scholarly journals Reflections on telomere dynamics and ageing-related diseases in humans

2018 ◽  
Vol 373 (1741) ◽  
pp. 20160436 ◽  
Author(s):  
Abraham Aviv ◽  
Jerry W. Shay
Keyword(s):  
African Ancestry ◽  
Geographical Location ◽  
Active Role ◽  
Epidemiological Studies ◽  
European Ancestry ◽  
Evolutionary Forces ◽  
Trade Offs ◽  
Telomere Biology ◽  
Telomere Dynamics

Epidemiological studies have principally relied on measurements of telomere length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL (LTL) displays vast variation across individuals—a phenomenon already observed in newborns. It is highly heritable, longer in females than males and in individuals of African ancestry than European ancestry. LTL is also longer in offspring conceived by older men. The traditional view regards LTL as a passive biomarker of human ageing. However, new evidence suggests that a dynamic interplay between selective evolutionary forces and TL might result in trade-offs for specific health outcomes. From a biological perspective, an active role of TL in ageing-related human diseases could occur because short telomeres increase the risk of a category of diseases related to restricted cell proliferation and tissue degeneration, including cardiovascular disease, whereas long telomeres increase the risk of another category of diseases related to increased proliferative growth, including major cancers. To understand the role of telomere biology in ageing-related diseases, it is essential to expand telomere research to newborns and children and seek further insight into the underlying causes of the variation in TL due to ancestry and geographical location. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

scholarly journals Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nathan Nakatsuka ◽  
Nick Patterson ◽  
Nikolaos A. Patsopoulos ◽  
Nicolas Altemose ◽  
Arti Tandon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
African American ◽  
African Americans ◽  
Odds Ratio ◽  
African Ancestry ◽  
Epidemiological Studies ◽  
Chromosome 1 ◽  
European Ancestry ◽  
Increased Risk ◽  
West Africans

Abstract Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.

A Genome-Wide Assessment of Inherited Genetic Variants and the Risk of Langerhans Cell Histiocytosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4059-4059
Author(s):  
Erin Peckham ◽  
Philip J Lupo ◽  
Michael E Scheurer ◽  
Rikhia Chakraborty ◽  
John Belmont ◽  
...  
Keyword(s):  
Association Analysis ◽  
Genetic Variants ◽  
Langerhans Cell Histiocytosis ◽  
African Ancestry ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
P Value ◽  
Genome Wide ◽  
A Genome

Abstract Introduction: Langerhans cell histiocytosis (LCH) is a disease characterized by inflammatory lesions including pathologic CD207+ dendritic cells. Clinically, LCH is highly variable ranging from single lesions to highly aggressive, disseminated disease involving multiple organs and requiring intensive chemotherapy. Recent data support a model of pathogenesis in which activating somatic mutations in MAPK pathway genes arise in myeloid DC precursors. However, little is known about genetic susceptibility to this condition. Therefore, we conducted a genome-wide association study to characterize the role of inherited genetic variants on disease risk. Methods: We utilized a case-parent trio approach, which is immune to the effects of population stratification bias. Specifically, this allows for the inclusion of individuals regardless of genetic ancestry. LCH case-parent trios (n=134) were recruited from Texas Children's Cancer Center. Genotyping was performed using the Illumina Omni-5 Quad BeadChip. Genetic ancestry was determined using the bioinformatics algorithm STRUCTURE. To inform this algorithm, a set of 12,898 autosomal ancestry informative markers specifically identified to infer population substructure was extracted from the study trios. Estimated genomic ancestral proportions were then used to classify each study participant as either of European ancestry, Amerindian ancestry, or of African ancestry. For the association analysis, we focused on the role of common variants (i.e., minor allele frequency ≥5%). The association analysis was conducted utilizing the PREMIM-EMIM algorithm, an established, multinomial log-likelihood approach for assessing case-parent trios GWAS data. This method allows for the inclusion of "incomplete" trios (e.g., mother-case duos). We applied a genome-wide statistical significance cutoff of p<1.0x10-5. Results: In this GWAS, LCH cases were predominantly male (54%), and based on the genetic ancestry analysis, 60% were of European ancestry, 36% Amerindian ancestry, and 4% African ancestry. Among the 343 individuals included in the analysis, 1,672,105 SNPs autosomal SNPs were assessed and an overview of the results is displayed using a Manhattan plot. We identified five potential inherited genomic regions associated with LCH susceptibility. The strongest associations between inherited SNPs and childhood LCH were seen in SMAD6 on chromosome 15 (p-value = 2.38x10-7) and in ECE1 on chromosome 1 (p-value = 2.15x10-6). Conclusions: In this genome-wide assessment of the role of inherited genetic variation on the risk of LCH, we identified SNPs with significant effects in genes implicated in diverse pathways including embryogenesis and cellular division. Among the proteins encoded by the regions identified, SMAD6and ECE1 have both been reported to impact ERK activation, a critical feature of LCH pathogenesis. These findings support potential for inherited genetic variants to influence risk of developing LCH. Disclosures Allen: NovImmune: Consultancy, Other: unpaid; Roche: Consultancy, Other: unpaid.

scholarly journals The role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing

2018 ◽  
Vol 373 (1741) ◽  
pp. 20160452 ◽  
Author(s):  
Andrew J. Young
Keyword(s):  
Life History ◽  
Evolutionary Biology ◽  
Life History Evolution ◽  
Telomere Maintenance ◽  
Causal Role ◽  
Telomere Attrition ◽  
Trade Offs ◽  
Evolution Of Life ◽  
Telomere Biology

Evolutionary biology and biomedicine have seen a surge of recent interest in the possibility that telomeres play a role in life-history trade-offs and ageing. Here, I evaluate alternative hypotheses for the role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing, and highlight outstanding challenges. First, while recent findings underscore the possibility of a proximate causal role for telomeres in current–future trade-offs and ageing, it is currently unclear (i) whether telomeres ever play a causal role in either and (ii) whether any causal role for telomeres arises via shortening or length-independent mechanisms. Second, I consider why, if telomeres do play a proximate causal role, selection has not decoupled such a telomere-mediated trade-off between current and future performance. Evidence suggests that evolutionary constraints have not rendered such decoupling impossible. Instead, a causal role for telomeres would more plausibly reflect an adaptive strategy, born of telomere maintenance costs and/or a function for telomere attrition (e.g. in countering cancer), the relative importance of which is currently unclear. Finally, I consider the potential for telomere biology to clarify the constraints at play in life-history evolution, and to explain the form of the current–future trade-offs and ageing trajectories that we observe today. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

scholarly journals International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline M. Nievergelt ◽  
Adam X. Maihofer ◽  
Torsten Klengel ◽  
Elizabeth G. Atkinson ◽  
Chia-Yen Chen ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Meta Analysis ◽  
African Ancestry ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Design prototyping as a translational tool for medical device commercialization

2020 ◽  
Vol 6 (2) ◽  
pp. 215-232 ◽  
Author(s):  
Rowan Page ◽  
Kieran John
Keyword(s):  
Medical Device ◽  
Real World ◽  
Design Research ◽  
Interdisciplinary Collaboration ◽  
Effective Communication ◽  
Active Role ◽  
End Users ◽  
Trade Offs ◽  
Real World Applications

Translational design is an increasingly important objective for universities as research institutions are seeking to play a more active role in the commercialization of fundamental medical research. Practice-based designers working within these academic contexts have a skill set that positions them to make a contribution to translating fundamental research into real-world applications. Real world applications of research that are informed by the needs of end-users and actioned through the creation of medical device prototypes. The translational designer’s toolkit includes a range of methodologies, frameworks, procedures and processes to identify problems, conceptualize ideas and create functional prototypes. Progressing research towards commercialization through prototyping is one of the most important skills leveraged by translational design researchers. This article details two case studies of practice-based design research within a large Australian university. It discusses the role of design prototyping as a key part of a lean and integrated development process that relies on accumulative rounds of iteration and interdisciplinary collaboration mediated through artefacts. Design prototyping is used within these projects to bring ideas to life and enable more effective communication between diverse stakeholder groups spanning across academia and industry, and across the boundaries of research and application. This article unpacks the key role of prototyping as a translational tool to iteratively test, refine and conceptually verify ideas, while additionally providing boundary objects for effective communication. This discussion addresses the benefits and limitations of prototyping as a translational tool, including the ability of prototyping to save time and development costs, explore constraints and trade-offs, and communicate with industry partners and end-users through tactile objects and/or real experiences. Design prototyping is an efficient and effective process that embraces failure in early stages of development, where the consequences are limited and the benefit substantial. The article explores how prototyping can provide the backbone to industrial design researchers working in translational contexts to drive development to real-world application and to effectively engage with research end-users.

scholarly journals Coexpression network analysis identified lncRNAs-mRNAs with potential relevance in African ancestry prostate cancer

2021 ◽  
pp. FSO749
Author(s):  
Rafael Parra-Medina ◽  
Liliana López-Kleine ◽  
Sandra Ramírez-Clavijo ◽  
César Payán-Gómez
Keyword(s):  
Prostate Cancer ◽  
Network Analysis ◽  
African Ancestry ◽  
European Ancestry ◽  
Coexpression Network ◽  
Future Studies ◽  
Impact On Survival ◽  
Antisense Lncrnas ◽  
Coexpression Network Analysis

Aim: This study aims to investigate similarities and differences using lncRNA and mRNA coexpression network analysis in African ancestry (AA) and European ancestry (EA) among prostate cancer (PCa) patients. Methods: We performed weighted gene coexpression network analysis of the expression from 49 of AA and 49 of EA to identify lncRNAs-mRNAs. Results: 27 lncRNAs and 36 mRNAs were highly expressed in patients of AA. Two mRNAs and their antisense lncRNAs were expressed. Additionally, seven mRNAs were DE or coexpressed and had an impact on survival. Conclusion: We present a list of lncRNAs and mRNAs that were DE and coexpressed when comparing patients of AA and EA, and these data are a resource for future studies to understand the role of lncRNAs.

Role of spectrin in membrane fusion and in shape change of human erythrocyte ghost

1978 ◽  
Vol 36 (2) ◽  
pp. 328-329
Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston
Keyword(s):  
Conformational Changes ◽  
Human Erythrocyte ◽  
Shape Change ◽  
Membrane Surface ◽  
Slight Modification ◽  
Active Role ◽  
Main Role ◽  
Bank Blood ◽  
Human Erythrocyte Ghost

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.

Elucidation of block boundaries as the dissolution channels in hydrated cement

1978 ◽  
Vol 36 (1) ◽  
pp. 484-485
Author(s):  
N.V. Belov ◽  
U.I. Papiashwili ◽  
B.E. Yudovich
Keyword(s):  
Liquid Phase ◽  
Grain Boundaries ◽  
Benzoyl Peroxide ◽  
Phase Contrast ◽  
Active Role ◽  
Point Of View ◽  
Hardened Cement ◽  
Hydrated Cement ◽  
Hardened Cement Paste

It has been almost universally adopted that dissolution of solids proceeds with development of uniform, continuous frontiers of reaction.However this point of view is doubtful / 1 /. E.g. we have proved the active role of the block (grain) boundaries in the main phases of cement, these boundaries being the areas of hydrate phases' nucleation / 2 /. It has brought to the supposition that the dissolution frontier of cement particles in water is discrete. It seems also probable that the dissolution proceeds through the channels, which serve both for the liquid phase movement and for the drainage of the incongruant solution products. These channels can be appeared along the block boundaries.In order to demonsrate it, we have offered the method of phase-contrast impregnation of the hardened cement paste with the solution of methyl metacrylahe and benzoyl peroxide. The viscosity of this solution is equal to that of water.

Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms

2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Review Paper ◽  
Heart Diseases ◽  
Folk Medicine ◽  
Active Role ◽  
Current Review ◽  
Different Types ◽  
Positive Effect

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.

Russia’s Market of Mergers and Acquisitions: Stages, Features and Prospects

2009 ◽  
pp. 23-45 ◽  
Author(s):  
A. Radygin
Keyword(s):  
Open Access ◽  
Mergers And Acquisitions ◽  
Corporate Control ◽  
Active Role ◽  
Data Bases ◽  
2008 Financial Crisis ◽  
Legal Norms ◽  
Role Of The State ◽  
Access Data

The article deals with key tendencies in the development of Russia’s market of mergers and acquisitions in the first decade of the 21st century. Quantitative parameters are analyzed by using available in the open access data bases for the years 2003-2008 taking into consideration new tendencies relating to 2008 financial crisis. An active role of the state played in the market of corporate control represents an important factor. Special attention is given to issues of development of Russia’s system of legal norms regulating the market of mergers and acquisitions.

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