Mitogen Stimulation of Lymphocytes in Pigs with Hereditary Vitamin C Deficiency

Recently an inherited vitamin G deficiency in the pigs presumably based on an autosomal recessive gene was decribed* Homozygotes are in contrast to heterozygotes and normal pigs unable to synthesize ascorbic acid. In an experiment comprising 3 littermate pigs, 2 homozygous and 1 heterozygous for the vitamin C deficiency gene, the influence of ascorbic acid depletion, and repletion on mitogen stimulation of peripheral blood lymphocytes was studied. Ascorbic acid depletion of the vitamin C dependent pigs resulted in a rapid decline in plasma ascorbic acid. Response of lymphocytes to stimular tion with Concanavalin A (Con A) and phytohemagglutinin M (PHA) decreased more slowly reaching a minimum, which coincidedi with the occurrence of the first clinical symptoms of scurvy. Following resupplementation with vitamin C the plasma content of ascorbic acid rapidly returned to normal, while the lymphocyte response to Con A and PHA stimulation only gradually approached the initial values. The repletion with ascorbic acid caused a transitory increase in the response to pokeweed mitogen (PWM) stimulation. The significance of these findings in relation to the cellular immune system in normal pigs is discussed.     

Assignment of the dipeptidylpeptidase IV (DPP4) gene to pig Chromosome 15q21

A porcine 2-kb partial dipeptidylpeptidase IV (DPP4, EC 3.4.14.5) cDNA clone and a porcine 16-kb genomic fragment containing parts of the DPP4 gene were isolated, characterized, and used as probes to map the DPP4 gene to pig Chr (Chr) 15q21 by fluorescence in situ hybridization. A two-allele RFLP was revealed for the DPP4 gene. This polymorphism was utilized in a linkage test against the erythrocyte antigen G (EAG), previously assigned to Chr 15, and the microsatellite S0088, which is linked to EAG. The linkage analyses revealed significant evidence for linkage confirming the assignment of DPP4 to Chr 15.     

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.     

CONSUMER–RESOURCE INTERACTIONS AND THE EVOLUTION OF MIGRATION

Theoretical studies have demonstrated that selection will favor increased migration when fitnesses vary both temporally and spatially, but it is far from clear how pervasive those theoretical conditions are in nature. Although consumer–resource interactions are omnipresent in nature and can generate spatial and temporal variation, it is unknown even in theory whether these dynamics favor the evolution of migration. We develop a mathematical model to address whether and how migration evolves when variability in fitness is determined at least in part by consumer–resource coevolutionary interactions. Our analyses show that such interactions can drive the evolution of migration in the resource, consumer, or both species and thus supplies a general explanation for the pervasiveness of migration. Over short time scales, we show the direction of change in migration rate is determined primarily by the state of local adaptation of the species involved: rates increase when a species is locally maladapted and decrease when locally adapted. Our results reveal that long‐term evolutionary trends in migration rates can differ dramatically depending on the strength or weakness of interspecific interactions and suggest an explanation for the evolutionary divergence of migration rates among interacting species.     

Bacillus thuringiensis in fecal samples from greenhouse workers after exposure to B. thuringiensis-based pesticides

In a study of occupational exposure to Bacillus thuringiensis, 20 exposed greenhouse workers were examined for Bacillus cereus-like bacteria in fecal samples and on biomonitoring filters. Bacteria with the following characteristics were isolated from eight individuals: intracellular crystalline inclusions characteristic of B. thuringiensis, genes for and production of B. cereus enterotoxins, and positivity for cry11 as determined by PCR. DNA fingerprints of the fecal isolates were identical to those of strains isolated from the commercial products used. Work processes (i.e., spraying) correlated with the presence of B. thuringiensis in the fecal samples (10(2) to 10(3) CFU/g of feces). However, no gastrointestinal symptoms correlated with the presence of B. thuringiensis in the fecal samples.     

Clavulanic acid degradation in Streptomyces clavuligerus fed-batch cultivations

Clavulanic acid (CA) is an important antibiotic that is produced by Streptomyces clavuligerus. CA is unstable and product degradation has turned out to have a major impact on product titers in fed-batch cultivations. Three different types of experiments have been used to elucidate CA degradation under fed-batch cultivation conditions. First, the influence of individual medium compounds was examined. Second, degradation was monitored during the exponential growth phase in batch cultivations. Third, CA degradation was studied in the supernatant of samples taken during a fed-batch. In addition, data from six fed-batch cultivations were studied to derive information about CA degradation during the production phase. These cultivations were based on a mineral medium, containing glycerol, glutamate, ammonium, and phosphate as the main nutrients. The ammonium concentration had a large influence on the degradation rate constant. In addition, either changes in the substrate availability or high concentrations of ammonium or glycerol cause a major increase in the degradation rate constant. Finally, a linear and a fuzzy logic model were made to predict CA degradation rates in these fed-batches.     

Small molecule ago-allosteric modulators of the human glucagon-like peptide-1 (hGLP-1) receptor

Following our previous publication describing the biological profiles, we herein describe the structure-activity relationships of a core set of quinoxalines as the hGLP-1 receptor agonists. The most potent and efficacious compounds are 6,7-dichloroquinoxalines bearing an alkyl sulfonyl group at the C-2 position and a secondary alkyl amino group at the C-3 position. These findings serve as a valuable starting point for the discovery of more drug-like small molecule agonists for the hGLP-1 receptor.     

Repeated inhalations of diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase (OGG1) deficient mice

DNA repair may prevent increased levels of oxidatively damaged DNA from prolonged oxidative stress induced by, e.g. exposure to diesel exhaust particles (DEP). We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 × 1.5 h inhalations of DEP (20 mg/m³) in Ogg1^- / -  and wild type (WT) mice with similar extent of inflammation. DEP exposure increased lung levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in Ogg1^- / -  mice, whereas no effect on 8-oxodG or oxidized purines in terms of formamidopyrimidine DNA glycosylase (FPG) sites was observed in WT mice. In both unexposed and exposed Ogg1^- / -  mice the level of FPG sites in the lungs was 3-fold higher than in WT mice. The high basal level of FPG sites in Ogg1^- / -  mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Ogg1^- / -  mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP.