Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock

A neonate with left pulmonary artery thrombosis and left lung hypoplasia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous intrauterine arterial thrombosis and congenital pulmonary hypoplasia are rare conditions and have not been reported to occur together. The literature rather includes two reports of babies with neonatal pulmonary artery occlusion and post-infarction cysts of the lungs.</p> <p>Case presentation</p> <p>We report a case of a live Caucasian male newborn with left lung hypoplasia that occurred in association with left pulmonary artery thrombosis. Despite a critical neonatal course, including extracorporeal membrane oxygenation, this infant is alive and well at 18 months of age without any neurodevelopmental sequelae or reactive airway disease.</p> <p>Conclusion</p> <p>This association suggests the possibility of an intrauterine vascular event between the fifth and eighth weeks of gestation during early pulmonary artery and lung development.</p

Multimodal Chemosensory Integration through the Maxillary Palp in Drosophila

Drosophila melanogaster has an olfactory organ called the maxillary palp. It is smaller and numerically simpler than the antenna, and its specific role in behavior has long been unclear. Because of its proximity to the mouthparts, I explored the possibility of a role in taste behavior. Maxillary palp was tuned to mediate odor-induced taste enhancement: a sucrose solution was more appealing when simultaneously presented with the odorant 4-methylphenol. The same result was observed with other odors that stimulate other types of olfactory receptor neuron in the maxillary palp. When an antennal olfactory receptor was genetically introduced in the maxillary palp, the fly interpreted a new odor as a sweet-enhancing smell. These results all point to taste enhancement as a function of the maxillary palp. It also opens the door for studying integration of multiple senses in a model organism

Decreased blood antioxidant capacity and increased lipid peroxidation in young cigarette smokers compared to nonsmokers: Impact of dietary intake

<p>Abstract</p> <p>Background</p> <p>Blood of cigarette smokers routinely displays decreased antioxidant capacity and increased oxidized lipids compared to nonsmokers. This is thought to be due to both chronic exposure to cigarette smoke in addition to low intake of dietary antioxidants, and is a routine finding in veteran smokers. No study to date has determined the independent and combined impact of dietary intake and cigarette smoking on blood antioxidant capacity and oxidative stress in a sample of young, novice smokers.</p> <p>Methods</p> <p>We compared resting plasma antioxidant reducing capacity (ARC; expressed in uric acid equivalents), serum trolox-equivalent antioxidant capacity (TEAC), whole blood total glutathione, plasma malondialdehyde (MDA), and plasma oxidized low density lipoprotein (oxLDL) between 15 young (24 ± 4 years), novice smokers (pack-year history: 3 ± 2) and 13 nonsmokers of similar age (24 ± 5 years). Detailed dietary records were maintained during a seven-day period for analysis of total energy, macro- and micronutrient intake.</p> <p>Results</p> <p>ARC (0.0676 ± 0.0352 vs. 0.1257 ± 0.0542 mmol·L^-1; mean ± SD, p = 0.019), TEAC (0.721 ± 0.120 vs. 0.765 ± 0.130 mmol·L^-1, p = 0.24) and glutathione (835 ± 143 vs. 898 ± 168 μmol·L^-1, p = 0.28) were lower in smokers compared to nonsmokers, with only the former being statistically significant. MDA (0.919 ± 0.32 vs. 0.647 ± 0.16 μmol·L^-1, p = 0.05) and oxLDL were both higher in smokers compared to nonsmokers (229 ± 94 vs. 110 ± 62 ng·mL^-1, p = 0.12), although only the MDA comparison was of statistical significance. Interestingly, these findings existed despite no differences in dietary intake, including antioxidant micronutrient consumption, between both smokers and nonsmokers.</p> <p>Conclusion</p> <p>These data, with specificity to young, novice cigarette smokers, underscore the importance of smoking abstinence. Future studies with larger sample sizes, inclusive of smokers of different ages and smoking histories, are needed to extend these findings.</p

A colanic acid operon deletion mutation enhances induction of early antibody responses by live attenuated salmonella vaccine strains

Colanic acid (CA) is a common exopolysaccharide produced by many genera in the Enterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue by Salmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into two Salmonella vaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophic Salmonella vaccine strain with the deletion mutation Δ(wza-wcaM)8 developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. In Salmonella vaccine strains with RDAS, the strain with the Δ(wza-wcaM)8 mutation resulted in higher levels of protective antigen production during in vitro growth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 10(8) and 10(9) CFU. Thus, the mutation Δ(wza-wcaM)8 will be included in various recombinant attenuated Salmonella vaccine (RASV) strains with RDAS derived from Salmonella enterica serovar Paratyphi A and Salmonella enterica serovar Typhi to induce protective immunity against bacterial pathogens

The brain monitoring with information technology (BrainIT) collaborative network: EC feasibility study results

The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain injured patients towards providing a more efficient infrastructure for assessing new health technology. Materials and methods Over a 2 year period, core dataset data (grouped by nine categories) were collected from 200 head-injured patients by local nursing staff. Data were uploaded by the BrainIT web and random samples of received data were selected automatically by computer for validation by data validation (DV) research nurse staff against gold standard sources held in the local centre. Validated data was compared with original data sent and percentage error rates calculated by data category. Findings Comparisons, 19,461, were made in proportion to the size of the data received with the largest number checked in laboratory data (5,667) and the least in the surgery data (567). Error rates were generally less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Conclusions The BrainIT core dataset (with the exception of the surgery classification) is feasible and accurate to collect. The surgery classification needs to be revised

Oxidative stress in children late after Kawasaki disease: relationship with carotid atherosclerosis and stiffness

Background: Persistent arterial dysfunction in patients with a history of Kawasaki disease (KD) and an integral role of oxidative stress in the development of cardiovascular disease are increasingly recognized. We sought to test the hypothesis that oxidative stress is increased in KD patients and related to carotid atherosclerotic changes and stiffness. Methods: We compared the serum levels of oxidative stress biomarkers, carotid intima-media thickness (IMT), and carotid stiffness index among KD patients with coronary aneurysms (n = 32), those without coronary complications (n = 19), and controls (n = 32). Results: Compared with controls, patients with coronary aneurysms had significantly higher serum levels of malonaldehyde (2.62 ± 0.12 μM vs 2.22 ± 0.07 μM, p = 0.014) and hydroperoxides (26.50 ± 1.13 μM vs 22.50 ± 0.62 μM, p = 0.008). A linear trend of the magnitude of oxidative stress in relation to inflammatory damage was observed for malonaldehyde (p = 0.018) and hydroperoxides (p = 0.014) levels. Serum malonaldehyde and hydroperoxide levels correlated positively with carotid IMT (p < 0.001 and p = 0.034, respectively) and stiffness index (p = 0.001 and p = 0.021, respectively). Multiple linear regression analysis identified serum malonaldehyde level as a significant determinant of carotid IMT (β = 0.31, p = 0.006) and stiffness (β = 0.27, p = 0.008). Conclusion: Our findings suggestoxidative stress is increased in KD patients with coronary aneurysms and is associated with carotid intima-media thickening and stiffening. © 2008 Cheung et al; licensee BioMed Central Ltd.published_or_final_versio

Mechanosensory interactions drive collective behaviour in Drosophila.

Collective behaviour enhances environmental sensing and decision-making in groups of animals. Experimental and theoretical investigations of schooling fish, flocking birds and human crowds have demonstrated that simple interactions between individuals can explain emergent group dynamics. These findings indicate the existence of neural circuits that support distributed behaviours, but the molecular and cellular identities of relevant sensory pathways are unknown. Here we show that Drosophila melanogaster exhibits collective responses to an aversive odour: individual flies weakly avoid the stimulus, but groups show enhanced escape reactions. Using high-resolution behavioural tracking, computational simulations, genetic perturbations, neural silencing and optogenetic activation we demonstrate that this collective odour avoidance arises from cascades of appendage touch interactions between pairs of flies. Inter-fly touch sensing and collective behaviour require the activity of distal leg mechanosensory sensilla neurons and the mechanosensory channel NOMPC. Remarkably, through these inter-fly encounters, wild-type flies can elicit avoidance behaviour in mutant animals that cannot sense the odour--a basic form of communication. Our data highlight the unexpected importance of social context in the sensory responses of a solitary species and open the door to a neural-circuit-level understanding of collective behaviour in animal groups

Effect of bilirubin on cytochrome c oxidase activity of mitochondria from mouse brain and liver

<p>Abstract</p> <p>Background</p> <p>The unbound, free concentration (B_f) of unconjugated bilirubin (UCB), and not the total UCB level, has been shown to correlate with bilirubin cytotoxicity, but the key molecular mechanisms accounting for the toxic effects of UCB are largely unknown.</p> <p>Findings</p> <p>Mouse liver mitochondria increase unbound UCB oxidation, consequently increasing the apparent rate constant for unbound UCB oxidation by HRP (Kp), higher than in control and mouse brain mitochondria, emphasizing the importance of determining Kp in complete systems containing the organelles being studied. The <it>in vitro </it>effects of UCB on cytochrome <it>c </it>oxidase activity in mitochondria isolated from mouse brain and liver were studied at B_franging from 22 to 150 nM. The results show that UCB at B_fup to 60 nM did not alter mitochondrial cytochrome <it>c </it>oxidase activity, while the higher concentrations significantly inhibited the enzyme activity by 20% in both liver and brain mitochondria.</p> <p>Conclusions</p> <p>We conclude that it is essential to include the organelles being studied in the medium used in measuring both Kp and B_f. A moderately elevated, pathophysiologically-relevant B_fimpaired the cytochrome <it>c </it>oxidase activity modestly in mitochondria from mouse brain and liver.</p