The peerage of England, or A genealogical and historical account of all the families of this kingdom, that have born the dignity of peerage, either by tenure, summons to parliament, investiture, or creation, & c. from the conquest to this present year, 1713. Vol. II, [in 2 pt.]

Mode of access: Internet.

?This is not for you?: Nihilism and the House that Jacques Built

Slocombe, William, '?This is not for you?: Nihilism and the House that Jacques Built', Modern Fiction Studies (2005) 51 (1) pp.88-109 RAE2008

The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop

Spider venoms contain a plethora of insecticidal peptides that act on neuronal ion channels and receptors. Because of their high specificity, potency and stability, these peptides have attracted much attention as potential environmentally friendly insecticides. Although many insecticidal spider venom peptides have been isolated, the molecular target, mode of action and structure of only a small minority have been explored. Sf1a, a 46-residue peptide isolated from the venom of the tube-web spider Segesteria florentina, is insecticidal to a wide range of insects, but nontoxic to vertebrates. In order to investigate its structure and mode of action, we developed an efficient bacterial expression system for the production of Sf1a. We determined a high-resolution solution structure of Sf1a using multidimensional 3D/4D NMR spectroscopy. This revealed that Sf1a is a knottin peptide with an unusually large β-hairpin loop that accounts for a third of the peptide length. This loop is delimited by a fourth disulfide bond that is not commonly found in knottin peptides. We showed, through mutagenesis, that this large loop is functionally critical for insecticidal activity. Sf1a was further shown to be a selective inhibitor of insect voltage-gated sodium channels, consistent with its 'depressant' paralytic phenotype in insects. However, in contrast to the majority of spider-derived sodium channel toxins that function as gating modifiers via interaction with one or more of the voltage-sensor domains, Sf1a appears to act as a pore blocker.

Phosphine resistance in India is characterised by a dihydrolipoamide dehydrogenase variant that is otherwise unobserved in eukaryotes

Phosphine (PH3) fumigation is the primary method worldwide for controlling insect pests of stored commodities. Over-reliance on phosphine, however, has led to the emergence of strong resistance. Detailed genetic studies previously identified two loci, rph1 and rph2, that interact synergistically to create a strong resistance phenotype. We compared the genetics of phosphine resistance in strains of Rhyzopertha dominica and Tribolium castaneum from India and Australia, countries having similar pest species but widely differing in pest management practices. Sequencing analysis of the rph2 locus, dihydrolipoamide dehydrogenase (dld), identified two structurally equivalent variants, Proline49>Serine (P49S) in one R. dominica strain and P45S in three strains of T. castaneum from India. These variants of the DLD protein likely affect FAD cofactor interaction with the enzyme. A survey of insects from storage facilities across southern India revealed that the P45/49S variant is distributed throughout the region at very high frequencies, in up to 94% of R. dominica and 97% of T. castaneum in the state of Tamil Nadu. The abundance of the P45/49S variant in insect populations contrasted sharply with the evolutionary record in which the variant was absent from eukaryotic DLD sequences. This suggests that the variant is unlikely to provide a strong selective advantage in the absence of phosphine fumigation.

Chemical communication in Ropalidia marginata: Dufour's gland contains queen signal that is perceived across colonies and does not contain colony signal

Queens of the primitively eusocial wasp Ropalidia marginata appear to maintain reproductive monopoly through pheromone rather than through physical aggression. Upon queen removal, one of the workers (potential queen, PQ) becomes extremely aggressive but drops her aggression immediately upon returning the queen. If the queen is not returned, the PQ gradually drops her aggression and becomes the next queen of the colony. In a previous study, the Dufour's gland was found to be at least one source of the queen pheromone. Queen-worker classification could be done with 100% accuracy in a discriminant analysis, using the compositions of their respective Dufour's glands. In a bioassay, the PQ dropped her aggression in response to the queen's Dufour's gland macerate, suggesting that the queen's Dufour's gland contents mimicked the queen herself. In the present study, we found that the PQ also dropped her aggression in response to the macerate of a foreign queen's Dufour's gland. This suggests that the queen signal is perceived across colonies. This also suggests that the Dufour's gland in R. marginata does not contain information about nestmateship, because queens are attacked when introduced into foreign colonies, and hence PQ is not expected to reduce her aggression in response to a foreign queen's signal. The latter conclusion is especially significant because the Dufour's gland chemicals are adequate to classify individuals correctly not only on the basis of fertility status (queen versus worker) but also according to their colony membership, using discriminant analysis. This leads to the additional conclusion (and precaution) that the ability to statistically discriminate organisms using their chemical profiles does not necessarily imply that the organisms themselves can make such discrimination. (C) 2010 Elsevier Ltd. All rights reserved.

Molecular Phylogeny of Geographical Isolates of Bursaphelenchus xylophilus: Implications on the Origin and Spread of this Species in China and Worldwide

The genetic diversity and phylogeny of 26 isolates of Bursaphelenchus xlophilus from China, Japan, Portugal and North America were investigated based on the D2/3 domain of 28S rDNA, nuclear ribosomal Internal Transcribed Spacer (ITS) sequences, and random amplified polymorphic DNA (RAPD) analysis. The genetic diversity analysis showed that the D2/3 domain of 28S rDNA of isolates of B. xlophilus from China, Portugal, Japan and the US were identical and differed at one to three nucleotides compared to those from Canada. ITS sequences of isolates from China and Portugal were the same; they differed at one or two nucleotides compared to those of Japanese isolates and at four and 23 nucleotides compared to those front the US and Canada, respectively. The phylogenetic analysis indicated that Chinese isolates share a common ancestor with one of the two Japanese clades and that the Canadian isolates form a sister group of the clade comprised of isolates from China, Portugal,Japan, and the US. The relationship between Japanese isolates and those from China was closer than with the American isolates. The Canadian isolates were the basal group of B. xylophilus. This suggests that B. xlophilus originated in North America and that the B. xylphilus that occurs in China could have been first introduced from Japan. Further analysis based on RAPD analysis revealed that the relationship among isolates from Guangdong, Zhejiang, Shandong, Anhui provinces and Nanjing was the closest, which suggests that pine wilt disease in these Chinese locales was probably dispersed from Nanjing, where this disease first occurred in China.

Factors that effect antioxidant activity of C-phycocyanins from Spirulina platensis

Currently, antioxidants are added in the human diet to prevent free radical-induced cell damage, and there has been an explosive interest in the use of antioxidant nutritional supplements. The effects of different factors on the antioxidant activity of phycocyanins (PCs) were studied. The results showed that PCs generated hydroxyl radicals in the light, while scavenging them in the dark. When PCs were denatured by sodium dodecyl sulfate, urea and in alkaline condition, their ability to generate hydroxyl radicals disappeared and that of scavenging them greatly increased. This showed that the phycobilin moiety is the main part of PC involved in scavenging hydroxyl radicals. Trypsin hydrolysis of PCs showed that the apoprotein portion of the molecule also made a significant contribution to the antioxidant activity.

Interacting Supernovae and Supernova Impostors: SN 2009ip, is this the End?

We report the results of a three-year-long dedicated monitoring campaign of a restless luminous blue variable (LBV) in NGC 7259. The object, named SN 2009ip, was observed photometrically and spectroscopically in the optical and near-infrared domains. We monitored a number of erupting episodes in the past few years, and increased the density of our observations during eruptive episodes. In this paper, we present the full historical data set from 2009 to 2012 with multi-wavelength dense coverage of the two high-luminosity events between 2012 August and September. We construct bolometric light curves and measure the total luminosities of these eruptive or explosive events. We label them the 2012a event (lasting ~50 days) with a peak of 3 × 1041 erg s-1, and the 2012b event (14 day rise time, still ongoing) with a peak of 8 × 1042 erg s-1. The latter event reached an absolute R-band magnitude of about -18, comparable to that of a core-collapse supernova (SN). Our historical monitoring has detected high-velocity spectral features (~13,000 km s-1) in 2011 September, one year before the current SN-like event. This implies that the detection of such high-velocity outflows cannot, conclusively, point to a core-collapse SN origin. We suggest that the initial peak in the 2012a event was unlikely to be due to a faint core-collapse SN. We propose that the high intrinsic luminosity of the latest peak, the variability history of SN 2009ip, and the detection of broad spectral lines indicative of high-velocity ejecta are consistent with a pulsational pair-instability event, and that the star may have survived the last outburst. The question of the survival of the LBV progenitor star and its future fate remain open issues, only to be answered with future monitoring of this historically unique explosion.

CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells

Although they are considered as antigen presenting cells (APC), the role of antigen-unspecific B-lymphocytes in antigen presentation and T lymphocyte stimulation remains controversial. In this paper, we tested the capacity of normal human peripheral activated B cells to stimulate T cells using melanoma antigens or melanoma cell lysates. B lymphocytes activated through CD40 ligation and then pulsed with tumor antigens efficiently processed and presented MHC class II restricted peptides to specific CD4+ T cell clones. This suggests that CD40-activated B cells have the functional and molecular competence to present MHC class II epitopes when pulsed with exogenous antigens, thereby making them a relevant source of APC to generate T cells. To test this hypothesis, CD40-activated B cells were pulsed with a lysate prepared from melanoma cells and used to stimulate peripheral autologous T cells. Interestingly, T cells specific to melanoma antigens were generated. Further analysis of these T cell clones revealed that they recognized MHC class II restricted epitopes from tyrosinase, a known melanoma tumor antigen. The efficient antigen presentation by antigen-unspecific activated B cells was correlated with a down-regulation in the expression of HLA-DO, a B cell specific protein known to interfere with HLA-DM function. Because HLA-DM is important in MHC class II peptide loading, the observed decrease in HLA-DO may partially explain the enhanced antigen presentation following B-cell activation. Results globally suggest that when they are properly activated, antigen-unspecific B-lymphocytes can present exogenous antigens by MHC class II molecules and stimulate peripheral antigen-specific T cells. Antigen presentation by activated B cells could be exploited for immunotherapy by allowing the in vitro generation of T cells specific against antigens expressed by tumors or viruses.

From "This is my body" to the Church in the twenty-first century: the Last Supper as the decisive moment and criterion of a renewed ecclesiology

Certains symptômes sont les indicateurs incontestés des très graves problèmes que connaît l’Église. S’ils existent aussi dans des confessions et des religions diverses, seuls seront examinés ici ceux qui concernent l’Église catholique. Parmi les plus significatifs figurent un fort déclin dans la participation à des activités religieuses comme les célébrations eucharistiques dominicales, surtout chez les jeunes, une pénurie presque catastrophique de prêtres ordonnés, une perte de prestige et d’influence de l’enseignement dispensé par l’Église. Ces symptômes varient en intensité selon les pays, mais les statistiques indiquent qu’ils se multiplient. Nombre de ces problèmes sont attribuables à l’extrême vélocité de changements qui surviennent partout et à l’apparente inaptitude de l’Église à s’adapter, en raison notamment de son attachement à la pensée néo-scolastique et à la tradition tridentine. Cette fidélité absolue à une tradition vieille de quatre cents ans l’empêche de se faire à un environnement en évolution rapide et radicale. Des changements appropriés s’imposent pratiquement partout dans l’Église. Or, pour que ceux-ci soient efficaces et respectueux de la nature propre de l’Église, la tradition est un guide qui ne suffit pas. S’appuyant sur les termes de l’encyclique Ecclesia de Eucharistia, « le moment décisif où elle (l’Église) a pris forme est certainement celui où a eu lieu l’institution de l’Eucharistie, dans la chambre à l’étage », la thèse présentée suit le plus près possible l’interprétation donnée aux paroles de Jésus, ceci est mon corps, telles qu’elles ont été prononcées la première fois. Selon cette évidence, il est permis d’affirmer que les caractéristiques définitoires de l’Église provenant de ces mots sont agape, unité, service. Tel doit être le principe directeur des changements. C’est sur une telle base que sont décrits les secteurs où les changements s’imposent ainsi que les aspects visés. Ces changements comprennent les points suivants : liturgie, sacrements, catéchèse, mystagogie, théologie, structure, gouvernance de l’Église et ses enseignements, évangélisation. Ces secteurs exigent des efforts sérieux dans la préparation des personnes touchées par ces changements et dans l’attention portée à l’exigence primordiale voulant qu’agape, unité et service soient les principes actifs et évidents régissant l’Église.

This recovery is different. CEPS Commentary 6 September 2012

The misguided belief that “this time is different” led policy-makers to permit the credit boom of the early 2000s to continue for too long, thus preparing the ground for the biggest financial crisis in living memory. But when it comes to the recovery this around, CEPS Director Daniel Gros argues in this Commentary that the belief that this time should not be different might be equally dangerous.

Evidence that indirect inhibition of saccade initiation improves saccade accuracy

Saccadic eye-movements to a visual target are less accurate if there are distracters close to its location (local distracters). The addition of more distracters, remote from the target location (remote distracters), invokes an involuntary increase in the response latency of the saccade and attenuates the effect of local distracters on accuracy. This may be due to the target and distracters directly competing (direct route) or to the remote distracters acting to impair the ability to disengage from fixation (indirect route). To distinguish between these we examined the development of saccade competition by recording saccade latency and accuracy responses made to a target and local distracter compared with those made with an addition of a remote distracter. The direct route would predict that the remote distracter impacts on the developing competition between target and local distracter, while the indirect route would predict no change as the accuracy benefit here derives from accessing the same competitive process but at a later stage. We found that the presence of the remote distracter did not change the pattern of accuracy improvement. This suggests that the remote distracter was acting along an indirect route that inhibits disengagement from fixation, slows saccade initiation, and enables more accurate saccades to be made.

Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response

An NMR-based pharmacometabonomic approach was applied to investigate inter-animal variation in response to isoniazid (INH; 200 and 400 mg/kg) in male Sprague-Dawley rats, alongside complementary clinical chemistry and histopathological analysis. Marked inter-animal variability in central nervous system (CNS) toxicity was identified following administration of a high dose of INH, which enabled characterization of CNS responders and CNS non-responders. High-resolution post-dose urinary (1)H NMR spectra were modeled both by their xenobiotic and endogenous metabolic information sets, enabling simultaneous identification of the differential metabolic fate of INH and its associated endogenous metabolic consequences in CNS responders and CNS non-responders. A characteristic xenobiotic metabolic profile was observed for CNS responders, which revealed higher urinary levels of pyruvate isonicotinylhydrazone and β-glucosyl isonicotinylhydrazide and lower levels of acetylisoniazid compared to CNS non-responders. This suggested that the capacity for acetylation of INH was lower in CNS responders, leading to increased metabolism via conjugation with pyruvate and glucose. In addition, the endogenous metabolic profile of CNS responders revealed higher urinary levels of lactate and glucose, in comparison to CNS non-responders. Pharmacometabonomic analysis of the pre-dose (1)H NMR urinary spectra identified a metabolic signature that correlated with the development of INH-induced adverse CNS effects and may represent a means of predicting adverse events and acetylation capacity when challenged with high dose INH. Given the widespread use of INH for the treatment of tuberculosis, this pharmacometabonomic screening approach may have translational potential for patient stratification to minimize adverse events.

Speech therapy after stroke: trial shows only that practice varies

Bowen and colleagues’ methods and conclusions raise concerns.1 At best, the trial evaluates the variability in current practice. In no way is it a robust test of treatment. Two communication impairments (aphasia and dysarthria) were included. In the post-acute stage spontaneous recovery is highly unpredictable, and changes in the profile of impairment during this time are common.2 Both impairments manifest in different forms,3 which may be more or less responsive to treatment. A third kind of impairment, apraxia of speech, was not excluded but was not targeted in therapy. All three impairments can and do co-occur. Whether randomised controlled trial designs can effectively cope with such complex disorders has been discussed elsewhere.4 Treatment was defined within terms of current practice but was unconstrained. Therefore, the treatment group would have received a variety of therapeutic approaches and protocols, some of which may indeed be ineffective. Only 53% of the contact time with a speech and language therapist was direct (one to one), the rest was impairment based therapy. In contrast, all of the visitors’ time was direct contact, usually in conversation. In both groups, the frequency and length of contact time varied. We already know that the transfer from impairment based therapy to functional communication can be limited and varies across individuals.5 However, it is not possible to conclude from this trial that one to one impairment based therapy should be replaced. For that, a well defined impairment therapy protocol must be directly compared with a similarly well defined functional communication therapy, with an attention control.

Promoter analysis and immunolocalisation show that puroindoline genes are exclusively expressed in starchy endosperm cells of wheat grain

The purolindolines are small cysteine-rich proteins which are present in the grain of wheat. They have a major impact on the utilisation of the grain as they are the major determinants of grain texture, which affects both milling and baking properties. Bread and durum wheats were transformed with constructs comprising the promoter regions of the Puroindoline a (Pina) and Puroindoline b (Pinb) genes fused to the uidA (GUS) reporter gene. Nine lines showing 3:1 segregation for the transgene and comprising all transgene/species combinations were selected for detailed analysis of transgene expression during grain development. This showed that transgene expression occurred only in the starchy endosperm cells and was not observed in any other seed or vegetative tissues. The location of the puroindoline proteins in these cells was confirmed by tissue printing of developing grain, using a highly specific monoclonal antibody for detection and an antibody to the aleurone-localised 8S globulin as a control. This provides clear evidence that puroindolines are only synthesised and accumulated in the starchy endosperm cells of the wheat grain.