The conformational landscape of human transthyretin revealed by cryo-EM.

Transthyretin (TTR) is a natively tetrameric thyroxine transporter found in blood and cerebrospinal fluid whose misfolding and aggregation causes transthyretin amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndaqel/Vyndamax) as an effective stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency-approved for the treatment of TTR amyloidosis. Despite 50 years of structural studies on TTR and this triumph of structure-based drug design, there remains a notable dearth of structural information available to understand ligand binding allostery and amyloidogenic TTR unfolding intermediates.

Analysis of Erythrocyte Sedimentation Rate Order in Epithelial Ovarian Cancer.

Erythrocyte sedimentation rate order (ESRO), platelet-lymphocyte ratio (PLR), red cell distribution width (RDW), and neutrophil-lymphocyte ratio (NLR) are hematological parameters that reflect the presence of biomarkers in epithelial ovarian cancer (EOC). This study evaluated the best haematological parameter in order to distinguish between EOC patients and healthy individuals. There were a total of 33 patients with EOC as subjects treated in Dr.

Divergent Proteome Reactivity Influences Arm-Selective Activation of the Unfolded Protein Response by Pharmacological Endoplasmic Reticulum Proteostasis Regulators.

Pharmacological activation of the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR) has proven useful for ameliorating proteostasis deficiencies in cellular and mouse models of numerous etiologically diverse diseases. Previous high-throughput screening efforts identified the small molecule AA147 as a potent and selective ATF6 activating compound that operates through a mechanism involving metabolic activation of its 2-amino--cresol substructure affording a quinone methide, which then covalently modifies a subset of endoplasmic reticulum (ER) protein disulfide isomerases (PDIs). Another compound identified in this screen, AA132, also contains a 2-amino--cresol moiety; however, this compound showed less transcriptional selectivity, instead globally activating all three arms of the UPR.

The Association between Unhealthy Food Consumption and Impaired Glucose Metabolism among Adults with Overweight or Obesity: A Cross-Sectional Analysis of the Indonesian Population.

Background: It has been shown that dietary patterns are associated with glucose control. However, the association between the types of food consumed and blood glucose in overweight or obese individuals is still unclear. The present study aimed to determine the association between unhealthy food consumption and impaired glucose metabolism in adults with overweight or obesity.

Divergent Proteome Reactivity Influences Arm-Selective Activation of Pharmacological Endoplasmic Reticulum Proteostasis Regulators.

Pharmacological activation of the activating transcription factor 6 (ATF6) arm of the Unfolded Protein Response (UPR) has proven useful for ameliorating proteostasis deficiencies in a variety of etiologically diverse diseases. Previous high-throughput screening efforts identified the small molecule AA147 as a potent and selective ATF6 activating compound that operates through a mechanism involving metabolic activation of its 2-amino- -cresol substructure affording a quinone methide, which then covalently modifies a subset of ER protein disulfide isomerases (PDIs). Intriguingly, another compound identified in this screen, AA132, also contains a 2-amino- -cresol moiety; however, this compound showed less transcriptional selectivity, instead globally activating all three arms of the UPR.