scholarly journals SWS/NTE-dependent neuropathy is the model system to study neurodegeneration

2020 ◽  
Vol 26 ◽  
pp. 67-71
Author(s):  
N. P. Matiytsiv
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Glial Cells ◽  
Neurodegenerative Disorders ◽  
Organophosphorus Compounds ◽  
Transmembrane Protein ◽  
Therapeutic Agents ◽  
Model System ◽  
Neuropathy Target Esterase ◽  
Swiss Cheese

Today there is many described neurodegenerative D. melanogaster mutants, which characterized by development of degenerative changes in brain. One of them are a swiss cheese (sws) gene mutants. Mutations in this gene causes apoptosis of neurons and hyperwrapping of their somas by the glial cells, reducing of life expectancy and decrease of locomotion. The sws gene is the ortholog of mammal’s neuropathy target esterase (NTE / PNPLA6). NTE is s neuronal, transmembrane protein, that possesses serinesterase activity, and can be the target for neurotoxic organophosphorus compounds activity. Mutations in PNPLA6 gene cause number hereditary neurodegenerative disorders, which nowadays are incurable. The search for therapeutic agents require use of model objects because researches on humans have both methodical and ethical limitations. During two last decades D. melanogaster has proven itself as a good model for study of neurodegenerative diseases. In this review, we described general characteristics of D. melanogaster gene sws, consequences of its mutations and provided evidences of high conservatism of gene product. Keywords: gene swiss cheese, neuropathy target esterase, neurodegeneration, brain, life span.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

scholarly journals Dynamics of life expectancy and life span equality

2020 ◽  
Vol 117 (10) ◽  
pp. 5250-5259 ◽  
Author(s):  
José Manuel Aburto ◽  
Francisco Villavicencio ◽  
Ugofilippo Basellini ◽  
Søren Kjærgaard ◽  
James W. Vaupel
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Health Policies ◽  
Public Health Policies ◽  
Dynamic Relationship ◽  
Mortality Increase ◽  
Long Time ◽  
Underlying Causes ◽  
The Relationship ◽  
Over Time

As people live longer, ages at death are becoming more similar. This dual advance over the last two centuries, a central aim of public health policies, is a major achievement of modern civilization. Some recent exceptions to the joint rise of life expectancy and life span equality, however, make it difficult to determine the underlying causes of this relationship. Here, we develop a unifying framework to study life expectancy and life span equality over time, relying on concepts about the pace and shape of aging. We study the dynamic relationship between life expectancy and life span equality with reliable data from the Human Mortality Database for 49 countries and regions with emphasis on the long time series from Sweden. Our results demonstrate that both changes in life expectancy and life span equality are weighted totals of rates of progress in reducing mortality. This finding holds for three different measures of the variability of life spans. The weights evolve over time and indicate the ages at which reductions in mortality increase life expectancy and life span equality: the more progress at the youngest ages, the tighter the relationship. The link between life expectancy and life span equality is especially strong when life expectancy is less than 70 y. In recent decades, life expectancy and life span equality have occasionally moved in opposite directions due to larger improvements in mortality at older ages or a slowdown in declines in midlife mortality. Saving lives at ages below life expectancy is the key to increasing both life expectancy and life span equality.

FEATURES OF THE BIOLOGICAL DEVELOPMENT OF THE BIRD CHERRY-OAT APHID (RHOPALOSIPHUM PADI) IN THE LABORATORY

2021 ◽  
pp. 142-148
Author(s):  
YA.YU. GOLIVANOV ◽  
◽  
V.V. ZELENENKO ◽  
V.V. GRITSENKO
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Average Duration ◽  
Rhopalosiphum Padi ◽  
Reproductive Period ◽  
Average Life ◽  
Average Life Expectancy ◽  
Entire Life ◽  
Biological Development

The article presents data on the assessment of some issues of the ontogenesis of the bird cherryoat aphid: the average life expectancy, the number of offspring over a lifetime, the beginning of the reproductive period, the end of the reproductive period, the duration of the reproductive period, the life span of aphids and the number of offspring. The author found that the average life expectancy of animals was 21.55 days. The beginning of the reproductive period, on average, was on days 7–8, the end – on day 19. The average duration of the reproductive period was 12.5 days. The average number of offspring over the entire life for individuals in the sample was 34 nymphs, in a separate litter – 2–3 nymphs.

scholarly journals Growing Income-Based Inequalities in Old-Age Life Expectancy in Sweden, 2006–2015

Demography ◽  
2021 ◽  
Author(s):  
Stefan Fors ◽  
Jonas W. Wastesson ◽  
Lucas Morin
Keyword(s):  
Income Inequality ◽  
Life Expectancy ◽  
Life Span ◽  
Old Age ◽  
Remaining Life ◽  
Neighborhood Deprivation ◽  
Income Gap ◽  
Remaining Life Expectancy ◽  
Mortality Improvement ◽  
Income Quartile

Abstract Sweden is known for high life expectancy and economic egalitarianism, yet in recent decades it has lost ground in both respects. This study tracked income inequality in old-age life expectancy and life span variation in Sweden between 2006 and 2015, and examined whether patterns varied across levels of neighborhood deprivation. Income inequality in remaining life expectancy at ages 65, 75, and 85 increased. The gap in life expectancy at age 65 grew by more than a year between the lowest and the highest income quartiles, for both men (from 3.4 years in 2006 to 4.5 years in 2015) and women (from 2.3 to 3.4 years). This widening income gap in old-age life expectancy was driven by different rates of mortality improvement: individuals with higher incomes increased their life expectancy at a faster rate than did those with lower incomes. Women with the lowest incomes experienced no improvement in old-age life expectancy. Furthermore, life span variation increased in the lowest income quartile, while it decreased slightly among those in the highest quartile. Income was found to be a stronger determinant of old-age life expectancy than neighborhood deprivation.

scholarly journals Case Report: Synucleinopathy Associated With Phalaris Neurotoxicity in Sheep

2021 ◽  
Vol 8 ◽  
Author(s):  
Mourad Tayebi ◽  
Pedro Pinczowski ◽  
Umma Habiba ◽  
Rizwan Khan ◽  
Monique A. David ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neurodegenerative Disorders ◽  
Lewy Bodies ◽  
Model System ◽  
Neuronal Function ◽  
Immunofluorescence Analysis ◽  
Common Endpoint ◽  
Clear Link ◽  
Plant Poisoning ◽  
Pasture Plants

Chronic intoxication with tryptamine-alkaloid-rich Phalaris species (spp.) pasture plants is known colloquially as Phalaris staggers syndrome, a widely occurring neurological disorder of sheep, cattle, horses, and kangaroos. Of comparative interest, structurally analogous tryptamine-alkaloids cause experimental parkinsonism in primates. This study aimed to investigate the neuropathological changes associated with spontaneous cases of Phalaris staggers in sheep with respect to those encountered in human synucleinopathy. In sheep affected with Phalaris staggers, histological, immunohistochemical, and immunofluorescence analysis revealed significant accumulation of neuromelanin and aggregated α-synuclein in the perikaryon of neurons in the cerebral cortex, thalamus, brainstem, and spinal cord. Neuronal intracytoplasmic Lewy bodies inclusions were not observed in these cases of ovine Phalaris staggers. These important findings established a clear link between synucleinopathy and the neurologic form of Phalaris plant poisoning in sheep, demonstrated in six of six affected sheep. Synucleinopathy is a feature of a number of progressive and fatal neurodegenerative disorders of man and may be a common endpoint of such disorders, which in a variety of ways perturb neuronal function. However, whether primary to the degenerative process or a consequence of it awaits clarification in an appropriate model system.

scholarly journals Modulation of Opioid Actions by Nitric Oxide Signaling

2009 ◽  
Vol 110 (1) ◽  
pp. 166-181 ◽  
Author(s):  
Noboru Toda ◽  
Shiroh Kishioka ◽  
Yoshio Hatano ◽  
Hiroshi Toda ◽  
David S. Warner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Glial Cells ◽  
Withdrawal Syndrome ◽  
Therapeutic Agents ◽  
Nitric Oxide Signaling ◽  
Endogenous Nitric Oxide ◽  
Oxide Synthase ◽  
New Strategies

Nitric oxide (NO) plays pivotal roles in controlling physiological functions, participates in pathophysiological intervention, and is involved in mechanisms underlying beneficial or untoward actions of therapeutic agents. Endogenous nitric oxide is formed by three isoforms of nitric oxide synthase: endothelial, neurogenic and inducible. The former two are constitutively present mainly in the endothelium and nervous system, respectively, and the latter one is induced by lipopolysaccharides or cytokines mainly in mitochondria and glial cells. Constitutively formed nitric oxide modulates the actions of morphine and related analgesics by either enhancing or reducing antinociception. Tolerance to and dependence on morphine or its withdrawal syndrome are likely prevented by nitric oxide synthase inhibition. Information concerning modulation of morphine actions by nitric oxide is undoubtedly useful in establishing new strategies for efficient antinociceptive treatment and for minimizing noxious and unintended reactions.

The Framingham Heart Study: a pivotal legacy of the last millennium

2000 ◽  
Vol 9 (2) ◽  
pp. 147-151 ◽  
Author(s):  
LG Futterman ◽  
L Lemberg
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Framingham Heart Study ◽  
Life Time ◽  
Environmental Safety ◽  
Average Life Span ◽  
Safety Standards ◽  
Greco Roman ◽  
Heart Study ◽  
Cv Disease

The life span at birth in the Greco-Roman era (200-300 BC) was 27 years. The life span in 1900 was 47 years, representing a gain of 20 years in more than 2000 years, or an increase of 1 year per century. At the close of the 20th century, the average life span was 77 years. This is a 30-year gain in life expectancy in only 1 century, or an average of 3 years for every decade in the last century. Compare that with only 1 year gain in life expectancy per century for the previous 20 centuries. It must be quite evident from this brief review that in the last century the Framingham Heart Study played a pivotal role in influencing physicians and the public to place major emphasis on the prevention of CV disease. To be sure, the control of epidemics, cure of infections with antibiotics, universal vaccination, and establishing food and environmental safety standards in the last century were instrumental in extending the life span. Nevertheless, major and direct influences on the explosive expansion in longevity during our life time were the contributions of the Framingham Heart Study. To paraphrase W. B. Kannel, a chief investigator in the Framingham Heart Study, "A cardiovascular event should be regarded as a medical failure rather than the first indication for the need to treat."

Achievement Domain and Life Expectancies in Japanese Civilization

1997 ◽  
Vol 44 (2) ◽  
pp. 103-114 ◽  
Author(s):  
Dean Keith Simonton
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Multiple Regression ◽  
Violent Death ◽  
Religious Leaders ◽  
Current Investigation ◽  
Regression Analyses ◽  
Historical Figures ◽  
Domain Differences

Previous studies have found that the expected life span of eminent personalities may vary systematically according to the domain of achievement. The current investigation examines this phenomenon more closely by 1) introducing methodological controls for potential gender and cohort artifacts, 2) adding substantive predictors (e.g., suicide and homicide) that provide clues regarding the substantive basis for the differences, 3) scrutinizing a greater variety of achievement domains in both creativity and leadership, and 4) using a non-Western sample of historical figures (1,632 Japanese born between 450 and 1883 A.D.). Multiple regression analyses revealed domain contrasts in life expectancy (e.g., the shorter life spans of fiction authors and political figures, but the longer life spans of religious leaders and sword makers). In addition, the analyses helped decipher the extent to which these domain differences were due to violent death or to the stress of occupying high positions of power.

scholarly journals Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1803 ◽  
Author(s):  
Amira Mbarek ◽  
Ghina Moussa ◽  
Jeanne Leblond Chain
Keyword(s):  
Cardiovascular Disease ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Mechanistic Studies ◽  
Molecular Tweezers ◽  
The Past ◽  
Pharmaceutical Applications ◽  
Controlled Motion

Synthetic acyclic receptors, composed of two arms connected with a spacer enabling molecular recognition, have been intensively explored in host-guest chemistry in the past decades. They fall into the categories of molecular tweezers, clefts and clips, depending on the geometry allowing the recognition of various guests. The advances in synthesis and mechanistic studies have pushed them forward to pharmaceutical applications, such as neurodegenerative disorders, infectious diseases, cancer, cardiovascular disease, diabetes, etc. In this review, we provide a summary of the synthetic molecular tweezers, clefts and clips that have been reported for pharmaceutical applications. Their structures, mechanism of action as well as in vitro and in vivo results are described. Such receptors were found to selectively bind biological guests, namely, nucleic acids, sugars, amino acids and proteins enabling their use as biosensors or therapeutics. Particularly interesting are dynamic molecular tweezers which are capable of controlled motion in response to an external stimulus. They proved their utility as imaging agents or in the design of controlled release systems. Despite some issues, such as stability, cytotoxicity or biocompatibility that still need to be addressed, it is obvious that molecular tweezers, clefts and clips are promising candidates for several incurable diseases as therapeutic agents, diagnostic or delivery tools.

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