TARGETING MULTI-DRUG RESISTANT PATHOGENS WITH NOVEL ANTIMICROBIAL PEPTIDES

The emergence of antibiotic resistance is a notorious problem worldwide. In the United States alone, antibiotic-resistant bacteria infect at least two million people and kill around 23,000 patients each year. Half of these infections are attributed to the bacterial pathogen, methicillin resistant Staphylococcus aureus (MRSA) according to a report published in 2013 by the Centers for Disease Control and Prevention (CDC). Similarly, S. pseudintermedius is a leading cause of opportunistic infections in pet animals and has zoonotic potential. Furthermore, the marked increase in the incidence of infections due to extensively drug-resistant and pandrug-resistant isolates of Pseudomonas aeruginosa and Acinetobacter baumannii presents an alarming challenge that necessitates the development of novel therapeutic alternatives to traditional antibiotics in order to address this scourge

Efficacy of Short Novel Antimicrobial and Anti-Inflammatory Peptides in a Mouse Model of Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection

The therapeutic efficacy of two novel short antimicrobial and anti-inflammatory peptides (RR and RRIKA) was evaluated in a mouse model of staphylococcal skin infection. RR (2%) and RRIKA (2%) significantly reduced the bacterial counts and the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, in methicillin-resistant Staphylococcus aureusUSA 300-0114 skin lesions. Furthermore, the combined therapy of RRIKA (1%) and lysostaphin (0.5%) had significantly higher antistaphylococcal and anti-inflammatory activity compared to monotherapy. This study supports the potential use of these peptides for topical treatment of methicillin-resistant Staphylococcus aureus skin infections

Conductivity and Dissociation in Metallic Hydrogen: Implications for Planetary Interiors

Liquid metallic hydrogen (LMH) was recently produced under static compression and high temperatures in bench-top experiments. Here, we report a study of the optical reflectance of LMH in the pressure region of 1.4-1.7 Mbar and use the Drude free-electron model to determine its optical conductivity. We find static electrical conductivity of metallic hydrogen to be 11,000-15,000 S/cm. A substantial dissociation fraction is required to best fit the energy dependence of the observed reflectance. LMH at our experimental conditions is largely atomic and degenerate, not primarily molecular. We determine a plasma frequency and the optical conductivity. Properties are used to analyze planetary structure of hydrogen rich planets such as Jupiter

Residual theory, partial adjustment, and information content on dividend payments decisions : an integration and extension / BEBR No. 760

Bibliography: p. 31-32

Antibacterial Activity of Novel Cationic Peptides against Clinical Isolates of Multi-Drug Resistant Staphylococcus pseudintermedius from Infected Dogs

Staphylococcus pseudintermedius is a major cause of skin and soft tissue infections in companion animals and has zoonotic potential. Additionally, methicillin-resistant S. pseudintermedius (MRSP) has emerged with resistance to virtually all classes of antimicrobials. Thus, novel treatment options with new modes of action are required. Here, we investigated the antimicrobial activity of six synthetic short peptides against clinical isolates of methicillin-susceptible and MRSP isolated from infected dogs. All six peptides demonstrated potent antistaphylococcal activity regardless of existing resistance phenotype. The most effective peptides were RRIKA (with modified C terminus to increase amphipathicity and hydrophobicity) and WR-12 (α-helical peptide consisting exclusively of arginine and tryptophan) with minimum inhibitory concentration50 (MIC50) of 1 µM and MIC90 of 2 µM. RR (short anti-inflammatory peptide) and IK8 ‘‘D isoform’’ demonstrated good antimicrobial activity with MIC50 of 4 µM and MIC90 of 8 µM. Penetratin and (KFF)3K (two cell penetrating peptides) were the least effective with MIC50 of 8 µM and MIC90 of 16 µM. Killing kinetics revealed a major advantage of peptides over conventional antibiotics, demonstrating potent bactericidal activity within minutes. Studies with propidium iodide and transmission electron microscopy revealed that peptides damaged the bacterial membrane leading to leakage of cytoplasmic contents and consequently, cell death. A potent synergistic increase in the antibacterial effect of the cell penetrating peptide (KFF)3K was noticed when combined with other peptides and with antibiotics. In addition, all peptides displayed synergistic interactions when combined together. Furthermore, peptides demonstrated good therapeutic indices with minimal toxicity toward mammaliancells. Resistance to peptides did not evolve after 10 passages of S. pseudintermedius at sub-inhibitory concentration. However, the MICs of amikacin and ciprofloxacin increased 32 and 8 fold, respectively; under similar conditions. Taken together, these results support designing of peptide-based therapeutics for combating MRSP infections, particularly for topical application

Limiting velocities as running parameters and superluminal neutrinos

In the context of theories where particles can have different limiting velocities, we review the running of particle speeds towards a common limiting velocity at low energy. Motivated by the recent OPERA experimental results, we describe a model where the neutrinos would deviate from the common velocity by more than do other particles in the theory, because their running is slower due to weaker interactions.Comment: 5 pages, 3 figure