167 research outputs found

    Subsurface Fish Handling to Limit Decompression Effects on Deepwater Species

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    A method of handling hooked fish at intermediate depth was developed for species which occur deeper than conventional scuba depths. Juvenile pink snappers, Pristipomoides filamentosus, were hauled from 65-100 m to a depth of only 30 m, where the ambient pressure change was a fraction of that produced by hauling fish to the sea surface. This method afforded a unique opportunity to acoustically tag deepwater, physoclistous fish without the need to alter the fish's original swim bladder volume and without the high risk of further injury associated with surface handling. Tagged P. filamentosus survived and behaved well and were tracked successfully. This basic method could be applied to a variety of deepwater species in a number of research approaches, including tagging and dietary studies

    Modeling Vortex Swarming In Daphnia

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    Based on experimental observations in \textit{Daphnia}, we introduce an agent-based model for the motion of single and swarms of animals. Each agent is described by a stochastic equation that also considers the conditions for active biological motion. An environmental potential further reflects local conditions for \textit{Daphnia}, such as attraction to light sources. This model is sufficient to describe the observed cycling behavior of single \textit{Daphnia}. To simulate vortex swarming of many \textit{Daphnia}, i.e. the collective rotation of the swarm in one direction, we extend the model by considering avoidance of collisions. Two different ansatzes to model such a behavior are developed and compared. By means of computer simulations of a multi-agent system we show that local avoidance - as a special form of asymmetric repulsion between animals - leads to the emergence of a vortex swarm. The transition from uncorrelated rotation of single agents to the vortex swarming as a function of the swarm size is investigated. Eventually, some evidence of avoidance behavior in \textit{Daphnia} is provided by comparing experimental and simulation results for two animals.Comment: 24 pages including 11 multi-part figs. Major revisions compared to version 1, new results on transition from uncorrelated rotation to vortex swarming. Extended discussion. For related publications see http://www.sg.ethz.ch/people/scfrank/Publication

    Prediction of mesophotic coral distributions in the Auβ€˜au Channel, Hawaii

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    The primary objective of this study was to predict the distribution of mesophotic hard corals in the Auβ€˜au Channel in the Main Hawaiian Islands (MHI). Mesophotic hard corals are light-dependent corals adapted to the low light conditions at approximately 30 to 150 m in depth. Several physical factors potentially influence their spatial distribution, including aragonite saturation, alkalinity, pH, currents, water temperature, hard substrate availability and the availability of light at depth. Mesophotic corals and mesophotic coral ecosystems (MCEs) have increasingly been the subject of scientific study because they are being threatened by a growing number of anthropogenic stressors. They are the focus of this spatial modeling effort because the Hawaiian Islands Humpback Whale National Marine Sanctuary (HIHWNMS) is exploring the expansion of its scopeβ€”beyond the protection of the North Pacific Humpback Whale (Megaptera novaeangliae)β€”to include the conservation and management of these ecosystem components. The present study helps to address this need by examining the distribution of mesophotic corals in the Auβ€˜au Channel region. This area is located between the islands of Maui, Lanai, Molokai and Kahoolawe, and includes parts of the Kealaikahiki, Alalākeiki and Kalohi Channels. It is unique, not only in terms of its geology, but also in terms of its physical oceanography and local weather patterns. Several physical conditions make it an ideal place for mesophotic hard corals, including consistently good water quality and clarity because it is flushed by tidal currents semi-diurnally; it has low amounts of rainfall and sediment run-off from the nearby land; and it is largely protected from seasonally strong wind and wave energy. Combined, these oceanographic and weather conditions create patches of comparatively warm, calm, clear waters that remain relatively stable through time. Freely available Maximum Entropy modeling software (MaxEnt 3.3.3e) was used to create four separate maps of predicted habitat suitability for: (1) all mesophotic hard corals combined, (2) Leptoseris, (3) Montipora and (4) Porites genera. MaxEnt works by analyzing the distribution of environmental variables where species are present, so it can find other areas that meet all of the same environmental constraints. Several steps (Figure 0.1) were required to produce and validate four ensemble predictive models (i.e., models with 10 replicates each). Approximately 2,000 georeferenced records containing information about mesophotic coral occurrence and 34 environmental predictors describing the seafloor’s depth, vertical structure, available light, surface temperature, currents and distance from shoreline at three spatial scales were used to train MaxEnt. Fifty percent of the 1,989 records were randomly chosen and set aside to assess each model replicate’s performance using Receiver Operating Characteristic (ROC), Area Under the Curve (AUC) values. An additional 1,646 records were also randomly chosen and set aside to independently assess the predictive accuracy of the four ensemble models. Suitability thresholds for these models (denoting where corals were predicted to be present/absent) were chosen by finding where the maximum number of correctly predicted presence and absence records intersected on each ROC curve. Permutation importance and jackknife analysis were used to quantify the contribution of each environmental variable to the four ensemble models

    FRA2A is a CGG repeat expansion associated with silencing of AFF3

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    Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship

    Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study

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    Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics

    Hyperpolarization-activated and cyclic nucleotide-gated channels are differentially expressed in juxtaglomerular cells in the olfactory bulb of mice

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    In the olfactory bulb, input from olfactory receptor neurons is processed by neuronal networks before it is relayed to higher brain regions. In many neurons, hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels generate and control oscillations of the membrane potential. Oscillations also appear crucial for information processing in the olfactory bulb. Four channel isoforms exist (HCN1–HCN4) that can form homo- or heteromers. Here, we describe the expression pattern of HCN isoforms in the olfactory bulb of mice by using a novel and comprehensive set of antibodies against all four isoforms. HCN isoforms are abundantly expressed in the olfactory bulb. HCN channels can be detected in most cell populations identified by commonly used marker antibodies. The combination of staining with marker and HCN antibodies has revealed at least 17 different staining patterns in juxtaglomerular cells. Furthermore, HCN isoforms give rise to an unexpected wealth of co-expression patterns but are rarely expressed in the same combination and at the same level in two given cell populations. Therefore, heteromeric HCN channels may exist in several cell populations in vivo. Our results suggest that HCN channels play an important role in olfactory information processing. The staining patterns are consistent with the possibility that both homomeric and heteromeric HCN channels are involved in oscillations of the membrane potential of juxtaglomerular cells

    Identification of a PA-Binding Peptide with Inhibitory Activity against Influenza A and B Virus Replication

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    There is an urgent need for new drugs against influenza type A and B viruses due to incomplete protection by vaccines and the emergence of resistance to current antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2 and PA subunits, represents a promising target for the development of new drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between the PB1 and PA subunits of the polymerase complex of influenza A virus using a small peptide derived from the PA-binding domain of PB1. However, this influenza A virus-derived peptide did not affect influenza B virus polymerase activity. Here we report that the PA-binding domain of the polymerase subunit PB1 of influenza A and B viruses is highly conserved and that mutual amino acid exchange shows that they cannot be functionally exchanged with each other. Based on phylogenetic analysis and a novel biochemical ELISA-based screening approach, we were able to identify an influenza A-derived peptide with a single influenza B-specific amino acid substitution which efficiently binds to PA of both virus types. This dual-binding peptide blocked the viral polymerase activity and growth of both virus types. Our findings provide proof of principle that protein-protein interaction inhibitors can be generated against influenza A and B viruses. Furthermore, this dual-binding peptide, combined with our novel screening method, is a promising platform to identify new antiviral lead compounds

    Peptide Array X-Linking (PAX): A New Peptide-Protein Identification Approach

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    Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Array-formatted bait peptides containing an amino acid-derived cross-linker are photo-induced to crosslink with interacting proteins from lysates of interest. Indirect associations are removed by high stringency washes under denaturing conditions. Covalently trapped proteins are subsequently identified by LC-MS/MS and screened by cluster analysis and domain scanning. We apply this methodology to peptides with different proline-containing consensus sequences and show successful identifications from brain lysates of known and novel proteins containing polyproline motif-binding domains such as EH, EVH1, SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to capture and subsequently identify proteins by mass spectrometry is relatively broad and robust. Additionally, the approach is rapid and applicable to cell or tissue fractions from any source, making the approach a flexible tool for initial protein-protein interaction discovery.National Institutes of Health (U.S.) (Grant R21-CA-140030-01

    Multishot versus Single-Shot Pulse Sequences in Very High Field fMRI: A Comparison Using Retinotopic Mapping

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    High-resolution functional MRI is a leading application for very high field (7 Tesla) human MR imaging. Though higher field strengths promise improvements in signal-to-noise ratios (SNR) and BOLD contrast relative to fMRI at 3 Tesla, these benefits may be partially offset by accompanying increases in geometric distortion and other off-resonance effects. Such effects may be especially pronounced with the single-shot EPI pulse sequences typically used for fMRI at standard field strengths. As an alternative, one might consider multishot pulse sequences, which may lead to somewhat lower temporal SNR than standard EPI, but which are also often substantially less susceptible to off-resonance effects. Here we consider retinotopic mapping of human visual cortex as a practical test case by which to compare examples of these sequence types for high-resolution fMRI at 7 Tesla. We performed polar angle retinotopic mapping at each of 3 isotropic resolutions (2.0, 1.7, and 1.1 mm) using both accelerated single-shot 2D EPI and accelerated multishot 3D gradient-echo pulse sequences. We found that single-shot EPI indeed led to greater temporal SNR and contrast-to-noise ratios (CNR) than the multishot sequences. However, additional distortion correction in postprocessing was required in order to fully realize these advantages, particularly at higher resolutions. The retinotopic maps produced by both sequence types were qualitatively comparable, and showed equivalent test/retest reliability. Thus, when surface-based analyses are planned, or in other circumstances where geometric distortion is of particular concern, multishot pulse sequences could provide a viable alternative to single-shot EPI
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