scholarly journals Mapping axon initial segment structure and function by multiplexed proximity biotinylation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hamdan Hamdan ◽  
Brian C. Lim ◽  
Tomohiro Torii ◽  
Abhijeet Joshi ◽  
Matthias Konning ◽  
...  
Keyword(s):  
Action Potentials ◽  
Molecular Mechanisms ◽  
Structure And Function ◽  
Molecular Organization ◽  
Neuronal Polarity ◽  
Intracellular Membrane ◽  
Polarized Trafficking ◽  
And Function ◽  
And Control ◽  
Axon Initial Segments

AbstractAxon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons.

scholarly journals Exotoxins of Staphylococcus aureus

2000 ◽  
Vol 13 (1) ◽  
pp. 16-34 ◽  
Author(s):  
Martin M. Dinges ◽  
Paul M. Orwin ◽  
Patrick M. Schlievert
Keyword(s):  
Staphylococcus Aureus ◽  
Toxic Shock Syndrome ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Food Poisoning ◽  
Structure And Function ◽  
Toxic Shock ◽  
The Family ◽  
Toxic Shock Syndrome Toxin ◽  
And Function

SUMMARY This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.

scholarly journals Targeting Age-Related Pathways in Heart Failure

2020 ◽  
Vol 126 (4) ◽  
pp. 533-551 ◽  
Author(s):  
Haobo Li ◽  
Margaret H. Hastings ◽  
James Rhee ◽  
Lena E. Trager ◽  
Jason D. Roh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Elderly Population ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Structure And Function ◽  
Experimental Platform ◽  
Age Related ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Increased Susceptibility

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.

Oral mucosa, saliva, and speech

2018 ◽  
Author(s):  
Hugh Devlin ◽  
Rebecca Craven
Keyword(s):  
Oral Mucosa ◽  
Normal Structure ◽  
Structure And Function ◽  
Oral Precancer ◽  
And Function ◽  
And Control

Oral mucosa, saliva, and speech in relation to dentistry are the topics in this chapter. The chapter starts with the normal structure and function of oral mucosa, leading on to a discussion of problems in normal physiology leading to ulceration and to oral precancer and carcinoma. This is followed by a consideration of saliva, its production and properties, and important issues arising from lack of saliva. Swallowing, its phases and control and dental relevance, are next discussed. The concluding section deals with speech, vocalization, phonation, and articulation together with problems of dental relevance, that may arise.

Impact of artificial reefs on sediment bacterial structure and function in Bohai Bay

2019 ◽  
Vol 65 (3) ◽  
pp. 191-200 ◽  
Author(s):  
Yu Wang ◽  
Jinsheng Sun ◽  
Enjun Fang ◽  
Biao Guo ◽  
Yuanyuan Dai ◽  
...  
Keyword(s):  
Artificial Reef ◽  
Control Area ◽  
Structure And Function ◽  
Artificial Reefs ◽  
Rrna Genes ◽  
Bohai Bay ◽  
Reef Area ◽  
The Future ◽  
And Function ◽  
And Control

Artificial reefs have significantly altered ecological and environmental conditions compared with natural reefs, but how these changes affect sediment bacteria structure and function is unknown. Here, we compared the structure and function of the sediment bacterial community in the artificial reef area, the future artificial reef area, and the control area in Bohai Bay by 16S rRNA genes sequencing. Our results indicated that bacteria communities in the sediment were both taxonomically and functionally different between the reef area and control area. In the artificial reef area, the α-diversity was significantly lower, whereas the β-diversity was significantly higher. Functional genes related to chemo-heterotrophy, nitrate reduction, hydrocarbon degradation, and the human pathogens and human gut were more abundant, whereas genes related to the metabolism of sulfur compounds were less abundant in the artificial reef than in the control area. The differences in bacterial communities were primarily determined by depth in the artificial reef area, and by total organic carbon in the future reef area and control area. This study provides the first overview of molecular ecology to assess the impacts of artificial reefs on the bacteria community.

scholarly journals General discussion summary

2002 ◽  
Vol 357 (1426) ◽  
pp. 1419-1420 ◽  
Keyword(s):  
Water Splitting ◽  
Molecular Mechanisms ◽  
Structure And Function ◽  
X Ray ◽  
X Ray Crystallography ◽  
And Function ◽  
Splitting Process

This general discussion was chaired by A. W. Rutherford ( Service de Bioénergétique, Saclay, France ) and revolved around two major topics: (i) the implications of X–ray crystallography on the relationships between structure and function; (ii) the molecular mechanisms of the water–splitting process.

scholarly journals Structure and Function of HIV-1 Reverse Transcriptase: Molecular Mechanisms of Polymerization and Inhibition

2009 ◽  
Vol 385 (3) ◽  
pp. 693-713 ◽  
Author(s):  
Stefan G. Sarafianos ◽  
Bruno Marchand ◽  
Kalyan Das ◽  
Daniel M. Himmel ◽  
Michael A. Parniak ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Molecular Mechanisms ◽  
Structure And Function ◽  
And Function ◽  
Hiv 1

scholarly journals Recent progress in research on molecular mechanisms of autophagy in the heart

2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Heart Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Degradation Process ◽  
Structure And Function ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Dysfunction

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.

scholarly journals Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fernando A. Vicentini ◽  
Catherine M. Keenan ◽  
Laurie E. Wallace ◽  
Crystal Woods ◽  
Jean-Baptiste Cavin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Structure And Function ◽  
Enteric Neurons ◽  
Intestinal Function ◽  
Gi Tract ◽  
Enteric Glia ◽  
And Function

Abstract Background The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and ENS. Microbiota-dependent molecular mechanisms of ENS neuronal survival and neurogenesis were also assessed. Results Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion secretion, and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia was only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion, but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, short-chain fatty acids (SCFA) were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo. Conclusions Our results demonstrate a role for the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies.

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