact with all three elements of the cytoskeleton: actin, microtubules and intermediate filaments. The analysis of mutant phenotypes in BPAG1 in mouse and short stop in Drosophila demonstrates that spectraplakins have diverse roles. These include linking the plasma membrane and the cytoskeleton, linking together different elements of the cytoskeleton and organising membrane domains.Katja Röper, Stephen L. Gregory and Nicholas H. Brow

β2 Integrin CD11d/CD18: From Expression to an Emerging Role in Staged Leukocyte Migration

CD11d/CD18 is the most recently discovered and least understood β2 integrin. Known CD11d adhesive mechanisms contribute to both extravasation and mesenchymal migration – two key aspects for localizing peripheral leukocytes to sites of inflammation. Differential expression of CD11d induces differences in monocyte/macrophage mesenchymal migration including impacts on macrophage sub-set migration. The participation of CD11d/CD18 in leukocyte localization during atherosclerosis and following neurotrauma has sparked interest in the development of CD11d-targeted therapeutic agents. Whereas the adhesive properties of CD11d have undergone investigation, the signalling pathways induced by ligand binding remain largely undefined. Underlining each adhesive and signalling function, CD11d is under unique transcriptional control and expressed on a sub-set of predominately tissue-differentiated innate leukocytes. The following review is the first to capture the nearly three decades of CD11d research and discusses the emerging role of CD11d in leukocyte migration and retention during the progression of a staged immune response

Herschel/PACS View Of Disks Around Low-Mass Stars And Brown Dwarfs In The TW Hydrae Association

We conducted Herschel/PACS observations of five very low-mass stars or brown dwarfs located in the TW Hya association with the goal of characterizing the properties of disks in the low stellar mass regime. We detected all five targets at 70 mu m and 100 mu m and three targets at 160 mu m. Our observations, combined with previous photometry from 2MASS, WISE, and SCUBA-2, enabled us to construct spectral energy distributions (SEDs) with extended wavelength coverage. Using sophisticated radiative transfer models, we analyzed the observed SEDs of the five detected objects with a hybrid fitting strategy that combines the model grids and the simulated annealing algorithm and evaluated the constraints on the disk properties via the Bayesian inference method. The modeling suggests that disks around low-mass stars and brown dwarfs are generally flatter than their higher mass counterparts, but the range of disk mass extends to well below the value found in T Tauri stars, and the disk scale heights are comparable in both groups. The inferred disk properties (i.e., disk mass, flaring, and scale height) in the low stellar mass regime are consistent with previous findings from large samples of brown dwarfs and very low-mass stars. We discuss the dependence of disk properties on their host stellar parameters and find a significant correlation between the Herschel far-IR fluxes and the stellar effective temperatures, probably indicating that the scaling between the stellar and disk masses (i.e., M-disk proportional to M-star) observed mainly in low-mass stars may extend down to the brown dwarf regime.Natural Science Foundation of Jiangsu Province of China BK20141046Youth Qianren Program of the National Science Foundation of ChinaNational Aeronautics and Space AdministrationStrategic Priority Research Program >The Emergence of Cosmological Structures> of the Chinese Academy of Sciences XDB09000000Astronom

Neural population partitioning and a concurrent brain-machine interface for sequential motor function

Although brain-machine interfaces (BMIs) have focused largely on performing single-targeted movements, many natural tasks involve planning a complete sequence of such movements before execution. For these tasks, a BMI that can concurrently decode the full planned sequence before its execution may also consider the higher-level goal of the task to reformulate and perform it more effectively. Using population-wide modeling, we discovered two distinct subpopulations of neurons in the rhesus monkey premotor cortex that allow two planned targets of a sequential movement to be simultaneously held in working memory without degradation. Such marked stability occurred because each subpopulation encoded either only currently held or only newly added target information irrespective of the exact sequence. On the basis of these findings, we developed a BMI that concurrently decodes a full motor sequence in advance of movement and can then accurately execute it as desired.National Institutes of Health (U.S.) (DP1 OD003646

Langevin Simulation of Thermally Activated Magnetization Reversal in Nanoscale Pillars

Numerical solutions of the Landau-Lifshitz-Gilbert micromagnetic model incorporating thermal fluctuations and dipole-dipole interactions (calculated by the Fast Multipole Method) are presented for systems composed of nanoscale iron pillars of dimension 9 nm x 9 nm x 150 nm. Hysteresis loops generated under sinusoidally varying fields are obtained, while the coercive field is estimated to be 1979 $\pm$ 14 Oe using linear field sweeps at T=0 K. Thermal effects are essential to the relaxation of magnetization trapped in a metastable orientation, such as happens after a rapid reversal of an external magnetic field less than the coercive value. The distribution of switching times is compared to a simple analytic theory that describes reversal with nucleation at the ends of the nanomagnets. Results are also presented for arrays of nanomagnets oriented perpendicular to a flat substrate. Even at a separation of 300 nm, where the field from neighboring pillars is only $\sim$ 1 Oe, the interactions have a significant effect on the switching of the magnets.Comment: 19 pages RevTeX, including 12 figures, clarified discussion of numerical technique

Neural population partitioning and a concurrent brain-machine interface for sequential motor function

While brain-machine interfaces (BMIs) have largely focused on performing single-targeted movements, many natural tasks involve planning a complete sequence of such movements before execution. For these tasks, a BMI that can concurrently decode the full planned sequence prior to its execution may also consider the higher-level goal of the task to reformulate and perform it more effectively. Here, we show that concurrent BMI decoding is possible. Using population-wide modeling, we discover two distinct subpopulations of neurons in the rhesus monkey premotor cortex that allow two planned targets of a sequential movement to be simultaneously held in working memory without degradation. Such surprising stability occurred because each subpopulation encoded either only currently held or only newly added target information irrespective of the exact sequence. Based on these findings, we develop a BMI that concurrently decodes a full motor sequence in advance of movement and then can accurately execute it as desired

Choice Bundling Increases Valuation of Delayed Losses More Than Gains in Cigarette Smokers

Choice bundling, in which a single choice produces a series of repeating consequences over time, increases valuation of delayed monetary and non-monetary gains. Interventions derived from this manipulation may be an effective method for mitigating the elevated delay discounting rates observed in cigarette smokers. No prior work, however, has investigated whether the effects of choice bundling generalize to reward losses. In the present study, an online panel of cigarette smokers (N = 302), recruited using survey firms Ipsos and InnovateMR, completed assessments for either monetary gains or losses (randomly assigned). In Step 1, participants completed a delay-discounting task to establish Effective Delay 50 (ED50), or the delay required for an outcome to lose half of its value. In Step 2, participants completed three conditions of an adjusting-amount task, choosing between a smaller, sooner (SS) adjusting amount and a larger, later (LL) fixed amount. The bundle size (i.e., number of consequences) was manipulated across conditions, where a single choice produced either 1 (control), 3, or 9 consequences over time (ascending/descending order counterbalanced). The delay to the first LL amount in each condition, as well as the intervals between all additional SS and LL amounts (where applicable), were set to individual participants’ ED50 values from Step 1 to control for differences in discounting of gains and losses. Results from Step 1 showed significantly higher ED50 values (i.e., less discounting) for losses compared to gains (p \u3c 0.001). Results from Step 2 showed that choice bundling significantly increased valuation of both LL gains and losses (p \u3c 0.001), although effects were significantly greater for losses (p \u3c 0.01). Sensitivity analyses replicated these conclusions. Future research should examine the potential clinical utility of choice bundling, such as development of motivational interventions that emphasize both the bundled health gains associated with smoking cessation and the health losses associated with continued smoking

Noradrenergic α1 Receptor Antagonist Treatment Attenuates Positive Subjective Effects of Cocaine in Humans: A Randomized Trial

Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α(1) receptor antagonist doxazosin on the positive subjective effects of cocaine.Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind.Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p<.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p<.05). There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p<.10).Medications that block noradrenergic α₁ receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further.Clinicaltrials.gov NCT01062945