Emergence and Collapse of Peace with Friend Selection Strategies

A society consisting of agents who can freely choose to attack or not to attack others inevitably evolves into a battling society (a \'war of all against all\'). We investigated whether strategies based on C. Schmitt\'s concept of the political, the distinction of a friend and an enemy, lead to the emergence and collapse of social order. Especially, we propose \'friend selection strategies\' (FSSs), one of which we called the \'us-TFT\' (tit for tat) strategy, which requires an agent to regard one who did not attack him or his \'friends\' as a \'friend\'. We carried out evolutionary simulations on an artificial society consisting of FSS agents. As a result, we found that the us-TFT results in a peaceful society with the emergence of an us-TFT community. In addition, we found that the collapse of a peaceful society is triggered by another FSS strategy called a \'coward\'.Community, Carl Schmitt, a Friend and an Enemy, Tit for Tat, Coward, Evolutionary Simulation

Leucine/glutamine and v-ATPase/lysosomal acidification via mTORC1 activation are required for position-dependent regeneration

n animal regeneration, control of position-dependent cell proliferation is crucial for the complete restoration of patterned appendages in terms of both, shape and size. However, detailed mechanisms of this process are largely unknown. In this study, we identified leucine/glutamine and v-ATPase/lysosomal acidification, via mechanistic target of rapamycin complex 1 (mTORC1) activation, as effectors of amputation plane-dependent zebrafish caudal fin regeneration. mTORC1 activation, which functions in cell proliferation, was regulated by lysosomal acidification possibly via v-ATPase activity at 3 h post amputation (hpa). Inhibition of lysosomal acidification resulted in reduced growth factor-related gene expression and suppression of blastema formation at 24 and 48 hpa, respectively. Along the proximal-distal axis, position-dependent lysosomal acidification and mTORC1 activation were observed from 3 hpa. We also report that Slc7a5 (L-type amino acid transporter), whose gene expression is position-dependent, is necessary for mTORC1 activation upstream of lysosomal acidification during fin regeneration. Furthermore, treatment with leucine and glutamine, for both proximal and distal fin stumps, led to an up-regulation in cell proliferation via mTORC1 activation, indicating that leucine/glutamine signaling possesses the ability to change the position-dependent regeneration. Our findings reveal that leucine/glutamine and v-ATPase/lysosomal acidification via mTORC1 activation are required for position-dependent zebrafish fin regeneration.This study was supported by grants from Grant-in-Aid for Scientific Research from the JSPS (KAKENHI JP15J05983) to K.T

The three-dimensional structure of the colicin E3 immunity protein by distance geometry calculation

AbstractThe three-dimensional solution structure of the colicin E3 immunity protein (84 residues) was determined by distance geometry calculations. The hydrophilic side of a four-stranded antiparallel β-sheet constitutes a part of the surface of the protein, and two loops lie on the hydrophobic side of the sheet. All the three specificity-determining residues, which are included in the center of the β-sheet, display their side groups on the protein surface

Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3

The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded b-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)3 RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the b-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family

Protocol for a single-arm confirmatory trial of adjuvant chemoradiation for patients with high-risk rectal submucosal invasive cancer after local resection: Japan Clinical Oncology Group Study JCOG1612 (RESCUE study)

Introduction: Intestinal resection with lymph node dissection is the current standard treatment for high-risk lower rectal submucosal invasive cancer after local resection; however, surgery affects patients’ quality of life due to stoma placement or impaired anal sphincter function. A recent study demonstrated that adjuvant chemoradiation yields promising results. Methods and analysis: This study aims to confirm the non-inferiority of adjuvant chemoradiation, consisting of capecitabine and concurrent radiotherapy (45 Gy in 25 fractions), measured by 5-year relapse-free survival (RFS), over standard surgery in patients with high-risk lower rectal submucosal invasive cancer after local resection. The primary endpoint is 5 year RFS. The secondary endpoints are 10 years RFS, 5-year and 10-year overall survival, 5-year and 10-year local RFS, 5-year and 10-year proportion of anus-preservation without stoma, Wexner score, low anterior resection syndrome score, adverse events and serious adverse events. During the 5-year trial period, 210 patients will be accrued from 65 Japanese institutions. Ethics and dissemination: The National Cancer Center Hospital East Certified Review Board approved this study protocol in October 2018. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Clinical Trials Act. Written informed consent will be obtained from all eligible patients prior to registration. The primary results of this study will be published in an English article. In addition, the main results will be published on the websites of Japan Clinical Oncology Group (www.jcog.jp) and jRCT (https://jrct.niph.go.jp/). As to data curation, it has not been prepared yet. Trial registration number: jRCT103118007

The Anti-Obesity Effect of the Palatinose-Based Formula Inslow is Likely due to an Increase in the Hepatic PPAR-α and Adipocyte PPAR-γ Gene Expressions

Abdominal obesity is a principal risk factor in the development of metabolic syndrome. Previously, we showed that a palatinose-based liquid formula, Inslow/MHN-01, suppressed postprandial plasma glucose level and reduced visceral fat accumulation better than the standard formula (SF). To elucidate the mechanism of Inslow-mediated anti-obesity effect, expression levels of genes involved in the glucose and lipid metabolism were compared in Inslow- and SF-fed rats. Both fasting plasma insulin level and average islet sizes were reduced in the Inslow group. We also found less abdominal fat accumulation and reduced hepatic triacylglycerol content in the Inslow group. Expression of the β-oxidation enzymes and uncoupling potein-2 (UCP-2) mRNAs in the liver of the Inslow group were higher than the SF group, which was due to a concomitant higher expression of the peroxisome proliferator-activated receptor (PPAR)-α mRNA in the former. Furthermore, expression of the UCP-2 and adiponectin mRNAs in the epididymal fat were higher in the Inslow group than the SF group, and were stimulated by a concomitant increase of the PPAR-γ gene expression in the former. These results strongly suggested that the anti-obesity effect of Inslow was due to an increase in the hepatic PPAR-α and adipocyte PPAR-γ gene expressions

Comparison between short-term food restriction and exercise on whole body glucose disposal in high-fat fed rats

High-fat diets induce whole-body insulin resistance. The aim of this study was to compare the effect of two interventions:3-day food restriction (66%of ad libitum fed) and 3-day exercise training (voluntary running wheels), on decreased insulin-mediated whole body glucose uptake in high-fat fed rats (5 mo old) using the hyperinsulinemic euglycemic clamp procedure. The control group was maintained on rat chow alone. After high-fat feeding for2wk, insulin-stimulated whole body glucose utilization was significantly decreased by26%. The exercise training was more effective than food restriction in lowering plasma concentrations of insulin and triacylglycerol and tissue concentrations of triacylglycerol in soleus muscles. Diminished whole-body glucose uptake resulting from high-fat feeding was reversed completely by exercise training, but only partially by food restriction. The time course of starvation on insulin-stimulated glucose uptake was also observed in high-fat fed rats. Although the extension of starvation time to 48h resulted in decreased plasma glucose, insulin and triacylglycerol concentrations, whole body glucose uptake did not increase further. These findings suggest that short-term exercise has a higher restorative effect on insulin sensitivity in high-fat fed rats than food restriction, in spite of the same loss in body weight, presumably due in part to improved local lipid availability

Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine

The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)