Screen for Genetic Modifiers of stbm Reveals that Photoreceptor Fate and Rotation Can Be Genetically Uncoupled in the Drosophila Eye

BACKGROUND: Polarity of the Drosophila compound eye arises primarily as a consequence of two events that are tightly linked in time and space: fate specification of two photoreceptor cells, R3 and R4, and the subsequent directional movement of the unit eyes of the compound eye, or ommatidia. While it is thought that these fates dictate the direction of ommatidial rotation, the phenotype of mutants in the genes that set up this polarity led to the hypothesis that these two events could be uncoupled. METHODOLOGY/PRINCIPAL FINDINGS: To definitively demonstrate these events are genetically separable, we conducted a dominant modifier screen to determine if genes, when misexpressed, could selectively enhance subclasses of mutant ommatidia in which the direction of rotation does not follow the R3/R4 cell fates, yet not affect the number of ommatidia in which rotation follows the R3/R4 cell fates. We identified a subset of P element lines that exhibit this selective enhancement. We also identified lines that behave in the opposite manner: They enhance the number of ommatidia that rotate in the right direction, but do not alter the number of ommatidia that rotate incorrectly with respect to the R3/R4 fates. CONCLUSIONS/SIGNIFICANCE: These results indicate that fate and direction of rotation can be genetically separated, and that there are genes that act between R3/R4 fate specification and direction of ommatidial rotation. These data affirm what has been a long-standing assumption about the genetic control of ommatidial polarity

A topological Dirac insulator in a quantum spin Hall phase : Experimental observation of first strong topological insulator

When electrons are subject to a large external magnetic field, the conventional charge quantum Hall effect \cite{Klitzing,Tsui} dictates that an electronic excitation gap is generated in the sample bulk, but metallic conduction is permitted at the boundary. Recent theoretical models suggest that certain bulk insulators with large spin-orbit interactions may also naturally support conducting topological boundary states in the extreme quantum limit, which opens up the possibility for studying unusual quantum Hall-like phenomena in zero external magnetic field. Bulk Bi$_{1-x}$Sb$_x$ single crystals are expected to be prime candidates for one such unusual Hall phase of matter known as the topological insulator. The hallmark of a topological insulator is the existence of metallic surface states that are higher dimensional analogues of the edge states that characterize a spin Hall insulator. In addition to its interesting boundary states, the bulk of Bi$_{1-x}$Sb$_x$ is predicted to exhibit three-dimensional Dirac particles, another topic of heightened current interest. Here, using incident-photon-energy-modulated (IPEM-ARPES), we report the first direct observation of massive Dirac particles in the bulk of Bi$_{0.9}$Sb$_{0.1}$, locate the Kramers' points at the sample's boundary and provide a comprehensive mapping of the topological Dirac insulator's gapless surface modes. These findings taken together suggest that the observed surface state on the boundary of the bulk insulator is a realization of the much sought exotic "topological metal". They also suggest that this material has potential application in developing next-generation quantum computing devices.Comment: 16 pages, 3 Figures. Submitted to NATURE on 25th November(2007

Analytical, Optimal, and Sparse Optimal Control of Traveling Wave Solutions to Reaction-Diffusion Systems

This work deals with the position control of selected patterns in reaction-diffusion systems. Exemplarily, the Schl\"{o}gl and FitzHugh-Nagumo model are discussed using three different approaches. First, an analytical solution is proposed. Second, the standard optimal control procedure is applied. The third approach extends standard optimal control to so-called sparse optimal control that results in very localized control signals and allows the analysis of second order optimality conditions.Comment: 22 pages, 3 figures, 2 table

Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change

The North Atlantic Oscillation (NAO) obtained using instrumental and documentary proxy predictors from Eurasia is found to be characterized by a quasi 60-year dominant oscillation since 1650. This pattern emerges clearly once the NAO record is time integrated to stress its comparison with the temperature record. The integrated NAO (INAO) is found to well correlate with the length of the day (since 1650) and the global surface sea temperature record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can be used as a good proxy for global climate change, and that a 60-year cycle exists in the global climate since at least 1700. Finally, the INAO ~60-year oscillation well correlates with the ~60- year oscillations found in the historical European aurora record since 1700, which suggests that this 60-year dominant climatic cycle has a solar-astronomical origin

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Childhood adversity, mental ill-health and aggressive behavior in an African orphanage: Changes in response to trauma-focused therapy and the implementation of a new instructional system

<p>Abstract</p> <p>Background</p> <p>The number of orphans in Sub-Saharan Africa is constantly rising. While it is known that family or community care is preferable over institutional care of African orphans, little is known about the quality of care in orphanages and possibilities of improvement.</p> <p>Study 1</p> <p>Methods</p> <p>Exposure to traumatic stress, experiences of violence in the home, school and orphanage, as well as mental ill-health and aggression of 38 children (mean age of <it>M </it>= 8.64 years) living in an orphanage in rural Tanzania were assessed at two time points. The severity of post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and internalizing and externalizing problems were used as indicators of mental ill-health.</p> <p>Results</p> <p>Violence experienced in the orphanage correlated more strongly with all indicators of mental ill-health than violence in the former home, school or neighborhood at time point 1. Additionally, violence experienced in the orphanage had a positive relationship with the aggressive behavior of the children at time point 2.</p> <p>Study 2</p> <p>Methods</p> <p>With the help of the pre-post assessment of Study 1, the implementation of a new instructional system and psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.</p> <p>Results</p> <p>In response to both, a change in the instructional system and psychotherapeutic treatment of PTSD, a massive decline in experienced violence and in the severity of PTSD-symptoms was found, whereas depressive symptoms and internalizing and externalizing problems exhibited little change.</p> <p>Conclusions</p> <p>These studies show that violence, especially in the orphanage, can severely contribute to mental ill-health in orphans and that mental health can be improved by implementing a new instructional system and psychotherapeutic treatment in an orphanage. Moreover, the results indicate that the experience of violence in an orphanage also plays a crucial role in aggressive behavior of the orphans.</p

Multimodality Imaging of Abnormal Vascular Perfusion and Morphology in Preclinical 9L Gliosarcoma Model

This study demonstrates that a dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) perfusion parameter may indicate vascular abnormality in a brain tumor model and reflects an effect of dexamethasone treatment. In addition, X-ray computed tomography (CT) measurements of vascular tortuosity and tissue markers of vascular morphology were performed to investigate the underpinnings of tumor response to dexamethasone.One cohort of Fisher 344 rats (N = 13), inoculated intracerebrally with 9L gliosarcoma cells, was treated with dexamethasone (i.p. 3 mg/kg/day) for five consecutive days, and another cohort (N = 11) was treated with equal volume of saline. Longitudinal DSC-MRI studies were performed at the first (baseline), third and fifth day of treatments. Relative cerebral blood volume (rCBV) was significantly reduced on the third day of dexamethasone treatment (0.65 ± .13) as compared to the fifth day during treatment (1.26 ±.19, p < 0.05). In saline treated rats, relative CBV gradually increased during treatment (0.89 ±.13, 1.00 ± .21, 1.13 ± .23) with no significant difference on the third day of treatment (p>0.05). In separate serial studies, microfocal X-ray CT of ex vivo brain specimens (N = 9) and immunohistochemistry for endothelial cell marker anti-CD31 (N = 8) were performed. Vascular morphology of ex vivo rat brains from micro-CT analysis showed hypervascular characteristics in tumors, and both vessel density (41.32 ± 2.34 branches/mm(3), p<0.001) and vessel tortuosity (p<0.05) were significantly reduced in tumors of rats treated with dexamethasone compared to saline (74.29 ± 3.51 branches/mm(3)). The vascular architecture of rat brain tissue was examined with anti-CD31 antibody, and dexamethasone treated tumor regions showed reduced vessel area (16.45 ± 1.36 µm(2)) as compared to saline treated tumor regions (30.83 ± 4.31 µm(2), p<0.001) and non-tumor regions (22.80 ± 1.11 µm(2), p<0.01).Increased vascular density and tortuosity are culprit to abnormal perfusion, which is transiently reduced during dexamethasone treatment

Establishing an implementation network: lessons learned from community-based participatory research

<p>Abstract</p> <p>Background</p> <p>Implementation of evidence-based mental health assessment and intervention in community public health practice is a high priority for multiple stakeholders. Academic-community partnerships can assist in the implementation of efficacious treatments in community settings; yet, little is known about the processes by which these collaborations are developed. In this paper, we discuss our application of community-based participatory research (CBPR) approach to implementation, and we present six lessons we have learned from the establishment of an academic-community partnership.</p> <p>Methods</p> <p>With older adults with psychosis as a focus, we have developed a partnership between a university research center and a public mental health service system based on CBPR. The long-term goal of the partnership is to collaboratively establish an evidence-based implementation network that is sustainable within the public mental healthcare system.</p> <p>Results</p> <p>In building a sustainable partnership, we found that the following lessons were instrumental: changing attitudes; sharing staff; expecting obstacles and formalizing solutions; monitoring and evaluating; adapting and adjusting; and taking advantage of emerging opportunities. Some of these lessons were previously known principles that were modified as the result of the CBPR process, while some lessons derived directly from the interactive process of forming the partnership.</p> <p>Conclusion</p> <p>The process of forming of academic-public partnerships is challenging and time consuming, yet crucial for the development and implementation of state-of-the-art approaches to assessment and interventions to improve the functioning and quality of life for persons with serious mental illnesses. These partnerships provide necessary organizational support to facilitate the implementation of clinical research findings in community practice benefiting consumers, researchers, and providers.</p

A cluster-randomised, controlled trial to assess the impact of a workplace osteoporosis prevention intervention on the dietary and physical activity behaviours of working women: study protocol

Background Osteoporosis is a debilitating disease and its risk can be reduced through adequate calcium consumption and physical activity. This protocol paper describes a workplace-based intervention targeting behaviour change in premenopausal women working in sedentary occupations. Method/Design A cluster-randomised design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the clusters and units of randomisation and intervention. Sample size calculations incorporated the cluster design. Final number of clusters was determined to be 16, based on a cluster size of 20 and calcium intake parameters (effect size 250 mg, ICC 0.5 and standard deviation 290 mg) as it required the highest number of clusters. Sixteen workplaces were recruited from a pool of 97 workplaces and randomly assigned to intervention and control arms (eight in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organisation wide educational activities. Workplaces in the control/standard care arm received print resources. Intervention workshops were guided by self-efficacy theory and included participatory activities such as goal setting, problem solving, local food sampling, exercise trials, group discussion and behaviour feedback. Outcomes measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, four weeks and six months post intervention. Discussion This study addresses the current lack of evidence for behaviour change interventions focussing on osteoporosis prevention. It addresses missed opportunities of using workplaces as a platform to target high-risk individuals with sedentary occupations. The intervention was designed to modify behaviour levels to bring about risk reduction. It is the first to address dietary and physical activity components each with unique intervention strategies in the context of osteoporosis prevention. The intervention used locally relevant behavioural strategies previously shown to support good outcomes in other countries. The combination of these elements have not been incorporated in similar studies in the past, supporting the study hypothesis that the intervention will be more efficacious than standard practice in osteoporosis prevention through improvements in calcium intake and physical activity

Computer Simulation of Cellular Patterning Within the Drosophila Pupal Eye

We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD) as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier–Graner–Hogeweg model (GGH) for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo