scholarly journals TNNI1 Mutated in Autosomal Dominant Proximal Arthrogryposis

2021 ◽  
Vol 8 (1) ◽  
pp. e649
Author(s):  
Yukako Nishimori ◽  
Aritoshi Iida ◽  
Masashi Ogasawara ◽  
Mariko Okubo ◽  
Yuki Yonenobu ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Genomic Analysis ◽  
Microscopic Analysis ◽  
Electron Microscopic ◽  
Japanese Family ◽  
Genetic Studies ◽  
C Terminus ◽  
The Family

ObjectivesThe main objective of this case report is to identify a gene associated with a Japanese family with autosomal dominant arthrogryposis.MethodsWe performed clinicopathologic diagnosis and genomic analysis using trio-based exome sequencing.ResultsA 14-year-old boy had contractures in the proximal joints, and the serum creatine kinase level was elevated. Muscle biopsy demonstrated a moth-eaten appearance in some type 1 fibers, and electron microscopic analysis revealed that type 1 fibers had Z disk streaming. We identified a heterozygous nonsense variant, c.523A>T (p.K175*), in TNNI1 in the family.DiscussionThe altered amino acid residue is within the tropomyosin-binding site near the C-terminus, in a region homologous to the variational hotspot of Troponin I2 (TNNI2), which is associated with distal arthrogryposis type 1 and 2b. Compared with patients with TNNI2 variants, our patient had a milder phenotype and proximal arthrogryposis. We report here a case of proximal arthrogryposis associated with a TNNI1 nonsense variant, which expands the genetic and clinical spectrum of this disease. Further functional and genetic studies are required to clarify the role of TNNI1 in the disease.

scholarly journals The role of genetic research with family design in the study of affective disorders

2019 ◽  
pp. 106-108
Author(s):  
E. D. Kasyanov ◽  
G. E. Maso ◽  
A. O. Kibitov
Keyword(s):  
Affective Disorders ◽  
Bipolar Affective Disorder ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Important Criterion ◽  
Genetic Studies ◽  
The Family ◽  
Polygenic Diseases ◽  
Potential Biomarkers

Affective disorders (recurrent depressive disorder and bipolar affective disorder) are multifactorial and polygenic diseases, which suggests the involvement of multiple neurobiological mechanisms. The phenotype of affective disorders is a heterogeneous group of clinically similar psychopathological symptoms, which also makes it difficult to detect potential biomarkers and new therapeutic targets. To study families at high risk of developing affective disorders using both clinical and molecular genetic approaches can help to study the neurobiological basis of depressive conditions, as well as to identify endophenotypes of affective disorders. The most important criterion for an endophenotype is its heritability, which can be proved only within the framework of the family design of the study. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.

scholarly journals DSS1 and ssDNA regulate oligomerization of BRCA2

2020 ◽  
Vol 48 (14) ◽  
pp. 7818-7833 ◽  
Author(s):  
Hang Phuong Le ◽  
Xiaoyan Ma ◽  
Jorge Vaquero ◽  
Megan Brinkmeyer ◽  
Fei Guo ◽  
...  
Keyword(s):  
Replication Fork ◽  
Microscopic Analysis ◽  
Filament Formation ◽  
Electron Microscopic ◽  
Microscopic Imaging ◽  
Cellular Events ◽  
Self Association ◽  
Oligomeric Forms

Abstract The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic analysis (3), but the functional significance of the different BRCA2 assemblies remains to be determined. Here, we used biochemistry and electron microscopic imaging to demonstrate that the multimerization of BRCA2 is counteracted by DSS1 and ssDNA. When validating the findings, we identified three self-interacting regions and two types of self-association, the N-to-C terminal and the N-to-N terminal interactions. The N-to-C terminal self-interaction of BRCA2 is sensitive to DSS1 and ssDNA. The N-to-N terminal self-interaction is modulated by ssDNA. Our results define a novel role of DSS1 to regulate BRCA2 in an RPA-independent fashion. Since DSS1 is required for BRCA2 function in recombination, we speculate that the monomeric and oligomeric forms of BRCA2 might be active for different cellular events in recombinational DNA repair and replication fork stabilization.

scholarly journals Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3447-3449 ◽  
Author(s):  
Melanie J. Percy ◽  
Matthew J. S. Gillespie ◽  
Geraldine Savage ◽  
Anne E. Hughes ◽  
Mary Frances McMullin ◽  
...  
Keyword(s):  
Cytochrome B5 ◽  
Novel Mutations ◽  
Genetic Studies ◽  
Cytochrome B5 Reductase ◽  
The United Kingdom ◽  
The Family ◽  
Exon 9 ◽  
Nadh Cytochrome ◽  
Reduced Nicotinamide Adenine Dinucleotide

In 1943, the first description of familial idiopathic methemoglobinemia in the United Kingdom was reported in 2 members of one family. Five years later, Quentin Gibson (then of Queen's University, Belfast, Ireland) correctly identified the pathway involved in the reduction of methemoglobin in the family, thereby describing the first hereditary trait involving a specific enzyme deficiency. Recessive congenital methemoglobinemia (RCM) is caused by a deficiency of reduced nicotinamide adenine dinucleotide (NADH)–cytochrome b5 reductase. One of the original propositi with the type 1 disorder has now been traced. He was found to be a compound heterozygote harboring 2 previously undescribed mutations in exon 9, a point mutation Gly873Ala predicting a Gly291Asp substitution, and a 3-bp in-frame deletion of codon 255 (GAG), predicting loss of glutamic acid. A brother and a surviving sister are heterozygous; each bears one of the mutations. Thirty-three different mutations have now been recorded for RCM. The original authors' optimism that RCM would provide material for future genetic studies has been amply justified.

A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

2005 ◽  
Vol 125 (11) ◽  
pp. 1189-1194 ◽  
Author(s):  
Yoshihiro Noguchi ◽  
Takatoshi Yashima ◽  
Akio Hatanaka ◽  
Masamichi Uzawa ◽  
Michio Yasunami ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Autosomal Dominant ◽  
Low Frequency ◽  
Wolfram Syndrome ◽  
Sensorineural Hearing ◽  
Syndrome Type ◽  
Japanese Family

scholarly journals Expression and Differential Intracellular Localization of Two Major Forms of Human 8-Oxoguanine DNA Glycosylase Encoded by Alternatively Spliced OGG1 mRNAs

1999 ◽  
Vol 10 (5) ◽  
pp. 1637-1652 ◽  
Author(s):  
Kenichi Nishioka ◽  
Toshio Ohtsubo ◽  
Hisanobu Oda ◽  
Toshiyuki Fujiwara ◽  
Dongchon Kang ◽  
...  
Keyword(s):  
Intracellular Localization ◽  
Nuclear Extract ◽  
Dna Glycosylase ◽  
Mitochondrial Targeting ◽  
Electron Microscopic ◽  
C Terminus ◽  
Alternatively Spliced ◽  
Targeting Signal ◽  
Processed Form

We identified seven alternatively spliced forms of human 8-oxoguanine DNA glycosylase (OGG1) mRNAs, classified into two types based on their last exons (type 1 with exon 7: 1a and 1b; type 2 with exon 8: 2a to 2e). Types 1a and 2a mRNAs are major in human tissues. Seven mRNAs are expected to encode different polypeptides (OGG1–1a to 2e) that share their N terminus with the common mitochondrial targeting signal, and each possesses a unique C terminus. A 36-kDa polypeptide, corresponding to OGG1–1a recognized only by antibodies against the region containing helix-hairpin-helix-PVD motif, was copurified from the nuclear extract with an activity introducing a nick into DNA containing 8-oxoguanine. A 40-kDa polypeptide corresponding to a processed form of OGG1–2a was detected in their mitochondria using antibodies against its C terminus. Electron microscopic immunocytochemistry and subfractionation of the mitochondria revealed that OGG1–2a locates on the inner membrane of mitochondria. Deletion mutant analyses revealed that the unique C terminus of OGG1–2a and its mitochondrial targeting signal are essential for mitochondrial localization and that nuclear localization of OGG1–1a depends on the NLS at its C terminus.

scholarly journals Stimulating and toxic effects of copper and cobalt nanopowders on rice seedlings

2020 ◽  
pp. 42-52
Author(s):  
I. V. Obidina ◽  
G. I. Churilov ◽  
S. D. Polischuk ◽  
A. Yu. Tarara ◽  
S. S. Gomozova ◽  
...  
Keyword(s):  
Chemical Nature ◽  
Microscopic Analysis ◽  
Rice Seedlings ◽  
Electron Microscopic ◽  
Regional Center ◽  
Scientific Equipment ◽  
Wide Range ◽  
Object Of Study ◽  
Positive Effect

Metal nanopowders have a stimulating effect on the growth and development of plants. The biological activity of nanoparticles depends on size, concentration, and chemical composition. Nanoparticles require further study because they have a wide range of applications in medicine and agriculture. Being biocompatible, copper and cobalt can play the role of growth stimulant, are not toxic and can be used for contact with living systems. The object of study was rice, as an economically important culture. The study addressed the effect of cobalt and copper nanoparticles on the germination and development of rice seedlings. The optimal concentration of ultrafine solutions of these nanopowders for pre-sowing treatment of seeds was determined. Although copper and cobalt have different chemical nature, the nanoparticles show similar impact and doze-dependent effect. Minimum concentrations of the nanoparticles had a positive effect on the morphological and biometric indicators of sprouts. The activity of oxidase enzymes was measured and it showed a reversible nature of oxidative stress. An increase in superoxide dismutase activity and a decrease in catalase activity by less than 30% indicates the stress resistance of rice sprouts and the absence of phytotoxic effects of the nanopowders. The presence of these metals in the seedling homogenate was determined to define the toxic effect. The electron microscopic analysis of the partition of metals in the tissues of experimental plants did not reveal significant deviations from control values. The experiments were performed using scientific equipment of Regional Center for Collective Use of Probe Microscopy in Ryazan State Radio Engineering University.

Unstable inheritance of maize B-type chromosomes that lack centric heterochromatin

Genome ◽  
2006 ◽  
Vol 49 (5) ◽  
pp. 420-431 ◽  
Author(s):  
Wayne R Carlson
Keyword(s):  
B Chromosome ◽  
Chromosome 9 ◽  
Pollen Mitosis ◽  
Genetic Studies ◽  
Telocentric Chromosome ◽  
Deletion Derivative ◽  
Translocation Heterozygote ◽  
Second Pollen Mitosis

The B chromosome of maize undergoes frequent non-disjunction at the second pollen mitosis. In B–A translocations, the B–A chromosome retains the capacity for non-disjunction. We have collected deletion-derivative TB-9Sb stocks. One derivative, the "type 1 telocentric", has a B–9 chromosome that lacks centric heterochromatin. It produces few recessive (non-disjunctional) phenotypes in pollen parent testcrosses of the translocation heterozygote, 9 9–B telo B–9. The finding helped demonstrate the role of centric heterochromatin in non-disjunction. An isochromo some derivative of the type 1 telocentric was also recovered. It was tested in the 9–B 9–B iso B–9 constitution. This is equivalent to 9 9–B telo B–9 in terms of chromosome 9 dosage. Surprisingly, crosses with the isochromosome gave significant levels of recessive phenotypes. In addition, high levels of variegated phenotypes were found. Recently, a circumstance was found that makes inheritance of the type 1 telocentric chromosome somewhat similar to that of the isochromosome. Crosses with hypoploid 9–B 9–B telo B–9 plants showed significant levels of recessive and variegated phenotypes. These crosses were investigated to help explain the source(s) of the phenotypes. Cytological and genetic studies were performed. Centric misdivision was found to account for the variegated phenotypes. A mixture of conventional B non-disjunction and centric misdivision produced the recessive phenotypes. The significance of conventional non-disjunction in the absence of centric heterochromatin is discussed.Key words: cytogenetics, B chromosome, centromere, maize.

scholarly journals A novel mutation in the human mineralocorticoid receptor gene in a Japanese family with autosomal-dominant pseudohypoaldosteronism type 1

2016 ◽  
Vol 25 (4) ◽  
pp. 135-138 ◽  
Author(s):  
Yoshimi Nishizaki ◽  
Makoto Hiura ◽  
Hidetoshi Sato ◽  
Yohei Ogawa ◽  
Akihiko Saitoh ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Receptor Gene ◽  
Japanese Family ◽  
Pseudohypoaldosteronism Type

scholarly journals Structure and Capsid Association of the Herpesvirus Large Tegument Protein UL36

2010 ◽  
Vol 84 (18) ◽  
pp. 9408-9414 ◽  
Author(s):  
William W. Newcomb ◽  
Jay C. Brown
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Microscopic Analysis ◽  
Molecular Weight Protein ◽  
High Molecular Weight Protein ◽  
Electron Microscopic ◽  
Tegument Proteins ◽  
Weight Protein ◽  
Simplex Virus

ABSTRACT The tegument of all herpesviruses contains a high-molecular-weight protein homologous to herpes simplex virus (HSV) UL36. This large (3,164 amino acids), essential, and multifunctional polypeptide is located on the capsid surface and present at 100 to 150 copies per virion. We have been testing the idea that UL36 is important for the structural organization of the tegument. UL36 is proposed to bind directly to the capsid with other tegument proteins bound indirectly by way of UL36. Here we report the results of studies carried out with HSV type 1-derived structures containing the capsid but lacking a membrane and depleted of all tegument proteins except UL36 and a second high-molecular-weight protein, UL37. Electron microscopic analysis demonstrated that, compared to capsids lacking a tegument, these capsids (called T36 capsids) had tufts of protein located at the vertices. Projecting from the tufts were thin, variably curved strands with lengths (15 to 70 nm) in some cases sufficient to extend across the entire thickness of the tegument (∼50 nm). Strands were sensitive to removal from the capsid by brief sonication, which also removed UL36 and UL37. The findings are interpreted to indicate that UL36 and UL37 are the components of the tufts and of the thin strands that extend from them. The strand lengths support the view that they could serve as organizing features for the tegument, as they have the potential to reach all parts of the tegument. The variably curved structure of the strands suggests they may be flexible, a property that could contribute to the deformable nature of the tegument.

Electron Microscopic Analysis of Subcellular Distribution and Translocation of Ca ION in Human Platelet

1979 ◽  
Author(s):  
M. Kazama ◽  
T. Daimon ◽  
K. Nakamura ◽  
J. Matsuda ◽  
I. Naito ◽  
...  
Keyword(s):  
Subcellular Distribution ◽  
Human Platelet ◽  
Microscopic Analysis ◽  
Clot Retraction ◽  
Potassium Oxalate ◽  
Electron Microscopic ◽  
Platelet Suspension ◽  
Dense Bodies ◽  
Transmission Electron

For the analysis of the subcellular distribution of Ca ion in human platelet, the washed platelet suspension was fixed in the potassium antimonate-OsO4 method or in the potassium oxalate-glutaraldehyde method without post-fixation with OSO4. The STEM-images were observed with scanning image system fitted with the transmission electron microscope without electron staining.The dense deposition of antimonate or oxalate was found in plasmalemma, the membrane of open canalicular system, mitochondria, α-granules and dense bodies. It was revealed with the energy dispersive type electron probe x-ray microanalyzer system that the deposition of oxalate was exclusively composed of Ca.In the process of platelet aggregation with various agents, α-granules and dense bodies were expelled out together with Ca, which suggested the least role of these ion depositions in the aggregation and clot retraction. The translocation of antimonate deposits was not observed in the Verapamil-treated platelets even after the addition of aggregation agents. This phenomenon indicated that this drug inhibited the release of Ca from the Ca-storing organelles. The distribution of Ca was identical in the platelets of a case of thrombasthenia and the translocation of Ca was not observed with the addition of various aggregating agents.

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