Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament

AbstractActin filaments have key roles in cell motility but are generally claimed to be passive interaction partners in actin-myosin-based motion generation. Here, we present evidence against this static view based on an altered myosin-induced actin filament gliding pattern in an in vitro motility assay at varied [MgATP]. The statistics that characterize the degree of meandering of the actin filament paths suggest that for [MgATP] ≥ 0.25 mM, the flexural rigidity of heavy meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or slightly lower (with phalloidin) than that of HMM-free filaments observed in solution without surface tethering. When [MgATP] was reduced to ≤0.1 mM, the actin filament paths in the in vitro motility assay became appreciably more winding in both the presence and absence of phalloidin. This effect of lowered [MgATP] was qualitatively different from that seen when HMM was mixed with ATP-insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25–30%). In particular, the addition of NEM-HMM increased a non-Gaussian tail in the path curvature distribution as well as the number of events in which different parts of an actin filament followed different paths. These effects were the opposite of those observed with reduced [MgATP]. Theoretical modeling suggests a 30–40% lowered flexural rigidity of the actin filaments at [MgATP] ≤ 0.1 mM and local bending of the filament front upon each myosin head attachment. Overall, the results fit with appreciable structural changes in the actin filament during actomyosin-based motion generation, and modulation of the actin filament mechanical properties by the dominating chemomechanical actomyosin state

Evolution of living donor liver transplantation over 10 years: experience of a single center.

PURPOSE: To evaluate the changes in living donor liver transplantations (LDLTs) over the last 10 years, we analyzed our experience of performing LDLT in a single center. METHODS: We performed 73 LDLTs over the 10 years between 1997 and 2007 in Nagasaki University Hospital, Japan. RESULTS: Initially, from 1997 to 2003, LDLT was performed for pediatric patients; then, between 2004 and 2007, adult-to-adult LDLT was introduced, primarily for hepatocellular carcinoma (HCC) in liver cirrhosis. We also began performing LDLTs for adults with ABO-incompatible blood type combination in the latter period. As the number of adult-to-adult LDLTs increased, left-sided grafts became fi rst choice for these patients. Survival rates were 88.3%, 77.2%, 70.2% at 1, 3, and 5 years, respectively. There was a relatively low incidence of arterial complications, and although the incidence of biliary complications was high initially, it decreased with experience. Likewise, the operative time, blood loss, and hospital stay after LDLT also improved remarkably. CONCLUSION: Over the last 10 years the indications for, and operative techniques used in LDLT have changed dramatically, even in a single center in Japan

Hybrid Procedure in Living Donor Liver Transplantation

Background We have previously reported a hybrid procedure that uses a combination of laparoscopic mobilization of the liver and subsequent hepatectomy under direct vision in living donor liver transplantation (LDLT). We present the details of this hybrid procedure and the outcomes of the procedure. Methods Between January 1997 and August 2014, 204 LDLTs were performed at Nagasaki University Hospital. Among them, 67 recent donors underwent hybrid donor hepatectomy. Forty-one donors underwent left hemihepatectomy, 25 underwent right hemihepatectomy, and 1 underwent posterior sectionectomy. First, an 8-cm subxiphoid midline incision was made; laparoscopic mobilization of the liver was then achieved with a hand-assist through the midline incision under the pneumoperitoneum. Thereafter, the incision was extended up to 12 cm for the right lobe and posterior sector graft and 10 cm left lobe graft procurement. Under direct vision, parenchymal transection was performed by means of the liver-hanging maneuver. The hybrid procedure for LDLT recipients was indicated only for selected cases with atrophic liver cirrhosis without a history of upper abdominal surgery, significant retroperitoneal collateral vessels, or hypertrophic change of the liver (n = 29). For total hepatectomy and splenectomy, the midline incision was sufficiently extended. Results All of the hybrid donor hepatectomies were completed without an extra subcostal incision. No significant differences were observed in the blood loss or length of the operation compared with conventional open procedures. All of the donors have returned to their preoperative activity level, with fewer wound-related complaints compared with those treated with the use of the conventional open procedure. In recipients treated with the hybrid procedure, no clinically relevant drawbacks were observed compared with the recipients treated with a regular Mercedes-Benz-type incision. Conclusions Our hybrid procedure was safely conducted with the same quality as the conventional open procedure in both LDLT donors and recipients

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

Can sacrificial feeding areas protect aquatic plants from herbivore grazing? Using behavioural ecology to inform wildlife management

Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems

Tracking Performance of the Scintillating Fiber Detector in the K2K Experiment

The K2K long-baseline neutrino oscillation experiment uses a Scintillating Fiber Detector (SciFi) to reconstruct charged particles produced in neutrino interactions in the near detector. We describe the track reconstruction algorithm and the performance of the SciFi after three years of operation.Comment: 24pages,18 figures, and 1 table. Preprint submitted to NI

Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.</p> <p>Case presentation</p> <p>A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no <it>de novo </it>malignancy. Neither of the siblings has developed an HCV infection.</p> <p>Conclusions</p> <p>A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.</p

Regeneration of Graft Livers and Limited Contribution of Extrahepatic Cells After Partial Liver Transplantation in Humans

Background Liver regeneration is still not fully understood. Partial liver transplantation (LT) can provide the opportunity to investigate the mechanisms of liver regeneration, including the contribution of extrahepatic cells to liver regeneration. Methods Of 61 patients transplanted with partial liver graft between August 1997 and October 2006, 56 patients were studied, including 49 adults and 7 children. Sequential computed tomography volumetric analysis was performed for volume measurement, while proliferating cell nuclear antigen (PCNA) labeling index was investigated for liver cell proliferation in nonprotocol liver biopsy specimens. In addition, 15 male recipients who had female liver grafts were investigated in order to detect Y chromosomes as extrahepatic cells in nonprotocol liver biopsy specimens. Results Graft volume per standard liver volume was markedly increased after adult-to-adult living-donor (LD) LT. In pediatric transplants, there was no volume increase over time. PCNA labeling index was vigorous in adult-to-adult LDLT in the early period after LDLT. No Y chromosome was evident in hepatocytes from female-donor male-recipient grafts during or after liver regeneration. However, in the cases of failing grafts of this type, many Y-chromosome-positive cells were observed in the graft liver. The character of those cells was CD34(−), CK9(−), hepatocyte-specific antigen(−), and CD68(+/−). Conclusion In adult-to-adult LDLT, vigorous liver regeneration occurs in the graft liver, demonstrated by not only volumetric but cell kinetic analysis. Involvement of extrahepatic cells in normal liver regeneration seems limited