scholarly journals The face of TSR revealed

2002 ◽  
Vol 159 (2) ◽  
pp. 203-206 ◽  
Author(s):  
Roy L. Silverstein
Keyword(s):  
Structural Information ◽  
Structural Data ◽  
Type I ◽  
The Novel ◽  
Multifunctional Protein ◽  
Binding Partners ◽  
Multiple Binding ◽  
Great Insight ◽  
The Face ◽  
Insight Into

In this issue, Tan et al. (2002) report the first high resolution (1.9 Å) structural data for thrombospondin (TSP)-1, a large multifunctional protein that regulates cell adhesion, angiogenesis, cell proliferation and survival, TGFβ activation, and protease function (for review see Chen et al., 2000). Because TSP-1 has multiple binding partners and many functions, precise structural information is crucial to understanding its biology. The structure now reported, derived from crystals of the second and third type I repeats of TSP-1 is of particular interest because of the specific functions attributed to these repeats and because domains homologous to the repeats appear in many other proteins in nature. The novel layered fold motif described brings great insight into how the complicated functions of TSP-1 and related molecules are affected.

scholarly journals Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2316
Author(s):  
Nodoka Kasajima ◽  
Keita Matsuno ◽  
Hiroko Miyamoto ◽  
Masahiro Kajihara ◽  
Manabu Igarashi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ebola Virus ◽  
Structural Information ◽  
Site Directed Mutagenesis ◽  
Genome Replication ◽  
Type I ◽  
Multifunctional Protein ◽  
Functional Sites ◽  
Inhibitory Function ◽  
Inhibitory Domain

Viral protein 35 (VP35) of Ebola virus (EBOV) is a multifunctional protein that mainly acts as a viral polymerase cofactor and an interferon antagonist. VP35 interacts with the viral nucleoprotein (NP) and double-stranded RNA for viral RNA transcription/replication and inhibition of type I interferon (IFN) production, respectively. The C-terminal portion of VP35, which is termed the IFN-inhibitory domain (IID), is important for both functions. To further identify critical regions in this domain, we analyzed the physical properties of the surface of VP35 IID, focusing on hydrophobic patches, which are expected to be functional sites that are involved in interactions with other molecules. Based on the known structural information of VP35 IID, three hydrophobic patches were identified on its surface and their biological importance was investigated using minigenome and IFN-β promoter-reporter assays. Site-directed mutagenesis revealed that some of the amino acid substitutions that were predicted to disrupt the hydrophobicity of the patches significantly decreased the efficiency of viral genome replication/transcription due to reduced interaction with NP, suggesting that the hydrophobic patches might be critical for the formation of a replication complex through the interaction with NP. It was also found that the hydrophobic patches were involved in the IFN-inhibitory function of VP35. These results highlight the importance of hydrophobic patches on the surface of EBOV VP35 IID and also indicate that patch analysis is useful for the identification of amino acid residues that directly contribute to protein functions.

scholarly journals BECOMING THE POSTHUMAN: THE DESTABILISATION OF THE SUBJECT IN THOMAS GLAVINIC’S NIGHT WORK

2021 ◽  
pp. 223
Author(s):  
Branka B. Ognjanović
Keyword(s):  
Urban Environment ◽  
The State ◽  
Night Work ◽  
The Other ◽  
The Novel ◽  
Organic Life ◽  
The Uncanny ◽  
The Face ◽  
The Subject ◽  
Insight Into

The paper provides an insight into the destabilisation of the subject and the emergence of the posthuman condition in the novel Night Work (Die Arbeit der Nacht, 2006) by Austrian writer Thomas Glavinic. The first part briefly discusses previous analyses of the novel and the definitions of posthumanism as an umbrella term for a heterogeneous theory dedicated to the questions of what follows after the re-consideration of the humanist ideals and after decentring the human. The posthuman is interpreted as non-fixed, in the state of constant reconstruction as opposed to the humanist subject’s fixedness and integrity. The analysis examines the ‘uncanny’ setting of the novel and the power of survival in the face of death, which becomes the protagonist’s point of demise and divergence from consciousness and rationality. The urban environment devoid of all organic life replaces the Other applied traditionally to other humans. The Sleeper as the nightly doppelgänger and the filming of the environment further add to the transgression of the boundaries between material and immaterial, the living and the non-living, the real and the dreamlike/artificial, and ultimately determine the protagonist’s posthuman existence in the state of ‘becoming’ rather than ‘being’.

scholarly journals Death in the Line of Duty: Caregivers in the Plague narratives

2020 ◽  
Vol 12 (5) ◽  
Author(s):  
Seema Sinha ◽  
Keyword(s):  
Professional Ethics ◽  
The Other ◽  
Close Reading ◽  
The Novel ◽  
History Record ◽  
The Face ◽  
Novel Coronavirus ◽  
Insight Into

The dystopian tropes in the plague narratives shift our gaze from the presence of professional ethics to the Gothic horror that unfolds subsequently. Yet whether it is the Great Plague of London in the year 1665, or the Novel Coronavirus in Mumbai in the year 2020, the rampant spread of the contagion and the associated dread bring into focus the selflessness of the caregivers, namely, the medical and the para-medic staff. Comparing the occurrences, one historical, the other still unfolding, this study examines the eery similarities that delineate contagion as metaphor, and the role of doctors in the pandemics. The aim is to find out what happens when the doctors stumble – to succumb to fear, to fall prey to diseases that flesh is subject to, or to violate the oath of Hippocrates. We intend to scrutinize if like soldiers on the battle-front, these frontline warriors also keep their tryst with death in the line of duty, or does History record otherwise. Whether the pestilence be classical or modern, the response of the caregivers is the cornerstone on which any society is grounded. The purpose of this study is to evaluate if courage in the face of disaster is still relevant in this age of anxiety, or does self-preservation win against ethics and morality. A close reading of Daniel Defoe’s A Journal of the Plague Year gives us an insight into the timelessness of such issues, especially in a world that is plagued with maladies of its own making.

scholarly journals Probing protein flexibility reveals a mechanism for selective promiscuity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nicolas A Pabon ◽  
Carlos J Camacho
Keyword(s):  
Regulatory Proteins ◽  
Structural Basis ◽  
Structural Flexibility ◽  
Multiple Partners ◽  
Binding Partners ◽  
Multiple Binding ◽  
Binding Cavity ◽  
Hydrophobic Binding ◽  
Biophysical Approach ◽  
Insight Into

Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anticancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity. Specificity is then established by additional contacts that stabilize the PD-1 cavity into distinct bound-like modes. Collectively, our studies provide insight into the structural basis and evolution of multiple binding partners, and also suggest a biophysical approach to exploit innate binding pathways to drug seemingly undruggable targets.

scholarly journals Relevence and Effectiveness of Mathematical Models Dealing with Covid-19 Pandemic

2020 ◽  
Vol 6 (10) ◽  
pp. 130-133
Author(s):  
Dr. Uma Shankar Shukla
Keyword(s):  
Mathematical Models ◽  
Real World ◽  
Health Workers ◽  
Decision Makers ◽  
The Novel ◽  
The Face ◽  
Simplifying Assumptions ◽  
The Government ◽  
Novel Coronavirus ◽  
Insight Into

How does COVID-19 pandemic affect the India? How many people can be hit in a state and how many of them will succumb to the disease? When is it going to peak? How long should the government continue with the lockdown? What is the damage to the economy and what is its impact on each sector? These are some of the questions that haunt not only the decision makers but every sensible people in India. Mathematical models developed by mathematicians and epidemiologists has come to assist decision makers in evaluating the effects of countermeasures to an epidemic before they actually deploy them. The model could give political and beuricatic person's critical insights into the best steps they could take to counter the spread of disease in the face of pandemics. Mathematicians use modeling to represent, analyze and make predictions or otherwise provide insight into real world phenomena. Real world scenarios can be designed into a mathematical model to bring clarity to big messy questions amid fast changing variables. These models aim to make simplifying assumptions in order to arrive at tractable equations. Dealing with the novel coronavirus is an unprecedented situation which the world could not have foreseen. In order to track the COVID-19 pandemic, make predictions about the disease's progression and take decisions, as of now, the government is solely dependent on data from doctors and health workers.

scholarly journals Pre-partition India and the Rise of Indian Nationalism in Amitav Ghosh’s 'The Shadow Lines'

2020 ◽  
Vol 9 (2) ◽  
pp. 156-165
Author(s):  
Sheikh Zobaer
Keyword(s):  
Indian Subcontinent ◽  
Colonial Period ◽  
Colonial Rule ◽  
The Novel ◽  
Colonial India ◽  
Indian Nationalism ◽  
Great Insight ◽  
Revolutionary Movements ◽  
British Colonial ◽  
Insight Into

The Shadow Lines is mostly celebrated for capturing the agony and trauma of the artificial segregation that divided the Indian subcontinent in 1947. However, the novel also provides a great insight into the undivided Indian subcontinent during the British colonial period. Moreover, the novel aptly captures the rise of Indian nationalism and the struggle against the British colonial rule through the revolutionary movements. Such image of pre-partition India is extremely important because the picture of an undivided India is what we need in order to compare the scenario of pre-partition India with that of a postcolonial India divided into two countries, and later into three with the independence of Bangladesh in 1971. This paper explores how The Shadow Lines captures colonial India and the rise of Indian nationalism through the lens of postcolonialism.

See How We Roll

2021 ◽  
Author(s):  
Melinda Hinkson
Keyword(s):  
Indigenous People ◽  
Colonial State ◽  
Urban Streets ◽  
Shared Purpose ◽  
Great Insight ◽  
The Face ◽  
The City ◽  
Insight Into

In See How We Roll Melinda Hinkson follows the experiences of Nungarrayi, a Warlpiri woman from the Central Australian desert, as she struggles to establish a new life for herself in the city of Adelaide. Banished from her hometown, Nungarrayi energetically navigates promises of transformation as well as sedimented racialized expectations on the urban streets. Drawing on a decades-long friendship, Hinkson explores these circumstances through Nungarrayi's relationships: those between her country and kin that sustain and confound life beyond the desert, those that regulate her marginalized citizenship, and the new friendships called out by displacement and metropolitan life. An intimate ethnography, See How We Roll provides great insight into the enduring violence of the settler colonial state while illuminating the efforts of Indigenous people to create lives of dignity and shared purpose in the face of turbulence, grief, and tightening governmental controls.

scholarly journals Ellen Glasgow’s In This Our Life: “The Betrayals of Life” in the Crumbling Aristocratic South

2019 ◽  
Vol 33 (1) ◽  
pp. 69-88
Author(s):  
Iulia Andreea Milică
Keyword(s):  
Family Relationships ◽  
Racial Inequality ◽  
Industrial Revolution ◽  
American South ◽  
The Novel ◽  
The South ◽  
The Face ◽  
The American South ◽  
Ellen Glasgow ◽  
Insight Into

AbstractEllen Glasgow’s works have received, over time, a mixed interpretation, from sentimental and conventional, to rebellious and insightful. Her novel In This Our Life (1941) allows the reader to have a glimpse of the early twentieth-century South, changed by the industrial revolution, desperately clinging to dead codes, despairing and struggling to survive. The South is reflected through the problems of a family, its sentimentality and vulnerability, but also its cruelty, pretensions, masks and selfishness, trying to find happiness and meaning in a world of traditions and codes that seem powerless in the face of progress. The novel, apparently simple and reduced in scope, offers, in fact, a deep insight into various issues, from complicated family relationships, gender pressures, racial inequality to psychological dilemmas, frustration or utter despair. The article’s aim is to depict, through this novel, one facet of the American South, the “aristocratic” South of belles and cavaliers, an illusory representation indeed, but so deeply rooted in the world’s imagination. Ellen Glasgow is one of the best choices in this direction: an aristocratic woman but also a keen and profound writer, and, most of all, a writer who loved the South deeply, even if she exposed its flaws.

scholarly journals Rings in the Extreme: PCNA Interactions and Adaptations in the Archaea

Archaea ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jody A. Winter ◽  
Karen A. Bunting
Keyword(s):  
Structural Analysis ◽  
Protein Binding ◽  
Protein Interactions ◽  
Extreme Environments ◽  
Binding Partners ◽  
Great Insight ◽  
Dna Replication And Repair ◽  
Evolution Of Proteins ◽  
Insight Into

Biochemical and structural analysis of archaeal proteins has enabled us to gain great insight into many eukaryotic processes, simultaneously offering fascinating glimpses into the adaptation and evolution of proteins at the extremes of life. The archaeal PCNAs, central to DNA replication and repair, are no exception. Characterisation of the proteins alone, and in complex with both peptides and protein binding partners, has demonstrated the diversity and subtlety in the regulatory role of these sliding clamps. Equally, studies have provided valuable detailed insight into the adaptation of protein interactions and mechanisms that are necessary for life in extreme environments.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

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