The Role of Arg228 in the phosphorylation of galactokinase: The mechanism of GHMP kinases by QM/MM studies

GHMP kinases are a group of structurally-related small molecule kinases. They have been found in all kingdoms of life and are mostly responsible for catalysing the ATP-dependent phosphorylation of intermediary metabolites. Although the GHMP kinases are of clinical, pharmaceutical and biotechnological importance, the mechanism of GHMP-kinases is controversial. A catalytic base mechanism was suggested for mevalonate kinase that has a structural feature of the ?-phosphate of ATP close to an aspartate residue; however, for one GHMP member, homoserine kinase, where the residue acting as general base is absent, a direct phosphorylation mechanism was suggested. Furthermore, it has been proposed by some authors that all the GHMP kinases function via the direct phosphorylation mechanism. This controversy in mechanism has limited our ability to exploit these enzymes as drug targets and in biotechnology. Here the phosphorylation reaction mechanism of the human galactokinase, a member of GHMP kinase was investigated using molecular dynamics simulations and density functional theory-based QM/MM calculations (B3LYP-D/AMBER99). The reaction coordinates were localized by potential energy scan using adiabatic mapping method. Our results indicate that a highly conserved Glu174 captures Arg105 to the proximity of the a-phosphate of ATP forming a H-bond network, therefore the mobility of ATP in the large oxyanion hole is restricted. Arg228 functions to stabilize the negative charge developed at the ß,?-bridging oxygen of the ATP during bond cleavage. The reaction occurs via direct phosphorylation mechanism and the Asp186 in proximity of ATP does not directly participate in the reaction pathway. Since Arg228 is not conserved among GHMP kinases, reagents which form interactions with Arg228, and therefore can interrupt its function in phosphorylation may be developed into potential selective inhibitors for galactokinase.

Transnational Fantômas: The Influence of Feuillade’s Series on International Cinema during the 1910s

The influence of Fantômas novels and films on global popular culture is widely acknowledged. From the 1915 Spanish musical "Cine-fantomas" to the 1960s Italian comic book series "Diabolik," "Kriminal" and "Satanik," from Turkish B-movies such as "Fantoma Istanbulda Bulusalim" (dir. Natuk Baytan, 1967) to Julio Cortazar’s anti-imperialist pamphlet "Fantômas contra los vampiros multinacionales" (1975), Pierre Souvestre and Marcel Allain’s original literary series have engendered uncountable translations, adaptations, imitations and plagiarisms that have spread the character’s fame worldwide since its first appearance in 1911.
By focusing on the influence of Louis Feuillade’s film adaptations during the first decade of Fantômas’ long history as a transnational and transmedia icon, this paper aims to contribute to the growing interdisciplinary field that deals with the history of the supranational cultural sphere created by modern media culture. As a sort of archaeology of contemporary cultural globalization, this form of study intends to enrich previous historical surveys that had only taken into consideration specific national contexts. Moreover, it might also rebalance certain “colonizing” accounts that overemphasize the role of the cultural superpowers such as France, the UK or the US, often forgetting the appropriation of the products of international popular culture to be found in other countries. Therefore, this paper examines the transnational circulation of Fantômas films and, in particular, the creative processes engendered outside of France their origin country. As a controversial character and a central player in the relationship between cinema and literature in the crucial years when the feature and serial film boosted and legitimized the film industry, Fantômas represents an exemplary case study to discuss the cross-cultural and cross-media dynamics engendered by popular fiction.

Pots, prestige and ritual in neolithic southern Italy,

Malone, C.A.T., in Papers in Italian Archaeology IV. Vol. ii. Prehistory, C.A.T. Malone and S.K.F. Stoddart, (eds.). 1985, British Archaeological Reports, Oxford: Cambridge. p. 118-151.

Effect of interleukin-6 polymorphisms on human longevity:a systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozygous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I2=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I2=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

Weathering rinds as mirror images of palaeosols: Examples from the Western Alps with correlation to Antarctica and Mars

Weathering rinds have been used for decades as relative age indicators to differentiate glacial deposits in long Quaternary sequences, but only recently has it been shown that rinds contain long and extensive palaeoenvironmental records that often extend far beyond mere repositories of chemical weathering on both Earth and Mars. When compared with associated palaeosols in deposits of the same age, rinds often carry a zonal weathering record that can be correlated with palaeosol horizon characteristics, with respect to both abiotic and biotic parameters. As demonstrated with examples from the French and Italian Alps, rinds in coarse clastic sediment contain weathering zones that correlate closely with horizon development in associated palaeosols of presumed Late Glacial age. In addition to weathering histories in both rinds and palaeosols, considerable evidence exists to indicate that the black mat impact (12.8 ka) reached the European Alps, a connection with the Younger Dryas readvance supported by both mineral and chemical composition. Preliminary metagenomic microbial analysis using density gradient gel electrophoresis suggests that the eubacterial microbial population found in at least one Ah palaeosol horizon associated with a rind impact site is different from that in other Late Glacial and Younger Dryas surface palaeosol horizons. © 2013 The Geological Society of London.

Exploring consumer's preferences for farmed sea bream

Sea bream (Sparus aurata) production plays a significant part in Italian aquaculture, contributing to almost 18% of national pisciculture sales revenue. In recent years, Italian firms faced higher competition from countries with lower production costs. This prompted responses toward both cost reduction and product differentiation. The objective of this study was to investigate the preferences of Italian consumers for sea bream from fish farms, with a focus on aspects of product differentiation as gleaned from the analysis of the market situation: price, product origin, type and place of fish farming, and, in particular, type of feed. Data were collected with a consumers’ survey using personal interviews conducted on a questionnaire that included a choice experiment. Consumer preferences were analyzed with choice models based on stated preference data. The models made it possible to evaluate the potential of products with different combinations of attributes for which there is currently no market information available. In particular, the country of origin emerged as an important element of consumer choice, and to a lesser degree, organic certification and fish farming in marine cages also play a relevant role and may command a price premium.

Country-of-origin effects on Russian wine consumers

In recent years, Russia has experienced significant economic growth. The wine industry is among those most affected by increases in disposable income. As a consequence, Russian wine importers have widened the range at the upper end of the quality spectrum. In the current scenario, some key questions arise concerning consumer attitudes toward wine and the way it is perceived in this evolving market. This article attempts to investigate such concerns through a choice experiment approach conducted by means of a questionnaire-based survey submitted to 388 Russian households located in the country's three largest cities (Moscow, Saint Petersburg, and Novosibirsk). In the experiment, respondents were asked to choose their favorite wine among seven dry red wines. The stated choices are analyzed using a random utility model to obtain an estimation of the price effect through a triangular distribution. Our results indicate the presence of three distinct market segments in the Russian wine market: a segment with only high-quality, highly priced Italian and French wines, a medium-quality segment currently limited to Spanish wines, and a much lower quality segment of wines in which demand for alcohol is essentially satisfied.

Cathelicidin-like Helminth Defence Molecules (HDMs):Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.

Evidence for chronic morbillivirus infection in the Mediterranean striped dolphin (Stenella coeruleoalba)

In the summer of 1990 an epizootic infection caused by a morbillivirus (DMV) killed several thousand striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea. In 1991 and 1992 the epizootic reached Italian and Greek waters. The infection by DMV in the acute period of the epizootic caused encephalitis, pneumonia and depletion of lymph nodes. After 1990, the systemic infection apparently disappeared from the Catalonian coast, giving way to cases of chronic infection of the CNS. Dolphins that died between 1991 and May 1994 were necropsied, and investigated for lesions due to DMV, and for the presence of morbillivirus antigen in tissues. Encephalitis occurred in 6 dolphins in which DMV antigen was demonstrated in the CNS and which were without lesions or antigen in other, non-nervous tissues. Inflammatory lesions, gliosis, and DMV antigen decreased in density and amount from cerebral grey matter, through the thalamic areas to the medulla oblongata. The cerebellum was usually spared. Lesions consisted of non-suppurative encephalitis, with diffuse gliosis and glial nodules and neuronophagia, and loss of neurons. Perivascular cuffing of lymphocytes and plasma cells was present in the cerebral cortex and the white matter beneath the cortex. Multinucleate syncytia were not detected in any of the dolphins. The haemagglutinin of DMV was detected mainly in neurons in the cerebral cortical areas. There was no clear relationship between the presence and amount of DMV antigen and the density or chronicity of lesions. Viral inclusions were seen in haematoxylin and eosin stained sections in 3/6 dolphins, principally in the nucleus and the cytoplasm of neurons. In the immunoperoxidase stained sections, dense granular deposits of chromogen, similar to viral inclusions, were evident in all 6 dolphins. The change in the distribution of lesions and of DMV antigen, from systemic to localized in the CNS, and the clustering of systemic DMV infections in the first four months of the epizootic, giving rise to sporadic occurrence of local CNS infection in the subsequent four years, as well as the chronic nature of the CNS lesions, which closely resembles subacute sclerosing panencephalitis, strongly support the existence of a chronic morbillivirus infection in the striped dolphin, as a delayed consequence of the 1990 epizootic.

Early Implementation of Building Information Modeling into a Cold-Formed Steel Company: Providing Novel Project Management Techniques and Solutions to Industry

The ability of building information modeling (BIM) to positively impact projects in the AEC through greater collaboration and integration is widely acknowledged. This paper aims to examine the development of BIM and how it can contribute to the cold-formed steel (CFS) building industry. This is achieved through the adoption of a qualitative methodology encompassing a literature review, exploratory interviews with industry experts, culminating in the development of e-learning material for the sector. In doing so, the research team have collaborated with one of the United Kingdom’s largest cold-formed steel designer/fabricators. By demonstrating the capabilities of BIM software and providing technical and informative videos in its creation, this project has found two key outcomes. Firstly, to provide invaluable assistance in the transition from traditional processes to a fully collaborative 3D BIM as required by the UK Government under the “Government Construction Strategy” by 2016 in all public sector projects. Secondly, to demonstrate BIM’s potential not only within CFS companies, but also within the AEC sector as a whole. As the flexibility, adaptability and interoperability of BIM software is alluded to, the results indicate that the introduction and development of BIM and the underlying ethos suggests that it is a key tool in the development of the industry as a whole.

Do Nonagenarians siblings provide mutual support? Insights from the EU GeHA project

Introduction.– Sibling relationships have been described as intimate,
congenial, loyal, apathetic or hostile but little is known about
sibling relationships in very old age.Weasked nonagenarian brothers
and sisters from the EU-funded Genetics of Healthy Ageing
(GeHA) project whether they had felt supported by having a living
sibling to have better coping abilities.
Methods and results.– Nonagenarian siblings were a convenience
sample from four countries from the GeHA study–Italy, Poland,
N Ireland, Finland. All were consented willing participants. Most
male/female dyads demonstrated healthy respect for each other’s
opinion and their sibling relationship fits the “loyal” type, though
with a clear sense of independence.Noneof the eight female/female
nor the one male/male dyad seemed to fit the “intimate” description;
two might be described as “apathetic”, while the other two
seemed to show aspects of family “loyalty”, alongside other traits
perhaps best described as “congenial”. There were apparent different
cultural influences across Europe with siblings in Italy and
Poland more likely to report supportive siblinghood, compared to
sibling pairs/trios in Finland or N Ireland where self-resilience and
independence seemed more common. Polish and Italian nonagenarians
often felt supported by their religious faith and church.
Conclusions.– In general, nonagenarian siblings most often demonstrated
loyal family relationships, which may have helped each
other’s coping and survival mechanisms. However, there was
widespread evidence of tolerance for individual decision-making.
Perhaps rather, these 90-year-olds survive because they are
resilient and independent and don’t need to depend on each other!

Rethinking the Sacred and Secular Divide. Accounting and Accountability Practices in the Diocese of Ferrara (1431-1457)

Purpose – Informed by the work of Laughlin and Booth, the paper analyses the role of accounting and accountability practices within the 15th century Roman Catholic Church, more specifically within the Diocese of Ferrara (northern Italy), in order to determine the presence of a sacred-secular dichotomy. Pope Eugenius IV had embarked upon a comprehensive reform of the Church to counter the spreading moral corruption within the clergy and the subsequent disaffection with the Church by many believers. The reforms were notable not only for the Pope’s determination to restore the moral authority and power of the Church but for the essential contributions of ‘profane’ financial and accounting practices to the success of the reforms.
Design/methodology/approach – Original 15th century Latin documents and account books of the Diocese of Ferrara are used to highlight the link between the new sacred values imposed by Pope Eugenius IV’s reforms and accounting and accountability practices.
Findings – The documents reveal that secular accounting and accountability practices were not regarded as necessarily antithetical to religious values, as would be expected by Laughlin and Booth. Instead, they were seen to assume a role which was complementary to the Church’s religious mission. Indeed, they were essential to its sacred mission during a period in which the Pope sought to arrest the moral decay of the clergy and reinstate the Church’s authority. Research implications/limitations – The paper shows that the sacred-secular dichotomy cannot be considered as a priori valid in space and time. There is also scope for examining other Italian dioceses where there was little evidence of Pope Eugenius’ reforms.
Originality/value – The paper presents a critique of the sacred-secular divide paradigm by considering an under-researched period and a non Anglo-Saxon context.

Brunetta’s reform swan song? An assessment of its success in local governments through the analysis of its tools

The work aims at assessing the success of Brunetta’s reform (Legislative Decree n. 150/2009), a far-reaching reform that aimed at improving both organizational and individual performance in Italian public administration through a specific planning and control process (the performance cycle) and most of all through two new tools, Performance Plan and Performance Report. The success of the reform is assessed, with particular emphasis on local governments, analyzing the diffusion and use of these new tools. The study has been conducted using a deductive-inductive methodology. Thus, after a study of managerial reforms in Italy and performance measurement literature, a possible model (PerformEL Model) local governments could follow to draw up Performance Plan and Report as effective tools for performance measurement has been designed (deductive phase). Performance Plans 2011-2013 and Performance Report 2011 downloaded from Italian big sized municipalities’ websites have been analyzed in the light of PerformEL Model, to assess the diffusion of the documents and their coherence with legal requirements and suggestions from literature (inductive phase). Data arising from the empirical analysis have been studied to evaluate the diffusion and the effectiveness of big sized municipalities’ Performance Plans and Reports as performance measurement tools and thus to assess the success of the reform (feedback phase). The study shows a scarce diffusion of the documents; they are mostly drew up because of their compulsoriness or to gain legitimization. The results testify the failure of Brunetta’s reform, at least with regard to local governments.

The European Convention on Human Rights and the United Kingdom's Supreme Court

This article reviews the attitudes displayed by the UK's Supreme Court towards claims based on human rights law.