scholarly journals Quantitative profiling of protease specificity

2020 ◽  
Author(s):  
B. I. Ratnikov ◽  
P. Cieplak ◽  
A. G. Remacle ◽  
E. Nguyen ◽  
J. W. Smith
Keyword(s):  
Substrate Recognition ◽  
Quantitative Measure ◽  
Detailed Knowledge ◽  
Important Class ◽  
Protease Specificity ◽  
Pathologic Processes ◽  
Catalytic Cleft ◽  
Insight Into ◽  
Generation Sequencing ◽  
Quantitative Profiling

AbstractProteases comprise an important class of enzymes, whose activity is central to many physiologic and pathologic processes. Detailed knowledge of protease specificity is key to understanding their function. Although many methodologies have been developed to profile specificities of proteases, few have the diversity and quantitative grasp necessary to fully define specificity of a protease, both in terms of substrate numbers and their catalytic efficiencies. We have developed a concept of “selectome”, which defines the set of substrates that uniquely represents specificity of a protease. We applied it to two closely related members of the Matrixin family – MMP-2 and MMP-9 by using substrate phage display coupled with Next Generation Sequencing and information theory-based data analysis. We have also derived a quantitative measure of substrate specificity, which accounts for both the numbers and relative catalytic efficiencies of substrates. Using these advances greatly facilitates uncovering selectivity between closely related members of protease families and provides insight into to the degree of contribution of catalytic cleft specificity to protein substrate recognition, thus providing basis to overcoming two of the major challenges in the field of proteolysis: 1) development of highly selective activity probes and inhibitors for studying proteases with overlapping specificities, and 2) distinguishing targeted proteolysis from bystander proteolytic events.

scholarly journals Quantitative profiling of protease specificity

2021 ◽  
Vol 17 (2) ◽  
pp. e1008101
Author(s):  
Boris I. Ratnikov ◽  
Piotr Cieplak ◽  
Albert G. Remacle ◽  
Elise Nguyen ◽  
Jeffrey W. Smith
Keyword(s):  
Quantitative Measure ◽  
Amino Acid Sequences ◽  
Detailed Knowledge ◽  
Substrate Selectivity ◽  
Protease Specificity ◽  
Pathologic Processes ◽  
Catalytic Cleft ◽  
Insight Into ◽  
Generation Sequencing ◽  
Quantitative Profiling

Proteases are an important class of enzymes, whose activity is central to many physiologic and pathologic processes. Detailed knowledge of protease specificity is key to understanding their function. Although many methods have been developed to profile specificities of proteases, few have the diversity and quantitative grasp necessary to fully define specificity of a protease, both in terms of substrate numbers and their catalytic efficiencies. We have developed a concept of “selectome”; the set of substrate amino acid sequences that uniquely represent the specificity of a protease. We applied it to two closely related members of the Matrixin family–MMP-2 and MMP-9 by using substrate phage display coupled with Next Generation Sequencing and information theory-based data analysis. We have also derived a quantitative measure of substrate specificity, which accounts for both the number of substrates and their relative catalytic efficiencies. Using these advances greatly facilitates elucidation of substrate selectivity between closely related members of a protease family. The study also provides insight into the degree to which the catalytic cleft defines substrate recognition, thus providing basis for overcoming two of the major challenges in the field of proteolysis: 1) development of highly selective activity probes for studying proteases with overlapping specificities, and 2) distinguishing targeted proteolysis from bystander proteolytic events.

The Three-Dimensional Surface Topographic Characterisation of Diamond Grinding Wheels

2010 ◽  
Vol 126-128 ◽  
pp. 690-695
Author(s):  
David Lee Butler
Keyword(s):  
Measurement Techniques ◽  
Three Dimensional ◽  
Surface Measurement ◽  
Grinding Wheel ◽  
Profile Measurement ◽  
Detailed Knowledge ◽  
Grinding Wheels ◽  
Diamond Grinding ◽  
Insight Into ◽  
Dimensional Surface

Surface measurement using three-dimensional stylus instruments is a relatively new technique that offers numerous advantages over more traditional profilometry methods. The information generated is, unlike profile measurement, less subjective and more statistical providing additional insight into the surface structure. One application of surface measurement that has encountered problems when using the profilometry method is that of grinding wheel characterisation. The wheel surface texture (topography) and the conditions under which it is generated have a profound effect upon the grinding performance as characterised by the grinding forces, power consumption, temperature, and surface integrity of components. A detailed knowledge of the nature of the topography of the grinding wheel would provide further insight into surface interactions between the wheel and workpiece as well as enabling improved control of the grinding process in general. In this paper four diamond grinding wheels of 91 and 181 micron grit size were subjected to differing dressing conditions to produce varying final wheel topographies. Three-dimensional surface measurement techniques were employed to quantitatively characterise the topographic change and provide an aerial estimation of the number of cutting grains. The results demonstrate that the techniques can distinguish between a worn and dressed wheel. In addition, the parametric values generated from the various surfaces can aid the user in determining when re-dressing is required.

scholarly journals Insight into origins, mechanisms, and utility of DNA methylation in B-cell malignancies

Blood ◽  
2018 ◽  
Vol 132 (10) ◽  
pp. 999-1006 ◽  
Author(s):  
Christopher C. Oakes ◽  
Jose I. Martin-Subero
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Driver Mutations ◽  
Detailed Knowledge ◽  
B Cell Differentiation ◽  
B Cell Malignancies ◽  
Essential Information ◽  
A Genome ◽  
Cytidine Deaminase Activity ◽  
Insight Into

AbstractUnderstanding how tumor cells fundamentally alter their identity is critical to identify specific vulnerabilities for use in precision medicine. In B-cell malignancy, knowledge of genetic changes has resulted in great gains in our understanding of the biology of tumor cells, impacting diagnosis, prognosis, and treatment. Despite this knowledge, much remains to be explained as genetic events do not completely explain clinical behavior and outcomes. Many patients lack recurrent driver mutations, and said drivers can persist in nonmalignant cells of healthy individuals remaining cancer-free for decades. Epigenetics has emerged as a valuable avenue to further explain tumor phenotypes. The epigenetic landscape is the software that powers and stabilizes cellular identity by abridging a broad genome into the essential information required per cell. A genome-level view of B-cell malignancies reveals complex but recurrent epigenetic patterns that define tumor types and subtypes, permitting high-resolution classification and novel insight into tumor-specific mechanisms. Epigenetic alterations are guided by distinct cellular processes, such as polycomb-based silencing, transcription, signaling pathways, and transcription factor activity, and involve B-cell-specific aspects, such as activation-induced cytidine deaminase activity and germinal center–specific events. Armed with a detailed knowledge of the epigenetic events that occur across the spectrum of B-cell differentiation, B-cell tumor–specific aberrations can be detected with improved accuracy and serve as a model for identification of tumor-specific events in cancer. Insight gained through recent efforts may prove valuable in guiding the use of both epigenetic- and nonepigenetic-based therapies.

scholarly journals Link between Diabetes and Alzheimer’s Disease Due to the Shared Amyloid Aggregation and Deposition Involving Both Neurodegenerative Changes and Neurovascular Damages

2020 ◽  
Vol 9 (6) ◽  
pp. 1713 ◽  
Author(s):  
Gabriela Dumitrita Stanciu ◽  
Veronica Bild ◽  
Daniela Carmen Ababei ◽  
Razvan Nicolae Rusu ◽  
Alina Cobzaru ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Impact ◽  
Significant Risk ◽  
Amyloid Β ◽  
Detailed Knowledge ◽  
Amyloid Aggregation ◽  
Islet Amyloid ◽  
Type 3 ◽  
Insight Into

Diabetes and Alzheimer’s disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms “diabetes type 3” or “brain diabetes” have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer’s disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

scholarly journals Enabling cutting-edge semiconductor simulation through grid technology

2009 ◽  
Vol 367 (1897) ◽  
pp. 2573-2584 ◽  
Author(s):  
Dave Reid ◽  
Campbell Millar ◽  
Scott Roy ◽  
Gareth Roy ◽  
Richard Sinnott ◽  
...  
Keyword(s):  
Semiconductor Industry ◽  
Complementary Metal Oxide Semiconductor ◽  
Oxide Semiconductor ◽  
Detailed Knowledge ◽  
Grid Technology ◽  
Physical Processes ◽  
Statistical Variations ◽  
Scientific Results ◽  
The Many ◽  
Insight Into

The progressive scaling of complementary metal oxide semiconductor (CMOS) transistors drives the success of the global semiconductor industry. Detailed knowledge of transistor behaviour is necessary to overcome the many fundamental challenges faced by chip and systems designers. Grid technology has enabled the unavoidable statistical variations introduced by scaling to be examined in unprecedented detail. Over 200 000 transistors have been simulated, the results of which provide detailed insight into underlying physical processes. This paper outlines recent scientific results of the nanoCMOS project and describes the way in which the scientific goals have been reflected in the grid-based e-Infrastructure.

Profiling Protease Specificity: Combining Yeast ER Sequestration Screening (YESS) with Next Generation Sequencing

2017 ◽  
Vol 12 (2) ◽  
pp. 510-518 ◽  
Author(s):  
Qing Li ◽  
Li Yi ◽  
Kam Hon Hoi ◽  
Peter Marek ◽  
George Georgiou ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Protease Specificity ◽  
Generation Sequencing

Beyond the sensory/functional dichotomy

2001 ◽  
Vol 24 (3) ◽  
pp. 480-481 ◽  
Author(s):  
George S. Cree ◽  
Ken McRae
Keyword(s):  
Binary Classification ◽  
Detailed Knowledge ◽  
Knowledge Types ◽  
Functional Knowledge ◽  
Knowledge Type ◽  
Insight Into

Most current theories of category-specific semantic deficits appeal to the role of sensory and functional knowledge types in explaining patients' impairments. We discuss why this binary classification is inadequate, point to a more detailed knowledge type taxonomy, and suggest how it may provide insight into the relationships between category-specific semantic deficits and impairments of specific aspects of knowledge.

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