Enhancing the Drug-Like Profile of a Potent Peptide PACE4 Inhibitor by the Formation of a Host-Guest Inclusion Complex with β-Cyclodextrin.

The enzyme PACE4 has been validated as a promising therapeutic target to expand the range of prostate cancer (PCa) treatments. In recent years, we have developed a potent peptidomimetic inhibitor, namely, compound C23 (Ac-(DLeu)LLLRVK-4-amidinobenzylamide). Like many peptides, C23 suffers from an unfavorable drug-like profile which, despite our efforts, has not yet benefited from the usual SAR studies.

Efficacy of PACE4 pharmacotherapy in JHU-LNCaP-SM preclinical model of androgen independent prostate cancer.

Prostate cancer (PCa) is a complex disease progressing from in situ to invasive or metastatic tumors while also being capable of modulating its androgen dependence. Understanding how novel therapies are working across the different stages of the disease is critical for their proper positioning in the spectrum of PCa treatments. The targeting of proprotein convertase PACE4 (Paired basic Amino Acid-Cleaving Enzyme 4) has been proposed as a novel approach to treat PCa.

Climate impact from agricultural management practices in the Canadian Prairies: Carbon equivalence due to albedo change.

It is generally accepted that land use and land management practices impact climate change through sequestration of carbon in soils, but modulation of surface energy budget can also be important. Using Landsat data to characterize cropland albedos in Canada's three prairie soil zones, this study estimates the atmospheric carbon equivalent drawdown of albedo radiative forcing for three management practices: 1) moving from conventional tillage to no-till, 2) eliminating summer fallow in crop rotations, and 3) growing crops with higher albedos. In a 50-year time horizon, conversion from conventional tillage to no-till results in a total equivalent atmospheric CO (CO-eq) drawdown of 1.

Natural climate solutions for Canada.

Alongside the steep reductions needed in fossil fuel emissions, natural climate solutions (NCS) represent readily deployable options that can contribute to Canada's goals for emission reductions. We estimate the mitigation potential of 24 NCS related to the protection, management, and restoration of natural systems that can also deliver numerous co-benefits, such as enhanced soil productivity, clean air and water, and biodiversity conservation. NCS can provide up to 78.

An indicator of freeze-kill damages to fruit trees during flowering.

This paper demonstrates the use of climatological data and published information to develop a thaw-freeze/freeze-kill indicator for fruit trees during flowering. In fruit-producing regions, when budding and flowering occur before the last spring freeze, a freeze-kill event can cause substantial losses. As spring onset is occurring earlier with climate change, thaw-freeze events have the potential to become more of a hazard both in terms of current production and in terms of potential adaptation strategies.