Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram‐Negative Bacteria

Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram‐negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU‐N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer‐membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de‐energization of the efflux pump rather than by direct interaction of the molecule with the pump. This suggests that depowering the efflux pump provides another strategy to address antibiotic resistance.     

Prototype e-cigarette and the capillary aerosol generator (CAG) comparison and qualification for use in subchronic inhalation exposure testing

Our objective was to evaluate the suitability of using a capillary aerosol generator (CAG) instead of using e-cigarette devices in 90-day or longer inhalation studies. Aerosol characteristics for both the CAG (which uses heat to produce a condensation aerosol) and e-cigarette generators have been previously reported, but a side-by-side comparison with the identical formulation has not been reported. Aerosols from both devices were analyzed immediately after generation for chemicals in the formulation (propylene glycol [PG], glycerin, water, and nicotine), selected carbonyls (acetaldehyde, acrolein, and formaldehyde) by ultra-performance liquid chromatography with ultraviolet detection (UPLC-UV), and a chemical fingerprint analysis using gas chromatography-mass spectroscopy (GC-MS). Aerosol capture methods for chemical analysis included Cambridge filter pads or two impingers in series each containing solution to trap and stabilize selected carbonyl compounds. Particle size distribution (cascade impactor) and exposure port uniformity (gravimetric) was measured in four rodent inhalation exposure chambers under inhalation study conditions. The aerosol of both generators contained the same known and unknown chemicals. Similar levels of compounds in the formula except for PG were detected in the aerosol of both generators. CAG produced more consistent particulate aerosol than e-cigarette generator and had lower levels of carbonyls primarily due to lower levels of formaldehyde. Exposure port concentrations were consistent and closer to target values with the CAG compared to the e-cigarette aerosol generator. CAG was easier to operate on a daily basis although more difficult to maintain because it required daily cleaning compared to single-use e-cigarettes. CAG was determined to be suitable for use in 90-day or longer inhalation studies.

Copyright © 2016 American Association for Aerosol Research     

Structure and Properties of Nanocomposites Formed by the Occlusion of Block Copolymer Worms and Vesicles Within Calcite Crystals

This article describes an experimentally versatile strategy for producing inorganic/organic nanocomposites, with control over the microstructure at the nano‐ and mesoscales. Taking inspiration from biominerals, CaCO₃ is coprecipitated with anionic diblock copolymer worms or vesicles to produce single crystals of calcite occluding a high density of the organic component. This approach can also be extended to generate complex structures in which the crystals are internally patterned with nano‐objects of differing morphologies. Extensive characterization of the nanocomposite crystals using high resolution synchrotron powder X‐ray diffraction and vibrational spectroscopy demonstrates how the occlusions affect the short and long‐range order of the crystal lattice. By comparison with nanocomposite crystals containing latex particles and copolymer micelles, it is shown that the effect of these occlusions on the crystal lattice is dominated by the interface between the inorganic crystal and the organic nano‐objects, rather than the occlusion size. This is supported by in situ atomic force microscopy studies of worm occlusion in calcite, which reveal flattening of the copolymer worms on the crystal surface, followed by burial and void formation. Finally, the mechanical properties of the nanocomposite crystals are determined using nanoindentation techniques, which reveal that they have hardnesses approaching those of biogenic calcites.     

Electronic transmittance phase extracted from mesoscopic interferometers

The usual experimental set-up for measuring the wave function phase shift of electrons tunneling through a quantum dot (QD) embedded in a ring (i.e., the transmittance phase) is the so-called ‘open’ interferometer as first proposed by Schuster et al. in 1997, in which the electrons back-scattered at source and the drain contacts are absorbed by additional leads in order to exclude multiple interference. While in this case one can conveniently use a simple two-path interference formula to extract the QD transmittance phase, the open interferometer has also a number of draw-backs, such as a reduced signal and some uncertainty regarding the effects of the extra leads. Here we present a meaningful theoretical study of the QD transmittance phase in ‘closed’ interferometers (i.e., connected only to source and drain leads). By putting together data from existing literature and giving some new proofs, we show both analytically and by numerical simulations that the existence of phase lapses between consecutive resonances of the ‘bare’ QD is related to the signs of the corresponding Fano parameters - of the QD + ring system. More precisely, if the Fano parameters have the same sign, the transmittance phase of the QD exhibits a Π lapse. Therefore, closed mesoscopic interferometers can be used to address the ‘universal phase lapse’ problem. Moreover, the data from already existing Fano interference experiments from Kobayashi et al. in 2003 can be used to infer the phase lapses.     

Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.     

Dry-Aging Effects on Palatability of Beef Longissimus Muscle

ABSTRACT: Beef strip loins and short loins were vacuum aged for 7 or 14 d, then these cuts were dry aged for 7, 14, or 21 d. At 2, 9, and 16 d of post-dry-aging vacuum storage, strip steaks were analyzed for sensory, physical, and microbial differences. Controls were vacuum aged for 14 d. Dry aging for 14 and 21 d produced steaks with greater (P < 0.05) dry-aged flavor, tenderness, and juiciness than controls or steaks dry aged for 7 d. Shear forces were lower (P < 0.05) for steaks dry aged for 21 d. Time of vacuum storage before and after dry aging had minimal effects on development of dry-aged flavor attributes.     

Transportation of cytotoxic liposomes to malignant cells using a carbohydrate determinant

A method of the synthesis of lipophilic glycoconjugates (vectors) on the basis of polyethyleneglycol-containing detergent was proposed. It has been shown by flow cytofluorometry that fluorescent labeled liposomes equipped with beta-galactosyl conjugate are bound human leukosis HL-60 cells more effectively than liposomes embedded with the beta-glucosyl conjugate or vector-free liposomes. A new lipid derivative of antitumor drug rubomycin (daunorubicin), N-(rac-1,2-dioleoylglycero-3-oxalyl)rubomycin (RubDG) has been synthesized. Liposomes loaded with RubDG and equipped with galactosyl vector showed higher cytotoxic activity in vitro against HL-60 cells than analogous unvectored liposomes or liposomes bearing glucosyl conjugate.     

Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining

To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.