ADAMTSL6β promotes fibrillin‐1 microfibril assembly, which is possibly mediated via binding through the third thrombospondin type I domain to fibrillin‐1

2020 ◽  
Vol 44 (7) ◽  
pp. 1436-1446
Author(s):  
Ai Orimoto ◽  
Tomokazu Fukuda
Keyword(s):  
Type I ◽  
The Third ◽  
Microfibril Assembly ◽  
Fibrillin 1

scholarly journals Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

2021 ◽  
Vol 22 (1) ◽  
pp. 429
Author(s):  
Luca Bini ◽  
Domitille Schvartz ◽  
Chiara Carnemolla ◽  
Roberta Besio ◽  
Nadia Garibaldi ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Tandem Mass ◽  
Type Ii ◽  
Type Iii ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Fibrillin 1 ◽  
Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

ELECTROLYTIC EXCHANGE FEATURES DURING MYOCARDIAL INFARCTION WITH RECURRENT EPISODES OF ISCHEMIA IN MEN UNDER 60 YEARS OLD

2021 ◽  
pp. 120-126
Author(s):  
Golikov A.V. ◽  
Epifanov S.Yu. ◽  
Reiza V.A.
Keyword(s):  
Myocardial Infarction ◽  
Blood Serum ◽  
Absolute Risk ◽  
Risk Groups ◽  
Unfavorable Outcome ◽  
Study Group ◽  
Type I ◽  
Sodium Potassium ◽  
The Third ◽  
Recurrent Myocardial Infarction

Relevance. Recurrent myocardial infarction and early postinfarction angina negatively effects on the prognosis of myocardial infarction. Aim. To evaluate myocardial infarction sodium, potassium, chlorides, calcium metabolism, features in men under 60 years old with recurrent myocardial infarction and early postinfarction angina to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with recurrent myocardial infarction - 110 patients; II - control, without it - 555 patients. A comparative analysis of blood serum electrolyte levels, their dynamics from the first hours to the end of the third week of myocardial infarction in the selected groups were performed. Their impact on the risk of recurrent ischemia and unfavorable outcome was assessed. Results. In the study group, in the first hours of the disease, the levels of chloride were higher (103.7±5.5 and 101.7±4.7 (mmol/l); p=0.002), and total calcium at the end of the third week of myocardial infarction (2.3±0.2 mmol/l) - lower than in the control (2.46±0.16; p=0.001). With an unfavorable outcome in the study group, the sodium level was lower in the first hours of the disease (138.7±4.9 and 142.7±6.6 (mmol/l); p=0.049). Moreover, the risk of its development was associated with sodium levels ≥148.0 mmol/l (absolute risk: 100.0%; relative - 13.8; p<0.0001) and potassium levels ≥5.3 mmol/l (absolute: 71,4%; relative - 12.4; p<0.0001). The risk of developing recurrent episodes of ischemia in the examined increased at chloride levels ≥104.7 mmol/l (absolute: 28.4%; relative: 3.1; p=0.0001) and sodium ≥139.0 mmol/l (absolute: 19.5%; relative: 1.7; p=0.03) in the first hours of myocardial infarction and calcium (<2.4 mmol/l) at the end of the third week of the disease (absolute: 31.0%; relative: 4.9; p=0.003). Conclusions. The listed combinations of levels of basic electrolytes in blood serum are markers of recurrence of ischemia in myocardial infarction and poor outcome. They should be used to identify risk groups with the necessary preventive measures and for predictive modeling.

Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Paul E. Goss ◽  
Kathrin Strasser
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Clinical Status ◽  
Phase Iii ◽  
Type I ◽  
Third Generation ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Third

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

scholarly journals Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution

2006 ◽  
Vol 100 (4) ◽  
pp. 1431-1432
Author(s):  
Yasmin ◽  
Ian B. Wilkinson ◽  
Kevin M. O’Shaughnessy
Keyword(s):  
Mechanical Properties ◽  
Pulse Pressure ◽  
Aortic Stiffness ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Increased Risk ◽  
Fibrillin 1 ◽  
Echo Tracking

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28–81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G\?\T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype ( P = 0.005). Pulse pressure also was increased in the 2-3 genotype ( P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.

Why Schools Should Care About Intellectual Styles

2012 ◽  
Vol 11 (3) ◽  
pp. 256-270 ◽  
Author(s):  
Li-fang Zhang
Keyword(s):  
Research Evidence ◽  
School Context ◽  
Educational Institutions ◽  
Type I ◽  
Type Ii ◽  
Learning And Development ◽  
The Third ◽  
Intellectual Styles ◽  
Processing Information ◽  
Research Findings

Traditionally, many educators and psychologists believed that successes and failures within the school context are attributable mainly to individual differences in such classic variables as ability, personality, and learning motivation. This article presents research evidence demonstrating that intellectual styles, that is, people’s preferred ways of processing information and dealing with tasks, also play critical roles in students’ learning and development and in teachers’ practices. It further demonstrates that some styles are more valued than are others and that styles are malleable.The article is divided into four parts. The first part briefly introduces the background of the research to be presented. The second reviews the key literature, supporting the position that intellectual styles are value laden, with creativity-generating styles (also known as Type I styles) being more adaptive than are norm-favoring styles (also known as Type II styles). The third part highlights some research findings indicating that styles can be modified. The final and fourth part of the article discusses the implications of the research evidence for various parties of educational institutions at all levels—generally referred to as “schools” in this article.

scholarly journals Structure of the Fibrillin-1 N-Terminal Domains Suggests that Heparan Sulfate Regulates the Early Stages of Microfibril Assembly

Structure ◽  
2013 ◽  
Vol 21 (10) ◽  
pp. 1743-1756 ◽  
Author(s):  
David A. Yadin ◽  
Ian B. Robertson ◽  
Joanne McNaught-Davis ◽  
Paul Evans ◽  
David Stoddart ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Early Stages ◽  
Microfibril Assembly ◽  
Fibrillin 1 ◽  
Terminal Domains

scholarly journals Subtractive Hybridization Reveals a Type I Polyketide Synthase Locus Specific to Mycobacterium ulcerans

2003 ◽  
Vol 185 (23) ◽  
pp. 6870-6882 ◽  
Author(s):  
Grant A. Jenkin ◽  
Timothy P. Stinear ◽  
Paul D. R. Johnson ◽  
John K. Davies
Keyword(s):  
Genetic Basis ◽  
Polyketide Synthase ◽  
Buruli Ulcer ◽  
Subtractive Hybridization ◽  
Mycobacterial Infection ◽  
Mycobacterium Ulcerans ◽  
Suppressive Subtractive Hybridization ◽  
Type I ◽  
The Third ◽  
Close Genetic Relationship

ABSTRACT Mycobacterium ulcerans causes Buruli ulcer, the third most prevalent mycobacterial infection of immunocompetent humans after tuberculosis and leprosy. Recent work has shown that the production by M. ulcerans of mycolactone, a novel polyketide, may partly explain the pathogenesis of Buruli ulcer. To search for the genetic basis of virulence in M. ulcerans, we took advantage of the close genetic relationship between M. ulcerans and Mycobacterium marinum by performing genomic suppressive subtractive hybridization of M. ulcerans with M. marinum. We identified several DNA fragments specific to M. ulcerans, in particular, a type I polyketide synthase locus with a highly repetitive modular arrangement. We postulate that this locus is responsible for the synthesis of mycolactone in M. ulcerans.

scholarly journals Bioinformatics Analysis Identifies a Small ORF in the Genome of Fish Nidoviruses of Genus Oncotshavirus Predicted to Encode a Novel Integral Protein

2021 ◽  
Vol 12 (4) ◽  
pp. 753-764
Author(s):  
Frederick Kibenge ◽  
Ashley McKibbon ◽  
Molly Kibenge ◽  
Yingwei Wang
Keyword(s):  
Bioinformatics Analysis ◽  
Signal Sequence ◽  
Open Reading Frame ◽  
Type I ◽  
Structural Protein ◽  
Genome Sequence Analysis ◽  
Reading Frame ◽  
The Third ◽  
E Protein ◽  
Small Open Reading Frame

Genome sequence analysis of Atlantic salmon bafinivirus (ASBV) revealed a small open reading frame (ORF) predicted to encode a Type I membrane protein with an N-terminal cleaved signal sequence (110 aa), likely an envelope (E) protein. Bioinformatic analyses showed that the predicted protein is strikingly similar to the coronavirus E protein in structure. This is the first report to identify a putative E protein ORF in the genome of members of the Oncotshavirus genus (subfamily Piscavirinae, family Tobaniviridae, order Nidovirales) and, if expressed would be the third family (after Coronaviridae and Arteriviridae) within the order to have the E protein as a major structural protein.

scholarly journals DIFFERENCES OF BONE REGENERATION USING BOVINE HYDROXYAPATITE AND BOVINE HYDROXYAPATITE WITH FREEZE-DRIED PLATELET RICH PLASMA ALLOGRAFT IN BONE DEFECT OF FEMORAL WHITE RABBIT

2020 ◽  
Vol 9 (2) ◽  
pp. 34
Author(s):  
Mouli Edward ◽  
Henry Dominica ◽  
Ferdiansyah Mahyudin ◽  
Fedik Abdul Rantam
Keyword(s):  
Alkaline Phosphatase ◽  
Treatment Group ◽  
Type I Collagen ◽  
Platelet Rich Plasma ◽  
Bone Defects ◽  
Type I ◽  
The Third ◽  
Woven Bone ◽  
Freeze Dried ◽  
Bovine Hydroxyapatite

Background: Bone defects to date have been a significant problem in the Orthopedics field. Hydroxyapatite is a bone graft that is often chosen if it has osteoconductive properties. Platelet-rich plasma (PRP) has a higher platelet concentration than the concentration in normal blood, capable of providing many bioactive molecules in physiological proportions. Hydroxyapatite given freeze-dried PRP is expected to create a graft that can strengthen the matrix while promoting osteoinduction.Methods: This study compares the effects of regeneration on the bone between bovine hydroxyapatite (BHA) and bovine hydroxyapatite with freeze-dried platelet-rich plasma (FD-PRP) as a bone graft in bone defect of the femoral white rabbit. The 12 equal New Zealand white rabbits aged 6-9 months are divided into two groups. Bone defects were made in the lower femoral meta-diaphysis with a diameter of 2.5 mm. The defects were filled with BHA with FD-PRP allograft in the treatment group and BHA in the control group. Both groups will be sacrificed in the third and sixth weeks, then evaluated histologically for microvascular structure, osteoblasts, woven bone, type-I collagen, osteocalcin, alkaline phosphatase, and immunoglobulin G.Results: During the evaluation in week 3 and 6, microvascular structure, osteoblast, and type-I collagen decreased in both groups with insignificant differences (p>0.05). Woven bone, osteocalcin, and immunoglobulin G increased in the treatment group but was not significant (p>0.05). Alkaline phosphatase increased higher in the treatment group, with a considerable difference in the sixth week (p=0.008).Conclusion: The elevation in the production of woven bone, osteocalcin, and alkaline phosphatase at the third and sixth-week evaluations highlight the possibility that administering BHA given FD-PRP may have contributed to the healing of bone defects.

scholarly journals Proteolysis of fibrillin-2 microfibrils is essential for normal skeletal development

2021 ◽  
Author(s):  
Timothy J. Mead ◽  
Daniel R. Martin ◽  
Lauren W. Wang ◽  
Stuart A. Cain ◽  
Cagri Gulec ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Postnatal Life ◽  
Mrna Levels ◽  
Skeletal Defects ◽  
Microfibril Assembly ◽  
Protease Substrate ◽  
Fibrillin 1 ◽  
Vitro Analysis ◽  
In Vitro Analysis

AbstractThe extracellular matrix (ECM) undergoes an orchestrated transition from embryonic to mature ECM that is essential for postnatal life, yet the developmental transition mechanisms for ECM components and macromolecular complexes are poorly defined. Fibrillin microfibrils are macromolecular ECM complexes with important structural and regulatory roles. In mice, Fbn1 and Fbn2 mRNAs, which encode the major microfibrillar components, are strongly expressed during embryogenesis. Fbn2 mRNA levels rapidly decline postnatally, consistent with fibrillin-1 being the major component of adult tissue microfibrils. Here, by combining transgenic and N-terminomics strategies with in vitro analysis of microfibril assembly and intermolecular interactions, we identify cooperative proteolysis of fibrillin-2 by the secreted metalloproteases ADAMTS6 and ADAMTS10 as a mechanism contributing to postnatal fibrillin-1 dominance. The primacy of the protease-substrate relationship between ADAMTS6 and fibrillin-2 was unequivocally established by demonstrating a dramatic reversal of skeletal defects in Adamts6−/− embryos by Fbn2 haploinsufficiency.

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