Structural and mechanistic insight into DNA bending by antitumour calicheamicins

Author(s):  
Alberto Mills ◽  
Federico Gago

Among the class of enediyne antibiotics endowed with potent antitumour activities, the calicheamicin derivative known as ozogamicin is selectively targeted to several leukaemia cell types by means of tailor-made immunoconjugates....

2021 ◽  
Author(s):  
Kapil Gupta ◽  
Christine Toelzer ◽  
Maia Kavanagh Williamson ◽  
Deborah Shoemark ◽  
A. Sofia F. Oliveira ◽  
...  

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants which is of particular concern due to their potential for increased transmissibility and pathology. In addition to this entrenched variant diversity in circulation, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation by passaging SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike glycoprotein an eight amino-acid deletion encompassing the furin recognition motif and S1/S2 cleavage site. Here, we analyzed the structure, function and molecular dynamics of this variant spike, providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity, allowing the virus to probe diverse trajectories in distinct cell types to evolve viral fitness.


2019 ◽  
Vol 1860 (8) ◽  
pp. 628-639 ◽  
Author(s):  
Harry G. Sherman ◽  
Carolyn Jovanovic ◽  
Alaa Abuawad ◽  
Dong-Hyun Kim ◽  
Hilary Collins ◽  
...  

2018 ◽  
Vol 2 ◽  
pp. 239821281878389 ◽  
Author(s):  
Elizabeth E. Manning ◽  
Susanne E. Ahmari

Obsessive-compulsive disorder is a debilitating psychiatric disorder that is characterised by perseverative thoughts and behaviours. Cognitive and affective disturbances play a central role in this illness, and it is therefore not surprising that clinical neuroimaging studies have demonstrated widespread alterations in prefrontal cortex functioning in patients. Preclinical mouse experimental systems provide the opportunity to gain mechanistic insight into the neurobiological changes underlying prefrontal cortex dysfunction through new technologies that allow measurement and manipulation of activity in discrete neural populations in awake, behaving mice. However, recent preclinical research has focused on striatal dysfunction, and has therefore provided relatively little insight regarding the role of the prefrontal cortex in obsessive-compulsive disorder–relevant behaviours. Here, we will discuss a number of translational prefrontal cortex–dependent paradigms, including obsessive-compulsive disorder–relevant tasks that produce compulsive responding, and how they can be leveraged in this context. Drawing on recent examples that have led to mechanistic insight about specific genes, cell types and circuits that mediate prefrontal cortex contributions to distinct aspects of cognition, we will provide a framework for applying similar strategies to identify neural mechanisms underlying obsessive-compulsive disorder–relevant behavioural domains. We propose that research using clinically relevant paradigms will accelerate translation of findings from preclinical mouse models, thus supporting the development of novel therapeutics targeted to specific pathophysiological mechanisms.


RSC Advances ◽  
2021 ◽  
Vol 11 (34) ◽  
pp. 20961-20969
Author(s):  
Yunqing He ◽  
Wanli Nie ◽  
Ying Xue ◽  
Qishan Hu

Hydrosilylation or amination products? It depends on water amount and nucleophiles like excess water or produced/added amines.


2021 ◽  
Vol 154 (12) ◽  
pp. 124313
Author(s):  
L. M. Hunnisett ◽  
P. F. Kelly ◽  
S. Bleay ◽  
F. Plasser ◽  
R. King ◽  
...  

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