scholarly journals Biological sex and age shape melanoma tumour evolution

2019 ◽  
Author(s):  
Martin Lotz ◽  
Simon J. Furney ◽  
Amaya Virós
Keyword(s):  
Cell Division ◽  
Ultraviolet Light ◽  
Environmental Damage ◽  
Induced Mutations ◽  
Biological Sex ◽  
Age Related ◽  
Rate Shaping ◽  
Cancer Types ◽  
Melanoma Subtypes ◽  
Cancer Tissues

AbstractMany cancer types display sex and age disparity in incidence and outcome. Here, we establish a mathematical approach using cancer mutational data to analyze how sex and age shape the tumour genome. We model how age-related (clock-like) somatic mutations that arise during cell division, and extrinsic (environmental) mutations accumulate in cancer genomes. As a proof-of-concept, we apply our approach to melanoma, a cancer driven by cell-intrinsic age-related mutations and extrinsic ultraviolet light-induced mutations, and show these mutation types differ in magnitude, chronology and by sex in the distinct molecular melanoma subtypes.Our model confirms age and sex are determinants of cellular mutation rate, shaping the final mutation composition. We show mathematically for the first time how, similar to non-cancer tissues, melanoma genomes reflect a decline in cell division during ageing. We find clock-like mutations strongly correlate with the acquisition of ultraviolet light-induced mutations, but critically, males present a higher number and rate of cell division-linked mutations. These data indicate the contribution of environmental damage to melanoma likely extends beyond genetic damage to affect cell division.

scholarly journals Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate With Differences in the Expression of Selected Retinal miRNAs

2021 ◽  
Vol 11 ◽  
Author(s):  
Anca Hermenean ◽  
Maria Consiglia Trotta ◽  
Sami Gharbia ◽  
Andrei Gelu Hermenean ◽  
Victor Eduard Peteu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Amorphous Materials ◽  
Retinal Pigment ◽  
Ultrastructural Changes ◽  
Male Mice ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Female Mice ◽  
Biological Sex ◽  
Age Related

Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75–85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related miRNA expression profile analysis. Retinas of both sexes showed a steady decline in retinal thickness as follows: photoreceptor (PS) and outer layers (p < 0.01 for the aged male vs. control; p < 0.05 for the aged female vs. control); the inner retinal layers were significantly affected by the aging process in the males (p < 0.01) but not in the aged females. Electron microscopy revealed more abnormalities which involve the retinal pigment epithelium (RPE) and Bruch’s membrane, outer and inner layers, vascular changes, deposits of amorphous materials, and accumulation of lipids or lipofuscins. Age-related miRNAs, miR-27a-3p (p < 0.01), miR-27b-3p (p < 0.05), and miR-20a-5p (p < 0.05) were significantly up-regulated in aged male mice compared to the controls, whereas miR-20b-5p was significantly down-regulated in aged male (p < 0.05) and female mice (p < 0.05) compared to the respective controls. miR-27a-3p (5.00 fold; p < 0.01) and miR-27b (7.58 fold; p < 0.01) were significantly up-regulated in aged male mice vs. aged female mice, whereas miR-20b-5p (−2.10 fold; p < 0.05) was significantly down-regulated in aged male mice vs. aged female mice. Interestingly, miR-27a-3p, miR-27b-3p, miR-20a-5p, and miR-20b-5p expressions significantly correlated with the thickness of the retinal PS layer (p < 0.01), retinal outer layers (p < 0.01), and Bruch’s membrane (p < 0.01). Our results showed that biological sex can influence the structure and function of the retina upon aging, suggesting that this difference may be underlined by the dysregulation of age-related mi-RNAs.

Development of potential inhibitors of cell division protein kinase 2 by ligand based drug design

2021 ◽  
pp. 1-10
Author(s):  
Vildan Enisoğlu Atalay ◽  
Büşra Savaş
Keyword(s):  
Hydrogen Bond ◽  
Cell Division ◽  
Drug Design ◽  
Discovery Studio ◽  
Cyclin Dependent Kinases ◽  
Hydrogen Bond Interactions ◽  
Damage Repair ◽  
Cancer Types ◽  
Potential Inhibitors ◽  
Cycle Regulation

Cyclin-dependent kinases (CDKs) are commonly known by their role in cell cycle regulation which affects cancer mechanism. In many cancer types, CDKs show extreme activity or CDK inhibiting proteins are dysfunctional. Specifically, CDK2 plays an indispensable role in cell division especially in the G1/S phase and DNA damage repair. Therefore, it is important to find new potential CDK2 inhibitors. In this study, ligand-based drug design is used to design new potential CDK2 inhibitors. Y8 L ligand is obtained from the X-ray crystal structure of human CDK2 (PDB ID: 2XNB) (www.pdb.org) and used as a structure model. By adding hydrophilic and hydrophobic groups to the structure, a training set of 36 molecules is generated. Each molecule examined with Spartan’14 and optimized structures are used for docking to CDK2 structure by AutoDock and AutoDock Vina programs. Ligand-amino acid interactions are analysed with Discovery Studio Visualizer. Van der Waals, Pi-Pi T-shaped, alkyl, pi-alkyl, conventional hydrogen bond and carbon-hydrogen bond interactions are observed. By docking results and viewed interactions, some molecules are identified and discussed as potential CDK2 inhibitors. Additionally, 8 different QSAR descriptors obtained from Spartan’14, Preadmet and ALOGPS 2.1 programs are investigated with multiple linear regulation (MLR) analysis with SPSS program for their impact on affinity value.

scholarly journals Putatively cancer-specific exon–exon junctions are shared across patients and present in developmental and other non-cancer cells

NAR Cancer ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Julianne K David ◽  
Sean K Maden ◽  
Benjamin R Weeder ◽  
Reid F Thompson ◽  
Abhinav Nellore
Keyword(s):  
Rna Splicing ◽  
Tissue Expression ◽  
The Body ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Rna Seq ◽  
Normal Tissues ◽  
Cancer Types ◽  
Exon Junctions ◽  
Cancer Tissues

Abstract This study probes the distribution of putatively cancer-specific junctions across a broad set of publicly available non-cancer human RNA sequencing (RNA-seq) datasets. We compared cancer and non-cancer RNA-seq data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) Project and the Sequence Read Archive. We found that (i) averaging across cancer types, 80.6% of exon–exon junctions thought to be cancer-specific based on comparison with tissue-matched samples (σ = 13.0%) are in fact present in other adult non-cancer tissues throughout the body; (ii) 30.8% of junctions not present in any GTEx or TCGA normal tissues are shared by multiple samples within at least one cancer type cohort, and 87.4% of these distinguish between different cancer types; and (iii) many of these junctions not found in GTEx or TCGA normal tissues (15.4% on average, σ = 2.4%) are also found in embryological and other developmentally associated cells. These findings refine the meaning of RNA splicing event novelty, particularly with respect to the human neoepitope repertoire. Ultimately, cancer-specific exon–exon junctions may have a substantial causal relationship with the biology of disease.

scholarly journals Bilingual experience and executive control over the adult lifespan: The role of biological sex

2018 ◽  
Vol 22 (04) ◽  
pp. 733-751 ◽  
Author(s):  
SIVANIYA SUBRAMANIAPILLAI ◽  
MARIA NATASHA RAJAH ◽  
STAMATOULA PASVANIS ◽  
DEBRA TITONE
Keyword(s):  
Executive Control ◽  
Cognitive Aging ◽  
Wisconsin Card Sort Test ◽  
Adult Women ◽  
Language Experience ◽  
Card Sort ◽  
Adult Lifespan ◽  
Biological Sex ◽  
Age Related ◽  
Improved Performance

We investigated whether bilingual language experience over the lifespan impacts women and men in a manner that differentially buffers against age-related declines in executive control. To this end, we investigated whether executive control performance in a lifespan sample of adult women and men were differentially impacted by individual differences in bilingual language experience, assessed using an unspeeded measure of executive control: the Wisconsin Card Sort Test. The results suggested that women showed both the greatest degree of age-related decline across WCST measures, and a greater likelihood than men to express improved performance as a function of increased bilingual experience. We consider implications of this finding for advancing our understanding of the relation between bilingualism and cognition, and also the effects of biological sex on cognitive aging.

scholarly journals Thymic involution and rising disease incidence with age

2018 ◽  
Vol 115 (8) ◽  
pp. 1883-1888 ◽  
Author(s):  
Sam Palmer ◽  
Luca Albergante ◽  
Clare C. Blackburn ◽  
T. J. Newman
Keyword(s):  
T Cell ◽  
Power Law ◽  
Wide Spectrum ◽  
Disease Incidence ◽  
Thymic Involution ◽  
Incidence Data ◽  
Age Related ◽  
Exponential Decline ◽  
Combining Data ◽  
Cancer Types

For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation. In humans, the thymus atrophies from infancy, resulting in an exponential decline in T cell production with a half-life of ∼16 years, which we use as the basis for a minimal mathematical model of disease incidence. Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. This framework provides mechanistic insight into cancer emergence, suggesting that age-related decline in T cell output is a major risk factor.

scholarly journals Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3718-3723 ◽  
Author(s):  
Andrzej Bartke
Keyword(s):  
Mammalian Species ◽  
Induced Mutations ◽  
Average Life ◽  
Average Life Span ◽  
Enhanced Resistance ◽  
Age Related ◽  
Igf I ◽  
Extended Longevity ◽  
Resistance To Stress

Abstract The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH biosynthesis, GH actions, or sensitivity to IGF-I lead to extended longevity. Increases in the average life span in these mutants range from approximately 20–70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. Extended longevity of hypopituitary and GH-resistant mice appears to be due to multiple mechanisms including reduced insulin levels, enhanced insulin sensitivity, alterations in carbohydrate and lipid metabolism, reduced generation of reactive oxygen species, enhanced resistance to stress, reduced oxidative damage, and delayed onset of age-related disease. There is considerable evidence to suggest that the genetic and endocrine mechanisms that influence aging and longevity in mice may play a similar role in other mammalian species, including the human.

scholarly journals ULTRAVIOLET LIGHT AND THE MITOTIC CYCLE IN THE SEA URCHIN'S EGG

1954 ◽  
Vol 37 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Harold F. Blum ◽  
Elizabeth Flagler Kauzmann ◽  
George B. Chapman
Keyword(s):  
Cell Division ◽  
Ultraviolet Light ◽  
Refractory Period ◽  
Mitotic Cycle ◽  
Sperm Nucleus ◽  
Cell Division Cycle

The effect of ultraviolet light in delaying certain events in the cell division cycle has been examined. The time to fusion of the egg and sperm nucleus is not affected by doses of ultraviolet that cause considerable delay in other parts of the cycle. The principal delay occurs before anaphase. Between anaphase and cleavage there is only slight delay. The "refractory period" during which the radiation does not delay the immediate cycle of cell division, does not seem to represent complete refractoriness of the mitotic cycle to interference during this period.

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