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Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of th...
List causative genes for autosomal recessive forms of monogenic Parkinson's disease
we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene
Invasion of human trophoblasts is promoted through activation of wingless (Wnt) signaling, suggesting a role of the pathway in placental development and morphogenesis. However, details on the process such as involvement of canonical and/or noncanonical Wnt signaling cascades as well as their target genes are largely un...
Is there any cross-talk between the Wnt and the Akt pathways?
Chemical inhibition of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3beta and trophoblast motility but did not affect appearance of activated beta-catenin or Wnt/TCF reporter activity.
A rapid, sensitive and versatile liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed for the comprehensive analyses of the chemical constituents contained in the Chinese medicine-Venenum Bufonis (VB, Chan' Su in Chinese). LC analysis was carried out on an Agilent E...
What is the content of the METLIN database?
METLIN accurate mass matching database (DB) established according to those reported in the literatures
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor recently approved as prophylaxis in stem cell transplant recipients. In further studies of emerging drug resistance, a baseline laboratory CMV strain was serially propagated in cell culture under a combination of letermovir and ganciclovir. In eight experi...
List two indications of Letermovir?
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor recently approved as prophylaxis in stem cell transplant recipients.
Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate CD4(+) T cell depletion. Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses. We asked whether loss of Tregs during HIV infection mediates immune activation ...
Are Tregs CD4(+)CD25(+) regulatory T cells a positive regulator of the immune response?
Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses.
Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or ...
What process involves metabolite-sensing mRNAs to control gene expression?
Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation.
Widespread introduction of rotavirus vaccines has led to major reductions in the burden of rotavirus gastroenteritis worldwide. Vaccine effectiveness is diminished, however, in low income countries, that harbour the greatest burden of rotavirus attributed morbidity and mortality. Indirect effects of rotavirus vaccine (...
Is there a vaccine for rotavirus?
While rotavirus vaccine indirect effects have been demonstrated in high and middle income countries, there are very little data from low income countries where force of infection, population structures and vaccine schedules differ.
Alzheimer's disease (AD) is the most common form of dementia among the aging population and is characterized pathologically by the progressive intracerebral accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The level of proangiogenic growth factors and inflammatory mediators with proangiogenic ...
Is endostatin a proangiogenic factor?
accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic
The activity of KRAS inhibitors against brain metastases is relatively unexplored. The recent work on preclinical models and preliminary data from the ongoing KRYSTAL-1 phase Ib clinical trial support the potential of adagrasib (MRTX849) to penetrate the central nervous system and provide control of KRASG12C brain meta...
What is the mechanism of action of Adagrasib?
The activity of KRAS inhibitors against brain metastases is relatively unexplored. The recent work on preclinical models and preliminary data from the ongoing KRYSTAL-1 phase Ib clinical trial support the potential of adagrasib (MRTX849) to penetrate the central nervous system and provide control of KRASG12C brain meta...
Research in bioinformatics primarily involves collection and analysis of a large volume of genomic data. Naturally, it demands efficient storage and transfer of this huge amount of data. In recent years, some research has been done to find efficient compression algorithms to reduce the size of various sequencing data. ...
Which algorithms are used for compression of SAM files?
In this paper, we present SAMZIP, a specialized encoding scheme, for sequence alignment data in SAM (Sequence Alignment/Map) format, which improves the compression ratio of existing compression tools available.
Most of the dioxygen on earth is generated by the oxidation of water by photosystem II (PS II) using light from the sun. This light-driven, four-photon reaction is catalyzed by the Mn(4)CaO(5) cluster located at the lumenal side of PS II. Various X-ray studies have been carried out at cryogenic temperatures to understa...
Where is X-ray free electron laser used?
In this paper we report room temperature X-ray diffraction data of PS II microcrystals obtained using ultrashort (< 50 fs) 9 keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source.
This paper exploits three rounds of panel data provided by the Peruvian dataset of the Young Lives study to investigate the relationship between child cognition and obesity status among the poor. Child weight status is measured by a full distribution of child weight, from severely thin to obese, using data from a z-sco...
Is obesity related to cognitive decline?
The initial results suggests that obese children have higher cognitive scores and that this result is driven by those who are female, non-indigenous and live in an urban region.
Retrons are distinct DNA sequences that code for a reverse transcriptase (RT) similar to the RTs produced by retroviruses and other types of retroelements. Retron DNAs are commonly associated with prophage DNA and are found in the genomes of a wide variety of different bacteria. The retron RT is used to synthesize a st...
What is the msDNA?
msDNA is actually a complex of DNA, RNA, and probably protein. It is composed of a small, single-stranded DNA, linked to a small, single-stranded RNA molecule. The 5' end of the DNA molecule is joined to an internal guanosine residue of the RNA molecule by a unique 2'-5' phosphodiester bond. msDNA is produced in many ...
Women of childbearing age are at risk for developing systemic rheumatic diseases. Pregnancy can be challenging to manage in patients with rheumatic diseases for a variety of reasons including the impact of physiological and immunological changes of pregnancy on underlying disease activity, the varied presentation of rh...
What are the pregnancy outcomes in rheumatoid arthritis?
Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied.
To investigate the expression profile of protein tyrosine kinases (PTKs) in normal human epidermal keratinocytes (NHEK) in response to UVA and UVB we employed a reversed transcriptase polymerase chain reaction (PCR) approach using degenerate primers derived from the conserved catalytic domain of PTKs. Quantitative real...
Does the Abelson-related gene (ARG) gene encode for a serine kinase?
Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation.
CARM1 represses replicative senescence by methylating HuR and thereby enhancing HuR's ability to regulate the turnover of cyclin A, cyclin B1, c-fos, SIRT1, and p16 mRNAs.
Which are the main functions of the human HuR (ELAVL1) protein in fibroblasts?
CARM1 represses replicative senescence by methylating HuR and thereby enhancing HuR's ability to regulate the turnover of cyclin A, cyclin B1, c-fos, SIRT1, and p16 mRNAs.
The phase problem is inherent to crystallographic, astronomical and optical imaging where only the intensity of the scattered signal is detected and the phase information is lost and must somehow be recovered to reconstruct the object's structure. Modern imaging techniques at the molecular scale rely on utilizing novel...
Where is X-ray free electron laser used?
Modern imaging techniques at the molecular scale rely on utilizing novel coherent light sources like X-ray free electron lasers for the ultimate goal of visualizing such objects as individual biomolecules rather than crystals.
In mass spectrometry-based shotgun proteomics, protein quantification and protein identification are two major computational problems. To quantify the protein abundance, a list of proteins must be firstly inferred from the raw data. Then the relative or absolute protein abundance is estimated with quantification method...
What is the "protein inference problem"?
the protein inference problem can be regarded as a special protein quantification problem in the sense that truly present proteins are those proteins whose abundance values are not zero.
Dynamin mediates various membrane fission events, including the scission of clathrin-coated vesicles. Here, we provide direct evidence for cooperative membrane recruitment of dynamin with the BIN/amphiphysin/Rvs (BAR) proteins, endophilin and amphiphysin. Surprisingly, endophilin and amphiphysin recruitment to membrane...
What is membrane scission?
Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins.
The chronic course of endometriosis suggests that the immune system may play a role in its aetiology. There may be resistance to cell lysis, as well as an immune defect underlying endometriosis. Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular i...
What is Granzyme B?
Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis.
Bacterial artificial chromosomes (BACs) derived from genomes of large DNA viruses are powerful tools for functional delineation of viral genes. Current methods for cloning the genomes of large DNA viruses as BACs require prior knowledge of the viral sequences or the cloning of viral DNA fragments, and are tedious becau...
List the existing methods for genetic manipulation of cells.
Bacterial artificial chromosomes (BACs) derived from genomes of large DNA viruses are powerful tools for functional delineation of viral genes.
Metformin is an oral anti-diabetic drug of the biguanide class that is commonly used to treat type 2 diabetes mellitus. This study examined the molecular mechanism for the action of metformin on osteoblast differentiation. Metformin-induced mRNA expression of the osteogenic genes and small heterodimer partner (SHP) in ...
What is the mechanism of action of the biguanide class of diabetes drugs?
Metformin is an oral anti-diabetic drug of the biguanide class that is commonly used to treat type 2 diabetes mellitus.
IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE.
Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?
IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE.
Tay syndrome or IBIDS is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and abnormal brittle hair (trichothiodystrophy). Other features include photosensitivity, abnormal nails and multiple developmental defects affecting organs mainly derived from neuroectoderm. The exact prevalence...
List two common features of Tay syndrome.
Tay syndrome or IBIDS is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and abnormal brittle hair (trichothiodystrophy). Other features include photosensitivity, abnormal nails and multiple developmental defects affecting organs mainly derived from neuroectoderm.
Acetaminophen (APAP)-induced liver injury in mice is associated with activation of the coagulation cascade and deposition of fibrin in liver. Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis. PAI-1 expr...
What is the function of Plasminogen activator inhibitor 1?
Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis.
Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that ...
What are the symptoms of Rotor syndrome?
The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we ana...
The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined. Coimmunoprecipitation studies using solubilized cell extracts demonstrated that transferrin (Tf) competed with HFE for binding to the transferrin receptor (TfR) similar to previous in vitro stu...
Which conditions is caused by mutations in HFE?
The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined
Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently ...
Which type of pluripotency is Otx2 associated with?
Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency.
Scurvy is caused by prolonged dietary deficiency of vitamin C, the plasma concentration of which appears inversely related to mortality from all causes. Its clinical importance relates principally to its role as a cofactor in a number of enzyme reactions involved in collagen synthesis, dysfunction of which disrupts con...
What causes Scurvy?
Scurvy is caused by prolonged dietary deficiency of vitamin C, the plasma concentration of which appears inversely related to mortality from all causes
The natriuretic peptides are a family of structurally related peptides, products of at least three genes, which share a common, 17-membered, internal disulfide ring. Three major subtypes (A-, B-, and C-type natriuretic peptides) exist, and each is present in various tissues in multiple N- and C-terminally extended or s...
Please list the natriuretic peptides.
The recent description of the C-type peptide CNP, the major brain-derived peptide, has suggested that original studies examining the endocrine actions of the natriuretic peptides using A-type (ANP) or B-type (BNP) isoforms might have underestimated some of the biopotency of the natriuretic peptides or even failed to de...
CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we co...
What is the preferred orientation of CTCF binding sites for chromatin looping?
Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops.
The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potentially harmful effects on genome integrity owing to the fragility of the displaced DNA coding stra...
Which DNA sequences are more prone for the formation of R-loops?
Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements
Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy. Here we report an immunohistological analysis of the first FSE-affected cheetah born in France. The duration of clinical signs, of which ataxia was the ...
Please summarize Feline Spongiform Encephalopathy(FSE
Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy.
Tissue patterning is established by extracellular growth factors or morphogens. Although different theoretical models explaining specific patterns have been proposed, our understanding of tissue pattern establishment in vivo remains limited. In many animal species, left-right patterning is governed by a reaction-diffus...
Is the protein lefty an inhibitor of nodal?
Nodal, and an inhibitor, Lefty.
Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales. This large group of obligate intracellular alpha-Proteobacteria includes the family Rickettsiaceae and several rickettsia-like endosymbionts (RLEs). Detailed phylogenetic analysis of small subunit (SSU) rRNA and ...
Which species of bacteria did the mitochondria originate from?
Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales.
Macular edema is the most frequent cause of visual deterioration in noninfectious uveitis. The treatment of noninfectious uveitis with associated macular edema commonly includes systemic or locally administered corticosteroids, with long-term use limited by significant side effects. The need for a treatment with an imp...
What was the phase of the clinical trial PEACHTREE?
Recent results from the PEACHTREE trial (ClinicalTrials.gov Identifier: NCT02595398), a phase III trial with two suprachoroidal injections of CLS-TA at 0 and 12 weeks with follow up lasting 24 weeks, showed the significant improvement in visual acuity and reduction in central subfield thickness, all without increasing ...
Deadenylation is the exoribonucleolytic shortening of eukaryotic poly(A) tails. It is often the first and rate-limiting step for mRNA decay and translational silencing. The process is catalysed by a diversity of deadenylases, which provide robust and flexible means to control mRNA levels and gene expression. Poly(A)-sp...
What is the role of deadenylases in the cell?
In this context, the wide repertoire of RBPs and molecules that regulate PARN activity, together with the established role of deadenylases in miRNA-mediated regulation of mRNA expression, suggest that mRNA turnover is more complex than it was previously thought and PARN holds a key role in this process.
Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not dose-limiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).
Is Dupilumab used for treatment of atopic dermatitis?
Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity.
Primary intestinal lymphangiectasia (Waldmann's disease) is characterized by protein-losing enteropathy occurring more frequently in childhood. Chronic diarrhea and diffuse edema are the main clinical manifestations. Peripheral lymphedema may also be associated. Lymphedema is usually present at the time of diagnosis or...
Which diseases are associated with Primary intestinal lymphangiectasia (PIL)?
Primary intestinal lymphangiectasia (Waldmann's disease) is characterized by protein-losing enteropathy occurring more frequently in childhood.
Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis. Integrin stimulation protects cells from anoikis, but the responsible mechanisms are not well known. Here, we demonstrated that a pro-apoptotic GTP-binding protein, DAP3 (death-associated protein 3), is critical f...
Which type of cell death is known as anoikis?
Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis. Integrin stimulation protects cells from anoikis, but the responsible mechanisms are not well known.
The HDM2-p53 loop is crucial for monitoring p53 level and human pathologies. Therefore, identification of novel molecules involved in this regulatory loop is necessary for understanding the dynamic regulation of p53 and treatment of human diseases. Here, we characterized that the ribosomal protein L6 binds to and suppr...
Which protein is the E3-ubiquitin ligase that targets the tumor suppressor p53 for proteasomal degradation?
Together, our study identifies the crucial function of RPL6 in regulating HDM2-p53 pathway, which highlights the importance of RPL6 in human genetic diseases and cancers.
Most pregnancies in women with rheumatologic disease will result in the delivery of a healthy baby. Pregnancy can be particularly risky in women with active disease or on teratogenic medications, making contraception an important issue for these women. All women with rheumatologic disease have contraceptive options, in...
What are the pregnancy outcomes in rheumatoid arthritis?
Rheumatoid arthritis typically improves and does not have a major impact on pregnancy outcomes.
Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose. Thirteen emergency departments enrolled 326 patients in this double-blind, placebo-controlled trial; 162 patients were randomly allocated to receive flumazenil (maximum dose, 30 ml, provid...
Which drug should be used as an antidote in benzodiazepine overdose?
Among the benzodiazepine-positive patients, 9 (53%) of 17 patients from the flumazenil group responded to the additional flumazenil, and 58 (81%) of patients previously given placebo responded.
Origins of DNA replication on eukaryotic genomes have been observed to fire during S phase in a coordinated manner. Studies in yeast indicate that origin firing is affected by several factors, including checkpoint regulators and chromatin modifiers. However, it is unclear what the mechanisms orchestrating this coordina...
How does Rif1 regulate DNA replication?
In mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures. Regulation of chromatin architecture by Rif1 may be linked to other chromosome transactions including recombination, repair, or transcription.
Nuclear RNA degradation pathways are highly conserved across eukaryotes and play important roles in RNA quality control. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). It has recently been reported that the nuclear exosome is inactivated during meiosis ...
Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?
We find that TRAMP mutants produce high levels of CUTs during meiosis that are undetectable in wild-type cells, showing that the nuclear exosome remains functional for CUT degradation, and we further report that the meiotic exosome complex contains Rrp6.
Adoptive cellular immunotherapy with anti CD19 chimeric antigen receptor (CAR)-T cell has changed the treatment landscape in relapsed/refractory B cell lymphomas. They have emerged as effective therapy in patients with multiple relapsed/refractory disease, capable of sustaining durable remissions. Two CAR-T cell produc...
Describe the mechanism of action of Lisocabtagene maraleucel.
A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon.
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder that manifests in females, typically after the first year of life. It is a leading cause of mental retardation and autistic behavior in girls and women; a hallmark of the disease is incessant hand movements in the form of wringing, twisting, or cla...
Which methyl-CpG-binding protein when mutant becomes the hallmark for Rett syndrome?
Molecular studies have identified MECP2 mutations in up to 80% of classic RTT patients; mutation type has some effect on the phenotypic manifestation of RTT, but the pattern of X inactivation seems to determine phenotypic severity.
Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was l...
Which peptide plays a pivotal role in human cystatin C fibrillization?
Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was l...
Normal tissue damage from ionizing radiation during radiotherapy is a major concern in cancer treatment. Tea polyphenols (TPs) have been shown to reduce radiation-induced damage in multiple studies, but their pharmacological application is still limited due to poor bioavailability. The present study was aimed at to inc...
List radioprotection agents.
Tea polyphenols (TPs) have been shown to reduce radiation-induced damage in multiple studies,
Contraction of the large Igh and Igkappa loci brings all V genes, spanning >2.5 Mb in each locus, in proximity to DJ(H) or J(kappa) genes. CCCTC-binding factor (CTCF) is a transcription factor that regulates gene expression by long-range chromosomal looping. We therefore hypothesized that CTCF may be crucial for the co...
Where does CTCF colocalize with cohesin?
Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination.
Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g...
Is the optogenetics tool ChR2 light-sensitive?
Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g...
De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy With Contractures, Macrocephaly, and Dyskinesias Helbig KL, Lauerer RJ, Bahr JC, et al. Am J Hum Genet. 2019;104(3):562. Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in ...
List characteristics of Developmental and Epileptic Encephalopathies (DEEs).
ental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on electroencephalogram (EEG), and developmental impairment or regression. CACNA1E is
Calciphylaxis is a metastatic calcification-induced vasculopathy that results in the occlusion of small blood vessels. Although calciphylaxis is normally associated with end-stage renal disease, calciphylaxis from non-uremic origin occurs as well. While the number of reports continues to increase, a standard treatment ...
What is calciphylaxis
Calciphylaxis is a metastatic calcification-induced vasculopathy that results in the occlusion of small blood vessels.
CXCL7, a chemokine highly expressed in platelets, orchestrates neutrophil recruitment during thrombosis and related pathophysiological processes by interacting with CXCR2 receptor and sulfated glycosaminoglycans (GAG). CXCL7 exists as monomers and dimers, and dimerization (~50 μM) and CXCR2 binding (~10 nM) constants i...
Is CXCL7 a chemokine?
CXCL7, a chemokine highly expressed in platelets,
Introduction and expression of multiple transgenes is frequently required for basic and applied studies. However, at present, multigene transformation is very difficult due to technical limitations of existing methods. Here, we describe a vector system for efficient multigene assembly and transformation. The system con...
List the existing methods for genetic manipulation of cells.
Here, we describe a vector system for efficient multigene assembly and transformation. The system consists of a transformation-competent artificial chromosome (TAC)-based acceptor vector together with two donor vectors. By exploiting the CreloxP recombination system and homing endonucleases, multiple rounds of gene ass...
Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that ...
Which transcription factors are essential for the melanocyte lineage?
The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma.
Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues...
what is the effect of Bisphenol A in the body?
In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit.In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues.
Viliuisk encephalomyelitis is an acute, often fatal, meningoencephalitis that tends to develop into a prolonged chronically progressive panencephalitis. Clinical, neuropathologic, and epidemiologic data argue for an infectious cause, although multiple attempts at pathogen isolation have been unsuccessful. To assess mec...
Viliuisk encephalomyelitis is diagnosed in which geographical area?
Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease.
Currently DNA profiling methods only compare a suspect's DNA with DNA left at the crime scene. When there is no suspect, it would be useful for the police to be able to predict what the person of interest looks like by analysing the DNA left behind in a crime scene. Determination of the age of the suspect is an importa...
Can chronological age be predicted by measuring telomere length?
Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths.
We developed a method called residue contact frequency (RCF), which uses the complex structures generated by the protein-protein docking algorithm ZDOCK to predict interface residues. Unlike interface prediction algorithms that are based on monomers alone, RCF is binding partner specific. We evaluated the performance o...
List programs suitable for protein docking
a method called residue contact frequency (RCF), which uses the complex structures generated by the protein-protein docking algorithm ZDOCK to predict interface residues
A new paradigm has emerged in recent years characterizing transcription initiation as a bidirectional process encompassing a larger proportion of the genome than previously thought. Past concepts of coding genes thinly scattered among a vast background of transcriptionally inert noncoding DNA have been abandoned. A ric...
Is transcription of eRNA bidirectional?
A new paradigm has emerged in recent years characterizing transcription initiation as a bidirectional process encompassing a larger proportion of the genome than previously thought.
The post-translational modification of tubulin appears to be a highly controlled mechanism that regulates microtubule functioning. Acetylation of the ε-amino group of Lys-40 of α-tubulin marks stable microtubules, although the causal relationship between tubulin acetylation and microtubule stability has remained poorly...
Which are the enzymes involved in the control of tubulin acetylation?
We found that whereas both pharmacological inhibition of HDAC6 as well as its depletion enhance microtubule acetylation, only pharmacological inhibition of HDAC6 activity leads to an increase in microtubule stability against cold and nocodazole-induced depolymerizing conditions.
A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers. Three hundred and thirty adolescent smokers at the Smoking Cessation Clinic of Child Guidance Clinic, Institute of Health, Singapore, were randomly assigned in equal...
What is known about the effect of acupuncture in smoking cessation ?
A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers.
More than 150 million people worldwide have diabetes, the prevalence of which is increasing so rapidly that the number of adults with diabetes in the world will rise to 300 million by the year 2025. In the US, approximately 21 million people have diabetes and in some areas of the country, the prevalence is as high as 5...
What drugs are included in the Avandamet pill?
metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes. As insulin resistan
Septins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying m...
What are Septins?
eptins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying me...
Dairy cows mobilise body tissues to support milk production and, because glucose supplies are limited, lipids are used preferentially for energy production. Lipogenic activity is switched off and lipolytic mechanisms in adipose tissue increase through changes in the expression of several key enzymes. This results in a ...
Has the protein TIEG1 been associated with apoptosis?
The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway
The great majority of viral mRNAs in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV) have a common 3' end at the early polyadenylation site which is 23 nucleotides (nt) downstream of a canonical poly(A) consensus signal. Twenty percent of BPV mRNA from productively infected cells bypasses the early p...
What is the most prominent sequence consensus for the polyadenylation site?
the early poly(A) consensus signal was mutated from AAUAAA to UGUAAA
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone ...
Is Tisagenlecleucel effective for B-Cell Lymphoma?
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organism...
What is the 959 Nematode Genomes initiative?
To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/).
Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans. It is unclear how operons have become abundant in nematode genomes. The "one-way street" hypothesis asserts that once f...
What percentage of C. elegans genes reside in operons?
Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans.
Oxygen based neurotransmitters in the synapses of the brain are proposed to play an important role in the generation of consciousness. They include the amino acids glutamate and GABA which use Krebs cycle precursors for their synthesis, and the monoamines dopamine, noradrenalin, adrenalin and serotonin, which are deriv...
Is amantadine effective for treatment of disorders conciousness?
Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic...
Multiple familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck. However, multiple familial trichoe...
Which pathological conditions are caused by mutations in the CYLD gene?
Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT
Transcription factor-induced lineage reprogramming or transdifferentiation experiments are essential for understanding the plasticity of differentiated cells. These experiments helped to define the specific role of transcription factors in conferring cell identity and played a key role in the development of the regener...
How can B-cells transdifferentiate into macrophages?
We here investigated the acquisition of DNA methylation changes during C/EBPα-induced pre-B cell to macrophage transdifferentiation.
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in...
What is the biological function of the SRY circular RNA (circRNA)?
Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner
Interstitial cell of Cajal (ICC) hyperplasia has been documented in conditions associated with multiple gastrointestinal stromal tumours (GISTs) (familial GIST syndromes, Carney's triad and von Recklinghausen's disease) and rarely in the vicinity of sporadic GISTs. The incidence of sporadic ICC hyperplasia and the so-c...
Which cancers compose Carney's triad?
Interstitial cell of Cajal (ICC) hyperplasia has been documented in conditions associated with multiple gastrointestinal stromal tumours (GISTs) (familial GIST syndromes, Carney's triad and von Recklinghausen's disease) and rarely in the vicinity of sporadic GISTs.
A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases. In addition, telomestatin induced telomere shortening, but its ratio was extremely fast...
Is telomestatin, a novel statin drug used to treat high cholesterol?
In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening.
The phosphorylation of rat cardiac microsomal proteins was investigated with special attention to the effects of okadaic acid (an inhibitor of protein phosphatases), inhibitor 2 of protein phosphatase 1 and inhibitor of cyclic AMP-dependent protein kinase (protein kinase A). The results showed that okadaic acid (5 micr...
Which protein phosphatases have been found to dephosphorylate phospholamban?
These results are consistent with the views that protein phosphatase 1 is capable of dephosphorylating membrane-associated phospholamban when it is phosphorylated by protein kinase A, but not by calcium/calmodulin kinase, and that under certain conditions, calcium/calmodulin-stimulated protein phosphatase (protein phos...
Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings. We report a young male patient who presented with painless diminution of vision associated with hearing loss. The importance of oph...
What is the Triad of Alport Syndrome?
Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings.
Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation fact...
What is the role of thyroid hormone in Stem cell differentiation?
This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days
Angiogenesis, the growth of new blood vessels, is essential during tissue repair. In contrast, uncontrolled angiogenesis promotes tumor. A balance between proangiogenic and antiangiogenic growth factors and cytokines tightly controls angiogenesis. With the identification of several proangiogenic molecules such as the v...
Is endostatin a proangiogenic factor?
specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin
Automated methods for NMR structure determination of proteins are continuously becoming more robust. However, current methods addressing larger, more complex targets rely on analyzing 6-10 complementary spectra, suggesting the need for alternative approaches. Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipe...
What is the 4D-CHAINS algorithm?
Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins.
Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET recept...
Which receptors are targeted by a drug Macitentan?
In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats.
piRNAs silence foreign genes, such as transposons, to preserve genome integrity, but they also target endogenous mRNAs by mechanisms that are poorly understood. Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway. To assess the dysregu...
Are piRNAs involved in gene silencing?
Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway.
The multiple kinase inhibitor dovitinib is currently under clinical investigation for hepatocellular carcinoma (HCC). Here, we investigated the mechanistic basis for the effects of dovitinib in HCCs. Dovitinib showed significant antitumor activity in HCC cell lines PLC5, Hep3B, Sk-Hep1, and Huh-7. Dovitinib downregulat...
Which molecules are inhibited by anticancer drug Dovitinib?
The multiple kinase inhibitor dovitinib is currently under clinical investigation for hepatocellular carcinoma (HCC).
Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during ...
Can botulism poisoning of a pregnant woman harm her fetus?
From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.
An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site. Two variations of NEMO's zinc finger are implicated in various disease states including ectodermal dysplasia and adult-onset glaucoma. To d...
Is NEMO a zinc finger protein?
An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site.
Seasonal influenza infections are associated with an estimated 250-500 000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have prom...
What is the generic name of the Xofluza?
Baloxavir marboxil (Xofluza®), recently approved for clinical use, inhibits cap-snatching endonuclease.
The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers. In the present study, we assessed the molecular and cellular mechanisms underlying human arrhythmias by a...
What is the role of the histidine rich calcium binding protein (HRC) in cardiomyopathy?
The HRC(S96A) mutant exacerbated the inhibitory effects of HRC(WT) on the amplitude of Ca(2+) transients, prolongation of Ca(2+) decay time, and caffeine-induced sarcoplasmic reticulum Ca(2+) release. Consistent with these findings, HRC(S96A) reduced maximal sarcoplasmic reticulum calcium uptake rate to a higher extent...
It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. This effect may be of therapeutic relevance. Therefore, the present study has investigated potential signaling mechanisms unde...
Does thyroid hormone affect cardiac remodeling?
It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape.
Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet fu...
List mouse models for autism spectrum disorder (ASD).
fmr1 knockout mouse model
CTCF is a zinc finger DNA-binding protein that regulates the epigenetic states of numerous target genes. Using allelic regulation of mouse insulin-like growth factor II (Igf2) as a model, we demonstrate that CTCF binds to the unmethylated maternal allele of the imprinting control region (ICR) in the Igf2/H19 imprinting...
Do polycomb group proteins (PcG) mediate the formation of chromatin loops?
CTCF governs gene expression by orchestrating chromatin loop structures and by serving as a DNA-binding protein scaffold to recruit and bind polycomb repressive complexes
Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Using the EpFosER mammary tumour model we show that during EMT, upregulation of the transcriptional regulator deltaEF1 coincided with transcriptional repression of E-cadherin. ...
Which transcription factors are involved in E-cadherin repression during EMT?
ownregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression.
Spinal and bulbar muscular atrophy (SBMA) is an X-linked adult motor neuron disorder caused by an abnormal CAG-repeat expansion in the first exon of the androgen receptor gene. This disease associates progressive lower motor neuron affection and endocrine disturbances. Bulbar symptoms appear usually late in the clinica...
What is Spinal-bulbar muscular atrophy (SBMA)?
Spinal and bulbar muscular atrophy (SBMA) is an X-linked adult motor neuron disorder caused by an abnormal CAG-repeat expansion in the first exon of the androgen receptor gene.
Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated Cy...
Which molecule is inhibited by encorafenib?
Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials.
The SWR1 complex (SWR1C) in yeast catalyzes the replacement of nucleosomal H2A with the H2AZ variant, which ensures full activation of underlying genes. We compared the phenotype of mutants in the homologs of SWR1C components in Arabidopsis thaliana. Mutations in Arabidopsis SWC6 (AtSWC6), SUPPRESSOR OF FRIGIDA 3 (SUF3...
Which protein mediates the replacement of H2A by H2A.Z in the yeast Saccharomyces cerevisiae?
The SWR1 complex (SWR1C) in yeast catalyzes the replacement of nucleosomal H2A with the H2AZ variant, which ensures full activation of underlying genes.
IgG4 related thoracic aortitis is a recent addition to the differential diagnosis for inflammatory aortic disease - a condition which is often underappreciated until complications arise such as aneurysmal formation or aortic dissection. Currently, IgG4 aortitis remains a post-surgical diagnosis reliant on positive immu...
What is Aortitis?
IgG4 related thoracic aortitis is a recent addition to the differential diagnosis for inflammatory aortic disease - a condition which is often underappreciated until complications arise such as aneurysmal formation or aortic dissection. C
Monoclonal antibodies (mAb) have had tremendous success in treating a variety of cancers over the past twenty years. Yet despite their widespread clinical use, which includes treatments for haematological malignancies, there are still no approved mAb therapies for multiple myeloma (MM). This is likely to change within ...
Which molecule is targeted by Daratumumab?
This is likely to change within the next few years with a number of mAb therapies being assessed in late stage clinical trials, most notably, the anti-CS-1 mAb, elotuzumab, and the anti-CD38 mAb, daratumumab, which are currently being evaluated in Phase III clinical trials for MM.
The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi. The Sphincter of Oddi is a small smooth muscle sphincter strategically placed at the junction of the bile duct, pancreatic duct, and duodenum. The sphincter controls flow of bile and pancreatic juices...
What 3 organs are the sphincter of Oddi associated with?
The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi.
Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for their alignment on the spindle apparatus and segregation in mitosis. Budding yeast cohesin first associates with chromosomes in G1. Then, during DNA replication in S-phase, the replication fork-associated acetyltransf...
Is there any link between CTF4 and CTF18 during sister chromatid cohesion?
In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles
The advantage of using the tobacco (Nicotiana tabacum var. xanthi) mutagenicity assay is the ability to analyze and compare on the same plants under identical treatment conditions both the induced acute DNA damage in somatic cells as measured by the Comet assay and the yield of induced leaf somatic mutations. Gamma-irr...
Does a comet assay measure radiation induced mutations?
ir of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose. Data on the kinetic