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Background and purpose Tetanus neurotoxin has many potential therapeutic applications, due to its ability to increase localised muscle tone when injected directly into a muscle. It is a closely related molecule to botulinum neurotoxin (most commonly known as Botox), which has been widely used to release muscle tension for therapeutic and cosmetic applications. However, tetanus toxin has been relegated to the “maybe pile” for protein therapeutics — as most of the population is vaccinated, leading to highly effective antibody-mediated protection against the toxin. The potential for tetanus-based therapeutics remains substantial if the problem of pre-existing immunity can be resolved. Experimental approach A well-established murine model of localised muscular contraction was utilised. We administered functional tetanus toxin combined with an immunogenic, but functionally inactive, decoy molecule. Key results Incorporation of the decoy molecule greatly reduces the dose of active toxin required to induce a localised increase in muscle tone in mice vaccinated with the human toxoid vaccine. Conclusion and implications Our results clearly demonstrate that the barriers to developing a tetanus toxin therapeutic are not insurmountable and the technology presented here is the first major step towards realising the therapeutic potential of this powerful neurotoxin. Opening the therapeutic potential of tetanus toxin will have huge implications for the wide range of diseases caused by low-tone muscle.

For thousands of years, arches have been used as durable structures that are easy to build and that rely on gravity for their inherent stability. Since then, many researchers and engineers have studied their stability either when subjected to gravity or inertial loading. Currently, given the Insight mission to Mars and the ambitious Artemis program to the Moon, it has become apparent that there will soon be the need to design and build the first resilient extraterrestrial structures and arches represent an ideal option for such structures. This paper focuses on the stability of parabolic arches with different embrace angles subjected to different levels of equivalent inertial loading in low-gravity conditions. The results are contrasted with the well-studied circular arches. More specifically, this investigation employs variational principles to identify the imminent mechanisms and numerical methods based on the limit thrust line concept in order to estimate the minimum required thickness of parabolic arches for a given loading and in different gravitational fields. The paper shows that although parabolic arches can be much more efficient than their circular counterparts for gravitational-only loading, this is not the case for different combinations of inertial loading and embrace angles where the opposite can be true. It highlights the dominant effect of low-gravity conditions on the minimum thickness requirements for both types of arches and considers the effect of a potential additional infill for radiation shielding. Furthermore, this study reveals a self-similar behaviour, introduces a “universal” inertial loading and showcases, through the use of master curves, the areas where the parabolic arches are more efficient than their circular counterparts and those where the opposite is true. These areas can be used for the preliminary design of such structures. Additionally, the paper identifies hidden patterns associated with the developed mechanisms between the two different geometries for the different gravitational fields. Finally, it presents a case study where the need to optimise the structural form of extraterrestrial structures becomes evident.

Background Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross‐reactivity. Despite sequence similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns, and T‐cell reactivity. Methods We investigated the differences between four tropomyosins—the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach), and Ani s 3 (fish parasite)—in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T‐cell cross‐reactivity in a BALB/c murine model. Results Tropomyosins displayed different melting temperatures, which did not correlate with amino acid sequence similarities. Endolysosomal degradation experiments demonstrated differential proteolytic digestion, as a function of thermal stability, generating different peptide repertoires. Pen m 1 (Tm 42°C) and Der p 10 (Tm 44°C) elicited similar patterns of endolysosomal degradation, but not Bla g 7 (Tm 63°C) or Ani s 3 (Tm 33°C). Pen m 1–specific T‐cell clones, with specificity for regions highly conserved in all four tropomyosins, proliferated weakly to Der p 10, but did not proliferate to Bla g 7 and Ani s 3, indicating lack of T‐cell epitope cross‐reactivity. Conclusions Tropomyosin T‐cell cross‐reactivity, unlike IgE cross‐reactivity, is dependent on structural stability rather than amino acid sequence similarity. These findings contribute to our understanding of cross‐sensitization among different invertebrates and design of suitable T‐cell peptide‐based immunotherapies for shrimp and related allergies., Allergenic tropomyosins have dissimilar structural stabilities despite having high amino acid sequence similarity. Tropomyosins are differentially degraded in the endolysosomal compartment of antigen‐presenting cells due to differences in their structural stability. Tropomyosin T‐cell cross‐reactivity, unlike IgE antibody cross‐reactivity, is dependent on structural stability rather than amino acid sequence similarity.

Seafood refers to several distinct groups of edible aquatic animals including fish, crustacean, and mollusc. The two invertebrate groups of crustacean and mollusc are, for culinary reasons, often combined as shellfish but belong to two very different phyla. The evolutionary and taxonomic diversity of the various consumed seafood species poses a challenge in the identification and characterisation of the major and minor allergens critical for reliable diagnostics and therapeutic treatments. Many allergenic proteins are very different between these groups; however, some pan-allergens, including parvalbumin, tropomyosin and arginine kinase, seem to induce immunological and clinical cross-reactivity. This extensive review details the advances in the bio-molecular characterisation of 20 allergenic proteins within the three distinct seafood groups; fish, crustacean and molluscs. Furthermore, the structural and biochemical properties of the major allergens are described to highlight the immunological and subsequent clinical cross-reactivities. A comprehensive list of purified and recombinant allergens is provided, and the applications of component-resolved diagnostics and current therapeutic developments are discussed.

Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins (THDPs) to ensure their efficient distribution through the blood and cerebrospinal fluid in vertebrates. Albumin is a THDP in the blood of all studied species of vertebrates, so may be the original vertebrate THDP. However, albumin has weak affinity for THs. Transthyretin (TTR) has been identified in the blood across different lineages in adults vs juveniles. TTR has intermediate affinity for THs. Thyroxine-binding globulin has only been identified in mammals and has high affinity for THs. Of these THDPs, TTR is the only one known to be synthesised in the brain and is involved in moving THs from the blood into the cerebrospinal fluid. We analysed the rates of evolution of these three THDPs: TTR has been most highly conserved and albumin has had the highest rate of divergence.

Jane Porter’s later career illustrates the difficulties faced by writers who must balance political beliefs with affective responsibilities. After her brother, the artist Sir Robert Ker Porter, married into a prominent Russian family, Porter was constantly divided between a desire to publicly support Polish sovereignty and a familial need to placate her Russian in-laws. When Robert took a diplomatic position in Gran Colombia, Porter secretly used her literary connections to promulgate her brother’s achievements. The Court Journal and United Service Journal and Naval and Military Magazine gave her access to political and military readers who might aid Robert’s career, but she hid her own identity behind a range of initials and pseudonyms. Building on recent discussions of Romantic literary families, this essay considers the conflicts behind Porter’s periodical writings and the affective strategies she deployed to navigate her public and private opinions.

Templating has been demonstrated to be an efficient method of nanocapsule preparation. However, there have been no reports of using protein-only nanocapsules as an antigen delivery system. Such a system would enable the delivery of antigen without additional polymers. This study focused on defining the structural and cellular characteristics of nanocapsules consisting of antigen (ovalbumin) alone, synthesized by the templating method using highly monodispersed solid core mesoporous shell (SC/MS) and mesoporous (MS) silica nanoparticles of 410 nm and 41 nm in diameter, respectively. The synthesized ovalbumin nanocapsules were homogeneous in structure, and cellular uptake was observed in DC2.4 murine immature dendritic cells with minimal cytotoxicity. The nanocapsules were localized intracellularly and induced antigen presentation by the cross-presentation pathway. The templating system, using SC/MS and MS silica nanoparticles, was demonstrated to be an effective nanocapsule synthesis method for a new antigen delivery system.

It has been suggested that gluten consumption is linked to schizophrenia, with this link strengthened through the presence of circulating anti-native gliadin antibodies (AGAs). The human leukocyte antigen (HLA) system is crucial for antigen presentation and antibody secretion but no study has examined the relationship between HLA-II variants and circulating antibodies against gliadin peptides. In this study, HLA-II variants were genotyped in patients with schizophrenia and the relationship between these variants and plasma AGA levels was examined. Although there was no association found, HLA-AGA associations could potentially serve as a marker of gluten sensitivity in patients with schizophrenia.

This article examines the extent to which changes in Swedish values and culture are undermining what has come to be known as the penal exceptionalism of that society. It does this by contrasting the two very different pictures of Swedish society that are to be found in the detective novels of Maj Sjöwall and Per Wahlöö, set in the 1960s and early 1970s, and those of Henning Mankell, set in the 1990s onwards. Notwithstanding the extensive social change we find reflected in them, it is argued that Sweden’s penal exceptionalism has been reconfigured rather than swept aside. It largely remains intact for those on the legitimate side of the barriers and divisions that mass immigration has constructed around it, but those whose ethnicity denies them this status are likely to find themselves excluded from it.

He was at a Small Evening party at the Poet Sotheby’s. I was not aware of his being in the room, or even that he had been invited, when I was arrested from listening to the person conversing with me by the Sounds of the most melodious Speaking Voice I had ever heard. It was gentle and beautifully modulated. I turned round to look for the Speaker, and then saw a Gentleman in black of an Elegant form (for nothing of his lameness could be discovered), and with a face I never shall forget. The features of the finest proportions. The Eye deep set, but mildly lustrous; and the Complexion what I at the time described to my Sister as a Sort of moonlight paleness. It was so pale, yet with all so Softly brilliant. I instantly asked my Companion who that Gentleman was. He replied, ‘Lord Byron’. I was astonished, for there was no Scorn, no disdain, nothing in that noble Countenance then of the proud Spirit which has since soared to Heaven, illuminating the Horizon far and wide.

Biographies of Edmund Kean occasionally mention his disastrous one-night performance in Jane Porter's play Switzerland in February 1819. While several commentators have blamed the work's failure on its inferior quality, Porter's unpublished letters tell a more complicated story. Using Porter's correspondence with Mary Kean, the Drury Lane committee, and various friends, this essay sheds light on her experiences in the London theatrical world and suggests interesting parallels between the careers of Porter and John Keats. Porter read Endymion with interest and hoped to meet the author, but she probably did not know that they shared a dangerous fascination with Edmund Kean.

Despite recent scholarly interest in the historical novel and national tale, Jane Porter has not received the critical attention paid to other Romantic-era novelists like Sir Walter Scott, Maria Edgeworth, and Lady Morgan. This essay argues for the importance of Porter's work, in particular her 1803 novel Thaddeus of Warsaw, in the development of the historical novel. The essay's first half examines Porter's literary and epistolary responses to the novels and celebrity of Sir Walter Scott as well as Scott's responses to Porter's work, and then considers explanations for the scholarly neglect of Porter. The second half argues that Thaddeus of Warsaw anticipates several key features of the historical novel identified by Georg Lukacs, features that would regularly reappear in the Waverley novels. Porter's interest in human virtue links her to eighteenth-century writers like Mackenzie and Richardson, but she differs from those predecessors in focusing on the actions of virtuous individuals in periods of historical disruption, thus moving the man of feeling onto scenes of revolution.

IN DECEMBER 1916 A WRITER FOR THE IRISH BOOK LOVER LAMENTED THAT THE centenary of the birth of Frances Brown, once known far and wide as 'the blind girl of Donegal,' which occurred on 16th January last, did not elicit a single line in any journal, as far as I am aware, showing, alas! how transient a thing is a literary reputation." Though Brown's name is "sought in vain in the 'Dictionary of National Biography,'" the anonymous writer believed "our northern province is not so rich in women writers that it can afford to neglect one, who, in her day, brought to it some degree of fame, as much by her widely acknowledged abilities as her heroic struggle to overcome the results of her early affliction." (1) Almost ninety years later, the life and work of Frances Brown (or Browne, as it is more often written) remain neglected, though her biography is as extraordinary as any writer's in the nineteenth century, and her poetry evinces a strong personal voice and a rich variety of subjects. While Browne's nationalistic lyric "Songs of Our Land" was a particular favorite in the Victorian era, other poems feature Muslim, Jewish or Christian protagonists, and her settings cover five continents. Her longest works include "The Vision of Schwartz," about a twelfth-century monk's search for the philosopher's stone, and the subject of this essay, The Star of Atteghei, a tragic romance set in nineteenth-century Circassia. Such a range of historical and geographical interests is unusual though not unique among women poets of the 1840s; but it becomes rather startling when we consider that Frances Browne became blind before the age of two and spent the first thirty years of her life far from the literary centers of Ireland or Britain. Browne's lifelong fascination with world history certainly influenced her choice of subject matter, but it was not simply a taste for the exotic that inspired her to choose Circassia as the setting and subject of her longest poem. A number of travelogues describing the Caucasus had recently appeared, and British newspapers regularly reported the Circassians' struggles with Russia from the mid1830s onwards, reaching something of a peak in early 1844, the year The Star of Atteghei appeared. Browne's work is the major poetic response in the English language to a conflict that resulted in the forced removal of more than one million Circassians and Turkic Caucasians from their homeland, a conflict directly related to Russia's ongoing struggle in Chechnya. Browne draws inspiration from Lord Byron's Eastern Tales of the 1810s and from the psychologically-charged portraits of women crafted in the following two decades by Felicia Hemans and Letitia Landon; but she extends her predecessors' work by situating her mysterious and courageous heroine in a narrative based on recent historical events. Thus her poem is also an intriguing expression of nineteenth-century concepts of nationalism, bringing together three nations whose struggles for independence and national identity were well known in the Victorian era: Circassia, Poland, and Ireland. In doing so it also associates Russia and England as fellow oppressors. Norman Vance has recently noted that "Victorian Ulster and its writers have been little explored, perhaps because of a suspicion that the most British province could not possibly be authentically Irish." (2) My essay begins to address this oversight by focusing on one poet whose favored themes of exile and national identity mirrored the major issues facing nineteenth-century Ireland. In the first half I sketch the life of Frances Browne and the contemporary situation in Circassia, at least the reports of that situation then available to British and Irish readers. In the second half I focus on The Star of Atteghei, analyzing its representations of nationalistic sentiments and the surprising ways Browne uses nationality and gender to tell her story. Despite her perceived economic, physical, and geographical limitations, "the blind girl of Donegal" recognized in the Caucasus war a struggle with striking similarities to the situation in Poland and troubling associations with the recent history of her homeland. …