Impact of climate change and anthropogenic activities on aquatic ecosystem - A review.

All living things depend on their natural environment, either directly or indirectly, for their high quality of life, growth, nutrition, and development. Due to the fast emissions of greenhouse gases (GHGs), the Earth's climate system is being negatively impacted by global warming. Stresses caused by climate change, such as rising and hotter seas, increased droughts and floods, and acrid waters, threaten the world's most populated areas and aquatic ecosystems. As a result, the aquatic ecosystems of the globe are quickly reaching hazardous conditions. Marine ecosystems are essential parts of the world's environment and provide several benefits to the human population, such as water for drinking and irrigation, leisure activities, and habitat for commercially significant fisheries. Although local human activities have influenced coastal zones for millennia, it is still unclear how these impacts and stresses from climate change may combine to endanger coastal ecosystems. Recent studies have shown that rising levels of greenhouse gases are causing ocean systems to experience conditions not seen in several million years, which may cause profound and irreversible ecological shifts. Ocean productivity has declined, food web dynamics have changed, habitat-forming species are less common, species ranges have changed, and disease prevalence has increased due to human climate change. We provide an outline of the interaction between global warming and the influence of humans along the coastline. This review aims to demonstrate the significance of long-term monitoring, the creation of ecological indicators, and the applications of understanding how aquatic biodiversity and ecosystem functioning respond to global warming. This review discusses the effects of current climate change on marine biological processes both now and in the future, describes present climate change concerning historical change, and considers the potential roles aquatic systems could play in mitigating the effects of global climate change.

New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines.

The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH(2). Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC(50) values range from 0.55 to 8.5 nM), with N'-(2-pyrimidyl)piperizine (IC(50) values range from 0.5 to 21.6 nM), with N-N'- L-piperazinocolinamide (IC(50) values range from 0.001 - 0.25 nM), or N-N'-L-piperazinocolin-N-methylamide (IC(50) values range from 0.015 - 7.3 nM).

Inhibition of a viral enzyme by a small-molecule dimer disruptor.

We identified small-molecule dimer disruptors that inhibit an essential dimeric protease of human Kaposi's sarcoma-associated herpesvirus (KSHV) by screening an alpha-helical mimetic library. Next, we synthesized a second generation of low-micromolar inhibitors with improved potency and solubility. Complementary methods including size exclusion chromatography and 1H-13C HSQC titration using selectively labeled 13C-Met samples revealed that monomeric protease is enriched in the presence of inhibitor. 1H-15N HSQC titration studies mapped the inhibitor binding site to the dimer interface, and mutagenesis studies targeting this region were consistent with a mechanism where inhibitor binding prevents dimerization through the conformational selection of a dynamic intermediate. These results validate the interface of herpesvirus proteases and other similar oligomeric interactions as suitable targets for the development of small-molecule inhibitors.