scholarly journals A Personal History of Using Crystals and Crystallography to Understand Biology and Advanced Drug Discovery

Crystals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 676
Author(s):  
Tom L. Blundell
Keyword(s):  
Growth Factors ◽  
Drug Discovery ◽  
Cell Surface ◽  
Small Molecule ◽  
Personal History ◽  
X Ray ◽  
Surface Receptors ◽  
The Past ◽  
Industry Collaboration ◽  
History Of

Over the past 60 years, the use of crystals to define structures of complexes using X-ray analysis has contributed to the discovery of new medicines in a very significant way. This has been in understanding not only small-molecule inhibitors of proteins, such as enzymes, but also protein or peptide hormones or growth factors that bind to cell surface receptors. Experimental structures from crystallography have also been exploited in software to allow prediction of structures of important targets based on knowledge of homologues. Crystals and crystallography continue to contribute to drug design and provide a successful example of academia–industry collaboration.

scholarly journals On Remembering Le premier festival culturel panafricain d’Alger 1969

Lateral ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna Jayne Kimmel
Keyword(s):  
International Relations ◽  
Political Ideology ◽  
Third World ◽  
Foreign Affairs ◽  
Personal History ◽  
Global Politics ◽  
The Past ◽  
Remarkable Event ◽  
History Of ◽  
Pandemic Response

This assembled interview centers both Elaine Mokhtefi and Le premier festival culturel panafricain d’Alger 1969 (PANAF), a festival which she organized and attended as a part of the Algerian Ministry of Information, noting it as an exemplary instance of the power of performance at the nexus of political ideology, activist history, and the subsequent nostalgia for that era of liberation. It is equally an attempt to overcome a distant relationship to each, reflecting on the potential of oral histories to open up new pathways through the past. This history—of entangled international relations negotiated under the guise of a festive performance, a complicated trajectory of global politics which culminated in a remarkable event of celebration and solidarity—remains understudied, a footnote to more “political” concerns of Third World agendas, decolonial reorderings, and capitalist critiques. Yet through Mokhtefi’s testimony, interwoven with searching tendrils of archival detail, we can see that this festival was not a superficial exaltation in extravagance, but a pivotal moment in foreign affairs. More importantly, through her personal history, we can trace the central role that women played in these politics, if often unacknowledged. Edited in 2020, it also counters the pejorative label of non-essential labor applied to most cultural activities during the contemporary pandemic response to COVID-19.

On One Approach to the Control of Uncertain Systems

1993 ◽  
Vol 115 (2B) ◽  
pp. 373-380 ◽  
Author(s):  
G. Leitmann
Keyword(s):  
Dynamical Systems ◽  
Lyapunov Stability ◽  
Stability Theory ◽  
Uncertain Systems ◽  
Lyapunov Stability Theory ◽  
Personal History ◽  
The Past ◽  
History Of ◽  
Control Of Uncertain Systems

This paper is a personal history of one area of research with which I have been concerned over the past twenty years and which continues to attract my albeit waning attention, the control of dynamical systems based on uncertain models. Thus, it is a subjective account of various factors which I believe to have steered me to approach the problem via a constructive use of Lyapunov stability theory.

scholarly journals X-ray crystallography over the past decade for novel drug discovery – where are we heading next?

2015 ◽  
Vol 10 (9) ◽  
pp. 975-989 ◽  
Author(s):  
Heping Zheng ◽  
Katarzyna B Handing ◽  
Matthew D Zimmerman ◽  
Ivan G Shabalin ◽  
Steven C Almo ◽  
...  
Keyword(s):  
Drug Discovery ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Past ◽  
Novel Drug

scholarly journals CD4 T cells: fates, functions, and faults

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1557-1569 ◽  
Author(s):  
Jinfang Zhu ◽  
William E. Paul
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Surface Receptors ◽  
The Past ◽  
History Of ◽  
Th1 And Th2

Abstract In 1986, Mosmann and Coffman identified 2 subsets of activated CD4 T cells, Th1 and Th2 cells, which differed from each other in their pattern of cytokine production and their functions. Our understanding of the importance of the distinct differentiated forms of CD4 T cells and of the mechanisms through which they achieve their differentiated state has greatly expanded over the past 2 decades. Today at least 4 distinct CD4 T-cell subsets have been shown to exist, Th1, Th2, Th17, and iTreg cells. Here we summarize much of what is known about the 4 subsets, including the history of their discovery, their unique cytokine products and related functions, their distinctive expression of cell surface receptors and their characteristic transcription factors, the regulation of their fate determination, and the consequences of their abnormal activation.

scholarly journals Untreated Active Tuberculosis in Pregnancy with Intraocular Dissemination: A Case Report and Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Shadi Rezai ◽  
Stephen LoBue ◽  
Daniel Adams ◽  
Yewande Oladipo ◽  
Ramses Posso ◽  
...  
Keyword(s):  
Case Report ◽  
Developed Countries ◽  
Physiological Changes ◽  
Review Of The Literature ◽  
X Ray ◽  
Delay In Diagnosis ◽  
The Past ◽  
History Of ◽  
Chest X Ray ◽  
Patient Refusal

Background.Tuberculosis (TB) is a disease that affects hundreds of millions of people across the world. However, the incidence in developed countries has decreased over the past decades causing physicians to become unfamiliar with its unspecific symptoms. Pregnant individuals are especially difficult because many symptoms of active TB can mimic normal physiological changes of pregnancy. We present a case report of a 26-year-old multiparous woman, G4P3003, at 38-week gestation with a history of positive PPD who emigrated from Ghana 6 years ago. She came to the hospital with an initial complaint of suprapubic pain, pressure, and possible leakage of amniotic fluid for the past week. Patient also complained of a productive cough for the past 3 to 4 months with a decrease in vision occurring with the start of pregnancy. Visual acuity was worse than 20/200 in both eyes. Definitive diagnosis of active TB was delayed due to patient refusal of chest X-ray. Fortunately, delay in diagnosis was minimized since patient delivered within 24 hours of admission. Active TB was confirmed with intraocular dissemination. Patient had optic atrophy OS (left eye) and papillitis, choroiditis, and uveitis OD (right eye) due to TB infiltration. Fetus was asymptomatic and anti-TB therapy was started for both patients.

scholarly journals Discovery of an MLLT1/3 YEATS Domain Chemical Probe

2018 ◽  
Author(s):  
Moses Moustakim ◽  
Thomas Christott ◽  
Octovia P. Monteiro ◽  
James Bennett ◽  
Charline Giroud ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Crystal Structures ◽  
Small Molecule ◽  
Therapeutic Potential ◽  
Selective Inhibitor ◽  
Target Engagement ◽  
Chemical Probe ◽  
X Ray ◽  
Cellular Target ◽  
Excellent Selectivity

<p>YEATS domain (YD) containing proteins are an emerging</p> <p>class of epigenetic targets in drug discovery. Dysregulation of these modified lysine binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterisation of the first small molecule chemical probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3 -histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed. Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small molecule X-ray co-crystal structures with the MLLT1 YD are also reported. This first in class probe molecule can be used to understand MLLT1/3 associated biology and the therapeutic potential of small molecule YD inhibitors.</p>

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