Radiation-induced intercellular signaling mediated by cytochrome-c via a p53-dependent pathway in hepatoma cells

The tumor suppressor p53 has a crucial role in cellular response to DNA damage caused by ionizing radiation, but it is still unclear whether p53 can modulate radiation-induced bystander effects (RIBE). In the present work, three different hepatoma cell lines, namely HepG2 (wild p53), PLC/PRF/5 (mutation p53) and Hep3B (p53 null), were irradiated with c-rays and then co-cultured with normal Chang liver cell (wild p53) in order to elucidate the mechanisms of RIBE. Results showed that the radiosensitivity of HepG2 cells was higher than that of PLC/PRF/5 and Hep3B cells. Only irradiated HepG2 cells, rather than irradiated PLC/PRF/5 or Hep3B cells, could induce bystander effect of micronuclei (MN) formation in the neighboring Chang liver cells. When HepG2 cells were treated with 20 mu M pifithrin-alpha, an inhibitor of p53 function, or 5 lM cyclosporin A (CsA), an inhibitor of cytochrome- c release from mitochondria, the MN induction in bystander Chang liver cells was diminished. In fact, it was found that after irradiation, cytochrome- c was released from mitochondria into the cytoplasm only in HepG2 cells in a p53- dependent manner, but not in PLC/PRF/5 and Hep3B cells. Interestingly, when 50 lg/ml exogenous cytochrome- c was added into cell co- culture medium, RIBE was significantly triggered by irradiated PLC/PRF/5 and Hep3B cells, which previously failed to provoke a bystander effect. In addition, this exogenous cytochrome- c also partly recovered the RIBE induced by irradiated HepG2 cells even with CsA treatment. Our results provide new evidence that the RIBE can be modulated by the p53 status of irradiated hepatoma cells and that a p53- dependent release of cytochrome- c may be involved in the RIBE. Oncogene (2011) 30, 1947- 1955; doi: 10.1038/onc. 2010.567; published online 6 December 2010

Predator diversity enhances secondary production and decreases the likelihood of trophic cascades

We manipulated the diversity of top predators in a three trophic level marine food web. The food web included four top benthic marine fish predators (black goby, rock goby, sea scorpion and shore rockling), an intermediate trophic level of small fish, and a lower trophic level of benthic invertebrates. We kept predator density constant and monitored the response of the lower trophic levels. As top predator diversity increased, secondary production increased. We also observed that in the presence of the manipulated fish predators, the density of small gobiid fish (intermediate consumers) was suppressed, releasing certain groups of benthic invertebrates (caprellid amphipods, copepods, nematodes and spirorbid worms) from heavy intermediate predation pressure. We attribute the mechanism responsible for this trophic cascade to a trait-mediated indirect interaction, with the small gobiid fish changing their use of space in response to altered predator diversity. In the absence of top fish predators, a full-blown trophic cascade occurs. Therefore the diversity of predators reduces the likelihood of trophic cascades occurring and hence provides insurance against the loss of an important ecosystem function (i.e. secondary production).

How resource quality differentially affects motivation and ability to fight in hermit crabs

Contesting animals typically gather information about the resource value and that information affects fight motivation. However, it is possible that particular resource characteristics alter the ability to fight independently of the motivation. Using hermit crabs, we investigate how the resource in terms of shell quality affects both motivation and ability to fight. These crabs fight for shells, but those shells have to be carried and may impose physiological costs that impede fight vigour. We find that the shell has different effects on motivation and ability. Potential attackers in very small shells were highly motivated to attack but, rather than having enhanced ability, unexpectedly quickly fatigued and subsequently were not more successful in the fights than were crabs in larger shells. We also examined whether defending crabs could gather information about the attacker's shell from the vigour of the attack. Defending crabs gave up quickly when a potential gain had been assessed, indicating that such information had been gathered. However, there was no indication that this could be owing to the activity of the attacker and the information is probably gathered via visual assessment of the shell.

Observations on the mechanism of eggshell formation in the liver fluke, Fasciola hepatica

A mechanism for eggshell production in Schistosoma mansoni has been proposed (Wells & Cordingley, 1991), and suggests that the release of eggshell protein globules from the vitelline cells occurs under alkaline conditions within the ootype followed by their subsequent fusion to form the eggshell. Fusion and tanning of these components produces eggshell which autofluoresces. The present study was carried out to determine whether a similar process operates in Fasciola hepatica. A number of drug treatments were used to disrupt key steps in the maturation of vitelline cells. Treatment with the calcium ionophore lasalocid (1 x 10(-5) M) led to the premature release of eggshell globules from the vitelline cells but not their fusion. Incubation in monensin (1 x 10(-6) M), a sodium ionophore and ammonium chloride (NH4Cl) (5 x 10(-2) M), a weak base, resulted in the premature fusion of eggshell protein globules within the vitelline cells and premature tanning of the eggshell protein material. The copper-containing enzyme, phenol oxidase, is thought to be involved in the tanning process during the production of eggs. Diethyldithiocarbamate (DDC, 1 x 10(-3) M) is a phenol oxidase inhibitor and treatment with this compound, in combination treatments with monensin and NH4Cl, prevented fusion of the vitelline cell globules and tanning of the shell protein material. The results of the study suggest that the mechanism for eggshell formation in F. hepatica is similar to that proposed for S. mansoni and may be common to other trematodes as well.

THE EFFECT OF THE SULFOXIDE METABOLITE OF TRICLABENDAZOLE (FASINEX) ON THE TEGUMENT OF MATURE AND IMMATURE STAGES OF THE LIVER FLUKE, FASCIOLA-HEPATICA

The effects of the novel benzimidazole, triclabendazole (TCBZ) ('Fasinex', Ciba-Geigy), in its active sulphoxide metabolite form (TCBZ-SX), on the tegumental ultrastructure of Fasciola hepatica were determined in vitro by transmission electron microscopy (TEM), using both intact flukes and tissue-slice material. At a concentration of 15 mu g/ml, the tegument of the whole adult fluke showed ultrastructural changes only after prolonged time-periods, with vacuolation at the base of the syncytium and accumulation of T2 secretory bodies in the tegumental cells. At a concentration of 50 mu g/ml, with both whole flukes and tissue-slices, the tegument appeared extremely abnormal with accumulation of secretory bodies towards the base of the syncytium. With longer incubation times, the tegument was completely sloughed away and the tegumental cells became synthetically inactive. The tegument of the 3-week-old juvenile became progressively convoluted at the apex, while in the basal regions there was severe vacuolation. In the tegumental cells, there were accumulations of T1 secretory bodies. These results confirm TCBZ as a potent fasciolicide, being very effective in disrupting the fluke tegument. They may go some way to explain the mode of action of this important fasciolicide.

Poverty and power: the Irish Poor Law in a north Antrim town 1861-1921

This examines the workings of the Irish Poor Law in the town of Ballymoney, Co. Antrim, during the period between the end of the Great Famine and Partition. It focuses both on those who administered and those who used the poor law and argues that for the former it provided an important route into local politics and for the latter it represented a crucial strand in the limited strategies for survival open to them. It also demonstrates the impact that local political outlook had on both the administration and the experience of poor relief.

The importance of solid-phase distribution on the oral bioaccessibility of Ni and Cr in soils overlying Palaeogene basalt lavas, Northern Ireland

Potentially toxic elements (PTEs) including nickel and chromium are often present in soils overlying basalt at concentrations above regulatory guidance values due to the presence of these elements in underlying geology. Oral bioaccessibility testing allows the risk posed by PTEs to human health to be assessed; however, bioaccessibility is controlled by factors including mineralogy, particle size, solid-phase speciation and encapsulation. X-ray diffraction was used to characterise the mineralogy of 12 soil samples overlying Palaeogene basalt lavas in Northern Ireland, and non-specific sequential extraction coupled with chemometric analysis was used to determine the distribution of elements amongst soil components in 3 of these samples. The data obtained were related to total concentration and oral bioaccessible concentration to determine whether a relationship exists between the overall concentrations of PTEs, their bioaccessibility and the soils mineralogy and geochemistry. Gastric phase bioaccessible fraction (BAF %) ranged from 0.4 to 5.4 % for chromium in soils overlying basalt and bioaccessible and total chromium concentrations are positively correlated. In contrast, the range of gastric phase BAF for nickel was greater (1.4–43.8 %), while no significant correlation was observed between bioaccessible and total nickel concentrations. However, nickel BAF was inversely correlated with total concentration. Solid-phase fractionation information showed that bioaccessible nickel was associated with calcium carbonate, aluminium oxide, iron oxide and clay-related components, while bioaccessible chromium was associated with clay-related components. This suggests that weathering significantly affects nickel bioaccessibility, but does not have the same effect on the bioaccessibility of chromium.

A tale of two chitons: Is habitat specialisation linked to distinct associated bacterial communities?

Although most chitons (Mollusca: Polyplacophora) are shallow-water molluscs, diverse species also occur in deep-sea habitats. We investigated the feeding strategies of two species, Leptochiton boucheti and Nierstraszella lineata, recovered on sunken wood sampled in the western Pacific, close to the Vanuatu Islands. The two species display distinctly different associations with bacterial partners. Leptochiton boucheti harbours Mollicutes in regions of its gut epithelium and has no abundant bacterium associated with its gill. Nierstraszella lineata displays no dense gut-associated bacteria, but harbours bacterial filaments attached to its gill epithelium, related to the Deltaproteobacteria symbionts found in gills of the wood-eating limpet Pectinodonta sp. Stable carbon and nitrogen isotope signatures and an absence of cellulolytic activity give evidence against a direct wood-feeding diet; both species are secondary consumers within the wood food web. We suggest that the distinct associations with bacterial partners are linked to niche specialisations of the two species. Nierstraszella lineata is in a taxonomic family restricted to sunken wood and is possibly adapted to more anoxic conditions thanks to its gill-associated bacteria. Leptochiton boucheti is phylogenetically more proximate to an ancestral form not specialised on wood and may itself be more of a generalist; this observation is congruent with its association with Mollicutes, a bacterial clade comprising gut-associated bacteria occurring in several metazoan phyla.

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.

Effect of two different rice dehusking procedures on total arsenic concentration in rice

Pollution of subterranean water by arsenic (As) in Asia has resulted in the worst chemical disaster in human history. For populations living on subsistence rice diets, As contamination of rice grain contributes greatly to dietary As exposure. The main objectives of this study were to compare two dehusking processes: (a) wet process (soaking of rice, boiling and mechanical hulling) and (b) dry process (mechanical hulling), and recommend the method leading to a lower As content in commercial rice. In general, hulling of paddy rice (373 mu g As kg(-1)) significantly decreased As content in rice grain (311 mu g As kg(-1)). The final As concentrations in boiled rice (final product of the wet process) and atab rice (dry process) were 332 and 290 mu g kg(-1). Thus, the dry method is recommended for dehusking paddy rice if not As-free water is available. However, villagers can reduce the As content in the wet system by discarding the soaking water and using new water for the light boiling. Finally, it is not recommended to use rice husk for feeding animals because the As concentration is very high, approximately 1,000 mu g As kg(-1).

Government decisions before and during the First World War and the living standards in Germany during a drastic natural experiment

The First World War hit Germany severely, particularly the agricultural sector, because the outbreak came unexpected and its duration exceeded all expectations. Many resources necessary for agricultural production were required by the war economy and led to shortages and shrinking supplies. Many agricultural laborers were drafted and the blockade imposed by the allies prevented Germany from a great deal of imports. As a consequence, the nutritional situation was devastating, particularly after 1916, and hit all groups of the German society. The period under observation provides one of most drastic natural experiments in the 20th century. This study uses anthropometric data from German soldiers who served in the Second World War to trace living standards between the 1900s and the 1920s. In contrast to other approaches, this paper is able to distinguish between social groups by occupation, religious denominatio\n, regional origin, and city size. The results suggest that although all social strata were hit by famine conditions, the height of farmers, urban citizens, Catholics, and especially individuals born in the highly integrated food-import regions along the coast and the banks of the Rhine declined most.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.