The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex

The MAGE (Melanoma-associated antigen) protein family members are structurally related to each other by a MAGEhomology domain comprised of 2 winged helix motifs WH/A and WH/B. This family specifically evolved in placental mammals although single homologs designated NSE3 (non-SMC element) exist in most eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight subcomplex of the structural maintenance of chromosomes SMC5–6 complex. Previously, we showed that interactions of the WH/B motif of the MAGE proteins with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1-NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs acquired new RING-finger containing partners through their evolution and form MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed the yeast 2-hybrid system to screen a human RING-finger protein library against several MAGE baits. We identified a number of potential MAGE-RING interactions and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41) in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co-factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may have evolved from an ancestral NSE1-NSE3-NSE4 complex

Binomial Sampling of Western Flower Thrips Infesting Flowering Greenhouse Crops Using Incidence-Mean Models

Accurate assessments of thrips density are important for effective thrips management programs. Complicating the development of sampling plans for western flower thrips (WFT) Frankliniella occidentalis (Pergande) in greenhouse crops are the facts that they are small, difficult to detect, and attack a variety of crops, which may be grown concurrently within the same greenhouse. Binomial sampling was evaluated as an alternative to sampling plans based on complete enumeration. This work included comparison of incidence-mean models across diverse plant species (impatiens, cucumber, and marigold) to determine the possibility of using a generic model for sampling WFT in mixed crops. Data from laboratory-processed flower samples revealed that infestation rates calculated using a tally threshold of three thrips per flower provided the best estimates of thrips population densities in each tested crop and in the combined crops (composite data set). Distributions of thrips populations were similar across the three plant species, indicating potential for development of a generic sampling plan for mixed floral crops. Practical sampling methods for simple and complex flowers tested in the greenhouse (in situ) were evaluated via construction of binomial count operating characteristic functions. In the case of simple flowers (impatiens), visual inspections provided adequate estimates of thrips infestation rates at a low tally threshold, which ultimately enabled accurate estimation of thrips densities. However, visual inspection and tap-sampling of complex flowers (marigold) provided unreliable results. These findings indicate that use of binomial sampling methods in mixed floral crops will require development of more accurate sampling technique

Early detection of acute myocardial infarction with the new marker Fatty Acid-Binding Protein : rapid testing and diagnostic value

There are several requirements for the early detection of AMI with biochemical markers: The biochemical marker should be: - Specific - Sensitive - Fast elevated after the clinical onset of the symptoms. The test should be: - Easy to perform - Give a fast result - Preferably bedside - Inexpensive Here, we demonstrate the biochemical characteristics of heart-type Fatty Acid-Binding Protein (FABP) in AMI and UAP patients. Also, we show some preliminary data on a new in-house made quantitative rapid test with simple test procedures. - Patients: 50 patients of the CCU of PWH are included in the study diagnosed with UAP or AMI. Eight blood samples per patient were taken at 0-72 hours after admission and analyzed with a laboratory ELISA test. - Rapid test procedure: 80 ml plasma or serum is added on the sample pad. Within 5 minutes, the strip can be read out with an optical reader (the PART from LRE, Munich, Germany). A release curve for AMI patients shows a significantly elevated FABP concentration already 1 hour after infarction, whereas for CPK, this is found after 3 hours. Comparing the ROC curve for patients arriving at the hospital and 1 hour later for FABP and CPK demonstrates the preference of FABP over CPK. The preliminary results of the rapid test show for selected plasma and serum samples a measuring range of 0-200 ng/ml FABP. The availability of a rapid bedside test for FABP enables faster diagnosis in patients with no clear ECG. This can be used for both inclusion or exclusion of AMI

A deep Chandra observation of the poor cluster AWM 4 - I. Properties of the central radio galaxy and its effects on the intracluster medium

Using observations from the Chandra X-ray Observatory and Giant Metrewave Radio Telescope, we examine the interaction between the intracluster medium and central radio source in the poor cluster AWM 4. In the Chandra observation a small cool core or galactic corona is resolved coincident with the radio core. This corona is capable of fuelling the active nucleus, but must be inefficiently heated by jet interactions or conduction, possibly precluding a feedback relationship between the radio source and cluster. A lack of clearly detected X-ray cavities suggests that the radio lobes are only partially filled by relativistic plasma. We estimate a filling factor of phi=0.21 (3 sigma upper limit phi<0.42) for the better constrained east lobe. We consider the particle population in the jets and lobes, and find that the standard equipartition assumptions predict pressures and ages which agree poorly with X-ray estimates. Including an electron population extending to low Lorentz factors either reduces (gamma_min=100) or removes (gamma_min=10) the pressure imbalance between the lobes and their environment. Pressure balance can also be achieved by entrainment of thermal gas, probably in the first few kiloparsecs of the radio jets. We estimate the mechanical power output of the radio galaxy, and find it to be marginally capable of balancing radiative cooling.Comment: Accepted for publication in MNRAS, 18 pages, 9 postscript figures

Impact of Polychlorinated Biphenyls Contamination on Estrogenic Activity in Human Male Serum

Polychlorinated biphenyls (PCBs) are thought to cause numerous adverse health effects, but their impact on estrogen signaling is still not fully understood. In the present study, we used the ER-CALUX bioassay to determine estrogenic/antiestrogenic activities of the prevalent PCB congeners and PCB mixtures isolated from human male serum. The samples were collected from residents of an area with an extensive environmental contamination from a former PCB production site as well as from a neighboring background region in eastern Slovakia. We found that the lower-chlorinated PCBs were estrogenic, whereas the prevalent higher-chlorinated PCB congeners 138, 153, 170, 180, 187, 194, 199, and 203, as well as major PCB metabolites, behaved as anti-estrogens. Coplanar PCBs had no direct effect on estrogen receptor (ER) activation in this in vitro model. In human male serum samples, high levels of PCBs were associated with a decreased ER-mediated activity and an increased dioxin-like activity, as determined by the DR-CALUX assay. 17β-Estradiol (E(2)) was responsible for a major part of estrogenic activity identified in total serum extracts. Significant negative correlations were found between dioxin-like activity, as well as mRNA levels of cytochromes P450 1A1 and 1B1 in lymphocytes, and total estrogenic activity. For sample fractions containing only persistent organic pollutants (POPs), the increased frequency of anti-estrogenic samples was associated with a higher sum of PCBs. This suggests that the prevalent non-dioxin-like PCBs were responsible for the weak antiestrogenic activity of some POPs fractions. Our data also suggest that it might be important to pay attention to direct effects of PCBs on steroid hormone levels in heavily exposed subjects

Object-Oriented Echo Perception and Cortical Representation in Echolocating Bats

Echolocating bats can identify three-dimensional objects exclusively through the analysis of acoustic echoes of their ultrasonic emissions. However, objects of the same structure can differ in size, and the auditory system must achieve a size-invariant, normalized object representation for reliable object recognition. This study describes both the behavioral classification and the cortical neural representation of echoes of complex virtual objects that vary in object size. In a phantom-target playback experiment, it is shown that the bat Phyllostomus discolor spontaneously classifies most scaled versions of objects according to trained standards. This psychophysical performance is reflected in the electrophysiological responses of a population of cortical units that showed an object-size invariant response (14/109 units, 13%). These units respond preferentially to echoes from objects in which echo duration (encoding object depth) and echo amplitude (encoding object surface area) co-varies in a meaningful manner. These results indicate that at the level of the bat's auditory cortex, an object-oriented rather than a stimulus-parameter–oriented representation of echoes is achieved

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Community Preferences for the Allocation &Donation of Organs - The PAraDOx Study

<p>Abstract</p> <p>Background</p> <p>Transplantation is the treatment of choice for people with severe organ failure. However, demand substantially exceeds supply of suitable organs; consequently many people wait months, or years to receive an organ. Reasons for the chronic shortage of deceased organ donations are unclear; there appears to be no lack of 'in principle' public support for organ donation.</p> <p>Methods/Design</p> <p>The PAraDOx Study examines community preferences for organ donation policy in Australia. The aims are to 1) determine which factors influence decisions by individuals to offer their organs for donation and 2) determine the criteria by which the community deems the allocation of donor organs to be fair and equitable. Qualitative and quantitative methods will be used to assess community preferences for organ donation and allocation.</p> <p>Focus group participants from the general community, aged between 18-80, will be purposively sampled to ensure a variety of cultural backgrounds and views on organ donation. Each focus group will include a ranking exercise using a modified nominal group technique. Focus groups of organ recipients, their families, and individuals on a transplant waiting list will also be conducted.</p> <p>Using the qualitative work, a discrete choice study will be designed to quantitatively assess community preferences. Discrete choice methods are based on the premise that goods and services can be described in terms of a number of separate attributes. Respondents are presented with a series of choices where levels of attributes are varied, and a mathematical function is estimated to describe numerically the value respondents attach to different options. Two community surveys will be conducted in approximately 1000 respondents each to assess community preferences for organ donation and allocation. A mixed logit model will be used; model results will be expressed as parameter estimates (β) and the odds of choosing one option over an alternative. Trade-offs between attributes will also be calculated.</p> <p>Discussion</p> <p>By providing a better understanding of current community preferences in relation to organ donation and allocation, the PAraDOx study will highlight options for firstly, increasing the rate of organ donation and secondly, allow for more transparent and equitable policies in relation to organ allocation.</p