New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina,a Forgotten Edible Alpine Plant

Thirteen acylated flavonoid glycosides, 1 – 13 , including eleven new congeners, 3 – 13 , were isolated from the aerial parts of Pritzelago alpina (Brassicaceae) by a combination of column chromatography on Sephadex LH‐20, and preparative and semi‐preparative HPLC. The structures were established by extensive NMR and MS experiments in combination with acid hydrolysis and sugar analysis by GC/MS. The new compounds were shown to be kaempferol and quercetin glycosides acylated for most of them by a branched short chain fatty acid or a hydroxycinnamic acid residue on the sugar portion. As shown by a HPLC‐DAD analysis of a MeOH extract, these compounds are the main phenolic constituents in the aerial parts of the plant.     

Square‐Centimeter‐Sized High‐Efficiency Polymer Solar Cells: How the Processing Atmosphere and Film Quality Influence Performance at Large Scale

Organic solar cells based on two benzodithiophene‐based polymers (PTB7 and PTB7‐Th) processed at square centimeter‐size under inert atmosphere and ambient air, respectively, are investigated. It is demonstrated that the performance of solar cells processed under inert atmosphere is not limited by the upscaling of photoactive layer and the interfacial layers. Thorough morphological and electrical characterizations of optimized layers and corresponding devices reveal that performance losses due to area enlargement are only caused by the sheet resistance of the transparent electrode reducing the efficiency from 9.3% of 7.8% for PTB7‐Th in the condition that both photoactive layer and the interfacial layers are of high layer quality. Air processing of photoactive layer and the interfacial layers into centimeter‐sized solar cells lead to additional, but only slight, losses (<10%) in all photovoltaic parameters, which can be addressed to changes in the electronic properties of both active layer and ZnO layers rather than changes in layer morphology. The demonstrated compatibility of polymer solar cells using solution‐processed photoactive layer and interfacial layers with large area indicates that the introduction of a standard active area of 1 cm² for measuring efficiency of organic record solar cells is feasible. However electric standards for indium tin oxides (ITO) or alternative transparent electrodes need to be developed so that performance of new photovoltaic materials can be compared at square centimeter‐size.     

Rigorous Training of Dogs Leads to High Accuracy in Human Scent Matching-To-Sample Performance

Human scent identification is based on a matching-to-sample task in which trained dogs are required to compare a scent sample collected from an object found at a crime scene to that of a suspect. Based on dogs’ greater olfactory ability to detect and process odours, this method has been used in forensic investigations to identify the odour of a suspect at a crime scene. The excellent reliability and reproducibility of the method largely depend on rigor in dog training. The present study describes the various steps of training that lead to high sensitivity scores, with dogs matching samples with 90% efficiency when the complexity of the scents presented during the task in the sample is similar to that presented in the in lineups, and specificity reaching a ceiling, with no false alarms in human scent matching-to-sample tasks. This high level of accuracy ensures reliable results in judicial human scent identification tests. Also, our data should convince law enforcement authorities to use these results as official forensic evidence when dogs are trained appropriately.     

On the Use of a Test to Exhaustion Specific to Tennis (TEST) with Ball Hitting by Elite Players

PurposeWe aimed to a) introduce a new Test to Exhaustion Specific to Tennis (TEST) and compare performance (test duration) and physiological responses to those obtained during the 20-m multistage shuttle test (MSST), and b) determine to which extent those variables correlate with performance level (tennis competitive ranking) for both test procedures.MethodsTwenty-seven junior players (8 males, 19 females) members of the national teams of the French Tennis Federation completed MSST and TEST, including elements of the game (ball hitting, intermittent activity, lateral displacement), in a randomized order. Cardiorespiratory responses were compared at submaximal (respiratory compensation point) and maximal loads between the two tests.ResultsAt the respiratory compensation point oxygen uptake (50.1 ± 4.7 vs. 47.5 ± 4.3 mL.min^-1.kg^-1, p = 0.02), but not minute ventilation and heart rate, was higher for TEST compared to MSST. However, load increment and physiological responses at exhaustion did not differ between the two tests. Players’ ranking correlated negatively with oxygen uptake measured at submaximal and maximal loads for both TEST (r = -0.41; p = 0.01 and -0.55; p = 0.004) and MSST (r = -0.38; P = 0.05 and -0.51; p = 0.1).ConclusionUsing TEST provides a tennis-specific assessment of aerobic fitness and may be used to prescribe aerobic exercise in a context more appropriate to the game than MSST. Results also indicate that VO₂ values both at submaximal and maximal load reached during TEST and MSST are moderate predictors of players competitive ranking.     

Formal Models of the Network Co-occurrence Underlying Mental Operations

Systems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-unconstrained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition.     

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.     

Full validation of therapeutic antibody sequences by middle-up mass measurements and middle-down protein sequencing

The regulatory bodies request full sequence data assessment both for innovator and biosimilar monoclonal antibodies (mAbs). Full sequence coverage is typically used to verify the integrity of the analytical data obtained following the combination of multiple LC-MS/MS datasets from orthogonal protease digests (so called “bottom-up” approaches). Top-down or middle-down mass spectrometric approaches have the potential to minimize artifacts, reduce overall analysis time and provide orthogonality to this traditional approach. In this work we report a new combined approach involving middle-up LC-QTOF and middle-down LC-MALDI in-source decay (ISD) mass spectrometry. This was applied to cetuximab, panitumumab and natalizumab, selected as representative US Food and Drug Administration- and European Medicines Agency-approved mAbs. The goal was to unambiguously confirm their reference sequences and examine the general applicability of this approach. Furthermore, a new measure for assessing the integrity and validity of results from middle-down approaches is introduced – the “Sequence Validation Percentage.” Full sequence data assessment of the 3 antibodies was achieved enabling all 3 sequences to be fully validated by a combination of middle-up molecular weight determination and middle-down protein sequencing. Three errors in the reference amino acid sequence of natalizumab, causing a cumulative mass shift of only ?2 Da in the natalizumab Fd domain, were corrected as a result of this work.     

Dealing with paralogy in RADseq data: in silico detection and single nucleotide polymorphism validation in Robinia pseudoacacia L.

The RADseq technology allows researchers to efficiently develop thousands of polymorphic loci across multiple individuals with little or no prior information on the genome. However, many questions remain about the biases inherent to this technology. Notably, sequence misalignments arising from paralogy may affect the development of single nucleotide polymorphism (SNP) markers and the estimation of genetic diversity. We evaluated the impact of putative paralog loci on genetic diversity estimation during the development of SNPs from a RADseq dataset for the nonmodel tree species Robinia pseudoacacia L. We sequenced nine genotypes and analyzed the frequency of putative paralogous RAD loci as a function of both the depth of coverage and the mismatch threshold allowed between loci. Putative paralogy was detected in a very variable number of loci, from 1% to more than 20%, with the depth of coverage having a major influence on the result. Putative paralogy artificially increased the observed degree of polymorphism and resulting estimates of diversity. The choice of the depth of coverage also affected diversity estimation and SNP validation: A low threshold decreased the chances of detecting minor alleles while a high threshold increased allelic dropout. SNP validation was better for the low threshold (4×) than for the high threshold (18×) we tested. Using the strategy developed here, we were able to validate more than 80% of the SNPs tested by means of individual genotyping, resulting in a readily usable set of 330 SNPs, suitable for use in population genetics applications.     

Effects of food abundance and early clutch predation on reproductive timing in a high Arctic shorebird exposed to advancements in arthropod abundance

Climate change may influence the phenology of organisms unequally across trophic levels and thus lead to phenological mismatches between predators and prey. In cases where prey availability peaks before reproducing predators reach maximal prey demand, any negative fitness consequences would selectively favor resynchronization by earlier starts of the reproductive activities of the predators. At a study site in northeast Greenland, over a period of 17 years, the median emergence of the invertebrate prey of Sanderling Calidris alba advanced with 1.27 days per year. Yet, over the same period Sanderling did not advance hatching date. Thus, Sanderlings increasingly hatched after their prey was maximally abundant. Surprisingly, the phenological mismatches did not affect chick growth, but the interaction of the annual width and height of the peak in food abundance did. Chicks grew especially better in years when the food peak was broad. Sanderling clutches were most likely to be depredated early in the season, which should delay reproduction. We propose that high early clutch predation may favor a later reproductive timing. Additionally, our data suggest that in most years food was still abundant after the median date of emergence, which may explain why Sanderlings did not advance breeding along with the advances in arthropod phenology.