Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles

We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS97xS99). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip–Syntaxin4 interaction

Changes in muscle activity after performing the FIFA 11+ programme part 2 for 4 weeks

Changes in muscle activity were evaluated by positron emission tomography–computed tomography (PET–CT) after performing part 2 of the Fédération Internationale de Football Association’s 11+ programme (11+) for 4 weeks. Eleven males performed part 2 of the 11+ for 20 min before and after 37 MBq of 18F-fluorodeoxyglucose (FDG) was injected intravenously. PET–CT images were obtained 50 min after FDG injection. The participants were then instructed to perform part 2 of the 11+ 3 times per week for 4 consecutive weeks, after which another set of PET–CT images was obtained following the same procedure. Regions of interest were defined within 30 muscles. The standardised uptake value (SUV) of FDG by muscle tissue per unit volume was calculated, and FDG accumulation was compared between pre- and post-training PET–CT results. Performing part 2 of the 11+ for 4 weeks increased mean SUV in the sartorius, semimembranosus, biceps femoris, abductor hallucis, and flexor hallucis brevis muscles (P < 0.05). In conclusion, routinely performing part 2 of the 11+ for 4 weeks increased glucose uptake related to muscle activity in the hamstrings and hallux muscles. We speculate that there is some possibility of this change of muscle activity contributing to a decrease in sports-related injuries. © 2016 Taylor & FrancisEmbargo Period 18 month

Associated factors with surgical site infections after hepatectomy: Predictions and countermeasures by a retrospective cohort study

Background: To clarify the factors associated with post-hepatectomy surgical site infections (SSIs), the clinicopathological data of 526 patients who underwent hepatectomy was retrospectively examined as a retrospectively cohort study. Methods: Patient demographics, liver functions, histological findings, surgical records and post-hepatectomy morbidity were compared between non-SSI and SSI groups; the SSI group included superficial and deep SSIs. Results: The prevalence of SSIs (5-8%) has not changed over an 18-year period. Deep SSIs were significantly more increased in male patients with lower performance statuses and American Society of Anesthesiologists (ASA) scores (p < 0.05). SSIs tended to be less prevalent, although not significant (p = 0.10), in patients who underwent laparoscopic hepatectomies compared to those who underwent laparotomies. For patients in whom hemostatic devices were used, the prevalence of superficial SSIs was significantly lower than those in whom the devices were not used (p < 0.05). Blood loss and transfusion were significantly more frequent in the deep SSI group compared to other groups (p < 0.01). Hospital stay in the deep SSI group was significantly longer compared to other groups. The incidence of morbidity was more frequent in the SSI groups compared with the non-SSI group (p < 0.001). A multivariate analysis showed that not using a vessel sealing device was significantly associated with superficial SSIs; male gender, hepatic failure and bile leakage were significantly associated with deep SSIs (p < 0.05). Conclusions: SSIs were important indicators of patient outcomes after hepatectomies, and preventing SSI development after surgical procedures is an important step in improving the overall prevalence of SSIs

Identification of nesfatin-1 as a satiety molecule in the hypothalamus

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus

Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema

Whole Body Muscle Activity during the FIFA 11+ Program Evaluated by Positron Emission Tomography

Purpose:This study investigated the effect of the FIFA 11+ warm-up program on whole body muscle activity using positron emission tomography.Methods:Ten healthy male volunteers were divided into a control group and a group that performed injury prevention exercises (The 11+). The subjects of the control group were placed in a sitting position for 20 min and 37 MBq of 18F-fluorodeoxyglucose (FDG) was injected intravenously. The subjects then remained seated for 45 min. The subjects of the exercise group performed part 2 of the 11+for 20 min, after which FDG was injected. They then performed part 2 of the 11+for 20 min, and rested for 25 min in a sitting position. Positron emission tomography-computed tomography images were obtained 50 min after FDG injection in each group. Regions of interest were defined within 30 muscles. The standardized uptake value was calculated to examine the FDG uptake of muscle tissue per unit volume.Results:FDG accumulation within the abdominal rectus, gluteus medius and minimus were significantly higher in the exercise group than in the control group (P<0.05).Conclusion:The hip abductor muscles and abdominal rectus were active during part 2 of the FIFA 11+ program. © 2013 Nakase et al

Validation of radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas: Japanese Orthopaedic Association Committee on Musculoskeletal Tumors Cooperative Study

AbstractBackgroundThe radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated.MethodsWe conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients’ overall survival using the Kaplan-Meier method and the log-rank test.ResultsThe JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing’s sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid.ConclusionsThe JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas

The prognostic factors of recurrent GCT: A cooperative study by the Eastern Asian Musculoskeletal Oncology Group

Background Giant-cell tumor (GCT) of bone is a common primary benign tumor with high local recurrence and potential distant metastasis or malignant transformation. We haveinvestigated the clinical behavior of recurrent GCT of bone in the extremities. Methods We retrospectively reviewed 110 patients with recurrent GCTs of bone in the extremities treated by the Eastern Asian Musculoskeletal Oncology Group. The factors that affected the number of recurrences and distant metastasis were analyzed. Results The median interval between initial surgery and the first recurrence of GCTwas 16 months (2-180 months). All patients received additional surgery for first recurrence. Twenty-five patients had a second recurrence and 6 patients had a third recurrence. The mean interval between theinitial surgery and the first recurrence correlated withthe eventual number of recurrences-14.1 months for the repeated recurrence groups (two and three recurrences) and 28.3 months for the single recurrence group (p = 0.016). Campanacci grade did not correlate with repeated recurrence (p = 0. 446). The venue of the initial surgery did not correlate with recurrence but did affect preservation of the adjacent joint (chi-squared test; p =0.046). Campanacci grade II and III also correlated withsacrifice of the adjacent joint (p = 0.020). The incidence of lung metastasis and malignant transformation were 7.5% (8 out of 107 patients) and 2.7% (3 out of 110 patients), respectively. Repeat recurrence was associated with lung metastasis (p = 0.018). © The Japanese Orthopaedic Association 2011

Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study

[Background] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. [Methods] A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. [Results] In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. [Conclusions] CTACK is a novel prognostic biomarker of IPF

ジョウホウ カデン システム ノ アンゼン ケンショウ

家電製品の発展は組込みシステムの発展の歴史でもあり、システムL81の高機能化と組込みソフトウエアが基盤技術として支えてきた.一方で，家電製品に対するユーザからの利便性への声も大きな役割を果たしてきた.もう一つの基盤技術がネットワーク技術で，家電製品をネットワークに接続することで情報家電と呼ばれるシステムにまで発展させた.本稿では情報家電のこれまでの発展と今後の動向を，提供するサーピスと利用形態に基づき3つの世代に分類して説明する.次に，世代が進むにつれて要求品質で扱うべき内容が広がりを見せてきている実態を紹介する.特に，ネットワークに接続されることによって，システムが援雑化しただけでなく，悪意あるユーザからの攻撃に耐えることが要求される.その上，複数の情報家篭が同時に動かされることから，それらの競合が深刻な問題となりつつある.最後に，代表的な実際の事例研究についても紹介する