Antibiotic resistance has become one of the greatest challenges in treating bacterial infections in healthcare. Inspired by the structures of bacteriainvading viruses and antimicrobial peptides (AMPs), we hypothesize that in addition to a balance of amphiphilicity and electropositivity, nanostructure is another important structural determinant that defines how membraneactive antibiotics remodel host membranes to gain desirable activity and selectivity. Here we study the structure-activity relationship of a series of polymer molecular brushes (PMBs) with well-defined nanostructures that mimic spherical and rod-shaped viruses. Our preliminary data based on PMBs with hydrophilic polymer brushes reveal that: (1) amphiphilicity is not a required trait-hydrophilic PMBs can be designed to have potent antibiotic performance as well with negligible hemolytic activity; (2) the nanoscale architecture of PMBs defines their double selectivity, not molecular weight per se; (3) PMBs are far more powerful antibiotics than individual linear-chain polymers that make up the PMBs; and (4) nanostructured PMBs induce topological changes of membranes by forming membrane pores that unlikely fit in with any known models of AMP action. These findings expand existing wisdom on designing synthetic mimics of AMPs and suggest that the spatially-defined, multivalent interactions inherent to nanostructured PMBs is of great significance for the development of new membrane-active antibiotics.

Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disorder. It is also among the most lethal as life expectancy is between 2 and 5 years after diagnosis. Sporadic ALS (sALS) makes up 90% of all ALS cases with little known about the exact mechanism of pathogenesis. Many potential regulators of sALS development have been proposed, several of which are examined in this review with supporting evidence. Interplay among these factors is examined more closely in hopes of shedding more light on sALS pathophysiology. There is a paucity of effective treatment options as the only FDA-approved drug for use, riluzole, has a positive but modest benefit in improving survival. Other treatments available merely target ameliorating symptoms of ALS. Alternative treatment options are also discussed. This study ultimately aims to make relevant connections among factors implicated in sALS development and to highlight alternative forms of treatment in improving neuron function and status, albeit controversial.

Peptide Nucleic Acids, DNA mimics featuring a peptide-like backbone and nucleobases that bind nucleic acids, are capable of impacting gene expression, are resistant to degradation, and show promise as therapeutic agents. PNAs are