scholarly journals Metals in ALS TDP-43 Pathology

2021 ◽  
Vol 22 (22) ◽  
pp. 12193
Author(s):  
Lassi Koski ◽  
Cecilia Ronnevi ◽  
Elina Berntsson ◽  
Sebastian K. T. S. Wärmländer ◽  
Per M. Roos
Keyword(s):  
Nerve Cells ◽  
Metal Exposure ◽  
Common Denominator ◽  
Cytoplasmic Inclusions ◽  
Dna And Rna ◽  
Sporadic Als ◽  
Aggregation Processes ◽  
Almost All ◽  
Cycle Regulation

Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology.

scholarly journals Hydrogen Peroxide and Amyotrophic Lateral Sclerosis: From Biochemistry to Pathophysiology

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 52
Author(s):  
Nitesh Sanghai ◽  
Geoffrey K. Tranmer
Keyword(s):  
Hydrogen Peroxide ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Complex Disease ◽  
Cytoplasmic Inclusions ◽  
Copper Zinc Superoxide Dismutase ◽  
Mechanistic Pathway ◽  
Sporadic Als ◽  
Lateral Sclerosis

Free radicals are unstable chemical reactive species produced during Redox dyshomeostasis (RDH) inside living cells and are implicated in the pathogenesis of various neurodegenerative diseases. One of the most complicated and life-threatening motor neurodegenerative diseases (MND) is amyotrophic lateral sclerosis (ALS) because of the poor understanding of its pathophysiology and absence of an effective treatment for its cure. During the last 25 years, researchers around the globe have focused their interest on copper/zinc superoxide dismutase (Cu/Zn SOD, SOD1) protein after the landmark discovery of mutant SOD1 (mSOD1) gene as a risk factor for ALS. Substantial evidence suggests that toxic gain of function due to redox disturbance caused by reactive oxygen species (ROS) changes the biophysical properties of native SOD1 protein thus, instigating its fibrillization and misfolding. These abnormal misfolding aggregates or inclusions of SOD1 play a role in the pathogenesis of both forms of ALS, i.e., Sporadic ALS (sALS) and familial ALS (fALS). However, what leads to a decrease in the stability and misfolding of SOD1 is still in question and our scientific knowledge is scarce. A large number of studies have been conducted in this area to explore the biochemical mechanistic pathway of SOD1 aggregation. Several studies, over the past two decades, have shown that the SOD1-catalyzed biochemical reaction product hydrogen peroxide (H2O2) at a pathological concentration act as a substrate to trigger the misfolding trajectories and toxicity of SOD1 in the pathogenesis of ALS. These toxic aggregates of SOD1 also cause aberrant localization of TAR-DNA binding protein 43 (TDP-43), which is characteristic of neuronal cytoplasmic inclusions (NCI) found in ALS. Here in this review, we present the evidence implicating the pivotal role of H2O2 in modulating the toxicity of SOD1 in the pathophysiology of the incurable and highly complex disease ALS. Also, highlighting the role of H2O2 in ALS, we believe will encourage scientists to target pathological concentrations of H2O2 thereby halting the misfolding of SOD1.

Michael Kelly, Hilary Footitt, Myriam Salama-Carr (eds.): The Palgrave Handbook of Languages and Conflict

2020 ◽  
Vol 55 (2) ◽  
Author(s):  
Ľubomír Zvada
Keyword(s):  
International Relations ◽  
Foreign Languages ◽  
Military Operations ◽  
Sources Of Information ◽  
War And Peace ◽  
Interdisciplinary Field ◽  
Speakers Of Other Languages ◽  
War And Conflict ◽  
Almost All

This Handbook maps the contours of an exciting and burgeoning interdisciplinary field concerned with the role of language and languages in situations of conflict. It explores conceptual approaches, sources of information that are available, and the institutions and actors that mediate language encounters. It examines case studies of the role that languages have played in specific conflicts, from colonial times through to the Middle East and Africa today. The contributors provide vibrant evidence to challenge the monolingual assumptions that have affected traditional views of war and conflict. They show that languages are woven into every aspect of the making of war and peace, and demonstrate how language shapes public policy and military strategy, setting frameworks and expectations. The Handbook's 22 chapters powerfully illustrate how the encounter between languages is integral to almost all conflicts, to every phase of military operations and to the lived experiences of those on the ground, who meet, work and fight with speakers of other languages. This comprehensive work will appeal to scholars from across the disciplines of linguistics, translation studies, history, and international relations; and provide fresh insights for a broad range of practitioners interested in understanding the role and implications of foreign languages in war.

Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽  
2020 ◽  
Vol 3 ◽  
Author(s):  
S. A. Sorokina ◽  
◽  
Yu. Yu. Stroilova ◽  
V. I. Muronets ◽  
Z. B. Shifrina ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Characteristics ◽  
Short Review ◽  
External Factors ◽  
Amyloid Aggregation ◽  
Amyloid Proteins ◽  
Molecular Parameters ◽  
Amyloid Aggregates ◽  
Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

ON EVALUATION OF THE ROLE OF THERMAL AND WIND FACTORS FOR A PHYSICAL MODEL OF THE WORLD OCEAN GENERAL CIRCULATION SYSTEM

2019 ◽  
Vol 47 (3) ◽  
pp. 80-91
Author(s):  
V. G. Neiman
Keyword(s):  
Physical Model ◽  
Ocean Circulation ◽  
General Circulation ◽  
World Ocean ◽  
Circulation System ◽  
The Public ◽  
The World ◽  
Almost All ◽  
Conceptual Foundations

The main content of the work consists of certain systematization and addition of longexisting, but eventually deformed and partly lost qualitative ideas about the role of thermal and wind factors that determine the physical mechanism of the World Ocean’s General Circulation System (OGCS). It is noted that the conceptual foundations of the theory of the OGCS in one form or another are contained in the works of many well-known hydrophysicists of the last century, but the aggregate, logically coherent description of the key factors determining the physical model of the OGCS in the public literature is not so easy to find. An attempt is made to clarify and concretize some general ideas about the two key blocks that form the basis of an adequate physical model of the system of oceanic water masses motion in a climatic scale. Attention is drawn to the fact that when analyzing the OGCS it is necessary to take into account not only immediate but also indirect effects of thermal and wind factors on the ocean surface. In conclusion, it is noted that, in the end, by the uneven flow of heat to the surface of the ocean can be explained the nature of both external and almost all internal factors, in one way or another contributing to the excitation of the general, or climatic, ocean circulation.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

Methyl mercury in the dutch rhine delta

1994 ◽  
Vol 30 (10) ◽  
pp. 213-219 ◽  
Author(s):  
Hendrik Pieters ◽  
Victor Geuke
Keyword(s):  
Suspended Matter ◽  
Methyl Mercury ◽  
Mercury Contamination ◽  
Benthic Organisms ◽  
Considerable Decrease ◽  
Continuous Sedimentation ◽  
Highly Correlated ◽  
High Level ◽  
Almost All

Samples of yellow eel from various locations in the Dutch Rhine area have been analyzed for trend monitoring of mercury since 1977. In the western Rhine delta mercury levels in eels have hardly changed since the seventies, whereas in the eastern part of the Dutch Rhine area a considerable decrease of mercury concentrations in eel has occurred. Because of continuous sedimentation of contaminated suspended matter transported from upstream regions, accumulation rates and concentrations of mercury in eel in the western Rhine delta remained at a relatively high level. Analyses of methyl mercury in biota have been performed to elucidate the role of methyl mercury in the mercury contamination of the Dutch Rhine ecosystem. Low percentages of methyl mercury were observed in zooplankton (3 to 35%). In benthic organisms (mussels) percentages of methyl mercury ranged from 30 to 57%, while in fish species and liver of aquatic top predator birds almost all the mercury was present in the form of methyl mercury (> 80%). During the period 1970-1990 mercury concentrations of suspended matter in the eastern Rhine delta have drastically decreased. These concentrations seemed to be highly correlated with mercury concentrations of eel (R = 0.84). The consequences of this relation are discussed.

Non-pharmacological Strategies Against Systemic Inflammation: Molecular Basis and Clinical Evidence

2020 ◽  
Vol 26 (22) ◽  
pp. 2620-2629 ◽  
Author(s):  
Rita Del Pinto ◽  
Davide Pietropaoli ◽  
Annalisa Monaco ◽  
Giovambattista Desideri ◽  
Claudio Ferri ◽  
...  
Keyword(s):  
Human Genome ◽  
Systemic Inflammation ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Lifestyle Changes ◽  
Common Denominator ◽  
Active Lifestyle ◽  
Systemic Impact ◽  
Public Health Strategies

Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders, and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management of these conditions. We performed an updated narrative review on the mechanisms behind the systemic impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate the resident microbial community. To date, evidence from high-quality human studies is sparse to allow the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the mechanisms behind future personalized medicine.

scholarly journals Crayfish hemocytes develop along the granular cell lineage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Li ◽  
Zaichao Zheng ◽  
Hongyu Li ◽  
Rongrong Fu ◽  
Limei Xu ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Cell Lineage ◽  
Granular Cell ◽  
Marker Genes ◽  
Hematopoietic Tissue ◽  
Differentiated Cells ◽  
Stage Of Development ◽  
Almost All ◽  
Relationship Of

AbstractDespite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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