Using isotopes of dissolved inorganic carbon species and water to separate sources of recharge in a cave spring, northwestern Arkansas, USA Blowing Spring Cave

Blowing Spring Cave in northwestern Arkansas is representative of cave systems in the karst of the Ozark Plateaus, and stable isotopes of water (δ18O and δ2H) and inorganic carbon (δ13C) were used to quantify soil-water, bedrock-matrix water, and precipitation contributions to cave-spring flow during storm events to understand controls on cave water quality. Water samples from recharge-zone soils and the cave were collected from March to May 2012 to implement a multicomponent hydrograph separation approach using δ18O and δ2H of water and dissolved inorganic carbon (δ13C–DIC). During baseflow, median δ2H and δ18O compositions were –41.6‰ and –6.2‰ for soil water and were –37.2‰ and –5.9‰ for cave water, respectively. Median DIC concentrations for soil and cave waters were 1.8 mg/L and 25.0 mg/L, respectively, and median δ13C–DIC compositions were –19.9‰ and –14.3‰, respectively. During a March storm event, 12.2 cm of precipitation fell over 82 h and discharge increased from 0.01 to 0.59 m3/s. The isotopic composition of precipitation varied throughout the storm event because of rainout, a change of 50‰ and 10‰ for δ2H and δ18O was observed, respectively. Although, at the spring, δ2H and δ18O only changed by approximately 3‰ and 1‰, respectively. The isotopic compositions of precipitation and pre-event (i.e., soil and bedrock matrix) water were isotopically similar and the two-component hydrograph separation was inaccurate, either overestimating (>100%) or underestimating (<0%) the precipitation contribution to the spring. During the storm event, spring DIC and δ13C–DIC decreased to a minimum of 8.6 mg/L and –16.2‰, respectively. If the contribution from precipitation was assumed to be zero, soil water was found to contribute between 23 to 72% of the total volume of discharge. Although the assumption of negligible contributions from precipitation is unrealistic, especially in karst systems where rapid flow through conduits occurs, the hydrograph separation using inorganic carbon highlights the importance of considering vadose-zone soil water when analyzing storm chemohydrographs.Keywords: carbon, stable isotopes, cave, hydrograph, Arkansas.DOI: 10.3986/ac.v42i2-3.66

Reducing Equifinality Using Isotopes in a Process-Based Stream Nitrogen Model Highlights the Flux of Algal Nitrogen from Agricultural Streams

The fate of bioavailable nitrogen species transported through agricultural landscapes remains highly uncertain given complexities of measuring fluxes impacting the fluvial N cycle. We present and test a new numerical model named Technology for Removable Annual Nitrogen in Streams For Ecosystem Restoration (TRANSFER), which aims to reduce model uncertainty due to erroneous parameterization, i.e., equifinality, in stream nitrogen cycle assessment and quantify the significance of transient and permanent removal pathways. TRANSFER couples nitrogen elemental and stable isotope mass‐balance equations with existing hydrologic, hydraulic, sediment transport, algal biomass, and sediment organic matter mass‐balance subroutines and a robust GLUE‐like uncertainty analysis. We test the model in an agriculturally impacted, third‐order stream reach located in the Bluegrass Region of Central Kentucky. Results of the multiobjective model evaluation for the model application highlight the ability of sediment nitrogen fingerprints including elemental concentrations and stable N isotope signatures to reduce equifinality of the stream N model. Advancements in the numerical simulations allow for illumination of the significance of algal sloughing fluxes for the first time in relation to denitrification. Broadly, model estimates suggest that denitrification is slightly greater than algal N sloughing (10.7% and 6.3% of dissolved N load on average), highlighting the potential for overestimation of denitrification by 37%. We highlight the significance of the transient N pool given the potential for the N store to be regenerated to the water column in downstream reaches, leading to harmful and nuisance algal bloom development

Towards the development of new subtype-specific muscarinic receptor radiopharmaceuticals-radiosynthesis and ex vivo biodistribution of [18F] 3-(4-(2-(2-(2-fluoroethoxy) ethoxy) ethylthio)-1, 2, 5-thiadiazol-3-yl)-1-methyl-1, 2, 5, 6-tetrahydropyridine

Muscarinic receptors have been implicated in neurological disorders including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Nineteen derivatives of thiadiazolyltetrahydropyridine (TZTP), a core that has previously shown high affinities towards muscarinic receptor subtypes, were synthesized and evaluated via in vitro binding assays. The title compound, a fluoro-polyethyleneglycol analog of TZTP (4c), was subsequently labelled with fluorine-18. Fluorine-18-labelled 4c was produced, via an automated synthesis, in an average radiochemical yield of 36% (uncorrected for decay), with high radiochemical purity (>99%) and high specific activity (326 GBq/µmol; end-of-bombardment), within 40 min (n = 3). Ex vivo biodistribution studies following tail-vein injection of [18F]4c in conscious rats displayed sufficient brain uptake (0.4%–0.7% injected dose / gram of wet tissue in all brain regions at 5 min post injection); however, there were substantial polar metabolites present in the brain, thereby precluding future use of [18F]4c for imaging in the central nervous system.peer-reviewe

Transcriptome sequencing of black grouse (Tetrao tetrix) for immune gene discovery and microsatellite development

The black grouse (Tetrao tetrix) is a galliform bird species that is important for both ecological studies and conservation genetics. Here, we report the sequencing of the spleen transcriptome of black grouse using 454 GS FLX Titanium sequencing. We performed a large-scale gene discovery analysis with a focus on genes that might be related to fitness in this species and also identified a large set of microsatellites. In total, we obtained 182 179 quality-filtered sequencing reads that we assembled into 9035 contigs. Using these contigs and 15 794 length-filtered (greater than 200 bp) singletons, we identified 7762 transcripts that appear to be homologues of chicken genes. A specific BLAST search with an emphasis on immune genes found 308 homologous chicken genes that have immune function, including ten major histocompatibility complex-related genes located on chicken chromosome 16. We also identified 1300 expressed sequence tag microsatellites and were able to design suitable flanking primers for 526 of these. A preliminary test of the polymorphism of the microsatellites found 10 polymorphic microsatellites of the 102 tested. Genomic resources generated in this study should greatly benefit future ecological, evolutionary and conservation genetic studies on this species

Disentangling Direct from Indirect Co-Evolution of Residues in Protein Alignments

Predicting protein structure from primary sequence is one of the ultimate challenges in computational biology. Given the large amount of available sequence data, the analysis of co-evolution, i.e., statistical dependency, between columns in multiple alignments of protein domain sequences remains one of the most promising avenues for predicting residues that are contacting in the structure. A key impediment to this approach is that strong statistical dependencies are also observed for many residue pairs that are distal in the structure. Using a comprehensive analysis of protein domains with available three-dimensional structures we show that co-evolving contacts very commonly form chains that percolate through the protein structure, inducing indirect statistical dependencies between many distal pairs of residues. We characterize the distributions of length and spatial distance traveled by these co-evolving contact chains and show that they explain a large fraction of observed statistical dependencies between structurally distal pairs. We adapt a recently developed Bayesian network model into a rigorous procedure for disentangling direct from indirect statistical dependencies, and we demonstrate that this method not only successfully accomplishes this task, but also allows contacts with weak statistical dependency to be detected. To illustrate how additional information can be incorporated into our method, we incorporate a phylogenetic correction, and we develop an informative prior that takes into account that the probability for a pair of residues to contact depends strongly on their primary-sequence distance and the amount of conservation that the corresponding columns in the multiple alignment exhibit. We show that our model including these extensions dramatically improves the accuracy of contact prediction from multiple sequence alignments

Screening and diagnosing depression in women visiting GPs' drop in clinic in Primary Health Care

<p>Abstract</p> <p>Background</p> <p>Only half of all depressions are diagnosed in Primary Health Care (PHC). Depression can remain undetected for a long time and entail high costs for care and low quality of life for the individuals. Drop in clinic is a common form of organizing health care; however the visits are short and focus on solving the most urgent problems. The aim of this study was to investigate the prevalence and severity of depression among women visiting the GPs' drop in clinic and to identify possible clues for depression among women.</p> <p>Methods</p> <p>The two-stage screening method with "high risk feedback" was used. Beck's Depression Inventory (BDI) was used to screen 155 women visiting two GPs' drop in clinic. Women who screened positive (BDI score ≥10) were invited by the GP to a repeat visit. Major depression (MDD) was diagnosed according to DSM-IV criteria and the severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). Women with BDI score <10 constituted a control group. Demographic characteristics were obtained by questionnaire. Chart notations were examined with regard to symptoms mentioned at the index visit and were categorized as somatic or mental.</p> <p>Results</p> <p>The two-stage method worked well with a low rate of withdrawals in the second step, when the GP invited the women to a repeat visit. The prevalence of depression was 22.4% (95% CI 15.6–29.2). The severity was mild in 43%, moderate in 53% and severe in 3%. The depressed women mentioned mental symptoms significantly more often (69%) than the controls (15%) and were to a higher extent sick-listed for a longer period than 14 days. Nearly one third of the depressed women did not mention mental symptoms. The majority of the women who screened as false positive for depression had crisis reactions and needed further care from health professionals in PHC. Referrals to a psychiatrist were few and revealed often psychiatric co-morbidity.</p> <p>Conclusion</p> <p>The prevalence of previously undiagnosed depression among women visiting GPs' drop in clinic was high. Clues for depression were identified in the depressed women's symptom presentation; they often mention mental symptoms when they visit the GP for somatic reasons e.g. respiratory infections. We suggest that GPs do selective screening for depression when women mention mental symptoms and offer to schedule a repeat visit for follow-up rather than just recommending that the patient return if the mental symptoms do not disappear.</p

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration: A united approach

Item does not contain fulltextCerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE)

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types