Inositol phosphates dynamically enhance stability, solubility and catalytic activity of mTOR.

Mechanistic Target of Rapamycin (mTOR) binds the small metabolite inositol hexakisphosphate (IP) as shown in structures of mTOR, however it remains unclear if IP, or any other inositol phosphate species, function as an integral structural element(s) or catalytic regulator(s) of mTOR. Here, we show that multiple, exogenously added inositol phosphate species can enhance the ability of mTOR and mTORC1 to phosphorylate itself and peptide substrates in in vitro kinase reactions, with the higher order phosphorylated species being more potent (IP=IP>IP>>IP). IP increased the V and decreased the apparent K of mTOR for ATP.

Rates and Risk Factors for Quadriceps and Patellar Tendon Repair Failure: A Single Institution Case Series.

Quadriceps and patellar tendon ruptures are rare but serious injuries that can severely disrupt function and quality of life. The aim of this study was to evaluate the rates and risk factors for failed quadriceps and patellar tendon repairs. A retrospective review of 78 patients undergoing surgical repair for quadriceps or patellar tendon rupture from March 2014 to December 2020 was performed.

The novel estrogen receptor beta agonist EGX358 and genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer's mouse model.

Introduction: Alzheimer's disease (AD) prevalence and severity are associated with increased age, female sex, and apolipoprotein E4 (APOE4) genotype. Although estrogen therapy (ET) effectively reduces symptoms of menopause including hot flashes and anxiety, and can reduce dementia risk, it is associated with increased risks of breast and uterine cancer due to estrogen receptor alpha (ERα)-mediated increases in cancer cell proliferation. Because ERβ activation reduces this cell proliferation, selective targeting of ERβ may provide a safer method of improving memory and reducing hot flashes in menopausal women, including those with AD.

A Novel Machine Learning Model to Predict Revision ACL Reconstruction Failure in the MARS Cohort.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights.

Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure.

Study Design: Cohort study; Level of evidence, 3.