Results 71 to 80 of about 6,998,855 (248)

The current agonists and positive allosteric modulators of α7 nAChR for CNS indications in clinical trials

Acta Pharmaceutica Sinica B, 2017
The alpha-7 nicotinic acetylcholine receptor (α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders.
Tao-yi Yang, Ting Xiao, Qi Sun, Kewei Wang   +3 more
semanticscholar   +1 more source

Structural insights into an engineered feruloyl esterase with improved MHET degrading properties

FEBS Letters, EarlyView.
A feruloyl esterase was engineered to mimic key features of MHETase, enhancing the degradation of PET oligomers. Structural and computational analysis reveal how a point mutation stabilizes the active site and reshapes the binding cleft, expading substrate scope.
Panagiota Karampa, Konstantinos Makryniotis, Theofani‐Iosifina Sousani, Evangelos Topakas, Vangelis Daskalakis, Maria Dimarogona   +5 more
wiley   +1 more source

Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification

Nature Communications, 2016
p53 plays a pivotal role in tumour suppression under stresses, such as DNA damage. ISG15 has been implicated in the control of tumorigenesis. Intriguingly, the expression of ISG15, UBE1L and UBCH8 is induced by DNA-damaging agents, such as ultraviolet ...
J. H. Park, Seung Wook Yang, J. Park, Seung Hyeun Ka, Ji-Hoon Kim, Y. Kong, Y. Jeon, J. Seol, C. Chung   +8 more
semanticscholar   +1 more source

Gut microbiome and aging—A dynamic interplay of microbes, metabolites, and the immune system

FEBS Letters, EarlyView.
Age‐dependent shifts in microbial communities engender shifts in microbial metabolite profiles. These in turn drive shifts in barrier surface permeability of the gut and brain and induce immune activation. When paired with preexisting age‐related chronic inflammation this increases the risk of neuroinflammation and neurodegenerative diseases.
Aaron Mehl, Eran Blacher
wiley   +1 more source

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

Breast Cancer Research, 2009
IntroductionAlterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma ...
R. Finn, J. Dering, D. Conklin, O. Kalous, David J Cohen, Amrita J. Desai, C. Ginther, M. Atefi, I. Chen, C. Fowst, G. Los, D. Slamon   +11 more
semanticscholar   +1 more source

A methionine‐lined active site governs carbocation stabilization and product specificity in a bacterial terpene synthase

FEBS Letters, EarlyView.
This study reveals a unique active site enriched in methionine residues and demonstrates that these residues play a critical role by stabilizing carbocation intermediates through novel sulfur–cation interactions. Structure‐guided mutagenesis further revealed variants with significantly altered product profiles, enhancing pseudopterosin formation. These
Marion Ringel, Carl P. O. Helmer, Shani Zev, Ronja Driller, Emily Buhr, Markus Reinbold, Renana Schwartz, Gabriel Foley, Mikael Boden, Daniel Garbe, Gerhard Schenk, Dan Thomas Major, Bernhard Loll, Thomas Brück   +13 more
wiley   +1 more source

The FAIL TO construction: A contrastive perspective [PDF]

, 2018
This article considers the various senses of the English FAIL TO construction in the light of its Norwegian translation correspondences. This construction has been alleged to be in the process of grammaticalising as a marker of negation in ...
Egan, Thomas Laurence
core  

Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.

Journal of Medicinal Chemistry, 2016
The N-methyl-D-aspartate receptor (NMDAR) is a Na(+) and Ca(2+) permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate.
M. Volgraf, Benjamin D. Sellers, Yu Jiang, Guosheng Wu, C. Ly, Elisia Villemure, Richard M Pastor, P. Yuen, A. Lu, Xifeng Luo, Mingcui Liu, Shun Zhang, Liang Sun, Yuhong Fu, P. Lupardus, H. Wallweber, B. Liederer, Gauri Deshmukh, E. Plise, Suzanne Tay, P. Reynen, J. Herrington, Amy Gustafson, Yichin Liu, Akim Dirksen, Matthias G. Dietz, Yanzhou Liu, Tzu-Ming Wang, Jesse E. Hanson, D. Hackos, K. Scearce-Levie, J. Schwarz   +31 more
semanticscholar   +1 more source

Valosin‐containing protein counteracts ATP‐driven dissolution of FUS condensates through its ATPase activity in vitro

FEBS Letters, EarlyView.
Biomolecular condensates formed by fused in sarcoma (FUS) are dissolved by high ATP concentrations yet persist in cells. Using a reconstituted system, we demonstrate that valosin‐containing protein (VCP), an AAA+ ATPase, counteracts ATP‐driven dissolution of FUS condensates through its D2 ATPase activity.
Hitomi Kimura, Shin‐ichi Tate, Kyota Yasuda   +2 more
wiley   +1 more source

On the interaction of aspect and ability in two Hindi/Urdu constructions [PDF]

Complex predicates with the Hindi/Urdu light verb le (‘take’) show an unexpected pattern of interpretation in composition with grammatical aspect. Perfective le has a completive meaning (Singh 1990), but a dispositional (modal) interpretation arises in ...
Nadathur, Prerna
core   +1 more source