65 research outputs found
Identification of New Genes Involved in Human Adipogenesis and Fat Storage
Since the worldwide increase in obesity represents a growing challenge for health care systems, new approaches are needed to effectively treat obesity and its associated diseases. One prerequisite for advances in this field is the identification of genes involved in adipogenesis and/or lipid storage. To provide a systematic analysis of genes that regulate adipose tissue biology and to establish a target-oriented compound screening, we performed a high throughput siRNA screen with primary (pre)adipocytes, using a druggable siRNA library targeting 7,784 human genes. The primary screen showed that 459 genes affected adipogenesis and/or lipid accumulation after knock-down. Out of these hits, 333 could be validated in a secondary screen using independent siRNAs and 110 genes were further regulated on the gene expression level during adipogenesis. Assuming that these genes are involved in neutral lipid storage and/or adipocyte differentiation, we performed InCell-Western analysis for the most striking hits to distinguish between the two phenotypes. Beside well known regulators of adipogenesis and neutral lipid storage (i.e. PPARγ, RXR, Perilipin A) the screening revealed a large number of genes which have not been previously described in the context of fatty tissue biology such as axonemal dyneins. Five out of ten axonemal dyneins were identified in our screen and quantitative RT-PCR-analysis revealed that these genes are expressed in preadipocytes and/or maturing adipocytes. Finally, to show that the genes identified in our screen are per se druggable we performed a proof of principle experiment using an antagonist for HTR2B. The results showed a very similar phenotype compared to knock-down experiments proofing the “druggability”. Thus, we identified new adipogenesis-associated genes and those involved in neutral lipid storage. Moreover, by using a druggable siRNA library the screen data provides a very attractive starting point to identify anti-obesity compounds targeting the adipose tissue
Natural Variation in an ABC Transporter Gene Associated with Seed Size Evolution in Tomato Species
Seed size is a key determinant of evolutionary fitness in plants and is a trait that often undergoes tremendous changes during crop domestication. Seed size is most often quantitatively inherited, and it has been shown that Sw4.1 is one of the most significant quantitative trait loci (QTLs) underlying the evolution of seed size in the genus Solanum—especially in species related to the cultivated tomato. Using a combination of genetic, developmental, molecular, and transgenic techniques, we have pinpointed the cause of the Sw4.1 QTL to a gene encoding an ABC transporter gene. This gene exerts its control on seed size, not through the maternal plant, but rather via gene expression in the developing zygote. Phenotypic effects of allelic variation at Sw4.1 are manifested early in seed development at stages corresponding to the rapid deposition of starch and lipids into the endospermic cells. Through synteny, we have identified the Arabidopsis Sw4.1 ortholog. Mutagenesis has revealed that this ortholog is associated with seed length variation and fatty acid deposition in seeds, raising the possibility that the ABC transporter may modulate seed size variation in other species. Transcription studies show that the ABC transporter gene is expressed not only in seeds, but also in other tissues (leaves and roots) and, thus, may perform functions in parts of the plants other than developing seeds. Cloning and characterization of the Sw4.1 QTL gives new insight into how plants change seed during evolution and may open future opportunities for modulating seed size in crop plants for human purposes
Disease concepts and treatment by tribal healers of an Amazonian forest culture
<p>Abstract</p> <p>Background</p> <p>The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture.</p> <p>Methods</p> <p>The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed.</p> <p>Results</p> <p>20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture.</p> <p>Conclusion</p> <p>The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.</p
What is the role of the film viewer? The effects of narrative comprehension and viewing task on gaze control in film
Film is ubiquitous, but the processes that guide viewers' attention while viewing film narratives are poorly understood. In fact, many film theorists and practitioners disagree on whether the film stimulus (bottom-up) or the viewer (top-down) is more important in determining how we watch movies. Reading research has shown a strong connection between eye movements and comprehension, and scene perception studies have shown strong effects of viewing tasks on eye movements, but such idiosyncratic top-down control of gaze in film would be anathema to the universal control mainstream filmmakers typically aim for. Thus, in two experiments we tested whether the eye movements and comprehension relationship similarly held in a classic film example, the famous opening scene of Orson Welles' Touch of Evil (Welles & Zugsmith, Touch of Evil, 1958). Comprehension differences were compared with more volitionally controlled task-based effects on eye movements. To investigate the effects of comprehension on eye movements during film viewing, we manipulated viewers' comprehension by starting participants at different points in a film, and then tracked their eyes. Overall, the manipulation created large differences in comprehension, but only produced modest differences in eye movements. To amplify top-down effects on eye movements, a task manipulation was designed to prioritize peripheral scene features: a map task. This task manipulation created large differences in eye movements when compared to participants freely viewing the clip for comprehension. Thus, to allow for strong, volitional top-down control of eye movements in film, task manipulations need to make features that are important to narrative comprehension irrelevant to the viewing task. The evidence provided by this experimental case study suggests that filmmakers' belief in their ability to create systematic gaze behavior across viewers is confirmed, but that this does not indicate universally similar comprehension of the film narrative
New Developments in the Casimir Effect
We provide a review of both new experimental and theoretical developments in
the Casimir effect. The Casimir effect results from the alteration by the
boundaries of the zero-point electromagnetic energy. Unique to the Casimir
force is its strong dependence on shape, switching from attractive to repulsive
as function of the size, geometry and topology of the boundary. Thus the
Casimir force is a direct manifestation of the boundary dependence of quantum
vacuum.
We discuss in depth the general structure of the infinities in the field
theory which are removed by a combination of zeta-functional regularization and
heat kernel expansion. Different representations for the regularized vacuum
energy are given. The Casimir energies and forces in a number of configurations
of interest to applications are calculated. We stress the development of the
Casimir force for real media including effects of nonzero temperature, finite
conductivity of the boundary metal and surface roughness. Also the combined
effect of these important factors is investigated in detail on the basis of
condensed matter physics and quantum field theory at nonzero temperature.
The experiments on measuring the Casimir force are also reviewed, starting
first with the older measurements and finishing with a detailed presentation of
modern precision experiments. The latter are accurately compared with the
theoretical results for real media.
At the end of the review we provide the most recent constraints on the
corrections to Newtonian gravitational law and other hypothetical long-range
interactions at submillimeter range obtained from the Casimir force
measurements.Comment: 275 pages,29 figures, to appear in Physics Report
Restructuring UK local government employment relations: pay determination and employee participation in tough times
The Conservative-led coalition government has been committed to shrinking the state and this has had a major impact on local government. This article examines the consequences of austerity measures for staff participation and pay determination in UK local government. Local government has been particularly hard hit by austerity measures and this has encouraged employers to change terms and conditions, review forms of staff participation and cut jobs. The implications for the institutional resilience of systems of employment regulation and employee involvement in the sector are considered
Objects of reference Their role in supporting learners with multiple disabilities : proceedings of a national conference held at the School of Education, University of Birmingham, 20th June 2002
Includes bibliographical referencesSIGLEAvailable from British Library Document Supply Centre- DSC:m03/20487 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
The management of urban fringe land development in Bangalore
5.00; Produced in association with Town and Country Planning Organisation, New Delhi (IN)Available from British Library Document Supply Centre- DSC:6393.42(32) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Birmingham Jewry Volume 2; more aspects 1740-1930
SIGLEAvailable from British Library Lending Division - LD:85/08576(Birmingham) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
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