A pairwise maximum entropy model accurately describes resting-state human brain networks

The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system. Here, we address this issue by demonstrating that a pairwise maximum entropy model, which takes into account region-specific activity rates and pairwise interactions, can be robustly and accurately fitted to resting-state human brain activities obtained by functional magnetic resonance imaging. Furthermore, to validate the approximation of the resting-state networks by the pairwise maximum entropy model, we show that the functional interactions estimated by the pairwise maximum entropy model reflect anatomical connexions more accurately than the conventional functional connectivity method. These findings indicate that a relatively simple statistical model not only captures the structure of the resting-state networks but also provides a possible method to derive physiological information about various large-scale brain networks

Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation

Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC). LRRC8A and at least one of the other LRRC8 isoforms assemble into heteromers to generate VRAC transport activities. Despite the availability of the LRRC8A structures, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. Here, we present the structure of the human LRRC8D isoform, which enables the permeation of organic substrates through VRAC. The LRRC8D homo-hexamer structure displays a two-fold symmetric arrangement, and together with a structure-based electrophysiological analysis, revealed two key features. The pore constriction on the extracellular side is wider than that in the LRRC8A structures, which may explain the increased permeability of organic substrates. Furthermore, an N-terminal helix protrudes into the pore from the intracellular side and may be critical for gating

Percutaneous Cryoablation of Pulmonary Metastases from Colorectal Cancer

Objective: To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. Methods: The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months. Results: The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8 % and 59%, respectively. The 3-years local progression free intervals of tumors #15 mm in diameter was 79.8 % and that of tumors.15 mm was 28.6 % (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. Conclusion: The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression fre

Topological Analysis of MAPK Cascade for Kinetic ErbB Signaling

Ligand-induced homo- and hetero-dimer formation of ErbB receptors results in different biological outcomes irrespective of recruitment and activation of similar effector proteins. Earlier experimental research indicated that cells expressing both EGFR (epidermal growth factor receptor) and the ErbB4 receptor (E1/4 cells) induced E1/4 cell-specific B-Raf activation and higher extracellular signal-regulated kinase (ERK) activation, followed by cellular transformation, than cells solely expressing EGFR (E1 cells) in Chinese hamster ovary (CHO) cells. Since our experimental data revealed the presence of positive feedback by ERK on upstream pathways, it was estimated that the cross-talk/feedback pathway structure of the Raf-MEK-ERK cascade might affect ERK activation dynamics in our cell system. To uncover the regulatory mechanism concerning the ERK dynamics, we used topological models and performed parameter estimation for all candidate structures that possessed ERK-mediated positive feedback regulation of Raf. The structure that reliably reproduced a series of experimental data regarding signal amplitude and duration of the signaling molecules was selected as a solution. We found that the pathway structure is characterized by ERK-mediated positive feedback regulation of B-Raf and B-Raf-mediated negative regulation of Raf-1. Steady-state analysis of the estimated structure indicated that the amplitude of Ras activity might critically affect ERK activity through ERK-B-Raf positive feedback coordination with sustained B-Raf activation in E1/4 cells. However, Rap1 that positively regulates B-Raf activity might be less effective concerning ERK and B-Raf activity. Furthermore, we investigated how such Ras activity in E1/4 cells can be regulated by EGFR/ErbB4 heterodimer-mediated signaling. From a sensitivity analysis of the detailed upstream model for Ras activation, we concluded that Ras activation dynamics is dominated by heterodimer-mediated signaling coordination with a large initial speed of dimerization when the concentration of the ErbB4 receptor is considerably high. Such characteristics of the signaling cause the preferential binding of the Grb2-SOS complex to heterodimer-mediated signaling molecules

Structural analysis of the factors pertaining to attitudes toward and consciousness of organ donation : Comparison between Japanese and Americans

The purpose of this study is to analyze the background factors relating to opinions on organ donation through factorial and structural comparisons between Japanese and Americans. The data were obtained from responses to a questionnaire (371 Japanese and 41 Americans). The main findings are as follows: 1. Most of the factors, ‘a will for organ donation depending on a recipient’, ‘view of remains’, ‘understanding of brain death’ and so on showed significant differences between Japanese and Americans. 2. Japanese had a better understanding of brain death. On the other hand, the ratio of Americans who were willing to donate an organ was higher than that of Japanese. 3. It was revealed that “the approval of organ donation for the third person, not only for one's family” had an impact for having donor card showing the approval for organ donation. Furthermore, as underlying factors generating differences on organ transplant opinions, differences were found among Japanese between “approval of organ transplant” and the attitude assuming that oneself or a member of one's family was the person concerned with organ transplantation. There were also differences between Japanese and Americans on ideas about a view for life and death such as soul existence or view of remains. The argument for transplantation in Japan should consider these structural differences

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