The Hydrogen–Deuterium Exchange at α-Carbon Atom in N,N,N-Trialkylglycine Residue: ESI-MS Studies

Derivatization of peptides as quaternary ammonium salts (QAS) is a known method for sensitive detection by electrospray ionization tandem mass spectrometry. Hydrogens at α-carbon atom in N,N,N-trialkylglycine residue can be easily exchanged by deuterons. The exchange reaction is base-catalyzed and is dramatically slow at lower pH. Introduced deuterons are stable in acidic aqueous solution and are not back-exchanged during LC-MS analysis. Increased ionization efficiency, provided by the fixed positive charge on QAS group, as well as the deuterium labeling, enables the analysis of trace amounts of peptides

Cue properties change timing strategies in group movement synchronisation

To maintain synchrony in group activities, each individual within the group must continuously correct their movements to remain in time with the temporal cues available. Cues might originate from one or more members of the group. Current research suggests that when synchronising movements, individuals optimise their performance in terms of minimising variability of timing errors (asynchronies) between external cues and their own movements. However, the cost of this is an increase in the timing variability of their own movements. Here we investigate whether an individual’s timing strategy changes according to the task, in a group scenario. To investigate this, we employed a novel paradigm that positioned six individuals to form two chains with common origin and termination on the circumference of a circle. We found that participants with access to timing cues from only one other member used a strategy to minimise their asynchrony variance. In contrast, the participant at the common termination of the two chains, who was required to integrate timing cues from two members, used a strategy that minimised movement variability. We conclude that humans are able to flexibly switch timekeeping strategies to maintain task demands and thus optimise the temporal performance of their movements

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Properties of Blood, Porphyrins, and Exposure to Legacy and Emerging Persistent Organic Pollutants in Surf Scoters (Melanitta perspicillata) Overwintering on the South Coast of British Columbia, Canada

The surf scoter (Melanitta perspicillata) is a little-studied species of North American sea duck. Estimates suggest it has experienced a precipitous decline in breeding numbers over the latter half of the past century. To investigate the potential role of contaminant uptake and toxicity in the population decline, this study undertook to measure blood chemistry, porphyrin concentrations, EROD, and organic contaminants in mature surf scoters wintering in the Strait of Georgia, BC, Canada. Hepatic organochlorine pesticide, polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran, polychlorinated biphenyl (PCB), polybrominated diphenyl ether, and nonylphenol concentrations were relatively low; for example, ΣTEQs (toxic equivalents) for PCBs, dioxins, and furans combined ranged from 4.7 ng/kg wet weight in reference-site (Baynes Sound) birds to 11.4 ng/kg wet weight in birds from Vancouver Harbour. Nonetheless, elevated EROD activity indicated that birds in Howe Sound were responding to an Ah-receptor-mediated stressor, which was also affecting hematocrit values and possibly vitamin A status. In addition, a low proportion of lymphocytes in individuals across locations in early spring samples was associated with poor body condition. The apparent loss of fitness just prior to the onset of northerly migrations to breeding grounds is of particular concern. Compromised health of mature birds at this point in the season might impact negatively on the productivity and survival of some individuals, particularly those overwintering in Howe Sound

Blow-up profile of rotating 2D focusing Bose gases

We consider the Gross-Pitaevskii equation describing an attractive Bose gas trapped to a quasi 2D layer by means of a purely harmonic potential, and which rotates at a fixed speed of rotation $\Omega$. First we study the behavior of the ground state when the coupling constant approaches $a\_*$ , the critical strength of the cubic nonlinearity for the focusing nonlinear Schr{\"o}dinger equation. We prove that blow-up always happens at the center of the trap, with the blow-up profile given by the Gagliardo-Nirenberg solution. In particular, the blow-up scenario is independent of $\Omega$, to leading order. This generalizes results obtained by Guo and Seiringer (Lett. Math. Phys., 2014, vol. 104, p. 141--156) in the non-rotating case. In a second part we consider the many-particle Hamiltonian for $N$ bosons, interacting with a potential rescaled in the mean-field manner $--a\_N N^{2\beta--1} w(N^{\beta} x), with$w$a positive function such that$\int\_{\mathbb{R}^2} w(x) dx = 1$. Assuming that$\beta < 1/2$and that$a\_N \to a\_*$sufficiently slowly, we prove that the many-body system is fully condensed on the Gross-Pitaevskii ground state in the limit$N \to \infty$

Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Correction: Metal complexes as a promising source for new antibiotics

Correction for ‘Metal complexes as a promising source for new antibiotics’ by Angelo Frei et al., Chem. Sci., 2020, 11, 2627–2639