The role of hypertension in the relationship between leisure screen time, physical activity and migraine: a 2-sample Mendelian randomization study.

Background: The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality.

Methods: Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set.

Molecular mechanism of contactin 2 homophilic interaction.

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (K ∼200 nM).

SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1α positive feedback loop.

Migraine is the second highest cause of disability worldwide, bringing a huge socioeconomic burden. Improving mitochondrial function has promise as an effective treatment strategy for migraine. Szeto-Schiller peptide (SS-31) is a new mitochondria-targeted tetrapeptide molecule that has been shown to suppress the progression of diseases by restoring mitochondrial function, including renal disease, cardiac disease, and neurodegenerative disease.

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine.

Background: Targeting metabolic pathways has emerged as a new migraine treatment strategy as researchers realize the critical role metabolism plays in migraine. Activated inflammatory cells undergo metabolic reprogramming and rely on glycolysis to function. The objective of this study was to investigate the glycolysis changes in the experimental model of migraine and the effect of glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) in the pathophysiology of migraine.

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs.

The global prevalence and ethnic heterogeneity of iron-refractory iron deficiency anaemia.

Background: Iron-refractory iron deficiency anaemia (IRIDA) is an autosomal recessive iron deficiency anaemia caused by mutations in the TMPRSS6 gene. Iron deficiency anaemia is common, whereas IRIDA is rare. The prevalence of IRIDA is unclear.

Chemically targeting the redox switch in AP1 transcription factor ΔFOSB.

The AP1 transcription factor ΔFOSB, a splice variant of FOSB, accumulates in the brain in response to chronic insults such as exposure to drugs of abuse, depression, Alzheimer's disease and tardive dyskinesias, and mediates subsequent long-term neuroadaptations. ΔFOSB forms heterodimers with other AP1 transcription factors, e.g.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.

Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine.

The localization and lateralization of fear aura and its surgical prognostic value in patients with focal epilepsy.

Objective: Fear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug-resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy.

Methods: The occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy.

One-step emulsification for controllable preparation of ethyl cellulose microcapsules and their sustained release performance.

A simple and versatile strategy for controlled production of monodisperse ethyl cellulose (EC) microcapsules by a single-stage emulsification method has been developed. Monodisperse oil-in-water emulsions, obtained by a microfluidic device, are used as templates for preparing EC microcapsules. Oil-soluble ethyl acetate (EA) is miscible with water, so the interfacial mass transfer between EA and water occurs sufficiently, which leads to water molecules pass through the phase interface and diffuse into emulsion interior.

The Nocebo Response in Pharmacologic Treatments of Primary Headache: A Systematic Review and Meta-Analysis.

The nature and magnitude of nocebo responses in primary headache disorders are still unknown. To assess the distribution and possible predictors of nocebo responses in primary headache treatments, databases, including PubMed, EMBASE, and Cochrane Library were searched from 1988 to December 31, 2020, for parallel-group, double-blind, randomized placebo-controlled trials of pharmacologic treatments of primary headaches. The nocebo responses were calculated using a random effects meta-analysis model.

A new mutation in the GNAL gene in familial dystonia presenting with mental symptoms.

GNAL mutations (DYT25) have lately been identified as the firstly proven cause of focal adult-onset dystonia. We report here a new mutation in the GNAL gene in two siblings with dystonia. The new mutation is called NM 001,142,339:c.

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats.

Background: The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission.

The global carrier frequency and genetic prevalence of Upshaw-Schulman syndrome.

Background: Upshaw-Schulman syndrome (USS) is an autosomal recessive disease characterized by thrombotic microangiopathies caused by pathogenic variants in ADAMTS13. We aimed to (1) curate the ADAMTS13 gene pathogenic variant dataset and (2) estimate the carrier frequency and genetic prevalence of USS using Genome Aggregation Database (gnomAD) data.

Methods: Studies were comprehensively retrieved.

Efficacy of Repetitive Transcranial Magnetic Stimulation Combined with Botulinum Toxin Type A for Benign Essential Blepharospasm Patients Accompanied by Anxiety and Depression.

Objective: To evaluate the improvement of motor, anxiety, and depression in patients with blepharospasm with the use of botulinum toxin type A (BTX-A) and repetitive transcranial magnetic stimulation (rTMS).

Methods: A total of 63 BEB patients accompanied by anxiety/depression were enrolled, among which 28 patients were treated with the injection of botulinum toxin type A (BTX-A) alone, while 35 patients were treated with BTX-A injection combined with rTMS. All patients were followed up for 6 months, and the overall efficacy was evaluated.

Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges.

Hevin is secreted by astrocytes and its synaptogenic effects are antagonized by the related protein, SPARC. Hevin stabilizes neurexin-neuroligin transsynaptic bridges in vivo. A third protein, membrane-tethered MDGA, blocks these bridges.

Highly Conserved Molecular Features in IgLONs Contrast Their Distinct Structural and Biological Outcomes.

Neuronal growth regulator 1 (NEGR1) and neurotrimin (NTM) are abundant cell-surface proteins found in the brain and form part of the IgLON (Immunoglobulin LSAMP, OBCAM, Neurotrimin) family. In humans, NEGR1 is implicated in obesity and mental disorders, while NTM is linked to intelligence and cognitive function. IgLONs dimerize homophilically and heterophilically, and they are thought to shape synaptic connections and neural circuits by acting in trans (spanning cellular junctions) and/or in cis (at the same side of a junction).

Screening Gene Mutations in Chinese Patients With Benign Essential Blepharospasm.

This study aimed to screen gene mutations in Chinese patients with benign essential blepharospasm (BEB) to understand its etiology. Twenty BEB patients diagnosed by clinical manifestations between April 2015 and October 2015 were enrolled. All the cases were investigated by questionnaires about general conditions, social behavioral factors, environmental factors, psychological factors, genetic factors, and previous diseases.

Botulinum toxin relieves anxiety and depression in patients with hemifacial spasm and blepharospasm.

Objective: To explore the efficacy of botulinum toxin type A (BTX-A) therapy in relieving anxiety and depression in patients with hemifacial spasm (HFS) and benign essential blepharospasm (BEB).

Patients And Method: Ninety idiopathic HFS patients and 90 BEB patients were enrolled. The anxiety and depression status were evaluated by self-rating anxiety scale (SAS) and self-rating depression scale (SDS), respectively, before and after the injection of BTX-A.

Mycobacterium tuberculosis type III-A CRISPR/Cas system crRNA and its maturation have atypical features.

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems are prokaryotic adaptive immune systems against invading nucleic acids. CRISPR locus variability has been exploited in evolutionary and epidemiological studies of Mycobacterium tuberculosis, the causative agent of tuberculosis, for over 20 yr, yet the biological function of this type III-A system is largely unexplored. Here, using cell biology and biochemical, mutagenic, and RNA-seq approaches, we show it is active in invader defense and has features atypical of type III-A systems: mature CRISPR RNA (crRNA) in its crRNA-CRISPR/Cas protein complex are of uniform length (∼71 nt) and appear not to be subject to 3'-end processing after Cas6 cleavage of repeat RNA 8 nt from its 3' end.

Transcription factor 7 like 2 promotes oligodendrocyte differentiation and remyelination.

Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination.

Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (), β-arrestin 2 () and kinesin family member 1C (), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS.

A new comorbidity model and the common pathological mechanisms of migraine and epilepsy.

A bi-directional relationship between epilepsy and migraine has been widely reported in epidemiological and clinical studies, but the mechanisms of interaction between these disorders have not been fully examined using animal models. The aim of the present study was to develop a new comorbidity model of migraine and epilepsy. Nociception was induced by applying an inflammatory soup to the dura mater; this procedure resulted in nociception similar to that expressed in inflammatory disorders such as migraine.

Structure and function of Mycobacterium smegmatis 7-keto-8-aminopelargonic acid (KAPA) synthase.

The biotin biosynthesis pathway is an attractive target for development of novel drugs against mycobacterial pathogens, however there are as yet no suitable inhibitors that target this pathway in mycobacteria. 7-Keto-8-aminopelargonic acid synthase (KAPA synthase, BioF) is the enzyme which catalyzes the first committed step of the biotin synthesis pathway, but both its structure and function in mycobacteria remain unresolved. Here we present the crystal structure of Mycobacterium smegmatis BioF (MsBioF).