Experimental Ca I oscillator strengths for the 4p-5s triplet

Context. Transition lines of neutral calcium are observed in the spectra of stellar and substellar objects. In particular, the abundance of α-elements in metal-poor stars can place important constraints on the galactic chemical evolution. Such stellar abundance analyses rely heavily on accurate values for the oscillator strength of the observable transitions. Theoretical oscillator strengths are available for most neutral calcium lines visible in stellar spectra, but there are a limited number of experimental values in the literature. Aims. We present new and improved experimental oscillator strengths for the optical Ca 

Behavioral profiles of adolescent alcohol-preferring/non-preferring (P/NP) and high/low alcohol-drinking (HAD/LAD) rats are dependent on line but not sex

Initial contact with alcohol generally occurs during adolescence, and high consumption during this period is associated with increased risk for later alcohol (AUDs) and/or substance use disorders (SUDs). Rodents selectively bred for high or low alcohol consumption are used to identify behavioral characteristics associated with a propensity for high or low voluntary alcohol intake. The multivariate concentric square field (TM) (MCSF) is a behavioral test developed to study rodents in a semi-naturalistic setting. Testing in the MCSF creates a comprehensive behavioral profile in a single trial. The current aim was to examine the behavioral profiles of adolescent, bidirectionally selectively bred male and female high alcohol-consuming (P and HAD1/2) and low alcohol-consuming (NP and LAD1/2) rat lines, and outbred Wistar rats. Alcohol-naive rats were tested once in the MCSF at an age between postnatal days 30 and 35. No common behavioral profile was found for either high or low alcohol-consuming rat lines, and the effect of sex was small. The P/NP and HAD2/LAD2 lines showed within pair-dependent differences, while the HAD1/LAD1 lines were highly similar. The P rats displayed high activity and risk-associated behaviors, whereas HAD2 rats displayed low activity, high shelter-seeking behavior, and open area avoidance. The results from P rats parallel clinical findings that denser family history and risk-taking behavior are strong predictors of future AUDs, often with early onset. Contrarily, the HAD2 behavioral profile was similar to individuals experiencing negative emotionality, which also is associated with a vulnerability to develop, often with a later onset, AUDs and/or SUDs

Electrotransfer of IL-15/IL-15Rα Complex for the Treatment of Established Melanoma

Gene electrotransfer (GET) is a safe, reliable, and effective method of delivering plasmid DNA (pDNA) to solid tumors. GET has been previously used to deliver interleukin-15 (IL-15) to mouse melanoma, resulting in long-term tumor regression and the survival of a percentage of treated animals after challenge. To enhance this effect, we evaluated modulating the expression levels of IL-15 and co-expressing its receptor, IL-15Rα. GET was used to deliver plasmids encoding IL-15 and IL-15Rα to established B16.F10 tumors on days 0, 4, and 7. Two delivery protocols that yielded different expression profiles were utilized. Mice that were tumor-free for 50 days were then challenged with B16.F10 cells on the opposite flank and monitored for an additional 50 days. The amount of IL-15 expressed and the presence or absence of IL-15Rα in the treated tumors did not significantly affect the tumor regression and long-term survival. Upon challenge, however, low levels of IL-15 were more protective and resulted in a greater production of anti-tumor cytokines such as IFN-γ and MIP-1β and a greater amount of CD11b+ and CD3e+ cells infiltrating tumors. While mice with high levels of IL-15 showed CD11b+ and CD3e+ cell infiltrate, there was a substantial presence of NK cells that was absent in other treated groups. We can conclude that the level of IL-15 expressed in tumors after GET is an important determinant of the therapeutic outcome, a finding that will help us finetune this type of therapy

Is sunlight good for our heart?

Humans evolved being exposed for about half of the day to the light of the sun. Nowadays, exposure to sunlight is actively discouraged for fear of skin cancer, and contemporary lifestyles are associated with long hours spent under artificial light indoors. Besides an increasing appreciation for the adverse effects of these life-style-related behavioural changes on our chronobiology, the balance between the beneficial and harmful effects of sunlight on human health is the subject of considerable debate, in both the scientific and popular press, and the latter is of major public health significance. While there is incontrovertible evidence that ultraviolet radiation (UVR) in the form of sunlight is a significant predisposing factor for non-melanoma and melanoma skin cancers in pale skinned people,1 a growing body of data suggest general health benefits brought about by sunlight.2 These are believed to be mediated either by melatonin or vitamin D. Melatonin is produced from serotonin by the pineal gland located in the centre of the brain during periods of darkness, and its release is suppressed as a function of the visible light intensity sensed through ocular photoreceptors. Vitamin D is formed by ultraviolet B (UVB)-mediated photolysis of 7-dehydrocholesterol in the skin. Both melatonin and vitamin D are pleiotropic hormones that exert a multitude of cellular effects by interacting with membrane and nuclear receptors, and receptor-independent actions. People with more heavily pigmented skin require higher doses of UVB to produce adequate amounts of vitamin D, and this may have been an evolutionary driver to the variation of human skin colour with latitude and intensity of solar irradiation. Our degree of exposure to sunlight is easily modified by behavioural factors such as the use of clothing, sunglasses, and sun-blocking creams, and time spent outdoors. Balancing the carcinogenic risks with the requirement for vitamin D has led to advice on moderating sun exposure, while supplementing food with vitamin D. Guidance on such behaviour is part of the public health campaigns in most countries with Caucasian populations. Following these suggestions, we may, however, be missing out on other health benefits provided by natural sunlight that are less obvious and unrelated to the above classical mediators

IL-12 Gene Electrotransfer Triggers a Change in Immune Response Within Mouse Tumors

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell composition after intratumoral injection of pIL-12 GET. The number of immune memory cells was markedly increased in pIL-12 GET melanoma groups compared to control group. This was validated using flow cytometry to analyze peripheral blood mononuclear cells as well as delineating immune cell content using immunohistochemistry. Significant differences in multiple cell types were observed, including CD8+ T cells, regulatory T cells and myeloid cells, which were induced to mount a CD8+PD1− T cells immune response. Taken together, these findings suggest a basic understanding of the sequence of immune activity following pIL-12 GET and also illuminates that adjuvant immunotherapy can have a positive influence on the host immune response to cancer

Electro-Gene Transfer to Skin Using a Noninvasive Multielectrode Array

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications

Electroporation-Mediated Gene Transfer Directly to the Swine Heart

In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on the anterior wall of the left ventricle were treated. Animals were killed 48 h after injection and electroporation and gene expression was determined. Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated. Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach. Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis in a Porcine Model of Cardiac Ischemia

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. Arteriograms suggest growth of new arteries as early as 2 weeks after treatment in electrotransfer animals. There is a significant reduction of infarct area and left ventricular contractility is improved in GET-treated group compared with controls. There was no significant difference in mortality of animals treated with GET of plasmid encoding VEGF-A from the control groups. Gene delivery of plasmid encoding VEGF-A to ischemic myocardium in a porcine model can be accomplished safely with potential for myocardial repair and regeneration