A linkage group on pig chromosome 4 comprising the loci for blood group L, GBA, ATP1B1 and three microsatellites

Restriction fragment length polymorphisms (RFLPs) were described for the porcine loci for β-glucosidase (GBA) and the β-polypeptide 1 of the Na⁺, K⁺-transporting ATPase (ATP1B1). Linkage analyses using a three-generation pedigree provided evidence for the assignment of ATP1B1, GBA and two microsatellite loci (S0001 and S0067) to a previously described linkage group comprising the loci for blood group L (EAL) and an anonymous microsatellite (S0097). The linear order of the six markers was determined with confidence by multipoint analyses and the length of the linkage group was estimated at 88 CM. This linkage group was assigned to pig chromosome 4 on the basis of a previous physical localization of the ATP1B1 gene. In situ hybridization data for S0001 presented in this study were consistent with a localization on chromosome 4 and suggested a regional localization to 4pl2-pl3. The present study reveals conflicting data concerning the genetic localization of the K88 loci controlling the expression of the receptors for the E. coli pilus antigens. One group has reported data suggesting a loose linkage between K88 and EAL, now mapped to chromosome 4, whereas two other groups have found linkage between K88 and the transferrin locus (TF), mapped to chromosome 13 by in situ hybridization.     

Efficient resolution of parentage in dogs by amplification of microsatellites

Parentage control has been performed for 15 litters from 12 different dog breeds by amplification of microsatellites. As it was possible to include all putative parents in all cases, they were solved by exclusion. Discrimination between parents/non-parents was made after genotyping of 6–9 microsatellite loci. In 12 of the cases all but one of the alleged fathers were excluded while in three cases it was unambiguously shown that superfecundation had taken place. Furthermore, one inclusion case concerning disputed maternity has been investigated. Maternity indices were calculated for 12 loci and probability of maternity was estimated to be 99-99%. These results testify that microsatellites can be applied very efficiently for resolution of parentage in dogs.     

Chromosomal assignment of porcine microsatellites by use of a somatic cell hybrid mapping panel

A well-established and characterized somatic cell hybrid panel was used to map three polymorphic microsatellites. Microsatellite S0072, representing the linkage group S0007-S0072, was assigned to porcine chromosome 14. Micro-satellite S0009, representing the unassigned linkage group EAM-S0009-S0071, was assigned tentatively to porcine chromosome 11. Finally, S0062 was tentatively mapped to chromosome 18. S0062 may represent the first marker for porcine chromosome 18.     

Pharmacological Implications of A Multiplicity of Adenosine Actions in the CNS

Abstract

Adenosine (50 nM - 50 μM) in brain extracellular space acts on two major classes of receptors present on virtually every cell. Specificity of action may be achieved by altering brain adenosine levels and by using partial agonists and/or drugs that affect more than one biochemical target.     

The Risk of Schizophrenia and Child Psychiatric Disorders in Offspring of Mothers with Lung Cancer and Other Types of Cancer: A Danish Nationwide Register Study

Background

Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements.

Methods

Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk.

Results

In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types.

Conclusions

In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking.     

Ratiometric Imaging of Extracellular pH in Bacterial Biofilms with C-SNARF-4

pH in the extracellular matrix of bacterial biofilms is of central importance for microbial metabolism. Biofilms possess a complex three-dimensional architecture characterized by chemically different microenvironments in close proximity. For decades, pH measurements in biofilms have been limited to monitoring bulk pH with electrodes. Although pH microelectrodes with a better spatial resolution have been developed, they do not permit the monitoring of horizontal pH gradients in biofilms in real time. Quantitative fluorescence microscopy can overcome these problems, but none of the hitherto employed methods differentiated accurately between extracellular and intracellular microbial pH and visualized extracellular pH in all areas of the biofilms. Here, we developed a method to reliably monitor extracellular biofilm pH microscopically with the ratiometric pH-sensitive dye C-SNARF-4, choosing dental biofilms as an example. Fluorescent emissions of C-SNARF-4 can be used to calculate extracellular pH irrespective of the dye concentration. We showed that at pH values of <6, C-SNARF-4 stained 15 bacterial species frequently isolated from dental biofilm and visualized the entire bacterial biomass in in vivo-grown dental biofilms with unknown species composition. We then employed digital image analysis to remove the bacterial biomass from the microscopic images and adequately calculate extracellular pH values. As a proof of concept, we monitored the extracellular pH drop in in vivo-grown dental biofilms fermenting glucose. The combination of pH ratiometry with C-SNARF-4 and digital image analysis allows the accurate monitoring of extracellular pH in bacterial biofilms in three dimensions in real time and represents a significant improvement to previously employed methods of biofilm pH measurement.     

Excess mortality in persons with severe mental disorders: a multilevel intervention framework and priorities for clinical practice,policy and research agendas

Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base are scarce. Furthermore, the majority of available interventions focus on a single or an otherwise limited number of risk factors. Here we present a multilevel model highlighting risk factors for excess mortality in persons with SMD at the individual, health system and socio‐environmental levels. Informed by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual‐focused, health system‐focused, and community level and policy‐focused interventions. Incorporating lessons learned from the multilevel model of risk and the comprehensive intervention framework, we identify priorities for clinical practice, policy and research agendas.     

Immunological differences in intestine and rectum of Atlantic cod (Gadus morhua L.)

The defence system of the distal gut (hindgut and rectum) of Atlantic cod, (Gadus morhua L.) was studied using (immuno)histochemical, electron microscopical and real-time quantitative PCR techniques. The uptake and transport of macromolecules in the intestinal epithelium was also investigated.In this study we observed that cod has many and large goblet cells in its intestinal epithelium and that IgM⁺ cells are present in the lamina propria and their number is considerably higher in the rectum than in the intestine. Myeloperoxidase staining revealed low numbers of granulocytes in and under the epithelium of the distal intestine, whereas high numbers were found clustered in the submucosa of the rectum. Electron microscopy not only confirmed these observations, but also revealed the presence of lymphoid cells and macrophages within the intestinal epithelium. Acid phosphatase staining demonstrated more positive macrophage-like cells in the rectum than in the distal intestine. Antigen uptake studies showed a diffused absorption of horse radish peroxidase (HRP) and LTB-GFP, whereas ferritin uptake could not be detected.Basal gene expression of cytokines (IL-1β, IL-8 and IL-10) and immune relevant molecules (hepcidin and BPI/LPB) were compared in both the intestine and rectum and revealed approximately 2–9 times higher expression in the rectum, of which IL-1β expression showed the most prominent difference.The present results clearly indicate that intestinal immunity is very prominent in the rectum of cod.