SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.

Background: Major depression and anxiety disorders are significant causes of disability and socioeconomic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions.

Acute Myocarditis Following Vaccination With the First Dose of the mRNA-1273 Vaccine.

Viral infections are a common cause of acute myocarditis. However, vaccines including influenza and smallpox have also been rarely implicated. Recently, the coronavirus disease 2019 (COVID-19) vaccines have been associated with acute myocarditis.

Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens.

Depression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression.

Study the Longitudinal and Cross-Sectional Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation.

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data or is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal and single-time-point MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis.

SUPPRESSOR OF GAMMA RESPONSE1 Links DNA Damage Response to Organ Regeneration.

In Arabidopsis, DNA damage-induced programmed cell death is limited to the meristematic stem cell niche and its early descendants. The significance of this cell-type-specific programmed cell death is unclear. Here, we demonstrate in roots that it is the programmed destruction of the mitotically compromised stem cell niche that triggers its regeneration, enabling growth recovery.

Imaging of Tau Pathology Using Magnetic Resonance Imaging Textural Analysis.

Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden.

Comparison of and MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between and MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution and MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry.

Testing Depression in Mice: a Chronic Social Defeat Stress Model.

A vast challenge within neuropsychiatric research has been the development of animal models that accurately reflect symptoms associated with affective disorders. An ethologically valid model that has been shown to be effective in studying depression is the chronic social defeat stress model. In this model, C57BL/6J mice are subjected to chronic social defeat stress induced by CD-1 aggressor mice for 10 consecutive days.

Connexin Hemichannels: Methods for Dye Uptake and Leakage.

It is now clear that connexin-based, gap junction "hemichannels" in an undocked state are capable of opening and connecting cytoplasm to the extracellular milieu. Varied studies also suggest that such channel activity plays a vital role in diverse cell processes and abnormal hemichannel activity contributes to pathogenesis. To pursue fundamental questions in this area, investigators require methods for studying hemichannel permeability and dynamics that are quantitative, sensitive, versatile, and available to most cellular and molecular laboratories.

Imaging the accumulation and suppression of tau pathology using multiparametric MRI.

Mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms relating to neurodegeneration, including tau-mediated and neurofibrillary tangle pathology-a major hallmark of the disease. In this work, we have used multiparametric magnetic resonance imaging (MRI) in a longitudinal study of neurodegeneration in the rTg4510 mouse model of tauopathy, a subset of which were treated with doxycycline at different time points to suppress the tau transgene. Using this paradigm, we investigated the sensitivity of multiparametric MRI to both the accumulation and suppression of pathologic tau.

Comparative assessments of CRISPR-Cas nucleases' cleavage efficiency in planta.

Custom-designed nucleases can enable precise plant genome editing by catalyzing DNA-breakage at specific targets to stimulate targeted mutagenesis or gene replacement. The CRISPR-Cas system, with its target-specifying RNA molecule to direct the Cas9 nuclease, is a recent addition to existing nucleases that bind and cleave the target through linked protein domains (e.g.

The effects of microsatellite selection on linked sequence diversity.

The genome-wide scan for selection is an important method for identifying loci involved in adaptive evolution. However, theory that underlies standard scans for selection assumes a simple mutation model. In particular, recurrent mutation of the selective target is not considered.

Conjugated polymer patterning through photooxidative backbone cleavage.

Photolithographic patterning of a xanthate precursor to poly(3,4-diphenyl-2,5-thienylene vinylene) is described. Unlike xanthate precursors to poly(p-phenylene vinylene), the thienylene vinylene analogue patterns as a positive tone resist. Characterization of irradiated films reveals photooxidative cleavage of the vinylene linker decreases the molecular weight of the polymer (increasing the solubility of the UV-exposed areas).

Airway drug pharmacokinetics via analysis of exhaled breath condensate.

Although the airway surface is the anatomic target for many lung disease therapies, measuring drug concentrations and activities on these surfaces poses considerable challenges. We tested whether mass spectrometric analysis of exhaled breath condensate (EBC) could be utilized to non-invasively measure airway drug pharmacokinetics and predicted pharmacological activities. Mass spectrometric methods were developed to detect a novel epithelial sodium channel blocker (GS-9411/P-680), two metabolites, a chemically related internal standard, plus naturally occurring solutes including urea as a dilution marker.

Acute hyperkalemia associated with inhalation of a potent ENaC antagonist: Phase 1 trial of GS-9411.

Background: Inhaled epithelial sodium channel (ENaC) blockers are designed to increase airway surface liquid volume, thereby benefiting cystic fibrosis patients. This study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of ENaC blocker GS-9411, in healthy participants.

Methods: This randomized, double-blind, placebo-controlled, parallel-group, residential, Phase 1 study evaluated inhaled GS-9411 (2.

A rapid assay to quantify the cleavage efficiency of custom-designed nucleases in planta.

Custom-designed nucleases are a promising technology for genome editing through the catalysis of double-strand DNA breaks within target loci and subsequent repair by the host cell, which can result in targeted mutagenesis or gene replacement. Implementing this new technology requires a rapid means to determine the cleavage efficiency of these custom-designed proteins in planta. Here we present such an assay that is based on cleavage-dependent luciferase gene correction as part of a transient dual-luciferase(®) reporter (Promega) expression system.

Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica).

We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids.

Thermally-activated pentanol delivery from precursor poly(p-phenylenevinylene)s for MEMS lubrication.

The synthesis of two new polyphenylene vinylene (PPV) precursor polymers which can be thermally induced to eliminate pentanol is presented. Pentanol has recently been discovered to be a very useful lubricant in MicroElectroMechanical Systems. The utilization of the elimination reaction of precursor polymers to PPV as a small molecule delivery platform has, to the best of our knowledge, not been previously reported.

Effect of topically applied epithelial sodium channel inhibitors on tear production in normal mice and in mice with induced aqueous tear deficiency.

Purpose: Dry eye syndromes affect a significant proportion of the population worldwide with reported prevalence ranging from 6% to more than 34%. Patients with dry eye can experience intense pain due to eye irritation, gritty/scratchy feeling in the eyes, blurry vision, and light sensitivity. Available treatments for dry eye syndromes remain mainly palliative.

Gap junction assembly: roles for the formation plaque and regulation by the C-terminus of connexin43.

Using an established gap junction (GJ) assembly system with experimentally reaggregated cells, we analyzed "formation plaques" (FPs), apparent sites of GJ assembly. Employing freeze-fracture electron microscopy methods combined with filipin labeling of sterols and immunolabeling for connexin43 (Cx43), we demonstrated that FPs constitute distinct membrane "domains" and that their characteristic 10-nm particles contain connexin43, thus representing precursors (i.e.

Targeted mutagenesis of zebrafish: use of zinc finger nucleases.

The modeling of human disease in the zebrafish (Danio rerio) is moving away from chemical mutagensis and transient downregulation using morpholino oligomers to more targeted and stable transgenic methods. In this respect, zinc finger nucleases offer a means of introducing mutations at targeted sites at high efficiency. We describe here the development of zinc finger nucleases and their general use in model systems with a focus on the zebrafish.

Photopatterning poly(p-phenylenevinylene) from xanthate precursor polymers.

A simple, direct method for photopatterning poly(p-phenylenevinylene) (PPV) from a xanthate precursor polymer is presented. The effect of UV exposure on the resultant PPV is examined by UV-Vis, XPS, FTIR, and DC conductivity measurements. By optimizing the photolithographic conditions, a spatial resolution of one micron is obtained, with minimal impact to the properties of the photopatterned PPV.

Rosette nanotubes with 1.4 nm inner diameter from a tricyclic variant of the Lehn-Mascal G--C base.

A new strategy to access rosette nanotubes with increased inner diameter is presented and demonstrated through the synthesis and self-assembly studies of a tricyclic variant of the Lehn-Mascal G--C base.