Faculty Opinions recommendation of Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate.

Reduced levels of p27Kip1 are frequent in human cancers and have been associated with poor prognosis. Skp2, a component of the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complex, has been implicated in p27Kip1 degradation. Increased Skp2 levels are seen in some solid tumors and are associated with reduced p27Kip1. We examined the expression of these proteins using single and double immunolabeling in a large series of lymphomas to determine if alterations in their relative levels are associated with changes in cell proliferation and lymphoma subgroups. We studied the expression of Skp2 in low-grade and aggressive B-cell lymphomas (n = 86) and compared them with p27Kip1 and the proliferation index (PI). Fifteen hematopoietic cell lines and peripheral blood lymphocytes were studied by Western blot analysis. In reactive tonsils, Skp2 expression was limited to proliferating germinal center and interfollicular cells. Skp2 expression in small lymphocytic lymphomas (SLLs) and follicular lymphomas (FCLs) was low (mean percentage of positive tumor cells, less than 20%) and was inversely correlated (r = −0.67;P < .0001) with p27Kip1 and positively correlated with the PI (r = 0.82;P < .005). By contrast, whereas most mantle cell lymphomas (MCLs) demonstrated low expression of p27Kip1 and Skp2, a subset (n = 6) expressed high Skp2 (exceeding 20%) with a high PI (exceeding 50%). Skp2 expression was highest in diffuse large B-cell lymphomas (DLBCLs) (mean, 22%) and correlated with Ki-67 (r = 0.55;P < .005) but not with p27Kip1. Cytoplasmic Skp2 was seen in a subset of aggressive lymphomas. Our data provide evidence for p27Kip1 degradative function of Skp2 in low-grade lymphomas. The absence of this relationship in aggressive lymphomas suggests that other factors contribute to deregulation of p27Kip1 expression in these tumors.

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Direct Observation of Crystalline Ordering In Naturally Graphitized Carbon Produced by Low Grade Metamorphism

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100078377 ◽

1977 ◽

Vol 35 ◽

pp. 162-163

Author(s):

Thomas R. McKee ◽

Peter R. Buseck

Keyword(s):

Crystallite Size ◽

Sedimentary Rocks ◽

Carbonaceous Material ◽

Low Grade ◽

X Ray ◽

Graphitized Carbon ◽

Transmission Electron ◽

Heat Treated ◽

Commercial Carbon ◽

Metamorphic Zone

Sediments commonly contain organic material which appears as refractory carbonaceous material in metamorphosed sedimentary rocks. Grew and others have shown that relative carbon content, crystallite size, X-ray crystallinity and development of well-ordered graphite crystal structure of the carbonaceous material increases with increasing metamorphic grade. The graphitization process is irreversible and appears to be continous from the amorphous to the completely graphitized stage. The most dramatic chemical and crystallographic changes take place within the chlorite metamorphic zone.The detailed X-ray investigation of crystallite size and crystalline ordering is complex and can best be investigated by other means such as high resolution transmission electron microscopy (HRTEM). The natural graphitization series is similar to that for heat-treated commercial carbon blacks, which have been successfully studied by HRTEM (Ban and others).

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Scanning Electron Microscope Study of Bacteria on Mineral Surfaces

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090634 ◽

1976 ◽

Vol 34 ◽

pp. 130-131

Author(s):

V.K. Berry

Keyword(s):

Oxidation Reaction ◽

Electron Microscope Study ◽

Elemental Sulfur ◽

Thiobacillus Ferrooxidans ◽

Physical Contact ◽

Metal Sulfides ◽

Low Grade ◽

Mineral Surfaces ◽

Mineral Surface ◽

Scanning Electron Microscope Study

There are two strains of bacteria viz. Thiobacillus thiooxidansand Thiobacillus ferrooxidanswidely mentioned to play an important role in the leaching process of low-grade ores. Another strain used in this study is a thermophile and is designated Caldariella .These microorganisms are acidophilic chemosynthetic aerobic autotrophs and are capable of oxidizing many metal sulfides and elemental sulfur to sulfates and Fe2+ to Fe3+. The necessity of physical contact or attachment by bacteria to mineral surfaces during oxidation reaction has not been fairly established so far. Temple and Koehler reported that during oxidation of marcasite T. thiooxidanswere found concentrated on mineral surface. Schaeffer, et al. demonstrated that physical contact or attachment is essential for oxidation of sulfur.

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TEM/AEM characterization of fine-grained clay minerals in very-low-grade rocks: Evaluation of contamination by empa involving celadonite family minerals

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100165938 ◽

1996 ◽

Vol 54 ◽

pp. 694-695

Author(s):

Gejing Li ◽

D. R. Peacor ◽

D. S. Coombs ◽

Y. Kawachi

Keyword(s):

Electron Microscopy ◽

Volcanic Rocks ◽

Analytical Electron Microscopy ◽

Metamorphic Rocks ◽

New Mineral ◽

Chemical Compositions ◽

Low Grade ◽

Fine Grained ◽

Depth Analysis ◽

Mineral Aggregates

Recent advances in transmission electron microscopy (TEM) and analytical electron microscopy (AEM) have led to many new insights into the structural and chemical characteristics of very finegrained, optically homogeneous mineral aggregates in sedimentary and very low-grade metamorphic rocks. Chemical compositions obtained by electron microprobe analysis (EMPA) on such materials have been shown by TEM/AEM to result from beam overlap on contaminant phases on a scale below resolution of EMPA, which in turn can lead to errors in interpretation and determination of formation conditions. Here we present an in-depth analysis of the relation between AEM and EMPA data, which leads also to the definition of new mineral phases, and demonstrate the resolution power of AEM relative to EMPA in investigations of very fine-grained mineral aggregates in sedimentary and very low-grade metamorphic rocks.Celadonite, having end-member composition KMgFe3+Si4O10(OH)2, and with minor substitution of Fe2+ for Mg and Al for Fe3+ on octahedral sites, is a fine-grained mica widespread in volcanic rocks and volcaniclastic sediments which have undergone low-temperature alteration in the oceanic crust and in burial metamorphic sequences.

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The ubiquitin–proteasome system and skeletal muscle wasting

Essays in Biochemistry ◽

10.1042/bse0410173 ◽

2005 ◽

Vol 41 ◽

pp. 173-186 ◽

Cited By ~ 110

Author(s):

Didier Attaix ◽

Sophie Ventadour ◽

Audrey Codran ◽

Daniel Béchet ◽

Daniel Taillandier ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Wasting ◽

Proteolytic Enzymes ◽

Cathepsin L ◽

Ubiquitin Proteasome System ◽

Complete Breakdown ◽

Skeletal Muscle Proteins ◽

Ubiquitin Proteasome ◽

Tripeptidyl Peptidase Ii ◽

F Box Protein

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

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Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

Clinical Science ◽

10.1042/cs20191213 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2243-2262

Author(s):

Danlin Liu ◽

Gavin Richardson ◽

Fehmi M. Benli ◽

Catherine Park ◽

João V. de Souza ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Molecular Targets ◽

Therapeutic Interventions ◽

Low Grade ◽

Cardiovascular Research ◽

Inflammatory Processes ◽

Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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