Comparison between chironomid-inferred July temperatures and meteorological data AD 1850-2001 from varved Lake Silvaplana, Switzerland

Inferred temperatures from chironomids preserved in the varved sediment of Lake Silvaplana in the Eastern Swiss Alps were compared with instrumental data obtained from a meteorological station in Sils-Maria, on the shore of Lake Silvaplana, for the time interval 1850-2001. At near-annual resolution, the general patterns of chironomid-inferred temperature changes followed the meteorological record over the last ∼150years (r Pearson=0.65, P=0.01) and 87% of the inferences had deviations from the instrumental data below the root-mean-square error of prediction (RMSEP). When the inferences were compared with a 2-year running mean in the meteorological data, 94% of the inferences had differences with the instrumental data below the RMSEP, indicating that more than half of the inaccurate inferences may have been due to errors in varve counting. Larger deviations from the instrumental data were also obtained from samples with low percentages of fossil taxa represented in the training set used for temperature reconstruction and/or assemblages with poor fit to temperature. Changes in total phosphorus (TP, as inferred by diatoms) and/or greater precipitation were possible factors affecting the accuracy of the temperature reconstruction. Although these factors might affect the quantitative estimates, obtaining >80% accurate temperature inferences suggests that chironomid analysis is a reliable tool for reconstructing mean July air temperature quantitatively over the last ∼150years in Lake Silvaplan

Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate

<p>Abstract</p> <p>Background</p> <p>Syringolin A, an important virulence factor in the interaction of the phytopathogenic bacterium <it>Pseudomonas syringae </it>pv. <it>syringae </it>B728a with its host plant <it>Phaseolus vulgaris </it>(bean), was recently shown to irreversibly inhibit eukaryotic proteasomes by a novel mechanism. Syringolin A is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase and consists of a tripeptide part including a twelve-membered ring with an N-terminal valine that is joined to a second valine via a very unusual ureido group. Analysis of sequence and architecture of the syringolin A synthetase gene cluster with the five open reading frames <it>sylA-sylE </it>allowed to formulate a biosynthesis model that explained all structural features of the tripeptide part of syringolin A but left the biosynthesis of the unusual ureido group unaccounted for.</p> <p>Results</p> <p>We have cloned a 22 kb genomic fragment containing the <it>sylA-sylE </it>gene cluster but no other complete gene into the broad host range cosmid pLAFR3. Transfer of the recombinant cosmid into <it>Pseudomonas putida </it>and <it>P. syringae </it>pv. <it>syringae </it>SM was sufficient to direct the biosynthesis of <it>bona fide </it>syringolin A in these heterologous organisms whose genomes do not contain homologous genes. NMR analysis of syringolin A isolated from cultures grown in the presence of NaH¹³CO₃revealed preferential ¹³C-labeling at the ureido carbonyl position.</p> <p>Conclusion</p> <p>The results show that no additional syringolin A-specific genes were needed for the biosynthesis of the enigmatic ureido group joining two amino acids. They reveal the source of the ureido carbonyl group to be bicarbonate/carbon dioxide, which we hypothesize is incorporated by carbamylation of valine mediated by the <it>sylC </it>gene product(s). A similar mechanism may also play a role in the biosynthesis of other ureido-group-containing NRPS products known largely from cyanobacteria.</p

Distorted octahedral coordination of tungstate in a subfamily of specific binding proteins

Bacteria and archaea import molybdenum and tungsten from the environment in the form of the oxyanions molybdate (MoO4 2−) and tungstate (WO4 2−). These substrates are captured by an external, high-affinity binding protein, and delivered to ATP binding cassette transporters, which move them across the cell membrane. We have recently reported a crystal structure of the molybdate/tungstate binding protein ModA/WtpA from Archaeoglobus fulgidus, which revealed an octahedrally coordinated central metal atom. By contrast, the previously determined structures of three bacterial homologs showed tetracoordinate molybdenum and tungsten atoms in their binding pockets. Until then, coordination numbers above four had only been found for molybdenum/tungsten in metalloenzymes where these metal atoms are part of the catalytic cofactors and coordinated by mostly non-oxygen ligands. We now report a high-resolution structure of A. fulgidus ModA/WtpA, as well as crystal structures of four additional homologs, all bound to tungstate. These crystal structures match X-ray absorption spectroscopy measurements from soluble, tungstate-bound protein, and reveal the details of the distorted octahedral coordination. Our results demonstrate that the distorted octahedral geometry is not an exclusive feature of the A. fulgidus protein, and suggest distinct binding modes of the binding proteins from archaea and bacteri

Coupling of multiple LSP and SPP resonances: interactions between an elongated nanoparticle and a thin metallic film

We study the coupling interactions between a progressively elongated silver nanoparticle and a silver film on a glass substrate. Specifically, we investigate how the coupling between localized surface plasmons (LSPs) and propagating surface plasmon polaritons (SPPs) is influenced by nanoparticle length. Although the multiple resonances supported by the nanoparticle are effectively standing wave surface plasmons, their interaction with the SPP continuum of the underlying Ag film indicates that their spectral response is still localized in nature. It is found that these LSP–SPP interactions are not limited to small particles, but that they are present as well for extremely long particles, with a transition to the SPP coupling interactions of a bilayer metallic film system beginning at a particle length of approximately 5 μm

Who Cares About Being Gentle? The Impact of Social Identity and the Gender of One’s Friends on Children’s Display of Same-Gender Favoritism

This research assessed children’s same-gender favoritism by examining whether children value traits descriptive of their own gender more than traits descriptive of the other gender. We also investigated whether children’s proportion of same-gender friends relates to their same-gender favoritism. Eighty-one third and fourth grade children from the Midwest and West Coast of the U.S. rated how well 19 personality traits describe boys and girls, and how important each trait is for their gender to possess. Results replicate and extend past trait assignment research by demonstrating that both genders valued same-gender traits significantly more than other-gender traits. Results also indicated that boys with many same-gender friends derogated feminine-stereotyped traits, which has implications for research on masculinity norms within male-dominated peer groups

Creating a critical mass eliminates the effects of stereotype threat on women's mathematical performance

BACKGROUND: Women in mathematical domains may become attuned to situational cues that signal a discredited social identity, contributing to their lower achievement and underrepresentation. AIM: This study examined whether heightened in-group representation alleviates the effects of stereotype threat on women's mathematical performance. It further investigated whether single-sex testing environments and stereotype threat influenced participants to believe that their ability was fixed (fixed mindset) rather than a trait that could be developed (growth mindset). SAMPLE AND METHOD: One hundred and forty-four female participants were assigned randomly to a self-as-target or group-as-target stereotype threat condition or to a control condition. They completed a modular arithmetic maths test and a mindset questionnaire either alone or in same-sex groups of 3-5 individuals. RESULTS: Participants solved fewer mathematical problems under self-as-target and group-as-target stereotype threat when they were tested alone, but these performance deficits were eliminated when they were tested in single-sex groups. Participants reported a weaker growth mindset when they were tested under stereotype threat and in single-sex groups. Moreover, evidence of inconsistent mediation indicated that single-sex testing environments negatively predicted mindset but positively predicted mathematical performance. CONCLUSIONS: These findings suggest that single-sex testing environments may represent a practical intervention to alleviate stereotype threat effects but may have a paradoxical effect on mindset

Modern NMR Pulse Sequences in Pharmaceutical R & D

NMR pulse sequences are surveyed for solution-state methods that serve as typical, robust techniques in pharmaceutical or chemical NMR laboratories. Attention is drawn to up-to-date methods capable of enhancing sensitivity, resolution, and information content. Sequences range from those used for pulse calibration and field homogeneity adjustment, through one- and two-dimensional homo- and heteronuclear methods for solution-phase work. Techniques used for editing, resolving, and simplifying data are highlighted and extensive use is made of sequence diagrams to present the basic structure of each pulse sequence in pictorial form. Where appropriate, descriptions of each sequence and some examples of data are provided and attention drawn to the advantages of using each technique

The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase II study SAKK 33/14

The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F positive MPN with a mutant allele burden >20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary endpoint, reduction of the JAK2-V617F allele burden ≥50%, was not reached in any of the patients. One patient achieved a 25% reduction in JAK2-V617F allele burden by 24 weeks. A small subgroup of patients showed hematological improvement. As a side study, bone marrow biopsies were evaluated in 20 patients.We found an increase in the nestin+ cells from a median of 1.09 (interquartile range 0.38-3.27)/mm2 to 3.95 (interquartile range 1.98-8.79)/mm2 (p<0.0001) and a slight decrease of reticulin fibrosis from a median grade of 1.0 (interquartile range 0-3) to 0.5 (interquartile range 0-2) (p=0.01) between start and end of mirabegron treatment. Despite the fact that the primary endpoint of reducing JAK2-V617F allele burden was not reached, the observed effects on nestin+ MSCs and reticulin fibrosis is encouraging and shows that mirabegron can modify the microenvironment where the JAK2-mutant stem cells are maintained

Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study.

Objectives The sensitivity of molecular and serological methods for COVID-19 testing in an epidemiological setting is not well described. The aim of the study was to determine the frequency of negative RT-PCR results at first clinical presentation as well as negative serological results after a follow-up of at least 3 weeks. Methods Among all patients seen for suspected COVID-19 in Liechtenstein (n=1921), we included initially RT-PCR positive index patients (n=85) as well as initially RT-PCR negative (n=66) for follow-up with SARS-CoV-2 antibody testing. Antibodies were detected with seven different commercially available immunoassays. Frequencies of negative RT-PCR and serology results in individuals with COVID-19 were determined and compared to those observed in a validation cohort of Swiss patients (n=211). Results Among COVID-19 patients in Liechtenstein, false-negative RT-PCR at initial presentation was seen in 18% (12/66), whereas negative serology in COVID-19 patients was 4% (3/85). The validation cohort showed similar frequencies: 2/66 (3%) for negative serology, and 16/155 (10%) for false negative RT-PCR. COVID-19 patients with negative follow-up serology tended to have a longer disease duration (p=0.05) and more clinical symptoms than other patients with COVID-19 (p<0.05). The antibody titer from quantitative immunoassays was positively associated with the number of disease symptoms and disease duration (p<0.001). Conclusions RT-PCR at initial presentation in patients with suspected COVID-19 can miss infected patients. Antibody titers of SARS-CoV-2 assays are linked to the number of disease symptoms and the duration of disease. One in 25 patients with RT-PCR-positive COVID-19 does not develop antibodies detectable with frequently employed and commercially available immunoassays

Lipid profiles of prostate cancer cells

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells