Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models of epileptic encephalopathy.

De novo mutations in voltage- and ligand-gated channels have been associated with an increasing number of cases of developmental and epileptic encephalopathies, which often fail to respond to classic antiseizure medications. Here, we examine two knock-in mouse models replicating de novo sequence variations in the human voltage-gated channel gene, p.G391D and p.

Routine data-based quality indicators for the treatment of gonarthrosis and coxarthrosis patients in the ambulatory care sector - A study protocol for a cluster-randomised pilot trial to evaluate the MobilE-ARTH study.

Background: In 2019, Germany had the highest rate of hip replacement surgery and the fourth highest rate of knee replacement surgery among more than 30 OECD countries. The age-standardised rates were estimated at 174 hip joint and 137 knee joint replacements per 100,000 population. Against this background, the contrast between financial incentives for surgery and missing incentives for non-surgical treatment options is repeatedly discussed.

Somatic Depolarization Enhances Hippocampal CA1 Dendritic Spike Propagation and Distal Input-Driven Synaptic Plasticity.

Synaptic inputs that target distal regions of neuronal dendrites can often generate local dendritic spikes that can amplify synaptic depolarization, induce synaptic plasticity, and enhance neuronal output. However, distal dendritic spikes are subject to significant attenuation by dendritic cable properties, and often produce only a weak subthreshold depolarization of the soma. Nonetheless, such spikes have been implicated in memory storage, sensory perception and place field formation.

Pursuing More Aggressive Timelines in the Surgical Treatment of Traumatic Spinal Cord Injury (TSCI): A Retrospective Cohort Study with Subgroup Analysis.

Background: The optimal timing of surgical therapy for traumatic spinal cord injury (TSCI) remains unclear. The purpose of this study is to evaluate the impact of "ultra-early" (<4 h) versus "early" (4-24 h) time from injury to surgery in terms of the likelihood of neurologic recovery.

Methods: The effect of surgery on neurological recovery was investigated by comparing the assessed initial and final values of the American Spinal Injury Association (ASIA) Impairment Scale (AIS).

Enkephalin release from VIP interneurons in the hippocampal CA2/3a region mediates heterosynaptic plasticity and social memory.

The hippocampus contains a diverse array of inhibitory interneurons that gate information flow through local cortico-hippocampal circuits to regulate memory storage. Although most studies of interneurons have focused on their role in fast synaptic inhibition mediated by GABA release, different classes of interneurons express unique sets of neuropeptides, many of which have been shown to exert powerful effects on neuronal function and memory when applied pharmacologically. However, relatively little is known about whether and how release of endogenous neuropeptides from inhibitory cells contributes to their behavioral role in regulating memory formation.

Zinc Concentration Dynamics Indicate Neurological Impairment Odds after Traumatic Spinal Cord Injury.

Traumatic Spinal Cord Injury (TSCI) is debilitating and often results in a loss of motor and sensory function caused by an interwoven set of pathological processes. Oxidative stress and inflammatory processes are amongst the critical factors in the secondary injury phase after TSCI. The essential trace element Zinc (Zn) plays a crucial role during this phase as part of the antioxidant defense system.

The Role of Magnesium in the Secondary Phase After Traumatic Spinal Cord Injury. A Prospective Clinical Observer Study.

In the secondary injury phase after traumatic spinal cord injury (TSCI), oxidative stress and neuroinflammatory responses at the site of injury constitute crucial factors controlling damage extent and may serve as potential therapeutic targets. We determined Magnesium (Mg) serum concentration dynamics in context with the potential of neurological remission in patients with TSCI as Mg is suspected to limit the production of reactive oxygen species and reduce lipid peroxidation. A total of 29 patients with acute TSCI were enrolled, and blood samples were drawn over 3 months at 11 time-points and Mg quantification was performed.

Paradoxical Excitatory Impact of SK Channels on Dendritic Excitability.

Dendritic excitability regulates how neurons integrate synaptic inputs and thereby influences neuronal output. As active dendritic events are associated with significant calcium influx they are likely to be modulated by calcium-dependent processes, such as calcium-activated potassium channels. Here we investigate the impact of small conductance calcium-activated potassium channels (SK channels) on dendritic excitability in male and female rat cortical pyramidal neurons and Using local applications of the SK channel antagonist apamin , we show that blocking somatic SK channels enhances action potential output, whereas blocking dendritic SK channels paradoxically reduces the generation of dendritic calcium spikes and associated somatic burst firing.

Novel approach to an early assessment of a patient's potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics.

Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI). Prospective Clinical Observational Study. BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.

Relation of selenium status to neuro-regeneration after traumatic spinal cord injury.

Introduction: The trace element selenium (Se) is crucial for the biosynthesis of selenoproteins. Both neurodevelopment and the survival of neurons that are subject to stress depend on a regular selenoprotein biosynthesis and sufficient Se supply by selenoprotein P (SELENOP).

Hypothesis: Neuro-regeneration after traumatic spinal cord injury (TSCI) is related to the Se status.

AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis by Myxococcus xanthus.

Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and lipids. It acts in the development of myxobacteria, which can produce this compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). A central reaction of aib is catalyzed by AibA/AibB, which acts as a cofactor-free decarboxylase despite belonging to the family of CoA-transferases.

Structural, mechanistic and functional insight into gliotoxin -thiomethylation in .

Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin -methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to -adenosylhomocysteine (1.

The AibR-isovaleryl coenzyme A regulator and its DNA binding site - a model for the regulation of alternative de novo isovaleryl coenzyme A biosynthesis in Myxococcus xanthus.

Isovaleryl coenzyme A (IV-CoA) is an important building block of iso-fatty acids. In myxobacteria, IV-CoA is essential for the formation of signaling molecules involved in fruiting body formation. Leucine degradation is the common source of IV-CoA, but a second, de novo biosynthetic route to IV-CoA termed AIB (alternative IV-CoA biosynthesis) was recently discovered in M.

The Impact of BK Channels on Cellular Excitability Depends on their Subcellular Location.

Large conductance calcium-activated potassium channels (or BK channels) fulfil a multitude of roles in the central nervous system. At the soma of many neuronal cell types they control the speed of action potential (AP) repolarization and therefore they can have an impact on neuronal excitability. Due to their presence in nerve terminals they also regulate transmitter release.

Crystal structure of AibC, a reductase involved in alternative de novo isovaleryl coenzyme A biosynthesis in Myxococcus xanthus.

Isovaleryl coenzyme A (IV-CoA) performs a crucial role during development and fruiting-body formation in myxobacteria, which is reflected in the existence of a de novo biosynthetic pathway that is highly upregulated when leucine, the common precursor of IV-CoA, is limited. The final step in de novo IV-CoA biosynthesis is catalyzed by AibC, a medium-chain dehydrogenase/reductase. Here, the crystal structure of AibC from Myxococcus xanthus refined to 2.

The Structure of LiuC, a 3-Hydroxy-3-Methylglutaconyl CoA Dehydratase Involved in Isovaleryl-CoA Biosynthesis in Myxococcus xanthus, Reveals Insights into Specificity and Catalysis.

Myxobacteria are able to produce the important metabolite isovaleryl coenzyme A by a route other than leucine degradation. The first step into this pathway is mediated by LiuC, a member of the 3-methylglutaconyl CoA hydratases (MGCH). Here we present crystal structures refined to 2.

Crystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus.

A critical step in bacterial isoprenoid production is the synthesis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) catalyzed by HMG-CoA synthase (HMGCS). In myxobacteria, this enzyme is also involved in a recently discovered alternative and acetyl-CoA-dependent isovaleryl CoA biosynthesis pathway. Here we present crystal structures of MvaS, the HMGCS from Myxococcus xanthus, in complex with CoA and acetylated active site Cys115, with the second substrate acetoacetyl CoA and with the product of the condensation reaction, 3-hydroxy-3-methylglutaryl CoA.

Impact of calcium-activated potassium channels on NMDA spikes in cortical layer 5 pyramidal neurons.

Active electrical events play an important role in shaping signal processing in dendrites. As these events are usually associated with an increase in intracellular calcium, they are likely to be under the control of calcium-activated potassium channels. Here, we investigate the impact of calcium-activated potassium channels onN-methyl-d-aspartate (NMDA) receptor-dependent spikes, or NMDA spikes, evoked by glutamate iontophoresis onto basal dendrites of cortical layer 5 pyramidal neurons.

Dendritic encoding of sensory stimuli controlled by deep cortical interneurons.

The computational power of single neurons is greatly enhanced by active dendritic conductances that have a large influence on their spike activity. In cortical output neurons such as the large pyramidal cells of layer 5 (L5), activation of apical dendritic calcium channels leads to plateau potentials that increase the gain of the input/output function and switch the cell to burst-firing mode. The apical dendrites are innervated by local excitatory and inhibitory inputs as well as thalamic and corticocortical projections, which makes it a formidable task to predict how these inputs influence active dendritic properties in vivo.