Deficiency of cholesterol 7α-hydroxylase in bile acid synthesis exacerbates alcohol-induced liver injury in mice.

Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic relevance of increased bile acids in AFLD and the underlying mechanism of increasing the bile acid pool by alcohol feeding are still unclear.

Increased ethanol-inducible cytochrome P450-2E1 and cytochrome P450 isoforms in exosomes of alcohol-exposed rodents and patients with alcoholism through oxidative and endoplasmic reticulum stress.

This study investigated the role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in enhancing CYP2E1 and other P450 proteins in extracellular vesicles (EVs) from alcohol-exposed rodents and human patients with alcoholism and their effects on oxidative hepatocyte injury. Female Fischer rats and wild-type or -null mice were exposed to three oral doses of binge ethanol or dextrose control at 12-hour intervals. Plasma EV and hepatic proteins from alcohol-exposed rodents, patients with alcoholism, and their respective controls were isolated and characterized.

Hairy and enhancer of split 6 prevents hepatic lipid accumulation through inhibition of expression.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARγ2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of expression and hepatic steatosis induced by diet.

Idiopathic pulmonary vein thrombosis?

Idiopathic pulmonary vein thrombosis (PVT) is a rare disease which is likely under-diagnosed because of nebulous presentations. Accurate diagnosis is essential to prevent complications.

Early Cytoskeletal Protein Modifications Precede Overt Structural Degeneration in the DBA/2J Mouse Model of Glaucoma.

Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins, and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma.

Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals.

The etiology of tinnitus is known to be diverse in the human population. An appropriate animal model of tinnitus should incorporate this pathological diversity. Previous studies evaluating the effect of acoustic over exposure (AOE) have found that animals typically display increased spontaneous firing rates and bursting activity of auditory neurons, which often has been linked to behavioral evidence of tinnitus.

Benefits of Stimulus Exposure: Developmental Learning Independent of Task Performance.

Perceptual learning (training-induced performance improvement) can be elicited by task-irrelevant stimulus exposure in humans. In contrast, task-irrelevant stimulus exposure in animals typically disrupts perception in juveniles while causing little to no effect in adults. This may be due to the extent of exposure, which is brief in humans while chronic in animals.

Gaussian Process Modeling of Protein Turnover.

We describe a stochastic model to compute in vivo protein turnover rate constants from stable-isotope labeling and high-throughput liquid chromatography-mass spectrometry experiments. We show that the often-used one- and two-compartment nonstochastic models allow explicit solutions from the corresponding stochastic differential equations. The resulting stochastic process is a Gaussian processes with Ornstein-Uhlenbeck covariance matrix.

Contextual Modulation of Vocal Behavior in Mouse: Newly Identified 12 kHz "Mid-Frequency" Vocalization Emitted during Restraint.

While several studies have investigated mouse ultrasonic vocalizations (USVs) emitted by isolated pups or by males in mating contexts, studies of behavioral contexts other than mating and vocalization categories other than USVs have been limited. By improving our understanding of the vocalizations emitted by mice across behavioral contexts, we will better understand the natural vocal behavior of mice and better interpret vocalizations from mouse models of disease. Hypothesizing that mouse vocal behavior would differ depending on behavioral context, we recorded vocalizations from male CBA/CaJ mice across three behavioral contexts including mating, isolation, and restraint.

Propofol restores TRPV1 sensitivity via a TRPA1-, nitric oxide synthase-dependent activation of PKCε.

We previously demonstrated that the intravenous anesthetic, propofol, restores the sensitivity of transient receptor potential vanilloid channel subtype-1 (TRPV1) receptors via a protein kinase C epsilon (PKCε)-dependent and transient receptor potential ankyrin channel subtype-1 (TRPA1)-dependent pathway in sensory neurons. The extent to which the two pathways are directly linked or operating in parallel has not been determined. Using a molecular approach, our objectives of the current study were to confirm that TRPA1 activation directly results in PKCε activation and to elucidate the cellular mechanism by which this occurs.

The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance.

Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox) homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS).

Excitatory and inhibitory projections in parallel pathways from the inferior colliculus to the auditory thalamus.

Individual subdivisions of the medial geniculate body (MG) receive a majority of their ascending inputs from 1 or 2 subdivisions of the inferior colliculus (IC). This establishes parallel pathways that provide a model for understanding auditory projections from the IC through the MG and on to auditory cortex. A striking discovery about the tectothalamic circuit was identification of a substantial GABAergic component.

Ultrastructural characterization of GABAergic and excitatory synapses in the inferior colliculus.

In the inferior colliculus (IC) cells integrate inhibitory input from the brainstem and excitatory input from both the brainstem and auditory cortex. In order to understand how these inputs are integrated by IC cells identification of their synaptic arrangements is required. We used electron microscopy to characterize GABAergic synapses in the dorsal cortex, central nucleus, and lateral cortex of the IC (ICd, ICc, and IClc) of guinea pigs.

Descending projections from auditory cortex to excitatory and inhibitory cells in the nucleus of the brachium of the inferior colliculus.

Descending projections from the auditory cortex (AC) terminate in subcortical auditory centers from the medial geniculate nucleus (MG) to the cochlear nucleus, allowing the AC to modulate the processing of acoustic information at many levels of the auditory system. The nucleus of the brachium of the inferior colliculus (NBIC) is a large midbrain auditory nucleus that is a target of these descending cortical projections. The NBIC is a source of several auditory projections, including an ascending projection to the MG.

Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma.

Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these deficits are poorly understood. Previous work suggests that anterograde transport is affected earlier and to a larger degree than retrograde transport, yet this has never been examined directly in vivo.

Developmental hearing loss impairs signal detection in noise: putative central mechanisms.

Listeners with hearing loss have difficulty processing sounds in noisy environments. This is most noticeable for speech perception, but is reflected in a basic auditory processing task: detecting a tonal signal in a noise background, i.e.

Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus.

Experiments in several species have identified direct projections to the medial geniculate nucleus (MG) from cells in subcollicular auditory nuclei. Moreover, many cochlear nucleus cells that project to the MG send collateral projections to the inferior colliculus (IC) (Schofield et al., 2014).

Interplay between low threshold voltage-gated K(+) channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis.

Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue.

Distribution of GABAergic cells in the inferior colliculus that project to the thalamus.

A GABAergic component has been identified in the projection from the inferior colliculus (IC) to the medial geniculate body (MG) in cats and rats. We sought to determine if this GABAergic pathway exists in guinea pig, a species widely used in auditory research. The guinea pig IC contains GABAergic cells, but their relative abundance in the IC and their relative contributions to tectothalamic projections are unknown.

Projections from the dorsal and ventral cochlear nuclei to the medial geniculate body.

Direct projections from the cochlear nucleus (CN) to the medial geniculate body (MG) mediate a high-speed transfer of acoustic information to the auditory thalamus. Anderson etal. (2006) used anterograde tracers to label the projection from the dorsal CN (DCN) to the MG in guinea pigs.