KREH2 helicase represses ND7 mRNA editing in procyclic-stage Trypanosoma brucei by opposite modulation of canonical and 'moonlighting' gRNA utilization creating a proposed mRNA structure.

Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration.

Transmission of classical scrapie using lymph node inoculum.

Scrapie is a fatal, transmissible neurodegenerative disease that affects sheep and goats. Replication of PrP in the lymphoid tissue allows for the scrapie agent to be shed into the environment. Brain and retropharyngeal lymph node (RPLN) from a sheep inoculated with the classical scrapie agent was used to compare infectivity of these tissues.

Quantitative proteome dynamics across embryogenesis in a model chordate.

The evolution of gene expression programs underlying the development of vertebrates remains poorly characterized. Here, we present a comprehensive proteome atlas of the model chordate , covering eight developmental stages and ∼7,000 translated genes, accompanied by a multi-omics analysis of co-evolution with the vertebrate . Quantitative proteome comparisons argue against the widely held hourglass model, based solely on transcriptomic profiles, whereby peak conservation is observed during mid-developmental stages.

Perfluorooctanesulfonic Acid Alters the Plant's Phosphate Transport Gene Network and Exhibits Antagonistic Effects on the Phosphate Uptake.

Per- and polyfluoroalkyl substances (PFASs), with significant health risks to humans and wildlife, bioaccumulate in plants. However, the mechanisms underlying plant uptake remain poorly understood. This study deployed transcriptomic analysis coupled with genetic and physiological studies using to investigate how plants respond to perfluorooctanesulfonic acid (PFOS), a long-chain PFAS.

Short incubation periods of atypical H-type BSE in cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation.

In 2006, a case of atypical H-type BSE (H-BSE) was found to be associated with a germline mutation in the gene that resulted in a lysine substitution for glutamic acid at codon 211 (E211K). The E211K amino acid substitution in cattle is analogous to E200K in humans, which is associated with the development of genetic Creutzfeldt-Jakob disease (CJD). In the present study, we aimed to determine the effect of the EK211 prion protein genotype on incubation time in cattle inoculated with the agent of H-BSE; to characterize the molecular profile of H-BSE in KK211 and EK211 genotype cattle; and to assess the influence of serial passage on BSE strain.

Length and saturation of fatty acids in phosphatidylserine determine the rate of lysozyme aggregation simultaneously altering the structure and toxicity of amyloid oligomers and fibrils.

Abrupt aggregation of misfolded proteins is the underlying molecular cause of numerous severe pathologies including Alzheimer's and Parkinson's diseases. Protein aggregation yields small oligomers that can later propagate into amyloid fibrils, β-sheet-rich structures with a variety of topologies. A growing body of evidence suggests that lipids play an important role in abrupt aggregation of misfolded proteins.

Effect of inoculation with prion dilutions within the dynamic range of ELISA absorbance on prion incubation period.

This study examines the effect of various infectious prion titers within the dynamic range as measured by ELISA on incubation period. We inoculated ovinized transgenic mice with seven decreasing dilutions of a fast-incubating scrapie strain. The highest inoculum group was a 20% w/v brain homogenate from a sheep with scrapie.

Transmission of Raccoon-Passaged Chronic Wasting Disease Agent to White-Tailed Deer.

The transmission characteristics of prion diseases are influenced by host prion protein sequence and, therefore, the host species. Chronic wasting disease (CWD), a prion disease of cervids, has widespread geographical distribution throughout North America and occurs in both wild and farmed populations. CWD prions contaminate the environment through scattered excrement and decomposing carcasses.

Levetiracetam in the prophylactic treatment of episodic migraine: A prospective open label study.

Background: The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults.

Botulinum Toxin A Treatment in HIV Infected Patients-A Long-Term Observational Study.

Objective: It is unknown whether interactions between HIV infection and the safety of botulinum toxin A (BTX) exist.

Methods: We studied eight patients with HIV infection who were treated with BTX every three months for up to nine years. All patients were on antiretroviral treatment.

Increasing human motor skill acquisition by driving theta-gamma coupling.

Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Some learning paradigms, particularly in the memory domain, are closely associated with gamma activity that is amplitude modulated by the phase of underlying theta activity, but whether such nested activity patterns also underpin skill learning is unknown. Here, we addressed this question by using transcranial alternating current stimulation (tACS) over sensorimotor cortex to modulate theta-gamma activity during motor skill acquisition, as an exemplar of a non-hippocampal-dependent task.

GCN2 adapts protein synthesis to scavenging-dependent growth.

Pancreatic cancer cells with limited access to free amino acids can grow by scavenging extracellular protein. In a murine model of pancreatic cancer, we performed a genome-wide CRISPR screen for genes required for scavenging-dependent growth. The screen identified key mediators of macropinocytosis, peripheral lysosome positioning, endosome-lysosome fusion, lysosomal protein catabolism, and translational control.

CGRP release in an experimental human trigeminal pain model.

Background: Migraine and trigemino-autonomic cephalalgia attacks are associated with an increase of α-calcitonin-gene related peptide levels in the ipsilateral jugular vein. It is however unknown whether trigeminal pain stimulation in healthy subjects without headache disorders also induces increase of calcitonin-gene related peptide levels.

Findings: We measured α-calcitonin-gene related peptide levels in eight healthy subjects after subcutaneous injection of capsaicin in the forehead and in the mandibular region and after injection of sodium chloride in the forehead.

Very young age of onset in trigemino-autonomic cephalalgias - case report and review of the literature.

Background: Trigemino-autonomic cephalalgias are very rare disorders and even rarer in children and adolescents. We report the onset of paroxysmal hemicrania in a very young girl and reviewed the scientific literature for similar cases.

Findings: We describe the case of a 1.

S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation.

A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications.

Primary headache and migraine in headache specialists - does personal history of doctors matter?

Objective: Migraine is a common disorder affecting more than 10% of the population. The prevalence of migraine among physicians and, in particular, among headache specialists is widely unknown as is the impact of suffering from migraine on the attitudes towards migraine and on treatment recommendations of physicians. We designed a survey among headache specialists and neurologists and compared the results to general pain specialists and general practitioners.

Design and evolution of an enzyme with a non-canonical organocatalytic mechanism.

The combination of computational design and laboratory evolution is a powerful and potentially versatile strategy for the development of enzymes with new functions. However, the limited functionality presented by the genetic code restricts the range of catalytic mechanisms that are accessible in designed active sites. Inspired by mechanistic strategies from small-molecule organocatalysis, here we report the generation of a hydrolytic enzyme that uses N-methylhistidine as a non-canonical catalytic nucleophile.

Genomic discovery of ion channel genes in the central nervous system of the lamprey Petromyzon marinus.

The lamprey is a popular animal model for a number of types of neurobiology studies, including organization and operation of locomotor and respiratory systems, behavioral recovery following spinal cord injury (SCI), cellular and synaptic neurophysiology, comparative neuroanatomy, neuropharmacology, and neurodevelopment. Yet relatively little work has been done on the molecular underpinnings of nervous system function in lamprey. This is due in part to a paucity of gene information for some of the most fundamental proteins involved in neural activity: ion channels.

The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides.

Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods for amide bond formation, including those that are catalyzed by enzymes, is therefore of significant interest. The ATP-dependent amide bond synthetase (ABS) enzyme McbA, from Marinactinospora thermotolerans, catalyzes the formation of amides as part of the biosynthetic pathway towards the marinacarboline secondary metabolites.

An Aminocaprolactam Racemase from Ochrobactrum anthropi with Promiscuous Amino Acid Ester Racemase Activity.

The kinetic resolution of amino acid esters (AAEs) is a useful synthetic strategy for the preparation of single-enantiomer amino acids. The development of an enzymatic dynamic kinetic resolution (DKR) process for AAEs, which would give a theoretical yield of 100 % of the enantiopure product, would require an amino acid ester racemase (AAER); however, no such enzyme has been described. We have identified low AAER activity of 15 U mg in a homologue of a PLP-dependent α-amino ϵ-caprolactam racemase (ACLR) from Ochrobactrum anthropi.

Structural Basis for Phospholyase Activity of a Class III Transaminase Homologue.

Pyridoxal-phosphate (PLP)-dependent enzymes catalyse a remarkable diversity of chemical reactions in nature. A1RDF1 from Arthrobacter aurescens TC1 is a fold type I, PLP-dependent enzyme in the class III transaminase (TA) subgroup. Despite sharing 28 % sequence identity with its closest structural homologues, including β-alanine:pyruvate and γ-aminobutyrate:α-ketoglutarate TAs, A1RDF1 displayed no TA activity.

Evaluation of guideline-adherent treatment in cluster headache.

Background: Several treatment guidelines exist for cluster headache. However, it is not yet known how many cluster headache patients are treated according to these guidelines.

Methods: We enrolled 434 cluster headache patients with confirmed diagnosis referred to two tertiary pain centers.

Musical ability is associated with enhanced auditory and visual cognitive processing.

Background: Musical ability has always been linked to enhanced cognitive and intellectual skills. We were interested in the relation between musical ability and short-time cognitive processing as measured by event-related potentials, in particular in visual processing, since previous studies have already suggested such a link for acoustic cognitive processing. We measured auditory and visual event-related potentials as elicited by an oddball paradigm in 20 healthy subjects (10 musicians and 10 non-musicians; 10 female; mean age 24 ± 2 years).

Sleep apnea in patients with cluster headache: a case-control study.

Objective: Polysomnographic investigations have shown an unspecific association between cluster headache and obstructive sleep apnea syndrome. The aim of this study was to investigate this association in a cluster episode compared with a symptom free interval, and to further characterize this association.

Methods: We investigated 42 patients with episodic (n = 26) or chronic (n = 16) cluster headache by means of polygraphic screening for sleep apnea and compared the data to 28 healthy control subjects matched according to age, sex, and BMI.

Exploding head syndrome: six new cases and review of the literature.

Background: Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.

Methods: We present six new cases extending the clinical experience with the syndrome. We also reviewed all available cases from the scientific literature and evaluated the typical features of EHS.