Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway.

Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes a protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into the molecular role of PCDH19 in the brain, we investigated the PCDH19 interactome in the developing mouse hippocampus and cortex.

ERK Inhibition Improves Anti-PD-L1 Immune Checkpoint Blockade in Preclinical Pancreatic Ductal Adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint blockade (ICB) along the PD-1/PD-L1 axis. Variable PD-L1 expression in PDAC indicates a potential access issue of PD-L1-targeted therapy. To monitor target engagement of PD-L1-targeted therapy, we generated a PD-L1-targeted PET tracer labeled with zirconium-89 (Zr).

Association Between Management of Continuous Subcutaneous Basal Insulin Administration and HbA1C.

Background: While we expect that patients who adjust their insulin delivery algorithms between clinic visits to have better glucose control compared to those who do not, this effect has not been quantified.

Method: This is a single-center retrospective cohort study including pediatric and adult patients with type 1 diabetes evaluating insulin pump self-management behaviors. Basal insulin dose information was obtained from the Glooko-Diasend database, and used to quantify the frequency and magnitude of basal insulin daily dose adjustments within the 90-day window preceding HbA1c measurement.

Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder without effective neuroprotective therapy. Known genetic variants impair pathways, including RNA processing, axonal transport, and protein homeostasis. We report ALS-causing mutations within the gene encoding the glycosyltransferase GLT8D1.

A PET Imaging Strategy for Interrogating Target Engagement and Oncogene Status in Pancreatic Cancer.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, with a 5-year survival rate of less than 10%. Physicians often rely on biopsy or CT to guide treatment decisions, but these techniques fail to reliably measure the actions of therapeutic agents in PDAC. KRAS mutations are present in >90% of PDAC and are connected to many signaling pathways through its oncogenic cascade, including extracellular regulated kinase (ERK) and MYC.

Hay fever in a changing climate: linking an Internet-based diary with environmental data.

Investigating the impact of climate change on human health requires the development of efficient tools that link patient symptoms with changing environmental variables. We developed an internet-based hay fever diary linked to simultaneously recorded pollen load and weather variables in Canberra, Australia over spring 2010. We recruited 42 hay fever sufferers to complete a simple online pollen diary daily over a period of 60 days.

Abstraction and abstraction control in Scotland.

This paper explores the limited existing forms of control on abstractions in Scotland and considers the benefits and drawbacks of introducing a wider control mechanism. Institutional changes since 1996, which include the creation of the Scottish Environment Protection Agency (SEPA), the establishment of three Water Authorities and the transfer of devolved powers to the Scottish Parliament all impact on the issue of abstraction control. The implementation of various EU Directives in the same period has highlighted increased needs for abstraction control and the draft Water Framework Directive is expected to reinforce these.