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"Stahl, M."
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Right moves : the conservative think tank in American political culture since 1945
\"... traces the progression of think tanks from the rise of a broad conservative movement and the turn away from New Deal liberalism, their expanding role in advancing a neoconservative foreign policy through U.S. military power from the 1980s onward, and their current prominence as a counterweight to progressive political institutions and thought\"-- Provided by publisher.
Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate
2018
Psychosis is now widely hypothesized to involve neural networks beyond the classical dopaminergic mesolimbic pathway, including serotonin and glutamate systems as well.Psychosis is now widely hypothesized to involve neural networks beyond the classical dopaminergic mesolimbic pathway, including serotonin and glutamate systems as well.
Journal Article
Focal task specific dystonia: a review and update
by
Stahl, Christine M.
,
Frucht, Steven J.
in
Dystonia
,
Dystonic Disorders - diagnosis
,
Dystonic Disorders - etiology
2017
In this review, we summarize recent advances in understanding the etiology, risk factors and pathophysiology of focal task specific dystonia (FTSD), movement disorders characterized by abnormal motor activation during the performance of specific, repetitive actions. We focus on two common FTSD, musician’s dystonia and writer’s cramp. FTSD may pose a threat to the patient’s livelihood, and improved therapeutic treatments are needed.
Journal Article
NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis
2016
Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in
Nlrp3−/−
cells. The activation of caspase-8 during extrinsic apoptosis induced by TNF
α
/cycloheximide (TNF
α
/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1
β
secretion in response to TNF
α
/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNF
α
/CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not
Nlrp3−/−
or
ASC−/−
mice following ureteric unilateral obstruction
in vivo
. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells.
Journal Article
Magnetic Signatures of the Interaction Between Europa and Jupiter's Magnetosphere During the Juno Flyby
2024
Based on a hybrid model of Europa's magnetospheric interaction, we provide context for the magnetic field perturbations observed by the Juno spacecraft during its only close flyby of the moon in September 2022. By systematically varying the incident flow conditions and the density profile of Europa's atmosphere, we demonstrate that the observed, large‐scale signatures of magnetic field draping are consistent with a dawn‐dusk asymmetry in the moon's neutral envelope. During the flyby, such an asymmetry would have enhanced the magnetic perturbations in Europa's anti‐Jovian hemisphere, explaining why the spacecraft already detected strong field line draping while still several moon radii away. Conversely, a reduced neutral density in the sub‐Jovian hemisphere can explain why the perturbations in the flow‐aligned field component remained nearly constant as Juno approached Europa. While a dawn‐dusk asymmetry in Europa's atmosphere has been predicted by theoretical work, our results provide the first in situ hints of its presence. Plain Language Summary Located within Jupiter's magnetosphere, the small Galilean moon Europa is continuously exposed to a flow of magnetized plasma, traveling at a relative velocity of about 100 km/s. The deflection of this plasma around Europa generates perturbations to Jupiter's magnetic field, as observed for the first time in two decades during the flyby of the Juno spacecraft in 2022. The magnitude and extension of these magnetic perturbations are largely determined by the shape of Europa's atmosphere and ionosphere which represent obstacles to the incident magnetospheric plasma. To provide three‐dimensional context for the structure of Europa's magnetic environment at the time of the Juno flyby, we have applied a computer simulation to study the moon's interaction with the plasma flow. Comparison between modeled and observed magnetic fields suggests that, at the time when Juno collected these data, Europa's atmosphere may have been denser in the anti‐Jovian than in the Jupiter‐facing hemisphere. Theoretical predictions suggest such an asymmetry to be present in Europa's neutral envelope, partially generated by centrifugal and Coriolis forces acting on the gas molecules during the moon's rotation around Jupiter. Our study reveals first hints from a spacecraft flyby that such a hemispheric asymmetry may indeed exist in Europa's atmosphere. Key Points By applying a hybrid model (kinetic ions, fluid electrons), we study Europa's interaction with Jupiter's magnetosphere during the Juno flyby A dawn‐dusk asymmetry in Europa's atmosphere can reproduce the large‐scale structure of the draping signatures seen by the Juno magnetometer The spacecraft encountered the center of Europa's southern Alfven wing during ingress and the periphery of the northern wing during egress
Journal Article
Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis
by
Stahl, Alexander M.
,
Anada, Takahisa
,
Fukuda, Junji
in
3-D printers
,
Angiogenesis
,
Biomedical materials
2019
Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.
Journal Article
Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data
by
Laredo, Sarah
,
Morrissette, Debbi Ann
,
Stahl, Stephen M.
in
Antipsychotics
,
Bipolar disorder
,
Mental depression
2020
Cariprazine is one of the newest dopamine-serotonin partial agonists, also known as ‘atypical’ second generation antipsychotics. Originally approved for acute and maintenance treatment of schizophrenia as well as for acute mania and mixed mania/depression, cariprazine has now been approved for bipolar I depression. Additionally, post hoc analyses of bipolar I depressed subjects show that both those with and those without concurrent manic features were improved following treatment with cariprazine. Maintenance studies are in progress in bipolar disorder, as are studies to augment antidepressants in unipolar major depressive episodes insufficiently responsive to treatment. Here, we review specifically the efficacy and safety data of cariprazine in bipolar I disorder and discuss the hypothesized mechanism of action of cariprazine and how it could theoretically be linked to caprazine’s broad therapeutic actions across the mood disorder spectrum.
Journal Article
Development of Electrospun Chitosan-Polyethylene Oxide/Fibrinogen Biocomposite for Potential Wound Healing Applications
by
Yuan, Tony T.
,
Stahl, Jonathan M.
,
Johnson, Monica C.
in
Addition polymerization
,
Biological activity
,
Biomaterials
2018
Normal wound healing is a highly complex process that requires the interplay of various growth factors and cell types. Despite advancements in biomaterials, only a few bioactive wound dressings reach the clinical setting. The purpose of this research was to explore the feasibility of electrospinning a novel nanofibrous chitosan (CS)-fibrinogen (Fb) scaffold capable of sustained release of platelet-derived growth factor (PDGF) for the promotion of fibroblast migration and wound healing. CS-Fb scaffolds were successfully electrospun using a dual-spinneret electrospinner and directly evaluated for their physical, chemical, and biological characteristics. CS-polyethylene/Fb scaffolds exhibited thinner fiber diameters than nanofibers electrospun from the individual components while demonstrating adequate mechanical properties and homogeneous polymer distribution. In addition, the scaffold demonstrated acceptable water transfer rates for wound healing applications. PDGF was successfully incorporated in the scaffold and maintained functional activity throughout the electrospinning process. Furthermore, released PDGF was effective at promoting fibroblast migration equivalent to a single 50 ng/mL dose of PDGF. The current study demonstrates that PDGF-loaded CS-Fb nanofibrous scaffolds possess characteristics that would be highly beneficial as novel bioactive dressings for enhancement of wound healing.
Journal Article