Mercury loading within the Selenga River basin and Lake Baikal, Siberia.

Mercury (Hg) loading in Lake Baikal, a UNESCO world heritage site, is growing and poses a serious health concern to the lake's ecosystem due to the ability of Hg to transform into a toxic form, known as methylmercury (MeHg). Monitoring of Hg into Lake Baikal is spatially and temporally sparse, highlighting the need for insights into historic Hg loading. This study reports measurements of Hg concentrations from water collected in August 2013 and 2014 from across Lake Baikal and its main inflow, the Selenga River basin (Russia, Mongolia). We also report historic Hg contamination using sediment cores taken from the south and north basins of Lake Baikal, and a shallow lake in the Selenga Delta. Field measurements from August 2013 and 2014 show high Hg concentrations in the Selenga Delta and river waters, in comparison to pelagic lake waters. Sediment cores from Lake Baikal show that Hg enrichment commenced first in the south basin in the late-19th century, and then in the north basin in the mid-20th century. Hg flux was also 20-fold greater in the south basin compared to the north basin sediments. Hg enrichment was greatest in the Selenga Delta shallow lake (Enrichment Ratio (ER) = 2.3 in 1994 CE), with enrichment occurring in the mid-to late-20th century. Local sources of Hg are predominantly from gold mining along the Selenga River, which have been expanding over the last few decades. More recently, another source is atmospheric deposition from industrial activity in Asia, due to rapid economic growth across the region since the 1980s. As Hg can bioaccumulate and biomagnify through trophic levels to Baikal's top consumer, the world's only truly freshwater seal (Pusa sibirica), it is vital that Hg input at Lake Baikal and within its catchment is monitored and controlled.

Multiplexed Imaging Strategy to Distinguish Indeterminant Biliary Strictures: An Ex Vivo Study.

Introduction: Indeterminant biliary strictures can be either malignant or benign. Biliary intraepithelial neoplasia (BilIN) is the precursor lesion to cholangiocarcinoma, a deadly bile duct cancer. Current diagnostic methods are limited by inadequate amounts of cells and tissues collected. Aim: We aim to demonstrate use of fluorescently-labeled peptides specific for EGFR, claudin-1, and ErbB2 to perform multiplexed imaging of biliary neoplasia. Methods: Formalin fixed and paraffin embedded specimens resected from human biliary strictures were sectioned. A gastrointestinal pathologist used standard criteria to score immunohistochemistry from biliary neoplasia and adjacent normal epithelium from the same specimen. Peptides specific for EGFR, claudin-1, and ErbB2 were fluorescently-labeled with FITC, Cy5, and IRDye800, respectively. The fluorophores were chosen to provide spectral separation to distinguish the individual targets. Immuno fluorescence images were collected using confocal microscopy. Results: Target expression was validated using immunohistochemistry. Staining was visualized on the surface of biliary duct epithelial cells and not in the stroma. Greater fluorescence intensity was observed for peptide binding to biliary neoplasia by comparison with normal. The mean ratio for neoplasia-to-normal was 1.4, 1.7, and 1.6, respectively, and the average intensities were significantly greater for neoplasia than normal for each peptide. Peptides and antibody binding co-localized with correlation of ρ=0.64, 0.51 and 0.62, respectively. Conclusions: A panel of fluorescently-labeled peptides can distinguish BilIN and cholangiocarcinoma from normal biliary epithelium, and may be used for multiplexed imaging of indeterminant biliary strictures.

Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma.

Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting in the frameshift c.1253_1269dup p.(Thr424fs*49), has previously been described as pathogenic, for example, in cases of AOA4. The second variant, representing a nonsense mutation in exon 17, c.1545C>G p.(Tyr515*), has not yet been described and is predicted to cause a loss of the 7 C-terminal amino acids. This is the first description of AOA4 in a patient with central European descent. Furthermore, the occurrence of a pilocytic astrocytoma has not been described before in an AOA4 patient. Our data demonstrate compound heterozygous PNKP germline variants in a German patient with AOA4 and provide evidence for a possible link with tumor predisposition. Localization of the 2 variants in human PNKP NP_009185.2. NM_007254.3:c.1253_1269dup p.(Thr424fs*49) is predicted to cause a frameshift within the kinase domain, NM_007254.3:c.1545C>G p.(Tyr515*) is predicted to cause loss of 2 C-terminal amino acids of the kinase domain and 5 additional C-terminal amino acids.

The haemodynamic effect of an adjustable band in an arteriovenous fistula.

A number of treatment approaches exist for excessive flowrate arteriovenous fistulae. Banding has a number of advantages, yet there is concern over its use due to reported high post-surgery thrombosis rates. A computational study is conducted of a new technique, to elucidate the hemodynamics present in the process. The key improvement involves the use of an adjustable band which can be used to optimise the flowrate during the surgery. The pressure and flowrate changes are apparent from the computational results and the computational results also demonstrate that further optimization may be possible. We then present a small cohort of five cases where the new banding procedure has been implemented with success. The new technique was combined with intra-operative ultrasound flow monitoring.

Factors associated with thrombosis in pediatric patients with systemic lupus erythematosus.

OBJECTIVE: The risk of thrombosis is increased in patients with systemic lupus erythematosus (SLE). Few studies have assessed factors associated with thrombosis within the pediatric SLE (pSLE) population. We sought to better characterize these associated factors in pSLE patients using the Childhood Arthritis & Rheumatology Research Alliance (CARRA) registry. METHODS: Within the CARRA registry, patients with a history of thrombosis were compared to those without. Univariate logistic regression was used to calculate odds ratios. A multivariable logistic regression model was conducted that included variables from the univariate analysis that had a p value < 0.10 and other variables identified as clinically significant from published literature. RESULTS: Among the 979 pSLE patients in the CARRA registry, 24 (2.5%) patients had a history of arterial thrombosis and 35 (3.6%) of venous thrombosis. In the univariate analysis, the odds ratio of having a thrombotic event were found to be significantly higher in patients with a history of vasculitis, avascular necrosis (AVN), or antiphospholipid antibody (aPL). Similar results were found for vasculitis, AVN, and aPL in the multivariable analysis. CONCLUSION: Our study of pSLE patients suggests that vasculitis, positive APL, and AVN are associated with thrombotic events in this population.

Loss of function of PGAP1 as a cause of severe encephalopathy identified by Whole Exome Sequencing: Lessons of the bioinformatics pipeline.

We evaluated a multiple consanguineous Turkish family with two children, a boy and a girl, affected by severe encephalopathy, hypotonia, microcephaly and retinal dystrophy by a combination of linkage analysis and Whole Exome Sequencing (WES). We analyzed the sequence data by two different bioinformatics pipelines which did not differ in overall processing strategy but involved differences in software used, minor allele frequency (MAF) thresholds and reference data sets, the usage of in-house control exomes and filter settings to prioritize called variants. Assuming autosomal recessive mode of inheritance, only homozygous variants present in both children were considered. The resulting variant lists differed partially (nine variants identified by both pipelines, ten variants by only one pipeline). Major reasons for this discrepancy were different filters for MAF and different variant prioritizations. Combining the variant lists with the results of linkage analysis and further prioritization by expression data and prediction tools, an intronic homozygous splice variant (c.1090-2A>G; IVS9-2A>G; p.?) in PGAP1 (Post-GPI Attachment To Proteins 1) was identified and validated by cDNA analysis. PGAP1 ensures the first step of maturation of GPI (glycosylphosphatidylinositol)-anchor proteins. Recently, a homozygous loss-of-function mutation in PGAP1 has been reported in one family with two children affected by a similar phenotype. The present report not only illustrates the possible influence of specific filtering settings on the results of WES but also confirms PGAP1 as a cause of severe encephalopathy.

Relation between coumarate decarboxylase and vinylphenol reductase activity with regard to the production of volatile phenols by native Dekkera bruxellensis strains under 'wine-like' conditions.

Dekkera/Brettanomyces bruxellensis is considered a major cause of wine spoilage, and 4-ethylphenol and 4-ethylguaiacol are the most abundant off-aromas produced by this species. They are produced by decarboxylation of the corresponding hydroxycinnamic acids (HCAs), followed by a reduction of the intermediate 4-vinylphenols. The aim of the present study was to examine coumarate decarboxylase (CD) and vinylphenol reductase (VR) enzyme activities in 5 native D. bruxellensis strains and determine their relation with the production of ethylphenols under 'wine-like' conditions. In addition, biomass, cell culturability, carbon source utilization and organic acids were monitored during 60 days. All strains assayed turned out to have both enzyme activities. No significant differences were found in CD activity, whilst VR activity was variable among the strains. Growth of D. bruxellensis under 'wine-like' conditions showed two growth phases. Sugars were completely consumed during the first growth phase. Transformation of HCAs into ethylphenols also occurred during active growth of the yeast. No statistical differences were observed in volatile phenol levels produced by the strains growing under 'wine-like' conditions, independently of the enzyme activity previously recorded. Furthermore, our results demonstrate a relationship between the physiological state of D. bruxellensis and its ability to produce ethylphenols. Inhibition of growth of D. bruxellensis in wine seems to be the most efficient way to avoid ethylphenol production and the consequent loss of wine quality.

Effect of chronic corticosterone application on depression-like behavior in C57BL/6N and C57BL/6J mice.

Many studies using genetic mouse models are performed with animals on either one of the two closely related genetic backgrounds, C57BL/6J or C57BL/6N. These strains differ only in a few genetic loci, but have some phenotypic differences that also affect behavior. In order to determine the effects of chronic stress hormone exposure, which is relevant for the pathogenesis of psychiatric disorders, we investigated here the behavioral manifestations of long-term increase in corticosterone levels. Thus, male mice from both sub-strains were subcutaneously implanted with corticosterone (20 mg) or placebo pellets that released the hormone for a period of 21 days and resulted in significantly elevated plasma corticosterone levels. Corticosterone significantly increased food intake in B6N, but not in B6J mice. At various time points after pellet implantation, we performed tests relevant to activity and emotional behaviors. B6J mice displayed a generally higher activity in the home cage and the open field. Corticosterone decreased the activity. In B6N mice, corticosterone also decreased sucrose preference, worsened the coat state and increased forced swim immobility, while it had no effect in the B6J strain. Altogether, these results indicate that B6N mice are more sensitive to some of the effects of chronic corticosterone treatment than B6J mice.

The accuracy of a patient or parent-administered bleeding assessment tool administered in a paediatric haematology clinic.

Classifying and describing bleeding symptoms is essential in the diagnosis and management of patients with mild bleeding disorders (MBDs). There has been increased interest in the use of bleeding assessment tools (BATs) to more objectively quantify the presence and severity of bleeding symptoms. To date, the administration of BATs has been performed almost exclusively by clinicians; the accuracy of a parent-proxy BAT has not been studied. Our objective was to determine the accuracy of a parent-administered BAT by measuring the level of agreement between parent and clinician responses to the Condensed MCMDM-1VWD Bleeding Questionnaire. Our cross-sectional study included children 0-21 years presenting to a haematology clinic for initial evaluation of a suspected MBD or follow-up evaluation of a previously diagnosed MBD. The parent/caregiver completed a modified version of the BAT; the clinician separately completed the BAT through interview. The mean parent-report bleeding score (BS) was 6.09 (range: -2 to 25); the mean clinician report BS was 4.54 (range: -1 to 17). The mean percentage of agreement across all bleeding symptoms was 78% (mean κ = 0.40; Gwet's AC1 = 0.74). Eighty percent of the population had an abnormal BS (defined as ≥2) when rated by parents and 76% had an abnormal score when rated by clinicians (86% agreement, κ = 0.59, Gwet's AC1 = 0.79). While parents tended to over-report bleeding as compared to clinicians, overall, BSs were similar between groups. These results lend support for further study of a modified proxy-report BAT as a clinical and research tool.

A magnetically shielded room with ultra low residual field and gradient.

A versatile and portable magnetically shielded room with a field of (700 ± 200) pT within a central volume of 1 m × 1 m × 1 m and a field gradient less than 300 pT/m, achieved without any external field stabilization or compensation, is described. This performance represents more than a hundredfold improvement of the state of the art for a two-layer magnetic shield and provides an environment suitable for a next generation of precision experiments in fundamental physics at low energies; in particular, searches for electric dipole moments of fundamental systems and tests of Lorentz-invariance based on spin-precession experiments. Studies of the residual fields and their sources enable improved design of future ultra-low gradient environments and experimental apparatus. This has implications for developments of magnetometry beyond the femto-Tesla scale in, for example, biomagnetism, geosciences, and security applications and in general low-field nuclear magnetic resonance (NMR) measurements.

Probabilistic model for the spoilage wine yeast Dekkera bruxellensis as a function of pH, ethanol and free SO2 using time as a dummy variable.

The present study uses a probabilistic model to determine the growth/no growth interfaces of the spoilage wine yeast Dekkera bruxellensis CH29 as a function of ethanol (10-15%, v/v), pH (3.4-4.0) and free SO2 (0-50 mg/l) using time (7, 14, 21 and 30 days) as a dummy variable. The model, built with a total of 756 growth/no growth data obtained in a simile wine medium, could have application in the winery industry to determine the wine conditions needed to inhibit the growth of this species. Thereby, at 12.5% of ethanol and pH 3.7 for a growth probability of 0.01, it is necessary to add 30 mg/l of free SO2 to inhibit yeast growth for 7 days. However, the concentration of free SO2 should be raised to 48 mg/l to achieve a probability of no growth of 0.99 for 30 days under the same wine conditions. Other combinations of environmental variables can also be determined using the mathematical model depending on the needs of the industry.

Certified reference materials and reference methods for nuclear safeguards and security.

Confidence in comparability and reliability of measurement results in nuclear material and environmental sample analysis are established via certified reference materials (CRMs), reference measurements, and inter-laboratory comparisons (ILCs). Increased needs for quality control tools in proliferation resistance, environmental sample analysis, development of measurement capabilities over the years and progress in modern analytical techniques are the main reasons for the development of new reference materials and reference methods for nuclear safeguards and security. The Institute for Reference Materials and Measurements (IRMM) prepares and certifices large quantities of the so-called "large-sized dried" (LSD) spikes for accurate measurement of the uranium and plutonium content in dissolved nuclear fuel solutions by isotope dilution mass spectrometry (IDMS) and also develops particle reference materials applied for the detection of nuclear signatures in environmental samples. IRMM is currently replacing some of its exhausted stocks of CRMs with new ones whose specifications are up-to-date and tailored for the demands of modern analytical techniques. Some of the existing materials will be re-measured to improve the uncertainties associated with their certified values, and to enable laboratories to reduce their combined measurement uncertainty. Safeguards involve the quantitative verification by independent measurements so that no nuclear material is diverted from its intended peaceful use. Safeguards authorities pay particular attention to plutonium and the uranium isotope (235)U, indicating the so-called 'enrichment', in nuclear material and in environmental samples. In addition to the verification of the major ratios, n((235)U)/n((238)U) and n((240)Pu)/n((239)Pu), the minor ratios of the less abundant uranium and plutonium isotopes contain valuable information about the origin and the 'history' of material used for commercial or possibly clandestine purposes, and have therefore reached high level of attention for safeguards authorities. Furthermore, IRMM initiated and coordinated the development of a Modified Total Evaporation (MTE) technique for accurate abundance ratio measurements of the "minor" isotope-amount ratios of uranium and plutonium in nuclear material and, in combination with a multi-dynamic measurement technique and filament carburization, in environmental samples. Currently IRMM is engaged in a study on the development of plutonium reference materials for "age dating", i.e. determination of the time elapsed since the last separation of plutonium from its daughter nuclides. The decay of a radioactive parent isotope and the build-up of a corresponding amount of daughter nuclide serve as chronometer to calculate the age of a nuclear material. There are no such certified reference materials available yet.

A seasonal cycle of terrestrial inputs in Lake Van, Turkey.

Lake Van in Turkey is the world's largest soda lake (607 km(3)). The lake's catchment area is estimated to be ∼12,500 km(2), and the terrestrial input is carried through eolian, riverine, snowmelt and anthropogenic paths. Extent and seasonality of the terrestrial inputs to the lake have not been studied, but it is essential to evaluate its environmental status and to assess the use of environmental proxies to estimate the lake's response to climate changes. This study aims to measure seasonal changes in terrestrial input of natural and anthropogenic origin as recorded by the fluxes of pollen and biomarkers of soil bacteria and vascular or higher plants, as well as petrogenic biomarkers in monthly resolved sediment traps from August 2006 to July 2007. Fluxes of pollen, soil and higher plant biomarkers seem to be related to precipitation and snowmelt in autumn and spring. In addition, dust storms, which are common during the summer months, may have resulted in long-distance transport. Anthropogenic biomarker fluxes indicate year-round petrogenic contamination although some mature biomarker fluxes are higher in summer and in late winter-spring. The relative changes between petrogenic markers indicate variations in the pollutant sources.

Lethal Undiagnosed Very Long-Chain Acyl-CoA Dehydrogenase Deficiency with Mild C14-Acylcarnitine Abnormalities on Newborn Screening.

Newborn screening identifies patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency with disease-specific acylcarnitine profiles. We here present a patient who died at 16 months during a gastrointestinal infection because of undiagnosed VLCADD. The primary acylcarnitine profile on newborn screening performed at 55 h of life revealed C14-acylcarnitine values and ratios within the 1st percentile VLCAD disease range and C12-acylcarnitine values and ratios within the 10th percentile disease range. The acylcarnitine cumulative percentiles in neonatal dried blood spots analyzed by tandem mass spectrometry have been obtained by participants of the Region 4 Stork collaborative project. A secondary screen was requested by the screening laboratory as a result of the initial screen and was normal on day 8 of life. With the initial acylcarnitines only within the 1st-10th percentile disease range, newborn screening for VLCAD deficiency was in the end considered normal. The most important lesson learned is that acylcarnitine profiles from healthy newborns during catabolism and VLCAD-deficient patients can in certain cases not be distinguished by any means. With a known high incidence of false positive cases for VLCADD on newborn screening, it finally remains unknown, whether forced anabolism in the first days of life may result in normal acylcarnitine profiles in VLCAD-deficient patients resulting in missed cases and false negatives on newborn screening. Our observations are of great significance since they demonstrate the limitations of acylcarnitine analysis as screening tool for VLCAD-deficiency.

Yeast identification in grape juice concentrates from Argentina.

AIMS: The purpose of this study was to identify yeast species present in spoiled and unspoiled grape juice concentrates from Argentine industries. METHODS AND RESULTS: Osmophilic and osmotolerant yeasts were isolated from spoiled--visually effervescent--and unspoiled--without any visible damage--grape juice concentrates by the spread-plate technique in two culture media. Yeast identification was done by classical and molecular methods. Zygosaccharomyces rouxii was the only species isolated from spoiled grape juice concentrates. In unspoiled samples, five different species were identified: Z. rouxii was isolated at a higher frequency, followed in decreasing order by Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pichia anomala and Kluyveromyces delphensis. CONCLUSIONS: Yeasts isolated from grape juice concentrates were characterized by a limited taxonomic diversity, where Z. rouxii was the main species isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: Grape production in Argentina is mainly devoted to the industry where wine and grape juice concentrates represent major types of commercial products. Little information on common yeast contaminants is available for grape juice concentrates. This study constitutes the first report of osmophilic yeast species present in spoiled and unspoiled grape juice concentrates elaborated in Argentina.

Evolution of the snow area index of the subarctic snowpack in central Alaska over a whole season. consequences for the air to snow transfer of pollutants.

The detailed physical characteristics of the subarctic snowpack must be known to quantify the exchange of adsorbed pollutants between the atmosphere and the snow cover. For the first time, the combined evolutions of specific surface area (SSA), snow stratigraphy, temperature, and density were monitored throughout winter in central Alaska. We define the snow area index (SAI) as the vertically integrated surface area of snow crystals, and this variable is used to quantify pollutants' adsorption. Intense metamorphism generated by strong temperature gradients formed a thick depth hoar layer with low SSA (90 cm(2) g-1) and density (200 kg m(-3)), resulting in a low SAI. After snowpack buildup in autumn, the winter SAI remained around 1000 m(2)/m(2) of ground, much lower than the SAI of the Arctic snowpack, 2500 m(2) m-(2). With the example of PCBs 28 and 180, we calculate that the subarctic snowpack is a smaller reservoir of adsorbed pollutants than the Arctic snowpack and less efficiently transfers adsorbed pollutants from the atmosphere to ecosystems. The difference is greater for the more volatile PCB 28. With climate change, snowpack structure will be modified, and the snowpack's ability to transfer adsorbed pollutants from the atmosphere to ecosystems may be reduced, especially for the more volatile pollutants.

Role of land-surface changes in arctic summer warming.

A major challenge in predicting Earth's future climate state is to understand feedbacks that alter greenhouse-gas forcing. Here we synthesize field data from arctic Alaska, showing that terrestrial changes in summer albedo contribute substantially to recent high-latitude warming trends. Pronounced terrestrial summer warming in arctic Alaska correlates with a lengthening of the snow-free season that has increased atmospheric heating locally by about 3 watts per square meter per decade (similar in magnitude to the regional heating expected over multiple decades from a doubling of atmospheric CO2). The continuation of current trends in shrub and tree expansion could further amplify this atmospheric heating by two to seven times.