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Search Results: 1 - 10 of 3925 matches for " Adrian Britschgi "
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Hippo inactivation feeds tumor-initiating cells
Stephan Duss, Adrian Britschgi, Mohamed Bentires-Alj
Breast Cancer Research , 2012, DOI: 10.1186/bcr3190
Abstract: The Hippo signaling pathway was discovered more than 17 years ago in Drosophila mutant screens as a major regulator of organ size controlling proliferation and cell death [1]. This pathway is conserved and equally important in mammals and, not surprisingly, deregulation of the Hippo pathway plays fundamental roles in cancer [2,3]. Whereas the upstream components of the Hippo pathway (NF2, MST1/2, SAV1, LATS1/2, and MOB1A) are tumor suppressors, the downstream components (YAP1, TAZ and TEAD) are oncogenes [4]. The mammalian Hippo homolog kinases MST1/2 (macrophage stimulating 1/2) in complex with the scaffold protein SAV1 (salvador homolog 1), phosphorylate and activate the kinases LATS1/2 (large tumor suppressor homolog 1/2). LATS1/2 phosphorylate and inactivate the transcription co-activators YAP1 (Yes-associated protein 1) [5] and TAZ (transcriptional coactivator with PDZ-binding motif) [6]. Unphosphorylated YAP1/TAZ associate with TEAD (TEA domain family member 1) and activate their target genes [7] (Figure 1). TAZ binds heteromeric SMAD2/3-4, activates transforming growth factor-beta target genes and maintains human embryonic stem cell self-renewal [8]. Furthermore, TAZ enhances epithelial-to-mesenchymal transition (EMT), migration, invasion and tumorigenesis of breast cancer cell lines [6,9].Whereas many upstream components of the Hippo pathway in Drosophila [10] and zebrafish [11] have been identified, those in mammals remain poorly defined. The work of Cordenonsi and colleagues [12] indicates a role for EMT and the polarity gatekeeper Scribble upstream of the Hippo cascade in human breast tumor-initiating cells.To identify signaling pathways that drive breast tumorigenesis and heterogeneity, Cordenonsi and colleagues [12] analyzed a gene expression metadataset of breast tumors and found a TAZ/YAP signature to be correlated with high-grade (poorly differentiated) tumors. These tumors were previously shown to express embryonic and mammary stem cell signatures.
Male dominance linked to size and age, but not to 'good genes' in brown trout (Salmo trutta)
Alain Jacob, Sébastien Nusslé, Adrian Britschgi, Guillaume Evanno, Rudolf Müller, Claus Wedekind
BMC Evolutionary Biology , 2007, DOI: 10.1186/1471-2148-7-207
Abstract: We found significant additive genetic variance on embryo survival, i.e. males differed in their genetic quality. Older, heavier and larger males were more successful in intra-sexual selection. However, neither dominance nor dominance indicators like body length, weight or age were significantly linked to genetic quality measured as embryo or juvenile survival.We found no evidence that females can improve their offspring's genetic viability by mating with large and dominant males. If there still were advantages of mating with dominant males, they may be linked to non-genetic benefits or to genetic advantages that are context dependent and therefore possibly not revealed under our experimental conditions – even if we found significant additive genetic variation for embryo viability under such conditions.In mating systems with elaborate male-male competition, the winners usually get most mates and sire most of the offspring [1-10]. Such a skewed male mating success may either be explained by physically limited access of subdominant males to females and/or by female preference for dominant males [11-13]. Females may prefer more dominant and more attractive males because they provide more resources, better parental care [14,15] or better genes for the common offspring [2,16-18]. The latter hypothesis corresponds to the so-called 'good-genes' hypotheses of sexual selection, i.e. variation in genetic quality is then predicted to be linked to male characteristics that influence female mate choice. The problem of how such genetic variation can be maintained under sexual selection is known as the "lek paradox" [19], and a number of possible solutions for this paradox have been offered (reviewed in [20,21]). Although it is still not fully clear how the genetic variation is maintained, there is much evidence in various species that females can gain genetic advantages by preferring males with well-developed attractiveness traits [22]. Whether females gain genetic benefits by mat
Global Health: A Successful Context for Precollege Training and Advocacy
Ana L. Gervassi,Laura J. Collins,Theresa B. Britschgi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013814
Abstract: Despite a flourishing biomedical and global health industry [1] too few of Washington state's precollege students are aware of this growing sector and emerging ideas on bacteria, fungi, parasites and viruses. Against the backdrop of numerous reports regarding declining precollege student interest in science [2], a precollege program was envisioned at Seattle Biomedical Research Institute (as of 2010, Seattle BioMed) to increase youth engagement in biomedical research and global health, increase community interest in infectious diseases and mobilize a future biomedical workforce. Since 2005, 169 rising high school juniors have participated in the BioQuest Academy precollege immersion program at Seattle BioMed. Assembling in groups of 12, students conduct laboratory experiments (e.g., anopheline mosquito dissection, gene expression informed tuberculosis drug design and optimizing HIV immunization strategies) related to global health alongside practicing scientific mentors, all within the footprint the institute. Laudable short-term impacts of the program include positive influences on student interest in global health (as seen in the students' subsequent school projects and their participation in Seattle BioMed community events), biomedical careers and graduate school (e.g., 16.9% of teens departing 2008–2009 Academy report revised goals of attaining a doctorate rather than a baccalaureate diploma). Long-term, 97% of alumni (2005–2008) are attending postsecondary schools throughout North America; eight graduates have already published scientific articles in peer-reviewed journals and/or presented their scientific data at national and international meetings, and 26 have been retained by Seattle BioMed researchers as compensated technicians and interns. Providing precollege students with structured access to practicing scientists and authentic research environments within the context of advancing global health has been a robust means of both building a future pool of talented leaders and engaged citizenry and increasing the visibility of health disparities within the community.
Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice
Britschgi Markus,Takeda-Uchimura Yoshiko,Rockenstein Edward,Johns Hudson
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-220
Abstract: Background The neuronal microtubule-associated protein tau becomes hyperphosphorylated and forms aggregates in tauopathies but the processes leading to this pathological hallmark are not understood. Because tauopathies are accompanied by neuroinflammation and the complement cascade forms a key innate immune pathway, we asked whether the complement system has a role in the development of tau pathology. Findings We tested this hypothesis in two mouse models, which expressed either a central inhibitor of complement or lacked an inhibitor of the terminal complement pathway. Complement receptor-related gene/protein y is the natural inhibitor of the central complement component C3 in rodents. Expressing a soluble variant (sCrry) reduced the number of phospho-tau (AT8 epitope) positive neurons in the brain stem, cerebellum, cortex, and hippocampus of aged P301L mutant tau/sCrry double-transgenic mice compared with tau single-transgenic littermates (JNPL3 line). CD59a is the major inhibitor of formation of the membrane attack complex in mice. Intrahippocampal injection of adeno-associated virus encoding mutant human P301L tau into Cd59a / mice resulted in increased numbers of AT8-positive cells compared with wild-type controls. This was accompanied by neuronal and synaptic loss and reduced dendritic integrity. Conclusions Our data in two independent mouse models with genetic changes in key regulators of the complement system support the hypothesis that the terminal pathway has an active role in the development of tau pathology. We propose that inhibition of the terminal pathway may be beneficial in tauopathies.
What Is a Good Legislative Definition?  [PDF]
Adrian Sgarbi
Beijing Law Review (BLR) , 2013, DOI: 10.4236/blr.2013.41004

When normative authorities (that is to say, “Legislators”) assume the task of assigning the meaning of normative texts, they use, fundamentally, two techniques: these are called “interpretative laws” and “legislative definitions”. In this study, relating to the research “problems of production and normative performance”, we deal with the analysis of definitions in the legal field.

Lay Knowledge of Dyslexia  [PDF]
Adrian Furnham
Psychology (PSYCH) , 2013, DOI: 10.4236/psych.2013.412136

This study looks at the extent to which lay people believe many myths associated with dyslexia. It examined attitudes and beliefs about the causes, manifestations and treatments for dyslexia in a British population sample. A community sample of 380 participants (158 Male; 212 Female) completed a 62-item questionnaire on their attitudes to, and beliefs about, dyslexia. The statements were derived from various “dyslexia facts and myths” websites set up to help people understand dyslexia; academic research papers; and in-depth exploratory interviews with non-specialist people regarding their understanding of dyslexia. Item analysis showed participants were poorly informed about many aspects of dyslexia. Factor analysis returned a structure of latent attitudes in five factors (Characteristics, Biological and Social Causes, Treatment and Prevention). Regression analysis revealed that participant political orientation and education (formal and informal acquaintances with dyslexia sufferers) were the best predictors of attitudes concerning the behavioural manifestations, aetiology and treatments of dyslexia. Limitations and implications of this research were considered.

The Mystery of Freedom and Neurolaw  [PDF]
Adrian Sgarbi
Beijing Law Review (BLR) , 2015, DOI: 10.4236/blr.2015.62014
Abstract: In the case of Steward Mach. Co. v. Davis, Judge Benjamin Nathan Cardozo said that “Till now the law has been guided by a robust common sense which assumes the freedom of the will as a working hypothesis in the solution of its problems”. This hypothesis, which has previously been defended almost wholly within the confines of philosophical reflections on human responsibility, now seems to be undergoing a new wave of considerations. This is because neuroscience has been brought to bear in court proceedings in order to challenge the existence of human free will, in cases of both civil and criminal law. In the media, to a greater or lesser degree, various specialists have published the results of all kinds of experiments along with diagrams and graphs, technical advice and new machines to back up their claims. Currently, the use of some of these techniques in court and their lack of sustainability in many situations has, in turn, been emphasized, especially in the context of judicial proof (and reasonable doubt). In this sense, we can say that the issue of free will has been considered, but not always clearly, on three different levels: as a problem of description, of substance or of prescription. At the descriptive level is the question of what exactly we mean when we talk about free will. On the substantive level is the question of whether or not human beings actually possess this quality called free will. And finally, on the prescriptive level is the question of what we do with this knowledge. In this article, we offer an analysis of the problematic relationships between these three levels, beginning with a critical look at certain descriptive positions. In the end, it is suggested that these isolated descriptions, whether in the field of neuroscience, or philosophy, have led to an impasse whose effect is that the assertion that freedom in human behaviour is an illusion, and free will, a great mystery. As a possible way out, we present three modifications to the debate in order to extend its intelligibility beyond the boundaries of the legal profession.
What You Can and Can’t Change: Lay Perspectives on Seligman’s Guide  [PDF]
Adrian Furnham
Psychology (PSYCH) , 2015, DOI: 10.4236/psych.2015.612142
Abstract: Seligman (2007) reported 10 facts about what psychological processes and problems can be changed, and those that cannot be changed. Over 250 participants completed a questionnaire where they indicated the extent to which they agreed with Seligman, as well as a measure of the Big Five personality traits, CORE self-beliefs and a measure of Dweck’s (2012) “Change Mindset” questionnaire. Lay people did not agree with Seligman and factor analysis did not confirm his grouping. Regressions indicated that age, sex, religiousness and Mindset were related to beliefs about change. Limitations are noted.
Personality, Emotional and Self-Assessed Intelligence and Right Wing Authoritarianism  [PDF]
Adrian Furnham
Psychology (PSYCH) , 2015, DOI: 10.4236/psych.2015.616207
Abstract: Two studies examined correlates of right-wing authoritarianism (RWA). In the first study (N = 260), lower self-assessments of intelligence were associated with higher RWA scores. In the second study (N = 328), personality traits and emotional intelligence but not self-assessed intelligence were related to RWA beliefs. Higher RWA scorers tended to be Closed-to-Experience, Conscientious, and Neurotics with higher trait emotional intelligence. Together these accounted for 20% of the variance.
The Relationship between Cognitive Ability, Emotional Intelligence and Creativity  [PDF]
Adrian Furnham
Psychology (PSYCH) , 2016, DOI: 10.4236/psych.2016.72021
Abstract: The objective of this study was to investigate the relationship between IQ, EQ and creativity. In all 158 British adults completed a cognitive ability, creativity and emotional intelligence test. Cognitive ability was positively but not significantly correlated with divergent thinking (creativity) but significantly negatively with both facet and domain emotional intelligence scores.
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