Transcutaneous spinal cord stimulation neuromodulates pre- and postsynaptic inhibition in the control of spinal spasticity.

Aside from enabling voluntary control over paralyzed muscles, a key effect of spinal cord stimulation is the alleviation of spasticity. Dysfunction of spinal inhibitory circuits is considered a major cause of spasticity. These circuits are contacted by Ia muscle spindle afferents, which are also the primary targets of transcutaneous lumbar spinal cord stimulation (TSCS).

ExonSurfer: a web-tool to design primers at exon-exon junctions.

Background: Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others.

Rare phenomena of central rhythm and pattern generation in a case of complete spinal cord injury.

Lumbar central pattern generators (CPGs) control the basic rhythm and coordinate muscle activation underlying hindlimb locomotion in quadrupedal mammals. The existence and function of CPGs in humans have remained controversial. Here, we investigated a case of a male individual with complete thoracic spinal cord injury who presented with a rare form of self-sustained rhythmic spinal myoclonus in the legs and rhythmic activities induced by epidural electrical stimulation (EES).

Cerebral Malaria: Current Clinical and Immunological Aspects.

This review focuses on current clinical and immunological aspects of cerebral malaria induced by infection. Albeit many issues concerning the inflammatory responses remain unresolved and need further investigations, current knowledge of the underlying molecular mechanisms is highlighted. Furthermore, and in the light of significant limitations in preventative diagnosis and treatment of cerebral malaria, this review mainly discusses our understanding of immune mechanisms in the light of the most recent research findings.

Protein Structure Analysis and Prediction with Statistical Scoring Functions.

The PDB database provides more than 150,000 entries for biological macromolecular structures [...

Transcutaneous Spinal Cord Stimulation Enhances Walking Performance and Reduces Spasticity in Individuals with Multiple Sclerosis.

Gait dysfunction and spasticity are common debilitating consequences of multiple sclerosis (MS). Improvements of these motor impairments by lumbar transcutaneous spinal cord stimulation (tSCS) have been demonstrated in spinal cord injury. Here, we explored for the first time the motor effects of lumbar tSCS applied at 50 Hz for 30 min in 16 individuals with MS and investigated their temporal persistence post-intervention.

Ipsi- and Contralateral Oligo- and Polysynaptic Reflexes in Humans Revealed by Low-Frequency Epidural Electrical Stimulation of the Lumbar Spinal Cord.

Epidural electrical stimulation (EES) applied over the human lumbosacral spinal cord provides access to afferent fibers from virtually all lower-extremity nerves. These afferents connect to spinal networks that play a pivotal role in the control of locomotion. Studying EES-evoked responses mediated through these networks can identify some of their functional components.

Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins.

Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far.

Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans.

Epidural electrical stimulation of the spinal cord is an emergent strategy for the neurological recovery of lower-extremity motor function. Motoneuron pools are thought to be recruited by stimulation of posterior roots. Here, we linked electromyographic data of epidurally evoked lower-extremity responses of 34 individuals with upper motoneuron disorders to a population model of the spinal cord constructed using anatomical parameters of thousands of individuals.

MHCII3D-Robust Structure Based Prediction of MHC II Binding Peptides.

Knowledge of MHC II binding peptides is highly desired in immunological research, particularly in the context of cancer, autoimmune diseases, or allergies. The most successful prediction methods are based on machine learning methods trained on sequences of experimentally characterized binding peptides. Here, we describe a complementary approach called MHCII3D, which is based on structural scaffolds of MHC II-peptide complexes and statistical scoring functions (SSFs).

Identification and Physicochemical Characterization of a New Allergen from .

To analyze the impact of infection on the pathogenesis and diagnosis of allergic diseases, new allergens should be identified. We report the identification of a new allergen, Asc l 5. The aim of this study was to evaluate the physicochemical and immunological features of the Asc l 5 allergen.

Design of Phl p 6 Variants With Altered Fold-Stability Significantly Impacts Antigen Processing, Immunogenicity and Immune Polarization.

Understanding, which factors determine the immunogenicity and immune polarizing properties of proteins, is an important prerequisite for designing better vaccines and immunotherapeutics. While extrinsic immune modulatory factors such as pathogen associated molecular patterns are well-understood, far less is known about the contribution of protein inherent features. Protein fold-stability represents such an intrinsic feature contributing to immunogenicity and immune polarization by influencing the amount of peptide-MHC II complexes (pMHCII).

A hybrid of two major Blomia tropicalis allergens as an allergy vaccine candidate.

Introduction: Allergen-specific immunotherapy (AIT) represents a curative approach for treating allergies. In the tropical and subtropical regions of the world, Blomia tropicalis (Blo t 5 and Blo t 21) is the likely dominant source of indoor allergens.

Aim: To generate a hypoallergenic Blo t 5/Blo t 21 hybrid molecule that can treat allergies caused by B tropicalis.

The Cell Wall PAC (Proline-Rich, Arabinogalactan Proteins, Conserved Cysteines) Domain-Proteins Are Conserved in the Green Lineage.

Plant cell wall proteins play major roles during plant development and in response to environmental cues. A bioinformatic search for functional domains has allowed identifying the PAC domain (Proline-rich, Arabinogalactan proteins, conserved Cysteines) in several proteins (PDPs) identified in cell wall proteomes. This domain is assumed to interact with pectic polysaccharides and -glycans and to contribute to non-covalent molecular scaffolds facilitating the remodeling of polysaccharidic networks during rapid cell expansion.

Few-monolayer yttria-doped zirconia films: Segregation and phase stabilization.

For most applications, zirconia (ZrO) is doped with yttria. Doping leads to the stabilization of the tetragonal or cubic phase and increased oxygen ion conductivity. Most previous surface studies of yttria-doped zirconia were plagued by impurities, however.

Using photoelectron spectroscopy to observe oxygen spillover to zirconia.

X-ray photoelectron spectroscopy (XPS) of five-monolayer-thick ZrO2 films reveals a core level binding energy difference of up to 1.8 eV between the tetragonal and monoclinic phase. This difference is explained by positively charged oxygen vacancies in the tetragonal films, which are slightly reduced.

A long-term follow-up study on otoacoustic emissions testing in paediatric patients with severe malaria in Gabon.

Background: In a previous study, severe and cerebral malaria have been connected with acute cochlear malfunction in children, demonstrated by a decrease of transitory evoked otoacoustic emissions (TEOAEs) reproducibility. This study aims to determine whether cochlear malfunction persists for 4 years after recovery from severe malaria in a subset of the previous study's collective. Follow-up TEOAEs were performed on site (CERMEL, Hôpital Albert Schweitzer, Lambaréné, Gabon) or at the participants' homes; 33 out of 90 participants included in the initial investigation by Schmutzhard et al.

Rational Design, Structure-Activity Relationship, and Immunogenicity of Hypoallergenic Pru p 3 Variants.

Scope: Allergies to lipid transfer proteins involve severe adverse reactions; thus, effective and sustainable therapies are desired. Previous attempts disrupting disulfide bonds failed to maintain immunogenicity; thus, the aim is to design novel hypoallergenic Pru p 3 variants and evaluate the applicability for treatment of peach allergy.

Methods And Results: Pru p 3 proline variant (PV) designed using in silico mutagenesis, cysteine variant (CV), and wild-type Pru p 3 (WT) are purified from Escherichia coli.

Compound heterozygous SZT2 mutations in two siblings with early-onset epilepsy, intellectual disability and macrocephaly.

Purpose: Mutations in SZT2 have been previously reported in several cases of early onset epilepsy and intellectual disability. In this study we investigate potential causal mutations in two male siblings affected by early onset epilepsy, intellectual disability and macrocephaly.

Methods: We use family-based whole-exome sequencing to identify candidate variants.

Dissecting the subcellular membrane proteome reveals enrichment of H+ (co-)transporters and vesicle trafficking proteins in acidic zones of Chara internodal cells.

The Characeae are multicellular green algae with very close relationship to land plants. Their internodal cells have been the subject of numerous (electro-)physiological studies. When exposed to light, internodal cells display alternating bands of low and high pH along their surface in order to facilitate carbon uptake required for photosynthesis.

Synergistic cross-talk of hedgehog and interleukin-6 signaling drives growth of basal cell carcinoma.

Persistent activation of hedgehog (HH)/GLI signaling accounts for the development of basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer with rising incidence. Targeting HH/GLI signaling by approved pathway inhibitors can provide significant therapeutic benefit to BCC patients. However, limited response rates, development of drug resistance, and severe side effects of HH pathway inhibitors call for improved treatment strategies such as rational combination therapies simultaneously inhibiting HH/GLI and cooperative signals promoting the oncogenic activity of HH/GLI.

Construction and evaluation of an ultrahigh-vacuum-compatible sputter deposition source.

A sputter deposition source for the use in ultrahigh vacuum (UHV) is described, and some properties of the source are analyzed. The operating principle is based on the design developed by Mayr et al. [Rev.

Resolving the Structure of a Well-Ordered Hydroxyl Overlayer on InO(111): Nanomanipulation and Theory.

Changes in chemical and physical properties resulting from water adsorption play an important role in the characterization and performance of device-relevant materials. Studies of model oxides with well-characterized surfaces can provide detailed information that is vital for a general understanding of water-oxide interactions. In this work, we study single crystals of indium oxide, the prototypical transparent contact material that is heavily used in a wide range of applications and most prominently in optoelectronic technologies.

Evaluation of transient-evoked otoacoustic emissions in a healthy 1 to 10 year pediatric cohort in Sub-Saharan Africa.

Objective: Transient-evoked otoacoustic emissions (TEOAEs) monitor cochlear function. High pass rates have been reported for industrialized countries. Pass rates in low and middle income countries such as Sub-Saharan Africa are rare, essentially lower and available for children up to 4 years of age and frequently based on hospital recruitments.