Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide.

Peptide hormones, a class of pharmacologically active molecules, have a critical role in regulating energy homeostasis. Prohormone convertase 1/3 (also known as PCSK1/3) represents a key enzymatic mechanism in peptide processing, as exemplified with the therapeutic target glucagon-like peptide 1 (GLP-1). However, the full spectrum of peptides generated by PCSK1 and their functional roles remain largely unknown.

High-throughput development and characterization of new functional nanobodies for gene regulation and epigenetic control in human cells.

Controlling gene expression and chromatin state via the recruitment of transcriptional effector proteins to specific genetic loci has advanced the potential of mammalian synthetic biology, but is still hindered by the challenge of delivering large chromatin regulators. Here, we develop a new method for generating small nanobodies against human chromatin regulators that can repress or activate gene expression. We start with a large and diverse nanobody library and perform enrichment against chromatin regulatory complexes using yeast display, followed by high-throughput pooled selection for transcriptional control when recruited to a reporter in human cells.

Inflationary Rebates For Generic Drugs Sold Through Medicaid Saved Billions During 2017-20.

State Medicaid programs cover nearly all Food and Drug Administration-approved prescription drugs in exchange for mandatory manufacturer rebates, including rebates that offset price increases beyond inflation. These inflationary rebates originally applied to brand-name drugs only, but in 2017 Congress expanded them to include generics. Using public Medicaid medication spending and utilization data and three different measures of drug prices, we found that nearly half of generic drugs were subject to inflationary rebates during the period 2017-20, offsetting 2-12 percent of the $53.

Frequency Of Generic Drug Price Spikes And Impact On Medicaid Spending.

Although generic drugs are typically inexpensive, rising prices among some generic drugs in recent years have raised concern. Using Medicaid data, we found that one in five generic drugs sold in the US experienced a price spike (defined as a doubling in price over the course of one year) initiated by at least one manufacturer during the period 2014-17. There was a trend toward fewer price spikes each year, from 7.

A Study of Gene Expression Changes in Human Spinal and Oculomotor Neurons; Identifying Potential Links to Sporadic ALS.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes compromised function of motor neurons and neuronal death. However, oculomotor neurons are largely spared from disease symptoms. The underlying causes for sporadic ALS as well as for the resistance of oculomotor neurons to disease symptoms remain poorly understood.