The geology and evolution of the Near-Earth binary asteroid system (65803) Didymos.

Images collected during NASA's Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters.

A simple 230 MHz photodetector based on exfoliated WSe multilayers.

We demonstrate 230 MHz photodetection and a switching energy of merely 27 fJ using WSe multilayers and a very simple device architecture. This improvement over previous, slower WSe devices is enabled by systematically reducing the RC constant of devices through decreasing the photoresistance and capacitance. In contrast to MoS, reducing the WSe thickness toward a monolayer only weakly decreases the response time, highlighting that ultrafast photodetection is also possible with atomically thin WSe.

Dual polarization-enabled ultrafast bulk photovoltaic response in van der Waals heterostructures.

The bulk photovoltaic effect (BPVE) originating from spontaneous charge polarizations can reach high conversion efficiency exceeding the Shockley-Queisser limit. Emerging van der Waals (vdW) heterostructures provide the ideal platform for BPVE due to interfacial interactions naturally breaking the crystal symmetries of the individual constituents and thus inducing charge polarizations. Here, we show an approach to obtain ultrafast BPVE by taking advantage of dual interfacial polarizations in vdW heterostructures.

Recent collisional history of (65803) Didymos.

The Double Asteroid Redirection Test (DART, NASA) spacecraft revealed that the primary of the (65803) Didymos near-Earth asteroid (NEA) binary system is not exactly the expected spinning top shape observed for other km-size asteroids. Ground based radar observations predicted that such shape was compatible with the uncertainty along the direction of the asteroid spin axis. Indeed, Didymos shows crater and landslide features, and evidence for boulder motion at low equatorial latitudes.

C9-Functionalized Doxycycline Analogs as Drug Candidates to Prevent Pathological α-Synuclein Aggregation and Neuroinflammation in Parkinson's Disease Degeneration.

Doxycycline, a semi-synthetic tetracycline, is a widely used antibiotic for treating mild-to-moderate infections, including skin problems. However, its anti-inflammatory and antioxidant properties, combined with its ability to interfere with α-synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long-term treatment of Parkinsonian patients.

Parkinson's disease-derived α-synuclein assemblies combined with chronic-type inflammatory cues promote a neurotoxic microglial phenotype.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications.

The two synthetic cannabinoid compounds 4'-F-CBD and HU-910 efficiently restrain inflammatory responses of brain microglia and astrocytes.

To study the anti-inflammatory potential of the two synthetic cannabinoids 4'-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4'-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4'-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively.

The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.

Over the years, evidence has accumulated on a possible contributive role of the cytosolic quinone reductase NQO2 in models of dopamine neuron degeneration induced by parkinsonian toxin, but most of the data have been obtained in vitro. For this reason, we asked the question whether NQO2 is involved in the in vivo toxicity of MPTP, a neurotoxin classically used to model Parkinson disease-induced neurodegeneration. First, we show that NQO2 is expressed in mouse substantia nigra dopaminergic cell bodies and in human dopaminergic SH-SY5Y cells as well.

The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and Worms.

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode as an in vivo model organism.

Rescue of Dopamine Neurons from Iron-Dependent Ferroptosis by Doxycycline and Demeclocycline and Their Non-Antibiotic Derivatives.

Several studies have reported that the tetracycline (TC) class antibiotic doxycycline () is effective against Parkinson's disease (PD) pathomechanisms. The aim of the present work was three-fold: (i) Establish a model system to better characterize neuroprotection by ; (ii) Compare the rescue effect of to that of other TC antibiotics; (iii) Discover novel neuroprotective TCs having reduced antibiotic activity. For that, we used cultures of mouse midbrain dopamine (DA) neurons and experimental conditions that model iron-mediated oxidative damage, a key mechanism in PD pathobiology.

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact.

Ejecta from the DART-produced active asteroid Dimorphos.

Some active asteroids have been proposed to be formed as a result of impact events. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA, in addition to having successfully changed the orbital period of Dimorphos, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation.

Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model.

The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate l-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve LID in l-DOPA-treated C57BL/6 mice presenting either moderate or intermediate lesions of the mesostriatal dopaminergic pathway generated by intrastriatal injections of 6-OHDA. Doxy, when given subcutaneously before l-DOPA at doses of 20 mg kg and 40 mg kg, led to significant LID reduction in mice with moderate and intermediate dopaminergic lesions, respectively.

Constraining surface properties of asteroid (162173) Ryugu from numerical simulations of Hayabusa2 mission impact experiment.

The Hayabusa2 mission impact experiment on asteroid Ryugu created an unexpectedly large crater. The associated regime of low-gravity, low-strength cratering remained largely unexplored so far, because these impact conditions cannot be re-created in laboratory experiments on Earth. Here we show that the target cohesion may be very low and the impact probably occurred in the transitional cratering regime, between strength and gravity.

Effects of a New Natural Catechol--methyl Transferase Inhibitor on Two In Vivo Models of Parkinson's Disease.

A tetrahydroisoquinoline identified in ((1,3)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid, compound ) was synthesized and assessed for its pharmacological profile and effects in two animal models of Parkinson's disease. Compound inhibits catechol--methyltransferase (COMT) with no affinity for the dopaminergic receptors or the dopamine transporter. It restores dopamine-mediated motor behavior when it is co-administered with L-DOPA to worms with 1-methyl-4-phenylpyridinium-damaged dopaminergic neurons.

Annonaceae Consumption Worsens Disease Severity and Cognitive Deficits in Degenerative Parkinsonism.

Background: High consumption of Annona muricata fruit has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands.

Objective: We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism.

Methods: We analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance.

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects.

Inferring interiors and structural history of top-shaped asteroids from external properties of asteroid (101955) Bennu.

Asteroid interiors play a key role in our understanding of asteroid formation and evolution. As no direct interior probing has been done yet, characterisation of asteroids' interiors relies on interpretations of external properties. Here we show, by numerical simulations, that the top-shaped rubble-pile asteroid (101955) Bennu's geophysical response to spinup is highly sensitive to its material strength.