Pseudo-single crystal electrochemistry on polycrystalline electrodes : visualizing activity at grains and grain boundaries on platinum for the Fe2+/Fe3+ redox reaction

The influence of electrode surface structure on electrochemical reaction rates and mechanisms is a major theme in electrochemical research, especially as electrodes with inherent structural heterogeneities are used ubiquitously. Yet, probing local electrochemistry and surface structure at complex surfaces is challenging. In this paper, high spatial resolution scanning electrochemical cell microscopy (SECCM) complemented with electron backscatter diffraction (EBSD) is demonstrated as a means of performing ‘pseudo-single-crystal’ electrochemical measurements at individual grains of a polycrystalline platinum electrode, while also allowing grain boundaries to be probed. Using the Fe2+/3+ couple as an illustrative case, a strong correlation is found between local surface structure and electrochemical activity. Variations in electrochemical activity for individual high index grains, visualized in a weakly adsorbing perchlorate medium, show that there is higher activity on grains with a significant (101) orientation contribution, compared to those with (001) and (111) contribution, consistent with findings on single-crystal electrodes. Interestingly, for Fe2+ oxidation in a sulfate medium a different pattern of activity emerges. Here, SECCM reveals only minor variations in activity between individual grains, again consistent with single-crystal studies, with a greatly enhanced activity at grain boundaries. This suggests that these sites may contribute significantly to the overall electrochemical behavior measured on the macroscale

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies

Daidzein Prevents the Increase in CD4+CD28null T Cells and B Lymphopoesis in Ovariectomized Mice: A Key Mechanism for Anti-Osteoclastogenic Effect

Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4+CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4+ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4+CD28null T cells, however, treatment with Daid increased the percentage of CD4+CD28+ T cells. Co-culture of CD4+CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4+CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220+ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Long-term outcome and prognosis of dissociative disorder with onset in childhood or adolescence

<p>Abstract</p> <p>Background</p> <p>In the majority of cases short-term treatment outcome of juvenile dissociative disorder is rather favourable. In contrast, the long-term course seems to be less positive, but meaningful results are still fragmentary. The aim of this follow-up study is to bridge this gap to some extent describing the long-term outcome of juvenile dissociative disorder in a clinical sample. To our knowledge there is no comparable other long-term follow-up study which is based on a case definition according to actual classification systems using standardized interviews for individual assessment of the patients at the time of follow-up.</p> <p>Methods</p> <p>The total study group was made up of all patients treated for dissociative disorder at our department for child and adolescent psychiatry between 1983 and 1992 (<it>N </it>= 62). Two of these former patients committed suicide during the follow-up period (3%). We got information on the clinical course of 27 former patients (44%). 17 out of these 27 former patients were female (63%). The mean age of onset of dissociative disorder was11.7 years and the mean follow-up time was 12.4 years. Most of the patients were reassessed personally (n = 23) at a mean age of 24.8 years using structured interviews covering dissociative disorders, other Axis I disorders and personality disorders (Heidelberg Dissociation Inventory HDI; Expert System for Diagnosing Mental Disorders, DIA-X; Structured Clinical Interview for DSM-IV, SCID-II). Social adjustment was assessed by a semi-structured interview and by patient self report (Social Adjustment Scale – Self Report, SAS-SR). Psychosocial outcome variables were additionally assessed in 36 healthy controls (67% female, mean age = 22.9 years).</p> <p>Results</p> <p>At the time of follow-up investigation 82.6% of the patients met the criteria for some form of psychiatric disorder, while 26.1% were still suffering from dissociative disorder. A total of 56.5% presented with an Axis I disorder (especially anxiety, dissociative and somatoform disorders). Personality disorders were seen in 47.8% (especially borderline, obsessive-compulsive and negativistic personality disorders). More dissociative symptoms and inpatient treatment in childhood or adolescence were significantly related to a lower level of psychosocial adjustment in adulthood.</p> <p>Conclusion</p> <p>Treatment strategies have to consider that in a significant portion of young patients initial recovery may not be stable over time. Limitations of the study refer to the small sample size and the low rate of former patients taking part in the follow-up investigation.</p

Comparison of the Virulence Potential of Acinetobacter Strains from Clinical and Environmental Sources

Several Acinetobacter strains have utility for biotechnology applications, yet some are opportunistic pathogens. We compared strains of seven Acinetobacter species (baumannii, Ab; calcoaceticus, Ac; guillouiae, Ag; haemolyticus, Ah; lwoffii, Al; junii, Aj; and venetianus, Av-RAG-1) for their potential virulence attributes, including proliferation in mammalian cell conditions, haemolytic/cytolytic activity, ability to elicit inflammatory signals, and antibiotic susceptibility. Only Ah grew at 102 and 104 bacteria/well in mammalian cell culture medium at 37°C. However, co-culture with colonic epithelial cells (HT29) improved growth of all bacterial strains, except Av-RAG-1. Cytotoxicity of Ab and Ah toward HT29 was at least double that of other test bacteria. These effects included bacterial adherence, loss of metabolism, substrate detachment, and cytolysis. Only Ab and Ah exhibited resistance to killing by macrophage-like J774A.1 cells. Haemolytic activity of Ah and Av-RAG-1 was strong, but undetectable for other strains. When killed with an antibiotic, Ab, Ah, Aj and Av-RAG-1 induced 3 to 9-fold elevated HT29 interleukin (IL)-8 levels. However, none of the strains altered levels of J774A.1 pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor-α). Antibiotic susceptibility profiling showed that Ab, Ag and Aj were viable at low concentrations of some antibiotics. All strains were positive for virulence factor genes ompA and epsA, and negative for mutations in gyrA and parC genes that convey fluoroquinolone resistance. The data demonstrate that Av-RAG-1, Ag and Al lack some potentially harmful characteristics compared to other Acinetobacter strains tested, but the biotechnology candidate Av-RAG-1 should be scrutinized further prior to widespread use

The Human Affectome

Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions—a framework for human affective research. In this capstone paper for the special issue “Towards an Integrated Understanding of the Human Affectome”, we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research