Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal ...maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.
Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) ...generally have decreased dose‐adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
A process‐based treatment of ice supersaturation and ice nucleation is implemented in the National Center for Atmospheric Research Community Atmosphere Model (CAM). The new scheme is designed to ...allow (1) supersaturation with respect to ice, (2) ice nucleation by aerosol particles, and (3) ice cloud cover consistent with ice microphysics. The scheme is implemented with a two‐moment microphysics code and is used to evaluate ice cloud nucleation mechanisms and supersaturation in CAM. The new model is able to reproduce field observations of ice mass and mixed phase cloud occurrence better than previous versions. The model is able to reproduce observed patterns and frequency of ice supersaturation. Simulations indicate homogeneous freezing of sulfate and heterogeneous freezing on dust are both important ice nucleation mechanisms, in different regions. Simulated cloud forcing and climate is sensitive to different formulations of the ice microphysics. Arctic surface radiative fluxes are sensitive to the parameterization of ice clouds. These results indicate that ice clouds are potentially an important part of understanding cloud forcing and potential cloud feedbacks, particularly in the Arctic.
We present high-resolution near-infrared spectropolarimetric observations using the SPIRou instrument at Canada-France-Hawaii Telescope (CFHT) during a transit of the recently detected young planet ...AU Mic b, with supporting spectroscopic data from iSHELL at NASA InfraRed Telescope Facility. We detect Zeeman signatures in the Stokes
V
profiles and measure a mean longitudinal magnetic field of ¯
B
ℓ
= 46.3 ± 0.7 G. Rotationally modulated magnetic spots likely cause long-term variations of the field with a slope of d
B
ℓ
/d
t
= −108.7 ± 7.7 G d
−1
. We apply the cross-correlation technique to measure line profiles and obtain radial velocities through CCF template matching. We find an empirical linear relationship between radial velocity and
B
ℓ
, which allows us to estimate the radial-velocity induced by stellar activity through rotational modulation of spots for the five hours of continuous monitoring of AU Mic with SPIRou. We model the corrected radial velocities for the classical Rossiter-McLaughlin effect, using MCMC to sample the posterior distribution of the model parameters. This analysis shows that the orbit of AU Mic b is prograde and aligned with the stellar rotation axis with a sky-projected spin-orbit obliquity of
λ
= 0°
−15°
+18°
. The aligned orbit of AU Mic b indicates that it formed in the protoplanetary disk that evolved into the current debris disk around AU Mic.
One of the prevailing hypotheses suggests schizophrenia as a neurodevelopmental disorder, involving dysfunction of dopaminergic and glutamatergic systems. Accumulating evidence suggests mitochondria ...as an additional pathological factor in schizophrenia. An attractive model to study processes related to neurodevelopment in schizophrenia is reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and differentiating them into different neuronal lineages. iPSCs from three schizophrenia patients and from two controls were reprogrammed from hair follicle keratinocytes, because of their accessibility and common ectodermal origin with neurons. iPSCs were differentiated into Pax6(+)/Nestin(+) neural precursors and then further differentiated into β3-Tubulin(+)/tyrosine hydroxylase(+)/DAT(+) dopaminergic neurons. In addition, iPSCs were differentiated through embryonic bodies into β3-Tubulin(+)/Tbox brain1(+) glutamatergic neurons. Schizophrenia-derived dopaminergic cells showed severely impaired ability to differentiate, whereas glutamatergic cells were unable to maturate. Mitochondrial respiration and its sensitivity to dopamine-induced inhibition were impaired in schizophrenia-derived keratinocytes and iPSCs. Moreover, we observed dissipation of mitochondrial membrane potential (Δψm) and perturbations in mitochondrial network structure and connectivity in dopaminergic along the differentiation process and in glutamatergic cells. Our data unravel perturbations in neural differentiation and mitochondrial function, which may be interconnected, and of relevance to dysfunctional neurodevelopmental processes in schizophrenia.
In a systematic study of the Au‐catalyzed reaction of o‐alkynylphenols with aryldiazonium salts, we find that essentially the same reaction conditions lead to a change in mechanism when a light ...source is applied. If the reaction is carried out at room temperature using a AuI catalyst, the diazonium salt undergoes electrophilic deauration of a vinyl AuI intermediate and provides access to substituted azobenzofurans. If the reaction mixture is irradiated with blue LED light, C−C bond formation due to N2‐extrusion from the diazonium salt is realized selectively, using the same starting materials without the need for an additional photo(redox) catalyst under aerobic conditions. We report a series of experiments demonstrating that the same vinyl AuI intermediate is capable of producing the observed products under photolytic and thermal conditions. The finding that a vinyl AuI complex can directly, without the need for an additional photo(redox) catalyst, result in C−C bond formation under photolytic conditions is contrary to the proposed mechanistic pathways suggested in the literature till date and highlights that the role of oxidation state changes in photoredox catalysis involving Au is thus far only poorly understood and may hold surprises for the future. Computational results indicate that photochemical activation can occur directly from a donor–acceptor complex formed between the vinyl AuI intermediate and the diazonium salt.
The Au‐catalyzed reaction of o‐alkynylphenols with aryldiazonium salts undergoes a change in mechanism when a light source is applied. If the reaction is carried out at room temperature using a AuI catalyst, the diazonium salt undergoes electrophilic deauration of a vinyl AuI intermediate generating substituted azobenzofurans. If the reaction mixture is irradiated with blue LED light, C−C bond formation due to N2‐extrusion from the diazonium salt is observed.
Abstract
Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their ...associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~ 3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.
ABSTRACT In this paper, we carry out simulations of radial velocity (RV) measurements of the mass of the 8–11 Myr Neptune-sized planet K2-33b using high-precision near-infrared velocimeters like ...SPIRou at the Canada–France–Hawaii Telescope. We generate an RV curve containing a planet signature and a realistic stellar activity signal, computed for a central wavelength of 1.8 µm and statistically compatible with the light curve obtained with K2. The modelled activity signal includes the effect of time-evolving dark and bright surface features hosting a 2 kG radial magnetic field, resulting in an RV signal of semi-amplitude ∼30 m s−1. Assuming a 3-month visibility window, we build RV time series including Gaussian white noise from which we retrieve the planet mass while filtering the stellar activity signal using Gaussian process regression. We find that 35/50 visits spread over three consecutive bright-time runs on K2-33 allow one to reliably detect planet RV signatures of, respectively, 10 and 5 m s−1 at precisions >3σ. We also show that 30 visits may end up being insufficient in some cases to provide a good coverage of the stellar rotation cycle, with the result that the planet signature can go undetected or the mass estimation be plagued by large errors.
ABSTRACT
Observations of the eclipsing binary system V471 Tau show that the time of the primary eclipses varies in an apparent periodic way. With growing evidence that the magnetically active K2 ...dwarf component might be responsible for driving the eclipse timing variations (ETVs), it is necessary to monitor the star throughout the predicted ∼35 yr activity cycle that putatively fuels the observed ETVs. We contribute to this goal with this paper by analysing spectropolarimetric data obtained with ESPaDOnS at the Canada–France–Hawaii Telescope in 2014 December and 2015 January. Using Zeeman–Doppler Imaging, we reconstruct the distribution of brightness inhomogeneities and large-scale magnetic field at the surface of the K2 dwarf. Compared to previous tomographic reconstructions of the star carried out with the same code, we probe a new phase of the ETVs cycle, offering new constraints for future works exploring whether a magnetic mechanism operating in the K2 dwarf star is indeed able to induce the observed ETVs of V471 Tau.
A variety of energy sources, ranging from dynamic processes, such as magnetic reconnection and waves, to quasi steady terms, such as plasma pressure, may contribute to the acceleration of the solar ...wind. We utilize a
combination of charged particle and magnetic field observations from the Parker Solar Probe (PSP) to attempt to quantify the steady-state contribution of the proton pressure, the electric potential, and the wave energy to the solar wind proton acceleration observed by PSP between 13.3 and ∼100 solar radii (R☉). The proton pressure provides a natural kinematic driver of the outflow. The ambipolar electric potential acts to couple the electron pressure to the protons, providing another definite proton acceleration term. Fluctuations and waves, while inherently dynamic, can act as an additional effective steady-state pressure term. To analyze the contributions of these terms, we utilize radial binning of single-point PSP measurements, as well as repeated crossings of the same stream at different distances on individual PSP orbits (i.e., fast radial scans). In agreement with previous work, we find that the electric potential contains sufficient energy to fully explain the acceleration of the slower wind streams. On the other hand, we find that the wave pressure plays an increasingly important role in the faster wind streams. The combination of these terms can explain the continuing acceleration of both slow and fast wind streams beyond 13.3 R☉.
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