Metabolic signatures of Huntington's disease (HD): 1H NMR analysis of the polar metabolome in post mortem human brain

Huntington’s disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using 1H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n=14) and frontal lobe (n=14) from HD sufferers and controls (n=28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (P<0.05; q<0.3). The metabolite which changed most overall was urea which decreased 3.25-fold in striatum (P<0.01). Four metabolites were consistently affected in both brain regions. These included the neurotransmitter precursors tyrosine and L-phenylalanine which were significantly depleted by 1.55-1.58-fold and 1.48-1.54-fold in striatum and frontal lobe, respectively (P=0.02-0.03). They also included L-leucine which was reduced 1.54-1.69-fold (P=0.04-0.09) and myo-inositol which was increased 1.26-1.37-fold (P<0.01). Logistic regression analyses performed with MetaboAnalyst demonstrated that data obtained from striatum produced models which were profoundly more sensitive and specific than those produced from frontal lobe. The brain metabolite changes uncovered in this first 1H NMR investigation of human HD offer new insights into the disease pathophysiology. Further investigations of striatal metabolite disturbances are clearly warranted.

Commentary on the Booksellers' Bill (1737)

This Bill marks the first occasion on which the British legislature proposed to confer upon authors a lifetime interest in their literary works (with an additional eleven year post-mortem term vesting in their estates), as well as limited rights of translation and abridgement. In addition the draft legislation proposed to render null and void any contract purporting to assign an author's rights to another for a period of longer than ten years.
The commentary describes the background to the Bill, and in particular the attempts of the London book trade to secure more extensive legislative protection in both 1735 and 1737. It argues that the 1737 Bill is significant precisely because it was never made into law, and because it did not suit the best interests of the metropolitan booksellers. Instead, the book trade increasingly turned to the courts to further secure their commercial interests, giving rise to what is commonly referred to as the ‘battle of the booksellers' throughout the next 40 years.

Commentary on Copyright Amendment Act 1842

The Act providing authors with the first post-mortem term of copyright protection. The term of copyright was to last either for the life of the author plus seven years after his or her death, or for forty-two years from the first publication of the same (whichever was longer). The commentary briefly discusses Thomas Noon Talfourd's repeated attempts to secure such legislation between 1837 and 1841, the opposition he experienced thereto (including Thomas Babington Macaulay's famous speech in the House of Commons on 5 February 1841 against extending the copyright term), and the success which Lord Mahon had in finally securing the Act in 1842.

Commentary on Fine Arts Copyright Act 1862

Legislation conferring copyright protection on paintings, drawings, and photographs for the life of the author plus a seven year post mortem term. The Act was also innovative in de-coupling the copyright term from the event of publication, in providing artists with a new form of ‘moral rights' protection, and in introducing the concept of "originality" as the standard threshold for copyright protection.
The commentary explores the background to the legislation, and in particular, the international copyright regime, the nature of the art market in eighteenth and early nineteenth centuries, the role of the Society of Artists in lobbying for legislative protection, and the impetus which the International Exhibition provided for securing the same. The commentary also considers how the 1862 Bill, in its earliest incarnation, incorporated elements that would have signalled a radical departure from established copyright norms. In particular, the Bill proposed: that copyright protection should not be contingent upon registration; and that protection should be offered on a universal basis, regardless of an artists' nationality, and regardless of where the work in question was created.

Combining histology, stable isotope analysis and ZooMS collagen fingerprinting to investigate the taphonomic history and dietary behaviour of extinct giant tortoises from the Mare aux Songes deposit on Mauritius

Taphonomic research of bones can provide additional insight into a site's formation and development, the burial environment and ongoing post-mortem processes. A total of 30 tortoise (Cylindraspis) femur bone samples from the Mare aux Songes site (Mauritius)were studied histologically, assessing parameters such as presence and type of microbial alteration, inclusions, staining/infiltrations, the degree of microcracking and birefringence. The absence of microbial attack in the 4200 year old Mare aux Songes bones suggests the animals rapidly entered the soil whole-bodied and were sealed anoxically, although they suffered frombiological and chemical degradation (i.e. pyrite formation/oxidation, mineral dissolution and staining) related to changes in the site's hydrology. Additionally, carbon and nitrogen stable isotopeswere analysed to obtain information on the animals' feeding behaviour. The results show narrowly distributed δ13C ratios, indicating a terrestrial C3 plant-based diet, combined with a wide range in δ15N ratios. This is most likely related to the tortoises' drought-adaptive ability to change their metabolic processes, which can affect the δ15N ratios. Furthermore, ZooMS collagen fingerprinting analysis successfully identified two tortoise species (C. triserrata and C. inepta) in the bone assemblage,which,when combined with stable isotope data, revealed significantly different δ15N ratios between the two tortoise species. As climatic changes around this period resulted in increased aridity in the Mascarene Islands, this could explain the extremely elevated δ15N ratio in our dataset. The endemic fauna was able to endure the climatic changes 4200 years ago, although human arrival in the 17th century changed the original habitat to such an extent that it resulted in the extinction of several species. Fortunately we are still able to study these extinct tortoises due to the beneficial conditions of their burial environment, resulting in excellent bone preservation.

Pig producer perspectives on the use of meat inspection as an animal health and welfare diagnostic tool in the Republic of Ireland and Northern Ireland

Background
Currently, there is growing interest in developing ante and post mortem meat inspection (MI) to incorporate measures of pig health and welfare for use as a diagnostic tool on pig farms. However, the success of the development of the MI process requires stakeholder engagement with the process. Knowledge gaps and issues of trust can undermine the effective exchange and utilisation of information across the supply chain. A social science research methodology was employed to establish stakeholder perspectives towards the development of MI to include measures of pig health and welfare. In this paper the findings of semi-structured telephone interviews with 18 pig producers from the Republic of Ireland and Northern Ireland are presented.

Results
Producers recognised the benefit of the utilisation of MI data as a health and welfare diagnostic tool. This acknowledgment, however, was undermined for some by dissatisfaction with the current system of MI information feedback, by trust and fairness concerns, and by concerns regarding the extent to which data would be used in the producers’ interests. Tolerance of certain animal welfare issues may also have a negative impact on how producers viewed the potential of MI data. The private veterinary practitioner was viewed as playing a vital role in assisting them with the interpretation of MI data for herd health planning.

Conclusions
The development of positive relationships based on trust, commitment and satisfaction across the supply chain may help build a positive environment for the effective utilisation of MI data in improving pig health and welfare. The utilisation of MI as a diagnostic tool would benefit from the development of a communication strategy aimed at building positive relationships between stakeholders in the pig industry.