Genome-Wide Tissue-Specific Occupancy of the Hox Protein Ultrabithorax and Hox Cofactor Homothorax in Drosophila

The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Climate change, precipitation and impacts on an estuarine refuge from disease

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e18849, doi:10.1371/journal.pone.0018849.Oysters play important roles in estuarine ecosystems but have suffered recently due to overfishing, pollution, and habitat loss. A tradeoff between growth rate and disease prevalence as a function of salinity makes the estuarine salinity transition of special concern for oyster survival and restoration. Estuarine salinity varies with discharge, so increases or decreases in precipitation with climate change may shift regions of low salinity and disease refuge away from optimal oyster bottom habitat, negatively impacting reproduction and survival. Temperature is an additional factor for oyster survival, and recent temperature increases have increased vulnerability to disease in higher salinity regions. We examined growth, reproduction, and survival of oysters in the New York Harbor-Hudson River region, focusing on a low-salinity refuge in the estuary. Observations were during two years when rainfall was above average and comparable to projected future increases in precipitation in the region and a past period of about 15 years with high precipitation. We found a clear tradeoff between oyster growth and vulnerability to disease. Oysters survived well when exposed to intermediate salinities during two summers (2008, 2010) with moderate discharge conditions. However, increased precipitation and discharge in 2009 reduced salinities in the region with suitable benthic habitat, greatly increasing oyster mortality. To evaluate the estuarine conditions over longer periods, we applied a numerical model of the Hudson to simulate salinities over the past century. Model results suggest that much of the region with suitable benthic habitat that historically had been a low salinity refuge region may be vulnerable to higher mortality under projected increases in precipitation and discharge. Predicted increases in precipitation in the northeastern United States due to climate change may lower salinities past important thresholds for oyster survival in estuarine regions with appropriate substrate, potentially disrupting metapopulation dynamics and impeding oyster restoration efforts, especially in the Hudson estuary where a large basin constitutes an excellent refuge from disease.Funding was provided by the Hudson River Foundation, grant number 00607A, and the New York State Department of Environmental Conservation (MOU 2008)

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

Sex- and age-specific trends in mortality from suicide and undetermined death in Germany 1991–2002

BACKGROUND: Over the last decade, significant downward linear time trends in suicide mortality were observed in most Western countries. To date, it is not established whether those favourable time trends developed homogeneously for sex and age groups and how they were affected by the number of undetermined deaths. METHODS: Data on suicide mortality and undetermined death from 1991 to 2002 in Germany were obtained from the German Federal Statistical Office. For each year, the age-standardised suicide rate (SR), undetermined death rate (UDR) and total rate (SR+UDR) was calculated by direct standardisation separately for men and women. Time trends were analyzed by Poisson regression estimating the average annual percentage change (AAPC) of the rates for sex and four age groups (15–24, 25–44, 45–74, ≥ 75 years). RESULTS: A significant decline of the SR was observed in all age groups but was less pronounced among the younger ages, particularly among men aged 15–24 years (AAPC -0.7%, p = 0.041). The SR in the oldest male age group (≥ 75 years) declined much stronger (AAPC -3.5%, p < 0.001). In women, the AAPC of the SR ranged from -1.7% to -4.6%. The average annual percentage changes in the age groups 25 – 74 years did not differ substantially for SR and SR+UDR. In contrast, due to an increase of undetermined deaths for subjects ≥ 75 years, time trends in this age group were affected by the number of undetermined deaths, especially in women. CONCLUSION: Observing downward trends in suicide mortality with lower declines for younger subjects, prevention strategies should focus in particular on younger subjects

A hybrid approach to protein folding problem integrating constraint programming with local search

<p>Abstract</p> <p>Background</p> <p>The protein folding problem remains one of the most challenging open problems in computational biology. Simplified models in terms of lattice structure and energy function have been proposed to ease the computational hardness of this optimization problem. Heuristic search algorithms and constraint programming are two common techniques to approach this problem. The present study introduces a novel hybrid approach to simulate the protein folding problem using constraint programming technique integrated within local search.</p> <p>Results</p> <p>Using the face-centered-cubic lattice model and 20 amino acid pairwise interactions energy function for the protein folding problem, a constraint programming technique has been applied to generate the neighbourhood conformations that are to be used in generic local search procedure. Experiments have been conducted for a few small and medium sized proteins. Results have been compared with both pure constraint programming approach and local search using well-established local move set. Substantial improvements have been observed in terms of final energy values within acceptable runtime using the hybrid approach.</p> <p>Conclusion</p> <p>Constraint programming approaches usually provide optimal results but become slow as the problem size grows. Local search approaches are usually faster but do not guarantee optimal solutions and tend to stuck in local minima. The encouraging results obtained on the small proteins show that these two approaches can be combined efficiently to obtain better quality solutions within acceptable time. It also encourages future researchers on adopting hybrid techniques to solve other hard optimization problems.</p

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae. Modifications to an in vitro chromatin assembly assay are described that allowed a brute force screen of temperature sensitive (ts) yeast strains in order to identify chromatin assembly defective extracts. This screen yielded mutations in genes encoding two ubiquitin protein ligases (E3s): RSP5, and a subunit of the Anaphase Promoting Complex (APC), APC5. Additional modifications are described that allow for a rapid analysis and an in vivo characterization of yeast chromatin assembly mutants, as well as any other mutant of interest. Our analysis suggests that the in vitro and in vivo chromatin assembly assays are responsive to different cellular signals, including cell cycle cues that involve different molecular networks

On the dynamics of a nonlinear energy harvester with multiple resonant zones

The dynamics of a nonlinear vibration energy harvester for rotating systems is investigated analytically through harmonic balance, as well as by numerical analysis. The electromagnetic harvester is attached to a spinning shaft at constant speed. Magnetic levitation is used as the system nonlinear restoring force for broadening the resonant range of the oscillator. The system is modelled as a Duffing oscillator with linear frequency variation under static, as well as harmonic excitation. Behaviour charts and backbone curves are extracted for the fundamental harmonic response and validated against frequency response curves for selected cases, using direct numerical integration. It is found that variation in stiffness, together with asymmetric forcing, gives rise to a novel structure of multiple resonant zones, incorporating mono-stable and bi-stable dynamics. Contrary to previously considered bi-stable energy harvesters, cross-well oscillations are realized through a transition from single-well potential energy to double-well with forward frequency sweep. Furthermore, in-well_oscillations present a hardening behaviour, unlike the well-known softening in-well response of bi-stable Duffing oscillators. The analysis shows that the proposed system has multiple resonant responses to a frequency sweep, influenced by consecutive interacting backbone curves similar to a multi-modal system. This combined effect of the transition to bi-stable dynamics and the hardening in-well oscillations induces resonant response of the harvester over multiple distinct frequency ranges. Thus, the system exhibits a broadened frequency response, enhancing its energy harvesting potential

Should methodological filters for diagnostic test accuracy studies be used in systematic reviews of psychometric instruments? a case study involving screening for postnatal depression

<p>Abstract</p> <p>Background</p> <p>Challenges exist when searching for diagnostic test accuracy (DTA) studies that include the design of DTA search strategies and selection of appropriate filters. This paper compares the performance of three MEDLINE search strategies for psychometric diagnostic test accuracy (DTA) studies in postnatal depression.</p> <p>Methods</p> <p>A reference set of six relevant studies was derived from a forward citation search via Web of Knowledge. The performance of the 'target condition and index test' method recommended by the Cochrane DTA Group was compared to two alternative strategies which included methodological filters. Outcome measures were total citations retrieved, sensitivity, precision and associated 95% confidence intervals (95%CI).</p> <p>Results</p> <p>The Cochrane recommended strategy and one of the filtered search strategies were equivalent in performance and both retrieved a total of 105 citations, sensitivity was 100% (95% CI 61%, 100%) and precision was 5.2% (2.6%, 11.9%). The second filtered search retrieved a total of 31 citations, sensitivity was 66.6% (30%, 90%) and precision was 12.9% (5.1%, 28.6%). This search missed the DTA study with most relevance to the DTA review.</p> <p>Conclusions</p> <p>The Cochrane recommended search strategy, 'target condition and index test', method was pragmatic and sensitive. It was considered the optimum method for retrieval of relevant studies for a psychometric DTA review (in this case for postnatal depression). Potential limitations of using filtered searches during a psychometric mental health DTA review should be considered.</p