Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.

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The guanine-plus-cytosine (G + C) contents of the deoxyribonucleic acids (DNAs) of Peptococcus asaccharolyticus ATCC 14963T (T = type strain), Peptococcus indolicus ATCC 29427 ', Peptococcus prevotii ATCC 9321T, and Peptococcus magnus ATCC 15794T ranged from 29 to 34 mol%, whereas the G+C content of the DNA of P eptococcus niger ATCC 27731T, the type species of the genus Peptococcus, is 51 mol%. The G+C content of the DNA of Peptostreptococcus anaerobius ATCC 27337T, the type species of the genus Peptostreptococcus, was 33 mol%. Thus, the DNA base compositions of Peptococcus asaccharolyticus, Peptococcus indolicus, Peptococcus prevotii, and Peptococcus magnus resemble the DNA base composition of the type species of the genus Peptostreptococcus rather than the DNA base composition of the type species of the genus Peptococcus. It is not desirable for the genus Peptococcus to include any species whose G+C content is far from the G+C content of the type species of the genus. The levels of DNA-DNA homology between Peptostreptococcus anaerobius ATCC 27337T and the four species of Peptococcus with low G+C DNA contents ranged from 23 to 36%. The cellular fatty acid profiles of Pep tococcus asaccharolyticus, Peptococcus indolicus, Peptococcus prevotii, and Peptococcus magnus also resembled the cellular fatty acid profile of the type species of Peptostreptococcus. Other biochemical characteristics of these species revealed their close resemblance to Peptostreptococcus anaerobius. For these reasons we propose transfer of the four Peptococcus species that have low G + C contents to the genus Peptostreptococcus as Peptostreptococcus asaccharolyticus (Distaso 1912) comb. nov., P eptostreptococcus indolicus (Christiansen 1934) comb. nov., Peptostreptococcus prevotii (Foubert and Douglas 1948) comb. nov., and Peptostreptococcus mangus (Prkvot 1933) Smith 1957 comb. rev. A group of organisms previously referred to as "Gamya anaerobia" (Choukevitch) Prevot is an identifiable Peptostreptococcus species based on phenotypic and genotypic characteristics. The name of Peptostreptococcus tetradius sp. nov. is proposed for this group of organisms. Strain GIFU 7672 (= ATCC 35098) is designated the type strain. Clinical strains of P. asacchurolyticus that were identified by conventional methods were divided into two homology groups and one unclassified group (A-1). DNA-DNA homology between the type strain of P. prevotii and clinical strains which had been received as P . prevotii ranged from 0 to 73%.

Neoadjuvant S-1 with concurrent hypofractionated radiotherapy is tolerable and appears promising for patients with R and BR PDAC.