An acceptability study of the introduction of total online or partial online PBL in a large classroom setting in biochemistry.

Background: Traditional problem-based learning (PBL) relying on tutored learning in small groups is very resource-intensive. Little is known about the benefits of PBL in a large classroom setting. This paper introduced a PBL case into the traditional didactic biochemistry course and investigated the acceptability of total online or partial online PBL in a large classroom setting introduced during the coronavirus pandemic.

The role of vitamin D through SphK1/S1P in the regulation of MS progression.

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear.

Meta-analyzing the efficacy of 3D printed models in anatomy education.

Three-dimensional printing models (3DPs) have been widely used in medical anatomy training. However, the 3DPs evaluation results differ depending on such factors as the training objects, experimental design, organ parts, and test content. Thus, this systematic evaluation was carried out to better understand the role of 3DPs in different populations and different experimental designs.

The benefits of using atypical presentations and rare diseases in problem-based learning in undergraduate medical education.

Background: The nature of student learning in problem-based learning (PBL) largely depends on the quality of the case scenarios presented to them. The effect of case scenarios with higher challenge degree, especially common disease with atypical symptoms (CDAS)- and rare disease (RD)-based case scenarios, on undergraduate medical students remains unclear. This study compared the impact of all scenarios pertaining to common disease with typical symptoms (CDTS) case scenarios, CDTS interspersed with CDAS case scenarios, and CDTS interspersed with RD case scenarios on perceptions of undergraduate students studying organ/system integration curriculum via PBL.

Crystal structure and catalytic activity of the PPM1K N94K mutant.

Protein Phosphatase Mg /Mn -Dependent 1K (PPM1K),also named as PP2Cm or branched-chain α-ketoacid dehydrogenase complex phosphatase, is a member of the metal-dependent phosphatase family and an important metabolic regulator. Single nucleotide polymorphisms (SNPs) in PPM1K contributing to protein functional defects have been found to be associated with numerous human diseases, such as cardiovascular disease, maple syrup urine disease, type 2 diabetes, and neurological disease. PPM1K N94K is an identified missense mutant produced by one of the SNPs in the human PPM1K coding sequence.

Computational Strategy for Bound State Structure Prediction in Structure-Based Virtual Screening: A Case Study of Protein Tyrosine Phosphatase Receptor Type O Inhibitors.

Accurate protein structure in the ligand-bound state is a prerequisite for successful structure-based virtual screening (SBVS). Therefore, applications of SBVS against targets for which only an apo structure is available may be severely limited. To address this constraint, we developed a computational strategy to explore the ligand-bound state of a target protein, by combined use of molecular dynamics simulation, MM/GBSA binding energy calculation, and fragment-centric topographical mapping.

Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation.

Slingshots are phosphatases that modulate cytoskeleton dynamics, and their activities are tightly regulated in different physiological contexts. Recently, abnormally elevated Slingshot activity has been implicated in many human diseases, such as cancer, Alzheimer's disease, and vascular diseases. Therefore, Slingshot-specific inhibitors have therapeutic potential.

Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation orchestrating 2 oncogenic pathways.

The protein tyrosine phosphatase nonreceptor type 12 (PTPN12) is a multifunctional protein and has elicited much research attention because its decreased protein level has been associated with poor prognosis of several types of cancers. Recently, we have solved the crystal structure of the phosphatase domain of PTPN12, which disclosed a specific PTPN12-insert-loop harboring a cyclin-dependent kinase 2 (CDK2) phosphorylation site. However, the functional significance of this phosphorylation is undefined.

Discovery of novel FFA4 (GPR120) receptor agonists with β-arrestin2-biased characteristics.

Background: Free fatty acid 4 (FFA4) (GPR120) receptor functions as a receptor for unsaturated long-chain free fatty acids by regulating the secretion of glucagon-like peptide-1 and suppressing the inflammatory process, in which these two distinct biological functions are modulated by two signaling pathways, Gq and β-arrestin2, respectively.

Results: By using pharmacophore modeling and virtual screening methods, several compounds are found with excellent activities for agonizing FFA4 receptor. It needs to be noted that among them, some molecules demonstrate appealing β-arrestin2-biased properties for the FFA4 receptor.

Identification of para-Substituted Benzoic Acid Derivatives as Potent Inhibitors of the Protein Phosphatase Slingshot.

Slingshot proteins form a small group of dual-specific phosphatases that modulate cytoskeleton dynamics through dephosphorylation of cofilin and Lim kinases (LIMK). Small chemical compounds with Slingshot-inhibiting activities have therapeutic potential against cancers or infectious diseases. However, only a few Slingshot inhibitors have been investigated and reported, and their cellular activities have not been examined.

The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes.