Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy

Macroautophagy/autophagy is an intracellular degradation process that delivers cytosolic materials and/or damaged organelles to lysosomes. De novo synthesis of the autophagosome membrane occurs within a phosphatidylinositol-3-phosphate-rich region of the endoplasmic reticulum, and subsequent expansion is critical for cargo encapsulation. This process is complex, especially in mammals, with many regulatory factors. In this study, by utilizing PRKN (parkin RBR E3 ubiquitin protein ligase)-mediated mitochondria autophagy (mitophagy)-inducing conditions in conjunction with chemical crosslinking and mass spectrometry, we identified human BCAS3 (BCAS3 microtubule associated cell migration factor) and C16orf70 (chromosome 16 open reading frame 70) as novel proteins that associate with the autophagosome formation site during both non-selective and selective autophagy. We demonstrate that BCAS3 and C16orf70 form a complex and that their association with the phagophore assembly site requires both proteins. In silico structural modeling, mutational analyses in cells and in vitro phosphoinositide-binding assays indicate that the WD40 repeat domain in human BCAS3 directly binds phosphatidylinositol-3-phosphate. Furthermore, overexpression of the BCAS3-C16orf70 complex affects the recruitment of several core autophagy proteins to the phagophore assembly site. This study demonstrates regulatory roles for human BCAS3 and C16orf70 in autophagic activity

cytokine profile of PFAPA

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings

A newly developed snack effective for enhancing bone volume

<p>Abstract</p> <p>Background</p> <p>The incidence of primary osteoporosis is higher in Japan than in USA and European countries. Recently, the importance of preventive medicine has been gradually recognized in the field of orthopaedic surgery with a concept that peak bone mass should be increased in childhood as much as possible for the prevention of osteoporosis. Under such background, we have developed a new bean snack with an aim to improve bone volume loss. In this study, we examined the effects of a newly developed snack on bone volume and density in osteoporosis model mice.</p> <p>Methods</p> <p>Orchiectomy (ORX) and ovariectomy (OVX) were performed for C57BL/6J mice of twelve-week-old (Jackson Laboratory, Bar Harbar, ME, USA) were used in this experiment. We prepared and given three types of powder diet <it>e.g.</it>: normal calcium diet (NCD, Ca: 0.9%, Clea Japan Co., Tokyo, Japan), low calcium diet (LCD, Ca: 0.63%, Clea Japan Co.,) and special diet (SCD, Ca: 0.9%). Eighteen weeks after surgery, all the animals were sacrified and prepared for histomorphometric analysis to quantify bone density and bone mineral content.</p> <p>Results</p> <p>As a result of histomorphometric examination, SCD was revealed to enhance bone volume irrespective of age and sex. The bone density was increased significantly in osteoporosis model mice fed the newly developmental snack as compared with the control mice. The bone mineral content was also enhanced significantly. These phenomena were revealed in both sexes.</p> <p>Conclusion</p> <p>It is shown that the newly developed bean snack is highly effective for the improvement of bone volume loss irrespective of sex. We demonstrated that newly developmental snack supplements may be a useful preventive measure for Japanese whose bone mineral density values are less than the ideal condition.</p

Shelf Slope Upwelling of High Nutrient Bottom Water in the Bungo Channel

豊後水道において陸棚斜面水が陸棚域底層に湧昇している現象が観測された。この湧昇水は高栄養であった。この湧昇水の直上にクロロフィルa濃度の高い水塊が観測され、陸棚湧昇が本海域中・底層の植物プランクトン生産に対する栄養塩供給源となっていることが示唆された。また、この湧昇水は潮流により移動しているが、速吸瀬戸までは達していないことが推測された。しかしながら、黒潮流軸の変化などの影響により、湧昇水の先端が速吸瀬戸まで達していることが予想された。The upwelling of shelf slope water onto the shelf of the Bongo Channel was observed. The shelf slope water contained high concentrations of nutrients. The high chlorophyll a concentration w as also observed at and around the tip of the up welling water. These results indicate that the nutrient rich shelf slope water would accelerate the phytoplankton growth on the shelf of the Bongo Channel. It was assumed that the tip of the upwelling water could not reach to the Hayasui Strait by tidal excursion but was expected to be achieved by the force accompanied by the fluctuation of offshore Kuroshio current

Combination of Nasolabial V-Y Advancement Flap and Glabellar Subcutaneous Pedicled Flap for Reconstruction of Medial Canthal Defect

A 77-year-old woman presented with a 1-year history of a right medial canthal tumor, which was histopathologically diagnosed as a basal cell carcinoma. After removal of the tumor with a 4-mm safety margin, the defect occupied the areas superior and inferior to the medial canthal tendon. We first reconstructed the lower part of the defect using a nasolabial V-Y advancement flap to make an elliptic defect in the upper part. We then created a glabellar subcutaneous pedicled flap to match the residual upper elliptic defect with the major axis set along a relaxed skin tension line. The pedicled glabellar flap was passed through a subcutaneous tunnel to the upper residual defect. At 6 months postoperatively, the patient showed no tumor recurrence and a good cosmetic outcome

Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women

The incidence of diabetes has been gradually increasing, not only in middle-aged individuals but also in young individuals. However, insulin and glucose patterns have not been investigated in apparently healthy young individuals, as they are typically grouped as controls. In this study, we investigated and classified glucose and insulin patterns in healthy young women. Sixty-two nonobese women without metabolic disease were recruited. The subjects underwent a 75 g oral glucose tolerance test (OGTT), physical measurements, and a biochemical examination. Two subjects displayed impaired glucose tolerance. The 62 subjects were categorized into four patterns by plasma glucose and insulin peak time during OGTT: normal type (n=39), insulin-late type (n=11), insulin- and glucose-late type (n=7), and insulin-very late type (n=5). OGTT glucose and insulin levels at all time points, insulinogenic index, HOMA-IR, and glucose area under the curve (AUC) significantly differed among the four groups. However, insulin AUC did not significantly differ. We did not detect significant differences in body condition or biochemical measurements. Our study demonstrated that some healthy young individuals might have delayed insulin secretion by OGTT. Early detection of altered glucose metabolism might be helpful to improve lifestyle choices and prevent progression to diabetes