Results 41 to 50 of about 441,995 (314)

Interpreting the effects of DNA polymerase variants at the structural level

Molecular Oncology, EarlyView.
Using MAVISp and molecular dynamics simulations, we analyzed over 60 000 missense variants in POLE and POLD1 from ClinVar, COSMIC, cBioPortal, and saturation mutagenesis. Identified mechanistic indicators, including stability, binding, and long‐range, enable structural interpretation, providing ACMG‐like evidence for possible reclassification of VUS ...
Matteo Arnaudi, Karolina Krzesińska, Ludovica Beltrame, Pablo Sánchez‐Izquierdo Besora, Matteo Tiberti, Mef Nilbert, Anna Rohlin, Elena Papaleo   +7 more
wiley   +1 more source

A computational tool to optimize clinical trial parameter selection in Duchenne muscular dystrophy: A practical guide and case studies

CPT: Pharmacometrics & Systems Pharmacology
Duchenne muscular dystrophy (DMD), a rare pediatric disease, presents numerous challenges when designing clinical trials, mainly due to the scarcity of available trial participants and the heterogeneity of disease progression.
Jordan Wilk, Varun Aggarwal, Mike Pauley, Diane Corey, Daniela J. Conrado, Karthik Lingineni, Juan Francisco Morales, Deok Yong Yoon, Yi Zhang, Zihan Cui, Jackson Burton, Jane Larkindale, Shu Chin Ma, Collin Hovinga, Terina Martinez, Klaus Romero, Ramona Belfiore‐Oshan, Sarah Kim, the Duchenne Regulatory Science Consortium (D‐RSC) and the CINRG DNHS investigators   +18 more
doaj   +1 more source

Exploring the evidence for the use of protein biomarkers of muscular damage and disease progression in Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis protocol

BMJ Open
Introduction Duchenne and Becker muscular dystrophies (DMD and BMD) are devastating conditions characterised by progressive muscle degeneration and weakness.
Stefania Mondello, Pietro Spitali, Alan J Russell, Amelia McGill, Ange Lu, Ramona Belfiore-Oshan, Paige B Martin   +6 more
doaj   +1 more source

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

Addressing the need for standardization of symptomatic medication documentation in Parkinson's disease clinical research: A call to action

Journal of Parkinson’s Disease
People with Parkinson's disease (PD) are prescribed a variety of medications to mitigate symptoms and improve their quality of life. These symptomatic therapies cover a range of pharmacological classes, including classical dopaminergic treatments, other ...
Mikayla Spott, Monica Javidnia, Anne Pedata, Martijn Müller, Laura Carrillo, Tanya Simuni, Gennaro Pagano, Kevin Kwok, Klaus Romero, Diane Stephenson   +9 more
doaj   +1 more source

Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease

Clinical and Translational Science, 2019
The Critical Path for Parkinson's (CPP) Imaging Biomarker and Modeling and Simulation working groups aimed to achieve qualification opinion by the European Medicines Agency (EMA) Committee for Medical Products for Human Use (CHMP) for the use of baseline
Klaus Romero, Daniela Conrado, Jackson Burton, Timothy Nicholas, Vikram Sinha, Sreeraj Macha, Malidi Ahamadi, Jesse Cedarbaum, John Seibyl, Kenneth Marek, Peter Basseches, Derek Hill, Ed Somer, Jill Gallagher, David T. Dexter, Arthur Roach, Diane Stephenson, for the Critical Path for Parkinson's (CPP) Consortium, the Parkinson's Progression Markers Initiative (PPMI)   +18 more
doaj   +1 more source

Analysing the significance of small conformational changes and low occupancy states in serial crystallographic data

FEBS Open Bio, EarlyView.
This protocol paper outlines methods to establish the success of a time‐resolved serial crystallographic experiment, by means of statistical analysis of timepoint data in reciprocal space and models in real space. We show how to amplify the signal from excited states to visualise structural changes in successful experiments.
Jake Hill, Yelyzaveta Pulnova, Elke De Zitter, Helen M. Ginn, Briony A. Yorke   +4 more
wiley   +1 more source

Optimal Allocation of Protective Resources in Shortest-Path Networks [PDF]

, 2008
We develop a game theoretic approach for allocating protection resources among the components of a network so as to maximize its robustness to external disruptions.
Cappanera, Paola, Scaparra, Maria Paola
core  

YlmG1 is localized exclusively to the chloroplast envelope membrane and is involved in preprotein translocation in Arabidopsis thaliana

FEBS Open Bio, EarlyView.
Cytosolically synthesized chloroplast preproteins are translocated across the outer and inner envelope membranes through translocons called TOC and TIC, respectively. In green algae and plants, the TIC core is composed of essential membrane proteins, Tic12, Tic20, and Tic214.
Mengyi Li, Xueyang Zhao, Masato Nakai
wiley   +1 more source

Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion

FEBS Open Bio, EarlyView.
This paper reveals how human lactoferrin–albumin fusion (hLF‐HSA) potently suppresses lung adenocarcinoma cell migration. hLF‐HSA upregulates NHE7, leading to Golgi alkalization, disruption of the Golgi secretome, downregulation of MMP1, and reversal of EMT. These findings suggest a novel Golgi‐targeting strategy to suppress cancer cell migration.
Hana Nopia, Masahiro Kimura, Daisuke Kurimoto, Atsushi Sato   +3 more
wiley   +1 more source