Isothiourea-Catalysed Acylative Kinetic Resolution of Tertiary Pyrazolone Alcohols.

The development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea-catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)-, C(4)- and C(5)-, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically >100) at generally low catalyst loadings (1 mol %).

Treated unruptured cerebral aneurysm in elderly patients: a single center study.

Introduction: The increase in life expectancy raises the question of the treatment of unruptured intracranial aneurysms in extremely old patients (>80 years). We present results in terms of occlusion and complications in both symptomatic and asymptomatic aneurysm.

Methods: All patients aged >80 years admitted to the Foundation Adolphe de Rothschild between January 1, 2005 and March, 2023 were included.

Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune-driven demyelination.

Objectives: Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease-modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.

Enantioselective, Intermolecular [2+2] Photocycloaddition Reactions of 2(1)-Quinolones and Bicyclo[1.1.0]butanes.

1-Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1)-quinolones upon irradiation (λ = 366 nm) in the presence of a chiral complexing agent.

Microsurgery and Endovascular Therapy for Distal Anterior Cerebral Artery Aneurysm: A Multicenter Retrospective Cohort Study.

Background: Distal anterior cerebral aneurysm (DACA) represents 4% of intracranial aneurysms. Two treatment modalities are available: microsurgery and endovascular therapy (EVT).

Objective: To compare the results between microsurgery and EVT in a modern French cohort.

Relative effect of hydraulics, physico-chemistry and other biofilm algae on benthic cyanobacteria assemblages in a regulated river.

The development of benthic cyanobacteria currently raises concern worldwide because of their potential to produce toxins. As a result, understanding which measures of biotic and abiotic parameters influence the development of cyanobacterial assemblages is of great importance to guide management actions. In this study, we investigate the relative contributions of abiotic and biotic parameters that may drive the development of cyanobacterial assemblages in river biofilms.

Evolutionary Divergence of Phosphorylation to Regulate Interactive Protein Networks in Lower and Higher Species.

The phosphorylation of proteins affects their functions in extensively documented circumstances. However, the role of phosphorylation in many interactive networks of proteins remains very elusive due to the experimental limits of exploring the transient interaction in a large complex of assembled proteins induced by stimulation. Previous studies have suggested that phosphorylation is a recent evolutionary process that differently regulates ortholog proteins in numerous lineages of living organisms to create new functions.

Clozapine reduces chemokine-mediated migration of lymphocytes by targeting NF-κB and AKT phosphorylation.

Multiple sclerosis is a disease characterised by demyelination of axons in the central nervous system. The atypical antipsychotic drug clozapine has been shown to attenuate disease severity in experimental autoimmune encephalomyelitis (EAE), a mouse model that is useful for the study of multiple sclerosis. However, the mechanism of action by which clozapine reduces disease in EAE is poorly understood.

Endovascular therapy for acute ischemic stroke: The importance of blood pressure control, sedation modality and anti-thrombotic management to improve functional outcomes.

Since 2015, endovascular therapy (EVT) following intravenous thrombolysis (IVT) is the gold standard treatment for patients suffering from acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO). Despite high recanalization rates, nearly half of successfully treated patients remain dependent at three months. This result underlines that other factors may have a prognostic value, such as blood pressure (BP) management, the sedation modality and anti-thrombotic strategy during and after EVT.

The Salvinorin Analogue, Ethoxymethyl Ether Salvinorin B, Promotes Remyelination in Preclinical Models of Multiple Sclerosis.

Multiple sclerosis is a neurodegenerative disease associated with demyelination and neuroinflammation in the central nervous system. There is an urgent need to develop remyelinating therapies to better treat multiple sclerosis and other demyelinating diseases. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating therapies; however, prototypical KOR agonists, such as U50,488 have side effects, which limit clinical use.

Temporal and sequential order of nonoverlapping gene networks unraveled in mated female Drosophila.

In this study, we reanalyzed available datasets of gene expression changes in female Drosophila head induced by mating. Mated females present metabolic phenotypic changes and display behavioral characteristics that are not observed in virgin females, such as repulsion to male sexual aggressiveness, fidelity to food spots selected for oviposition, and restriction to the colonization of new niches. We characterize gene networks that play a role in female brain plasticity after mating using AMINE, a novel algorithm to find dysregulated modules of interacting genes.

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".

The leaf homogenate of is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use.

Adaptive Variation of Endosymbiont Density in Aphid Host Controlled by Environmental Conditions.

The scarcity of transcriptional regulatory genes in , an obligate endosymbiont in aphids, suggests the stability of expressed gene patterns and metabolic pathways. This observation argues in favor of the hypothesis that this endosymbiont bacteria might contribute little to the host adaptation when aphid hosts are facing challenging fluctuating environment. Finding evidence for the increased expression or silenced genes involved in metabolic pathways under the pressure of stress conditions and/or a given environment has been challenging for experimenters with this bacterial symbiotic model.

Computational search of hybrid human/SARS-CoV-2 dsRNA reveals unique viral sequences that diverge from those of other coronavirus strains.

The role of the RNAi/Dicer/Ago system in degrading RNA viruses has been elusive in mammals in the past, which has prompted authors to think that interferon (IFN) synthesis is essential in this clade, relegating the RNAi defense strategy against viral infection as an accessory function. However, recent publications highlight the existence of abundant viral small interference and micro RNAs (VsiRNAs and VmiRNAs) in both cell-line and whole organism based experiments, indicating a contribution of these molecules in host responses and/or viral replication. We explore the theoretical possibility that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction, although this hypothesis seems counterintuitive.

Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency.

Background And Purpose: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency.

Methods: We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization).

Localisation of clozapine during experimental autoimmune encephalomyelitis and its impact on dopamine and its receptors.

Multiple sclerosis is a disease characterised by axonal demyelination in the central nervous system (CNS). The atypical antipsychotic drug clozapine attenuates experimental autoimmune encephalomyelitis (EAE), a mouse model used to study multiple sclerosis, but the precise mechanism is unknown and could include both peripheral and CNS-mediated effects. To better understand where clozapine exerts its protective effects, we investigated the tissue distribution and localisation of clozapine using matrix-assisted laser desorption ionization imaging mass spectrometry and liquid chromatography-mass spectrometry.

Nalfurafine reduces neuroinflammation and drives remyelination in models of CNS demyelinating disease.

Objectives: Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to the myelin sheath, resulting in physical and cognitive disability. There is currently no cure for MS, and finding effective treatments to prevent disease progression has been challenging. Recent evidence suggests that activating kappa opioid receptors (KOR) has a beneficial effect on the progression of MS.

Towards a predictive simulation of brace action in adolescent idiopathic scoliosis.

Bracing is the most common treatment to stop the progression of adolescent idiopathic scoliosis. Finite element modeling could help improve brace design, but model validation is still a challenge. In this work, the clinical relevance of a predictive and subject-specific model for bracing was evaluated in forty-six AIS patients.

Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.

The induction of an interferon-mediated response is the first line of defense against pathogens such as viruses. Yet, the dynamics and extent of interferon alpha (IFNα)-induced antiviral genes vary remarkably and comprise three expression clusters: early, intermediate and late. By mathematical modeling based on time-resolved quantitative data, we identified mRNA stability as well as a negative regulatory loop as key mechanisms endogenously controlling the expression dynamics of IFNα-induced antiviral genes in hepatocytes.

Unexpected Association of Desacyl-Ghrelin with Physical Activity and Chronic Food Restriction: A Translational Study on Anorexia Nervosa.

Anorexia nervosa (AN) is a severe metabopsychiatric disorder characterised by caloric intake restriction and often excessive physical exercise. Our aim is to assess in female AN patients and in a rodent model, the co-evolution of physical activity and potential dysregulation of acyl-(AG) and desacyl-(DAG) ghrelin plasma concentrations during denutrition and weight recovery. AN inpatients were evaluated at inclusion (T0, = 29), half-(T1) and total (T2) weight recovery, and one month after discharge (T3, = 13).

Computational prediction of miRNA/mRNA duplexomes at the whole human genome scale reveals functional subnetworks of interacting genes with embedded miRNA annealing motifs.

Perfect annealing between microRNAs (miRNAs) and messenger RNAs (mRNAs) was computationally searched at a broad scale in the human genome to determine whether theoretical pairing is restrictively represented in functional subnetworks or is randomly distributed. Massive RNA interference (RNAi) pairing motifs in genes constitute a remarkable subnetwork that displays highly genetically and biochemically interconnected genes. These analyses show unexpected repertoires of genes defined by their congruence in comatching with miRNAs at numerous sites and by their interconnection based on protein/protein interactions or proteins regulating the activity of others.

Emerging Organometallic Methods for the Synthesis of C-Branched (Hetero)aryl, Alkenyl, and Alkyl Glycosides: C-H Functionalization and Dual Photoredox Approaches.

Transition-metal-catalyzed C-H functionalization and photoredox nickel dual catalysis have emerged as innovative and powerful avenues for the synthesis of C-branched glycosides. These two concepts have been recently established and provide efficient and mild methods for accessing a series of valuable complex C-branched glycosides of great interest. Herein, recent developments in the synthesis of C-branched aryl/alkenyl/alkyl glycosides through these two approaches are highlighted.

Protein Phosphorylation Dynamics: Unexplored Because of Current Methodological Limitations: Dynamics of Processive Phosphorylation.

The study of intrinsic phosphorylation dynamics and kinetics in the context of complex protein architecture in vivo has been challenging: Method limitations have prevented significant advances in the understanding of the highly variable turnover of phosphate groups, synergy, and cooperativity between P-sites. However, over the last decade, powerful analytical technologies have been developed to determine the full catalog of the phosphoproteome for many species. The curated databases of phospho sites found by mass spectrometry analysis and the computationally predicted sites based on the linear sequence of kinase motifs are valuable tools.