Human induced pluripotent stem cells (iPSC) hold promise for modeling diseases in individual human genetic backgrounds and thus for developing precision medicine. Here, we generate sensorimotor organoids containing physiologically functional neuromuscular junctions (NMJs) and apply the model to different subgroups of amyotrophic lateral sclerosis (ALS). Using a range of molecular, genomic, and physiological techniques, we identify and characterize motor neurons and skeletal muscle, along with sensory neurons, astrocytes, microglia, and vasculature. Organoid cultures derived from multiple human iPSC lines generated from individuals with ALS and isogenic lines edited to harbor familial ALS mutations show impairment at the level of the NMJ, as detected by both contraction and immunocytochemical measurements. The physiological resolution of the human NMJ synapse, combined with the generation of major cellular cohorts exerting autonomous and non-cell autonomous effects in motor and sensory diseases, may prove valuable to understand the pathophysiological mechanisms of ALS.

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The ability of 17 Actinobacillus pkuropneumoniae isolates, representing serotypes 1, 2, 5, and 7, to adhere to tracheal rings maintained in culture was examined. Porcine tracheal rings were infected, and 8 h after inoculation, adherent bacterial cells were evaluated. A. pleuropneumoniae adhered to tracheal rings, and marked variations were observed between and even within serotypes, suggesting that adherence of this microorganism is not primarily related to the serotype of the isolate. No relationship was found between adherence to porcine tracheal rings and plasmid profiles, virulence in mice, hemagglutination, capsular material thickness, or whole-cell protein profiles. On the other hand, we observed that all isolates of serotypes and 5 had a semirough-type lipopolysaccharide (LPS), whereas isolates of serotypes 2 and 7 had a smooth-type LPS (75%) or a semirough-type LPS (25%). Results showed that 83% of isolates with a smooth-type LPS adhered in large numbers to tracheal rings, whereas 80% of isolates with a semirough-type LPS adhered poorly (P < 0.007). Our data indicated that the degree of adherence of A. pleuropneumoniae to porcine tracheal rings appeared to be related, at least in part, to LPS profiles. Furthermore, LPS seemed to be the adhesin of A. pleuropneumoniae, since purified LPS blocked adherence of this microorganism to porcine tracheal rings. * Corresponding author. (4226), and 5a (K17) were provided by A. Gunnarson, National Veterinary Institute, Uppsala, Sweden. A strain of serotype Sb (L20) was provided by R. Nielsen, State Veterinary Serum Laboratory, Copenhagen, Denmark. A strain representing serotype 7 (WF83) was obtained from S. Rosendal,

Actinobacilus pleuropneumoniae is the causative agent of porcine pleuropneumonia. The major adhesin ofA. pleuropneumoniae has been identified as the lipopolysaccharides (LPSs) (

Title: Heat but not mechanical hypersensitivity depends on voltage-gated Ca V 2.2 calcium channel activity in peripheral axon terminals innervating skin Abbreviated title: Peripheral Ca V 2.2 channels control heat hypersensitivity

The genetic determinant coding for F1651 fimbriae was cloned from the chromosome of the porcine Escherichia coliwild-type strain 4787 (0115: K-: H51: F165). The fimbrial determinant was further subcloned into the BmHI site of pACYC184 and a restriction map was established. On Southern hybridization, identity between the chromosomally encoded prs-like determinant of strain 4787 and its cloned counterparts was demonstrated. The cloned F1651 fimbriae and those of the wild-type strain possessed a major protein subunit of molecular mass 18.5 kDa. Strains expressing F1651 fimbriae were detected using an F165-specilic polyclonal antiserum and caused mannose-resistant haemagglutination and agglutination of Forssman latex beads. Antiserum against the cloned F16$4 fimbriae recognized a 18.5 kDa band in the parent strain 4787.

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