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Mohamedshah et al. present an enzymatic strategy for covalently linking nuclear localization sequence (NLS) peptides to DNA cassettes by incorporating a strained cyclooctyne and using SPAAC chemistry, greatly enhancing transfection efficiency compared to previous methods. [ https://www.nature.com/articles/s41467-025-68167-5](https://www.nature.com/articles/s41467-025-68167-5)
Efficient nuclear delivery of DNA remains a major challenge in non-viral gene therapy. Here the authors present an improved workflow for generating DNA oligonucleotide-peptide conjugates which are ligated to linear DNA and achieve nuclear localization.
A research team at Carnegie Mellon University has developed a new noninvasive brain stimulation technique, by showing how focused ultrasound affects the human brain. Using brainwave recordings from human participants, the team found that focused ultrasound can subtly influence brain activity without directly causing neurons to fire. The work clarifies conflicting results in the field and introduces a new approach to noninvasive brain stimulation. The study is published in Nature Communications.
Focused ultrasound has been studied for years, but its effects in humans are not well understood. One challenge is that the technology makes a quiet beeping sound that can trigger hearing pathways in the brain, making it hard to know whether changes are caused by the sound or by the ultrasound itself. Previous studies using MRI scans may also produce misleading signals.
To address these limitations, researchers conducted a resting-state study in 27 human participants using concurrent whole-brain EEG recordings. They compared low-intensity transcranial focused ultrasound (tFUS) alone, a mild electrical brain stimulation called tDCS, and a new approach that combines the two, deemed transcranial electro-acoustic stimulation (tEAS). When used alone, neither ultrasound nor electrical stimulation caused clear, targeted brain responses. However, when combined, they produced strong, specific activity in the targeted area.
Patients with symmetric PD can be identified with a simple and straightforward method, a ratio right by left hemibody score equalling 1. This requires no additional time, effort or specialised neuroimaging or laboratory resources.
Background Motor asymmetry is a hallmark of Parkinson’s disease (PD), but ~20% of patients present with symmetric motor signs, which are associated with faster disease progression and poorer dopaminergic response. The impact of motor symmetry on activities of daily living (ADL) outcomes following subthalamic deep brain stimulation (STN-DBS) remains unclear. We hypothesised that patients with symmetric PD experience less ADL improvement post-STN-DBS than asymmetric PD patients.
Methods This was a prospective, quasi-experimental, non-randomised, controlled, international multicentre study with a 6-month follow-up. The primary outcome was the Scales for Outcomes in Parkinson’s Disease-Motor ADL scale. Secondary outcomes included Unified Parkinson’s Disease Rating Scale motor examination and Parkinson’s Disease Questionnaire-8 (PDQ-8). We defined symmetric PD as a right-to-left hemibody motor score equalling 1. We analysed within-group longitudinal changes, between-group outcome differences, effect size and correlations between PDQ-8 and motor changes. We confirmed results in a propensity-score matched subcohort with well-balanced demographic and clinical parameters.
Results We included 200 patients with asymmetric and 54 with symmetric PD. In symmetric PD, ADL remained stable, which was not associated with the observed PDQ-8 improvement. In contrast, in asymmetric PD, ADL improved with a moderate effect size, which correlated moderately with PDQ-8 improvement. In symmetric PD, the absolute risk of experiencing no clinically relevant postoperative ADL improvement was 23.8% higher.
Some medical societies say recent studies may have overstated the risks of lung cancer screening, potentially discouraging eligible patients from being screened. While debates continue about false positives and overdiagnosis, many experts agree that routine screening with low-dose CT has clear benefits for people at high risk of lung cancer.
Three medical societies claim recent studies have overestimated the potential harms from lung cancer screening and may be deterring patients. Not everyone agrees.
The landscape for stage IV driver mutation-negative NSCLC is shifting toward even greater precision. ASCO has released critical updates to the Living Guidelines, emphasizing that the “absence” of a driver mutation is a vital biomarker in itself.
An interview with Joshua Reuss, MD, thoracic medical oncologist at Georgetown University and co-author of the guidelines.
David S. Yu & team now show SIRT2 deacetylates MRE11 facilitating DNA binding to promote DNA end resection and ATM-dependent DNA damage signaling:
The figure shows MRE11 K393 deacetylation by SIRT2 promotes DNA end resection after ionizing radiation exposure, in the osteosarcoma cell line U20S.
1Department of Radiation Oncology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
2Department of Biology, Clark Atlanta University, Atlanta, Georgia, USA.
3Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
