scholarly journals ADAMTS-12: Functions and Challenges for a Complex Metalloprotease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yamina Mohamedi ◽  
Tania Fontanil ◽  
Santiago Cal ◽  
Teresa Cobo ◽  
Álvaro J. Obaya
Keyword(s):  
Extracellular Matrix ◽  
Tumor Suppressor ◽  
Behavioral Disorders ◽  
Cancer Development ◽  
Proteinase Activity ◽  
Wide Range ◽  
Inflammatory Processes ◽  
20Th Anniversary ◽  
Neuronal Disorders

Nineteen members of the ADAMTS family of secreted zinc metalloproteinases are present in the human degradome. A wide range of different functions are being attributed to these enzymes and the number of their known substrates is considerably increasing in recent years. ADAMTSs can participate in processes such as fertility, inflammation, arthritis, neuronal and behavioral disorders, as well as cancer. Since its first annotation in 2001, ADAMTS-12 has been described to participate in different processes displayed by members of this family of proteinases. In this sense, ADAMTS-12 performs essential roles in modulation and recovery from inflammatory processes such as colitis, endotoxic sepsis and pancreatitis. ADAMTS-12 has also been involved in cancer development acting either as a tumor suppressor or as a pro-tumoral agent. Furthermore, participation of ADAMTS-12 in arthritis or in neuronal disorders has also been suggested through degradation of components of the extracellular matrix. In addition, ADAMTS-12 proteinase activity can also be modified by interaction with other proteins and thus, can be an alternative way of modulating ADAMTS-12 functions. In this review we revised the most relevant findings about ADAMTS-12 function on the 20th anniversary of its identification.

Report on CLEF 2019

2019 ◽  
Vol 53 (2) ◽  
pp. 108-118
Author(s):  
Martin Braschler ◽  
Linda Cappellato ◽  
Fabio Crestani ◽  
Nicola Ferro ◽  
Gundula Heinatz Bürki ◽  
...  
Keyword(s):  
Standard Test ◽  
Future Perspectives ◽  
Research Papers ◽  
Test Collections ◽  
Lessons Learnt ◽  
Wide Range ◽  
The Future ◽  
20Th Anniversary

This is a report on the tenth edition of the Conference and Labs of the Evaluation Forum (CLEF 2019), held from September 9--12, 2019, in Lugano, Switzerland. CLEF was a four day event combining a Conference and an Evaluation Forum. The Conference featured keynotes by Bruce Croft, Yair Neuman, and Miguel Martínez, and presentation of peer reviewed research papers covering a wide range of topics in addition to many posters. The Evaluation Forum consisted to nine Labs: CENTRE, CheckThat, eHealth, eRisk, ImageCLEF, LifeCLEF, PAN, PIR-CLEF, and ProtestNews, addressing a wide range of tasks, media, languages, and ways to go beyond standard test collections. CLEF 2019 marked the 20th anniversary of CLEF, which was celebrated with a dedicated session and a book on the lessons learnt in twenty years of evaluation activities and the future perspectives for CLEF. CLEF 2019 also introduced the Industry Days to further extend the reach and impact of CLEF.

scholarly journals Bound To Shock: Protection from Lethal Endotoxemic Shock by a Novel, Nontoxic, Alkylpolyamine Lipopolysaccharide Sequestrant

2007 ◽  
Vol 51 (8) ◽  
pp. 2811-2819 ◽  
Author(s):  
Diptesh Sil ◽  
Anurupa Shrestha ◽  
Matthew R. Kimbrell ◽  
Thuan B. Nguyen ◽  
Ashok K. Adisechan ◽  
...  
Keyword(s):  
Polymyxin B ◽  
In Vitro Assays ◽  
Critically Ill Patient ◽  
Peptide Antibiotic ◽  
Outer Membranes ◽  
Wide Range ◽  
Endotoxemic Shock ◽  
Inflammatory Processes ◽  
Shock Protection

ABSTRACT Lipopolysaccharide (LPS), or endotoxin, a structural component of gram-negative bacterial outer membranes, plays a key role in the pathogenesis of septic shock, a syndrome of severe systemic inflammation which leads to multiple-system organ failure. Despite advances in antimicrobial chemotherapy, sepsis continues to be the commonest cause of death in the critically ill patient. This is attributable to the lack of therapeutic options that aim at limiting the exposure to the toxin and the prevention of subsequent downstream inflammatory processes. Polymyxin B (PMB), a peptide antibiotic, is a prototype small molecule that binds and neutralizes LPS toxicity. However, the antibiotic is too toxic for systemic use as an LPS sequestrant. Based on a nuclear magnetic resonance-derived model of polymyxin B-LPS complex, we had earlier identified the pharmacophore necessary for optimal recognition and neutralization of the toxin. Iterative cycles of pharmacophore-based ligand design and evaluation have yielded a synthetically easily accessible N 1,mono-alkyl-mono-homologated spermine derivative, DS-96. We have found that DS-96 binds LPS and neutralizes its toxicity with a potency indistinguishable from that of PMB in a wide range of in vitro assays, affords complete protection in a murine model of LPS-induced lethality, and is apparently nontoxic in vertebrate animal models.

scholarly journals A FIJI macro for quantifying pattern in extracellular matrix

2021 ◽  
Vol 4 (3) ◽  
pp. e202000880
Author(s):  
Esther Wershof ◽  
Danielle Park ◽  
David J Barry ◽  
Robert P Jenkins ◽  
Antonio Rullan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Fractal Dimension ◽  
Quantitative Analysis ◽  
Comprehensive Description ◽  
End Points ◽  
Wide Range ◽  
Automated Pipeline ◽  
Cytoskeletal Networks ◽  
Alignment Length ◽  
Imagej Plugin

Diverse extracellular matrix patterns are observed in both normal and pathological tissue. However, most current tools for quantitative analysis focus on a single aspect of matrix patterning. Thus, an automated pipeline that simultaneously quantifies a broad range of metrics and enables a comprehensive description of varied matrix patterns is needed. To this end, we have developed an ImageJ plugin called TWOMBLI, which stands for The Workflow Of Matrix BioLogy Informatics. This pipeline includes metrics of matrix alignment, length, branching, end points, gaps, fractal dimension, curvature, and the distribution of fibre thickness. TWOMBLI is designed to be quick, versatile and easy-to-use particularly for non-computational scientists. TWOMBLI can be downloaded from https://github.com/wershofe/TWOMBLI together with detailed documentation and tutorial video. Although developed with the extracellular matrix in mind, TWOMBLI is versatile and can be applied to vascular and cytoskeletal networks. Here we present an overview of the pipeline together with examples from a wide range of contexts where matrix patterns are generated.

scholarly journals A FIJI Macro for quantifying pattern in extracellular matrix

2019 ◽  
Author(s):  
Esther Wershof ◽  
Danielle Park ◽  
David J Barry ◽  
Robert P Jenkins ◽  
Antonio Rullan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Quantitative Analysis ◽  
Comprehensive Description ◽  
Link Type ◽  
Wide Range ◽  
Automated Pipeline ◽  
Imagej Plugin

AbstractDiverse extracellular matrix patterns are observed in both normal and pathological tissue. However, most current tools for quantitative analysis focus on a single aspect of matrix patterning. Thus, an automated pipeline that simultaneously quantifies a broad range of metrics and enables a comprehensive description of varied matrix patterns is needed. To this end we have developed an ImageJ plugin called TWOMBLI, which stands for The Workflow Of Matrix BioLogy Informatics. TWOMBLI is designed to be quick, versatile and easy-to-use particularly for non-computational scientists. TWOMBLI can be downloaded from https://github.com/wershofe/TWOMBLI together with detailed documentation. Here we present an overview of the pipeline together with examples from a wide range of contexts where matrix patterns are generated.

scholarly journals Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia

Blood ◽  
1995 ◽  
Vol 85 (8) ◽  
pp. 2013-2016 ◽  
Author(s):  
H Sill ◽  
JM Goldman ◽  
NC Cross
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
P16 Gene ◽  
Number Of Patients ◽  
Wide Range ◽  
Homozygous Deletions

The p16 gene, also referred to as MTS1, INK4, CDK4I, or CDKN2, at chromosome 9p21 has recently been described as a tumor suppressor that may be involved in a wide range of tumors. We have used a semiquantitative multiplex polymerase chain reaction assay to search for deletions of the p16 gene in 34 patients with chronic myeloid leukemia in blast crisis (CML BC), 19 patients with acute lymphoblastic leukemia (ALL), and 25 patients with acute myeloid leukemia (AML). Homozygous deletions of p16 exons were found in 5 of 10 (50%) patients with CML in lymphoid BC and in 5 (26%) ALL patients, but in only 1 (2%) case with AML. No deletions were found in CML BC of nonlymphoid phenotype. Comparison of chronic phase DNA or remission DNA with acute leukemia DNA in 5 individuals showed that the p16 deletions were acquired and not inherited, directly implicating these lesions in the pathogenesis of the disease. We conclude that functional elimination of the p16 gene, or a closely mapping gene, is involved in a significant number of patients with CML in lymphoid transformation.

scholarly journals Neuroprotective Mechanisms of PPARδ: Modulation of Oxidative Stress and Inflammatory Processes

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Caroline I. Schnegg ◽  
Mike E. Robbins
Keyword(s):  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Cellular Processes ◽  
Wide Range ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Chronic Injuries ◽  
Neuroprotective Efficacy ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARα,δ, andγ) are ligand-activated transcription factors that regulate a wide range of cellular processes, including inflammation, proliferation, differentiation, metabolism, and energy homeostasis. All three PPAR subtypes have been identified in the central nervous system (CNS) of rodents. While PPARαand PPARγare expressed in more restricted areas of the CNS, PPARδis ubiquitously expressed and is the predominant subtype. Although data regarding PPARδare limited, studies have demonstrated that administration of PPARδagonists confers neuroprotection following various acute and chronic injuries to the CNS, such as stroke, multiple sclerosis, and Alzheimer's disease. The antioxidant and anti-inflammatory properties of PPARδagonists are thought to underly their neuroprotective efficacy. This review will focus on the putative neuroprotective benefits of therapeutically targeting PPARδin the CNS, and specifically, highlight the antioxidant and anti-inflammatory functions of PPARδagonists.

scholarly journals Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 978 ◽  
Author(s):  
Mariana I. Neves ◽  
Marco Araújo ◽  
Lorenzo Moroni ◽  
Ricardo M.P. da Silva ◽  
Cristina C. Barrias
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Biological Activity ◽  
Growth Factors ◽  
Mechanical Stability ◽  
Biological Molecules ◽  
Inhibiting Factors ◽  
Wide Range ◽  
Different Sources

Glycosaminoglycans (GAG) are long, linear polysaccharides that display a wide range of relevant biological roles. Particularly, in the extracellular matrix (ECM) GAG specifically interact with other biological molecules, such as growth factors, protecting them from proteolysis or inhibiting factors. Additionally, ECM GAG are partially responsible for the mechanical stability of tissues due to their capacity to retain high amounts of water, enabling hydration of the ECM and rendering it resistant to compressive forces. In this review, the use of GAG for developing hydrogel networks with improved biological activity and/or mechanical properties is discussed. Greater focus is given to strategies involving the production of hydrogels that are composed of GAG alone or in combination with other materials. Additionally, approaches used to introduce GAG-inspired features in biomaterials of different sources will also be presented.

scholarly journals Microglia Mediated Neuroinflammation: Focus on PI3K Modulation

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 137 ◽  
Author(s):  
Antonia Cianciulli ◽  
Chiara Porro ◽  
Rosa Calvello ◽  
Teresa Trotta ◽  
Dario Domenico Lofrumento ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Tissue Damage ◽  
Therapeutic Strategies ◽  
Focused Attention ◽  
Pathogen Invasion ◽  
Wide Range ◽  
Inflammatory Processes ◽  
The Central Nervous System

Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.

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