Prevalence of Chlamydia abortus in Belgian ruminants

Chlamydia (C.) abortus enzootic abortion still remains the most common cause of reproductive failure in sheep-breeding countries all over the world. Chlamydia abortus in cattle is predominantly associated with genital tract disease and mastitis. In this study, Belgian sheep (n=958), goats (n=48) and cattle (n=1849) were examined, using the ID Screen (TM) Chlamydia abortus indirect multi-species antibody ELISA. In the sheep, the highest prevalence rate was found in Limburg (4.05%). The animals of Antwerp, Brabant and Liege tested negative. The prevalence in the remaining five regions was low (0.24% to 2.74%). Of the nine goat herds, only one herd in Luxembourg was seropositive. In cattle, the highest prevalence rate was found in Walloon Brabant (4.23%). The animals of Limburg and Namur tested negative. The prevalence rate in the remaining seven regions ranged between 0.39% and 4.02%

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque

There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the expression of Kv3.1b in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labelled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons

Tolerance and safety evaluation of N, N-dimethylglycine, a naturally occurring organic compound, as a feed additive in broiler diets

N,N-dimethylglycine (DMG) is a tertiary amino acid that naturally occurs as an intermediate metabolite in choline-to-glycine metabolism. The objective of the present trial was to evaluate tolerance, safety and bioaccumulation of dietary DMG in broilers when supplemented at 1 g and 10 g Na-DMG/kg. A feeding trial was conducted using 480 1-d-old broiler chicks that were randomly allocated to twenty-four pens and fed one of three test diets added with 0, 1 or 10 g Na-DMG/kg during a 39 d growth period. Production performance was recorded to assess tolerance and efficacy of the supplement. At the end of the trial, toxicity was evaluated by means of haematology, plasma biochemistry and histopathology of liver, kidney and heart (n 12), whereas bioaccumulation was assessed on breast meat, liver, blood, kidney and adipose tissue (n 8). Carcass traits were similar between the control and 1 g Na-DMG/kg feed groups (P.0·05), but the feed:gain ratio was significantly improved at 1 g Na-DMG/kg feed compared with the control or the 10-fold dose (P¼0·008). Histological examinations showed no pathological effects and results of haematology and plasma biochemistry revealed similar values between the test groups (P.0·05). Bioaccumulation occurred at the 10-fold dose, but the resulting DMG content in breast meat was comparable with, for instance, wheat bran and much lower than uncooked spinach. In conclusion, DMG at 1 g Na-DMG/kg improved the feed:gain ratio in broilers without DMG being accumulated in consumer parts. Furthermore, dietary supplementation with DMG up to 10 g Na-DMG/kg did not induce toxicity or impaired performance in broilers

Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi

BACKGROUND: Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages. RESULTS: We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages. CONCLUSION: Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo

Microglial Expression of the Wnt Signaling Modulator DKK2 Differs between Human Alzheimer's Disease Brains and Mouse Neurodegeneration Models

Wnt signaling is crucial for synapse and cognitive function. Indeed, deficient Wnt signaling is causally related to increased expression of DKK1, an endogenous negative Wnt regulator, and synapse loss, both of which likely contribute to cognitive decline in Alzheimer's disease (AD). Increasingly, AD research efforts have probed the neuroinflammatory role of microglia, the resident immune cells of the CNS, which have furthermore been shown to be modulated by Wnt signaling. The DKK1 homolog DKK2 has been previously identified as an activated response and/or disease-associated microglia (DAM/ARM) gene in a mouse model of AD. Here, we performed a detailed analysis of DKK2 in mouse models of neurodegeneration, and in human AD brain. In APP/PS1 and APPNL-G-F AD mouse model brains as well as in SOD1G93A ALS mouse model spinal cords, but not in control littermates, we demonstrated significant microgliosis and microglial Dkk2 mRNA upregulation in a disease-stage-dependent manner. In the AD models, these DAM/ARM Dkk2+ microglia preferentially accumulated close to βAmyloid plaques. Furthermore, recombinant DKK2 treatment of rat hippocampal primary neurons blocked WNT7a-induced dendritic spine and synapse formation, indicative of an anti-synaptic effect similar to that of DKK1. In stark contrast, no such microglial DKK2 upregulation was detected in the postmortem human frontal cortex from individuals diagnosed with AD or pathologic aging. In summary, the difference in microglial expression of the DAM/ARM gene DKK2 between mouse models and human AD brain highlights the increasingly recognized limitations of using mouse models to recapitulate facets of human neurodegenerative disease.Significance StatementThe endogenous negative Wnt regulator Dkk2 is significantly upregulated at the mRNA level in microglia of Alzheimer's disease (AD) mouse models, implying that microglia derived Dkk2 protein may detrimentally contribute to a reduced Wnt signaling tone in the AD brain, a known pathophysiological manifestation. Indeed, recombinant DKK2 prevented Wnt-dependent synapse formation in cultured neurons. However, DKK2 upregulation was not recapitulated in postmortem human AD brains. The success of neurodegeneration animal models has relied on pathophysiology that for the most part correctly modelled human disease. Increasingly, however, limitations to the validity of mouse models to recapitulate human neurodegenerative disease have become apparent, as evidenced by the present study by the difference in microglial DKK2 expression between AD mouse models and human AD brain

Is age an independent determinant of mortality in cardiac surgery as suggested by the EuroSCORE?

BACKGROUND: The proportion of older patients in cardiac surgery is continuously increasing. 37% of patients undergoing heart surgery in Germany in the year 2000 were 70 years of age and older. We have studied the role of age as a determinant of mortality in cardiac surgery in our institutional patient population. METHODS: We have calculated the EuroSCORE and the corresponding age-adjusted EuroSCORE in 8769 patients who underwent heart surgery between January 1996 and January 2002 and collected the information on the occurrence of postoperative complications and 30-days mortality. RESULTS: The multimorbidity increased with ascending age. Both the EuroSCORE and the age-adjusted EuroSCORE values increased significantly with age in the whole group of patients as well as in the group of patients who were alive 30 days after heart surgery. The incidence of postoperative complications and 30-days mortality increased significantly with age. In patients who died within 30 days after surgery, the EuroSCORE increased significantly with age, whereas the age-adjusted EuroSCORE did not. The occurrence of diabetes mellitus, arterial hypertension and atrial fibrillation, i.e., the risk factors not considered by the EuroSCORE, exhibited a significant age dependence in our patients. The univariate analysis identified the significant dependence of 30-days mortality on diabetes and atrial fibrillation. The stepwise logistic regression analysis showed the dependence of mortality on diabetes. CONCLUSIONS: On the background of the well-known age-dependent structural and functional changes of different body organs, our data show that age is a significant risk indicator in cardiac surgery, strongly correlating with morbidity and mortality. Consequently, special preventive and therapeutic measures are required in clinical environment in the case of elderly patients undergoing cardiac surgery

Detecting Dark Matter annihilation lines with Fermi

Dark matter constitutes one of the most intriguing but so far unresolved issues in physics today. In many extensions of the Standard Model the existence of a stable Weakly Interacting Massive Particle (WIMP) is predicted. The WIMP is an excellent dark matter particle candidate and one of the most interesting scenarios include an annihilation of two WIMPs into two gamma-rays. If the WIMPs are assumed to be non-relativistic, the resulting photons will both have an energy equal to the mass of the WIMP and manifest themselves as a monochromatic spectral line in the energy spectrum. This type of signal would represent a 'smoking gun' for dark matter, since no other known astrophysical process should be able to produce it. In these proceedings we give an overview of the different approaches to a search for dark matter lines that the Fermi-LAT collaboration is pursuing and the various challenges involved

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification