Growth in vivo of l5178y-r murine leukaemic cells treated in vitro with cis-dichloro bis-(cyclopentylamine) platinum II.

ROSENBERG (1977) put forward a hypothesis concerning the mechanism of anticancer activity of cis-platinum complexes in vivo. According to this hypothesis, the simple cytotoxic effect is accompanied by an enhanced expression of cancer antigens on the surface of malignant cells. Therefore, the observed regression of malignant growth is at least partly due to the immunological response of the organism. An example supporting this assumption is the growth kinetics of ascites sarcoma 180 in ICR mice after injection of cis-dichlorodiammine cis-platinum (Rosenberg, 1978). For 4 days following injection the number of tumour cells increases. From the 5th day it falls, reaching zero in a cured animal. According to Rosenberg, this result is consistent with the suggestion that surviving cells are destroyed by the immune system. The hypothesis implies the existence of a ready defensive mechanism which can be stimulated by cisplatin-induced changes in the malignant cell surface. In an attempt to test this hypothesis, we used cis-dichloro bis-(cyclopentylamine) platinum (II) (cis-PAD) and L5178Y-R murine leukaemic cells. These cells are very sensitive to cis-PAD in vitro (Szumiel, 1979) and form ascites tumours in DBA/2 mice. The Pt complex is effective in vivo in mice against leukaemi

Effects of ebselen addition on emotional processing and brain neurochemistry in depressed patients unresponsive to antidepressant medication

Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias—an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively

Chicken Anti-Campylobacter Vaccine – Comparison of Various Carriers and Routes of Immunization

Campylobacter spp, especially the species Campylobacter jejuni, are important human enteropathogens responsible for millions of cases of gastro-intestinal disease worldwide every year. C. jejuni is a zoonotic pathogen, and poultry meat that has been contaminated by microorganisms is recognized as a key source of human infections. Although numerous strategies have been developed and experimentally checked to generate chicken vaccines, the results have so far had limited success. In this study, we explored the potential use of non-live carriers of Campylobacter antigen to combat Campylobacter in poultry. First, we assessed the effectiveness of immunization with orally or subcutaneously delivered GEM (Gram-positive Enhancer Matrix) particles carrying two Campylobacter antigens: CjaA and CjaD. These two immunization routes using GEMs as the vector did not protect against Campylobacter colonization. Thus, we next assessed the efficacy of in ovo immunization using various delivery systems: GEM particles and liposomes. The hybrid protein CjaAD, which is CjaA presenting CjaD epitopes on its surface, was employed as a model antigen. We found that CjaAD administered in ovo at embryonic development day 18 by both delivery systems resulted in significant levels of protection after challenge with a heterologous Campylobacter jejuni strain. In practice, in ovo chicken vaccination is used by the poultry industry to protect birds against several viral diseases. Our work showed that this means of delivery is also efficacious with respect to commensal bacteria such as Campylobacter. In this study, we evaluated the protection after one dose of vaccine given in ovo. We speculate that the level of protection may be increased by a post-hatch booster of orally delivered antigens

Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.

BACKGROUND: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. METHODS AND RESULTS: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. CONCLUSIONS: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far

A dietary feedback system for the delivery of consistent personalized dietary advice in the web-based multicenter Food4Me study

Background: Despite numerous healthy eating campaigns, the prevalence of diets high in saturated fatty acids, sugar, and salt and low in fiber, fruit, and vegetables remains high. With more people than ever accessing the Internet, Web-based dietary assessment instruments have the potential to promote healthier dietary behaviors via personalized dietary advice. Objective: The objectives of this study were to develop a dietary feedback system for the delivery of consistent personalized dietary advice in a multicenter study and to examine the impact of automating the advice system. Methods: The development of the dietary feedback system included 4 components: (1) designing a system for categorizing nutritional intakes; (2) creating a method for prioritizing 3 nutrient-related goals for subsequent targeted dietary advice; (3) constructing decision tree algorithms linking data on nutritional intake to feedback messages; and (4) developing personal feedback reports. The system was used manually by researchers to provide personalized nutrition advice based on dietary assessment to 369 participants during the Food4Me randomized controlled trial, with an automated version developed on completion of the study. Results: Saturated fatty acid, salt, and dietary fiber were most frequently selected as nutrient-related goals across the 7 centers. Average agreement between the manual and automated systems, in selecting 3 nutrient-related goals for personalized dietary advice across the centers, was highest for nutrient-related goals 1 and 2 and lower for goal 3, averaging at 92%, 87%, and 63%, respectively. Complete agreement between the 2 systems for feedback advice message selection averaged at 87% across the centers. Conclusions: The dietary feedback system was used to deliver personalized dietary advice within a multi-country study. Overall, there was good agreement between the manual and automated feedback systems, giving promise to the use of automated systems for personalizing dietary advice

Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder : results from the ENIGMA MDD Working Group

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD

Geographies of landscape: Representation, power and meaning

Green criminology has sought to blur the nature-culture binary and this article seeks to extend recent work by geographers writing on landscape to further our understanding of the shifting contours of the divide. The article begins by setting out these different approaches, before addressing how dynamics of surveillance and conquest are embedded in landscape photography. It then describes how the ways we visualize the Earth were reconfigured with the emergence of photography in the 19th century and how the world itself has been transformed into a target in our global media culture