FhCaBP4: A Fasciola hepatica calcium binding protein with EF-hand and dynein light chain domains

In trematodes, there is a family of proteins which combine EF-hand-containing domains with dynein light chain (DLC)-like domains. A member of this family from the liver fluke, Fasciola hepatica-FhCaBP4-has been identified and characterised biochemically. FhCaBP4 has an N-terminal domain containing two imperfect EF-hand sequences and a C-terminal dynein light chain-like domain. Molecular modelling predicted that the two domains are joined by a flexible linker. Native gel electrophoresis demonstrated that FhCaBP4 binds to calcium, manganese, barium and strontium ions, but not to magnesium or zinc ions. The hydrophobic, fluorescent probe 8-anilinonaphthalene-1-sulphonate bound more tightly to FhCaBP4 in the presence of calcium ions. This suggests that the protein undergoes a conformational change on ion binding which increases the number of non-polar residues on the surface. FhCaBP4 was protected from limited proteolysis by the calmodulin antagonist W7, but not by trifluoperazine or praziquantel. Protein-protein cross-linking experiments showed that FhCaBP4 underwent calcium ion-dependent dimerisation. Since DLCs are commonly dimeric, it is likely that FhCaBP4 dimerises through this domain. The molecular model reveals that the calcium ion-binding site is located close to a key sequence in the DLC-like domain, suggesting a plausible mechanism for calcium-dependent dimerisation.

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

PURPOSE:
To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation.
METHODS:
A prooxidant, paraquat (0.75 µM) was injected into the vitreous of C57BL/6J, CX3CR1(gpf/+), and CX3CR1(gfp/gfp) mice. Retinal lesions were investigated clinically by topic endoscopic fundus imaging and fluorescence angiography, and pathologically by light- and electron microscopy. Retinal immune gene expression was determined by real-time RT-PCR. Microglial activation and immune cell infiltration were examined by confocal microscopy of retinal flatmounts.
RESULTS:
Intravitreal injection of paraquat (0.75 µM) resulted in acute retinal capillary nonperfusion within 2 days, which improved from 4 days to 4 weeks postinjection (p.i.). Panretinal degeneration was observed at 4 days p.i. and progressed further at 4 weeks p.i. In the absence of CX3CR1, retinal degeneration was exaggerated and was accompanied by increased TNF-a, iNOS, IL-1ß, Ccl2, and Casp-1 gene expression. Confocal microscopy of retinal flatmounts revealed microglial activation and CD44(+)MHC-II(+) monocyte and GR1(+) neutrophil infiltration in paraquat-injected eyes. The number of activated microglia and infiltrating leukocytes was significantly higher in CX3CR1(gfp/gfp) mice than in CX3CR1(gfp/+) mice.
CONCLUSIONS:
Our results suggest that the CX3CR1 signaling pathway may play an important role in controlling retinal inflammation under oxidative and ischemia/reperfusion conditions. In the absence of CX3CR1, uncontrolled retinal inflammation results in exaggerated retinal degeneration.

Variation and Change in French Morphosyntax: The Case of Collective Nouns

Collective nouns such as majorité or foule have long been of interest to linguists for their unusual semantic properties, and provide a valuable source of new data on the evolution of French grammar. This book tests the hypothesis that plural agreement with collective nouns is becoming more frequent in French. Through an analysis of data from a variety of sources, including sociolinguistic interviews, gap-fill tests and corpora, the complex linguistic and external factors which affect this type of agreement are examined, shedding new light on their interaction in this context. Broader questions concerning the methodological challenges of studying variation and change in morphosyntax, and the application of sociolinguistic generalisations to the French of France, are also addressed.

Reviews:

‘Cet ouvrage constitue un apport majeur dans le champ de la linguistique variationniste et diachronique, tant par les résultats mis au jour que par la qualité de sa démarche méthodologique.’ — Sophie Prévost, French Studies 69.4, October 2015, 578-79

‘While language variation and change have been the focal point for linguists on this side of the Atlantic, Tristram argues that studies on morphosyntactic variation in French studies are lacking due to a focus on phonology and dialectology as well as denial of variation and change in the French language. Tristram’s book is thus a welcome contribution.’ — Samira Hassa, French Review 89.3, 2016, 108

‘Anyone teaching variation in French will want to talk about the findings and reflections reported in this study. A remarkable amount of ground is covered in a small compass. This is a highly welcome addition to the Legenda list, and one must hope that further linguistics titles will be added to it before very long.’ — Nigel Armstrong, Journal of French Language Studies 26.2, 2016, 211-13

Switchable Induced Polarization in LaAlO3/SrTiO3 Heterostructures

Demonstration of a tunable conductivity of the LaAlO3/SrTiO3 interfaces drew significant attention to the development of oxide electronic structures where electronic confinement can be reduced to the nanometer range. While the mechanisms for the conductivity modulation are quite different and include metal insulator phase transition and surface charge writing, generally it is implied that this effect is a result of electrical modification of the LaAlO3 surface (either due to electrochemical dissociation of surface adsorbates or free charge deposition) leading to the change in the two-dimensional electron. gas (2DEG) density at the LaAlO3/SrTiO3 (LAO/STO) interface. In this paper, using piezoresponse force microscopy we demonstrate a switchable electromechanical response of the LAO overlayer, which we attribute to the motion of oxygen vacancies through the LAO layer thickness. These electrically induced reversible changes in bulk stoichiometry of the LAO layer are a signature of a possible additional mechanism for nanoscale oxide 2DEG control on LAO/STO interfaces.

Resonant Rayleigh light scattering response of individual Au nanoparticles to antigen--antibody interaction

A proof-of-concept study was reported on analysis of antigen–antibody recognition based on resonant Rayleigh scattering response of single Au nanoparticles in an imaging chamber. As benefited by a traditional dark-field microscope and a spectrograph, individual Au nanoparticles (30 nm) were observed with high signal-to-noise ratio and they were effectively utilized to monitor changes in refractive index induced by specific binding of the adsorbates. Using PSA antigen as a model, a LSPR ?max shift of about 2.85 nm was recorded for a molecular binding corresponding to 0.1 pg ml-1 of the protein biomarker. This result successfully demonstrates a non-labeling detection system for proteins as well as thousands of different chemical or biological species, and it possesses a great potential as a sensitive, on-chip and multiplexing detection.

The ultrasensitive detection of prostate cancer biomarker based on resonant Rayleigh light-scattering response of single Au nanoparticle

A proof-of-concept study was reported on analysis of antigen-antibody recognition based on resonant Rayleigh scattering response of single Au nanoparticles on a microimaging chamber. As benefited by a traditional dark-field microscope and a spectrograph, tiny 30 nm Au nanoparticles were effectively used as nanosensors to monitor changes in refractive index induced by every single binding of the adsorbates. The individual Au nanoparticles were observed with very high signal-to-noise ratio, and a LSPR ?max shift of about 2.5 nm accounting for the detection of PSA antigen with concentration as low as 0.1 pg ml-1 was recorded. This resulted in the successful demonstration of a non-labelling detection system for proteins as well as thousands of different chemical or biological species with possibility of miniaturization and multiplexing scheme.

Matrilysin-1 mediates bronchiolization of alveoli, a potential premalignant change in lung cancer

Matrilysin-1 (also called matrix metalloproteinase-7) is expressed in injured lung and in cancer but not in normal epithelia. Bronchiolization of the alveoli (BOA), a potential precursor of lung cancer, is a histologically distinct type of metaplasia that is composed of cells resembling airway epithelium in the alveolar compartment. We demonstrate that there is increased expression of matrilysin-1 in human lesions and BOA in the CC10-human achaete-scute homolog-1 transgenic mouse model. Forced expression of the matrilysin-1 gene in immortalized human normal airway epithelial BEAS-2B and HPLD1 cells, which do not normally express matrilysin-1, promoted cellular migration, suggesting a functional link for BOA formation via bronchiolar cell migration. In addition, matrilysin-1 stimulated proliferation and inhibited Fas-induced apoptosis, while a knockdown by RNA interference decreased cell growth, migration, and increased sensitivity to apoptosis. Western blotting demonstrated increased levels of phospho-p38 and phospho-Erk1/2 kinases after matrilysin-1 expression. Gene expression analysis uncovered several genes that were related to cell growth, migration/movement, and death, which could potentially facilitate bronchiolization. In vivo, the formation of BOA lesions was reduced when CC10-human achaete-scute homolog-1 mice were crossed with matrilysin-1 null mice and was correlated with reduced matrilysin-1 expression in BOA. We conclude that matrilysin-1 may play an important role in the bronchiolization of alveoli by promoting proliferation, migration, and attenuation of apoptosis involving multiple genes in the MAP kinase pathway.

Morphologic fluorescein angiographic, and light microscopic features of experimental choroidal neovascularization

We induced choroidal neovascularization in the rhesus monkey by impoverishing the blood supply to the inner retina and producing defects in Bruch's membrane by photocoagulation. Fourteen of 46 eyes undergoing photocoagulation developed neovascular fronds which were identified and categorized by histopathologic examination and fluorescein angiography. All new vessels gained access to the retina through defects in Bruch's membrane at the site of photocoagulation marks. In eight eyes the new vessels remained localized to the immediate vicinity of photocoagulation marks. In four eyes neovascular fronds infiltrated the subretinal space for distances up to 6 disk diameters from the point of entry into the retina. In the two eyes choroidovitreal neovascular complexes developed but rapidly regressed shortly after gaining the vitreous cavity. Fluorescein angiography demonstrated that all neovascular fronds were grossly incompetent to dye but that formed feeding channels had some degree of integrity. Light microscopic studies showed the proliferating networks to be composed of capillaries with well-formed basement membranes and more mature vessels with the basic structure of choroidal arteries and veins.

Interaction-induced correlations and non-Markovianity of quantum dynamics

We investigate the conditions under which the trace distance between two different states of a given open system increases in time due to the interaction with an environment, therefore signaling non-Markovianity. We find that the finite-time difference in trace distance is bounded by two sharply defined quantities that are strictly linked to the occurrence of system-environment correlations created throughout their interaction and affecting the subsequent evolution of the system. This allows us to shed light on the origin of non-Markovian behaviors in quantum dynamics. We best illustrate our findings by tackling two physically relevant examples: a non-Markovian dephasing mechanism that has been the focus of a recent experimental endeavor and the open-system dynamics experienced by a spin connected to a finite-size quantum spin chain.

Dynamics of macronutrient self-medication and illness-induced anorexia in virally infected insects

Some animals change their feeding behaviour when infected with parasites, seeking out substances that enhance their ability to overcome infection. This 'self-medication' is typically considered to involve the consumption of toxins, minerals or secondary compounds. However, recent studies have shown that macronutrients can influence the immune response and that pathogen-challenged individuals can self-medicate by choosing a diet rich in protein and low in carbohydrates. Infected individuals might also reduce food intake when infected (i.e. illness-induced anorexia). Here, we examine macronutrient self-medication and illness-induced anorexia in caterpillars of the African armyworm (Spodoptera exempta) by asking how individuals change their feeding decisions over the time course of infection with a baculovirus. We measured self-medication behaviour across several full-sib families to evaluate the plasticity of diet choice and underlying genetic variation. Larvae restricted to diets high in protein (P) and low in carbohydrate (C) were more likely to survive a virus challenge than those restricted to diets with a low P : C ratio. When allowed free choice, virus-challenged individuals chose a higher protein diet than controls. Individuals challenged with either a lethal or sublethal dose of virus increased the P : C ratio of their chosen diets. This was mostly due to a sharp decline in carbohydrate intake, rather than an increased intake of protein, reducing overall food intake, consistent with an illness-induced anorexic response. Over time the P : C ratio of the diet decreased until it matched that of controls. Our study provides the clearest evidence yet for dietary self-medication using macronutrients and shows that the temporal dynamics of feeding behaviour depends on the severity and stage of the infection. The strikingly similar behaviour shown by different families suggests that self-medication is phenotypically plastic and not a consequence of genetically based differences in diet choice between families. © 2013 British Ecological Society.

Parasites that change predator or prey behaviour can have keystone effects on community composition

Parasites play pivotal roles in structuring communities, often via indirect interactions with non-host species. These effects can be density-mediated (through mortality) or trait-mediated (behavioural, physiological and developmental), and may be crucial to population interactions, including biological invasions. For instance, parasitism can alter intraguild predation (IGP) between native and invasive crustaceans, reversing invasion outcomes. Here, we use mathematical models to examine how parasite-induced trait changes influence the population dynamics of hosts that interact via IGP. We show that trait-mediated indirect interactions impart keystone effects, promoting or inhibiting host coexistence. Parasites can thus have strong ecological impacts, even if they have negligible virulence, underscoring the need to consider trait-mediated effects when predicting effects of parasites on community structure in general and biological invasions in particular.

Potential impacts of climate change on veterinary medicinal residues in livestock produce: An island of Ireland perspective

Residues of veterinary medicines are a food safety issue regulated by European legislation. The occurrence of animal diseases necessitating application of veterinary medicines is significantly affected by global and local climate changes. This review assesses potential impacts of climate change on residues in food produced on the island of Ireland. Use of various classes of veterinary drugs in light of predicted local climate change is reviewed with particular emphasis on anthelmintic drugs and consideration is given to residues accumulating in the environment. Veterinary medicine use is predicted to increase as disease burdens increase due to varied climate effects. Locally relevant mitigation and adaptation strategies are suggested to ensure climate change does not adversely affect food safety via increasing drug residues.

Climate change response in Europe: What's the reality? Analysis of adaptation and mitigation plans from 200 urban areas in 11 countries

Urban areas are pivotal to global adaptation and mitigation efforts. But how do cities actually perform in terms of climate change response? This study sheds light on the state of urban climate change adaptation and mitigation planning across Europe. Europe is an excellent test case given its advanced environmental policies and high urbanization. We performed a detailed analysis of 200 large and medium-sized cities across 11 European countries and analysed the cities' climate change adaptation and mitigation plans. We investigate the regional distribution of plans, adaptation and mitigation foci and the extent to which planned greenhouse gas (GHG) reductions contribute to national and international climate objectives. To our knowledge, it is the first study of its kind as it does not rely on self-assessment (questionnaires or social surveys). Our results show that 35 % of European cities studied have no dedicated mitigation plan and 72 % have no adaptation plan. No city has an adaptation plan without a mitigation plan. One quarter of the cities have both an adaptation and a mitigation plan and set quantitative GHG reduction targets, but those vary extensively in scope and ambition. Furthermore, we show that if the planned actions within cities are nationally representative the 11 countries investigated would achieve a 37 % reduction in GHG emissions by 2050, translating into a 27 % reduction in GHG emissions for the EU as a whole. However, the actions would often be insufficient to reach national targets and fall short of the 80 % reduction in GHG emissions recommended to avoid global mean temperature rising by 2 °C above pre-industrial levels. © 2013 Springer Science+Business Media Dordrecht.

Possibilities for change? Diversity in Post-Conflict Belfast

Belfast is often presented as an exemplary divided or post-conflict city. However, this focus can be limiting and an exploration of alternative narratives for Belfast is needed. This paper investigates the diversification of post-conflict Belfast in light of the substantial migration which has occurred in the last decade, outlining the complexities of an emerging narrative of diversity. We note discrepancies in how racial equality is dealt with at an institutional level and report on the unevenness of migrant geographies, issues which require future consideration. We also raise questions that problematize the easy assumption that cultural diversity ameliorates existing sectarian divisions.

Constitutive modeling, microstructure evolution, and processing map for a nitride-strengthened heat-resistant steel

A constitutive equation was established to describe the deformation behavior of a nitride-strengthened (NS) steel through isothermal compression simulation test. All the parameters in the constitutive equation including the constant and the activation energy were precisely calculated for the NS steel. The result also showed that from the stress-strain curves, there existed two different linear relationships between critical stress and critical strain in the NS steel due to the augmentation of auxiliary softening effect of the dynamic strain-induced transformation. In the calculation of processing maps, with the change of Zener-Hollomon value, three domains of different levels of workability were found, namely excellent workability region with equiaxed-grain microstructure, good workability region with “stripe” microstructure, and the poor workability region with martensitic-ferritic blend microstructure. With the increase of strain, the poor workability region first expanded, then shrank to barely existing, but appeared again at the strain of 0.6.