Are Dysregulated Inflammatory Responses to Commensal Bacteria Involved in the Pathogenesis of Hepatobiliary-Pancreatic Autoimmune Disease? An Analysis Using Mice Models of Primary Biliary Cirrhosis and Autoimmune Pancreatitis

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure in the pathogenesis of primary biliary cirrhosis (PBC) and autoimmune pancreatitis (AIP), both of which are broadly categorized as autoimmune disorders involving hepatobiliary-pancreatic lesions. Avirulent and/or commensal bacteria, which may have important role(s) as initiating factors in the pathogenesis of autoimmune disorders such as PBC and AIP, will be emphasized

Helicobacter pylori Exploits Host Membrane Phosphatidylserine for Delivery, Localization, and Pathophysiological Action of the CagA Oncoprotein

SummaryWhen delivered into gastric epithelial cells via type IV secretion, Helicobacter pylori CagA perturbs host cell signaling and thereby promotes gastric carcinogenesis. However, the mechanisms of CagA delivery, localization, and action remain poorly understood. We show that direct contact of H. pylori with epithelial cells induces externalization of the inner leaflet enriched host phospholipid, phosphatidylserine, to the outer leaflet of the host plasma membrane. CagA, which is exposed on the bacterial surface via type IV secretion, interacts with the externalized phosphatidylserine to initiate its entry into cells. CagA delivery also requires energy-dependent host cell processes distinct from known endocytic pathways. Within polarized epithelial cells, CagA is tethered to the inner leaflet of the plasma membrane through interaction with phosphatidylserine and binds the polarity-regulating host kinase PAR1/MARK to induce junctional and polarity defects. Thus, host membrane phosphatidylserine plays a key role in the delivery, localization, and pathophysiological action of CagA

Rice Mutants Lacking Starch Synthase I or Branching Enzyme IIb Activity Altered Starch Biosynthetic Protein Complexes

Amylopectin, the major component of starch, is synthesized by synergistic activity of multiple isozymes of starch synthases (SSs) and branching enzymes (BEs). The frequency and length of amylopectin branches determine the functionality of starch. In the rice endosperm, BEIIb generates short side chains of amylopectin and SSI elongates those branches, which can be further elongated by SSIIa. Absence of these enzymes greatly affects amylopectin structure. SSI, SSIIa, and BEIIb associate with each other and with other starch biosynthetic enzymes although SSIIa is low activity in japonica rice. The aim of the current study was to understand how the activity of starch biosynthetic enzyme complexes is compensated in the absence of SSI or BEIIb, and whether the compensatory effects are different in the absence of BEIIb or in the presence of inactive BEIIb. Interactions between starch biosynthetic enzymes were analyzed using one ss1 null mutant and two be2b japonica rice mutants (a mutant producing inactive BEIIb and a mutant that did not produce BEIIb). Soluble proteins extracted from the developing rice seeds were separated by gel filtration chromatography. In the absence of BEIIb activity, BEIIa was eluted in a broad molecular weight range (60–700 kDa). BEIIa in the wild-type was eluted with a mass below 300 kDa. Further, majority of inactive BEIIb co-eluted with SSI, SSIIa, and BEI, in a mass fraction over 700 kDa, whereas only small amounts of these isozymes were found in the wild-type. Compared with the be2b lines, the ss1 mutant showed subtle differences in protein profiles, but the amounts of SSIIa, SSIVb, and BEI in the over-700–kDa fraction were elevated. Immunoprecipitation revealed reduced association of SSIIa and BEIIb in the ss1 mutant, while the association of BEIIb with SSI, SSIIa, SSIVb, BEI, and BEIIa were more pronounced in the be2b mutant that produced inactive BEIIb enzyme. Mass spectrometry and western blotting revealed that SSI, SSIIa, SSIIIa, BEI, BEIIa, starch phosphorylase 1, and pullulanase were bound to the starch granules in the be2b mutants, but not in the wild-type and ss1 mutant. These results will aid the understanding of the mechanism of amylopectin biosynthesis

ジンカク ノ テキオウテキ ヘンヨウ ト スポーツ シンジョウ スポーツ カラノ リダツ ニチャクモクシテ

A large number of precedent setting research concerned with athelte-dropout from their activities has been treated in terms of : the reason for dropping out, and the pattern of dropout. In this study, the athlete-dropouts were observed from an idea suggested by Nakagomi (1993); "Dropout from sports is a sort of crisis in one\u27s normal development." This author proceed the study with a view that the most negative dropout can have a positive affect. Furthermore, this author presumed, one of the main factors, which causes maladjustment in their social environment after they quite their sport, was to form unusually irrational beliefs in sport. The processes of personal change were classified into three types based on beliefs about sport. Result were as following : 1) Beliefs changed before and after dropping out. 2) When the beliefs changed rationally, personality became adaptable. 3) In order to bring about adaptable personal change, it is necessary to feel a problem within onself and to try to solve it. 4) Among many who adapted their personality to their social environment, the remaking of their framework mostly appeared in the dropouts

Sur la nécessité des stages de formation pédagogique

Debutant ou experimente, tout enseignant a interet a se former tout au long de sa carriere. En effet, meme muni du titre d\u27enseignant du secondaire, l\u27enseignant qui debute n\u27a souvent jamais eu une veritable experience de terrain. De meme, l\u27enseignant avec de longues annees d\u27experience doit se mettre au fait de l\u27evolution des methodes qui se renouvellent sans cesse, en particulier depuis l\u27apparition du cadre commun europeen de reference pour les langues (le CECR). Pour repondre a tous ces besoins potentiels mais neanmoins bien reels, nombre de stages sont proposes non seulement au Japon mais egalement en France et dans d\u27autres pays francophones. Ces stages sont tout aussi bien destines aux enseignants experimentes qu\u27aux futurs enseignants. Cependant, on est oblige de constater que le nombre de candidats aux stages de formation organises au Japon est bien inferieur aux attentes des organisateurs. Il semblerait done que les annonces ou informations concernant ces stages fassent defaut, bien que d\u27autres facteurs rentrent evidemment en jeu. Get article a done pour but de fournir un certain nombre d\u27informations pour essayer de combler ce manque. Nous esperons ainsi eveiller la curiosite des enseignants et futurs enseignants en les incitant a reflechir sur l\u27interet des stages pedagogiques

Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain

遺伝子治療によるホスト脳の環境最適化が細胞移植効果を高める --ホスト脳へのL1CAMの強制発現によるマウス胎仔脳移植片の軸索伸長促進効果--. 京都大学プレスリリース. 2023-03-24.Combining cell transplantation and gene therapy to enhance axonal outgrowth in the central nervous system. 京都大学プレスリリース. 2023-04-06.Cell replacement therapy is expected as a new and more radical treatment against brain damage. We previously reported that transplanted human cerebral organoids extend their axons along the corticospinal tract in rodent brains. The axons reached the spinal cord but were still sparse. Therefore, this study optimized the host brain environment by the adeno-associated virus (AAV)-mediated expression of axon guidance proteins in mouse brain. Among netrin-1, SEMA3, and L1CAM, only L1CAM significantly promoted the axonal extension of mouse embryonic brain tissue-derived grafts. L1CAM was also expressed by donor neurons, and this promotion was exerted in a haptotactic manner by their homophilic binding. Primary cortical neurons cocultured on L1CAM-expressing HEK-293 cells supported this mechanism. These results suggest that optimizing the host environment by the AAV-mediated expression of axon guidance molecules enhances the effect of cell replacement therapy