A Substantial Amount of Hidden Magnetic Energy in the Quiet Sun

Deciphering and understanding the small-scale magnetic activity of the quiet solar photosphere should help to solve many of the key problems of solar and stellar physics, such as the magnetic coupling to the outer atmosphere and the coronal heating. At present, we can see only ${\sim}1$ of the complex magnetism of the quiet Sun, which highlights the need to develop a reliable way to investigate the remaining 99%. Here we report three-dimensional radiative tranfer modelling of scattering polarization in atomic and molecular lines that indicates the presence of hidden, mixed-polarity fields on subresolution scales. Combining this modelling with recent observational data we find a ubiquitous tangled magnetic field with an average strength of ${\sim}130$ G, which is much stronger in the intergranular regions of solar surface convection than in the granular regions. So the average magnetic energy density in the quiet solar photosphere is at least two orders of magnitude greater than that derived from simplistic one-dimensional investigations, and sufficient to balance radiative energy losses from the solar chromosphere.Comment: 21 pages and 2 figures (letter published in Nature on July 15, 2004

Quality of life in patients with various Barrett's esophagus associated health states

BACKGROUND: The management of Barrett's esophagus (BE), particularly high grade dysplasia (HGD), is an area of much debate and controversy. Surgical esophagectomy, intensive endoscopic surveillance and mucosal ablative techniques, especially photodynamic therapy (PDT), have been proposed as possible management strategies. The purpose of this study was to determine the health related quality of life associated with Barrett's esophagus and many of the pivotal health states associated with Barrett's HGD management. METHODS: 20 patients with Barrett's esophagus were enrolled in a pilot survey study at a large urban hospital. The utility of Barrett's esophagus without dysplasia (current health state) as well as various health states associated with HGD management (hypothetical states as the subject did not have HGD) were measured using a validated health utility instrument (Paper Standard Gamble). These specific health states were chosen for the study because they are considered pivotal in Barrett's HGD decision making. Information regarding Barrett's HGD was presented to the subject in a standardized format that was designed to be easily comprehendible. RESULTS: The average utility scores (0–1 with 0 = death and 1 = perfect health) for the various Barrett's esophagus associated states were: BE without dysplasia-0.95; Post-esophagectomy for HGD with dysphagia-0.92; Post-PDT for HGD with recurrence uncertainty-0.93; Post-PDT for HGD with recurrence uncertainty and dysphagia-0.91; Intensive endoscopic surveillance for HGD-0.90. CONCLUSION: We present the scores for utilities associated with Barrett's esophagus as well as various states associated with the management of HGD. The results of our study may be useful in advising patients and providers regarding expected outcomes of the various HGD management strategies as well as providing utility scores for future cost-effectiveness analyses

Quantifying the Spatial Ecology of Wide-Ranging Marine Species in the Gulf of California: Implications for Marine Conservation Planning

There is growing interest in systematic establishment of marine protected area (MPA) networks and representative conservation sites. This movement toward networks of no-take zones requires that reserves are deliberately and adequately spaced for connectivity. Here, we test the network functionality of an ecoregional assessment configuration of marine conservation areas by evaluating the habitat protection and connectivity offered to wide-ranging fauna in the Gulf of California (GOC, Mexico). We first use expert opinion to identify representative species of wide-ranging fauna of the GOC. These include leopard grouper, hammerhead sharks, California brown pelicans and green sea turtles. Analyzing habitat models with both structural and functional connectivity indexes, our results indicate that the configuration includes large proportions of biologically important habitat for the four species considered (25–40%), particularly, the best quality habitats (46–57%). Our results also show that connectivity levels offered by the conservation area design for these four species may be similar to connectivity levels offered by the entire Gulf of California, thus indicating that connectivity offered by the areas may resemble natural connectivity. The selected focal species comprise different life histories among marine or marine-related vertebrates and are associated with those habitats holding the most biodiversity values (i.e. coastal habitats); our results thus suggest that the proposed configuration may function as a network for connectivity and may adequately represent the marine megafauna in the GOC, including the potential connectivity among habitat patches. This work highlights the range of approaches that can be used to quantify habitat protection and connectivity for wide-ranging marine species in marine reserve networks

Thresholds of riparian forest use by terrestrial mammals in a fragmented Amazonian deforestation frontier

Species persistence in fragmented landscapes is intimately related to the quality, structure, and context of remaining habitat remnants. Riparian vegetation is legally protected within private landholdings in Brazil, so we quantitatively assessed occupancy patterns of terrestrial mammals in these remnants, examining under which circumstances different species effectively use them. We selected 38 riparian forest patches and five comparable riparian sites within continuous forest, at which we installed four to five camera-traps per site (199 camera-trap stations). Terrestrial mammal assemblages were sampled for 60 days per station during the dry seasons of 2013 and 2014. We modelled species occupancy and detection probabilities within riparian forest remnants, and examined the effects of patch size, habitat quality, and landscape structure on occupancy probabilities. We then scaled-up modelled occupancies to all 1915 riparian patches throughout the study region to identify which remnants retain the greatest potential to work as habitat for terrestrial vertebrates. Of the ten species for which occupancy was modelled, six responded to forest quality (remnant degradation, cattle intrusion, palm aggregations, and understorey density) or structure (remnant width, isolation, length, and area of the patch from which it originates). Patch suitability was lower considering habitat quality than landscape structure, and virtually all riparian remnants were unsuitable to maintain a high occupancy probability for all species that responded to forest patch quality or structure. Beyond safeguarding legal compliance concerning riparian remnant amount, ensuring terrestrial vertebrate persistence in fragmented landscapes will require curbing the drivers of forest degradation within private landholdings

miRNAs in Newt Lens Regeneration: Specific Control of Proliferation and Evidence for miRNA Networking

Background: Lens regeneration in adult newts occurs via transdifferentiation of the pigment epithelial cells (PECs) of the dorsal iris. The same source of cells from the ventral iris is not able to undergo this process. In an attempt to understand this restriction we have studied in the past expression patterns of miRNAs. Among several miRNAs we have found that mir-148 shows an up-regulation in the ventral iris, while members of the let-7 family showed down-regulation in dorsal iris during dedifferentiation. Methodology/Principal Findings: We have performed gain- and loss-of–function experiments of mir-148 and let-7b in an attempt to delineate their function. We find that up-regulation of mir-148 caused significant decrease in the proliferation rates of ventral PECs only, while up-regulation of let-7b affected proliferation of both dorsal and ventral PECs. Neither miRNA was able to affect lens morphogenesis or induction. To further understand how this effect of miRNA up-regulation is mediated we examined global expression of miRNAs after up-regulation of mir148 and let-7b. Interestingly, we identified a novel level of mirRNA regulation, which might indicate that miRNAs are regulated as a network. Conclusion/Significance: The major conclusion is that different miRNAs can control proliferation in the dorsal or ventral iris possibly by a different mechanism. Of interest is that down-regulation of the let-7 family members has also been documented in other systems undergoing reprogramming, such as in stem cells or oocytes. This might indicate tha

Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties.Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection

Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis

BACKGROUND: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests – including polymerase chain reaction – have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis. METHODS: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses. RESULTS: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests. CONCLUSIONS: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear

Delimiting the Origin of a B Chromosome by FISH Mapping, Chromosome Painting and DNA Sequence Analysis in Astyanax paranae (Teleostei, Characiformes)

Supernumerary (B) chromosomes have been shown to contain a wide variety of repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH) is a useful tool for ascertaining the origin of these genomic elements, especially when combined with painting from microdissected B chromosomes. In order to investigate the origin of B chromosomes in the fish species Astyanax paranae, these two approaches were used along with PCR amplification of specific DNA sequences obtained from the B chromosomes and its comparison with those residing in the A chromosomes. Remarkably, chromosome painting with the one-arm metacentric B chromosome probe showed hybridization signals on entire B chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA genes symmetrically placed in both arms of the B chromosome. These results support the hypothesis that the B chromosome of A. paranae is an isochromosome. Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The analysis of DNA sequence fragments of the histone and rRNA genes obtained from the microdissected B chromosomes showed high similarity with those obtained from 0B individuals, which supports the intraspecific origin of B chromosomes in A. paranae. Finally, the population hereby analysed showed a female-biased B chromosome presence suggesting that B chromosomes in this species could influence sex determinism.This research was funded by grants from the State of São Paulo Research Foundation (FAPESP) to DMZAS (2011/16825-3) and CO (2010/17009-2), grants from National Council for Research and Development (CNPq) to FF and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

An NF-κB and Slug Regulatory Loop Active in Early Vertebrate Mesoderm

BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease

Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer’s disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population