Rolling circle amplification-templated DNA nanotubes show increased stability and cell penetration ability

DNA nanotubes hold promise as scaffolds for protein organization, as templates of nanowires and photonic systems, and as drug delivery vehicles. We present a new DNA-economic strategy for the construction of DNA nanotubes with a backbone produced by rolling circle amplification (RCA), which results in increased stability and templated length. These nanotubes are more resistant to nuclease degradation, capable of entering human cervical cancer (HeLa) cells with significantly increased uptake over double-stranded DNA, and are amenable to encapsulation and release behavior. As such, they represent a potentially unique platform for the development of cell probes, drug delivery, and imaging tools.     

Optimal photosensitizers for photodynamic therapy of infections should kill bacteria but spare neutrophils

Photodynamic therapy (PDT) for localized microbial infections exerts its therapeutic effect both by direct bacterial killing and also by the bactericidal effects of host neutrophils stimulated by PDT. Therefore, PDT-induced damage to neutrophils must be minimized, while direct photoinactivation of bacteria is maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo. However, there has been no study in which the cytocidal effect of PDT on neutrophils was investigated. In this study, the cytocidal effects of PDT on neutrophils were evaluated using different antimicrobial photosensitizers to find suitable candidate photosensitizers for antimicrobial PDT. PDT on murine peripheral-blood neutrophils was performed in vitro using each photosensitizer at a concentration that exerted a maximum bactericidal effect on methicillin-resistant Staphylococcus aureus, and morphological alteration and viability of neutrophils were studied. Most neutrophils were viable (>80%) after PDT using toluidine blue-O (TB) or methylene blue (MB), while neutrophils showed morphological change and their viabilities were decreased (<70%) after PDT using other photosensitizers (erythrosine B, rose bengal, crystal violet, Photofrin, new methylene blue and Laserphyrin). These results suggest that PDT using TB or MB can preserve host neutrophils while exerting a significant therapeutic effect on in vivo localized microbial infection.     

Synthesis and characterization of positively charged pentacationic [60]fullerene monoadducts for antimicrobial photodynamic inactivation

We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C??(>ME?N??C?) (1) and C??(>ME?N??C?) (2), with variation of the methoxyethyleneglycol length. Each of these derivatives bears a well-defined number of cationic charges aimed to enhance and control their ability to target pathogenic Gram-positive and Gram-negative bacterial cells for allowing photodynamic inactivation. The synthesis was achieved by the use of a common synthon of pentacationic N,N′,N,N,N,N-hexapropylhexa(aminoethyl)amine arm (C?N??) having six attached propyl groups, instead of methyl or ethyl groups, to provide a well-balanced hydrophobicity-hydrophilicity character to pentacationic precursor intermediates and better compatibility with the highly hydrophobic C?? cage moiety. We demonstrated two plausible synthetic routes for the preparation of 1 and 2 with the product characterization via various spectroscopic methods.     

Linezolid and Vancomycin Decrease the Therapeutic Effect of Methylene Blue‐Photodynamic therapy in a Mouse Model of MRSA Bacterial Arthritis

We previously reported that photodynamic therapy (PDT) using intra‐articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin‐resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB‐PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real‐time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P < 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.     

Interfacing supramolecular and macromolecular chemistry: metallo-supramolecular triple-helicates incorporated into polymer networks

Metallo-supramolecular diiron(II) triple-helical cores based on pyridylimine ligands and decorated with acrylate or methacrylate units are copolymerised with methyl methacrylate (MMA) as major comonomer using AIBN.     

Low‐level Laser (Light) Therapy Increases Mitochondrial Membrane Potential and ATP Synthesis in C2C12 Myotubes with a Peak Response at 3–6 h

Low‐level laser (light) therapy has been used before exercise to increase muscle performance in both experimental animals and in humans. However, uncertainty exists concerning the optimum time to apply the light before exercise. The mechanism of action is thought to be stimulation of mitochondrial respiration in muscles, and to increase adenosine triphosphate (ATP) needed to perform exercise. The goal of this study was to investigate the time course of the increases in mitochondrial membrane potential (MMP) and ATP in myotubes formed from C2C12 mouse muscle cells and exposed to light‐emitting diode therapy (LEDT). LEDT employed a cluster of LEDs with 20 red (630 ± 10 nm, 25 mW) and 20 near‐infrared (850 ± 10 nm, 50 mW) delivering 28 mW cm² for 90 s (2.5 J cm²) with analysis at 5 min, 3 h, 6 h and 24 h post‐LEDT. LEDT‐6 h had the highest MMP, followed by LEDT‐3 h, LEDT‐24 h, LEDT‐5 min and Control with significant differences. The same order (6 h > 3 h > 24 h > 5 min > Control) was found for ATP with significant differences. A good correlation was found (r = 0.89) between MMP and ATP. These data suggest an optimum time window of 3–6 h for LEDT stimulate muscle cells.     

Solvable Groups Satisfying the Two-prime Hypothesis,Part I

In this paper, finite solvable groups satisfying the “-prime hypothesis” are considered. Specifically, a bound on the number of irreducible character degrees of such a group is obtained when . The general situation is also considered, and generalizations of the -prime hypothesis are analyzed. Presented by A. Verschoren.     

Three-dimensional organization of block copolymers on "DNA-minimal" scaffolds

Here, we introduce a 3D-DNA construction method that assembles a minimum number of DNA strands in quantitative yield, to give a scaffold with a large number of single-stranded arms. This DNA frame is used as a core structure to organize other functional materials in 3D as the shell. We use the ring-opening metathesis polymerization (ROMP) to generate block copolymers that are covalently attached to DNA strands. Site-specific hybridization of these DNA-polymer chains on the single-stranded arms of the 3D-DNA scaffold gives efficient access to DNA-block copolymer cages. These biohybrid cages possess polymer chains that are programmably positioned in three dimensions on a DNA core and display increased nuclease resistance as compared to unfunctionalized DNA cages.     

Science in Isolation: American Marine Geophysics Research, 1950–1968

The emergence of plate tectonics theory during the 1960s stemmed from large-scale efforts to investigate the sea floor and to interpret results in terms of a horizontally mobile crust. Many scientists, particularly those within the Soviet bloc, refused to accept the new ideas about the earth. Most authors fault the conservative Soviet scientific leadership for halting the progress of geophysics in the East. By contrast, this article examines facets of the Western scientific community that begin to explain both the exclusion of Soviet scientists from participating in the “plate tectonics revolution” and also the meteoric success of the theory in the West.