Dynamic HPLC of stereolabile iron(II) complexes on chiral stationary phases

A series of chiral tris-(1,10)-phenanthroline iron(II) complexes have been resolved by HPLC on chiral stationary phases based on either cellulose tris-(3,5-dimethylphenylcarbamate) or teicoplanin. At sub ambient temperatures, baseline separation of the enantiomers was observed for five different iron(II) complexes featuring substituted phenanthroline ligands. Dynamic HPLC profiles were observed near or above room temperature, indicating on-column Delta/Lambda enantiomerization. Rate constants for the Delta/Lambda interconversion in free solution and during chromatography were obtained by thermal racemization experiments and by computer simulation of the HPLC dynamic plots, respectively.     

Neutral ceramidase deficiency protects against cisplatin-induced acute kidney injury

Cisplatin is a commonly used chemotherapeutic for the treatment of many solid organ cancers; however, its effectiveness is limited by the development of acute kidney injury (AKI) in 30% of patients. AKI is driven by proximal tubule cell death, leading to rapid decline in renal function. It has previously been shown that sphingolipid metabolism plays a role in regulating many of the biological processes involved in cisplatin-induced AKI. For example, neutral ceramidase (nCDase) is an enzyme responsible for converting ceramide into sphingosine, which is then phosphorylated to become sphingosine-1-phosphate, and our lab previously demonstrated that nCDase knockout (nCDase?/?) in mouse embryonic fibroblasts led to resistance to nutrient and energy deprivation–induced cell death via upregulation of autophagic flux. In this study, we further characterized the role of nCDase in AKI by demonstrating that nCDase?/? mice are resistant to cisplatin-induced AKI. nCDase?/? mice display improved kidney function, reduced injury and structural damage, lower rates of apoptosis, and less ER stress compared to wild-type mice following cisplatin treatment. Although the mechanism of protection is still unknown, we propose that it could be mediated by increased autophagy, as chloroquine treatment resensitized nCDase?/? mice to AKI development. Taken together, we conclude that nCDase may represent a novel target to prevent cisplatin-induced nephrotoxicity.     

Sodium-conducting channels in cardiac membranes in low calcium.

With no Ca in the patch electrode, two kinds of channels conduct Na in spontaneously beating embryonic chick heart cells. One channel conducts Na primarily during the upstroke of the action potential and is blocked by tetrodotoxin (TTX). The other channel conducts Na primarily during the late plateau and early repolarization phase of the action potential, but only in Ca concentrations below 10(-6) M. This second channel is TTX-insensitive and has a conductance of 50 to 90 pS, depending upon the interpretation of open-channel flickering. These two Na-conducting channels correspond to the channels that normally carry the fast Na current (INa) and the slow Ca current (Isi).     

Quantitative study of optical and mechanical bone status using multispectral photoacoustics

Osteoporosis is a major public health problem worldwide. Here, we present a quantitative multispectral photoacoustic method for the evaluation of bone pathologies which has significant advantages over pure ultrasonic or pure optical methods as it provides both molecular information and bone mechanical status. This is enabled via a simultaneous measurement of the bone's optical properties as well as the speed of sound and ultrasonic attenuation in the bone. To test the method's quantitative predictions, a combined ultrasonic and photoacoustic system was developed. Excitation was performed optically via a portable triple laser‐diode system and acoustically via a single element transducer. Additional dual transducers were used for detecting the acoustic waves that were generated by the two modalities. Both temporal and spectral parameters were compared between different excitation wavelengths and measurement modalities. Short photoacoustic excitation wavelengths allowed sensing of the cortical layer while longer wavelengths produced results which were compatible with the quantitative ultrasound measurements.

     

Genome of ‘Charleston Gray’, the principal American watermelon cultivar,and genetic characterization of 1,365 accessions in the U.S. National Plant Germplasm System watermelon collection

Years of selection for desirable fruit quality traits in dessert watermelon (Citrullus lanatus) has resulted in a narrow genetic base in modern cultivars. Development of novel genomic and genetic resources offers great potential to expand genetic diversity and improve important traits in watermelon. Here, we report a high‐quality genome sequence of watermelon cultivar ‘Charleston Gray’, a principal American dessert watermelon, to complement the existing reference genome from ‘97103’, an East Asian cultivar. Comparative analyses between genomes of ‘Charleston Gray’ and ‘97103’ revealed genomic variants that may underlie phenotypic differences between the two cultivars. We then genotyped 1365 watermelon plant introduction (PI) lines maintained at the U.S. National Plant Germplasm System using genotyping‐by‐sequencing (GBS). These PI lines were collected throughout the world and belong to three Citrullus species, C. lanatus, C. mucosospermus and C. amarus. Approximately 25 000 high‐quality single nucleotide polymorphisms (SNPs) were derived from the GBS data using the ‘Charleston Gray’ genome as the reference. Population genomic analyses using these SNPs discovered a close relationship between C. lanatus and C. mucosospermus and identified four major groups in these two species correlated to their geographic locations. Citrullus amarus was found to have a distinct genetic makeup compared to C. lanatus and C. mucosospermus. The SNPs also enabled identification of genomic regions associated with important fruit quality and disease resistance traits through genome‐wide association studies. The high‐quality ‘Charleston Gray’ genome and the genotyping data of this large collection of watermelon accessions provide valuable resources for facilitating watermelon research, breeding and improvement.     

Fragmentation of purified mammalian DNA molecules by ultrasound below human therapeutic doses.

Because of the increasing medical use of ultrasound, especially in obstetrical diagnosis, it has become important to check its genetic harmlessness. Purified calf thymus DNA in solution was exposed to both therapeutic and obstetrical diagnostic doses of ultrasound. Intensities lower than those used in therapy have a drastic effect on purified DNA in solution, although intensities used in obstetrical diagnosis caused no visible effect.     

Autoradiography of Tracks from Beta-Particle Emitters in Tissues

Mounted paraffin sections, 2-4μ thick, ˙were stained, dehydrated, allowed to air dry, and given a thin coating of 1 % Plexi-glas solution in chloroform. The chloroform was allowed to evaporate completely in a dry atmosphere. An emulsion whose dried thickness was 100-150μ, was prepared from Ilford G5 type in gel form and glued to the section by means of a 15% solution of shellac in absolute alcohol. The surface of the emulsion was then cleaned with absolute ethyl alcohol, to remove the impermeable shellac layer. The exposure for radiation reaction was made at about 2°C and required, in the conditions of our experiment, about 24 hrs. The emulsions were processed by the “temperature-development method.” With the described procedure, autoradiographs have been obtained of various organs of albino rats, labeled with P³², S³⁵ and other radioisotopes, and very precise localizations of the origin of electron tracks was attempted. This technic has allowed the fixing and staining of the tissues by means of all the reagents commonly employed in histology, without any damage to the emulsion and the obtaining of good adhesion and minimum separation between specimen and emulsion, thus permitting reliable extrapolations of electron tracks. Due to the fact that the emulsion is fully sensitized when placed in contact with the preparation the limits of the exposure times were well defined. The uniform development at all depths of the emulsion achieved by the temperature-development method facilitated the work with fast electron tracks.