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Despite the importance of the insect nervous system for functional and developmental neuroscience, descriptions of insect brains have suffered from a lack of uniform nomenclature. Ambiguous definitions of brain regions and fiber bundles have contributed to the variation of names used to describe the same structure. The lack of clearly determined neuropil boundaries has made it difficult to document precise locations of neuronal projections for connectomics study. To address such issues, a consortium of neurobiologists studying arthropod brains, the Insect Brain Name Working Group, has established the present hierarchical nomenclature system, using the brain of Drosophila melanogaster as the reference framework, while taking the brains of other taxa into careful consideration for maximum consistency and expandability. The following summarizes the consortium's nomenclature system and highlights examples of existing ambiguities and remedies for them. This nomenclature is intended to serve as a standard of reference for the study of the brain of Drosophila and other insects., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

We herein report a case of intracholecystic papillary-tubular neoplasm (ICPN) of the gallbladder in which jaundice developed. A 58-year-old woman with jaundice was referred to our hospital. Computed tomography revealed a papillary tumor in the body of the gallbladder protruding into the bile duct. A transpapillary biopsy of the bile duct verified adenocarcinoma, and pancreatoduodenectomy with extended cholecystectomy was performed. The tumor spread macroscopically from the gallbladder body to the cystic duct, thus forming a polypoid mass protruding into the bile duct. This is a rare case of invasive carcinoma from ICPN leading to mechanical obstruction of the bile duct.

Background: The aim of the present study was to evaluate the usefulness of a single-balloon enteroscope (SBE) including a newly developed short SBE (SIF-Y0004) for therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y (R-Y) anastomosis., Patients and Methods: Therapeutic ERC using a SBE was attempted in 19 cases (41 procedures) with R-Y anastomosis after gastrectomy. A standard SBE (working length of 200 cm, working channel of 2.8 mm) was used in 11 cases (Group L), and a short SBE (working length of 152 cm, working channel of 3.2 mm) was used in eight cases (Group S)., Results: Insertion of the scope up to the major papilla was achieved in 79% (15/19) of cases. Average insertion time was 37.0 ± 13.8 min (range, 19-62 min). Bile duct cannulation rate was 79% (11/14) after exclusion of the initial case in which scope exchange was unsuccessful. Average procedure time was78.8 ± 26.9 min (18-119 min). The scheduled therapeutic procedure was completed in 67% (10/15) of the cases (53% [10/19] on an intention-to-treat basis). Cardiorespiratory suppression due to sedative agents resulting in scope withdrawal developed in one procedure (2.4%; 1/41). Although there was no significant difference in therapeutic results between the two groups, the number of procedures was smaller (1.8 ± 1.3 vs 3.6 ± 3.1; P = 0.286) in Group S than in Group L., Conclusions: Therapeutic ERC using a SBE for patients with R-Y anastomosis is considered to be safe and effective. A short SBE appears to be promising for further improvement in therapeutic results., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Background: In patients with unresectable malignant biliary obstruction (MBO), anticancer treatment is often administered. The impact of anticancer treatment on recurrent biliary obstruction in covered self-expandable metallic stents (SEMS) has not been fully elucidated., Methods: Data on 279 patients enrolled in a multicenter prospective cohort study of two different covered SEMS for distal MBO, WATCH study (141 partially covered WallFlex stents and 138 partially covered Wallstents) were retrospectively analyzed. The rates and causes of recurrent biliary obstruction (stent occlusion or migration) were compared between anticancer treatment group (n = 173) and best supportive care alone (BSC) group (n = 106). Cumulative time and prognostic factors for recurrent biliary obstruction were analyzed, using a proportional hazards model with death without recurrent biliary obstruction as a competing risk., Results: The overall rate (43 vs. 25%, P = 0.002) and the cumulative incidence (16.1 vs. 8.2, 27.9 vs. 18.9 and 44.1 vs. 26.6% at 3, 6 and 12 months, P = 0.030 by Gray's test) of recurrent biliary obstruction were significantly higher in anticancer treatment group compared with BSC group. The multivariate analysis revealed anticancer treatment [subdistribution hazard ratio (SHR) 1.93, P = 0.007) as well as the use of a partially covered WallFlex stent (SHR 0.65, P = 0.049) as prognostic factors., Conclusions: Anticancer treatment was a risk factor for recurrent biliary obstruction in covered SEMS for distal MBO. The superiority of a partially covered WallFlex stent was again confirmed in this competing risk analysis; UMIN-CTR: UMIN000002293.

Drosophila is increasingly used for understanding the neural basis of behavior through genetically targeted manipulation of specific neurons. The primary approach in this regard has relied on the suppression of neuronal activity. Here, we report the results of a novel approach to find and characterize neural circuits by expressing neuronal activators to stimulate subsets of neurons to induce behavior. Classical electrophysiological studies demonstrated that stimulation of command neurons could activate neural circuits to trigger fixed action patterns. Our method was designed to find such command neurons for diverse behaviors by screening flies in which random subsets of brain cells were activated. We took advantage of the large collection of Gal4 lines from the NP project and crossed 835 Gal4 strains with relatively limited Gal4 expression in the brain to flies carrying a UAS transgene encoding TRPM8, a cold-sensitive ion channel. Low temperatures opened the TRPM8 channel in Gal4-expressing cells, leading to their excitation, and in many cases induced overt behavioral changes in adult flies. Paralysis was reproducibly observed in the progeny of crosses with 84 lines, whereas more specific behaviors were induced with 24 other lines. Stimulation performed using the heat-activated channel, TrpA1, resulted in clearer and more robust behaviors, including flight, feeding, and egg-laying. Through follow-up studies starting from this screen, we expect to find key components of the neural circuits underlying specific behaviors, thus providing a new avenue for their functional analysis.

Escherichia coli cells that express the full six carotenoid biosynthesis genes (crtE, crtB, crtI, crtY, crtZ, and crtX) of the bacterium Pantoea ananatis have been shown to biosynthesize zeaxanthin 3,3'-β-D-diglucoside. We found that this recombinant E. coli also produced a novel carotenoid glycoside that contained a rare carbohydrate moiety, quinovose (chinovose; 6-deoxy-D-glucose), which was identified as 3-β-glucosyl-3'-β-quinovosyl zeaxanthin by chromatographic and spectroscopic analyses. The chirality of the aglycone of these zeaxanthin glycosides had been shown to be 3R,3'R, in which the hydroxyl groups were formed with the CrtZ enzyme. It was here demonstrated that zeaxanthin synthesized from β-carotene with CrtR or CYP175A1, the other hydroxylase with similar catalytic function to CrtZ, possessed the same stereochemistry. It was also suggested that the singlet oxygen-quenching activity of zeaxanthin 3,3'-β-D-diglucoside, which has a chemical structure close to the new carotenoid glycoside, was superior to that of zeaxanthin.

Many feeding behaviours are the result of stereotyped, organized sequences of motor patterns. These patterns have been the subject of neuroethological studies, such as electrophysiological characterization of neurons governing prey capture in toads. However, technical limitations have prevented detailed study of the functional role of these neurons, a common problem for vertebrate organisms. Complexities involved in studies of whole-animal behaviour can be resolved in Drosophila, in which remote activation of brain cells by genetic means enables us to examine the nervous system in freely moving animals to identify neurons that govern a specific behaviour, and then to repeatedly target and manipulate these neurons to characterize their function. Here we show neurons that generate the feeding motor program in Drosophila. We carried out an unbiased screen using remote neuronal activation and identified a critical pair of brain cells that induces the entire feeding sequence when activated. These 'feeding neurons' (here abbreviated to Fdg neurons for brevity) are also essential for normal feeding as their suppression or ablation eliminates sugar-induced feeding behaviour. Activation of a single Fdg neuron induces asymmetric feeding behaviour and ablation of a single Fdg neuron distorts the sugar-induced feeding behaviour to become asymmetric, indicating the direct role of these neurons in shaping motor-program execution. Furthermore, recording neuronal activity and calcium imaging simultaneously during feeding behaviour reveals that the Fdg neurons respond to food presentation, but only in starved flies. Our results demonstrate that Fdg neurons operate firmly within the sensorimotor watershed, downstream of sensory and metabolic cues and at the top of the feeding motor hierarchy, to execute the decision to feed.

Aim: The aim of the present study was to investigate the efficacy and safety of a newly available enteral WallFlex stent for malignant gastric outlet obstruction (GOO)., Methods: Twenty-one consecutive patients with symptomatic (unable to take solids) malignant GOO treated by a WallFlex stent from April 2010 to February 2012 were included and analyzed retrospectively. Main outcome measurements were technical success, early complications, clinical response (elimination of the need for nasogastric tube drainage), clinical success (improvement of oral intake to a GOO score of 2 or 3), and duration of sustaining a GOO score of 2 or 3 after clinical success (median duration until reworsening of GOO score to <2 by the Kaplan-Meier method). A four-point GOO scoring system (0-3) was used for estimation of oral intake., Results: Technical success rate was 100%. Bleeding and perforation after stent placement and stent dislocation/migration in the follow-up period did not occur in any patients, whereas one patient (5%) developed moderate post-procedural pancreatitis. Clinical response and clinical success was achieved in all patients and in 81% (17/21), respectively. In 17 patients whose GOO score had improved to 2 or 3 after stent placement, eight (47%) developed reworsening of the GOO score to <2 with a median time of 148 days (95% confidence interval [CI], 0-328; Kaplan-Meier method). Median survival time after the initial intervention was 61 days (95% CI, 40-82)., Conclusion: Placement of an enteral WallFlex stent in patients with malignant GOO is safe and effective., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Background and Aim: There is a paucity of data on the cell block (CB) method for bile cytology. We compared the diagnostic efficacy of the CB method with that of conventional smear cytology for bile obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial manner., Methods: A total of 137 patients with biliary tract lesions suspicious of malignancy who had undergone bile collection under ERCP were recruited to this study. After sampling, the bile was randomized to the CB method (n = 69) or to smear cytology (n = 68). CB sections were prepared using the sodium alginate method and subjected to hematoxylin-eosin, Alcian blue-periodic acid-Schiff stain, and immunohistochemical stains. Both Papanicolaou and Giemsa stains were used for smear cytology., Results: The final diagnosis was malignancy in 94 patients: bile duct cancer, 42; pancreatic head cancer, 34; gallbladder cancer, 16; and ampullary cancer, two. The diagnostic accuracy of the CB method and that of smear cytology were 64% and 53%, respectively (P = 0.20). The sensitivity of the CB method (53%) was significantly better than that of smear cytology (28%; P = 0.014). Their respective sensitivities were 80% and 31% (P = 0.002) for bile duct cancer, 20% and 15% (P = 1.0) for pancreatic head cancer, and 30% and 67% (P = 0.30) for gallbladder cancer., Conclusion: The CB method for bile cytology showed a higher diagnostic yield than smear cytology. Its diagnostic sensitivity was satisfactory in cases of bile duct cancer., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

A metal stent has a longer stent patency than a plastic stent in patients with unresectable malignant distal biliary stricture. However, treatment for stent dysfunction of a metal stent remains unresolved. A review of reported articles regarding reintervention for metal stent dysfunction showed that causes of stent dysfunction included tumor ingrowth/overgrowth, stone/sludge/food impaction, and stent migration. Cleaning of the stent is associated with an early relapse of stent dysfunction. Additional placement of a covered metal stent is expected to have a longer stent patency than that of other stents such as uncovered metal stents or plastic stents. It is recommended that occluded covered metal stents be removed if possible. Stent trimming with argon plasma coagulation is sometimes useful for the treatment of stent displacement. No strategy for occluded metal stents has been established yet. Further clinical trials regarding proper treatments are necessary., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Background: During development neurons are generated by sequential divisions of neural stem cells, or neuroblasts. In the insect brain progeny of certain stem cells form lineage-specific sets of projections that arborize in distinct brain regions, called clonal units. Though this raises the possibility that the entire neural network in the brain might be organized in a clone-dependent fashion, only a small portion of clones has been identified., Results: Using Drosophila melanogaster, we randomly labeled one of about 100 stem cells at the beginning of the larval stage, analyzed the projection patterns of their progeny in the adult, and identified 96 clonal units in the central part of the fly brain, the cerebrum. Neurons of all the clones arborize in distinct regions of the brain, though many clones feature heterogeneous groups of neurons in terms of their projection patterns and neurotransmitters. Arborizations of clones overlap preferentially to form several groups of closely associated clones. Fascicles and commissures were all made by unique sets of clones. Whereas well-investigated brain regions such as the mushroom body and central complex consist of relatively small numbers of clones and are specifically connected with a limited number of neuropils, seemingly disorganized neuropils surrounding them are composed by a much larger number of clones and have extensive specific connections with many other neuropils., Conclusions: Our study showed that the insect brain is formed by a composition of cell-lineage-dependent modules. Clonal analysis reveals organized architecture even in those neuropils without obvious structural landmarks., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An 82-year-old male was referred to our institution for evaluation and treatment of a protruding lesion in the stomach. Esophagogastroduodenoscopy (EGD) showed a small protruding lesion and a large superficial elevated lesion on the lesser curvature of the stomach (macroscopic type: 0-I and 0-IIa, resp.). CT and endoscopic ultrasonography (EUS) visualized a small round lymph node (LN) 11 mm in size near the lesser curvature, although submucosal invasion was not evident. These two lesions were resected en bloc by endoscopic submucosal dissection (ESD). Pathological examination of the resected specimen showed moderately differentiated tubular adenocarcinoma (tub2) and well-differentiated tubular adenocarcinoma (tub1), respectively, which were limited to the mucosal layer. Because lymphatic-vascular involvement was not detected by hematoxylin and eosin (HE) staining, additional gastrectomy was not performed. Two months after ESD, follow-up EUS and CT showed an enlarged LN. EUS-guided fine needle aspiration (EUS-FNA) for the LN revealed metastasis. Therefore, total gastrectomy with LN dissection was performed. His postoperative course was uneventful. After discharge, he has been followed up at the outpatient department without any sign of recurrence for 5 years. Histological reexamination of the ESD specimen using immunohistochemistry showed lymphatic invasion of cancer cells in the lamina propria of the 0-I lesion 13 mm in size.

The primary olfactory centers of both vertebrates and insects are characterized by glomerular structure. Each glomerulus receives sensory input from a specific type of olfactory sensory neurons, creating a topographic map of the odor quality. The primary olfactory center is also innervated by various types of neurons such as local neurons, output projection neurons (PNs), and centrifugal neurons from higher brain regions. Although recent studies have revealed how olfactory sensory input is conveyed to each glomerulus, it still remains unclear how the information is integrated and conveyed to other brain areas. By using the GAL4 enhancer-trap system, we conducted a systematic mapping of the neurons associated with the primary olfactory center of Drosophila, the antennal lobe (AL). We identified in total 29 types of neurons, among which 13 are newly identified in the present study. Analyses of arborizations of these neurons in the AL revealed how glomeruli are linked with each other, how different PNs link these glomeruli with multiple secondary sites, and how these secondary sites are organized by the projections of the AL-associated neurons., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Recently, the clinical application of diffusion-weighted magnetic resonance imaging (DWI) has been expanding to abdominal organs. However, only a few studies on gallbladder diseases have been published. The aim of this study was to evaluate the usefulness and limitations of high b-value DWI for gallbladder diseases., Methods: A total of 153 patients (mean age 60 ± 15 years, 78 males) who had undergone DWI for evaluating gallbladder wall thickening or polypoid lesions were included in this study. Of these 153 patients, 36 had gallbladder cancer and 117 had benign gallbladder diseases (67 chronic cholecystitis, 44 adenomyomatosis, four cholesterol polyp, one gallbladder adenoma, and one xanthogranulomatous cholecystitis). We evaluated the positive signal rate with DWI and the apparent diffusion coefficient (ADC) value of each disease., Results: The positive signal rate with DWI was significantly higher in gallbladder cancer (78 %) than in benign gallbladder diseases (22 %) (p < 0.001). The mean ADC value of gallbladder cancer was (1.83 ± 0.69) × 10(-3) mm(2)/s and that of benign gallbladder diseases was (2.60 ± 0.54) × 10(-3) mm(2)/s (p < 0.001). Benign gallbladder diseases with acute cholecystitis or a history of that had a higher positive signal rate with DWI (p < 0.001) and a lower ADC value (p = 0.018) than those without such conditions., Conclusion: DWI can contribute to the improvement of the diagnostic capability for gallbladder wall thickening or polypoid lesions by compensating for weaknesses of other modalities by its many advantages, although cases with acute cholecystitis or such history sometimes show false-positive on DWI.

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone. Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries. We examined the tooth enamel structure of an RDEB patient by scanning electron microscopy. It showed irregular enamel prisms, indicating structural enamel defects. To elucidate the pathomechanisms of enamel defects due to COL7 deficiency, we investigated tooth formation in Col7a1(-/-) and COL7-rescued humanized mice that we have established. The enamel from Col7a1(-/-) mice had normal surface structure. The enamel calcification and chemical composition of Col7a1(-/-) mice were similar to those of the wild type. However, transverse sections of teeth from the Col7a1(-/-) mice showed irregular enamel prisms, which were also observed in the RDEB patient. Furthermore, the Col7a1(-/-) mice teeth had poorly differentiated ameloblasts, lacking normal enamel protein-secreting Tomes' processes, and showed reduced mRNA expression of amelogenin and other enamel-related molecules. These enamel abnormalities were corrected in the COL7-rescued humanized mice expressing a human COL7A1 transgene. These findings suggest that COL7 regulates ameloblast differentiation and is essential for the formation of Tomes' processes. Collectively, COL7 deficiency is thought to disrupt epithelial-mesenchymal interactions, leading to defective ameloblast differentiation and enamel malformation in RDEB patients., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.

Background and Aim: Although reports on endosonography-guided biliary drainage (ESBD) have been increasing, only a few reports on deployment of a self-expandable metal stents (SEMS) have been reported. The aim of the present study was to evaluate the safety and efficacy of SEMS deployment in ESBD., Methods: Of 42 patients who underwent ESBD during the period from January 2007 to August 2011, 21 patients with unresectable malignant biliary obstruction in whom SEMS deployment had been attempted were included. In the first session, a plastic stent or SEMS was placed in a bilio-enteric anastomosis (BEA) method. SEMS was deployed with the one-step technique or with replacement of a plastic stent with a SEMS in the second session. The technical success, early and late complications, and stent patency of SEMS were evaluated., Results: One-step SEMS deployment was attempted in seven patients, and SEMS was deployed with stent exchange in 14. SEMS deployment was successful in all patients without any complications. Finally, SEMS was placed in a BEA method in 16 patients (extrahepatic bile duct, 13; intrahepatic bile duct, three), and with antegrade deployment in five. Late complications occurred in three patients who underwent deployment of SEMS in a BEA method (stent obstruction in two and reflux cholangitis in one). The mean stent patency period was 433 days., Conclusions: As SEMS deployment in ESBD is safe and provides long stent patency, a SEMS seems to be the stent of choice in ESBD for patients with unresectable malignant biliary obstruction in whom long survival is expected., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Background: Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs., Objective: To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force., Design: Multicenter, prospective study with a historical cohort., Setting: Twenty Japanese referral centers., Patients: This study involved patients with unresectable distal malignant biliary obstruction., Intervention: Placement of a new, commercially available, partially covered SEMS., Main Outcome Measurements: Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival., Results: Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%)., Limitations: Nonrandomized, controlled trial., Conclusion: Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Purpose: We evaluated a small group of patients with hemorrhagic lesions in the small intestine diagnosed preoperatively by video capsule endoscopy (VCE) and/or double-balloon endoscopy (DBE), who underwent surgery in our hospital., Methods: The subjects were 20 patients with hemorrhagic lesions in the small intestine diagnosed preoperatively by VCE and/or DBE, who underwent surgery between April 2004 and December 2008., Results: VCE, DBE, and computed tomography were performed in 12, 17, and 20 patients, respectively. Eleven patients also had a biopsy taken during DBE, resulting in a definitive diagnosis in eight. Because of the risk of hemorrhage during DBE in five patients, a biopsy was not taken and the sites of the lesion were marked in these patients. Twenty patients underwent surgery, and the diagnoses were small-intestinal cancer in eight, gastrointestinal stromal tumor in seven, arteriovenous malformation in two, and Crohn's disease, angioectasia, and leiomyoma in one each. The interval between the onset of symptoms and surgery was less than 50 days for six patients, 50-100 days for two, 100-200 days for five, and more than 200 days for seven., Conclusion: Preoperative small-bowel endoscopy proved useful for diagnosing the cause of hemorrhagic lesions in the small intestine.

Studying the insect visual system provides important data on the basic neural mechanisms underlying visual processing. As in vertebrates, the first step in visual processing in insects is through a series of retinotopic neurons. Recent studies on flies have found that these converge onto assemblies of columnar neurons in the lobula, the axons of which segregate to project to discrete optic glomeruli in the lateral protocerebrum. This arrangement is much like the fly's olfactory system, in which afferents target uniquely identifiable olfactory glomeruli. Here, whole-cell patch recordings show that even though visual primitives are unreliably encoded by single lobula output neurons because of high synaptic noise, they are reliably encoded by the ensemble of outputs. At a glomerulus, local interneurons reliably code visual primitives, as do projection neurons conveying information centrally from the glomerulus. These observations demonstrate that in Drosophila, as in other dipterans, optic glomeruli are involved in further reconstructing the fly's visual world. Optic glomeruli and antennal lobe glomeruli share the same ancestral anatomical and functional ground pattern, enabling reliable responses to be extracted from converging sensory inputs.

Aim:   To elucidate the diagnostic efficacy of the cell block (CB) method by comparing it with that of conventional smear cytology for pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial fashion., Methods:   A total of 170 patients with pancreatic lesions suspicious of being malignant who underwent pancreatic juice collection without giving secretin under ERCP were enrolled in this study. After sampling, the pancreatic juice was randomized to the CB method (n = 85) or to smear cytology (n = 85). CB sections were subjected to hematoxylin-eosin, periodic acid Schiff-Alcian blue, and immunohistochemical stains. Both Papanicolaou stain and Giemsa stain were used for smear cytology., Results:   The final diagnosis was malignancy in 54 patients: pancreatic cancer, 45; intraductal papillary-mucinous carcinoma, six; and endocrine tumor, three. The number of patients with a cytological borderline malignancy in the CB group (3.5%) was significantly smaller than that in the smear group (27.1%) (P < 0.001). The diagnostic accuracy of the CB method and that of smear cytology were 76.5% (65/85) and 74.1% (63/85), respectively (P = 0.72), and their respective sensitivities were 50% (14/28) and 38.5% (10/26) (P = 0.39). The sensitivity of the CB method (88.9%) was better than that of smear cytology (42.9%) for invasive ductal carcinoma in the pancreas head (P = 0.048)., Conclusions:   The CB method using immunostaining for pancreatic juice cytology showed a much lower rate of equivocal borderline malignancy and a tendency for a higher diagnostic yield compared with smear cytology. Its diagnostic sensitivity, however, was not satisfactory except for pancreatic-head cancer., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

The causes of benign biliary stricture include chronic pancreatitis, primary/immunoglobulin G4-related sclerosing cholangitis and complications of surgical procedures. Biliary stricture due to fibrosis as a result of inflammation is sometimes encountered in patients with chronic pancreatitis. Frey's procedure, which can provide pancreatic duct drainage with decompression of biliary stricture, can be an initial treatment for chronic pancreatitis with pancreatic and bile duct strictures with upstream dilation. When patients are high-risk surgical candidates or hesitate to undergo surgery, endoscopic treatment appears to be a potential second-line therapy. Placement of multiple plastic stents is currently considered to be the best choice as endoscopic treatment for biliary stricture due to chronic pancreatitis. Temporary placement with a fully covered metal stent has become an attractive option due to the lesser number of endoscopic retrograde cholangiopancreatography (ERCP) sessions and its large diameter. Further clinical trials comparing multiple placement of plastic stents with placement of a covered metal stent for biliary stricture secondary to chronic pancreatitis are awaited., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Oxygen levels in tissues including the embryonic brain are lower than those in the atmosphere. We reported previously that Notch signal activation induces demethylation of astrocytic genes, conferring astrocyte differentiation ability on midgestational neural precursor cells (mgNPCs). Here, we show that the oxygen sensor hypoxia-inducible factor 1α (HIF1α) plays a critical role in astrocytic gene demethylation in mgNPCs by cooperating with the Notch signaling pathway. Expression of constitutively active HIF1α and a hyperoxic environment, respectively, promoted and impeded astrocyte differentiation in the developing brain. Our findings suggest that hypoxia contributes to the appropriate scheduling of mgNPC fate determination., (Copyright © 2011 AlphaMed Press.)

Abstract: This review summarizes technical development of the functional manipulation of specific neural circuits through genetic techniques in Drosophila. Long after pioneers' efforts for the genetic dissection of behavior using this organism as a model, analyses with acute activation of specific neural circuits have finally become feasible using transgenic Drosophila that expresses light-, heat-, or cold-activatable cation channels by xxx/upstream activation sequence (Gal4/UAS)-based induction system. This methodology opened a new avenue to dissect functions of neural circuits to make dreams of the pioneers into reality.

Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory., Competing Interests: The authors have declared that no competing interests exist.

We herein report a case of pancreatic undifferentiated carcinoma involving intraductal pedunculated polypoid growth. Duodenoscopy disclosed a congested polypoid mass protruding from the orifice of the papilla of Vater. Endoscopic retrograde pancreatography (ERP) showed a polypoid lesion in Wirsung's duct and Santorini's duct. Pancreatic juice cytology using the cell block method revealed the presence of undifferentiated carcinoma. No extraductal invasion was detected on endoscopic ultrasonography and or intraductal ultrasonography. The patient therefore underwent pancreaticoduodenectomy. A histological examination revealed an intraductal polypoid tumor with a thin stalk without extraductal invasion. The tumor was composed of an abundant mixture of pleomorphic cells, spindle cells, giant cells, and a small amount of adenocarcinoma.

Aim: To evaluate the usefulness of a modified technique of endoscopic papillectomy (EP) for lessening the occurrence of complications., Methods: Indications for EP were adenoma or well-differentiated adenocarcinoma confined to the papilla of Vater (T1) without tumor spread into the bile/pancreatic duct. Sixteen patients underwent the modified technique, which consists of resection with the Endocut mode, followed by biliary/pancreatic sphincterotomy and stenting (Group A). Twelve patients who had undergone EP, using a cutting current, followed by pancreatic duct stenting were included as control (Group B). The frequency of complications and clinical outcomes were retrospectively compared between the two groups., Results: Sixteen patients had adenoma, and 12 had adenocarcinoma. Early complications occurred in 36% of all patients (hemorrhage, 7; cholangitis, 3; perforation, 2; cholecystitis, 1). The frequency of early complications in Group A was significantly lower than that in Group B (6% vs 75%, odds ratio [OR] 0.022, 95% confidence interval [CI], 0.0020-0.25). Late complications occurred in 18% of the patients (bile duct stone, 3; hemorrhage, 1; pancreatitis, 1). There was no significant difference in the late complication rate between Group A and Group B (19% vs 17%). Local recurrences were found in 14% of the patients, without a significant difference between Group A and Group B (19% vs 8%) during a mean follow-up period. All recurrent tumors were successfully treated with argon plasma coagulation., Conclusions: The modified technique of EP for ampullary neoplasm contributed to lessening the occurrence of early complications. However, further refinement of this technique is necessary for improving the clinical outcome., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal. Each ORN in Drosophila acquires one of three basic identities defined by the compound outcome of three iterated Notch signaling events during neurogenesis. Hamlet, the Drosophila Evi1 and Prdm16 proto-oncogene homolog, modifies cellular responses to these iteratively used Notch signals in a context-dependent manner, and controls odorant receptor gene choice and ORN axon targeting specificity. In nascent ORNs, Hamlet erases the Notch state inherited from the parental cell, enabling a modified response in a subsequent round of Notch signaling. Hamlet directs locus-specific modifications of histone methylation and histone density and controls accessibility of the DNA-binding protein Suppressor of Hairless at the Notch target promoter.

Despite its ubiquity and significance, behavioral habituation is poorly understood in terms of the underlying neural circuit mechanisms. Here, we present evidence that habituation arises from potentiation of inhibitory transmission within a circuit motif commonly repeated in the nervous system. In Drosophila, prior odorant exposure results in a selective reduction of response to this odorant. Both short-term (STH) and long-term (LTH) forms of olfactory habituation require function of the rutabaga-encoded adenylate cyclase in multiglomerular local interneurons (LNs) that mediate GABAergic inhibition in the antennal lobe; LTH additionally requires function of the cAMP response element-binding protein (CREB2) transcription factor in LNs. The odorant selectivity of STH and LTH is mirrored by requirement for NMDA receptors and GABA(A) receptors in odorant-selective, glomerulus-specific projection neurons(PNs). The need for the vesicular glutamate transporter in LNs indicates that a subset of these GABAergic neurons also releases glutamate. LTH is associated with a reduction of odorant-evoked calcium fluxes in PNs as well as growth of the respective odorant-responsive glomeruli. These cellular changes use similar mechanisms to those required for behavioral habituation. Taken together with the observation that enhancement of GABAergic transmission is sufficient to attenuate olfactory behavior, these data indicate that habituation arises from glomerulus-selective potentiation of inhibitory synapses in the antennal lobe. We suggest that similar circuit mechanisms may operate in other species and sensory systems.

A 60's man underwent a medical check-up and esophagogastroduodenoscopy revealed an exposed-type tumor at the ampulla of Vater. Endoscopic ultrasonography and intraductal ultrasonography showed a hypoechoic mass limited to the ampulla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a slightly dilated ventral pancreatic duct not connected to the dorsal duct. Endoscopic papillectomy was performed without pancreatic stent placement and his postprocedural course was uneventful. The specimen was histologically diagnosed as well-differentiated adenocarcinoma limited to the mucosa of the ampulla of Vater. Endoscopic papillectomy without pancreatic stent placement can be performed without a risk of post-ERCP pancreatitis for ampullary tumor limited to the mucosa of the ampulla of Vater associated with pancreas divisum.

A 40-year-old woman was hospitalized because of acute pancreatitis. CT showed a monolocular cyst thought to be a pseudocyst. The patient was followed as an outpatient. The size of the cyst decreased 6 years later. Ultrasonography 10 years later demonstrated an enlarged cyst with a cyst-in-cyst formation. A tendency to increase in size and the irregular wall thickening indicated that the cyst was a malignant mucinous cystic neoplasm (MCN) and distal pancreatectomy was performed. The tumor was diagnosed histologically as a mucinous cystadenoma. A case of MCN resected after long-term follow-up is extremely rare. The present case is thought to be important for elucidation of the natural history of MCNs.

Aversive olfactory memory is formed in the mushroom bodies in Drosophila melanogaster. Memory retrieval requires mushroom body output, but the manner in which a memory trace in the mushroom body drives conditioned avoidance of a learned odor remains unknown. To identify neurons that are involved in olfactory memory retrieval, we performed an anatomical and functional screen of defined sets of mushroom body output neurons. We found that MB-V2 neurons were essential for retrieval of both short- and long-lasting memory, but not for memory formation or memory consolidation. MB-V2 neurons are cholinergic efferent neurons that project from the mushroom body vertical lobes to the middle superiormedial protocerebrum and the lateral horn. Notably, the odor response of MB-V2 neurons was modified after conditioning. As the lateral horn has been implicated in innate responses to repellent odorants, we propose that MB-V2 neurons recruit the olfactory pathway involved in innate odor avoidance during memory retrieval.

It was more than 50 years ago that an appearance of birefringence in alginate gels prepared under cation flow was reported for the first time, however, the anisotropic structure of the alginate gel has not been studied in detail. In the present study, anisotropic Ca-alginate gels were prepared within dialysis tubing in a high Ca(2+)-concentration external bath, and optical and small-angle X-ray scattering (SAXS) measurements were performed to characterize the structure of the gel. The observations of the gel with crossed polarizers and with circular polarizers revealed the molecular orientation perpendicular to the direction of Ca(2+) flow. Analyses of the SAXS intensity profiles indicated the formation of rod-like fibrils consisting of a few tens of alginate molecules and that the anisotropy of the gel was caused by the circumferential orientation of the large fibrils. From the observed asymmetric SAXS pattern, it was found that the axis of rotational symmetry of the anisotropic structure was parallel to the direction of Ca(2+) flow. The alignment factor (A(f)) calculated from the SAXS intensity data confirmed that the orientation of the fibrils was perpendicular to the direction of Ca(2+) flow.

We herein report a case of ampullary cancer associated with pancreas divisum. Duodenoscopy revealed a tumor at the ampulla of Vater with a normal ampullary orifice. Intraductal ultrasonography showed a hypoechoic mass limited to the ampulla of Vater. ERCP showed an arborizing ventral pancreatic duct without connection to the dorsal duct. Endoscopic snare resection of the tumor was performed following biliary stenting. Histological examination revealed well-differentiated tubular adenocarcinoma limited to the ampulla of Vater. Endoscopic papillectomy with the assistance of a biliary stent is useful in cases of ampullary neoplasm with a normal ampullary orifice in order to avoid ductal injury.

Background and Aim: Biliary intraductal ultrasonography (IDUS) is highly sensitive in visualizing bile duct stones (BDS). Indications for IDUS, however, in cases of suspected BDS have not yet been established. The aim of the present study was to elucidate adequate indications for IDUS in cases that undergo endoscopic retrograde cholangiopancreatography (ERCP) due to suspected BDS., Methods: A total of 213 patients who were suspected of having BDS were included in this retrospective study. The patients were divided into two groups: Group A in which BDS was visualized by ERCP; and Group B in which BDS was demonstrated only by IDUS. Comparison between the groups was carried out., Results: ERCP successfully visualized BDS in 166 patients. Forty-seven patients underwent IDUS, which revealed BDS and biliary sludge in 12 and eight patients, respectively. The diameter of the largest stone was 13 ± 6 mm in Group A and 5 ± 1 mm in Group B (P < 0.001). The sensitivity, specificity, and accuracy of ERCP in the diagnosis of BDS were 93%, 100%, and 94%, respectively. The sensitivity was influenced by the size of BDS: 100% in cases of stones ≥ 8 mm in size, but 74% in those with stones < 8 mm. In cases with stones < 8 mm, the sensitivity was significantly affected by the bile duct diameter (≥ 12 mm vs < 12 mm, P < 0.05)., Conclusion:   When ERCP fails to visualize stones in patients with suspected BDS, IDUS is recommended, especially in those with a bile duct ≥ 12 mm in diameter., (© 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.)

The long history of neuroscience has accumulated information about numerous types of neurons in the brain of various organisms. Because such neurons have been reported in diverse publications without controlled format, it is not easy to keep track of all the known neurons in a particular nervous system. To address this issue we constructed an online database called Flybrain Neuron Database (Flybrain NDB), which serves as a platform to collect and provide information about all the types of neurons published so far in the brain of Drosophila melanogaster. Projection patterns of the identified neurons in diverse areas of the brain were recorded in a unified format, with text-based descriptions as well as images and movies wherever possible. In some cases projection sites and the distribution of the post- and presynaptic sites were determined with greater detail than described in the original publication. Information about the labeling patterns of various antibodies and expression driver strains to visualize identified neurons are provided as a separate sub-database. We also implemented a novel visualization tool with which users can interactively examine three-dimensional reconstruction of the confocal serial section images with desired viewing angles and cross sections. Comprehensive collection and versatile search function of the anatomical information reported in diverse publications make it possible to analyze possible connectivity between different brain regions. We analyzed the preferential connectivity among optic lobe layers and the plausible olfactory sensory map in the lateral horn to show the usefulness of such a database., (Copyright © 2010 Wiley-Liss, Inc.)

Background and Aim: For ampullary cancer, pancreaticoduodenectomy is considered to be the standard treatment. Endoscopic papillectomy (EP) has been utilized in cases of ampullary adenoma since the early 1980s. We aimed to provide a review concerning EP., Methods: We conducted a review of studies regarding EP for ampullary neoplasms., Results: Since neither lymphatic permeation, vascular invasion, nor lymph node metastasis is observed in patients with ampullary cancer limited to the mucosa, EP of such tumors without ductal infiltration into the pancreatic/bile duct can be justified as radical treatment. For its application in patients with ampullary neoplasms, accurate pretreatment staging is indispensable. EUS, which can be carried out on an outpatient basis with a low risk of complications, is useful for differential diagnosis as well as detection of periampullary tumors. Although intraductal US of the bile duct tends to result in overestimation of tumor staging in cases of ampullary neoplasm, it can provide useful information for making therapeutic decisions, especially in cases appropriate for EP. While the technical success rate of EP is high, the complication rate and recurrence rate are not as low as a satisfactory level. Pancreatic duct stenting after EP is expected to contribute to prevention of post-EP pancreatitis. There is no consensus regarding the mode of resection current nor the need for addition of biliary/pancreatic sphincterotomy and biliary stenting., Conclusions: EP has been reported to be useful in selected patients with ampullary neoplasms. Data on further long-term follow up after EP are awaited., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

Background: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend to spread intraepithelially along the pancreatic duct wall. We evaluated histopathological intraductal lateral spread (LS) along the main pancreatic duct (MPD) from branch-duct IPMN and investigated the usefulness of intraductal ultrasonography (IDUS) for its preoperative diagnosis., Patients and Methods: Twenty-four patients with branch-duct IPMN who had undergone preoperative IDUS and surgery were reviewed clinicopathologically. The prevalence and histological length of LS along the MPD from branch-duct IPMN, characteristics of the patients with LS, and efficacy of LS assessment by IDUS were examined., Results: LS along the MPD was observed in 54% of the subjects. In the group of patients with LS, its mean length was 25.2±16.8mm (5-50mm) and the diameter of the MPD was 6mm or greater. Of the patients with LS, those in whom the length of LS along the MPD was longer than the diameter of the cystically dilated branch accounted for 30%. The diameter of the MPD in the group with LS was significantly greater than that in the group without LS (P=0.03). The sensitivity, specificity, and overall accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively., Conclusion: LS along the MPD was detected in about half of the resected cases of branch-duct IPMN. Preoperative transpapillary IDUS may be beneficial for the determination of the resection line, especially in those branch-duct IPMN patients in whom the MPD is 6 mm or greater in diameter., (© 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.)