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Gene ablation studies in mice have revealed roles for gap junction proteins (connexins) in heart development. Of the 20 connexins in vertebrates, four are expressed in developing heart: connexin37 (Cx37), connexin40 (Cx40), connexin43 (Cx43), and connexin45 (Cx45). Although each cardiac connexin has a different pattern of expression, some heart cells coexpress multiple connexins during cardiac morphogenesis. Since different connexins could have overlapping functions, some developmental phenotypes may only become evident when more than one connexin is ablated. In this study, we interbred Cx[40.sup.-/-] and Cx[43.sup.-/-] mice to generate mice lacking both Cx[40.sup.-/-] and Cx[43.sup.-/-]. Cx[40.sup.-/-] Cx[43.sup.-/-] mice die around embryonic day 12.5 (E12.5), much earlier than either Cx[40.sup.-/-] or Cx[43.sup.-/-] mice, and they exhibit malformed hearts with ventricles that are abnormally rotated, suggesting a looping defect. Some Cx[40.sup.-/-] Cx[43.sup.-/-] animals also develop head defects characteristic of exencephaly. In addition, we examined mice lacking both Cx40 and Cx37 and found a high incidence of atrial and ventricular septal defects at birth. These results provide further evidence for the importance of gap junctions in embryonic development. Moreover, ablating different pairs of cardiac connexins results in distinct heart defects, suggesting both common and unique functions for Cx40, Cx43, and Cx37 during cardiac morphogenesis. Keywords: Connexin: Cx37: Cx40: Cx43; Gap junction; Intercellular communication; Cardiac development; Cardiac malformation; Exencephaly

Cells within the vascular wall are coupled by gap junctions, allowing for direct intercellular transfer of low molecular weight molecules. Although gap junctions are believed to be important for vascular development and function, their precise roles are not well understood. Mice lacking either connexin37 (Cx37) or connexin40 (Cx40), the predominant gap junction proteins present in vascular endothelium, are viable and exhibit phenotypes that are largely non-blood vessel related. Since Cx37 and Cx40 are coexpressed in endothelial cells and could overlap functionally, some roles of junctional communication may only be revealed by the elimination of both connexins. In this study, we interbreed Cx37 and Cx40 knockout mice to generate [Cx37.sup.-/-][Cx40.sup.-/-] animals and show that they display severe vascular abnormalities and die perinatally. [Cx37.sup.-/-][Cx40.sup.-/-] animals exhibit localized hemorrhages in skin, testis, gastrointestinal tissues, and lungs, with pronounced blood vessel dilatation and congestion occurring in some areas. Vascular anomalies were particularly striking in testis and intestine. In testis, abnormal vascular channels were present, with these channels coalescing into a cavernous, endothelium-lined blood pool resembling a hemangioma. These results provide evidence of a critical role for endothelial gap junction-mediated communication in the development and/or functional maintenance of segments of the mouse vasculature. Key Words: connexin; gap junction; intercellular communication; endothelium; vascular abnormality; hemorrhage; hemangioma; vascular malformation.

Abstract: Vaccination of chicks with Salmonella (S.) Typhimurium aroA deletion mutants has previously been shown to inhibit intestinal colonization of wild‐type S. Typhimurium strains. In Australia, Bioproperties VaxSafe™ STM1 strain is the only licensed and commercially available S. Typhimurium vaccine. This vaccine is a live attenuated aroA deletion mutant. Currently, it is recommended that the first dose of the STM1 vaccine is administered through coarse spray. It is unclear whether this mode of administration effectively permits intestinal colonization. Furthermore, it is not known whether the STM1 strain prevents or inhibits Salmonella colonization of chicks following this first dose. This study investigated both in vitro and in vivo colonization parameters. Invasiveness was assessed using an in vitro invasion assay into sections of ileum and caecum collected from day‐old chicks. The S. Typhimurium definitive types (DT) 9 and 44 exhibited the greatest invasion into both intestinal segments. STM1 was invasive but was significantly less so than both isolates of S. Typhimurium. In dual and triple infections, no competitive microbial interactions between STM1 and wild‐type Salmonella were observed. In vivo colonization inhibition was also tested. Vaccinated and nonvaccinated day‐old chicks were challenged with S. Typhimurium DT9. Both STM1 and S. Typhimurium DT9 were found in spleen, liver, ileum, caecum and caecal contents from day 2 postinfection. No significant exclusion effect was observed in vaccinated and challenged chicks. [ABSTRACT FROM AUTHOR]

Salmonella remains one of the most common causes of bacterial foodborne gastrointestinal disease in humans. Raw eggs or food items containing undercooked eggs are frequently identified as the source of Salmonella. Salmonella Typhimurium contamination of table eggs most commonly occurs when they are laid in a contaminated environment. Several control strategies, including vaccination, are widely used to mitigate the total Salmonella load. It is unclear, however, whether live attenuated Salmonella vaccines are efficacious over the life span of a layer hen. Live attenuated Salmonella vaccines have been favored due to their ability to illicit a strong humoral immune response. The lifespan of a layer hen ranges between 60 and 80 weeks and the long term efficacy of attenuated vaccine strains has not been investigated. In this study, commercial brown layer chicks were vaccinated at day old, 6 weeks of age, and again at 10 weeks of age with the Bioproperties VaxsafeTM STM1 aroA mutant vaccine. Birds were challenged at 18 weeks of age with Salmonella Typhimurium DT9 (MLVA 03 15 08 11 550). Feces and eggs were monitored for S. Typhimurium for 40 weeks post-infection. Birds produced a strong immune response following the final dose which was administered intramuscularly. The serum antibody response to S. Typhimurium DT9 infection did not differ between challenged groups. Fecal shedding and egg contamination was highly variable and did not differ significantly between vaccinated and unvaccinated birds that had been challenged with S. Typhimurium DT9. Total bacterial load in feces was quantified using qPCR. No significant difference was detected between unvaccinated and vaccinated birds after challenge. [ABSTRACT FROM AUTHOR]