scholarly journals Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin

2021 ◽  
Author(s):  
Jerzy Osipiuk ◽  
Pawel M Wydorski ◽  
Benjamin T Lanham ◽  
Christine Tesar ◽  
Michael Endres ◽  
...  
Keyword(s):  
Active Phase ◽  
Solution Nmr ◽  
Substrate Selectivity ◽  
Functional Protein ◽  
Protein Substrates ◽  
The World ◽  
Energetic Analysis ◽  
Interferon Stimulated Gene 15 ◽  
Dual Domain ◽  
Binding Interfaces

The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) genome is evolving as the viral pandemic continues its active phase around the world. The Papain-like protease (PLpro) is a domain of Nsp3 – a large multi-domain protein that is an essential component of the replication-transcription complex, making it a good therapeutic target. PLpro is a multi-functional protein encoded in coronaviruses that can cleave viral polyproteins, poly-ubiquitin and protective Interferon Stimulated Gene 15 product, ISG15, which mimics a head-to-tail linked ubiquitin (Ub) dimer. PLpro across coronavirus families showed divergent selectivity for recognition and cleavage of these protein substrates despite sequence conservation. However, it is not clear how sequence changes in SARS-CoV-2 PLpro alter its selectivity for substrates and what outcome this has on the pathogenesis of the virus. We show that SARS-CoV-2 PLpro preferentially binds ISG15 over Ub and K48-linked Ub2. We determined crystal structures of PLpro in complex with human K48-Ub2 and ISG15 revealing that dual domain recognition of ISG15 drives substrate selectivity over Ub and Ub2. We also characterized the PLpro substrate interactions using solution NMR, cross-linking mass spectrometry to support that ISG15 is recognized via two domains while Ub2 binds primarily through one Ub domain. Finally, energetic analysis of the binding interfaces between PLpro from SARS-CoV-1 and SARS-CoV-2 with ISG15 and Ub2 define the sequence determinants for how PLpros from different coronaviruses recognize two topologically distinct substrates and how evolution of the protease altered its substrate selectivity. Our work reveals how PLpro substrate selectivity may evolve in PLpro coronaviruses variants enabling design of more effective therapeutics.

scholarly journals The duration of the active phase on surge-type glaciers: contrasts between Svalbard and other regions

1991 ◽  
Vol 37 (127) ◽  
pp. 388-400 ◽  
Author(s):  
Julian A. Dowdeswell ◽  
Gordon S. Hamilton ◽  
Jon Ove Hagen
Keyword(s):  
Time Series ◽  
North America ◽  
Active Phase ◽  
Aerial Photographs ◽  
Polar Ice ◽  
Phase Duration ◽  
Field Surveys ◽  
The World ◽  
Glacier Surges ◽  
Fast Motion

AbstractMany glaciers in Svalbard and in other glacierized areas of the world are known to surge. However, the time series of observations required to assess the duration of fast motion is very restricted. Data on active-phase duration in Svalbard come from aerial photographs, satellite imagery, field surveys and airborne reconnaissance. Evidence on surge duration is available for eight Svalbard ice masses varying from 3 to 1250 km2. Worldwide, active-phase duration is recorded for less than 50 glaciers. Few observations are available on high polar ice masses. The duration of the active phase is significantly longer for Svalbard glaciers than for surge-type glaciers in other areas from which data are available. In Svalbard, the active phase may last from 3 to 10 years. By contrast, a surge duration of 1–2 years is more typical of ice masses in northwest North America, Iceland and the Pamirs. Ice velocities during the protracted active phase on Svalbard glaciers are considerably lower than those for many surge-type glaciers in these other regions. Mass is transferred down-glacier more slowly but over a considerably longer period. Svalbard surge-type glaciers do not exhibit the very abrupt termination of the active phase, over periods of a few days, observed for several Alaskan glaciers. The duration of the active phase in Svalbard is not dependent on parameters related to glacier size. The quiescent phase is also relatively long (50–500 years) for Svalbard ice masses. Detailed field monitoring of changing basal conditions through the surge cycle is required from surge-type glaciers in Svalbard in order to explain the significantly longer length of the active phase for glaciers in the archipelago, which may also typify other high polar ice masses. The finding that surge behaviour, in the form of active-phase duration, shows systematic differences between different regions and their environments has important implications for understanding the processes responsible for glacier surges.

Trimetallic Sulfide Catalysts for Hydrodesulfurization

2016 ◽  
pp. 240-262 ◽  
Author(s):  
Rafael Huirache-Acuña ◽  
Gabriel Alonso-Nuñez ◽  
Eric M. Rivera-Muñoz ◽  
Omar Gutierrez ◽  
Barbara Pawelec
Keyword(s):  
Active Phase ◽  
Diesel Oil ◽  
Catalyst Preparation ◽  
Refining Industry ◽  
Sulfide Catalysts ◽  
Hydrotreating Catalysts ◽  
Ternary Sulfide ◽  
The World ◽  
And Performance ◽  
State Of Art

The more stringent environmental regulations enacted throughout the world have increased the need of more active hydrotreating (HDT) catalysts, in the petroleum refining industry. Usually, the catalysts used for diesel oil hydrotreatment are ?-Al2O3 supported molybdenum or tungsten sulfides promoted with cobalt or nickel. Current strategies for the design of novel HDS catalysts often include variations in the support formulation, catalyst preparation method and active phase formulation. In this sense, the new generations of catalysts, such as NEBULA®, are based on a totally different concept of bulk-like. In this chapter, we present recent research related to the synthesis, characterization and performance of trimetallic sulfide nanocatalysts for hydrodesulfurization. The present chapter analyses the state of art of the ternary sulfide hydrotreating catalysts.

scholarly journals The duration of the active phase on surge-type glaciers: contrasts between Svalbard and other regions

1991 ◽  
Vol 37 (127) ◽  
pp. 388-400 ◽  
Author(s):  
Julian A. Dowdeswell ◽  
Gordon S. Hamilton ◽  
Jon Ove Hagen
Keyword(s):  
Time Series ◽  
North America ◽  
Active Phase ◽  
Aerial Photographs ◽  
Polar Ice ◽  
Phase Duration ◽  
Field Surveys ◽  
The World ◽  
Glacier Surges ◽  
Fast Motion

AbstractMany glaciers in Svalbard and in other glacierized areas of the world are known to surge. However, the time series of observations required to assess the duration of fast motion is very restricted. Data on active-phase duration in Svalbard come from aerial photographs, satellite imagery, field surveys and airborne reconnaissance. Evidence on surge duration is available for eight Svalbard ice masses varying from 3 to 1250 km2. Worldwide, active-phase duration is recorded for less than 50 glaciers. Few observations are available on high polar ice masses. The duration of the active phase is significantly longer for Svalbard glaciers than for surge-type glaciers in other areas from which data are available. In Svalbard, the active phase may last from 3 to 10 years. By contrast, a surge duration of 1–2 years is more typical of ice masses in northwest North America, Iceland and the Pamirs. Ice velocities during the protracted active phase on Svalbard glaciers are considerably lower than those for many surge-type glaciers in these other regions. Mass is transferred down-glacier more slowly but over a considerably longer period. Svalbard surge-type glaciers do not exhibit the very abrupt termination of the active phase, over periods of a few days, observed for several Alaskan glaciers. The duration of the active phase in Svalbard is not dependent on parameters related to glacier size. The quiescent phase is also relatively long (50–500 years) for Svalbard ice masses. Detailed field monitoring of changing basal conditions through the surge cycle is required from surge-type glaciers in Svalbard in order to explain the significantly longer length of the active phase for glaciers in the archipelago, which may also typify other high polar ice masses. The finding that surge behaviour, in the form of active-phase duration, shows systematic differences between different regions and their environments has important implications for understanding the processes responsible for glacier surges.

scholarly journals Margaret Thatcher's Vision on the Russian Factor in the International Relations System (Late Twentieth – Early Twenty-First Century)

2021 ◽  
pp. 363-376
Author(s):  
Oksana Cherevko ◽  
Keyword(s):  
International Relations ◽  
Interpersonal Relations ◽  
Active Phase ◽  
The United States ◽  
Political Regime ◽  
Early 21St Century ◽  
Scientific Legacy ◽  
Margaret Thatcher ◽  
The World

The article analyzes the memoirs and scientific legacy of the Prime Minister of the United Kingdom during 1979-1990 Margaret Thatcher on the role of the USSR and Russia in the international relations system of the last third of the 20th ─ early 21st century. The evolution of Soviet/Russian-British relations in the active phase of the Cold War and its gradual extinction is studied: from the categorical rejection of the Soviet political regime at a time of stagnation to the establishment of active dialogue during the period of rebuilding and Gorbachev's "new political thinking". The paper focuses on the predictions of a respected British politician regarding Russia's role in the future of Europe and the world. The role of the nuclear factor in the implementation of Soviet-British relations is analyzed. The process of implementation of the "German question" through the prism of these relations is considered. The role of the United States as an important factor influencing the course of the Soviet/Russian-British dialogue is defined, in particular in the context of NATO's role, operation “Desert Storm”. The paper describes the main problems of Europe and the world, exacerbated during the collapse of the Soviet Union. Particular attention is paid to the consideration of interpersonal relations between Margaret Thatcher and Mikhail Gorbachev and the characteristics of his successors as leader of the state: Boris Yeltsin and Vladimir Putin

scholarly journals Hidden dynamic signatures drive substrate selectivity in the disordered phosphoproteome

2020 ◽  
Vol 117 (38) ◽  
pp. 23606-23616
Author(s):  
Min-Hyung Cho ◽  
James O. Wrabl ◽  
James Taylor ◽  
Vincent J. Hilser
Keyword(s):  
Conformational Equilibrium ◽  
Energy Difference ◽  
Statistical Thermodynamic ◽  
Sequence Information ◽  
Substrate Selectivity ◽  
Phosphorylation Sites ◽  
Information Encoding ◽  
Conformational Ensembles ◽  
Protein Substrates ◽  
Conservation Patterns

Phosphorylation sites are hyperabundant in the eukaryotic disordered proteome, suggesting that conformational fluctuations play a major role in determining to what extent a kinase interacts with a particular substrate. In biophysical terms, substrate selectivity may be determined not just by the structural–chemical complementarity between the kinase and its protein substrates but also by the free energy difference between the conformational ensembles that are, or are not, recognized by the kinase. To test this hypothesis, we developed a statistical-thermodynamics-based informatics framework, which allows us to probe for the contribution of equilibrium fluctuations to phosphorylation, as evaluated by the ability to predict Ser/Thr/Tyr phosphorylation sites in the disordered proteome. Essential to this framework is a decomposition of substrate sequence information into two types: vertical information encoding conserved kinase specificity motifs and horizontal information encoding substrate conformational equilibrium that is embedded, but often not apparent, within position-specific conservation patterns. We find not only that conformational fluctuations play a major role but also that they are the dominant contribution to substrate selectivity. In fact, the main substrate classifier distinguishing selectivity is the magnitude of change in local compaction of the disordered chain upon phosphorylation of these mostly singly phosphorylated sites. In addition to providing fundamental insights into the consequences of phosphorylation across the proteome, our approach provides a statistical-thermodynamic strategy for partitioning any sequence-based search into contributions from structural–chemical complementarity and those from changes in conformational equilibrium.

scholarly journals Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR

2020 ◽  
Vol 21 (5) ◽  
pp. 1829 ◽  
Author(s):  
Yuji Tokunaga ◽  
Thibault Viennet ◽  
Haribabu Arthanari ◽  
Koh Takeuchi
Keyword(s):  
Dynamic Properties ◽  
Critical Role ◽  
Solution Nmr ◽  
Functional Protein ◽  
Structural Dynamic ◽  
Dynamic View ◽  
Analysis Of Dynamics ◽  
And Function ◽  
Functional Mechanisms ◽  
Applied Biology

Solution NMR spectroscopy is a unique and powerful technique that has the ability to directly connect the structural dynamics of proteins in physiological conditions to their activity and function. Here, we summarize recent studies in which solution NMR contributed to the discovery of relationships between key dynamic properties of proteins and functional mechanisms in important biological systems. The capacity of NMR to quantify the dynamics of proteins over a range of time scales and to detect lowly populated protein conformations plays a critical role in its power to unveil functional protein dynamics. This analysis of dynamics is not only important for the understanding of biological function, but also in the design of specific ligands for pharmacologically important proteins. Thus, the dynamic view of structure provided by NMR is of importance in both basic and applied biology.

scholarly journals Efficacy of Drotaverine in Comparison to Hyoscine Butylbromide in Augmentation of Labour

JMS SKIMS ◽  
2012 ◽  
Vol 15 (1) ◽  
pp. 39-43
Author(s):  
Sameena Ashraf Kirmani ◽  
Mohammad Sadiq Malla ◽  
Farkhand Mohi-ud-din Regoo
Keyword(s):  
Active Phase ◽  
Cervical Dilatation ◽  
Term Pregnancy ◽  
Hyoscine Butylbromide ◽  
Rectal Suppository ◽  
Active Labour ◽  
Products Of Conception ◽  
The World ◽  
Group A ◽  
Group B

BACKGROUND: Contractility of the myometrium is usually diminished during pregnancy to accommodate and protect the growing products of conception; drugs like Hyoscine butylbromide and Drotaverine are used to shorten the duration of labor in many hospitals all over the world. OBJECTIVE: To compare the effect of intravenous Drotaverine and Hyoscine Butylbromide rectal suppository on duration of labour and rate of cervical dilatation. METHODS: Three hundred pregnant women with term pregnancy in active labour were selected by simple randomization and were divided into three groups: Group A, where injection Drotaverine intravenous was given; Group B, where Hyoscine Butylbromide rectal suppository was instilled; and in Group C, where no drug was given. RESULTS: Mean duration of first stage of labour was 179.1 min, 159.3 min and 299.0 min in groups A, B and C, respectively. Rate of cervical dilatation in groups A, B and C was 2.6, 2.9 and 2.0 cm/hr, respectively. Most of the subjects delivered vaginally. No serious side effects were noted in both the drug groups. CONCLUSION: Hyoscine Butylbromide is more effective than Drotaverine in reducing the duration of active phase of labour. There is a significant improvement in the rate of cervical dilatation with Hyoscine Butylbromide when compared to Drotaverine. JMS 2012;15(1):39-43.

scholarly journals Pengaruh L14 terhadap Peningkatan Kontraksi pada Kala I Persalinan

2018 ◽  
Vol 9 (3) ◽  
pp. 433
Author(s):  
Neneng Siti Lathifah ◽  
Ledy Octaviani Iqmy
Keyword(s):  
Side Effects ◽  
Quantitative Research ◽  
Active Phase ◽  
Statistical Test ◽  
Labor Process ◽  
P Value ◽  
Test Results ◽  
Data Collection Tool ◽  
The World ◽  
Speed Up

<p>The old partus is one of the causes of maternal death. Based on the date The Renstra of Provincial Health Office (2015) found that the old average partus in the world caused maternal mortality by 8%, in Indonesia by 9% and in Lampung province by 0,63%. The purpose of this study is to determine the effect of L14 against increasing contraction  in the first stages labor mother in BPM Lia Maria Bandar Lampung Regency 2018. This type of research uses quantitative research with quasy experiment. The population in this study were all patients inpartu  in the first stages labor mother at BPM Lia Maria Bandar Lampung 2018. Amounted to 83 people. Samples to 42 people. Technic Sampling Purposive Sampling With sample criteria divided into two, namely inclusion and exclusion. The data collection tool used in this research is to fill in the observation sheet and fill partograph. The statistical test used is T-Test. Statistical test results obtained p-value 0.000&lt;0.05. For practice land or BPM can be used as a solution that massage at the L14 point given to the mother in part at the active phase affects the increase in contraction, so that it can speed up the labor process and without harmful side effects.</p>

scholarly journals Controlling COVID-19 Pandemic: A Mass Screening Experience in Saudi Arabia

2021 ◽  
Vol 8 ◽  
Author(s):  
Anas A. Khan ◽  
Hadil M. Alahdal ◽  
Reem M. Alotaibi ◽  
Hana S. Sonbol ◽  
Rana H. Almaghrabi ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Mass Screening ◽  
Screening Program ◽  
Demographic Data ◽  
Active Phase ◽  
World Health ◽  
High Risk Population ◽  
Cross Sectional ◽  
Screening Programs ◽  
The World

A highly accelerating number of people around the world have been infected with novel Coronavirus disease 2019 (COVID-19). Mass screening programs were suggested by the World Health Organization (WHO) as an effective precautionary measure to contain the spread of the virus. On 16 April 2020, a COVID-19 mass screening program was initiated in Saudi Arabia in multiple phases. This study aims to analyze the number of detected COVID-19 cases, their demographic data, and regions most affected in the initial two phases of these mass screening programs. A retrospective cross-sectional study was conducted among the high-risk population as part of the COVID-19 mass screening program across all regions in Saudi Arabia during April and May 2020. A Chi-square-test was used to determine the associations between positive cases and various demographic variables. Out of 71,854 screened individuals, 13.50% (n = 9701) were COVID-19 positive, of which 83.27% (n = 59,835) were males. Among positive cases, in the 30–39 years age group, 6.36% were in the active phase, and 2.19% were in the community phase. Based on our experience, launching mass screening programs is crucial for early case detection, isolation, and pattern recognition for immediate public interventions.

scholarly journals Increase in Cancer Patient Load during COVID-19 Pandemic: The Faridabad Experience

2021 ◽  
Vol 10 (01) ◽  
pp. 36-38
Author(s):  
Sumant Gupta ◽  
Anamika Pandey ◽  
Neha Gupta ◽  
Faran Naim ◽  
Rakesh Gupta ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Active Phase ◽  
Linear Increase ◽  
Cancer Case ◽  
The World ◽  
Patient Load ◽  
Travel Restrictions ◽  
Oncology Care ◽  
Risk Of Exposure

Abstract Introduction Coronavirus disease 2019 (COVID-19) has affected oncology care differently across the world. We evaluated our experience of infusional chemotherapy during the active phase of ongoing pandemic. Methods Prospectively collected month wise data from January 2019 to November 2020 was compared between the 2 years. Results A total of 6,003 chemotherapy infusions were administered between January 1, 2019 and November 30, 2020 (2,548 in 11 months of 2019 and 3,455 in the same 11 months of 2020). Between May 1 and October 31, 2020, 2,337 chemotherapy infusions were administered to 570 patients all of whom were also tested for COVID-19 positivity, of which 65 (11.4%) were COVID-19 positive. The majority (63/65; 97%) could receive their chemotherapy infusions safely. Discussion Paradoxically, our hospital recorded an increase in the number of cancer patients receiving infusional chemotherapy in 2020, with a linear increase in the cancer case being treated (from 309 in June to 398 in November 2020). We believe that this was possible because cancer patients wanted treatment near their homes to avoid/minimize risk of exposure to COVID-19, cross state border travel restrictions was an additional roadblock, and our quality of service provided earned the trust of cancer patients.

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