The Metalloprotease Meprin β Is an Alternative β-Secretase of APP.

The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments.

Increased Motor-Impairing Effects of the Neuroactive Steroid Pregnanolone in Mice with Targeted Inactivation of the GABA Receptor γ2 Subunit in the Cerebellum.

Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABA receptors. In recombinant receptors and genetic mouse models their actions depend on the α, β, and δ subunits of the receptor, especially on those that form extrasynaptic GABA receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched γ2 subunit-containing receptors and even on αβ binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5β-pregnan-3α-ol-20-one is altered in genetically engineered mouse models that have deficient GABA receptor-mediated synaptic inhibition in selected neuronal populations.

Adverse Social Experiences in Adolescent Rats Result in Enduring Effects on Social Competence, Pain Sensitivity and Endocannabinoid Signaling.

Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual's well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models.

Contextual Interactions in Grating Plaid Configurations Are Explained by Natural Image Statistics and Neural Modeling.

Processing natural scenes requires the visual system to integrate local features into global object descriptions. To achieve coherent representations, the human brain uses statistical dependencies to guide weighting of local feature conjunctions. Pairwise interactions among feature detectors in early visual areas may form the early substrate of these local feature bindings.

The Composite Effect Is Face-Specific in Young but Not Older Adults.

In studying holistic face processing across the life-span there are only few attempts to separate face-specific from general aging effects. Here we used the complete design of the composite paradigm (Cheung et al., 2008) with faces and novel non-face control objects (watches) to investigate composite effects in young (18-32 years) and older adults (63-78 years).

Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission.

Structural Brain Network Characteristics Can Differentiate CIS from Early RRMS.

Focal demyelinated lesions, diffuse white matter (WM) damage, and gray matter (GM) atrophy influence directly the disease progression in patients with multiple sclerosis. The aim of this study was to identify specific characteristics of GM and WM structural networks in subjects with clinically isolated syndrome (CIS) in comparison to patients with early relapsing-remitting multiple sclerosis (RRMS). Twenty patients with CIS, 33 with RRMS, and 40 healthy subjects were investigated using 3 T-MRI.

Positive Emotional Language in the Final Words Spoken Directly Before Execution.

How do individuals emotionally cope with the imminent real-world salience of mortality? DeWall and Baumeister as well as Kashdan and colleagues previously provided support that an increased use of positive emotion words serves as a way to protect and defend against mortality salience of one's own contemplated death. Although these studies provide important insights into the psychological dynamics of mortality salience, it remains an open question how individuals cope with the immense threat of mortality prior to their imminent actual death. In the present research, we therefore analyzed positivity in the final words spoken immediately before execution by 407 death row inmates in Texas.

Switching Attention Within Working Memory is Reflected in the P3a Component of the Human Event-Related Brain Potential.

The flexible access to information in working memory is crucial for adaptive behavior. It is assumed that this is realized by switching the focus of attention within working memory. Switching of attention is mirrored in the P3a component of the human event-related brain potential (ERP) and it has been argued that the processes reflected by the P3a are also relevant for selecting information within working memory.

An N-terminal deletion variant of HCN1 in the epileptic WAG/Rij strain modulates HCN current densities.

Rats of the Wistar Albino Glaxo/Rij (WAG/Rij) strain show symptoms resembling human absence epilepsy. Thalamocortical neurons of WAG/Rij rats are characterized by an increased HCN1 expression, a negative shift in I h activation curve, and an altered responsiveness of I h to cAMP. We cloned HCN1 channels from rat thalamic cDNA libraries of the WAG/Rij strain and found an N-terminal deletion of 37 amino acids.

Impact of cancer on the effectiveness of cardiac Troponin I to predict right ventricular dysfunction in acute pulmonary embolism.

Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are connected with a poor outcome in cancer patients. We aimed to investigate the impact of cancer on the effectiveness of cardiac Troponin I (cTnI) to predict right ventricular dysfunction (RVD) in acute PE.

Methods: We retrospectively analyzed the data of 182 patients with confirmed PE.

Comparing Subjective With Objective Sleep Parameters Via Multisensory Actigraphy in German Physical Education Students.

This study compared subjective with objective sleep parameters among 72 physical education students. Furthermore, the study determined whether 24-hr recording differs from nighttime recording only. Participants wore the SenseWear Armband™ for three consecutive nights and kept a sleep log.

The sensitivity to replacement and displacement of the eyes region in early adolescence, young and later adulthood.

Recent evidence suggests a rather gradual developmental trajectory for processing vertical relational face information, lasting well into late adolescence (de Heering and Schlitz, 2008). Results from another recent study (Tanaka et al., 2014) indicate that children and young adolescents use a smaller spatial integration field for faces than do adults, which particularly affects assessment of long-range vertical relations.

Non-cell autonomous and non-catalytic activities of ATX in the developing brain.

The intricate formation of the cerebral cortex requires a well-coordinated series of events, which are regulated at the level of cell-autonomous and non-cell autonomous mechanisms. Whereas cell-autonomous mechanisms that regulate cortical development are well-studied, the non-cell autonomous mechanisms remain poorly understood. A non-biased screen allowed us to identify Autotaxin (ATX) as a non-cell autonomous regulator of neural stem cells.

Two routes to actorhood: lexicalized potency to act and identification of the actor role.

The inference of causality is a crucial cognitive ability and language processing is no exception: recent research suggests that, across different languages, the human language comprehension system attempts to identify the primary causer of the state of affairs described (the "actor") quickly and unambiguously (Bornkessel-Schlesewsky and Schlesewsky, 2009). This identification can take place verb-independently based on certain prominence cues (e.g.

Stochastic model predicts evolving preferences in the Iowa gambling task.

Learning under uncertainty is a common task that people face in their daily life. This process relies on the cognitive ability to adjust behavior to environmental demands. Although the biological underpinnings of those cognitive processes have been extensively studied, there has been little work in formal models seeking to capture the fundamental dynamic of learning under uncertainty.

BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion.

BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals.

The complete design in the composite face paradigm: role of response bias, target certainty, and feedback.

Some years ago an improved design (the "complete design") was proposed to assess the composite face effect in terms of a congruency effect, defined as the performance difference for congruent and incongruent target to no-target relationships (Cheung et al., 2008). In a recent paper Rossion (2013) questioned whether the congruency effect was a valid hallmark of perceptual integration, because it may contain confounds with face-unspecific interference effects.

Holistic face perception in young and older adults: effects of feedback and attentional demand.

Evidence exists for age-related decline in face cognition ability. However, the extents to which attentional demand and flexibility to adapt viewing strategies contribute to age-related decline in face cognition tests is poorly understood. Here, we studied holistic face perception in older (age range 65-78 years, mean age 69.

Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback.

The role of literal meaning in figurative language comprehension: evidence from masked priming ERP.

The role of literal meaning during the construction of meaning that goes beyond pure literal composition was investigated by combining cross-modal masked priming and ERPs. This experimental design was chosen to compare two conflicting theoretical positions on this topic. The indirect access account claims that literal aspects are processed first, and additional meaning components are computed only if no satisfactory interpretation is reached.

MicroRNA-138 is a potential regulator of memory performance in humans.

Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate "memory genes," these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older.