Effects on mitochondria of mitochondria-induced nitric oxide release from a ruthenium nitrosyl complex

The ruthenium nitrosyl complex trans-[Ru(NO)(NH(3))(4)(py)](PF(6))(3) (pyNO), a nitric oxide (NO) donor, was studied in regard to the release of NO and its impact both on isolated mitochondria and HepG2 cells. In isolated mitochondria, NO release from pyNO was concomitant with NAD(P)H oxidation and, in the 25-100 mu M range, it resulted in dissipation of mitochondrial membrane potential, inhibition of state 3 respiration, ATP depletion and reactive oxygen species (ROS) generation. In the presence of Ca(2+), mitochondrial permeability transition (MPT), an unspecific membrane permeabilization involved in cell necrosis and some types of apoptosis, was elicited. As demonstrated by externalization of phosphatidylserine and activation of caspase-9 and caspase-3, pyNO (50-100 mu M) induced HepG2 cell death, mainly by apoptosis. The combined action of the NO itself, the peroxynitrite yielded by NO in the presence of reactive oxygen species (ROS) and the oxidative stress generated by the NAD(P)H oxidation is proposed to be involved in cell death by pyNO, both via respiratory chain inhibition and ROS levels increase, or even via MPT, if Ca(2+) is present. (c) 2008 Elsevier Inc. All rights reserved.

Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8

The effects on mitochondrial respiration and complex I NADH oxidase activity of cubebin and derivatives were evaluated. The compounds inhibited the state 3 glutamate/malate-supported respiration of hamster liver mitochondria with IC50 values ranging from 12.16 to 83.96M. NADH oxidase reaction was evaluated in submitochondrial particles. The compounds also inhibited this activity, showing the same order of potency observed for effects on state 3 respiration, as well as a tendency towards a non-competitive type of inhibition (KI values ranging from 0.62 to 16.1M). A potential binding mode of these compounds with complex I subunit B8, assessed by docking calculations, is proposed.

The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines

The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

The Ruthenium Complex cis-(Dichloro) Tetraammineruthenium(III) Chloride Presents Immune Stimulatory Activity on Human Peripheral Blood Mononuclear Cells

Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro) tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium( III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[ RuCl(2)(NH(3))(4)] Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl(2)(NH(3))(4)] Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10-100 mu g L(-1)), the cis-[ RuCl(2)(NH(3))(4)] Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.

ELUCIDATING ENIGMATIC FLORAL ISSUES IN COPAIFERA LANGSDORFFII DESF. (LEGUMINOSAE, CAESALPINIOIDEAE)

This study focuses on the floral development of Copaifera langsdorffii to elucidate uncertain features in its floral morphology, such as the tetramerous calyx, lack of petals, blackened anthers and their supposed sterility, as well as polyembryony. Buds and flowers were dissected and prepared for examination under scanning electron and light microscopes. The floral apex initiates two bracteoles, five sepals, five petals, five outer stamens, five inner stamens, and one carpel. Order is helical for sepals, reversed unidirectional for the petals, and unidirectional for two whorls of stamens. The tetramerous calyx results from the union of two adaxial sepal primordia, which forms one large sepal and three other smaller sepals. Although the flower lacks petals, the petal primordia are initiated but do not elongate like the other floral organs, remaining as petal rudiments. Ten stamens are formed in two distinct whorls. Formation within each whorl is almost simultaneous, and the inner whorl is formed shortly after the outer. During organ elongation, the inner stamen primordia bases are reoriented outward, resulting in a single whorl of stamens. The darkened anthers have viable pollen grains. Thus, there is no relation between sterility and the dark coloration of the anthers. No signs of extranumerary embryos are observed; therefore, polyembryony is not confirmed. Although studies on floral development of Detarieae have been reported, few Neotropical genera of the tribe (such as Copaifera) have been studied.

Beauty, Class and Discourse: Issues in Debate

In this text we proceed through a brief review of Naomi Lee`s (2009) article, highlighting her significant contributions to social and cultural psychology. In our dialogue with her text we inquire about some arguments and methodological procedures she presents. We raise some specific questions related to how the issue of beauty is framed, and we ponder on how a broadening of the scope to include history-of ideas, of relations-would bring some important elements to her approach. As Lee relates beauty and class, we examine the nuanced meanings of lack and deficiency in her analytical work. We also discuss her assumptions and position concerning discourse and dialogue which mark her ways of proceeding through the analysis of the interviews. We speculate that the depersonalized answer appointed in the interviewees` discourse can be related to a way of considering beauty as disembodied.

Major Issues in Business Process Management: An Expert Perspective

The results presented in this report form a part of a larger global study on the major issues in BPM. Only one part of the larger study is reported here, viz. interviews with BPM experts. Interviews of BPM tool vendors together with focus groups involving user organizations, are continuing in parallel and will set the groundwork for the identification of BPM issues on a global scale via a survey (including a Delphi study). Through this multi-method approach, we identify four distinct sets of outcomes. First, as is the focus of this report, we identify the BPM issues as perceived by BPM experts. Second, the research design allows us to gain insight into the opinions of organisations deploying BPM solutions. Third, an understanding of organizations’ misconceptions of BPM technologies, as confronted by BPM tool vendors is obtained. Last, we seek to gain an understanding of BPM issues on a global scale, together with knowledge of matters of concern. This final outcome is aimed to produce an industry driven research agenda which will inform practitioners and in particular, the research community world-wide on issues and challenges that are prevalent or emerging in BPM and related areas.

The Genetic Speciation of Archaeological Fish Bone: A Feasibility Study from Southeast Queensland

Current genetic methods enable highly specific identification of DNA from modern fish bone. The applicability of these methods to the identification of archaeological fish bone was investigated through a study of a sample from late Holocene southeast Queensland sites. The resultant overall success rate of 2% indicates that DNA analysis is, as yet, not feasible for identifying fish bone from any given site. Taphonomic issues influencing the potential of genetic identification methods are raised and discussed in light of this result.

Work issues for young people with psychosis: Barriers to employment

Young people who have had a mental illness face significant barriers to both gaining and maintaining employment. A study using a qualitative design and consisting of two focus groups, was conducted to focus on the issues experiencedby young people diagnosed with psychosis wanting to gain employment. The participants were 10 registered clients of an Australian mental health service that had a specialised early psychosis programme. The themes identified in this study concerned loss, low self-confidence and self-esteem, stigma, treatment issues, the need for support, and difficulties in identifying and achieving goals. Further research is warranted to gain a greater understanding of the type of programme that would best assist young people to gain and maintain employment.

Hemispheric contributions to lexical ambiguity resolution: Evidence from individuals with complex language impairment following left-hemisphere lesions

Nine individuals with complex language deficits following left-hemisphere cortical lesions and a matched control group (n 5 9) performed speeded lexical decisions on the third word of auditory word triplets containing a lexical ambiguity. The critical conditions were concordant (e.g., coin–bank–money), discordant (e.g., river–bank–money), neutral (e.g., day–bank– money), and unrelated (e.g., river–day–money). Triplets were presented with an interstimulus interval (ISI) of 100 and 1250 ms. Overall, the left-hemisphere-damaged subjects appeared able to exhaustively access meanings for lexical ambiguities rapidly, but were unable to reduce the level of activation for contextually inappropriate meanings at both short and long ISIs, unlike control subjects. These findings are consistent with a disruption of the proposed role of the left hemisphere in selecting and suppressing meanings via contextual integration and a sparing of the right-hemisphere mechanisms responsible for maintaining alternative meanings.

The resolution of complex spectral patterns by cochlear implant and normal-hearing listeners

The differences in spectral shape resolution abilities among cochlear implant ~CI! listeners, and between CI and normal-hearing ~NH! listeners, when listening with the same number of channels ~12!, was investigated. In addition, the effect of the number of channels on spectral shape resolution was examined. The stimuli were rippled noise signals with various ripple frequency-spacings. An adaptive 4IFC procedure was used to determine the threshold for resolvable ripple spacing, which was the spacing at which an interchange in peak and valley positions could be discriminated. The results showed poorer spectral shape resolution in CI compared to NH listeners ~average thresholds of approximately 3000 and 400 Hz, respectively!, and wide variability among CI listeners ~range of approximately 800 to 8000 Hz!. There was a significant relationship between spectral shape resolution and vowel recognition. The spectral shape resolution thresholds of NH listeners increased as the number of channels increased from 1 to 16, while the CI listeners showed a performance plateau at 4–6 channels, which is consistent with previous results using speech recognition measures. These results indicate that this test may provide a measure of CI performance which is time efficient and non-linguistic, and therefore, if verified, may provide a useful contribution to the prediction of speech perception in adults and children who use CIs.

BIO Logical Agents: Norms, Beliefs, Intentions in Defeasible Logic

In this paper we follow the BOID (Belief, Obligation, Intention, Desire) architecture to describe agents and agent types in Defeasible Logic. We argue, in particular, that the introduction of obligations can provide a new reading of the concepts of intention and intentionality. Then we examine the notion of social agent (i.e., an agent where obligations prevail over intentions) and discuss some computational and philosophical issues related to it. We show that the notion of social agent either requires more complex computations or has some philosophical drawbacks.

And then came Complex Project Management

The subject of management is renowned for its addiction to fads and fashions. Project Management is no exception. The issue of interest for this paper is the establishment of the 'College of Complex Project Managers' and their 'competency standard for complex project managers.' Both have generated significant interest in the Project Management community, and like any other human endeavour they should be subject to critical evaluation. The results of this evaluation show significant flaws in the definition of complex in this case, the process by which the College and its standard have emerged, and the content of the standard. However, there is a significant case for a portfolio of research that extends the existing bodies of knowledge into large-scale complicated (or major) projects that would be owned by the relevant practitioner communities, rather than focused on one organization. Research questions are proposed that would commence this stream of activity towards an intelligent synthesis of what is required to manage in both complicated and truly complex environments.