(2R,3aR,4S,7R,7aS,9R,10aR,11S,14R,14aS)-rel-3a,4,7,7a,10a,11,14,14aOctahydro-4,14:7,11-diepoxy-2,9propanonaphtho[1,2-f:5,6-f000]diisoindole1,3,8,10-tetrone (9CI): a cyclophane derived from naphtho[1,2-c:5,6-c]difuran

Sherpa Romeo green journal. Open access article. Creative Commons Attribution License (CC BY) applies.The title compound, C25H18N2O6, is a naphthalenophane styled in the manner of Warrener's alicyclic cyclo­phanes or mol­ecular racks wherein a trimethyl­ene tether is perfectly staggered between the two N atoms such that the central methyl­ene H atoms point toward the naphthalene [pi]-system. The dihedral angle between the mean planes of the two benzene rings is 7.61 (7)°.Ye

Novel bis(isobenzofuran)s and their utility in the synthesis of cyclophanes

x, 122 leaves : ill. ; 28 cm.The synthesis of 1,2-bis(5-isobenzofuranyl)ethene by two routes is described. The first route involved generation of 1,2-bis(5-isobenzofuranyl)ethene from a bis(acetal) precursor under basic conditions. However, the synthesis was lengthy with low-yielding steps, which led to it being abandoned. The second route involved generation of 1,2-bis(5-isobenzofuranyl)ethene from a bis(oxabicyclic) precursor with 3,6-di(2'-pyridyl)-s-tetrazine. Napththo[1,2-c:5,6-c] difuran and 1,2-bis(5isobenzofuranyl)ethene were used to construct novel cyclophanes by double Diels-Alder reactions with bis(maleimide)s. NMR, AM1 modeling, and X-ray studies of the cyclophanes are discused. Attempts to prepare phenanthro[2,3-c:6,7-c] difuran and its cyclophanes are discussed. None was successful, and investigations were hampered by the inability to obtain sufficient quantities of starting materials. Finally, several suggestions are given for improving the syntheses of 1,2-bis(5- isobenzofuranyl)ethene, phenanthro[2,3-c:6,7-c]difuran, and their cyclophanes. Future directions, such as the functionalization of the double bond of 1,2-bis(5-isobenzofuranyl)ethene, aromatization of the oxabicyclic rings of the cyclophanes, and further X-ray studies are discussed

Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma

Protein families encoded by transcripts that are differentially spliced in various types of HCC. Table S2. Bioinformatical prediction of functional changes caused by some of ASEs identified. Table S3. List of tumor suppressors for which AS is dysregulated in various types of HCC. Table S4. List of oncogenes for which AS is dysregulated in various types of HCC. Table S5. List of kinases for which AS is dysregulated in various types of HCC. Table S6. List of transcription factors for which AS is dysregulated in various types of HCC. Table S7. List of genes for which AS is dysregulated in all types of HCC. Table S8. List of genes uniquely dysregulated in HBV-associated HCC. Table S9. List of genes uniquely dysregulated in HCV-associated HCC. Table S10. List of genes uniquely dysregulated in HBV&HCV-associated HCC. Table S11. List of genes uniquely dysregulated in virus-free HCC. Figure S1. Characterization of splicing mysregulation in HCC. Figure S2. Characterization of ASEs that are modified in HBV- and HCV-associated HCC. Figure S3. AS modifications in transcripts encoded by kinases and transcriptions factores in HBV- and HCV-associated HCC. Figure S4. Global profiling of ASE modifications in both HBV&HCV-associated HCC and virus-free-associated HCC. Figure S5. RNA splicing factors in HCC. Figure S6. Modifications to AS of 96 transcripts in response to knockdown of splicing factors with specific siRNAs (PDF 6675 kb

River ecosystem conceptual models and non‐perennial rivers: A critical review

Conceptual models underpin river ecosystem research. However, current models focus on continuously flowing rivers and few explicitly address characteristics such as flow cessation and drying. The applicability of existing conceptual models to nonperennial rivers that cease to flow (intermittent rivers and ephemeral streams, IRES) has not been evaluated. We reviewed 18 models, finding that they collectively describe main drivers of biogeochemical and ecological patterns and processes longitudinally (upstream-downstream), laterally (channel-riparian-floodplain), vertically (surface water-groundwater), and temporally across local and landscape scales. However, perennial rivers are longitudinally continuous while IRES are longitudinally discontinuous. Whereas perennial rivers have bidirectional lateral connections between aquatic and terrestrial ecosystems, in IRES, this connection is unidirectional for much of the time, from terrestrial-to-aquatic only. Vertical connectivity between surface and subsurface water occurs bidirectionally and is temporally consistent in perennial rivers. However, in IRES, this exchange is temporally variable, and can become unidirectional during drying or rewetting phases. Finally, drying adds another dimension of flow variation to be considered across temporal and spatial scales in IRES, much as flooding is considered as a temporally and spatially dynamic process in perennial rivers. Here, we focus on ways in which existing models could be modified to accommodate drying as a fundamental process that can alter these patterns and processes across spatial and temporal dimensions in streams. This perspective is needed to support river science and management in our era of rapid global change, including increasing duration, frequency, and occurrence of drying.info:eu-repo/semantics/publishedVersio

Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG) storage using quantitative complementation procedures in <it>Drosophila melanogaster</it>. Based on our results from <it>Drosophila</it>, we performed a human population-based association study to investigate the effect of natural variation in <it>LAMA5 </it>gene on body composition in humans.</p> <p>Results</p> <p>We identified four candidate genes that contributed to differences in TAG storage between two strains of <it>D. melanogaster</it>, including <it>Laminin A </it>(<it>LanA</it>), which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable <it>LanA </it>mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. <it>Drosophila LanA </it>is closely related to human <it>LAMA5 </it>gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs) in the human <it>LAMA5 </it>gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA) and African American (AA) descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: <it>P </it>= 0.008; AA: <it>P </it>= 0.05) and lean mass (EA: <it>P= </it>0.003; AA: <it>P </it>= 0.03). We also found this SNP to be associated with height (<it>P </it>= 0.01), total fat mass (<it>P </it>= 0.01), and HDL-cholesterol (<it>P </it>= 0.003) but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (<it>P </it>= 0.02) and HDL-cholesterol (<it>P </it>= 0.03) were observed in AA women.</p> <p>Conclusion</p> <p>Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.</p

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist)

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children