Surface embedding, topology and dualization for spin networks

Spin networks are graphs derived from 3nj symbols of angular momentum. The surface embedding, the topology and dualization of these networks are considered. Embeddings into compact surfaces include the orientable sphere S^2 and the torus T, and the not orientable projective space P^2 and Klein's bottle K. Two families of 3nj graphs admit embeddings of minimal genus into S^2 and P^2. Their dual 2-skeletons are shown to be triangulations of these surfaces.Comment: LaTeX 17 pages, 6 eps figures (late submission to arxiv.org

More than just an eagle killer: The freshwater cyanobacterium Aetokthonos hydrillicola produces highly toxic dolastatin derivatives

Cyanobacteria are infamous producers of toxins. While the toxic potential of planktonic cyanobacterial blooms is well documented, the ecosystem level effects of toxigenic benthic and epiphytic cyanobacteria are an understudied threat. The freshwater epiphytic cyanobacterium Aetokthonos hydrillicola has recently been shown to produce the “eagle killer” neurotoxin aetokthonotoxin (AETX) causing the fatal neurological disease vacuolar myelinopathy. The disease affects a wide array of wildlife in the southeastern United States, most notably waterfowl and birds of prey, including the bald eagle. In an assay for cytotoxicity, we found the crude extract of the cyanobacterium to be much more potent than pure AETX, prompting further investigation. Here, we describe the isolation and structure elucidation of the aetokthonostatins (AESTs), linear peptides belonging to the dolastatin compound family, featuring a unique modification of the C-terminal phenylalanine-derived moiety. Using immunofluorescence microscopy and molecular modeling, we confirmed that AEST potently impacts microtubule dynamics and can bind to tubulin in a similar matter as dolastatin 10. We also show that AEST inhibits reproduction of the nematode Caenorhabditis elegans. Bioinformatic analysis revealed the AEST biosynthetic gene cluster encoding a nonribosomal peptide synthetase/polyketide synthase accompanied by a unique tailoring machinery. The biosynthetic activity of a specific N-terminal methyltransferase was confirmed by in vitro biochemical studies, establishing a mechanistic link between the gene cluster and its product

Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

Nedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy

Describing current use, barriers, and facilitators of patient portal messaging for research recruitment: Perspectives from study teams and patients at one institution

Abstract Introduction: The electronic health record (EHR) and patient portal are used increasingly for clinical research, including patient portal recruitment messaging (PPRM). Use of PPRM has grown rapidly; however, best practices are still developing. In this study, we examined the use of PPRM at our institution and conducted qualitative interviews among study teams and patients to understand experiences and preferences for PPRM. Methods: We identified study teams that sent PPRMs and patients that received PPRMs in a 60-day period. We characterized these studies and patients, in addition to the patients’ interactions with the PPRMs (e.g., viewed, responded). From these groups, we recruited study team members and patients for semi-structured interviews. A pragmatic qualitative inquiry framework was used by interviewers. Interviews were audio-recorded and analyzed using a rapid qualitative analysis exploratory approach. Results: Across ten studies, 35,037 PPRMs were sent, 33% were viewed, and 17% were responded to. Interaction rates varied across demographic groups. Six study team members completed interviews and described PPRM as an efficient and helpful recruitment method. Twenty-eight patients completed interviews. They were supportive of receiving PPRMs, particularly when the PPRM was relevant to their health. Patients indicated that providing more information in the PPRM would be helpful, in addition to options to set personalized preferences. Conclusions: PPRM is an efficient recruitment method for study teams and is acceptable to patients. Engagement with PPRMs varies across demographic groups, which should be considered during recruitment planning. Additional research is needed to evaluate and implement recommended changes by study teams and patients

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Life and death in the Chicxulub impact crater: A record of the Paleocene-Eocene Thermal Maximum

Thermal stress on the biosphere during the extreme warmth of the Paleocene-Eocene Thermal Maximum (PETM) was most severe at low latitudes, with sea surface temperatures at some localities exceeding the 35 C at which marine organisms experience heat stress. Relatively few equivalent terrestrial sections have been identified, and the response of land plants to this extreme heat is still poorly understood. Here, we present a new record of the PETM from the peak ring of the Chicxulub impact crater that has been identified based on nannofossil biostratigraphy, an acme of the dinoflagellate genus Apectodinium, and a negative carbon isotope excursion. Geochemical and microfossil proxies show that the PETM is marked by elevated TEXH 86-based sea surface temperatures (SSTs) averaging 37:8 C, an in- crease in terrestrial input and surface productivity, salinity stratification, and bottom water anoxia, with biomarkers for green and purple sulfur bacteria indicative of photic zone euxinia in the early part of the event. Pollen and plants spores in this core provide the first PETM floral assemblage described from Mexico, Central America, and the northern Caribbean. The source area was a diverse coastal shrubby tropical forest with a remarkably high abundance of fungal spores, indicating humid conditions. Thus, while seafloor anoxia devastated the benthic marine biota and dinoflagellate assemblages were heat-stressed, the terrestrial plant ecosystem thrived

A common polymorphism of the human cardiac sodium channel alpha subunit (SCN5A) gene is associated with sudden cardiac death in chronic ischemic heart disease

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio =1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. © 2015 Marcsa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

An interlaboratory study of TEX86 and BIT analysis of sediments, extracts and standard mixtures.

Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility ±3-4°C when translated to temperature) but a large spread in BIT measurements (reproducibility ±0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0°C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the "true" (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values