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In this issue of Neuron, Ibrahim et al. (2021) examine the rules by which top-down connections are made on visual cortical layer 1 interneurons, discovering activity-dependent cooperative interactions with visual input that are specific to neurogliaform cells and anterior cingulate cortex.Axon integrity depends on support by glia facilitating axonal maintenance and energy homeostasis, but the molecular mechanisms are not well understood. In this issue of Neuron, Chamberlain et al. (2021) provide evidence that oligodendrocyte-to-axon transfer of SIRT2 via extracellular vesicles (exosomes) enables deacetylation of mitochondrial proteins, enhancing axonal energy production.In this issue of Neuron, Stern et al. (2021) demonstrate that cell-type-specific ablation of RhoA differentially affects axon regeneration outcomes in spinal cord injury models. Their findings highlight the importance of considering cell-type-specific strategies to promote axon regeneration.Leveraging breadth and depth of the scientific workforce invites creativity, relevance, and differing views that directly tie into innovation and problem solving. The NIH BRAIN Initiative is using a multi-pronged strategy to enhance diversity and inclusion toward promoting the best science.In an interview with Neuron, Claire Wyart discusses how a year of pandemic and lockdowns has provided an opportunity to rediscover and prioritize a scientist's fundamental values-learning, brainstorming, sharing, and mentoring-in a more inclusive and equitable scientific environment.Aaron Gitler discusses inspirations derived from foundational basic science, international collaboration, secret mentors, and trainees. In an interview with Neuron, he shares how a thirst for connection grew into the Neuro Zoom phenomenon and why prioritizing family dinners, dog walking, and video games frees him to pursue his scientific interests.In this Neuron Q&A, Panayiota Poirazi reflects on this past year's lessons and shares her not-so-direct trajectory in pursuit of her passion for neuroscience. Reminding us that science is a team game, she shares actionable steps to improve representation in science.In an interview with Neuron, Yulong Li discusses optical tool development and next steps to interrogate the whole brain. He further shares the importance of interdisciplinarity; how new tools for neural imaging, perturbation, and artificial intelligence are revolutionizing neuroscience; and his inspirations from science fiction and a powerhouse scientific family.Bianca Jones Marlin draws inspiration for her work from people's stories. In an interview with Neuron, she talks about overcoming the challenges of the past year-opening a new lab, caring for a young family, and gaining the strength to speak her truth and create the inclusive community academia strives for.Tim Behrens discusses with Neuron creative ways to facilitate virtual meetings, the multiple ways that the pandemic has affected different people, and his advice for the younger generation of neuroscientists in general and computational scientists in particular.In an interview with Neuron, Yukiko Gotoh shares how limitations imposed by the pandemic have proven inspirational, including how neuroscience may inform the development of tools to improve virtual reality and online communication, and how technology and automation might help neuroscientists by easing laborious tasks and ensuring experimental reproducibility.Sensory neurons are modulated by context. For example, in mouse primary visual cortex (V1), neuronal responses to the preferred orientation are modulated by the presence of superimposed orientations ("plaids"). The effects of this modulation are diverse; some neurons are suppressed, while others have larger responses to a plaid than its components. We investigated whether this diversity could be explained by a unified circuit mechanism. We report that this masking is maintained during suppression of cortical activity, arguing against cortical mechanisms. Instead, the heterogeneity of plaid responses is explained by an interaction between stimulus geometry and orientation tuning. Highly selective neurons are uniformly suppressed by plaids, whereas the effects in weakly selective neurons depend on the spatial configuration of the stimulus, transitioning systematically between suppression and facilitation. Thus, the diverse responses emerge as a consequence of the spatial structure of feedforward inputs, with no need to invoke cortical interactions.The objective of the present study was to investigate the relationship between moderate-to-vigorous physical activity (MVPA) and arterial stiffness in pregnancy. Thirty-nine women participated in this study resulting in 68 measurements in non-pregnant (NP; n=21), first (TM1; n=8), second (TM2; n=20), and third trimesters (TM3; n=19). Compliance, distensibility, elasticity, β-stiffness, and carotid to femoral (central) and carotid to finger (peripheral) pulse wave velocity (PWV) were assessed. MVPA was measured using accelerometry. Multilevel linear regressions adjusted for multiple tests per participant using random effects to generate β coefficients and 95% confidence intervals (CI) were performed. Distensibility, elasticity, β-stiffness, central- and peripheral-PWV did not differ between pregnant and non-pregnant assessments. Carotid artery compliance was higher in TM2 compared to NP. Central PWV (β Coef -0.14, 95% CI -0.27, -0.02) decreased from early to mid-pregnancy and increased in late pregnancy. Meeting the MVPA guidelines was significantly associated with central-PWV (Adj. β Coef -0.34, 95% CI -0.62, -0.06, p=0.016), peripheral-PWV (Adj. β Coef -0.54, 95% CI -0.91, -0.16, p=0.005), and distensibility (Adj. β Coef -0.001, 95% CI -0.002, -0.0001, p=0.018), in pregnancy. These results suggest that MVPA may be associated with improved (i.e. reduced) arterial stiffness in pregnancy. Novelty Bullets • Central PWV, distensibility, compliance, elasticity, and ß-stiffness, but not peripheral PWV, exhibited curvilinear relationships with gestational age • Central and peripheral PWV were lower in pregnant women who met the physical activity guidelines of 150 minutes of moderate-to-vigorous physical activity per week.Rationale The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods In a parallel arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged ≥12 years were randomly assigned (11 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, while the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted forced expiratory volume in 1s (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, and stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results 117 patients (40% of target sample size) were randomized to an intervention (n=60) or control group (n=57). After 6 months, ΔFEV1 was significantly higher in the control group compared to the intervention group (2.70% predicted, 95% CI 0.13 to 5.26; p=0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group. Selleckchem Lomerizine Clinical trial registration available at www.clinicaltrials.gov, ID NCT01744561.Electronic coherence is of utmost importance for the access and control of quantum-mechanical solid-state properties. Using a purely electronic observable, the photocurrent, we measure a lower bound of the electronic coherence time of 22 ± 4 fs in graphene. link2 The photocurrent is ideally suited to measure electronic coherence, as it is a direct result of coherent quantum-path interference, controlled by the delay between two ultrashort two-color laser pulses. The maximum delay for which interference between the population amplitude injected by the first pulse interferes with that generated by the second pulse determines the electronic coherence time. In particular, numerical simulations reveal that the experimental data yields a lower bound on the electronic coherence time, masked by coherent dephasing due to the broadband absorption in graphene. We expect that our results will significantly advance the understanding of coherent quantum control in solid-state systems ranging from excitation with weak fields to strongly driven systems.Activated Cdc42-associated kinase 1 (ACK1/TNK2) is a nonreceptor tyrosine kinase with a unique structure. It not only can act as an activated transmembrane effector of receptor tyrosine kinases (RTKs) to transmit various RTK signals but also can play a corresponding role in epigenetic regulation. A number of studies have shown that ACK1 is a carcinogenic factor. Blockage of ACK1 has been proven to be able to inhibit cancer cell survival, proliferation, migration, and radiation resistance. Thus, ACK1 is a promising potential antitumor target. To date, despite many efforts to develop ACK1 inhibitors, no specific small molecule inhibitors have entered clinical trials. This Perspective provides an overview of the structural features, biological functions, and association with diseases of ACK1 and in vitro and in vivo activities, selectivity, and therapeutic potential of small molecule ACK1 inhibitors with different chemotypes.Portable near-infrared (NIR) light sources are in high demand for applications in spectroscopy, night vision, bioimaging, and many others. Typical phosphor designs feature isolated Cr3+ ion centers, and it is challenging to design broadband NIR phosphors based on Cr3+-Cr3+ pairs. Here, we explore the solid-solution series SrAl11.88-xGaxO190.12Cr3+ (x = 0, 2, 4, 6, 8, 10, and 12) as phosphors featuring Cr3+-Cr3+ pairs and evaluate structure-property relations within the series. We establish the incorporation of Ga within the magentoplumbite-type structure at five distinct crystallographic sites and evaluate the effect of this incorporation on the Cr3+-Cr3+ ion pair proximity. Electron paramagnetic measurements reveal the presence of both isolated Cr3+ and Cr3+-Cr3+ pairs, resulting in NIR luminescence at approximately 650-1050 nm. Unexpectedly, the origin of broadband NIR luminescence with a peak within the range 740-820 nm is related to the Cr3+-Cr3+ ion pair. link3 We demonstrate the application of the SrAl5.88Ga6O190.12Cr3+ phosphor, which possesses an internal quantum efficiency of ∼85%, a radiant flux of ∼95 mW, and zero thermal quenching up to 500 K. This work provides a further understanding of spectral shifts in phosphor solid solutions and in particular the application of the magentoplumbites as promising next-generation NIR phosphor host systems.
Homepage: https://www.selleckchem.com/products/lomerizine-hcl.html
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