scholarly journals THE PHYSIOPATHOLOGICAL ROLES OF ANDROGENS IN MOTONEURONS

2020 ◽  
Author(s):  
Angelo Poletti
Keyword(s):  
Androgen Receptor ◽  
Physiological Function ◽  
Muscular Atrophy ◽  
Target Cells ◽  
Male Sex ◽  
Polyglutamine Tract ◽  
High Level ◽  
The Brain ◽  
Very High ◽  
Cells Death

The androgen receptor has been purified in the ‘70s and cloned in the ‘80s. It is a member of the steroid receptor superfamily and mediated the most important effects of androgen in androgen dependent or sensitive tissues. Several physiological function of the brain are differentially controlled in the two sexes and androgens play specific role in the processes of sexual differentiation and it is involved in the maintenance of male sex behaviour in adulthood. When mutated, the androgen receptor may impact on many of these androgen-regulated activities because of a loss of androgenic function in target cells. However, in the case of a peculiar type of mutation, the elongation of the polyglutamine tract normally present in its N-terminus, the androgen receptor becomes neurotoxic and induces cells death of a number of motoneurons in the spinal cord, which express very high level of this protein. Here, we will briefly discuss the most important actions of androgen receptor-mediated androgen activity in the brain and the mechanisms by which the mutant androgen receptor may lead to neurodegeneration in Spinal and Bulbar Muscular Atrophy (SBMA).

scholarly journals SIK3–HDAC4 signaling regulates Drosophila circadian male sex drive rhythm via modulating the DN1 clock neurons

2017 ◽  
Vol 114 (32) ◽  
pp. E6669-E6677 ◽  
Author(s):  
Shinsuke Fujii ◽  
Patrick Emery ◽  
Hubert Amrein
Keyword(s):  
Distinct Pattern ◽  
M Cells ◽  
Locomotor Rhythm ◽  
Sex Drive ◽  
Short Period ◽  
Histone Deacetylase 4 ◽  
Male Sex ◽  
High Level ◽  
And Behavior ◽  
The Brain

The physiology and behavior of many organisms are subject to daily cycles. In Drosophila melanogaster the daily locomotion patterns of single flies are characterized by bursts of activity at dawn and dusk. Two distinct clusters of clock neurons—morning oscillators (M cells) and evening oscillators (E cells)—are largely responsible for these activity bursts. In contrast, male–female pairs of flies follow a distinct pattern, most notably characterized by an activity trough at dusk followed by a high level of male courtship during the night. This male sex drive rhythm (MSDR) is mediated by the M cells along with DN1 neurons, a cluster of clock neurons located in the dorsal posterior region of the brain. Here we report that males lacking Salt-inducible kinase 3 (SIK3) expression in M cells exhibit a short period of MSDR but a long period of single-fly locomotor rhythm (SLR). Moreover, lack of Sik3 in M cells decreases the amplitude of PERIOD (PER) cycling in DN1 neurons, suggesting that SIK3 non–cell-autonomously regulates DN1 neurons’ molecular clock. We also show that Sik3 reduction interferes with circadian nucleocytoplasmic shuttling of Histone deacetylase 4 (HDAC4), a SIK3 phosphorylation target, in clock neurons and that constitutive HDAC4 localization in the nucleus shortens the period of MSDR. Taking these findings together, we conclude that SIK3–HDAC4 signaling in M cells regulates MSDR by regulating the molecular oscillation in DN1 neurons.

scholarly journals Pharmaco-proteogenomic profiling of pediatric diffuse midline glioma to inform future treatment strategies

Oncogene ◽  
2021 ◽  
Author(s):  
Izac J. Findlay ◽  
Geoffry N. De Iuliis ◽  
Ryan J. Duchatel ◽  
Evangeline R. Jackson ◽  
Nicholas A. Vitanza ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Treatment Strategies ◽  
World Health ◽  
Driver Mutations ◽  
High Level ◽  
Based Medicine ◽  
The Brain ◽  
Very High ◽  
Diffuse Midline Glioma

AbstractDiffuse midline glioma (DMG) is a deadly pediatric and adolescent central nervous system (CNS) tumor localized along the midline structures of the brain atop the spinal cord. With a median overall survival (OS) of just 9–11-months, DMG is characterized by global hypomethylation of histone H3 at lysine 27 (H3K27me3), driven by recurring somatic mutations in H3 genes including, HIST1H3B/C (H3.1K27M) or H3F3A (H3.3K27M), or through overexpression of EZHIP in patients harboring wildtype H3. The recent World Health Organization’s 5th Classification of CNS Tumors now designates DMG as, ‘H3 K27-altered’, suggesting that global H3K27me3 hypomethylation is a ubiquitous feature of DMG and drives devastating transcriptional programs for which there are no treatments. H3-alterations co-segregate with various other somatic driver mutations, highlighting the high-level of intertumoral heterogeneity of DMG. Furthermore, DMG is also characterized by very high-level intratumoral diversity with tumors harboring multiple subclones within each primary tumor. Each subclone contains their own combinations of driver and passenger lesions that continually evolve, making precision-based medicine challenging to successful execute. Whilst the intertumoral heterogeneity of DMG has been extensively investigated, this is yet to translate to an increase in patient survival. Conversely, our understanding of the non-genomic factors that drive the rapid growth and fatal nature of DMG, including endogenous and exogenous microenvironmental influences, neurological cues, and the posttranscriptional and posttranslational architecture of DMG remains enigmatic or at best, immature. However, these factors are likely to play a significant role in the complex biological sequelae that drives the disease. Here we summarize the heterogeneity of DMG and emphasize how analysis of the posttranslational architecture may improve treatment paradigms. We describe factors that contribute to treatment response and disease progression, as well as highlight the potential for pharmaco-proteogenomics (i.e., the integration of genomics, proteomics and pharmacology) in the management of this uniformly fatal cancer.

Polyglutamine tract expansion of the androgen receptor in a motoneuronal model of spinal and bulbar muscular atrophy

2001 ◽  
Vol 56 (3-4) ◽  
pp. 215-220 ◽  
Author(s):  
F. Piccioni ◽  
S. Simeoni ◽  
I. Andriola ◽  
E. Armatura ◽  
S. Bassanini ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Polyglutamine Tract

التغير المناخي واثره في المقنن المائي لمحصول العنب في محافظة ديالى

2019 ◽  
Vol 1 (34) ◽  
pp. 391-422
Author(s):  
اشواق حسن حميد صالح
Keyword(s):  
Climate Change ◽  
Statistical Analysis ◽  
Wind Speed ◽  
Extreme Temperature ◽  
Solar Brightness ◽  
The Subject ◽  
Climate Station ◽  
The Times ◽  
High Level ◽  
Very High

Climate change and its impact on water resources is the problem of the times. Therefore, this study is concerned with the subject of climate change and its impact on the water ration of the grape harvest in Diyala Governorate. The study was based on the data of the Khanaqin climate station for the period 1973-2017, (1986-2017) due to lack of data at governorate level. The general trend of the elements of the climate and its effect on the water formula was extracted. The equation of change was extracted for the duration of the study. The statistical analysis was also used between the elements of the climate (actual brightness, normal temperature, micro and maximum degrees Celsius, wind speed m / s, relative humidity% The results of the statistical analysis confirm that the water ration for the study area is based mainly on the X7 evaporation / netting variable, which is affected by a set of independent variables X1 Solar Brightness X4 X5 Extreme Temperature Wind Speed ​​3X Minimal Temperature and Very High Level .

Territorial Distribution of Alcohol and Drug Addictions Mortality Concerning Regional Disparities in the Slovak Republic from Year 1996 to Year 2015

2020 ◽  
Keyword(s):  
Mortality Rate ◽  
Slovak Republic ◽  
Regional Disparities ◽  
Point Of View ◽  
Extreme Position ◽  
Data Set ◽  
Female Sex ◽  
Male Sex ◽  
The Individual ◽  
High Level

BACKGROUND: This paper deals with territorial distribution of the alcohol and drug addictions mortality at a level of the districts of the Slovak Republic. AIM: The aim of the paper is to explore the relations within the administrative territorial division of the Slovak Republic, that is, between the individual districts and hence, to reveal possibly hidden relation in alcohol and drug mortality. METHODS: The analysis is divided and executed into the two fragments – one belongs to the female sex, the other one belongs to the male sex. The standardised mortality rate is computed according to a sequence of the mathematical relations. The Euclidean distance is employed to compute the similarity within each pair of a whole data set. The cluster analysis examines is performed. The clusters are created by means of the mutual distances of the districts. The data is collected from the database of the Statistical Office of the Slovak Republic for all the districts of the Slovak Republic. The covered time span begins in the year 1996 and ends in the year 2015. RESULTS: The most substantial point is that the Slovak Republic possesses the regional disparities in a field of mortality expressed by the standardised mortality rate computed particularly for the diagnoses assigned to the alcohol and drug addictions at a considerably high level. However, the female sex and the male sex have the different outcome. The Bratislava III District keeps absolutely the most extreme position. It forms an own cluster for the both sexes too. The Topoľčany District bears a similar extreme position from a point of view of the male sex. All the Bratislava districts keep their mutual notable dissimilarity. Contrariwise, evaluation of a development of the regional disparities among the districts looks like notably heterogeneously. CONCLUSIONS: There are considerable regional discrepancies throughout the districts of the Slovak Republic. Hence, it is necessary to create a common platform how to proceed with the solution of this issue.

Relations between carbon removal rates, biofilm size and density of a novel anaerobic reactor: the inverse turbulent bed

2000 ◽  
Vol 41 (4-5) ◽  
pp. 253-260 ◽  
Author(s):  
P. Buffière ◽  
R. Moletta
Keyword(s):  
Removal Rate ◽  
Removal Rates ◽  
Carbon Removal ◽  
Biofilm Growth ◽  
Loading Rates ◽  
Biomass Activity ◽  
High Turbulence ◽  
The One ◽  
High Level ◽  
Very High

An anaerobic inverse turbulent bed, in which the biogas only ensures fluidisation of floating carrier particles, was investigated for carbon removal kinetics and for biofilm growth and detachment. The range of operation of the reactor was kept within 5 and 30 kgCOD· m−3· d−1, with Hydraulic Retention Times between 0.28 and 1 day. The carbon removal efficiency remained between 70 and 85%. Biofilm size were rather low (between 5 and 30 μm) while biofilm density reached very high values (over 80 kgVS· m−3). The biofilm size and density varied with increasing carbon removal rates with opposite trends; as biofilm size increases, its density decreases. On the one hand, biomass activity within the reactor was kept at a high level, (between 0.23 and 0.75 kgTOC· kgVS· d−1, i.e. between 0.6 and 1.85 kgCOD·kgVS · d−1).This result indicates that high turbulence and shear may favour growth of thin, dense and active biofilms. It is thus an interesting tool for biomass control. On the other hand, volatile solid detachment increases quasi linearly with carbon removal rate and the total amount of solid in the reactor levels off at high OLR. This means that detachment could be a limit of the process at higher organic loading rates.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

A Tight Connection Among Wealth, Income, Sustainability, and Accounting in an Ultra-Simplified Setting

2017 ◽  
Author(s):  
Martin L. Weitzman
Keyword(s):  
Economic Theory ◽  
Quantitative Relationship ◽  
Theoretical Relationship ◽  
Level Of Abstraction ◽  
Tight Connection ◽  
Basic Concepts ◽  
High Level ◽  
Very High

In theory, and under some very strong assumptions, there exists a tight quantitative relationship among the following four fundamental economic concepts: (1) ‘wealth’; (2) ‘income’; (3) ‘sustainability’; (4) ‘accounting’. These four basic concepts are placed in quotation marks here because a necessary first step will be to carefully and rigorously define what exactly is meant by each. This chapter reviews what is known about this important fourfold quantitative relationship in an ultra-simplified setting. It identifies some basic applications of this simplified economic theory of wealth and income (and sustainability and accounting). While the contents of this chapter are expressed at a very high level of abstraction and require many restrictive assumptions, the fundamental fourfold relationship it sharply highlights should be useful for conceptualizing, at least in principle, what is ‘wealth’ and what is its theoretical relationship to ‘income’, ‘sustainability’, and ‘accounting’.

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