Bioluminescent imaging of genetically selected induced pluripotent stem cell-derived cardiomyocytes after transplantation into infarcted heart of syngeneic recipients.

Cell loss after transplantation is a major limitation for cell replacement approaches in regenerative medicine. To assess the survival kinetics of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) we generated transgenic murine iPSC lines which, in addition to CM-specific expression of puromycin N-acetyl-transferase and enhanced green fluorescent protein (EGFP), also constitutively express firefly luciferase (FLuc) for bioluminescence (BL) in vivo imaging. While undifferentiated iPSC lines generated by random integration of the transgene into the genome retained stable FLuc activity over many passages, the BL signal intensity was strongly decreased in purified iPS-CM compared to undifferentiated iPSC.

Lost after translation: missorting of Tau protein and consequences for Alzheimer disease.

Tau is a microtubule-associated-protein that is sorted into neuronal axons in physiological conditions. In Alzheimer disease (AD) and other tauopathies, Tau sorting mechanisms fail and Tau becomes missorted into the somatodendritic compartment. In AD, aberrant amyloid-β (Aβ) production might trigger Tau missorting.

A review of novel optical imaging strategies of the stroke pathology and stem cell therapy in stroke.

Transplanted stem cells can induce and enhance functional recovery in experimental stroke. Invasive analysis has been extensively used to provide detailed cellular and molecular characterization of the stroke pathology and engrafted stem cells. But post mortem analysis is not appropriate to reveal the time scale of the dynamic interplay between the cell graft, the ischemic lesion and the endogenous repair mechanisms.

PET imaging in ischemic cerebrovascular disease: current status and future directions.

Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies.

Prenatal melamine exposure induces impairments of spatial cognition and hippocampal synaptic plasticity in male adolescent rats.

Our previous studies showed that chronic melamine exposure could affect hippocampal synaptic plasticity and impair learning and memory on adult rats. In this study, we investigated whether prenatal melamine exposure (PME) induced cognitive deficits and impairment of synaptic plasticity in postnatal offspring. An animal model was produced by melamine exposure throughout gestational period with 400mg/kg/day, while male offspring rats were employed.

Predicting goals in action episodes attenuates BOLD response in inferior frontal and occipitotemporal cortex.

Actions are usually made of several action steps gearing towards an overarching goal. During observation of such action episodes the overarching action goal becomes more and more clear and upcoming action steps can be predicted with increasing precision. To tap this process, the present fMRI study investigated the dynamic changes of neural activity during the observation of distinct action steps that cohere by an overarching goal.

An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults.

Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age.

A texture-processing model of the 'visual sense of number'.

It has been suggested that numerosity is an elementary quality of perception, similar to colour. If so (and despite considerable investigation), its mechanism remains unknown. Here, we show that observers require on average a massive difference of approximately 40% to detect a change in the number of objects that vary irrelevantly in blur, contrast and spatial separation, and that some naive observers require even more than this.

Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI.

Objects are reminiscent of actions often performed with them:knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation.

Hedgehog signaling sensitizes glioma stem cells to endogenous nano-irradiation.

The existence of therapy resistant glioma stem cells is responsible for the high recurrence rate and incurability of glioblastomas. The Hedgehog pathway activity plays an essential role for self-renewal capacity and survival of glioma stem cells. We examined the potential of the Sonic hedgehog ligand for sensitizing of glioma stem cells to endogenous nano-irradiation.

Vitamins C and E reverse melamine-induced deficits in spatial cognition and hippocampal synaptic plasticity in rats.

Albeit the pathogenesis of cognitive impairment after exposure to melamine has not been fully elucidated, factors such as oxidative stress is thought to play potential roles. In the present study, we investigated the effect of treatment with vitamin C (150mg/kg) and vitamin E (200mg/kg) on the impairment induced by melamine. Three-week-old male Wistar rats were submitted to oral gavage with 300mg/kg melamine in 1% carboxymethylcellulose (CMC) for 28 days (MEL-SAL group).

The integrity of the cholinergic system determines memory performance in healthy elderly.

The cholinergic system plays a central role in episodic memory-related processes in health and disease. Cerebral acetylcholinesterase (AChE) activity, a measure of the integrity of the cholinergic system, can be assessed in vivo using positron emission tomography (PET) and [(11)C]N-methyl-4-piperidyl acetate (MP4A). A close relationship between the kinetic constant k3 of MP4A and mnestic functions has been demonstrated for patients suffering from amnestic mild cognitive impairment and Alzheimer's disease.

Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity.

Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations.

In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats.

Neuroinflammation with microglia activation (MA) constitutes a key tissue response in acute stroke. Until now, its course in the chronic stage is less well defined. Here, we investigated (i) neuroinflammation in the chronic stage of a rat model of embolic stroke (n=6), and (ii) whether this process can be visualized in vivo by multimodal imaging using Magnetic Resonance Imaging (MRI) and Positron-Emission-Tomography (PET).

Neural correlates of sensorimotor gating: a metabolic positron emission tomography study in awake rats.

Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications.

Bioluminescence imaging of stroke-induced endogenous neural stem cell response.

Brain injury following stroke affects neurogenesis in the adult mammalian brain. However, a complete understanding of the origin and fate of the endogenous neural stem cells (eNSCs) in vivo is missing. Tools and technology that allow non-invasive imaging and tracking of eNSCs in living animals will help to overcome this hurdle.

Handedness and effective connectivity of the motor system.

Handedness denotes the individual predisposition to consistently use the left or right hand for most types of skilled movements. A putative neurobiological mechanism for handedness consists in hemisphere-specific differences in network dynamics that govern unimanual movements. We, therefore, used functional magnetic resonance imaging and dynamic causal modeling to investigate effective connectivity between key motor areas during fist closures of the dominant or non-dominant hand performed by 18 right- and 18 left-handers.

Die another day: a painless path to longevity.

Riera et al. identify a neuroendocrine circuit that controls longevity and the age-dependent onset of metabolic decline via the pain-transducing channel TRPV1. Thus, pharmacological inhibition of TRPV1 may provide a new approach to treat not only metabolic disorders but also a broader range of age-related pathologies.

Parkinson's disease subtypes show a specific link between dopaminergic and glucose metabolism in the striatum.

Background: Previous studies have shown different clinical and imaging pattern in tremordominant and akinetic-rigid Parkinson's disease (PD) subtypes. The association between dopaminergic and glucose metabolism has in contrast not been investigated yet. Therefore, this study compared PD subtypes with respect to clinical and imaging findings with the aim of establishing a relationship between clinical subtypes, dopamine and glucose metabolism.

Dissociating dynamic probability and predictability in observed actions-an fMRI study.

The present fMRI study investigated whether human observers spontaneously exploit the statistical structure underlying continuous action sequences. In particular, we tested whether two different statistical properties can be distinguished with regard to their neural correlates: an action step's predictability and its probability. To assess these properties we used measures from information theory.

Emerging modes of PINK1 signaling: another task for MARK2.

PTEN-induced kinase 1 (PINK1) acts at multiple levels to promote mitochondrial health, including regulatory influence on ATP-synthesis, protein quality control, apoptosis, mitochondrial transport, and destiny. PINK1 mutations are linked to Parkinson disease (PD) and mostly result in loss of kinase activity. But the molecular events responsible for neuronal death as well as the physiological targets and regulators of PINK1 are still a matter of debate.

T cell-intrinsic role of IL-6 signaling in primary and memory responses.

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response.

Identifying Neuroimaging Markers of Motor Disability in Acute Stroke by Machine Learning Techniques.

Conventional mass-univariate analyses have been previously used to test for group differences in neural signals. However, machine learning algorithms represent a multivariate decoding approach that may help to identify neuroimaging patterns associated with functional impairment in "individual" patients. We investigated whether fMRI allows classification of individual motor impairment after stroke using support vector machines (SVMs).