The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice

Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Comparative Structural Analysis of Lipid Binding START Domains

Steroidogenic acute regulatory (StAR) protein related lipid transfer (START) domains are small globular modules that form a cavity where lipids and lipid hormones bind. These domains can transport ligands to facilitate lipid exchange between biological membranes, and they have been postulated to modulate the activity of other domains of the protein in response to ligand binding. More than a dozen human genes encode START domains, and several of them are implicated in a disease.We report crystal structures of the human STARD1, STARD5, STARD13 and STARD14 lipid transfer domains. These represent four of the six functional classes of START domains.Sequence alignments based on these and previously reported crystal structures define the structural determinants of human START domains, both those related to structural framework and those involved in ligand specificity.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

A high implicit affiliation motive does not always make you happy: A corresponding explicit motive and corresponding behavior are further needed

Satisfaction of the implicit affiliation motive is known to be positively related to emotional well-being, whereas the frustration of the implicit affiliation motive leads to impairment of well-being. In the present research we specified two conditions that are responsible for the satisfaction and frustration of the implicit motive. Referring to research on the congruence of implicit and explicit motives, we assumed that a corresponding explicit affiliation motive leads to satisfaction of the implicit motive. Corresponding affiliation behavior constitutes the second condition. Three studies confirmed the hypothesis that both conditions must be fulfilled in order to positively connect the implicit affiliation motive to emotional well-being. Participants with high implicit and explicit affiliation motives and who additionally showed a large amount of affiliation behavior reported the lowest negative affectivity and the highest life satisfaction compared to participants who lacked one of the conditions

Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles

Avaliação de teratógenos potenciais na população brasileira Evaluation of potential teratogens in Brazilian population

O fato de agentes ambientais, nomeadamente fármacos, infecções maternas, e agentes químicos ou físicos poderem causar danos ao embrião ou feto em desenvolvimento é um problema reconhecido principalmente a partir do século 20. Nos países em desenvolvimento, existem características especiais que podem tornar esse problema mais agudo. Essas características incluem níveis educacionais e econômicos baixos da população, alta incidência de doenças infecciosas e carenciais, escassos recursos para saúde e pesquisa, prática freqüente e sem controle de automedicação, facilidade de obtenção de medicações que deveriam estar submetidas à prescrição médica e, finalmente, proibição legal de interrupção da gestação. Além disso, pode somar-se uma qualidade ambiental precária ou mesmo condições de trabalho insalubres durante a gravidez. No presente trabalho apresentamos as principais metodologias para detecção e monitorização de potenciais teratógenos, com ênfase especial nos programas desenvolvidos no Brasil e América Latina.<br>The fact that environmental agents, namely drugs, maternal infections, other chemical or physical agents could harm the developing embryo or fetus is a problem recognized specially since the XXth century. In developing countries there are some special characteristics that can make this problem more severe. These include low educational and economical level of the population, high incidence of infectious and carential diseases, habits of self-medication associated to easy ways to obtain prescription drugs and, finally no legal permission for pregnancy termination. More than that, sometimes there are also bad environmental conditions or unhealthy working conditions during pregnancy. In this article we present the main methodologies to detect and to monitorize potential teratogens, with special emphasis in present programs going on in Brazil and Latin America

Achievement incentives determine the effects of achievement-motive incongruence on flow experience

Previous research has shown that incongruence between implicit and explicit achievement motives impairs flow experience. We examined this relationship in a more differentiated manner by arguing that achievement-motive incongruence only exerts negative effects when individuals act in situations in which achievement incentives are present and arouse conflict between the two motives. In non-achievement situations, no negative effects of achievement-motive incongruence on flow experience are expected. Study 1 and Study 2 showed that participants with incongruent implicit and explicit achievement motives reported less flow in achievement- as compared to non-achievement-oriented sport situations. In Study 3, we experimentally manipulated achievement and non-achievement situations. Again, motive incongruence impaired the experience of flow in achievement but not in non-achievement situations

Finnish-Chinese intercultural negotiation : power positioning and search for common ground

‘Rising China’ is a term that has come to refer to China’s march to being number one, the speed of its economic growth, and its investment around the world during last two decades. In Finland, government agencies have been established to promote investment, trade, and co-operation with China, while regional and local governments are also actively involved. Meanwhile, much of the world is now competing for the attention of China, so the power dynamic is tending to shift in favour of the Chinese. This developing context has been examined in previous studies primarily from the perspectives of politics, economics, and management studies. The overarching aim of this study is to investigate emerging power relations between Finns as sellers of investment opportunities and products and Chinese as investors, buyers, and partners. The study predominantly builds on Positioning Theory (Harré, 1991). It uses methodological tools of ethnographically framed in terviewing and observation. The study comprises five articles - empirical research reports exploring the major themes in data collected – adjustment of Finns to the Chinese, search of common ground with Chinese representatives, guest-host positioning during delegation visits, humor in negotiations, and the language aspect in co-operation. Five styles of positioning regarding power and common ground were found – adjustment, use of existing common ground, autonomy, ‘soft’ power, and pressure / hedging; the character this typology was found to correspond to phases of the five Chinese elements (Wu Xing). While the data suggest that both Finnish and Chinese representatives use all of these strategies, Finnish representatives tended to rely on active responses such as adjustment and pressure/hedging, while Chinese representatives more often resorted to a stance of autonomy. The dynamic among these phases is illustrated using the model of a rope, which suggests the integral nature of change from one style into another, as well as the ways power, common ground, and culture are all intertwined. A variety of external and internal factors that influence the positioning of Finnish and Chinese representatives could also be traced from the articles, such as organizational roles, meeting places, discourses about national characteristics, and considerations of ‘face’. This further reveals the complexity of positioning regarding power and common ground