Neurons encode information by rapidly modifying synaptic protein complexes, which changes the strength of specific synaptic connections. Homer1 is abundantly expressed at glutamatergic synapses, and is known to alter its binding to metabotropic glutamate receptor 5 (mGlu5) in response to synaptic activity. However, Homer participates in many additional known interactions whose activity-dependence is unclear. Here, we used co-immunoprecipitation and label-free quantitative mass spectrometry to characterize activity-dependent interactions in the cerebral cortex of wildtype and Homer1 knockout mice. We identified a small, high-confidence protein network consisting of mGlu5, Shank2 and 3, and Homer1–3, of which only mGlu5 and Shank3 were significantly reduced following neuronal depolarization. We identified several other proteins that reduced their co-association in an activity-dependent manner, likely mediated by Shank proteins. We conclude that Homer1 dissociates from mGlu5 and Shank3 following depolarization, but our data suggest that direct Homer1 interactions in the cortex may be more limited than expected.
Background
Germline mutation of CDH1 is rare and leads to hereditary diffuse gastric cancer (DGC).
Methods
Patients (pts) with CDH1 mutation who underwent multidisciplinary counseling followed by open prophylactic total gastrectomy (PTG) by a single surgeon were reviewed.
Results
Fifty‐four pts with a median age of 41 years (16–70 years) underwent PTG between 2006 and 2021. Median operative time was 161 min, and median hospital stay was 7 days (range 6–12). There were 5 complications (9.2%) within 30 days, and two complications (pulmonary embolism and pancreatitis) required readmission. There were no anastomotic leaks. The pathologic analysis of the first 10 pts included the entire gastric mucosa, revealing a median of 15 foci of DGC (range 5–136). The subsequent 44 pts with more limited analysis had a median of 2 foci (range 0–5), and two pts (3.7%) had no foci identified. Median maximum weight loss was 19%. In long‐term follow‐up (median 4.6 years) of 20 pts, median global QOL was 2.0 (very good), the majority had persistent difficulty with certain foods or liquids, and all stated they would again elect PTG over surveillance endoscopy.
Conclusions
PTG can be performed safely at high‐volume referral centers with very good QOL but nutritional sequelae persist.
Randomized trials in the East have established minimally invasive gastrectomy as possibly superior for short-term outcomes and noninferior for long-term survival. Smaller randomized studies from Western countries have supported these findings. However, there are marked disparities in morbidity, mortality, and overall survival noted between Eastern and Western studies. In this article, we review the literature comparing open and minimally invasive gastrectomy in the East and West, and describe the possible reasons for differences in outcomes.
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