Inducing a pH-dependent conformational response by competitive binding to Zn2+ of a series of chiral ligands of disparate basicity

Molecules that change shape in response to environmental conditions are central to biological molecular communication devices and their synthetic chemical analogues. Here we report a molecular system in which a series of chiral anionic ligands of differing basicity are selectively protonated according to the pH of the medium. A cationic circular dichroism (CD) reporter complex responds to anion binding by selecting one of two alternative enantiomeric conformations. Exploiting the principle that less basic anions have, in general, weaker electrostatic interactions than more basic anions, a set of three chiral acids with large (>5 unit) pK(a) differences and differing configurations were sequentially deprotonated in acetonitrile by addition of base, allowing the most basic anion in the mixture at any time to bind to the reporter complex. A characteristic CD output resulted, which changed in sign as the next-most basic anion was revealed by the next deprotonation in the series. Four cycles of switching between three ligand-bound states were achieved with minimal changes in signal magnitude, by alternating addition of base and acid. The pH-dependent conformational response was used to transduce a signal by appending to the binding site a 2-aminoisobutyric acid (Aib) oligomer, whose M or P helical conformation depended on the chirality of the bound ligand, and was reported by a remote (13)C-labelled NMR reporter group. The multicomponent system thus converts a pH signal into a programmable conformational response which induces a remote spectroscopic effect

The enormous acidifying effect of the supersubstituent ᎐ ᎐ NSO 2 CF 3 on the acidity of derivatives of benzenesulfonamide and toluene-p- sulfonamide in the gas phase and in dimethyl sulfoxide

The effect of stepwise replacement of ᎐ ᎐ O oxygen atoms by ᎐ ᎐ NSO 2 CF 3 fragments in the sulfonyl group of toluenep-sulfonamide and benzenesulfonamide on their acidity has been studied in the gas phase and dimethyl sulfoxide (DMSO). Incorporation of the first ᎐ ᎐ NSO 2 CF 3 group into 4-MeC 6 H 4 SO 2 NH 2 increases its gas-phase acidity by 23.6 kcal mol Ϫ1 . Substituting the second ᎐ ᎐ O by the ᎐ ᎐ NSO 2 CF 3 group leads to an additional acidity increase of 10.7 kcal mol Ϫ1 ; the total acidity increase is thus 34.3 kcal mol Ϫ1 (25 powers of ten!). In DMSO solution the total acidity increase is 13 pK a units (17.7 kcal mol Ϫ1 ). These findings are also supported by computational studies using DFT B3LYP at the 6-31ϩG* level and the semiempirical PM3 method. The results of this work have potentially important implications for the design of new strongly acidic catalytic materials

Utility-Based Mechanism for Structural Self-Organization in Service-Oriented MAS

Structural relations established among agents influence the performance of decentralized service discovery process in multiagent systems. Moreover, distributed systems should be able to adapt their structural relations to changes in environmental conditions. In this article, we present a service-oriented multiagent systems, where agents initially self-organize their structural relations based on the similarity of their services. During the service discovery process, agents integrate a mechanism that facilitates the self-organization of their structural relations to adapt the structure of the system to the service demand. This mechanism facilitates the task of decentralized service discovery and improves its performance. Each agent has local knowledge about its direct neighbors and the queries received during discovery processes. With this information, an agent is able to analyze its structural relations and decide when it is more appropriate to modify its direct neighbors and select the most suitable acquaintances to replace them. The experimental evaluation shows how this self-organization mechanism improves the overall performance of the service discovery process in the system when the service demand changesThis work is partially supported by the Spanish Ministry of Science and Innovation through grants CSD2007-0022 (CONSOLIDER-INGENIO 2010), TIN2012-36586-C03-01, TIN2012-36586-C03-01, TIN2012-36586-C03-02, PROMETEOII/2013/019, and FPU grant AP-2008-00601 awarded to E. Del Val.Del Val Noguera, E.; Rebollo Pedruelo, M.; Vasirani, M.; Fernández, A. (2014). Utility-Based Mechanism for Structural Self-Organization in Service-Oriented MAS. ACM Transactions on Autonomous and Adaptive Systems. 9(3):1-24. https://doi.org/10.1145/2651423S12493Sherief Abdallah and Victor Lesser. 2007. 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Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: promoting interdisciplinary debate

Traditionally, bioanalytical laboratories do not report actual concentrations for samples with results below the LOQ (BLQ) in pharmacokinetic studies. BLQ values are outside the method calibration range established during validation and no data are available to support the reliability of these values. However, ignoring BLQ data can contribute to bias and imprecision in model-based pharmacokinetic analyses. From this perspective, routine use of BLQ data would be advantageous. We would like to initiate an interdisciplinary debate on this important topic by summarizing the current concepts and use of BLQ data by regulators, pharmacometricians and bioanalysts. Through introducing the limit of detection and evaluating its variability, BLQ data could be released and utilized appropriately for pharmacokinetic research

A global threats overview for Numeniini populations: synthesising expert knowledge for a group of declining migratory birds

The Numeniini is a tribe of thirteen wader species (Scolopacidae, Charadriiformes) of which seven are near-threatened or globally threatened, including two critically endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian - Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species

Analysis of copy number variation at DMBT1 and age-related macular degeneration

BACKGROUND: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. METHODS: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. RESULTS: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. CONCLUSIONS: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD

Landscape structure, human disturbance and crop management affect foraging ground selection by migrating geese

It is well known that agricultural intensification has caused severe population declines among bird species which use farmland for breeding and overwintering, while migrating bird species may benefit from intensive farming, but in turn damage crops. Knowledge of the habitat selection of migrating birds is important from both a conservation and agro-economic point of view. We investigated the habitat preferences of three common migrating goose species: White-fronted Goose Anser albifrons, Bean Goose A. fabalis and Greylag Goose A. anser during the autumn of 2009 in western Poland. A total of 24 flocks of these species were identified. Geese preferred large, elevated fields that were remote from forests and human settlements but in close proximity to a lake. Geese selected maize stubbles and avoided winter cereals. They selected sites in landscapes with a lower diversity of crops. Flock size was negatively correlated with the proportion of pastures in the landscape, but it increased with field size, distance to forest and distance to town. Our results are in contrast with the paradigm that less intensive farmland positively influences habitat use by birds during foraging. We advise the delayed ploughing of stubbles with the aim of creating appropriate foraging habitats for geese and minimizing damage to cereal crops

Predation Danger Can Explain Changes in Timing of Migration: The Case of the Barnacle Goose

Understanding stopover decisions of long-distance migratory birds is crucial for conservation and management of these species along their migratory flyway. Recently, an increasing number of Barnacle geese breeding in the Russian Arctic have delayed their departure from their wintering site in the Netherlands by approximately one month and have reduced their staging duration at stopover sites in the Baltic accordingly. Consequently, this extended stay increases agricultural damage in the Netherlands. Using a dynamic state variable approach we explored three hypotheses about the underlying causes of these changes in migratory behavior, possibly related to changes in (i) onset of spring, (ii) potential intake rates and (iii) predation danger at wintering and stopover sites. Our simulations showed that the observed advance in onset of spring contradicts the observed delay of departure, whereas both increased predation danger and decreased intake rates in the Baltic can explain the delay. Decreased intake rates are expected as a result of increased competition for food in the growing Barnacle goose population. However, the effect of predation danger in the model was particularly strong, and we hypothesize that Barnacle geese avoid Baltic stopover sites as a response to the rapidly increasing number of avian predators in the area. Therefore, danger should be considered as an important factor influencing Barnacle goose migratory behavior, and receive more attention in empirical studies