Mosaic Qβ coats as a new presentation model

AbstractThe new protein carrier was developed on the basis of recombinant RNA phage Qβ capsid. C-terminal UGA extension of the short form of Qβ coat, so-called A1 extension, served as a target for presentation of foreign peptides on the outer surface of mosaic Qβ particles. In conditions of enhanced UGA suppression, the proportion of A1-extended to short coats in mosaic particles dropped from 48% to 14%, with an increase of the length of A1 extension. A model insertion, short preS1 epitope 31-DPAFR-35 of hepatitis B surface antigen, demonstrated superficial location on the mosaic Qβ particles and ensured specific antigenicity and immunogenicity

Red Beetroot Juice and Stamina: An Experimental Study

Introduction: Red beet juice is increasingly used in sports to enhance the endurance of athletes. To increase the specific efficiency of red beet juice, the method of its fractionation by ultrafiltration was used for the first time. The purpose of the study was to evaluate the effect of fractionated beetroot juice on the strength and endurance of laboratory rats. Methods: Male Wistar rats (6 groups; n = 10) were used in the study. In addition to the standard chow, some groups of rats 2 h before the exercises received 0.5 ml of native (RBJ) or fractionated (FRBJ) per os. Three groups of animals were trained using a motorized wheel with a gradual speed increase over four weeks: 20 min/day for five days a week. Muscle strength of animals in all groups was measured by electronic dynamometry and the endurance of rats was evaluated once a week using electrical stimulation on a racetrack which moved at a speed of 15 m/min. The test was performed an hour after the ingestion of RBJ or FRBJ. At the end of the experiment, biochemical blood indices were determined. FRBJ was prepared by the original method. Results: Most significant differences in the chemical composition of RBJ and FRBJ were found for glutamic acid, of which the content was 67.2% higher than in native juice. The greatest changes during the experiment were in the mass of the rats’ calf muscles. Regular running exercise caused a 29% increase in muscle mass. The additional increase in m. gastrocnemius was also provided y FRBJ – 12%. The combination of physical activity and the introduction of red beet derivate led to the increase of the calf muscle mass by 121% within a month. Assessing the endurance of animals by frequency of falling from the treadmill, we can conclude that compared with untrained animals, trained rats receiving FRBJ had three times higher levels of endurance. Conclusion: Consumption of FRBJ led to increased muscle strength in rats and the ergogenic effect of the product was significantly higher in combination with physical activity.publishersversionPeer reviewe

Overview of Neuromuscular Disorder Molecular Diagnostic Experience for the Population of Latvia

Funding Information: The Article Processing Charge was funded by the authors. Publisher Copyright: © American Academy of Neurology.Background and ObjectivesGenetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary diseases, including neuromuscular disorders (NMDs). The reported average prevalence of individual inherited NMDs is 3.7-4.99 per 10,000. This number varies greatly in the selected populations after applying population-wide studies. The aim of this study was to evaluate the effect of genetic analysis as the first-tier test in patients with NMD and to calculate the disease prevalence and allelic frequencies for reoccurring genetic variants.MethodsPatients with NMD from Latvia with molecular tests confirming their diagnosis in 2008-2020 were included in this retrospective study.ResultsDiagnosis was confirmed in 153 unique cases of all persons tested. Next-generation sequencing resulted in a detection rate of 37%. Two of the most common childhood-onset NMDs in our population were spinal muscular atrophy and dystrophinopathies, with a birth prevalence of 1.01 per 10,000 newborns and 2.08 per 10,000 (male newborn population), respectively. The calculated point prevalence was 0.079 per 10,000 for facioscapulohumeral muscular dystrophy type 1, 0.078 per 10,000 for limb-girdle muscular dystrophy, 0.073 per 10,000 for nondystrophic congenital myotonia, 0.052 per 10,000 for spinobulbar muscular atrophy, and 0.047 per 10,000 for type 1 myotonic dystrophy.DiscussionDNA diagnostics is a successful approach. The carrier frequencies of the common CAPN3, FKRP, SPG11, and HINT1 gene variants as well as that of the SMN1 gene exon 7 deletion in the population of Latvia are comparable with data from Europe. The carrier frequency of the CLCN1 gene variant c.2680C>T p.(Arg894Ter) is 2.11%, and consequently, congenital myotonia is the most frequent NMD in our population.publishersversionPeer reviewe

The coat of RNA phage Q#beta# as a carrier for foreign epitopes

Summary in Latvian, English, RussianAvailable from Latvian Academic Library / LAL - Latvian Academic LibrarySIGLELVLatvi

Dupuytren's Contracture Cosegregation with Limb-Girdle Muscle Dystrophy

Limb-girdle muscular dystrophies (LGMDs) is a heterogeneous group of muscular dystrophies that mostly affect the pelvic and shoulder girdle muscle groups. We report here a case of neuromuscular disease associated with Dupuytren's contracture, which has never been described before as cosegregating with an autosomal dominant type of inheritance. Dupuytren's contracture is a common disease, especially in Northern Europe. Comorbid conditions associated with Dupuytren's contracture are repetitive trauma to the hands, diabetes, and seizures, but it has never before been associated with neuromuscular disease. We hypothesize that patients may harbor mutations in genes with functions related to neuromuscular disease and Dupuytren's contracture development

Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies

Background: Limb-girdle muscular dystrophies are characterized by predominant involvement of the shoulder and pelvic girdle and trunk muscle groups. Currently, there are 31 genes implicated in the different forms of limb-girdle muscular dystrophies, which exhibit similar phenotypes and clinical overlap; therefore, advanced molecular techniques are required to achieve differential diagnosis. Methods: We investigated 26 patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 565 healthy unrelated controls from general and ethnic populations using our developed test kit based on the Illumina VeraCode GoldenGate genotyping platform, Ion AmpliSeq Inherited Disease Panel and direct sequencing of mutations in calpain 3 (CAPN3), anoctamin 5 (ANO5) and fukutin related protein (FKRP) genes. Results: Analysis revealed a homozygous CAPN3 c.550delA mutation in eight patients and three heterozygous variants in controls: dysferlin (DYSF) c.5028delG, CAPN3 c.2288A > G, and FKRP c.135C > T. Additionally, three mutations within FKRP gene were found: homozygous c.826C > A, and two compound – c.826C > A/c.404_405insT and c.826C > A/c.204_206delCTC mutations, and one mutation within CLCN1 gene – c.2680C > T p.Arg894Ter. ANO5 c.191dupA was not present. Conclusions: Genetic diagnosis was possible in 12 of 60 patients (20 %). The allele frequency of CAPN3 gene mutation c.550delA in Latvia is 0.0016 and in Lithuania - 0.0029. The allele frequencies of CAPN3 gene mutation c.2288A > G and DYSF gene mutation c.4872delG are 0.003

A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia : Case report

Publisher Copyright: © 2021 The AuthorsHereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc.). There are two main types of these disorders – hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100) occurs in 1 out of 5000–10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia – XLHED) [2]. The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4]. We report here the case of a patient with a novel inherited allelic variant in the EDA gene – NM_001399.5:c.337C>T (p.Gln113*) – in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M).publishersversionPeer reviewe

Additional file 1: of Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies

Quality parameters and description of all mutations analyzed with Illumina VeraCode GoldenGate assay. (DOCX 69 kb