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Amontons' law states that the maximum static friction force on a solid object is proportional to the loading force and is independent of the apparent contact area. This law indicates that the static friction coefficient does not depend on the external pressure or object shape. Here, we numerically investigate the sliding motion of a 3D viscoelastic block on a rigid substrate using the finite element method (FEM). The macroscopic static friction coefficient decreases with an increase in the external pressure, length, or width of the object, which contradicts Amontons' law. Precursor slip occurs in the 2D interface between the block and substrate before bulk sliding. The decrease in the macroscopic static friction coefficient is scaled by the critical area of the precursor slip before bulk sliding. A theoretical analysis of the simplified models reveals that bulk sliding results from the instability of the quasi-static precursor slip caused by velocity-weakening local friction. We also show that the critical slip area determines the macroscopic static friction coefficient, which explains the results of the FEM simulation.

This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection.We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II/III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined.The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P0.001), and T pathological (pT) factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001).Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

Recently, methods for in vitro organogenesis have been broadly developed due to their strong potential for human applications in medicine. In the present study, we optimized the culturing method of human heart organoids (hHOs) from embryonic stem cells (ESCs) in the presence of the highly concentrated laminin-entactin and fibroblast growth factor 4. The resulting hHOs showed distinctive cardiac morphology with atrium- and ventricle-like chambers composed of cardiac cells as well as expressed the integral proteins of gap junctions and ion channels. In fact, isolated cardiomyocytes from these hHOs exhibited Na and Ca currents by patch clamp analysis. These results indicated that the present method will provide a powerful tool for cardiac safety assessment of newly developed drugs as an in vitro human ESC-derived test system.One-Sentence SummaryFGF4 and ECM contribute to the generation of human HOs with heart compartments and electrophysiological properties.

Amontons' law states that the maximum static friction force on a solid object is proportional to the loading force and is independent of the apparent contact area. This law indicates that the static friction coefficient does not depend on the external pressure or object shape. Here, we numerically investigate the sliding motion of a 3D viscoelastic block on a rigid substrate using the finite element method (FEM). The macroscopic static friction coefficient decreases with an increase in the external pressure, length, or width of the object, which contradicts Amontons' law. Precursor slip occurs in the 2D interface between the block and substrate before bulk sliding. The decrease in the macroscopic static friction coefficient is scaled by the critical area of the precursor slip before bulk sliding. A theoretical analysis of the simplified models reveals that bulk sliding results from the instability of the quasi-static precursor slip caused by velocity-weakening local friction. We also show that the critical slip area determines the macroscopic static friction coefficient, which explains the results of the FEM simulation., Comment: 11 pages, 6 figures; Supplementary Information 9 pages, 3 figures; 2 ancillary files (Supplementary Video) attached

A 65-year-old woman underwent distal gastrectomy with D2 lymph node dissection for advanced gastric cancer in November 2016. The histopathological diagnosis was pT3N0M0, pStage ⅡA, HER2-negative. In August 2019, transverse colon stenosis due to peritoneal dissemination was detected, and an ileum-transverse colon anastomosis was performed. Postoperatively, she received chemotherapy with S-1 plus oxaliplatin. After 6 courses, CT revealed an increase in ascites and dissemination nodules. We diagnosed her with progressive disease and initiated second-line chemotherapy, a ramucirumab plus nab-paclitaxel regimen. On the 20th day during the 5th course of treatment, she visited our hospital with acute abdominal pain. CT revealed free air, and we diagnosed acute panperitonitis with a gastrointestinal perforation. Emergency surgery was performed, and perforation of the appendix end and mild cloudy ascites were observed. We performed an appendectomy and intraperitoneal drainage. Histopathological examination revealed perforation of the appendix, possibly as an adverse effect of the ramucirumab. It should be noted that angiogenesis inhibitors may cause the fatal adverse effect of gastrointestinal perforation.

Chylothorax after esophagectomy is a relatively rare complication that can be difficult to manage. Here, we report a case of refractory chylothorax after surgery for esophageal cancer treated with lymphatic duct lipiodol imaging by inguinal lymph node puncture to confirm patency of the thoracic duct and thoracic duct ligation. A 71-year-old female with esophageal cancer(cT3N0M0)underwent video-assisted thoracoscopic esophagectomy with 2-field lymph node dissection, intrathoracic gastric tube reconstruction, and an enterostomy. A chylothorax appeared when we started enteral nutrition on the day after surgery. She became markedly dehydrated due to over 2,000 mL/day of drainage from the chest drain, and we managed her general condition in the ICU. We started octreotide acetate on postoperative day(POD)6 and etilefrine on POD 8, but neither was effective. Lymphatic duct lipiodol imaging by bilateral inguinal lymph node puncture was performed, and we confirmed leakage from the main thoracic duct. On POD 11, a thoracic duct ligation performed via a thoracotomy revealed that the volume of the chylothorax was remarkably decreased. The chest tube was removed on re-POD 12.

We experienced a case of kidney metastasis of a gastric tumor. An 81-year-old man underwent distal gastrectomy with D2 lymph node dissection and partial hepatic resection for antral gastric tumor with hepatic infiltration in July 2019. A histological examination showed undifferentiated tubular adenocarcinoma. The final stage was pT4bN1P0H0M0, Stage ⅢB. He rejected the recommended adjuvant chemotherapy. Seven months after surgery, abdominal enhanced CT showed a hypovascular mass, 20 mm in diameter, on the right upper pole of kidney. Eleven months after surgery, CT showed that the mass had enlarged to 35 mm, infiltrated the renal pelvis, and advanced to para-aortic lymph node metastasis. We performed a retroperitoneoscopic partial right nephrectomy and diagnosed kidney metastasis of the gastric tumor. His right flank pain worsened, and radiotherapy(50 Gy)was performed for the mass and para-aortic lymph node metastasis. His right flank pain resolved. Kidney metastasis of the gastric tumor is very rare. Radiotherapy effectively relieves pain.

Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP-G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short-term findings regarding the trial’s secondary endpoints. The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ : UMIN000005421). The key eligibility criteria were histologically confirmed cT2–4a and N0–2 gastric adenocarcinoma. Short-term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum-preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non-inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients. A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and

Only a few studies have been conducted regarding the palliative radiation therapy(RT)for gastric cancer(GC)bleeding. Data of 9 patients with gastric cancer requiring blood transfusions due to gastric bleeding who were treated with RT were reviewed. All patients were men with a median age of 83(range, 70-91)years. The clinical stage was ⅡB in 2 patients, Ⅲin 1, ⅣA in 1, and ⅣB in 5. Performing gastrectomy was difficult in 4 patients with distant metastasis or tumor invasion to adjacent organ, 3 with poor performance status, and 2 with advanced age. The median hemoglobin levels before RT was 6.0 (range, 3.3-7.7)g/dL, and all patients received blood transfusions before RT. Seven patients received 30 Gy RT and 2 patients received 50 Gy. Two patients received concurrent chemotherapy. A total of 2 hematological and 4 non-hematological treatment-related adverse events occurred. All patients improved conservatively. Hemorrhage occurred in 8 patients, except for 1. Of the 8 patients who responded to RT, 1 had rebleeding on day 81. The median rebleeding-free survival time from the beginning of RT was 125(range, 21-421)days. Palliative radiation therapy was useful for bleeding control in nonresectable gastric cancer.

The aim of this study was to compare the outcome of using trans-anal ileus tube and self-expandable metallic stent(SEMS) for obstructive colorectal cancer.Between 2014 and 2018, 14 patients received trans-anal ileus tube placement (group I)and 34 received SEMS insertion as bridge to surgery(BTS)and underwent primary resection.The technical success rate was 100%in both groups, and the clinical success rate was 85.7%(12/14 cases)in group I and 91.2%(31/34 cases)in group S. In group S, the CROSS score significantly improved, the rates of stoma construction and postoperative complications were significantly lower, and the period until oral intake and hospital discharge was significantly short.SEMS insertion is more effective than trans-anal ileus tube placement in terms of short-term outcome.

The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

Objective: To investigate the prognostic values of the preoperative modified Glasgow Prognostic Score (mGPS) and carcinoembryonic antigen (CEA) alone and combined in elderly patients with colorectal cancer (CRC) planning to receive curative surgery. Methods: We retrospectively analyzed 130 elderly patients (aged ≥80 years) with CRC who received curative surgery between 2008 and 2016. The preoperative mGPS and CEA levels were calculated. Results: Elevated preoperative mGPS or CEA level was significantly associated with shorter relapse-free survival (p = 0.005, both) and cancer-specific survival (p = 0.011 and p < 0.001, respectively). Combined use of these two factors improved the predictive accuracy for tumor recurrence relative to that of either factor. Conclusion: Both mGPS and CEA were independent prognostic factors of CRC in elderly patients receiving curative surgery, but their combination was more accurate.

Dysfunctional mTOR signaling is associated with the pathogenesis of neurodevelopmental and neuropsychiatric disorders. However, it is unclear what molecular mechanisms and pathogenic mediators are involved and whether mTOR-regulated autophagy continues to be crucial beyond neurodevelopment. Here, we selectively deleted Atg7 in forebrain GABAergic interneurons in adolescent mice and unexpectedly found that these mice showed a set of behavioral deficits similar to Atg7 deletion in forebrain excitatory neurons. By unbiased quantitative proteomic analysis, we identified γ-aminobutyric acid receptor-associated protein-like 2 (GABARAPL2) to differentially form high-molecular weight species in autophagy-deficient brains. Further functional analyses revealed a novel pathogenic mechanism involving the p62-dependent sequestration of GABARAP family proteins, leading to the reduction of surface GABAA receptor levels. Our work demonstrates a novel physiological role for autophagy in regulating GABA signaling beyond postnatal neurodevelopment, providing a potential mechanism for the reduced inhibitory inputs observed in neurodevelopmental and neuropsychiatric disorders with mTOR hyperactivation.

Perforated gastric cancer reported to be relatively rare and to have a poor prognosis. This study examined 9 patients with perforated gastric cancer. Two-thirds of the patients were male and the median age was 69 years. The timing of the diagnosis of gastric cancer was preoperative clinical findings in 4 cases, intraoperative surgical findings in 3 cases, and postoperative examination in 2 cases. The depths of tumor invasion were T3 in 3 cases, T4a in 4 cases, and T4b in 2 cases and 5 patients were Stage Ⅳ. Four patients underwent palliative gastrectomy and only 1 patient underwent curative(R0)gastrectomy. Four patients underwent repair surgery, 2 of which underwent omental patch repair during the initial surgery. One of patients with omental patch repair received 2-stage curative gastrectomy; the other patient received chemotherapy after recovering from acute peritonitis. The median overall survival was 17.9 months and the prognosis was favorable in cases with curative resection or chemotherapy. For patients with perforated gastric cancer, if curative resection cannot be expected, the initial surgery should be directed toward the treatment of peritonitis and radical oncological surgery or systemic chemotherapy should be planned following patient recovery.

The aim of this study was to clarify the risk factors of severe postoperative complications and prognostic factors in patients who underwent emergent surgery for colorectal cancer perforation. ASA-PSB3 and Mannheim Prognostic Index(MPI)B27 were selected as the independent risk factors for postoperative severe complications on multivariate analysis. Moreover, severe postoperative complications and non-curative surgery were selected as the independent factors of poor prognosis.

We investigate the propagation of a slip front in a visco-elastic body on a rigid substrate. The body is one-dimensional, and the loading stress is applied at one end. By employing a local friction law that has a quadratic form of the slip velocity and gives vanishing friction stress at vanishing velocity or above a certain velocity, we show analytically that macroscopic steady slippage and creep motion can be understood in a single framework. The critical values of the end-loading stress causing macroscopic steady slippage and the slip-front propagation velocity appear are obtained. These values are completely determined by the gradient of the slip velocity-friction curve at the vanishing friction stress. These results are extended to more general friction laws, and found to be consistent with numerical calculations. Furthermore, we discuss some seismological implications based on the analytical and numerical results., Comment: 12 pages, 11 figures, accepted for publication in J. Phys. Soc. Jpn. arXiv admin note: text overlap with arXiv:1801.05771

285 Background: A complete resection of the omentum has been believed as a standard procedure for advanced gastric cancer. However, there was no evidence for survival significance of omentectomy. Therefore, we conduct the Phase II trial (TOP-G trial) comparing gastrectomy with omentectomy and omentum preserving gastrectomy. Here, we present the short-term outcomes which was a secondary endpoint of TOP-G trial. Methods: Enrollment criteria included histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. The extent of nodal dissection was performed based on the Gastric Cancer Treatment Guidelines in Japan. All procedure was performed through laparotomy. Laparoscopic approach was not accepted. Surgical outcomes morbidity, and mortality were compared between gastrectomy with omentectomy group (group A) and omentum preserving gastrectomy group (group B). Postoperative complication was evaluated with Clavien-Dindo classification. Results: A total of 251 patients were randomly assigned to group A (n = 125) or group B (n = 126) between April 2011 and October 2018. After excluding patients who received bypass or no surgery, 246 patients were analyzed as actual treatment group. There was no difference between two groups in patient characteristics and pathological findings. There was no difference in operation time (median 244 vs 204 min, p = 0.156) and in blood loss (median 260 vs. 210 ml, p = 0.371). Median number of totally retrieved lymph nodes was similar (median 36 vs. 37, p = 0.758). There was no difference in the incidence of any postoperative complication (28.9% vs. 25.8%, p = 0.584). There was no mortality in both groups. Conclusions: Omentum preserving gastrectomy for advanced gastric cancer was similar short-term outcomes with gastrectomy with omentectomy. Clinical trial information: UMIN000005421.

Autophagy regulates social behaviors by affecting the ability of brain cells to receive inhibitory signaling., Dysfunctional mTOR signaling is associated with the pathogenesis of neurodevelopmental and neuropsychiatric disorders. However, it is unclear what molecular mechanisms and pathogenic mediators are involved and whether mTOR-regulated autophagy continues to be crucial beyond neurodevelopment. Here, we selectively deleted Atg7 in forebrain GABAergic interneurons in adolescent mice and unexpectedly found that these mice showed a set of behavioral deficits similar to Atg7 deletion in forebrain excitatory neurons. By unbiased quantitative proteomic analysis, we identified γ-aminobutyric acid receptor–associated protein-like 2 (GABARAPL2) to differentially form high–molecular weight species in autophagy-deficient brains. Further functional analyses revealed a novel pathogenic mechanism involving the p62-dependent sequestration of GABARAP family proteins, leading to the reduction of surface GABAA receptor levels. Our work demonstrates a novel physiological role for autophagy in regulating GABA signaling beyond postnatal neurodevelopment, providing a potential mechanism for the reduced inhibitory inputs observed in neurodevelopmental and neuropsychiatric disorders with mTOR hyperactivation.

In elderly patients, surgical procesure is decided considering the general condition and surgical invasion. The aim of this study was to clarify the appropriate rage of lymph node dissection for elderly colorectal cancer patients. One hundred forty one colorectal cancer patients aged 75 years or more, who underwent R0 colorectal resection with D2 or D3 lymph node dissection in clinical T3/T4 or clinical N+, were enrolled in this study. The patients whose tumor located in the rectum below the peritoneal reflection(Rb)were excluded. Five-year overall survival(OS)rate and disease specific survival(DSS)rate were 79.1% and 89.4%, respectively. More than 2 preoperative co-morbidities and macroscopic type 3-5 were independent prognostic factors in OS, whereas the rage of lymph node dissection was not risk factor. When comparing the outcomes of D2 and D3 dissections by age, D3 dissection was better tendency in DSS in patients aged under 80, however, D2 dissection was better tendency in patients aged 80 or more. In elderly colorectal cancer patients, there was no difference in prognosis between D2 and D3 dissection, and especially in patients aged 80 years or more, D2 might be sufficient if R0 resection was possible.

Morphological characteristics of dendritic spines form the basis of cognitive ability. However, molecular mechanisms involved in fine-tuning of spine morphology during development are not fully understood. Moreover, it is unclear whether, and to what extent, these developmental mechanisms determine the normal adult spine morphological features. Here, we provide evidence that α2-isoform of Rac-specific GTPase-activating protein α-chimaerin (α2-chimaerin) is involved in spine morphological refinement during late postnatal period, and furthermore show that this developmental α2-chimaerin function affects adult spine morphologies. We used a series of mice with global and conditional knock-out of α-chimaerin isoforms (α1-chimaerin and α2-chimaerin). α2-Chimaerin disruption, but not α1-chimaerin disruption, in the mouse results in an increased size (and density) of spines in the hippocampus. In contrast, overexpression of α2-chimaerin in developing hippocampal neurons induces a decrease of spine size. Disruption of α2-chimaerin suppressed EphA-mediated spine morphogenesis in cultured developing hippocampal neurons. α2-Chimaerin disruption that begins during the juvenile stage results in an increased size of spines in the hippocampus. Meanwhile, spine morphologies are unaltered when α2-chimaerin is deleted only in adulthood. Consistent with these spine morphological results, disruption of α2-chimaerin beginning in the juvenile stage led to an increase in contextual fear learning in adulthood; whereas contextual learning was recently shown to be unaffected when α2-chimaerin was deleted only in adulthood. Together, these results suggest that α2-chimaerin signaling in developmental stages contributes to determination of the morphological features of adult spines and establishment of normal cognitive ability.SIGNIFICANCE STATEMENTRecent studies of neurodevelopmental disorders in humans and their animal models have led to an attractive hypothesis that spine morphogenesis during development forms the basis of adult cognition. In particular, the roles of Rac and its regulators, such as Rac-specific GTPase-activating proteins (RacGAPs) and Rac guanine nucleotide exchange factors, are a topic of focus in spine morphogenesis and cognitive ability. Using a series of mice with global and conditional knock-out (KO) of RacGAP α-chimaerin isoforms (α1-chimaerin and α2-chimaerin), we provide compelling evidence demonstrating that α2-chimaerin is involved in spine morphological refinement during late postnatal development and that this developmental α2-chimaerin function affects adult spine morphologies. Furthermore, our results clearly showed that α2-chimaerin signaling during late postnatal development contributes to normal cognitive ability in adult mice.

The aim of this study is to evaluate complications of gastrectomy for gastric cancer in patients aged over 85 years.Thirteen patients received curative gastrectomy between April 2007 and March 2008. The surgical complications were evaluated using the Clavien-Dindo classification.There were 11 patients aged 85-89 years and 2 who were over 90 years old. The median body mass index was 18. Nine patients underwent distal gastrectomy and 4 underwent total gastrectomy. The median operation time was 142 minutes and the median blood loss was 148 mL. Complications greater than Grade 2 were observed in 5 patients(38.5%). All complications were Grade 2. No surgical mortality was observed.The morbidity rate in elderly patients over 85 years of age may be higher than in patients aged 75 and lower. Our results suggest that gastrectomy for patients aged over 85 years is acceptable.

The aim of this study was to evaluate the safety and feasibility of gastrectomy in elderly patients aged over 80 years.A total of 393 patients who underwent gastrectomy for gastric cancer were assigned to 2 groups: those aged over 80 years(n=48; elderly group)and those less than 80 years(n=345).Clinicopathological features, operative factors, post-operative complications(Clavien-Dindo Grade II or higher), and mortality were retrospectively analyzed.Rates of distal gastrectomy(73% vs 59%, p=0.043)and D1 or D1+dissection(73% vs 58%, p=0.046)were significantly higher in the elderly group.There were no significant differences in post-operative complication rates(23% vs 20.3%, p=0.255)or mortality rates(2.1% vs 0.6%).Our results indicate that gastrectomy in elderly patients aged over 80 years may be safe and feasible.

Since the start of the Feed-in Tariff Program in July 2012, the PV market in Japan has been growing and annual installed capacity reached 9 GW level in 2014. It is expected that cumulative PV installed capacity as of the end of year 2015 reach 33GW with newly additional capacity of 10 GW. The FIT program was introduced for aiming to lead cost reduction of PV systems. However, The Ministry of Economy, Trade and Industry (METI) decided to change the rules of setting the FIT level since METI concluded that the current framework of the FIT program was not fully contributed to the advancement of cost reduction. This paper analyses the status of PV system cost trends including soft cost and consider impacts of the proposed revision of the FIT program on cost structures.

We report phonon dispersion curves obtained at a $\mathrm{Mo}{\mathrm{S}}_{2}(0001)$ surface in the friction process with a load and shear. An atomic force microscope tip used to apply stresses generated lattice strain on an oscillating $\mathrm{Mo}{\mathrm{S}}_{2}(0001)$ surface, which dissipated via acoustic phonons. The dissipation energy of the phonons strongly depended on the size of the lattice strain. The motion of the acoustic phonons consisted of a longitudinal mode and a transverse mode, but the occurrence of their phonon modes depended on the crystallographic direction, which reflects the atomic arrangement of the $\mathrm{Mo}{\mathrm{S}}_{2}(0001)$ surface. Thus, we can control the energy dissipation and friction by using the phonon dissipation curves in the friction process with a load and shear.

Background Vertebrate-specific neuronal genes are expected to play a critical role in the diversification and evolution of higher brain functions. Among them, the glycosylphosphatidylinositol (GPI)-anchored netrin-G subfamily members in the UNC6/netrin family are unique in their differential expression patterns in many neuronal circuits, and differential binding ability to their cognate homologous post-synaptic receptors. Results To gain insight into the roles of these genes in higher brain functions, we performed comprehensive behavioral batteries using netrin-G knockout mice. We found that two netrin-G paralogs that recently diverged in evolution, netrin-G1 and netrin-G2 (gene symbols: Ntng1 and Ntng2, respectively), were responsible for complementary behavioral functions. Netrin-G2, but not netrin-G1, encoded demanding sensorimotor functions. Both paralogs were responsible for complex vertebrate-specific cognitive functions and fine-scale regulation of basic adaptive behaviors conserved between invertebrates and vertebrates, such as spatial reference and working memory, attention, impulsivity and anxiety etc. Remarkably, netrin-G1 and netrin-G2 encoded a genetic “division of labor” in behavioral regulation, selectively mediating different tasks or even different details of the same task. At the cellular level, netrin-G1 and netrin-G2 differentially regulated the sub-synaptic localization of their cognate receptors and differentiated the properties of postsynaptic scaffold proteins in complementary neural pathways. Conclusions Pre-synaptic netrin-G1 and netrin-G2 diversify the complexity of vertebrate behaviors and differentially regulate post-synaptic properties. Our findings constitute the first genetic analysis of the behavioral and synaptic diversification roles of a vertebrate GPI protein and presynaptic adhesion molecule family.

症例は60歳，女性．主訴は微熱．既往歴は他院で僧帽弁閉鎖不全症の診断で定期経過観察中であった．現病歴は，2007年9月下旬から微熱が持続した．近医を受診し精査の結果，感染性心内膜炎（IE）と診断された．加療目的に当院循環器内科入院となり，病状から保存的治療の方針となった．入院28日目に突然心窩部痛を訴えた．腹部超音波および腹部CTを施行したところ上腸間膜動脈瘤を認めた．上腸間膜動脈瘤の切迫破裂と考え，緊急手術を施行した．手術は，上腸間膜動脈結紮および動脈瘤縫縮術を施行した．術中，上腸間膜動脈を結紮しても遠位側腸管に虚血はみられず，血行再建は施行しなかった．術後，一時的に下痢症状がみられたが内服加療で経過良好となった．現在外来通院中である．感染性心内膜炎では，全身の動脈に感染性動脈瘤を形成している危険性があり，IE治療中および経過観察中の血管造影・造影CTが重要であると考えられた．

症例は75歳，男性．2007年11月に下血が出現し，精査目的で上部消化管内視鏡を施行した．胃体部に潰瘍を伴った2型腫瘍を認め，生検の結果small cell carcinomaであった．また，同時に施行した免疫染色では，Chromogranin Aが陽性であった．胃小細胞癌（T2（MP），N0，M0，H0，P0，c StageIB）の診断で，2008年2月幽門側胃切除術，D1+α郭清，Billroth-I再建術を施行した．術後病理診断は，pT2（MP），N1，M0，H0，P0，CYX，根治度Bであった．併存疾患に脳出血後遺症として認知症があり，術後補助化学療法を行わずに経過観察とした．術後4カ月目の腹部造影CT検査で多発肝転移を認め，TS-1 100mg/日の内服を開始した．術後5カ月目に肝転移が進行し永眠した．胃小細胞癌は比較的稀とされる疾患であり，予後はきわめて不良である．現在，標準治療は確立されていない．今回われわれは，胃小細胞癌の1例を経験したので，本邦報告例の治療法と予後についての検討を含めて報告をする．

The frictional phenomena appear in various systems. Their scales spread to extraordinary wide range. The frictional systems of large scale extend to landslide, glacier and earthquake, while those of small scale reach to sub-nanometer. There are universal behaviors in friction which are independent from the scale of the system. Typical examples are the maximum static frictional force, which is the threshold strength of the external force to cause the translational motion, and the kinetic frictional force, which results from energy dissipation accompanied by the caused motion. Besides these, stick-slip phenomena, memory effect of static frictional force, velocity dependence of kinetic frictional force and so on appear in various systems with wide range of scale. There are common mechanisms in these universal phenomena. Here we review frictional phenomena of various systems from a unified point of view.