scholarly journals MCMs in Cancer: Prognostic Potential and Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Si Yu ◽  
Guanqun Wang ◽  
Yue Shi ◽  
Haifeng Xu ◽  
Yongchang Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Replication Initiation ◽  
Current Evidence ◽  
Future Research ◽  
Hallmarks Of Cancer ◽  
Minichromosome Maintenance ◽  
Proliferation Markers ◽  
A Cell ◽  
Underlying Mechanisms ◽  
Insight Into

Enabling replicative immortality and uncontrolled cell cycle are hallmarks of cancer cells. Minichromosome maintenance proteins (MCMs) exhibit helicase activity in replication initiation and play vital roles in controlling replication times within a cell cycle. Overexpressed MCMs are detected in various cancerous tissues and cancer cell lines. Previous studies have proposed MCMs as promising proliferation markers in cancers, while the prognostic values remain controversial and the underlying mechanisms remain unascertained. This review provides an overview of the significant findings regarding the cellular and tumorigenic functions of the MCM family. Besides, current evidence of the prognostic roles of MCMs is retrospectively reviewed. This work also offers insight into the mechanisms of MCMs prompting carcinogenesis and adverse prognosis, providing information for future research. Finally, MCMs in liver cancer are specifically discussed, and future perspectives are provided.

scholarly journals High-frequency oscillations and the neurobiology of schizophrenia

2013 ◽  
Vol 15 (3) ◽  
pp. 301-313 ◽  
Keyword(s):  
High Frequency ◽  
Large Scale ◽  
Oscillatory Activity ◽  
Current Evidence ◽  
Neural Oscillations ◽  
Future Research ◽  
Normal Brain ◽  
Brain Functions ◽  
Critical Issues ◽  
Underlying Mechanisms

Neural oscillations at low- and high-frequency ranges are a fundamental feature of large-scale networks. Recent evidence has indicated that schizophrenia is associated with abnormal amplitude and synchrony of oscillatory activity, in particular, at high (beta/gamma) frequencies. These abnormalities are observed during task-related and spontaneous neuronal activity which may be important for understanding the pathophysiology of the syndrome. In this paper, we shall review the current evidence for impaired beta/gamma-band oscillations and their involvement in cognitive functions and certain symptoms of the disorder. In the first part, we will provide an update on neural oscillations during normal brain functions and discuss underlying mechanisms. This will be followed by a review of studies that have examined high-frequency oscillatory activity in schizophrenia and discuss evidence that relates abnormalities of oscillatory activity to disturbed excitatory/inhibitory (E/I) balance. Finally, we shall identify critical issues for future research in this area.

scholarly journals Identifying and prioritising unanswered research questions for people with hyperacusis: James Lind Alliance Hyperacusis Priority Setting Partnership

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e032178 ◽  
Author(s):  
Kathryn Fackrell ◽  
Linda Stratmann ◽  
Veronica Kennedy ◽  
Carol MacDonald ◽  
Hilary Hodgson ◽  
...  
Keyword(s):  
Lived Experience ◽  
Priority Setting ◽  
Healthcare Professionals ◽  
Research Priorities ◽  
Current Evidence ◽  
Future Research ◽  
James Lind Alliance ◽  
Essential Resource ◽  
Underlying Mechanisms ◽  
Priority Setting Partnership

ObjectiveTo determine research priorities in hyperacusis that key stakeholders agree are the most important.Design/settingA priority setting partnership using two international surveys, and a UK prioritisation workshop, adhering to the six-staged methodology outlined by the James Lind Alliance.ParticipantsPeople with lived experience of hyperacusis, parents/carers, family and friends, educational professionals and healthcare professionals who support and/or treat adults and children who experience hyperacusis, including but not limited to surgeons, audiologists, psychologists and hearing therapists.MethodsThe priority setting partnership was conducted from August 2017 to July 2018. An international identification survey asked respondents to submit any questions/uncertainties about hyperacusis. Uncertainties were categorised, refined and rephrased into representative indicative questions using thematic analysis techniques. These questions were verified as ‘unanswered’ through searches of current evidence. A second international survey asked respondents to vote for their top 10 priority questions. A shortlist of questions that represented votes from all stakeholder groups was prioritised into a top 10 at the final prioritisation workshop (UK).ResultsIn the identification survey, 312 respondents submitted 2730 uncertainties. Of those uncertainties, 593 were removed as out of scope, and the remaining were refined into 85 indicative questions. None of the indicative questions had already been answered in research. The second survey collected votes from 327 respondents, which resulted in a shortlist of 28 representative questions for the final workshop. Consensus was reached on the top 10 priorities for future research, including identifying causes and underlying mechanisms, effective management and training for healthcare professionals.ConclusionsThese priorities were identified and shaped by people with lived experience, parents/carers and healthcare professionals, and as such are an essential resource for directing future research in hyperacusis. Researchers and funders should focus on addressing these priorities.

scholarly journals Energy Starvation Induces a Cell Cycle Arrest in Escherichia coli by Triggering Degradation of the DnaA Initiator Protein

2021 ◽  
Vol 8 ◽  
Author(s):  
Godefroid Charbon ◽  
Belén Mendoza-Chamizo ◽  
Christopher Campion ◽  
Xiaobo Li ◽  
Peter Ruhdal Jensen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Growth Conditions ◽  
Chromosome Replication ◽  
Replication Initiation ◽  
Atp Depletion ◽  
Initiator Protein ◽  
Cycle Arrest ◽  
A Cell

During steady-state Escherichia coli growth, the amount and activity of the initiator protein, DnaA, controls chromosome replication tightly so that initiation only takes place once per origin in each cell cycle, regardless of growth conditions. However, little is known about the mechanisms involved during transitions from one environmental condition to another or during starvation stress. ATP depletion is one of the consequences of long-term carbon starvation. Here we show that DnaA is degraded in ATP-depleted cells. A chromosome replication initiation block is apparent in such cells as no new rounds of DNA replication are initiated while replication events that have already started proceed to completion.

scholarly journals GLI1: A Therapeutic Target for Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Justin T. Avery ◽  
Ruowen Zhang ◽  
Rebecca J. Boohaker
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Hedgehog Signaling ◽  
Dna Damage Repair ◽  
Therapeutic Benefit ◽  
Direct Inhibition ◽  
Hallmarks Of Cancer ◽  
Diagnostic Biomarkers ◽  
Damage Repair ◽  
Underlying Mechanisms

GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1 has been linked to the promotion of numerous hallmarks of cancer, such as proliferation, survival, angiogenesis, metastasis, metabolic rewiring, and chemotherapeutic resistance. All of these are driven, in part, by GLI1’s role in regulating cell cycle, DNA replication and DNA damage repair processes. The consequences of GLI1 oncogenic activity, specifically the activity surrounding DNA damage repair proteins, such as NBS1, and cell cycle proteins, such as CDK1, can be linked to tumorigenesis and chemoresistance. Therefore, understanding the underlying mechanisms driving GLI1 dysregulation can provide prognostic and diagnostic biomarkers to identify a patient population that would derive therapeutic benefit from either direct inhibition of GLI1 or targeted therapy towards proteins downstream of GLI1 regulation.

scholarly journals Biological activities of basil essential oil: a review of the current evidence

2021 ◽  
Vol 10 (12) ◽  
pp. e363101220409
Author(s):  
Mayara Zagoto ◽  
Gabriel Fernando Esteves Cardia ◽  
Edvalkia Magna Teobaldo da Rocha ◽  
Kathia Socorro Mathias Mourão ◽  
Vanderly Janeiro ◽  
...  
Keyword(s):  
Essential Oil ◽  
Biological Activities ◽  
Current Evidence ◽  
Future Research ◽  
Existing Problems ◽  
Treatment And Prevention ◽  
Low Toxicity ◽  
Pharmacological Potential ◽  
Clinical Conditions ◽  
Insight Into

Currently, natural products are being used as a therapeutic alternative in the treatment and prevention of several diseases due to their low toxicity and relevant pharmacological potential. Thus, we can highlight basil (Ocimum basilicum L), one of the most used aromatic plants worldwide. Therefore, we provide some current evidence and insight into the potential therapeutic effect of basil essential oil to expand the available knowledge. A narrative review was carried out by searching electronic databases, providing a comprehensive analysis of the literature, where it was possible to identify existing problems and gaps to facilitate future research on basil essential oil. The available literature on basil essential oil presents us with several important pharmacological activities, such as: antioxidant, antiviral, antimicrobial, analgesic, anti-inflammatory, and analgesic and diuretic properties, among others. However, further research must be carried out to increase knowledge about this plant with enormous potential and determine its effectiveness and use in clinical conditions.

scholarly journals Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Shanshan Zhao ◽  
Xue Zhang ◽  
Shuo Chen ◽  
Song Zhang
Keyword(s):  
Cancer Biology ◽  
Future Research ◽  
Hallmarks Of Cancer ◽  
Therapeutic Application ◽  
Antisense Transcripts ◽  
Research Directions ◽  
Natural Antisense Transcripts ◽  
Post Translational Modifications ◽  
Future Research Directions ◽  
Underlying Mechanisms

Abstract Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.

scholarly journals The phenotype of the minichromosome maintenance mutant mcm3 is characteristic of mutants defective in DNA replication.

1990 ◽  
Vol 10 (11) ◽  
pp. 5707-5720 ◽  
Author(s):  
S I Gibson ◽  
R T Surosky ◽  
B K Tye
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Arrest ◽  
Essential Gene ◽  
Replication Initiation ◽  
Yeast Cells ◽  
Chromosome Loss ◽  
Minichromosome Maintenance ◽  
Autonomously Replicating Sequence ◽  
Cycle Arrest

MCM3 is an essential gene involved in the maintenance of minichromosomes in yeast cells. It encodes a protein of 971 amino acids that shows striking homology to the Mcm2 protein. We have mapped the mcm3-1 mutation of the left arm of chromosome V approximately 3 kb centromere proximal of anp1. The mcm3-1 mutant was found to be thermosensitive for growth. Under permissive growth conditions, it was defective in minichromosome maintenance in an autonomously replicating sequence-specific manner and showed an increase in chromosome loss and recombination. Under nonpermissive conditions, mcm3-1 exhibited a cell cycle arrest phenotype, arresting at the large-bud stage with an undivided nucleus that had a DNA content of nearly 2n. These phenotypes are consistent with incomplete replication of the genome of the mcm3-1 mutant, possibly as a result of limited replication initiation at selective autonomously replicating sequences leading to cell cycle arrest before mitosis. The phenotype exhibited by the mcm3 mutant is very similar to that of mcm2, suggesting that the Mcm2 and Mcm3 protein may play interacting roles in DNA replication.

scholarly journals Disruption of Mechanisms That Prevent Rereplication Triggers a DNA Damage Response

2005 ◽  
Vol 25 (15) ◽  
pp. 6707-6721 ◽  
Author(s):  
Vincent Archambault ◽  
Amy E. Ikui ◽  
Benjamin J. Drapkin ◽  
Frederick R. Cross
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Origin Recognition Complex ◽  
Strand Break ◽  
Minichromosome Maintenance ◽  
Damage Response ◽  
Similar Phenotype ◽  
A Cell ◽  
Prereplicative Complex

ABSTRACT Eukaryotes replicate DNA once and only once per cell cycle due to multiple, partially overlapping mechanisms efficiently preventing reinitiation. The consequences of reinitiation are unknown. Here we show that the induction of rereplication by mutations in components of the prereplicative complex (origin recognition complex [ORC], Cdc6, and minichromosome maintenance proteins) causes a cell cycle arrest with activated Rad53, a large-budded morphology, and an undivided nucleus. Combining a mutation disrupting the Clb5-Orc6 interaction (ORC6-rxl) and a mutation stabilizing Cdc6 (CDC6ΔNT) causes a cell cycle delay with a similar phenotype, although this background is only partially compromised for rereplication control and does not exhibit overreplication detectable by fluorescence-activated cell sorting. We conducted a systematic screen that identified genetic requirements for the viability of these cells. ORC6-rxl CDC6ΔNT cells depend heavily on genes required for the DNA damage response and for double-strand-break repair by homologous recombination. Our results implicate an Mre11-Mec1-dependent pathway in limiting the extent of rereplication.

scholarly journals Concurrent processes setE. colicell division

2018 ◽  
Vol 4 (11) ◽  
pp. eaau3324 ◽  
Author(s):  
Gabriele Micali ◽  
Jacopo Grilli ◽  
Matteo Osella ◽  
Marco Cosentino Lagomarsino
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Single Cell ◽  
Chromosome Segregation ◽  
Genetic Material ◽  
Replication Initiation ◽  
Concurrent Processes ◽  
A Cell ◽  
Rate Limiting ◽  
Cell Data

A cell can divide only upon completion of chromosome segregation; otherwise, its daughters would lose genetic material. However, we do not know whether the partitioning of chromosomes is the key event for the decision to divide. We show how key trends in single-cell data reject the classic idea of replication-segregation as the rate-limiting process for cell division. Instead, the data agree with a model where two concurrent processes (setting replication initiation and interdivision time) set cell division on competing time scales. During each cell cycle, division is set by the slowest process (an “AND” gate). The concept of transitions between cell cycle stages as decisional processes integrating multiple inputs instead of cascading from orchestrated steps can affect the way we think of the cell cycle in general.

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