Genes,germs, and schizophrenia: an evolutionary perspective

Literature on schizophrenia and other mental illnesses has emphasized the compatibility of evidence with genetic causation without adequately considering alternative hypotheses of disease causation. Although some studies from the mid-20th century reported associations between certain pathogens and schizophrenia, only recently has the possibility of infectious causation of schizophrenia again become an active focus of research. Infectious causation of schizophrenia is still, however, generally regarded as less well demonstrated than genetic causation. This article evaluates the evidence that has been used to support genetic and infectious causation. Our consideration of infectious causation focuses on the protozoan Toxoplasma gondii but also assesses other pathogens that may contribute to the development of some of the illnesses currently categorized as schizophrenia. Although evidence generally accepted as demonstrating genetic causation can be readily explained by hypotheses of infectious causation, some of the evidence implicating infectious causation cannot be similarly explained by genetic causation. This asymmetry indicates that a scientific approach to the causation of schizophrenia needs to put a greater emphasis on tests that distinguish hypotheses of genetic causation from those of infectious causation.     

Pilgrims to Mecca, germs and the international community

With steam navigation, men, but also seeds of diseases, move faster. In 1865, the pilgrimage to Mecca induced a terrible cholera pandemic. This caused deep trauma in Europe and prompted the international community, recently born, to focus on the pilgrims who were regarded as the main "risk group" in the spread of epidemics. Through a series of international sanitary conferences, European powers, in agreement with the Ottoman Empire, imposed a heavy control over the pilgrims, much harsher than that applied to ordinary commercial navigation exchanges. These decisions led to the establishment of a huge quarantine device in the Red Sea and the Levant, including two lazaretto, one at the entrance and the other at the exit of the Red Sea, where the pilgrims were trapped and disinfected during their sacred journey. This contrasted with the concommitant disappearance of quarantines everywhere else. The pilgrims did not show hostility towards medical and prophylactic treatments but protested against the dehumanizing conditions of their realization. The combined pressures of nationalism and sovereignty claims from Saudi Arabia ended this system in 1957.     

Effect of X-irradiation on the development of postinfection immunity in tularemia and anthrax

Formation of postinfection (postvaccination) immunity in anthrax and tularemia in irradiated animals has been found to be highly resistant to the effect of X-irradiation and independent of the time interval between vaccination and irradiation. However, the development of immunity was slowed down. Discrepancy between low antibody response and pronounced ability to resist even massive doses of active infaction has been observed, indicating that the onset of postinfection immunity is associated with factors less susceptible to irradiation than is formation of antibodies. The mechanism of such phenomenon is discussed.     

Isolation and characterization of anti-Salmonella lactic acid bacteria from the porcine gastrointestinal tract

AIMS: To identify lactic acid bacteria (LAB) of porcine intestinal origin with anti-Salmonella activity. METHODS AND RESULTS: Samples were obtained from pig faeces and caeca and screened for the presence of anti-Salmonella LAB. The 11 most promising isolates were identified as belonging to the genera Lactobacillus and Pediococcus. The LAB exhibited large variation in their ability to survive in simulated gastric juice at pH 1.85. While Lactobacillus johnsonii species survived at levels of 80% for up to 30 min, Lactobacillus pentosus species declined to <0.001% in that time. All isolates tolerated porcine bile at a concentration of 0.3% (w/v), with some isolates capable of growth in the presence of up to 5% (w/v) bile. The ability of the LAB isolates to prevent Salmonella invasion of intestinal epithelial HT-29 cells varied, with reductions of between 30% (Lact. pentosus) and 80% (Lactobacillus murinus spp.) observed. CONCLUSIONS: LAB of porcine origin were observed to survive simulated passage through the GIT and inhibit growth of Salmonella and its invasion of the intestinal epithelium. SIGNIFICANCE AND IMPACT OF THE STUDY: The data demonstrate that some porcine intestinal LAB isolates may offer potential as probiotics for the reduction of Salmonella carriage in pigs.     

Differences in local anaesthetic and antiepileptic binding in the inactivated state of human sodium channel Nav1.4

Voltage-gated sodium channels play a vital role in nerve and muscle cells, enabling them to encode and transmit electrical signals. Currently, there exist several classes of drugs that aim to inhibit these channels for therapeutic purposes, including local anesthetics, antiepileptics and antiarrhythmics. However, sodium-channel-inhibiting drugs lack subtype specificity; instead, they inhibit all sodium channels in the human body. Improving understanding of the mechanisms of binding of existing nonselective drugs is important in providing insight into how subtype-selective drugs could be developed. This study used molecular dynamics simulations to investigate the binding of the antiepileptics carbamazepine and lamotrigine and the local anesthetic lidocaine in neutral and charged states to the recently resolved human Nav1.4 channel. Replica exchange solute tempering was used to enable greater sampling of each compound within the pore. It was found that all four compounds show similarities in their binding sites within the pore. However, the positions of the carbamazepine and lamotrigine did not occlude the center of the pore but preferentially bound to homologous domain DII and DIII. The charged and neutral forms of lidocaine positioned themselves more centrally in the pore, with more common interactions with DIV. The best localized binding site was for charged lidocaine, whose aromatic moiety interacted with Y1593, whereas the amine projected toward the selectivity filter. Comparisons with our previous simulations and published structures highlight potential differences between tonic and use-dependent block related to conformational changes occurring in the pore.     

Changes in the resistance of mice to whole-body lethal irradiation after local irradiation of the abdominal area

The resistance of mice to whole-body irradiation with lethal doses, after preirradiation of part of the abdomen, was studied with a reference to radiation dose, the volume of local exposure, and the interval between exposures. The radioresistance was found to increase when the preirradiated zone corresponded to the spleen projection, the interval between exposures was 3-7 days, and the dose of local exposure, 2 Gy.