PEPR DIADEM: Priority equipment and research program on the development of innovative materials using artificial intelligence.

The quest to develop efficient, sustainable materials from non-critical, non-toxic resources is one of today's most formidable challenges in the current context of energy, transport, digital or healthcare transitions. In response, France launched the pioneering Priority Equipment and Research Program (PEPR) DIADEM in 2022. This innovative initiative, focused on DIscovery Acceleration for the Deployment of Emerging Materials (DIADEM), leverages Artificial Intelligence (AI) to accelerate the innovation chain from conception to realization, revolutionizing Materials Science sustainably.

Gaseous emissions from brake wear can form secondary particulate matter.

Road traffic is an important source of urban air pollutants. Due to increasingly strict controls of exhaust emissions from road traffic, their contribution to the total emissions has strongly decreased over time in high-income countries. In contrast, non-exhaust emissions from road vehicles are not yet legislated and now make up the major proportion of road traffic emissions in many countries.

Human neutrophils communicate remotely via calcium-dependent glutamate-induced glutamate release.

Neutrophils are white blood cells that are critical to acute inflammatory and adaptive immune responses. Their swarming-pattern behavior is controlled by multiple cellular cascades involving calcium-dependent release of various signaling molecules. Previous studies have reported that neutrophils express glutamate receptors and can release glutamate but evidence of direct neutrophil-neutrophil communication has been elusive.

Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients.

Objectives: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir.

Methods: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record.

Assessment of unvaccinated and vaccinated patients with coronavirus disease 2019 (COVID-19) treated with monoclonal antibodies during the delta wave (July 1-August 20, 2021): a retrospective observational monocentric study.

Background: Monoclonal antibodies (mAb) prevent COVID-19 progression when administered early. We compared mAb treatment outcomes among vaccinated and unvaccinated patients during Delta wave and assessed the feasibility of implementing stricter eligibility criteria in the event of mAb scarcity.

Methods: We conducted a retrospective observational study of casirivimab/imdevimab recipients with mild-to-moderate COVID-19 infection in an emergency department or outpatient infusion center (July 1-August 20, 2021).

Impact of the KL2/Catalyst Medical Research Investigator Training (CMeRIT) Program on the careers of early-stage clinical and translational investigators.

The Harvard Catalyst KL2/CMeRIT program is a 2-year mentored institutional career award that includes KL2 grants funded by National Institutes of Health (NIH) and CMeRIT grants funded by Harvard Catalyst nonfederal funds. The purpose of this study was to compare outcomes for early-stage investigators funded by the KL2/CMeRIT program to a group of applicants who were not chosen for support to assess the potential impact of the program on early career outcomes. Career data, including academic promotions, subsequent grant funding, and publication rates, from both successful and unsuccessful 2008-2018 KL2/CMeRIT applicants were compiled throughout the year 2020.

Post-severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Treatment Hospitalizations as a Sentinel for Emergence of Viral Variants in New York City.

We partnered with the US Department of Health and Human Services to treat high-risk, nonadmitted coronavirus disease 2019 (COVID-19) patients with bamlanivimab in the Bronx, New York per Emergency Use Authorization criteria. Increasing posttreatment hospitalizations were observed monthly between December 2020 and March 2021 in parallel to the emergence of severe acute respiratory syndrome coronavirus 2 variants in New York City.

LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.

Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses.

Serotonin 5-HT receptor boosts functional maturation of dendritic spines via RhoA-dependent control of F-actin.

Activity-dependent remodeling of excitatory connections underpins memory formation in the brain. Serotonin receptors are known to contribute to such remodeling, yet the underlying molecular machinery remains poorly understood. Here, we employ high-resolution time-lapse FRET imaging in neuroblastoma cells and neuronal dendrites to establish that activation of serotonin receptor 5-HT (5-HTR) rapidly triggers spatially-restricted RhoA activity and G13-mediated phosphorylation of cofilin, thus locally boosting the filamentous actin fraction.

Author Correction: Disentangling astroglial physiology with a realistic cell model in silico.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses.

NMDA receptors (NMDARs) play key roles in the use-dependent adaptation of glutamatergic synapses underpinning memory formation. In the forebrain, these plastic processes involve the varied contributions of GluN2A- and GluN2B-containing NMDARs that have different signaling properties. Although the molecular machinery of synaptic NMDAR trafficking has been under scrutiny, the postsynaptic spatial organization of these two receptor subtypes has remained elusive.

Disentangling astroglial physiology with a realistic cell model in silico.

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K and generate Ca signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment.

Dopamine elevates and lowers astroglial Ca through distinct pathways depending on local synaptic circuitry.

Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca ] measurements, we also employed life-time imaging of the Ca indicator Oregon Green BAPTA-1.

Time-Resolved Imaging Reveals Heterogeneous Landscapes of Nanomolar Ca(2+) in Neurons and Astroglia.

Maintaining low intracellular calcium is essential to the functioning of brain cells, yet the phenomenology and mechanisms involved remain an enigma. We have advanced a two-photon excitation time-resolved imaging technique, which exploits high sensitivity of the OGB-1 fluorescence lifetime to nanomolar Ca(2+) concentration ([Ca(2+)]) and enables a high data acquisition rate in situ. The [Ca(2+)] readout is not affected by dye concentration, light scattering, photobleaching, micro-viscosity, temperature, or the main known concomitants of cellular activity.

Weight loss is not mandatory for exercise-induced effects on health indices in females with metabolic syndrome.

The aim of this study was to investigate the impact of moderate aerobic training on functional, anthropometric, biochemical, and health-related quality of life (HRQOL) parameters on women with metabolic syndrome (MS). Fifteen untrained women with MS performed moderate aerobic training for 15 weeks, without modifications of dietary behaviours. Functional, anthropometric, biochemical, control diet record and HRQOL parameters were assessed before and after the training.

Diversity of astroglial functions alludes to subcellular specialisation.

Rapid signal exchange between astroglia and neurons has emerged as an essential element of neural circuits of the brain. However, the increasing variety of mechanisms contributing to this signalling appears to be facing a conceptual stalemate. The communication medium of astroglia involves intracellular [Ca(2+)] waves, which until recently have been associated with slow, global [Ca(2+)] rises.

Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses.

NMDA-type glutamate receptors (NMDAR) are central actors in the plasticity of excitatory synapses. During adaptive processes, the number and composition of synaptic NMDAR can be rapidly modified, as in neonatal hippocampal synapses where a switch from predominant GluN2B- to GluN2A-containing receptors is observed after the induction of long-term potentiation (LTP). However, the cellular pathways by which surface NMDAR subtypes are dynamically regulated during activity-dependent synaptic adaptations remain poorly understood.

NMDA receptor activation: two targets for two co-agonists.

Neuronal N-methyl-D-aspartate receptors (NMDARs) play a critical role in synaptic plasticity. Their activation requires not only binding of their ligand glutamate and membrane depolarization but also the presence of a co-agonist, glycine or D-serine. An increasing body of experimental evidence suggests that different populations of NMDARs could be gated by different co-agonists.

D-Serine: a key to synaptic plasticity?

Two discoveries have put D-serine in the spotlight of neuroscience. First, D-serine was detected in brain tissue at high levels. Second, it was found to act on the N-methyl-D-aspartate receptor (NMDAR).

Glutamate receptor dynamics and protein interaction: lessons from the NMDA receptor.

The plasticity of excitatory glutamate synapses emerged over the last decades as a core cellular mechanism for the encoding and processing of various cognitive functions. This property relies in part on the ability to dynamically adjust the content of glutamate receptors in the postsynaptic membrane. Among these receptors, NMDA receptors (NMDAR), which are composed of two obligatory GluN1 and two regulatory GluN2/3 subunits, play a key role in the induction of many forms of plasticity processes.

Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization.

The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides.

Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins.

The relative content of NR2 subunits in the NMDA receptor confers specific signaling properties and plasticity to synapses. However, the mechanisms that dynamically govern the retention of synaptic NMDARs, in particular 2A-NMDARs, remain poorly understood. Here, we investigate the dynamic interaction between NR2 C termini and proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) scaffold proteins at the single molecule level by using high-resolution imaging.

Surface trafficking of N-methyl-D-aspartate receptors: physiological and pathological perspectives.

The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in shaping the strength of synaptic connections. Over the last decades, extensive studies have defined the cellular and molecular mechanisms by which synaptic NMDARs control the maturation and plasticity of synaptic transmission, and how altered synaptic NMDAR signaling is implicated in neurodegenerative and psychiatric disorders. It is now clear that activation of synaptic or extrasynaptic NMDARs produces different signaling cascades and thus neuronal functions.

A molecular clutch between the actin flow and N-cadherin adhesions drives growth cone migration.

The adhesion molecule N-cadherin plays important roles in the development of the nervous system, in particular by stimulating axon outgrowth, but the molecular mechanisms underlying this effect are mostly unknown. One possibility, the so-called "molecular clutch" model, could involve a direct mechanical linkage between N-cadherin adhesion at the membrane and intracellular actin-based motility within neuronal growth cones. Using live imaging of primary rat hippocampal neurons plated on N-cadherin-coated substrates and optical trapping of N-cadherin-coated microspheres, we demonstrate here a strong correlation between growth cone velocity and the mechanical coupling between ligand-bound N-cadherin receptors and the retrograde actin flow.

Genetic counseling of families with Marfan syndrome and other disorders showing a Marfanoid body habitus.

Eight pedigrees of patients with Marfan syndrome are presented. In addition, four pedigrees of patients with conditions sometimes showing a marfanoid body habitus are described: Wagner-Stickler syndrome, multiple endocrine neoplasia type III, Ehlers-Danlos syndrome type VIA, and congenital contractural arachnodactyly type II. Emphasis is placed on the importance of genetic information in the differential diagnosis and management of patients and family members by the ophthalmologist.