Prolonged High Fat Diet Worsens the Cellular Response to a Small, Covert-like Ischemic Stroke.

Obesity is associated with worse neurological outcomes following overt ischemic strokes. The majority of strokes however, are covert, small strokes that often evade detection. How obesity impacts the cellular response to covert strokes is unclear.

Dopamine modulates excitatory transmission to orexin neurons in a receptor subtype-specific manner.

Dopamine (DA) can promote or inhibit consummatory and reward-related behaviors by activating different receptor subtypes in the lateral hypothalamus and perifornical area (LH/PF). Because orexin neurons are involved in reward and localized in the LH/PF, DA may modulate these neurons to influence reward-related behaviors. To determine the cellular mechanism underlying dopaminergic modulation of orexin neurons, the effect of DA on excitatory transmission to these neurons was investigated using in vitro electrophysiology on rat brain slices.

Simultaneous Ridge Augmentation and Accelerated Molar Uprighting for Implant Site Development: Two Case Reports with a Split-Mouth Design.

Well-coordinated interdisciplinary dental treatments provide the best esthetic, functional, and long-term results for patients. However, the length of such treatment, which may involve orthodontics, ridge augmentation, and dental implants, often deters patients from pursuing them. The two case reports presented here aim to present the advantage of simultaneous orthodontic molar uprighting and ridge augmentation procedures for future implant site development.

Symptom word documentation: A novel approach to identifying and managing hospital-acquired infections.

An interprofessional team developed a symptom word documentation tool based on surveillance definitions for specific types of infections published by the Centers for Disease Control and Prevention. Nursing documentation was monitored pre- and postimplementation of the tool, revealing increased compliance with symptom documentation. Although symptom word documentation does not reduce the number of infections, it may impact the central line-associated bloodstream infection (CLABSI) rate by better differentiating CLABSI from other infection sources, as was observed in this institution.

High-Throughput Mass Spectrometric Analysis of Covalent Protein-Inhibitor Adducts for the Discovery of Irreversible Inhibitors: A Complete Workflow.

We have implemented a solid-phase extraction based time-of-flight mass spectrometer system in combination with novel informatics to rapidly screen and characterize the covalent binding of different irreversible inhibitors to intact proteins. This high-throughput screening platform can be used to accurately detect and quantitate the extent of formation of different covalent protein-inhibitor adducts between electrophilic inhibitors and nucleophilic residues such as cysteine or lysine. For a representative 19.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood.

Inhibitors of the lipid phosphatase SHIP2 discovered by high-throughput affinity selection-mass spectrometry screening of combinatorial libraries.

This manuscript describes the discovery and characterization of inhibitors of the lipid phosphatase SHIP2, an important target for the treatment of Type 2 diabetes, using the Automated Ligand Identification System. ALIS is an affinity selection-mass spectrometry platform for label-free, high throughput screening of mixture-based combinatorial libraries. We detail the mass-encoded synthesis of a library that yielded NGD-61338, a pyrazole-based SHIP2 inhibitor.

A high-throughput microfluidic assay for SH2 domain-containing inositol 5-phosphatase 2.

SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) is a potential drug target for the treatment of type 2 diabetes. This enzyme serves as a negative regulator of insulin-mediated signal transduction by catalyzing the dephosphorylation of the second messenger lipid molecule phosphatidylinositol 3,4,5-triphosphate. Traditionally, assays for phosphoinositide phosphatases such as SHIP2 have relied on radiolabeled phosphatidylinositol-containing lipid membranes and chromatographic separation of labeled phospholipid substrate from product by thin-layer chromatography.