scholarly journals Effects of Various Muscle Disuse States and Countermeasures on Muscle Molecular Signaling

2021 ◽  
Vol 23 (1) ◽  
pp. 468
Author(s):  
Kristina Sharlo ◽  
Sergey A. Tyganov ◽  
Elena Tomilovskaya ◽  
Daniil V. Popov ◽  
Alina A. Saveko ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structural Parameters ◽  
Work Capacity ◽  
Molecular Signaling ◽  
Negative Consequences ◽  
Muscle Disuse ◽  
Wide Range ◽  
Holistic Understanding ◽  
Muscle Loading ◽  
Muscle Changes

Skeletal muscle is capable of changing its structural parameters, metabolic rate and functional characteristics within a wide range when adapting to various loading regimens and states of the organism. Prolonged muscle inactivation leads to serious negative consequences that affect the quality of life and work capacity of people. This review examines various conditions that lead to decreased levels of muscle loading and activity and describes the key molecular mechanisms of muscle responses to these conditions. It also details the theoretical foundations of various methods preventing adverse muscle changes caused by decreased motor activity and describes these methods. A number of recent studies presented in this review make it possible to determine the molecular basis of the countermeasure methods used in rehabilitation and space medicine for many years, as well as to identify promising new approaches to rehabilitation and to form a holistic understanding of the mechanisms of gravity force control over the muscular system.

scholarly journals The Deep Roots of Addiction: A Comparative Perspective

2021 ◽  
pp. 1-8
Author(s):  
Nabil Karnib ◽  
Moira J. van Staaden
Keyword(s):  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Preventive Measures ◽  
Insect Herbivory ◽  
Plant Secondary Metabolites ◽  
Research Field ◽  
Neural Systems ◽  
Deep Roots ◽  
Wide Range ◽  
Holistic Understanding

Addiction is a debilitating condition that extracts enormous social and economic tolls. Despite several decades of research, our knowledge of its etiology, preventive measures, and treatments is limited. A relatively recent research field with the potential to provide a more holistic understanding, and subsequently treatments, takes a phylogenetic view of addiction. This perspective is based on deep homologies at the genetic, proteomic, and behavioral levels, which are shared across all metazoan life; particularly those organisms faced with plant secondary metabolites as defensive compounds against insect herbivory. These addictive alkaloids, such as nicotine, cocaine, or cathinone, are commonly referred to as “human drugs of abuse” even though humans had little to no role in the co-evolutionary processes that determined their initial emergence or continued selection. This commentary discusses the overwhelming homologies of addictive alkaloid effects on neural systems across a wide range of taxa, as we aim to develop a broader comparative view of the “addicted brain.” Taking nicotine as an example, homologous physiological responses to this compound identify common underlying cellular and molecular mechanisms that advocate for the adoption of a phylogenetic view of addiction.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Importance of $${{d}}_{{{xy}}}$$ orbital and electron correlation in iron-based superconductors revealed by phase diagram for 1111-system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tsuyoshi Kawashima ◽  
Shigeki Miyasaka ◽  
Hirokazu Tsuji ◽  
Takahiro Yamamoto ◽  
Masahiro Uekubo ◽  
...  
Keyword(s):  
Electron Correlation ◽  
Weak Coupling ◽  
Structural Parameters ◽  
Structural Flexibility ◽  
Superconducting Transition ◽  
Iron Based Superconductors ◽  
Wide Range ◽  
Band Filling ◽  
Iron Based ◽  
Correlation Strength

AbstractThe structural flexibility at three substitution sites in LaFeAsO enabled investigation of the relation between superconductivity and structural parameters over a wide range of crystal compositions. Substitutions of Nd for La, Sb or P for As, and F or H for O were performed. All these substitutions modify the local structural parameters, while the F/H-substitution also changes band filling. It was found that the superconducting transition temperature $$T_{\text{c}}$$ T c is strongly affected by the pnictogen height $$h_{Pn}$$ h Pn from the Fe-plane that controls the electron correlation strength and the size of the $$d_{xy}$$ d xy hole Fermi surface (FS). With increasing $$h_{Pn}$$ h Pn , weak coupling BCS superconductivity switches to the strong coupling non-BCS one where electron correlations and the $$d_{xy}$$ d xy hole FS may be important.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

scholarly journals Healthcare Providers’ Perceptions of Challenges with Frequent Users of Emergency Department Care in Switzerland: A Qualitative Study

2021 ◽  
Vol 58 ◽  
pp. 004695802110281
Author(s):  
Patrick Bodenmann ◽  
Miriam Kasztura ◽  
Madison Graells ◽  
Elodie Schmutz ◽  
Oriane Chastonay ◽  
...  
Keyword(s):  
Online Survey ◽  
Emergency Services ◽  
Healthcare Providers ◽  
Negative Consequences ◽  
Emergency Department Care ◽  
Frequent Users ◽  
Complex Needs ◽  
Wide Range ◽  
Ed Overcrowding ◽  
Ed Visits

Frequent users of emergency departments (FUED; ≥ 5 ED visits/year) commonly cumulate medical, social, and substance use problems requiring complex and sustained care coordination often unavailable in ED. This study aimed to explore ED healthcare providers’ challenges related to FUED care to gain insight into the support and resources required to address FUED complex needs. An online survey was sent to all general adult emergency services within Switzerland (N = 106). Participants were asked to indicate the extent to which they perceived that FUED represented a problem and to describe the main challenges encountered. In total, 208 physicians and nurses from 75 EDs (70.7%) completed the survey. Among the 208 participants, 134 (64%) reported that FUED represented a challenge and 133 described 1 to 5 challenges encountered. A conventional content analysis yielded 4 main categories of perceived challenges. Negative consequences in the ED secondary to FUED’s presence (eg, ED overcrowding, staff helplessness, and fatigue) was the most frequently reported challenge, followed by challenges related to FUEDs’ characteristics (eg, mental health and social problems) leading to healthcare complexity. The third most frequently encountered challenge was related to the ED inappropriateness and inefficiency to address FUEDs’ needs. Finally, challenges related to the lack of FUED healthcare network were the least often mentioned. ED healthcare providers experience a wide range of challenges related to FUED care. These findings suggest that currently EDs nor their staff are equipped to address FUEDs’ complex needs.

scholarly journals Anti-NLRP3 Inflammasome Natural Compounds: An Update

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 136
Author(s):  
Baolong Liu ◽  
Jiujiu Yu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Protein Complex ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Natural Compounds ◽  
Pyrin Domain ◽  
Inflammatory Protein ◽  
Wide Range ◽  
Activation Mechanisms ◽  
Stress Signals

The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. This pro-inflammatory protein complex plays critical roles in pathogenesis of a wide range of diseases including neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Therefore, intensive efforts have been devoted to understanding its activation mechanisms and to searching for its specific inhibitors. Approximately forty natural compounds with anti-NLRP3 inflammasome properties have been identified. Here, we provide an update about new natural compounds that have been identified within the last three years to inhibit the NLRP3 inflammasome and offer an overview of the underlying molecular mechanisms of their anti-NLRP3 inflammasome activities.

scholarly journals When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4617
Author(s):  
Styliana Kyriakoudi ◽  
Anthi Drousiotou ◽  
Petros P. Petrou
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Disease Development ◽  
Pathological Conditions ◽  
Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

scholarly journals Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors

2021 ◽  
Vol 22 (9) ◽  
pp. 4546
Author(s):  
Shiyao Chen ◽  
Yunqi Liu ◽  
Huchen Zhou
Keyword(s):  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Regulatory System ◽  
Transforming Growth Factor Β ◽  
Molecular Signaling ◽  
Post Translational Modification ◽  
The Past ◽  
Damage Repair ◽  
Wide Range ◽  
Cancer And Inflammation

Ubiquitylation and deubiquitylation are reversible protein post-translational modification (PTM) processes involving the regulation of protein degradation under physiological conditions. Loss of balance in this regulatory system can lead to a wide range of diseases, such as cancer and inflammation. As the main members of the deubiquitinases (DUBs) family, ubiquitin-specific peptidases (USPs) are closely related to biological processes through a variety of molecular signaling pathways, including DNA damage repair, p53 and transforming growth factor-β (TGF-β) pathways. Over the past decade, increasing attention has been drawn to USPs as potential targets for the development of therapeutics across diverse therapeutic areas. In this review, we summarize the crucial roles of USPs in different signaling pathways and focus on advances in the development of USP inhibitors, as well as the methods of screening and identifying USP inhibitors.

scholarly journals Crystallographic and structural characterization of heterometallic platinum complexes Part VI. Heterohexanuclear complexes

2014 ◽  
Vol 12 (11) ◽  
pp. 1101-1126 ◽  
Author(s):  
Milan Melník ◽  
Peter Mikuš ◽  
Clive Holloway
Keyword(s):  
Metal Ion ◽  
Structural Parameters ◽  
Bond Distance ◽  
Transition Element ◽  
Platinum Complexes ◽  
Hard Metals ◽  
Wide Range ◽  
Platinum Clusters ◽  
Soft Metal ◽  
Independent Molecules

AbstractThis review classifies and analyzes heterohexanuclear platinum clusters into seven types of metal combinations:Pt5M, Pt4M2, Pt3M3, Pt2M4, PtM5, Pt2M3M′, and Pt2M2M2′. The crystals of these clusters generally belong to six crystal classes: monoclinic, triclinic, orthorhombic, tetragonal, trigonal and cubic. Among the wide range of stereochemistry adopted by these clusters, octahedral and capped square-pyramidal are the most common. Although platinum is classified as a soft metal atom, it bonds to a variety of soft, borderline and hard metals. Nineteen different heterometal ions are involved in hexanuclear platinum clusters. The shortest Pt-M bond distance in the case of M being a non-transition element is 2.395(4) Å for germanium and for M being a transition metal ion it is 2.402(2) Å for Cobalt. The shortest Pt-Pt bond distance observed in these clusters is 2.532 Å. Several relationships between the structural parameters are identified and discussed. Some clusters exist in two isomeric forms and some show crystallographically independent molecules within the same crystal. Such isomers and independent molecules are examples of distortion isomerism.

Congenital adrenal hyperplasia: molecular mechanisms resulting in 21-hydroxylase deficiency

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S315-S320 ◽  
Author(s):  
Patricia A. Donohoue ◽  
Cornelis Van Dop ◽  
Nicholas Jospe ◽  
Claude J. Migeon
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Mechanisms ◽  
Sequence Data ◽  
Phenotypic Expression ◽  
Restriction Pattern ◽  
Class Iii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Wide Range ◽  
21 Hydroxylase Deficiency

Abstract 21-Hydroxylase deficiency resulting in congenital adrenal hyperplasia (CAH) is a HLA-linked autosomal recessive disorder that has a wide range of phenotypic expression. Two homologous 21-hydroxylase genes (21-OHA and 21-OHB) occur within the Class III region of the major histocompatibility complex, but only one (21-OHB) appears to function in adrenal steroidogenesis. Our restriction maps, and initial sequence data from White et al. (Pediatr Res 20:274A (1986)) for the two human 21-OH genes reveal a high degree of homology between these genes and a reading frame shift mutation in the 21-OHA gene respectively. Among fourteen control subjects, the intragenic restriction patterns of the 21-OHA and 21-OHB genes are invariant. The few restriction fragment length polymorphisms (RFLPs) found in some controls result from polymorphic restriction sites outside the 21-OH genes. In patients with CAH, several different mechanisms for mutation of the 21-OHB gene have been described: 1) deletion of the unique sequences of the 21-OHB gene, 2) conversion of the unique sequences of the 21-OHB gene to those of 21-OHA, and 3) mutations of 21-OHB which do not result in a detectable alteration of restriction pattern (e.g., point mutations). Duplication of the 21-OHA gene has been found in some patients with attenuated CAH; however, the significance of this finding remains unclear.

Sign in / Sign up

Export Citation Format

Share Document