Installation of an Indole on the BRCA1 Disordered Domain Using Triazine Chemistry.

The functionalization of protein sidechains with highly water-soluble chlorotriazines (or derivatives thereof) using nucleophilic aromatic substitution reactions has been commonly employed to install various functional groups, including poly(ethylene glycol) tags or fluorogenic labels. Here, a poorly soluble dichlorotriazine with an appended indole is shown to react with a construct containing the disordered domain of BRCA1. Subsequently, this construct can undergo proteolytic cleavage to remove the SUMO-tag: the -terminal poly(His) tag is still effective for purification.

Primary healthcare provider-perceived barriers to implementing an evidence-based pathway for undifferentiated lower gastrointestinal tract symptoms: A qualitative inquiry.

Background: Primary healthcare providers play a critical role in diagnosing and managing digestive disorders. Standardized clinical care guidelines have been developed, but with limited and inconsistent implementation. An evidence-based gastroenterology clinical care pathway (GUTLINK) has been proposed in one region of Canada; however, little is known in the medical literature about potential barriers to pathway implementation within primary care.

Long-term studies should provide structure for inclusive education and professional development.

Long-term studies are critical for ecological understanding, but they are underutilized as inclusive opportunities for training ecologists. We use our perspective from the Año Nuevo elephant seal programme along with surveys from community members to propose that long-term studies could be better leveraged to promote inclusive education and professional development in ecology. Drawing on our experiences as mentors and mentees, we demonstrate how long-term studies can use their resources, including rich data, robust logistics and extensive professional networks, to improve recruitment and retention of diverse groups of trainees.

Biophysics and electrophysiology of pulsed field ablation in normal and infarcted porcine cardiac ventricular tissue.

Pulsed Field Ablation (PFA) is a new ablation method being rapidly adopted for treatment of atrial fibrillation, which shows advantages in safety and efficiency over radiofrequency and cryo-ablation. In this study, we used an in vivo swine model (10 healthy and 5 with chronic myocardial infarct) for ventricular PFA, collecting intracardiac electrograms, electro-anatomical maps, native T1-weighted and late gadolinium enhancement MRI, gross pathology, and histology. We used 1000-1500 V pulses, with 1-16 pulse trains to vary PFA dose.

Profiling protease cleavage patterns in plasma for pancreatic cancer detection.

Proteases are promising biomarkers for cancer early detection. Their enzymatic activity against peptide substrates allows for their straightforward detection using low-cost tests. However, the complexity of the human proteome makes it challenging to develop sensitive and selective tests against a specific protease biomarker.