The Tree Shrew Model of Parkinson Disease: A Cost-Effective Alternative to Nonhuman Primate Models.

The surge in demand for experimental monkeys has led to a rapid increase in their costs. Consequently, there is a growing need for a cost-effective model of Parkinson disease (PD) that exhibits all core clinical and pathologic phenotypes. Evolutionarily, tree shrews (Tupaia belangeri) are closer to primates in comparison with rodents and could be an ideal species for modeling PD.

Development of a Medication-Use Evaluation Template for Andexanet Alfa in the Reversal of Anticoagulation With Factor Xa Inhibitors.

Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.

PyINETA: Open-source platform for INADEQUATE-JRES integration in NMR metabolomics.

Annotating compounds with high confidence is a critical element in metabolomics. C-detection NMR experiment INADEQUATE (incredible natural abundance double-quantum transfer experiment) stands out as a powerful tool for structural elucidation, whereas this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of community platform that provides structural information based INADEQUATE.

Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice.

The localization, number, and function of postsynaptic AMPA-type glutamate receptors (AMPARs) are crucial for synaptic plasticity, a cellular correlate for learning and memory. The Hippo pathway member WWC1 is an important component of AMPAR-containing protein complexes. However, the availability of WWC1 is constrained by its interaction with the Hippo pathway kinases LATS1 and LATS2 (LATS1/2).

Long-lived proteins and DNA as candidate predictive biomarkers for tissue associated diseases.

Protein turnover is an important mechanism to maintain proteostasis. Long-lived proteins (LLPs) are vulnerable to lose their function due to time-accumulated damages. In this study we employed stable isotope labeling in mice from birth to postnatal day 89.

Lumbar puncture increases Alzheimer's disease biomarker levels in cerebrospinal fluid of rhesus monkeys.

Cerebrospinal fluid (CSF) samples are commonly collected via lumbar puncture (LP) in both clinical and research settings for measurement of biomarkers of Alzheimer's disease (AD). To determine the effects of LP on CSF AD biomarkers, we collected CSF samples at seven different time points after an LP in rhesus monkeys. We find that amyloid-beta (Aβ) and Tau levels increased significantly on day 1, peaked on day 3, and returned to baseline on day 10 after LP.

Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats.

Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinformatics.

The underappreciated diversity of bile acid modifications.

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns.

Prefrontal cortical synaptoproteome profile combined with machine learning predicts resilience towards chronic social isolation in rats.

Chronic social isolation (CSIS) of rats serves as an animal model of depression and generates CSIS-resilient and CSIS-susceptible phenotypes. We aimed to investigate the prefrontal cortical synaptoproteome profile of CSIS-resilient, CSIS-susceptible, and control rats to delineate biochemical pathways and predictive biomarker proteins characteristic for the resilient phenotype. A sucrose preference test was performed to distinguish rat phenotypes.

Powering AI at the edge: A robust, memristor-based binarized neural network with near-memory computing and miniaturized solar cell.

Memristor-based neural networks provide an exceptional energy-efficient platform for artificial intelligence (AI), presenting the possibility of self-powered operation when paired with energy harvesters. However, most memristor-based networks rely on analog in-memory computing, necessitating a stable and precise power supply, which is incompatible with the inherently unstable and unreliable energy harvesters. In this work, we fabricated a robust binarized neural network comprising 32,768 memristors, powered by a miniature wide-bandgap solar cell optimized for edge applications.

Correction: Chaby et al. Cross-Platform Evaluation of Commercially Targeted and Untargeted Metabolomics Approaches to Optimize the Investigation of Psychiatric Disease. 2021, , 609.

In the original publication [...

scBrainMap: a landscape for cell types and associated genetic markers in the brain.

The great variety of brain cell types is a fundamental element for neuronal circuits. One major goal of modern neuroscience is to decipher the various types of cellular composition and characterize their properties. Due to the high heterogeneity of neuronal cells, until recently, it was not possible to group brain cell types at high resolution.

Chronic fluoxetine treatment in socially-isolated rats modulates the prefrontal cortex synaptoproteome.

Exposure to chronic social isolation (CSIS) and synapse dysfunction have been implicated in the etiology of major depressive disorder (MDD). Fluoxetine (Flx) has been widely used to treat MDD, but its mechanisms of action remain elusive. We employed comparative synaptoproteomics to investigate the changes in the levels of proteins and molecular signaling pathways in prefrontal cortical samples of adult male Wistar rats exposed to CSIS, a rat model of depression, and CSIS rats treated with chronic Flx and controls, using liquid chromatography coupled to tandem mass spectrometry.

Hippo-released WWC1 facilitates AMPA receptor regulatory complexes for hippocampal learning.

Learning and memory rely on changes in postsynaptic glutamergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor (AMPAR) number, spatial organization, and function. The Hippo pathway component WW and C2 domain-containing protein 1 (WWC1) regulates AMPAR surface expression and impacts on memory performance. However, synaptic binding partners of WWC1 and its hierarchical position in AMPAR complexes are largely unclear.

Delineation of biomarkers and molecular pathways of residual effects of fluoxetine treatment in juvenile rhesus monkeys by proteomic profiling.

Fluoxetine (Prozac™) is the only antidepressant approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in children. Despite its considerable efficacy as a selective serotonin reuptake inhibitor, the possible long-term effects of fluoxetine on brain development in children are poorly understood. In the current study, we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques () one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.

Chronic Fluoxetine Treatment of Socially Isolated Rats Modulates Prefrontal Cortex Proteome.

Fluoxetine (Flx) is the most commonly used antidepressant to treat major depressive disorder. However, its molecular mechanisms of action are not defined as yet. A comparative proteomic approach was used to identify proteome changes in the prefrontal cortex (PFC) cytosolic and non-synaptic mitochondria (NSM)-enriched fractions of adult male Wistar rats following chronic social isolation (CSIS), a rat model of depression, and Flx treatment in CSIS and control rats, using liquid chromatography online tandem mass spectrometry.

Gene networks under circadian control exhibit diurnal organization in primate organs.

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined.

Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2.

A single sub-anesthetic dose of ketamine produces a rapid and sustained antidepressant response, yet the molecular mechanisms responsible for this remain unclear. Here, we identified cell-type-specific transcriptional signatures associated with a sustained ketamine response in mice. Most interestingly, we identified the Kcnq2 gene as an important downstream regulator of ketamine action in glutamatergic neurons of the ventral hippocampus.

Antidepressant treatment effects on hippocampal protein turnover: Molecular and spatial insights from mass spectrometry.

A major challenge in managing depression is that antidepressant drugs take a long time to exert their therapeutic effects. For the development of faster-acting treatments, it is crucial to get an improved understanding of the molecular mechanisms underlying antidepressant mode of action. Here, we used a novel mass spectrometry-based workflow to investigate how antidepressant treatment affects brain protein turnover at single-cell and subcellular resolution.

Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice.

The primate-specific G72/G30 gene locus has been associated with major psychiatric disorders, such as schizophrenia and bipolar disorder. We have previously generated transgenic mice which carry the G72/G30 locus and express the longest G72 splice variant (LG72) protein encoded by this locus with schizophrenia-related symptoms. Here, we used a multi-omics approach, including quantitative proteomics and metabolomics to investigate molecular alterations in the hippocampus of G72/G30 transgenic (G72Tg) mice.