scholarly journals TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation

2020 ◽  
Vol 21 (22) ◽  
pp. 8871
Author(s):  
Roman O. Cherezov ◽  
Julia E. Vorontsova ◽  
Olga B. Simonova
Keyword(s):  
Molecular Mechanisms ◽  
Chromosomal Translocation ◽  
Centric Fusion ◽  
Related Factor ◽  
Robertsonian Translocations ◽  
General Transcription Factor ◽  
Acrocentric Chromosomes ◽  
First Time ◽  
Transcription Program ◽  
Insight Into

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.

scholarly journals The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Saishu Yoshida ◽  
Katsuhiko Aoki ◽  
Ken Fujiwara ◽  
Takashi Nakakura ◽  
Akira Kawamura ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
The Novel ◽  
Mammalian Development ◽  
Hh Signaling ◽  
Functional Analyses ◽  
First Time ◽  
Insight Into

Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate ciliogenesis can provide insight into the molecular mechanisms of embryogenesis and ciliopathy. Here, we demonstrate that DYRK2 acts as a novel mammalian ciliogenesis-related protein kinase. Loss of Dyrk2 in mice causes suppression of Hh signaling and results in skeletal abnormalities during in vivo embryogenesis. Deletion of Dyrk2 induces abnormal ciliary morphology and trafficking of Hh pathway components. Mechanistically, transcriptome analyses demonstrate down-regulation of Aurka and other disassembly genes following Dyrk2 deletion. Taken together, the present study demonstrates for the first time that DYRK2 controls ciliogenesis and is necessary for Hh signaling during mammalian development.

scholarly journals The function of LncRNA-H19 in cardiac hypertrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenhua Su ◽  
Qian Huo ◽  
Hao Wu ◽  
Lulin Wang ◽  
Xiaoxue Ding ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Adaptive Response ◽  
Molecular Mechanisms ◽  
Myocardial Hypertrophy ◽  
Noncoding Rnas ◽  
Biological Functions ◽  
Pathological Mechanism ◽  
First Time ◽  
Insight Into

AbstractCardiac hypertrophy, characterized by the enlargement of cardiomyocytes, is initially an adaptive response to physiological and pathological stimuli. Decompensated cardiac hypertrophy is related to fibrosis, inflammatory cytokine, maladaptive remodeling, and heart failure. Although pathological myocardial hypertrophy is the main cause of hypertrophy-related morbidity and mortality, our understanding of its mechanism is still poor. Long noncoding RNAs (lncRNAs) are noncoding RNAs that regulate various physiological and pathological processes through multiple molecular mechanisms. Recently, accumulating evidence has indicated that lncRNA-H19 is a potent regulator of the progression of cardiac hypertrophy. For the first time, this review summarizes the current studies about the role of lncRNA-H19 in cardiac hypertrophy, including its pathophysiological processes and underlying pathological mechanism, including calcium regulation, fibrosis, apoptosis, angiogenesis, inflammation, and methylation. The context within which lncRNA-H19 might be developed as a target for cardiac hypertrophy treatment is then discussed to gain better insight into the possible biological functions of lncRNA-H19 in cardiac hypertrophy.

scholarly journals The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Yujiao Chen ◽  
Wei Zhang ◽  
Xiaoli Guo ◽  
Jing Ren ◽  
Ai Gao
Keyword(s):  
Risk Assessment ◽  
Molecular Mechanisms ◽  
Ros Generation ◽  
Hematological Cancer ◽  
Exposed Workers ◽  
Different Types ◽  
First Time ◽  
The Relationship ◽  
Insight Into

Abstract Increasing evidence suggested that benzene exposure resulted in different types of hematological cancer. Both autophagy and apoptosis were reported to play vital roles in benzene toxicity, but the relationship between autophagy and apoptosis remain unclear in benzene-induced hematotoxicity. In this study, the toxic effect of benzene on autophagy and apoptosis in benzene-exposed workers and in vitro were verified. Results showed that benzene metabolite (1, 4-benzoquinone, 1, 4-BQ) dose-dependently induced autophagy and apoptosis via enhancing phosphorylation of Bcl-2 and beclin1. Finally, we also found that the elevated ROS was in line with enhancing the phosphorylation of Bcl-2 and beclin1 which contributed to 1, 4-BQ-induced autophagy and apoptosis. Taken together, this study for the first time found that the effect of 1, 4-BQ on the crosstalk between autophagy and apoptosis were modulated by the ROS generation via enhancing phosphorylation of Bcl-2(Ser70) and phosphorylation of beclin1(Thr119), which offered a novel insight into underlying molecular mechanisms of benzene-induced hematotoxicity, and specifically how the crosstalk between autophagy and apoptosis was involved in benzene toxicity. This work provided novel evidence for the toxic effects and risk assessment of benzene.

scholarly journals Prevalence and Phenotypic Impact of Robertsonian Translocations

2021 ◽  
Vol 12 (1) ◽  
pp. 1-11
Author(s):  
Martin Poot ◽  
Ron Hochstenbach
Keyword(s):  
General Population ◽  
Molecular Mechanisms ◽  
Uniparental Disomy ◽  
Gene Clusters ◽  
Chromosome 21 ◽  
Robertsonian Translocations ◽  
Nextgen Sequencing ◽  
Increased Risk ◽  
Acrocentric Chromosomes ◽  
Encoding Genes

Robertsonian translocations (RTs) result from fusion of 2 acrocentric chromosomes (e.g., 13, 14, 15, 21, 22) and consequential losses of segments of the p arms containing 47S rDNA clusters and transcription factor binding sites. Depending on the position of the breakpoints, the size of these losses vary considerably between types of RTs. The prevalence of RTs in the general population is estimated to be around 1 per 800 individuals, making RTs the most common chromosomal rearrangement in healthy individuals. Based on their prevalence, RTs are classified as “common,” rob(13;14) and rob(14;21), or “rare” (the 8 remaining nonhomologous combinations). Carriers of RTs are at an increased risk for offspring with chromosomal imbalances or with uniparental disomy. RTs are generally regarded as phenotypically neutral, although, due to RTs formation, 2 of the 10 ribosomal rDNA gene clusters, several long noncoding RNAs, and in the case of RTs involving chromosome 21, several mRNA encoding genes are lost. Nevertheless, recent evidence indicates that RTs may have a significant phenotypic impact. In particular, rob(13;14) carriers have a significantly elevated risk for breast cancer. While RTs are easily spotted by routine karyotyping, they may go unnoticed if only array-CGH and NextGen sequencing methods are applied. This review first discusses possible molecular mechanisms underlying the particularly high rates of RT formation and their incidence in the general population, and second, likely causes for the elevated cancer risk of some RTs will be examined.

TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova
Keyword(s):  
Viral Replication ◽  
Research Team ◽  
Molecular Mechanisms ◽  
Thick Ascending Limb ◽  
Rockefeller Institute ◽  
The Usa ◽  
Natural Inhibitor ◽  
Simplex Virus ◽  
First Time ◽  
New Protein

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 

Aleksey Peshkov as an editor of Samarskaya Gazeta

2020 ◽  
pp. 128-138
Author(s):  
A. S. Bik-Bulatov
Keyword(s):  
Local History ◽  
Organizational Skills ◽  
First Time ◽  
New Evidence ◽  
Insight Into ◽  
Shed Light

The article uses little known letters of M. Gorky, many of which were published for the first time in 1997, as well as findings of Samara-based experts in local history to shed light on the writer’s work as editor-in-chief of the Samarskaya Gazeta newspaper in 1895. The researcher introduces hitherto unstudied reminiscences of the journalist D. Linyov (Dalin) about this period, which reference a letter by Gorky, now lost. The paper details a newly discovered episode of Gorky’s professional biography as a journalist: it concerns his campaign against a Samara ‘she-wolf,’ the madam of a local brothel A. Neucheva. Linyov’s reminiscences turn out to be an important and interesting source, offering an insight into the daily grind of the young editor Gorky, providing new evidence of his excellent organizational skills, and describing his moral and social stance. The author presents his work in the context of a recently initiated broader discussion about the need to map out all Russian periodicals for the period until 1917, as well as all research devoted to individual publications.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

The Protective Effects of Green Tea Catechins in the Management of Neurodegenerative Diseases: A Review

2019 ◽  
Vol 16 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Tahereh Farkhondeh ◽  
Hanieh Shaterzadeh Yazdi ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Main Role ◽  
Related Factor ◽  
Protective Effects ◽  
Tea Catechins ◽  
Green Tea Catechins ◽  
And Control

Background: The therapeutic strategies to manage neurodegenerative diseases remain limited and it is necessary to discover new agents for their prevention and control. Oxidative stress and inflammation play a main role in the pathogenesis of neurodegenerative diseases. The aim of this study is to review the effects of green tea catechins against the Neurodegenerative Diseases. Methods: In this study, we extensively reviewed all articles on the terms of Green tea, catechins, CNS disorders, and different diseases in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that catechins, the major flavonoids in green tea, are powerful antioxidants and radical scavengers which possess the potential roles in the management of neurodegenerative diseases. Catechins modulate the cellular and molecular mechanisms through the inflammation-related NF-&amp;#954;B and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Conclusion: The findings of the present review shows catechins could be effective against neurodegenerative diseases due to their antioxidation and anti-inflammation effects and the involved biochemical pathways including Nrf2 and NF-kB signaling pathways.<P&gt;

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Comparative Study of Chemical Compositions and Antioxidant Capacities of Oils Obtained from 15 Macadamia (Macadamia integrifolia) Cultivars in China

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1031
Author(s):  
Xixiang Shuai ◽  
Taotao Dai ◽  
Mingshun Chen ◽  
Ruihong Liang ◽  
Liqing Du ◽  
...  
Keyword(s):  
Palmitoleic Acid ◽  
Linear Regression Analysis ◽  
Monounsaturated Fatty Acids ◽  
Multiple Linear Regression Analysis ◽  
Chemical Compositions ◽  
Macadamia Integrifolia ◽  
Antioxidant Capacities ◽  
Squalene Content ◽  
First Time ◽  
Insight Into

The planting area of macadamia in China accounted for more than one third of the world’s planted area. The lipid compositions, minor components, and antioxidant capacities of fifteen varieties of macadamia oil (MO) in China were comparatively investigated. All varieties of MO were rich in monounsaturated fatty acids, mainly including oleic acid (61.74–66.47%) and palmitoleic acid (13.22–17.63%). The main triacylglycerols of MO were first time reported, including 19.2–26.1% of triolein, 16.4–18.2% of 1-palmitoyl-2,3-dioleoyl-glycerol, and 11.9–13.7% of 1-palmitoleoyl-2-oleoyl-3-stearoyl-glycerol, etc. The polyphenol, α-tocotrienol and squalene content varied among the cultivars, while Fuji (791) contained the highest polyphenols and squalene content. Multiple linear regression analysis indicated the polyphenols and squalene content positively correlated with the antioxidant capacity. This study can provide a crucial directive for the breeding of macadamia and offer an insight into industrial application of MO in China.

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