Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation.

Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau inclusions. However, the exact mechanistic link between these two AD lesions remains enigmatic. Through injection of human AD-brain-derived pathological tau (AD-tau) into Aβ plaque-bearing mouse models that do not overexpress tau, we recapitulated the formation of three major types of AD-relevant tau pathologies: tau aggregates in dystrophic neurites surrounding Aβ plaques (NP tau), AD-like neurofibrillary tangles (NFTs) and neuropil threads (NTs).

Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development.

In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development.

Exhaled breath volatile organic and inorganic compound composition in end-stage renal disease.

Aims: Patients with end-stage renal disease (ESRD) are characterized by uremia and increased oxidative stress. The aim of this study was to investigate the influence of hemodialysis on breath ammonia and volatile oxidative stress parameters.

Methods: Breath analysis was performed in 18 ESRD patients prior, during, and 30 minutes after a hemodialysis session.

Normal and epilepsy-associated pathologic function of the dentate gyrus.

The dentate gyrus plays critical roles both in cognitive processing, and in regulation of the induction and propagation of pathological activity. The cellular and circuit mechanisms underlying these diverse functions overlap extensively. At the cellular level, the intrinsic properties of dentate granule cells combine to endow these neurons with a fundamental reluctance to activate, one of their hallmark traits.

Dysregulation of synaptogenesis genes antecedes motor neuron pathology in spinal muscular atrophy.

The motor neuron (MN) degenerative disease, spinal muscular atrophy (SMA) is caused by deficiency of SMN (survival motor neuron), a ubiquitous and indispensable protein essential for biogenesis of snRNPs, key components of pre-mRNA processing. However, SMA's hallmark MN pathology, including neuromuscular junction (NMJ) disruption and sensory-motor circuitry impairment, remains unexplained. Toward this end, we used deep RNA sequencing (RNA-seq) to determine if there are any transcriptome changes in MNs and surrounding spinal cord glial cells (white matter, WM) microdissected from SMN-deficient SMA mouse model at presymptomatic postnatal day 1 (P1), before detectable MN pathology (P4-P5).

Protracted postnatal development of sparse, specific dentate granule cell activation in the mouse hippocampus.

The dentate gyrus (DG) is a critical entry point regulating function of the hippocampus. Integral to this role are the sparse, selective activation characteristics of the principal cells of the DG, dentate granule cells (DGCs). This sparse activation is important both in cognitive processing and in regulation of pathological activity in disease states.

Comparative evaluation of oxidative and antioxidative capacity during high-flux hemodialysis using two different membranes.

Aim: In patients with end-stage renal disease (ESRD) cardiovascular morbidity and mortality are increased. Apart from traditional and uremia-specific factors oxidative stress has been implicated as a main risk factor. This study investigated the influence of two different high-flux hemodialysis membranes on parameters of oxidative stress during a dialysis session.

Effects of excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion in rats.

The influence of bilateral excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion (CTA) was examined in two experiments. In Experiment 1, rats with thalamic lesions showed normal latent inhibition by acquiring a CTA that was significantly weaker when the conditioned stimulus (CS) was familiar than when it was novel. In Experiment 2, the preconditioned element (sodium chloride) of a compound CS blocked the acquisition of a CTA to the novel element (sucrose) in normal rats.

Comparison of the new polyethersulfone high-flux membrane DIAPES HF800 with conventional high-flux membranes during on-line haemodiafiltration.

Background: Current modalities of renal replacement therapy allow only a limited removal of larger, possibly toxic molecules, which accumulate in uraemia. Recently, a haemodiafilter has been made available with the new, high-flux, polyethersulfone-based membrane DIAPES HF800. We performed a study to compare DIAPES HF800 with two conventional high-flux membranes in on-line haemodiafiltration (HDF), with respect to the removal properties for the two marker proteins, beta(2)-microglobulin (beta(2)m, 11.

Simple behavioral methods to assess the effect of drugs or toxins on sensory experience.

When behavioral pharmacologists/toxicologists study conditioned taste aversions (CTAs), or other conditioned responses, as a means to investigate the effects of various drugs or toxins on a learned response, failure to discover a CTA is frequently attributed to the treatment's influence on the associative process. This kind of analysis may fail to identify drug-induced sensory changes that may influence conditioned stimulus (CS) or unconditioned stimulus (US) saliency. The current paper outlines a simple method by which a drug's influence on CS or US sensation may be determined.

Paradoxical effects of ketamine on the memory of fetuses of different ages.

Brain N-methyl-D-aspartate (NMDA) glutamate receptors have been implicated as important mediators of both learning and neuronal development. The current study investigated how ketamine (a well-known NMDA-receptor blocking drug) influences taste-mediated conditioned motor responses (CMRs) in perinatal rats. Dams pregnant with either embryonic day 18 (E18) or E19 rat fetuses were injected with 0 or 100 mg/kg ketamine HCl (i.

Detection of novelty by perinatal rats.

This study investigated the development of fetal/neonatal rats' ability to distinguish between a novel and familiar taste. Here, we report that neonatal rats alter their orofacial movements (e.g.

Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector.

The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-I provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell lines that had the same phenotype (CD4+, CD5+, HLA class II+, interleukin 2 receptor alpha-chain +) as lymphocytes transformed by cocultivation with HTLV-I.