Genetic control of lifespan: studies from animal models

1999 ◽  
Vol 1 (20) ◽  
pp. 1-12 ◽  
Author(s):  
Gary Van Zant ◽  
Gerald de Haan
Keyword(s):  
Animal Models ◽  
Large Scale ◽  
Genetic Research ◽  
Murine Models ◽  
Longevity Genes ◽  
History Of ◽  
Mammalian Genetics ◽  
History Of Use ◽  
Human And Mouse ◽  
Shed Light

The premise that there are genes that wield a strong influence on longevity has, until recently, not been a popular one and there has been no concerted effort to find such genes. However, the finding that single genes can have large effects on the lifespans of yeast, worms and flies raises the possibility that individual genes in mammals may similarly have relatively large effects on longevity. Recent advances in mammalian genetics, many associated with the large-scale efforts to sequence the human and mouse genomes, have accelerated the search for longevity genes, principally in mice. Here, we review results using animal models that have recently shed light on genes regulating longevity and ageing patterns. A large number of genetically defined strains of mice are available and this, together with their established history of use in genetic research and their relatively short lifespans, has made murine models particularly useful. We also review our own work in which genes regulating mouse lifespan and those regulating cell cycling of haematopoietic progenitor cells have been mapped to the same locations in the genome. These results suggest that some of the same genes affect both traits, and further suggest a cause-and-effect relationship between cumulative cell-cycle activity and longevity of an organism.

The “Millstätter Predigten” (Millstatt Sermons), Petrus Berchorius, and Mechthild of Magdeburg

Daphnis ◽  
2021 ◽  
Vol 50 (1) ◽  
pp. 59-84
Author(s):  
Sabine Seelbach
Keyword(s):  
Cultural Memory ◽  
Educational History ◽  
Mechthild Of Magdeburg ◽  
The World ◽  
History Of ◽  
History Of Use ◽  
Shed Light

Abstract This article presents the project “Virtual Benedictine library Millstatt” (www.virtbibmillstatt.com/), which is dedicated to the cultural memory and educational history of Carinthia in the broadest sense. It aims to reconstruct the hitherto little-known and little-researched corpus of manuscripts from the Benedictine Abbey of Millstatt, to identify its texts, and to shed light on their history of use. Against the background of the eventful history of ownership of the Millstatt library, the problems that arise when trying to reliably assign manuscripts scattered around the world to the Millstatt corpus are outlined. Examples will be used to show the extent to which external features (binding, signature system, accessories), but also text-internal indications, make the origin and ownership history of the manuscripts traceable. Spectacular new finds are presented, but also erroneous assumptions about the affiliation of certain texts to the reading canon of the Millstatt Benedictines are pointed out.

Iron Age landscape, society, and regionality : The material culture

2018 ◽  
Author(s):  
Stephen Rippon
Keyword(s):  
Material Culture ◽  
Iron Age ◽  
Large Scale ◽  
Good Reason ◽  
First Century ◽  
The Political ◽  
Symbolic Meanings ◽  
Big Picture ◽  
History Of ◽  
Shed Light

In his review of South East Britain in the later Iron Age, Hill (2007, 16) observed that ‘Since the 1980s, little attention has been given to large-scale social explanations and narratives in British Iron Age archaeology. Debates over core–periphery models, the interpretation of hillforts, and the nature of social organization, were—for good reason—eclipsed by a focus on the symbolic meanings of space, structured deposition, and ritual.’ He goes on to argue that British archaeology is in need of more ‘straightforward storyboards’ around which data can be arranged (Hill 2007, 16), and Brudenell (2012, 52) has similarly noted how ‘close-grained understandings have often been won at the expense of broader pictures . . . [and that] with a few exceptions, recent approaches have atomized the study of later prehistoric society, focussing on the specifics of the local social milieu at the expense of broader scales of social analysis’. There have been some ‘big picture’ studies—most notably Cunliffe’s (1974; 1978; 1991; 2005) Iron Age Communities in Britain—but all too often studies of this period have focused on specific counties, types of site, or artefact, and it is noticeable how little systematic mapping of data there was in three recent collections of papers (Gwilt and Haselgrove 1997; Haselgrove and Moore 2007; Haselgrove and Pope 2007). This study, in contrast, aims to shed light on one important ‘storyboard’: the territorial structures within which communities built their landscapes. The written history of Britain begins in the first century BC when we first get insights into its political and territorial arrangements, although as this was a period when the island was becoming embroiled in the political instability caused by the expansion of the Roman world, the trends seen then may not reflect the longer-term patterns of territorial stability or instability that preceded it. In 54 BC, for example, Caesar describes how his major opponents were a civitas (usually translated as ‘tribe’) who had recently surpassed the neighbouring Trinovantes as the paramount group in South East Britain (Gallic War, 20–1; Dunnett 1975, 8; Moore 2011).

scholarly journals Glycemia Lowering Effect of an Aqueous Extract of Hedychium coronarium Leaves in Diabetic Rodent Models

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 629 ◽  
Author(s):  
Ling-Shan Tse ◽  
Po-Lin Liao ◽  
Chi-Hao Tsai ◽  
Ching-Hao Li ◽  
Jiunn-Wang Liao ◽  
...  
Keyword(s):  
Animal Models ◽  
Aqueous Extract ◽  
Low Density Lipoprotein ◽  
Folk Medicine ◽  
Density Lipoprotein ◽  
Insulin Level ◽  
Diabetic Animal ◽  
Hedychium Coronarium ◽  
History Of ◽  
History Of Use

Hedychium coronarium has a long history of use worldwide as a food and in folk medicine. In this study, we aimed to investigate the effect of an aqueous extract of H. coronarium leaves (HC) on type 2 diabetes mellitus (T2DM). Two types of animal models were used in this study: Streptozotocin (STZ)-induced T2DM (Wistar rats; N = 8) and C57BKSdb/db mice (N = 5). After treatment with HC for 28 days, glucose tolerance improved in both of the diabetic animal models. As significant effects were shown after 14 days of treatment in the STZ-induced T2DM model, we carried out the experiments with it. After 28 days of treatment with HC, the levels of cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein were significantly improved in the STZ-induced T2DM model. The lesions degree of islet β-cells was decreased after the HC treatment. Although the insulin level increased moderately, the aldosterone level was significantly decreased in the HC-treated groups, suggesting that aldosterone might play an important role in this effect. In summary, HC is a natural product and it is worth exploring its effect on T2DM.

scholarly journals A New Analysis of Population History in Sabah and Sarawak

2018 ◽  
Vol 6 (4) ◽  
pp. 106-113
Author(s):  
Hashom Mohd Hakim ◽  
Japareng Lalung ◽  
Suresh Narayanen ◽  
Nasha Rodziadi Khaw ◽  
Geoffrey Keith Chambers ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Large Scale ◽  
Genetic Research ◽  
Jel Classification ◽  
Population History ◽  
Current View ◽  
Genetic Lineages ◽  
Niah Cave ◽  
History Of ◽  
Sabah And Sarawak

Objective - This study is a comprehensive account of contemporary knowledge concerning pre-historic communities in Sabah and Sarawak based on newly available evidence from genomic and archaeological research. Methodology/Technique - The data presented in this review was obtained from primary literature including recent reports on several Neolithic excavation sites including Gua Sireh, Bukit Tengkorak, Melanta Tutup, and Bukit Kamiri. Findings - Pre-neolithic populations existed in Borneo long before the arrival of Austronesians as is evident from Niah Cave remains. These considerably pre-date the arrival of the latter new immigrants around 3,500 years ago. Further genetic research is needed, as the current view of the history of the population is based on a limited number of ethnic groups among those currently living in Borneo and to date, no trace has been found of any surviving genetic lineages from the earliest settlers. Novelty - This review paints a contemporary picture from existing information. In particular, it highlights the need for further research on the topic, as the current view of the genetic history of the population in Sabah and Sarawak is only available on a limited number of ethnic groups currently living in Borneo. Developing a conclusive and composite view on this topic will require widespread genetic surveys of many more ethnic groups scattered throughout the Sabah and Sarawak areas. This will require large-scale next-generation techniques (such as genome-wide SNP surveys and whole genome sequencing etc.). These methods should be enhanced by examination of ancient materials including human remains and their associated artefacts. These initiatives will require a number of well-planned excavations of recent settlements (last 10,000 years) and the application of trace and ancient DNA methodology. Type of Paper - Review. Keywords: Population Genetics; Archaeology; Borneo; Sabah and Sarawak; Malaysia; Population History. JEL Classification: N90, Z10.

scholarly journals A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245962
Author(s):  
Jeremy D. Baker ◽  
Rikki L. Uhrich ◽  
Gerald C. Kraemer ◽  
Jason E. Love ◽  
Brian C. Kraemer
Keyword(s):  
Hepatitis C ◽  
Drug Development ◽  
Large Scale ◽  
Previous History ◽  
Drug Repurposing ◽  
Lead Compounds ◽  
Main Protease ◽  
History Of ◽  
History Of Use

Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of ~6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found ~50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 μM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.

scholarly journals Medical Marijuana Knowledge and Attitudes: A Survey of the California Pharmacists Association

2019 ◽  
Vol 10 ◽  
pp. 215013271983187 ◽  
Author(s):  
Dara Szyliowicz ◽  
Peter Hilsenrath
Keyword(s):  
Health Care Providers ◽  
Federal Policy ◽  
Medical Marijuana ◽  
Care Providers ◽  
Knowledge And Attitudes ◽  
Widespread Agreement ◽  
History Of ◽  
Level Of Knowledge ◽  
History Of Use ◽  
Shed Light

Views on the medical efficacy and acceptability of marijuana have changed over the years. California was the first state permitting individuals to use medical marijuana. Even with a long history of use and widespread agreement around the effectiveness of medical marijuana, the literature is sparse about the role health care providers, including pharmacists, play in this interaction. The purpose of this article is to shed light on knowledge and attitudes of pharmacists regarding medical marijuana. We developed a survey for pharmacists about their level of knowledge and attitudes toward medical marijuana. The survey was distributed using SurveyMonkey. It consisted of 44 questions and an opportunity to provide comments. We collaborated with the California Pharmacists Association who provided a link to the survey in October 2017 to their members. Results from 474 responses indicate a majority of providers believe that marijuana has medical efficacy. Yet most providers report that they neither have much information about medical marijuana nor do they know where to get such information. One area of particular concern is the potential for drug interactions. Pharmacists would feel more comfortable discussing medical marijuana if it was approved by the Food and Drug Administration. Moreover, they believe more research needs to occur. The variance between California and federal policy leads to dysfunction among pharmacists providing information to patients. We believe federal policy should change.

scholarly journals NHC-gold compounds mediate immune suppression through induction of AHR-TGFβ1 signalling in vitro and in scurfy mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Xinlai Cheng ◽  
Stefanie Haeberle ◽  
Iart Luca Shytaj ◽  
Rodrigo. A. Gama-Brambila ◽  
Jannick Theobald ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Aryl Hydrocarbon ◽  
Gold Compounds ◽  
Extended Lifespan ◽  
History Of ◽  
Chemical Inhibition ◽  
History Of Use ◽  
Human And Mouse

AbstractGold compounds have a long history of use as immunosuppressants, but their precise mechanism of action is not completely understood. Using our recently developed liver-on-a-chip platform we now show that gold compounds containing planar N-heterocyclic carbene (NHC) ligands are potent ligands for the aryl hydrocarbon receptor (AHR). Further studies showed that the lead compound (MC3) activates TGFβ1 signaling and suppresses CD4+ T-cell activation in vitro, in human and mouse T cells. Conversely, genetic knockdown or chemical inhibition of AHR activity or of TGFβ1-SMAD-mediated signaling offsets the MC3-mediated immunosuppression. In scurfy mice, a mouse model of human immunodysregulation polyendocrinopathy enteropathy X-linked syndrome, MC3 treatment reduced autoimmune phenotypes and extended lifespan from 24 to 58 days. Our findings suggest that the immunosuppressive activity of gold compounds can be improved by introducing planar NHC ligands to activate the AHR-associated immunosuppressive pathway, thus expanding their potential clinical application for autoimmune diseases.

Investigating the Dynamics of Suicidal Ideation

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Nina Hallensleben ◽  
Lena Spangenberg ◽  
Thomas Forkmann ◽  
Dajana Rath ◽  
Ulrich Hegerl ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Small Sample Size ◽  
Unipolar Depression ◽  
Small Sample ◽  
History Of ◽  
Severity Of Depression ◽  
Ecological Momentary ◽  
Depressive Episodes ◽  
Ema Method ◽  
Shed Light

Abstract. Background: Although the fluctuating nature of suicidal ideation (SI) has been described previously, longitudinal studies investigating the dynamics of SI are scarce. Aim: To demonstrate the fluctuation of SI across 6 days and up to 60 measurement points using smartphone-based ecological momentary assessments (EMA). Method: Twenty inpatients with unipolar depression and current and/or lifetime suicidal ideation rated their momentary SI 10 times per day over a 6-day period. Mean squared successive difference (MSSD) was calculated as a measure of variability. Correlations of MSSD with severity of depression, number of previous depressive episodes, and history of suicidal behavior were examined. Results: Individual trajectories of SI are shown to illustrate fluctuation. MSSD values ranged from 0.2 to 21.7. No significant correlations of MSSD with several clinical parameters were found, but there are hints of associations between fluctuation of SI and severity of depression and suicidality. Limitations: Main limitation of this study is the small sample size leading to low power and probably missing potential effects. Further research with larger samples is necessary to shed light on the dynamics of SI. Conclusion: The results illustrate the dynamic nature and the diversity of trajectories of SI across 6 days in psychiatric inpatients with unipolar depression. Prediction of the fluctuation of SI might be of high clinical relevance. Further research using EMA and sophisticated analyses with larger samples is necessary to shed light on the dynamics of SI.

Materials for the history of the gospel-Baptist movement in Ukraine

1996 ◽  
pp. 4-15
Author(s):  
S. Golovaschenko ◽  
Petro Kosuha
Keyword(s):  
Large Scale ◽  
Religious Studies ◽  
Theological Seminary ◽  
National Academy Of Sciences ◽  
Evangelical Christians ◽  
Evangelical Christian ◽  
First Results ◽  
History Of ◽  
Fruitful Cooperation ◽  
Academy Of Sciences

The report is based on the first results of the study "The History of the Evangelical Christians-Baptists in Ukraine", carried out in 1994-1996 by the joint efforts of the Department of Religious Studies at the Institute of Philosophy of the National Academy of Sciences of Ukraine and the Odessa Theological Seminary of Evangelical Christian Baptists. A large-scale description and research of archival sources on the history of evangelical movements in our country gave the first experience of fruitful cooperation between secular and church researchers.

Editorial Introduction

2020 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Editors of the JIOWS
Keyword(s):  
Nineteenth Century ◽  
Indian Ocean ◽  
Western Indian Ocean ◽  
Late Nineteenth Century ◽  
Fourth Volume ◽  
History Of ◽  
The Indian Ocean ◽  
Complex Relationships ◽  
Indian Ocean World ◽  
Shed Light

The editors are proud to present the first issue of the fourth volume of the Journal of Indian Ocean World Studies. This issue contains three articles, by James Francis Warren (Murdoch University), Kelsey McFaul (University of California, Santa Cruz), and Marek Pawelczak (University of Warsaw), respectively. Warren’s and McFaul’s articles take different approaches to the growing body of work that discusses pirates in the Indian Ocean World, past and present. Warren’s article is historical, exploring the life and times of Julano Taupan in the nineteenth-century Philippines. He invites us to question the meaning of the word ‘pirate’ and the several ways in which Taupan’s life has been interpreted by different European colonists and by anti-colonial movements from the mid-nineteenth century to the present day. McFaul’s article, meanwhile, takes a literary approach to discuss the much more recent phenomenon of Somali Piracy, which reached its apex in the last decade. Its contribution is to analyse the works of authors based in the region, challenging paradigms that have mostly been developed from analysis of works written in the West. Finally, Pawelczak’s article is a legal history of British jurisdiction in mid-late nineteenth-century Zanzibar. It examines one of the facets that underpinned European influence in the western Indian Ocean World before the establishment of colonial rule. In sum, this issue uses two key threads to shed light on the complex relationships between European and other Western powers and the Indian Ocean World.

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