Cardiac fibroblast-derived 3D extracellular matrix seeded with mesenchymal stem cells as a novel device to transfer cells to the ischemic myocardium.

Purpose: Demonstrate a novel manufacturing method to generate extracellular matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal stem cell-transfer device.

Materials And Methods: Rat CF were cultured at high-density (~1.6×10/cm) for 10-14 days.

Pathophysiological defects and transcriptional profiling in the RBM20-/- rat model.

Our recent study indicated that RNA binding motif 20 (Rbm20) alters splicing of titin and other genes. The current goals were to understand how the Rbm20(-/-) rat is related to physiological, structural, and molecular changes leading to heart failure. We quantitatively and qualitatively compared the expression of titin isoforms between Rbm20(-/-) and wild type rats by real time RT-PCR and SDS agarose electrophoresis.

Sensorial suppression of self-generated sounds and its dependence on attention.

The auditory processing of self-generated sounds is characterized by an attenuated vertex N1-component of the event-related potential (ERP) compared to the responses elicited by externally generated sounds. Typically, a motor condition where sounds are actively produced by button presses is compared with a passive listening condition. While this effect is usually interpreted as reflection of an internal forward model system, the impact of attention and arousal on the so called self-generation effect has not been systematically controlled in these studies: Is the auditory stimulation more attended during the active task compared to passive listening, e.

I know what is missing here: electrophysiological prediction error signals elicited by omissions of predicted "what" but not "when".

In the present study we investigated the neural code of sensory predictions. Grounded on a variety of empirical findings, we set out from the proposal that sensory predictions are coded via the top-down modulation of the sensory units whose response properties match the specific characteristics of the predicted stimulus (Albright, 2012; Arnal and Giraud, 2012). From this proposal, we derive the hypothesis that when the specific physical characteristics of the predicted stimulus cannot be advanced, the sensory system should not be able to formulate such predictions, as it would lack the means to represent them.

High-content adhesion assay to address limited cell samples.

Cell adhesion is a broad topic in cell biology that involves physical interactions between cells and other cells or the surrounding extracellular matrix, and is implicated in major research areas including cancer, development, tissue engineering, and regenerative medicine. While current methods have contributed significantly to our understanding of cell adhesion, these methods are unsuitable for tackling many biological questions requiring intermediate numbers of cells (10(2)-10(5)), including small animal biopsies, clinical samples, and rare cell isolates. To overcome this fundamental limitation, we developed a new assay to quantify the adhesion of ~10(2)-10(3) cells at a time on engineered substrates, and examined the adhesion strength and population heterogeneity via distribution-based modeling.

The N1-suppression effect for self-initiated sounds is independent of attention.

Background: If we initiate a sound by our own motor behavior, the N1 component of the auditory event-related brain potential (ERP) that the sound elicits is attenuated compared to the N1 elicited by the same sound when it is initiated externally. It has been suggested that this N1 suppression results from an internal predictive mechanism that is in the service of discriminating the sensory consequences of one's own actions from other sensory input. As the N1-suppression effect is becoming a popular approach to investigate predictive processing in cognitive and social neuroscience, it is important to exclude an alternative interpretation not related to prediction.

A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats.

Consumption of a high-fat diet (HFD) in experimental animal models initiates a series of molecular events and outcomes, including insulin resistance and obesity, that mimic the metabolic syndrome in humans. The relationship among, and order of, the molecular events linking a diet high in fat to pathologies is often unclear. In the present study, we provide several novel insights into the relationship between a HFD and AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism and whole-body energy balance.

RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.

Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. By positional cloning using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the underlying cause of pathological titin isoform expression. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations.

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α₁-AMPK-/- mice.

Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might be an effective way of expending excess calories. Because of the established role of AMP-activated protein kinase (AMPK) as a "metabolic master switch" and its extremely high levels of activity in BAT, it was hypothesized that AMPK might play a central role in regulating BAT metabolism.

Sustained selective intermodal attention modulates processing of language-like stimuli.

Intermodal attention (IA) is assumed to allocate limited neural processing resources to input from one specific sensory modality. We investigated effects of sustained IA on the amplitude of a 40-Hz auditory (ASSR) and a 4.3-Hz visual steady-state response (VSSR).

Caloric restriction does not alter effects of aging in cardiac side population cells.

The aged heart displays a loss of cardiomyocyte number and function, possibly due to the senescence and decreased regenerative potential that has been observed in some cardiac progenitor cells. An important cardiac progenitor that has not been studied in the context of aging is the cardiac side population (CSP) cell. To address this, flow cytometry-assisted cell sorting was used to isolate CSP cells from adult (6-10 months old) and aged (24-32 months old) C57Bl/6 mice that were fed either a control diet or an anti-aging diet (caloric restriction, CR).

Caloric restriction attenuates the age-associated increase of adipose-derived stem cells but further reduces their proliferative capacity.

White adipose tissue is a promising source of mesenchymal stem cells. Currently, little is known about the effect of age and caloric restriction (CR) on adipose-derived stem cells (ASC). This is important for three reasons: firstly, age and CR cause extensive remodeling of WAT; it is currently unknown how this remodeling affects the resident stem cell population.

Energy restriction does not compensate for the reduced expression of hepatic drug-processing genes in mice with aging.

Liver is the major organ that eliminates xenobiotics from the body, a process that is accomplished by a series of drug-processing genes (DPGs). These genes encode transporters on both basolateral and apical membranes of hepatocytes, as well as phase I and II enzymes. The current study compares the expression of hepatic DPGs in adult and aged mouse livers and explores the potential effects of energy restriction (ER) on these genes during aging.

Spatial selective attention in a complex auditory environment such as polyphonic music.

To investigate the influence of spatial information in auditory scene analysis, polyphonic music (three parts in different timbres) was composed and presented in free field. Each part contained large falling interval jumps in the melody and the task of subjects was to detect these events in one part ("target part") while ignoring the other parts. All parts were either presented from the same location (0 degrees; overlap condition) or from different locations (-28 degrees, 0 degrees, and 28 degrees or -56 degrees, 0 degrees, and 56 degrees in the azimuthal plane), with the target part being presented either at 0 degrees or at one of the right-sided locations.

Neural mechanisms of intermodal sustained selective attention with concurrently presented auditory and visual stimuli.

We investigated intermodal attention effects on the auditory steady-state response (ASSR) and the steady-state visual evoked potential (SSVEP). For this purpose, 40-Hz amplitude-modulated tones and a stream of flickering (7.5 Hz) random letters were presented concurrently.

Effects of intermodal attention on the auditory steady-state response and the event-related potential.

The aim of the present study was to simultaneously measure and compare intermodal attention effects in event-related brain potentials (ERPs) and auditory steady-state responses (ASSRs). For this purpose, 40-Hz amplitude modulated tones and a visual fixation cross were presented concurrently. By means of target detection tasks either on the sounds or on the fixation cross, participants' attention was directed to the respective modality.

A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg(-1) day(-1)), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles.

Downregulation of plasma insulin levels and hepatic PPARgamma expression during the first week of caloric restriction in mice.

Calorie restriction extends lifespan by decreasing the rate of tumor formation, an effect occurring within 8 weeks of initiating a restricted diet. Our goal was to define how the first weeks of a calorie restricted diet (60% of ad libitum calories) affects putative mediators of the calorie restriction phenotype, focusing on regulators of fatty acid biosynthesis. In C57Bl/6 mice, insulin decreased over 50% (p<0.

Automatic detection of lexical change: an auditory event-related potential study.

We investigated the detection of rare task-irrelevant changes in the lexical status of speech stimuli. Participants performed a nonlinguistic task on word and pseudoword stimuli that occurred, in separate conditions, rarely or frequently. Task performance for pseudowords was deteriorated relative to words, suggesting unintentional lexical analysis.

Energy restriction-induced changes in body composition are age specific in mice.

Restricting energy intake while supplying adequate micronutrients slows aging and extends maximal lifespan, whereas loss of body weight with exercise training does not. Our goal was to test the hypothesis that weight loss via energy restriction (ER) alters body composition in a way that is: 1) distinct from exercise-induced weight loss; and 2) conserved regardless of the age at which ER is initiated. An experimental model was developed where matched losses in weight could be induced with 6 mo of ER (approximately 55% of ad libitum energy intake) or voluntary exercise on a running wheel in adult (12 mo) male C57BL/6 mice and a similar amount of ER-induced weight loss could be induced in aged mice (24 mo).

Local delivery of PKCepsilon-activating peptide mimics ischemic preconditioning in aged hearts through GSK-3beta but not F1-ATPase inactivation.

In adult heart, selective PKCepsilon activation limits ischemia (I)-reperfusion (R) damage and mimics the protection associated with ischemic preconditioning. We sought to determine whether local delivery of PKCepsilon activator peptide psiepsilon-receptor for activated C-kinase (psiepsilon-RACK) is sufficient to produce a similarly protected phenotype in aged hearts. Langendorff-perfused hearts isolated from adult (5 mo; n = 9) and aged (24 mo; n = 9) male Fisher 344 rats were perfused with psiepsilon-RACK conjugated to Tat (500 nM) or Tat only (500 nM) for 10 min before global 31-min ischemia.

Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse.

AMPK (adenosine monophosphate-activated protein kinase), a key regulator of cellular energy metabolism and whole-body energy balance, is present in brown adipose tissue but its role in regulating the acute metabolic state and chronic thermogenic potential of this metabolically unique tissue is unknown. To address this, the AMPK signalling system in brown and white adipose tissue was studied in C57Bl/6 mice under control conditions, during acute and chronic cold exposure, and during chronic adrenergic stimulation. In control mice AMPK activity in brown adipose tissue was higher than in any tissue yet reported (3-fold the level in liver) secondary to a high level of expression of the alpha1 isoform.

Aging elevates basal adenosine monophosphate-activated protein kinase (AMPK) activity and eliminates hypoxic activation of AMPK in mouse liver.

Despite the central role of adenosine monophosphate-activated protein kinase (AMPK) in the cellular stress response, it is unknown whether age-related changes in AMPK activity play a role in the diminished stress tolerance that is characteristic of aging. To address this question, we determined in the mouse liver how normal aging affects 1) basal AMPK activity, and 2) the degree to which AMPK activity is increased by in vivo hypoxia. We found that the basal activity of AMPK alpha1, but not alpha2, was higher in livers from 24-month-old mice compared to those from 5-month-old mice.

Effects of aging on cardiac and skeletal muscle AMPK activity: basal activity, allosteric activation, and response to in vivo hypoxemia in mice.

Although a diminished ability of tissues and organisms to tolerate stress is a clinically important hallmark of normal aging, little is known regarding its biochemical basis. Our goal was to determine whether age-associated changes in AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism during the stress response, might contribute to the poor stress tolerance of aged cardiac and skeletal muscle. Basal AMPK activity and the degree of activation of AMPK by AMP and by in vivo hypoxemia (arterial Po2 of 39 mmHg) were measured in cardiac and skeletal muscle (gastrocnemius) from 5- and 24-mo-old C57Bl/6 mice.

Metabolic adaptations to fasting and chronic caloric restriction in heart, muscle, and liver do not include changes in AMPK activity.

Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a central role in allowing cells to adapt to nutrient deprivation in vitro. This link between AMPK activity and nutritional status has raised the possibility that AMPK plays a role in the metabolic adaptation to acute and chronic nutritional stress. However, the effects of nutritional stress on AMPK activity in vivo have not been systematically evaluated.