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1.
Nat Commun ; 12(1): 5309, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34493726

ABSTRACT

Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.


Subject(s)
Adrenal Gland Neoplasms/genetics , Adrenal Glands/metabolism , Membrane Glycoproteins/genetics , Neoplasm Proteins/genetics , Neuroblastoma/genetics , Receptor, trkB/genetics , Transcriptome , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/mortality , Adrenal Gland Neoplasms/pathology , Adrenal Glands/pathology , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Differentiation , Cell Nucleus/genetics , Cell Nucleus/metabolism , Child, Preschool , Chromaffin Cells/metabolism , Chromaffin Cells/pathology , Early Diagnosis , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Membrane Glycoproteins/metabolism , Mice , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Neuroblastoma/metabolism , Neuroblastoma/mortality , Neuroblastoma/pathology , Receptor, trkB/metabolism , Risk Assessment , Single-Cell Analysis , Species Specificity , Survival Analysis
2.
Biochemistry (Mosc) ; 82(4): 521-528, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28371610

ABSTRACT

Exogenous short biologically active peptides epitalon (Ala-Glu-Asp-Gly), bronchogen (Ala-Glu-Asp-Leu), and vilon (Lys-Glu) at concentrations 10-7-10-9 M significantly influence growth, development, and differentiation of tobacco (Nicotiana tabacum) callus cultures. Epitalon and bronchogen, in particular, both increase growth of calluses and stimulate formation and growth of leaves in plant regenerants. Because the regulatory activity of the short peptides appears at low peptide concentrations, their action to some extent is like that of the activity of phytohormones, and it seems to have signaling character and epigenetic nature. The investigated peptides modulate in tobacco cells the expression of genes including genes responsible for tissue formation and cell differentiation. These peptides differently modulate expression of CLE family genes coding for known endogenous regulatory peptides, the KNOX1 genes (transcription factor genes) and GRF (growth regulatory factor) genes coding for respective DNA-binding proteins such as topoisomerases, nucleases, and others. Thus, at the level of transcription, plants have a system of short peptide regulation of formation of long-known peptide regulators of growth and development. The peptides studied here may be related to a new generation of plant growth regulators. They can be used in the experimental botany, plant molecular biology, biotechnology, and practical agronomy.


Subject(s)
Gene Expression Regulation, Plant/drug effects , Genes, Plant , Nicotiana/genetics , Oligopeptides/drug effects , Real-Time Polymerase Chain Reaction
3.
Ontogenez ; 45(1): 28-41, 2014.
Article in Russian | MEDLINE | ID: mdl-25720263

ABSTRACT

In this study, the morphological and cytoembryological analyses of the tomato plants transformed with the genes encoding chitin-binding proteins (ac and RS-intron-Shir) from Amaranthus caudatus L. andA. retroflexus L., respectively, as well as the gene amp2 encoding hevein-like antimicrobial peptides from Stellaria media L., have been performed. The transgenic lines were adapted to soil and grown the greenhouse. The analysis of putative transgenic tomato plants revealed several lines that did not differ phenotypically from the wild type plants and three lines with disruption in differentiation of the inflorescence shoot and the flower, as well as the fruit formation (modified plants of each line were transformed with a single gene as noted before). Abnormalities in the development of the generative organs were maintained for at least six vegetative generations. These transgenic plants were shown to be defective in the mail gametophyte formation, fertilization, and, consequently, led to parthenocarpic fruits. The detailed analysis of growing ovules in the abnormal transgenic plants showed that the replacement tissue was formed and proliferated instead of unfertilized embryo sac. The structure of the replacement tissue differed from both embryonic and endosperm tissue of the normal ovule. The formation of the replacement tissue occurred due to continuing proliferation of the endothelial cells that lost their ability for differentiation. The final step in the development of the replacement tissue was its death, which resulted in the cell lysis. The expression of the genes used was confirmed by RT-PCR in all three lines with abnormal phenotype, as well as in several lines that did not phenotypically differ from the untransformed control. This suggests that abnormalities in the organs of the generative sphere in the transgenic plants do not depend on the expression of the foreign genes that were introduced in the tomato genome. Here, we argue that agrobacterial transformation affects, directly or indirectly, expression of genes encoding for transcription factors that can activate a gene cascade responsible for the normal plant development.


Subject(s)
Amaranthus/genetics , Antimicrobial Cationic Peptides , Carrier Proteins , Flowers , Meristem , Plant Proteins , Plants, Genetically Modified , Solanum lycopersicum , Antimicrobial Cationic Peptides/biosynthesis , Antimicrobial Cationic Peptides/genetics , Carrier Proteins/biosynthesis , Carrier Proteins/genetics , Flowers/cytology , Flowers/genetics , Flowers/metabolism , Gene Expression , Solanum lycopersicum/cytology , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Meristem/cytology , Meristem/genetics , Meristem/metabolism , Plant Proteins/biosynthesis , Plant Proteins/genetics , Plants, Genetically Modified/cytology , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism
4.
Izv Akad Nauk Ser Biol ; (6): 586-96, 2014.
Article in Russian | MEDLINE | ID: mdl-25739307

ABSTRACT

The influence of explant type as well as of the type of growth regulators and concentration on callus induction processes and somatic organogenesis of shoots was studied in vitro on four tomato genotypes of Russian breeding. Cytological study of callus tissue was conducted. It was established that tomato varieties possess a substantially greater ability to indirect shoot organogenesis compared with the F1 hybrid. The highest frequency of somatic organogenesis of shoots, as well as their number per explant, was observed for most of the genotypes studied during the cultivation of cotyledons on Murashige-Skoog culture medium containing 2 mg/l of zeatin in combination with 0.1 mg/l of 3-indoleacetic acid. An effective protocol of indirect somatic organogenesis of shoots from different explants of tomato varieties with a frequency of more than 80% was developed.


Subject(s)
Culture Media , Organogenesis, Plant/genetics , Plant Growth Regulators/pharmacology , Plant Shoots , Solanum lycopersicum , Culture Media/chemistry , Genotype , Solanum lycopersicum/drug effects , Solanum lycopersicum/genetics , Solanum lycopersicum/growth & development , Organogenesis, Plant/drug effects , Plant Development/drug effects , Plant Development/genetics , Plant Shoots/drug effects , Plant Shoots/genetics , Plant Shoots/growth & development , Regeneration , Seeds/drug effects , Seeds/genetics , Seeds/growth & development
5.
Science ; 340(6130): 273, 2013 Apr 19.
Article in English | MEDLINE | ID: mdl-23599463

ABSTRACT

Conrad et al. (Reports, 10 August 2012, p. 742) reported a doubling of RNA polymerase II (Pol II) occupancy at X-linked promoters to support 5' recruitment as the key mechanism for dosage compensation in Drosophila. However, they employed an erroneous data-processing step, overestimating Pol II differences. Reanalysis of the data fails to support the authors' model for dosage compensation.


Subject(s)
DNA Polymerase II/metabolism , Dosage Compensation, Genetic , Drosophila Proteins/metabolism , Drosophila/genetics , Genes, X-Linked , Promoter Regions, Genetic , X Chromosome/genetics , Animals , Female , Male
6.
Genetika ; 46(10): 1430-4, 2010 Oct.
Article in Russian | MEDLINE | ID: mdl-21254570

ABSTRACT

For the dosage compensation to occur, genes on the single male X chromosomes in Drosophila must be selectively bound and acetylated by the ribonucleoprotein complex called MSL complex. It remained unknown how such exquisite specificity is achieved, and whether specific DNA sequences were involved. In the present work we demonstrate that it is transcription of the gene on the X chromosome that is important for MSL targeting, irrespective of gene origin and DNA sequence.


Subject(s)
Chromosomes, Insect/metabolism , Dosage Compensation, Genetic/physiology , Drosophila Proteins/metabolism , Ribonucleoproteins/metabolism , Transcription, Genetic/physiology , X Chromosome/metabolism , Animals , Chromosomes, Insect/genetics , Drosophila Proteins/genetics , Drosophila melanogaster , Male , Ribonucleoproteins/genetics , X Chromosome/genetics
7.
Izv Akad Nauk Ser Biol ; (6): 669-75, 2007.
Article in Russian | MEDLINE | ID: mdl-19768960

ABSTRACT

The effect of the parameters of biolistic transformation (rupture disk pressure of helium, vacuum pressure, stopping screen to target tissue distance, material (gold or tungsten) and size of particles, and duration of explant culturing before bombardment) on the level of transient expression of GFP reporter gene was studied in barley embryos. The highest transient expression was observed after explant preincubation for 12-14 days and bombardment with 1 microm gold particles at the helium pressure of 61.24-74.85 atm, vacuum pressure of 0.064 atm, and distance to target of 9 cm.


Subject(s)
Biolistics/methods , Gene Expression , Genes, Reporter , Green Fluorescent Proteins/genetics , Hordeum/genetics , Plants, Genetically Modified , Transformation, Genetic , Helium , Pressure , Seeds/genetics
8.
Urologiia ; (1): 19-22, 2005.
Article in Russian | MEDLINE | ID: mdl-15776826

ABSTRACT

The study was made to improve preoperative diagnosis of the stage of prostatic cancer (PC) to raise efficacy of subsequent treatment. A total of 152 patients entered the study who had undergone in 1997-2002 a radical prostatectomy for local PC. Basing on pathomorphological findings, the patients were divided into two groups: with localized CP (68 patients) and spread CP (84 patients). The comparison of clinical and pathomorphological diagnosis in the same patients demonstrated that there is a correlation between them, therefore it is possible to predict pathomorphological diagnosis at the stage of clinical diagnosis. The formula of establishment of a pathomorphological stage of the disease has been developed and its efficacy was tested in 30 control patients. The mathematical model of complex evaluation of the symptoms allows in 81% of cases to correctly determine the spread of CP while examination of separate symptoms provides a correct diagnosis in less than half the cases. The model can prognosticate radicality of the future operative intervention and duration of recurrence-free course and, consequently, to reduce the rate of intra- and postoperative complications and design further treatment policy.


Subject(s)
Prostatic Neoplasms/diagnosis , Humans , Male , Models, Theoretical , Neoplasm Staging , Prognosis , Prostate/pathology , Prostatic Neoplasms/surgery
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