Project description:Inclisiran (Leqvio®; Novartis) is a first-in-class, cholesterol-lowering small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine carbohydrates (GalNAc). Inclisiran received its first approval in December 2020 in the EU for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is intended for use in combination with a statin or a statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol goals with the maximum tolerated statin dose. In patients who are statin-intolerant or for whom a statin is contraindicated, inclisiran can be used alone or in combination with other lipid-lowering therapies. Inclisiran is administered as a twice-yearly subcutaneous injection. This article summarizes the milestones in the development of inclisiran leading to this first approval for primary hypercholesterolaemia or mixed dyslipidaemia.
Project description:In over 100 neuroscience genetics reports on SLC6A4 published in the first part of 2012, >40% reported data from genotyping only the serotonin transporter-linked promoter region [5HTTLPR] indel, omitting genotyping of two nearby SNPs that substantially alter 5HTTLPR allele frequencies and functionality. And 25% of these papers did not report ethnicity of the subjects genotyped, another factor that alters allele frequencies. This field thus seems stultified. Improved science for the present and future will be better served by attention to more complete methods for genotyping and subject sample reporting.
Project description:Although calcareous anatomical structures have evolved in diverse animal groups, such structures have been unknown in insects. Here, we report the discovery of high-magnesium calcite [CaMg(CO3)2] armor overlaying the exoskeletons of major workers of the leaf-cutter ant Acromyrmex echinatior. Live-rearing and in vitro synthesis experiments indicate that the biomineral layer accumulates rapidly as ant workers mature, that the layer is continuously distributed, covering nearly the entire integument, and that the ant epicuticle catalyzes biomineral nucleation and growth. In situ nanoindentation demonstrates that the biomineral layer significantly hardens the exoskeleton. Increased survival of ant workers with biomineralized exoskeletons during aggressive encounters with other ants and reduced infection by entomopathogenic fungi demonstrate the protective role of the biomineral layer. The discovery of biogenic high-magnesium calcite in the relatively well-studied leaf-cutting ants suggests that calcareous biominerals enriched in magnesium may be more common in metazoans than previously recognized.
Project description:The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing the membrane stiffness and lowering the lipid fluidity. The nanoshell also serves as armor to protect cells and improve their viability against mechanical stress from osmotic imbalance, centrifugal forces, and fluid shear stress. Moreover, it enables mediated cell-cell interactions for effective and robust multicellular assembly. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy but also as a platform for cell and cell membrane manipulation.