Inherited copper toxicosis with emphasis on copper toxicosis in Bedlington terriers

Canine copper toxicosis is an important inherited disease in Bedlington terriers, because of its high prevalence rate and similarity to human copper storage disease. It can lead to chronic liver disease and occasional haemolytic anaemia due to impaired copper excretion. The responsible gene for copper toxicosis in Bedlington terriers has been recently identified and was found not to be related to human Wilson's disease gene ATP7B. Although our understanding of copper metabolism in mammals has improved through genetic molecular technology, the diversity of gene mutation related to copper metabolism in animals will help identify the responsible genes for non-Wilsonian copper toxicoses in human. This review paper discusses our knowledge of normal copper metabolism and the pathogenesis, molecular genetics and current research into copper toxicosis in Bedlington terriers, other animals and humans. (C) 2004 Elsevier GmbH. All rights reserved.

Reduction of β-Endorphin-Containing Immune Cells in Inflamed Paw Tissue Corresponds with a Reduction in Immune-Derived Antinociception: Reversible by Donor Activated Lymphocytes

The functional integrity of the immune system is essential for peripheral antinociception. Previous studies have demonstrated that immune cells elicit potent antinociception in inflamed tissues and that corticotropin-releasing factor-induced antinociception is significantly inhibited in animals that have undergone cyclosporin A (CsA)-induced immunosuppression. In this study, we examined the effect of a single bolus of CsA on inflammatory nociception. CsA-treated rats had substantially increased nociception compared with nonimmunosuppressed rats, consistent with a reduction in circulating and infiltrating lymphocytes. Furthermore, CsA-treated rats had inhibition of corticotropin-releasing factor-induced immune-derived antinociception, which was dose-dependently reversed by IV injection of concanavalin A-activated donor lymphocytes (1.0-7.0 X 10(6) cells/0.1 mL). In conclusion, our findings provided further evidence that opioid-containing immune cells are essential for peripheral analgesia. It is evident from these findings that control of inflammatory pain relies heavily on a functioning immune system.

Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum

To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

Real-time reverse transcriptase PCR for the endogenous koala retrovirus reveals an association between plasma viral load and neoplastic disease in koalas

Koala retrovirus (KoRV) is a newly described endogenous retrovirus and is unusual in that inserts comprise a full-length replication competent genome. As koalas are known to suffer from an extremely high incidence of leukaemia/lymphoma, the association between this retrovirus and disease in koalas was examined. Using quantitative real-time reverse transcriptase PCR it was demonstrated that KoRV RNA levels in plasma are significantly increased in animals suffering from leukaemia or lymphoma when compared with healthy animals. Increased levels of KoRV were also seen for animals with clinical chlamydiosis. A significant positive association between viral RNA levels and age was also demonstrated. Real-time PCR demonstrated as much as 5 log variation in KoRV proviral DNA levels in genomic DNA extracted from whole blood from different animals. Taken together these data indicate that KoRV is an active endogenous retrovirus and suggests that it may be causally linked to neoplastic disease in koalas.

Small regulatory RNAs in mammals

Mammalian cells harbor numerous small non-protein-coding RNAs, including small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), short interfering RNAs (siRNAs) and small double-stranded RNAs, which regulate gene expression at many levels including chromatin architecture, RNA editing, RNA stability, translation, and quite possibly transcription and splicing. These RNAs are processed by multistep pathways from the introns and exons of longer primary transcripts, including protein-coding transcripts. Most show distinctive temporal- and tissue-specific expression patterns in different tissues, including embryonal stem cells and the brain, and some are imprinted. Small RNAs control a wide range of developmental and physiological pathways in animals, including hematopoietic differentiation, adipocyte differentiation and insulin secretion in mammals, and have been shown to be perturbed in cancer and other diseases. The extent of transcription of non-coding sequences and the abundance of small RNAs suggests the existence of an extensive regulatory network on the basis of RNA signaling which may underpin the development and much of the phenotypic variation in mammals and other complex organisms and which may have different genetic signatures from sequences encoding proteins.

Parasitic castration by the digenian trematode Allopodocotyle sp alters gene expression in the brain of the host mollusc Haliotis asinina

Infection of molluscs by digenean trematode parasites typically results in the repression of reproduction - the so-called parasitic castration. This is known to occur by altering the expression of a range of host neuropeptide genes. Here we analyse the expression levels of 10 members of POU, Pax, Sox and Hox transcription factor gene families, along with genes encoding FNIRFamide, prohormone convertase and P-tubulin, in the brain ganglia of actively reproducing (summer), non-reproducing (winter) and infected Haliotis asinina (a vetigastropod mollusc). A number of the regulatory genes are differentially expressed in parasitised H. asinina, but in only a few cases do expression patterns in infected animals match those occurring in animals where reproduction is normally repressed. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Water balance in goats subjected to feed restriction

The effect of feed restriction on water balance and nutrient utilization was investigated in individually penned Boer x Saanen kids. Twenty-two male Boer x Saanen kids with an initial average live weight (LW) of 15 kg were used. Seven kids were slaughtered at the beginning of the experiment (reference animals) and the remainders were allocated to one of the three treatments (0, 30 and 60% restriction) and therefore there were five kids per treatment. The feed intake for the 0% restriction treatment animals determined the intake for the animals in the 30 and 60% restriction treatment. When the animals in the 0% restriction treatment group reached 25 kg LW, the animals in the 30 and 60% restriction treatment groups were also slaughtered. There was a negative relationship between DMI and water intake. The digestibility coefficients for DM, OM, carbohydrates, ash, ether extract, energy, NDF, ADF and lignin did not differ between treatments, whereas the digestibility coefficient for CP was different between treatment groups. The highest metabolic water production was in animals in the 0% restriction treatment group. No significant differences were observed in the composition of gastro-intestinal tract contents of the goats in the different treatments. Lower water retention was found in the animals in the 60% restriction treatment group. The study showed that feed restriction affected water intake, CP digestibility and water retention in the body of the kid goats. This experiment demonstrated that DM:water intake ratio changed when severe feed restriction was applied (60% restriction) and water was freely available. It shows a different pattern of behaviour of penned goats, particularly if feed intake is restricted and perhaps caution is needed to extrapolate results from nutritional and physiological trials in pens to goats at pasture. (c) 2005 Elsevier BX All rights reserved.

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial

Background The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. Methods In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. Findings 1383 participants underwent full shin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new shin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100 000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100 000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100 000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100 000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100 000; 0.61 [0.46-0.81]). Interpretation There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Event related potential (ERP) evidence for selective impairment of verbal recollection in abstinent recreational methylenedioxymethamphetamine (“Ecstasy”)/polydrug users

Objectives Ecstasy is a recreational drug whose active ingredient, 3,4-methylenedioxymethamphetamine (MDMA), acts predominantly on the serotonergic system. Although MDMA is known to be neurotoxic in animals, the long-term effects of recreational Ecstasy use in humans remain controversial but one commonly reported consequence is mild cognitive impairment particularly affecting verbal episodic memory. Although event-related potentials (ERPs) have made significant contributions to our understanding of human memory processes, until now they have not been applied to study the long-term effects of Ecstasy. The aim of this study was to examine the effects of past Ecstasy use on recognition memory for both verbal and non-verbal stimuli using ERPs. Methods We compared the ERPs of 15 Ecstasy/polydrug users with those of 14 cannabis users and 13 non-illicit drug users as controls. Results Despite equivalent memory performance, Ecstasy/polydrug users showed an attenuated late positivity over left parietal scalp sites, a component associated with the specific memory process of recollection. Conlusions This effect was only found in the word recognition task which is consistent with evidence that left hemisphere cognitive functions are disproportionately affected by Ecstasy, probably because the serotonergic system is laterally asymmetrical. Experimentally, decreasing central serotonergic activity through acute tryptophan depletion also selectively impairs recollection, and this too suggests the importance of the serotonergic system. Overall, our results suggest that Ecstasy users, who also use a wide range of other drugs, show a durable abnormality in a specific ERP component thought to be associated with recollection.

Inhibition of collagen I accumulation reduces glomerulosclerosis by a Hic-5-dependent mechanism in experimental diabetic nephropathy

Glomerulosclerosis of any cause is characterized by loss of functional glomerular cells and deposition of excessive amounts of interstitial collagens including collagen I. We have previously reported that mesangial cell attachment to collagen I leads to upregulation of Hic-5 in vitro, which mediates mesangial cell apoptosis. Furthermore, glomerular Hic-5 expression was increased during the progression of experimental glomerulosclerosis. We hypothesized that reducing collagen I accumulation in glomerulosclerosis would in turn lower Hic-5 expression, reducing mesangial cell apoptosis, and thus maintaining glomerular integrity. We examined archive renal tissue from rats undergoing experimental diabetic glomerulosclerosis, treated with the transglutaminase-2 inhibitor NTU281. Untreated animals exhibited increased glomerular collagen I accumulation, associated with increased glomerular Hic-5 expression, apoptosis, and mesangial myofibroblast transdifferentiation characterized by a-smooth muscle actin (a-SMA) expression. NTU281 treatment reduced glomerular collagen I accumulation, Hic-5 and a-SMA expression, and apoptosis. Proteinurea and serum creatinine levels were significantly reduced in animals with reduced Hic-5 expression. In vitro studies of Hic-5 knockdown or overexpression show that mesangial cell apoptosis and expression of both a-SMA and collagen I are Hic-5 dependent. Together, these data suggest that there exists, in vitro and in vivo, a positive feedback loop whereby increased levels of collagen I lead to increased mesangial Hic-5 expression favoring not only increased apoptosis, but also mesangial myofibroblast transdifferentiation and increased collagen I expression. Prevention of collagen I accumulation interrupts this Hic-5-dependent positive feedback loop, preserving glomerular architecture, cellular phenotype, and function. © 2013 USCAP, Inc All rights reserved.

Seasonal variations of EPG levels in gastro-intestinal parasitic infection in a southeast asian controlled locale:a statistical analysis

We present a data based statistical study on the effects of seasonal variations in the growth rates of the gastro-intestinal (GI) parasitic infection in livestock. The alluded growth rate is estimated through the variation in the number of eggs per gram (EPG) of faeces in animals. In accordance with earlier studies, our analysis too shows that rainfall is the dominant variable in determining EPG infection rates compared to other macro-parameters like temperature and humidity. Our statistical analysis clearly indicates an oscillatory dependence of EPG levels on rainfall fluctuations. Monsoon recorded the highest infection with a comparative increase of at least 2.5 times compared to the next most infected period (summer). A least square fit of the EPG versus rainfall data indicates an approach towards a super diffusive (i. e. root mean square displacement growing faster than the square root of the elapsed time as obtained for simple diffusion) infection growth pattern regime for low rainfall regimes (technically defined as zeroth level dependence) that gets remarkably augmented for large rainfall zones. Our analysis further indicates that for low fluctuations in temperature (true on the bulk data), EPG level saturates beyond a critical value of the rainfall, a threshold that is expected to indicate the onset of the nonlinear regime. The probability density functions (PDFs) of the EPG data show oscillatory behavior in the large rainfall regime (greater than 500 mm), the frequency of oscillation, once again, being determined by the ambient wetness (rainfall, and humidity). Data recorded over three pilot projects spanning three measures of rainfall and humidity bear testimony to the universality of this statistical argument. © 2013 Chattopadhyay and Bandyopadhyay.

Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in white adipose tissue

The effect of cancer cachexia on the TAG/FA substrate cycle in white adipose tissue was determined in vivo using the MAC16 murine model of cachexia. When compared with non-tumor-bearing animals, the rate of TAG-glycerol production was found to be increased almost threefold in animals bearing the MAC13 tumor, which does not induce cachexia, but was not further elevated in animals bearing the MAC16 tumor. In both cases TAG-glycerol production and de novo synthesis of TAG-FA were also increased above non-tumor-bearing animals. In animals bearing the MAC16 tumor, the TAG-FA rates were significantly higher than in animals bearing the MAC13 tumor. This suggests that the presence of the tumor alone is sufficient to cause an increase in cycling rate, and in the absence of an elevated energy intake (MAC16) this may contribute to the depletion of adipose tissue.

Ultrastructural basis and function of iridescent blue colour of fruits in Elaeocarpus

Iridescent colour, caused by physical effects (thin-film interference, diffraction and Tyndall scattering), is relatively common in animals but exceedingly rare among plants1. Some benthic marine algae produce blue to violet iridescence2,3, and the upper leaf surfaces of a few vascular plants from the shady environments of humid tropical forests are iridescent blue4–6. Blue fruit colour has been assumed to be caused by anthocyanins7. A survey of such fruits (26 species in 18 genera) in Costa Rica, India, Florida and Malaysia, showed this to be the case, except for the iridescent colour in fruits of Elaeocarpus angustifolius Blume (Elaeocarpaceae). There I show that the colour is caused by a remarkable structure in the epidermis, and provide evidence for its selective advantage.

Brominated flame retardants and biomagnification factors in marine species in the North-East Atlantic

BACKGROUND: Concentrations of brominated flame retardants (BFRs) are reported to increase in marine ecosystems. OBJECTIVES: Characterize exposure to BFRs in animals from different trophic levels in North-East Atlantic coastal marine ecosystems along a latitudinal gradient from southern Norway to Spitsbergen, Svalbard, in the Arctic. Calanoid species were collected from the Oslofjord (59°N), Froan (64°N), and Spitsbergen (> 78°N); Atlantic cod (Gadus morhua) from the Oslofjord and Froan; polar cod (Boreogadus saida) from Bear Island (74°N) and Spitsbergen; harbor seal (Phoca vitulina) from the Oslofjord, Froan, and Spitsbergen; and ringed seal (Phoca vitulina) from Spitsbergen. Eggs of common tern (Sterna hirundo) were collected from the Oslofjord, and eggs of arctic terns (Sterna paradisaea) from Froan and Spitsbergen. RESULTS: Levels of polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD) generally decreased as a function of increasing latitude, reflecting distance from release sources. The clear latitudinal decrease in levels of BFRs was not pronounced in the two tern species, most likely because they are exposed during migration. The decabrominated compound BDE-209 was detected in animals from all three ecosystems, and the highest levels were found in arctic tern eggs from Spitsbergen. HBCD was found in animals from all trophic levels, except for in calanoids at Froan and Spitsbergen. CONCLUSIONS: Even though the levels of PBDEs and HBCD are generally low in North-East Atlantic coastal marine ecosystems, there are concerns about the relatively high presence of BDE-209 and HBCD.