Linear ubiquitination‐induced necrotic tumor remodeling elicits immune evasion

Tumor-elicited inflammation confers tumorigenic properties, including cell death resistance, proliferation, or immune evasion. To focus on inflammatory signaling in tumors, we investigated linear ubiquitination, which enhances the nuclear factor-κB signaling pathway and prevents extrinsic programmed cell death under inflammatory environments. Here, we showed that linear ubiquitination was augmented especially in tumor cells around a necrotic core. Linear ubiquitination allowed melanomas to tolerate the hostile tumor microenvironment and to extend a necrosis-containing morphology. Loss of linear ubiquitination resulted in few necrotic lesions and growth regression, further leading to repression of innate anti-PD-1 therapy resistance signatures in melanoma as well as activation of interferon responses and antigen presentation that promote immune-mediated tumor eradication. Collectively, linear ubiquitination promotes tumor-specific tissue remodeling and the ensuing immune evasion

Process of parenting a child with RB

Background : Retinoblastoma（RB） occurs at a very young age. Since the disease is diagnosed at an early age, the family is responsible for the care of the childʼs disease acceptance. Objective : This study aims to explore the parenting process of children with RB toward disease acceptance. Methods : Parents of eleven children with RB living in Japan were interviewed, and the data were analyzed using the Modified Grounded Theory Approach of Kinoshita（M-GTA）. Results : There were twenty-one concepts representing the process of parenting a child with RB while guiding him or her toward disease acceptance, and nineteen of them were classified into ten categories based on semantic similarities. The two other concepts showed similar interpretability to categories. These categories and concepts were summarized into two core categories : “Helping the child develop a positive mindset to define the disease as a part of him/herself ” and “Paving the way in advance for the child to live comfortably when his or her living space expands”. Conclusions : In a cyclical framework of parenting, consisting of two core categories described in Results, the parents coordinated these two approaches while maintaining balance by “Avoiding saying anything that does not need to be said” and established their process of parenting a child with RB while guiding him or her toward disease acceptance, according to their household situation. The results suggest the necessity of recognizing that in childhood-onset cancers, such as RB, and diseases involving genetic issues, problems tend to occur not only during the treatment period but also at the time of life events and providing support from a comprehensive perspective

OCNSのがんゲノム医療への関与

The purpose of this study was to clarify the current status of oncology certified nurse specialist（OCNS） involvement in cancer genome medicine. A survey of 235 OCNSs who consented to participate in the study revealed that those involved in cancer genome medicine had a better understanding of hereditary tumors. Through descriptive content analysis, 8 learning needs were identified in relation to cancer genome medicine. Among these needs,［ basic knowledge of hereditary tumors and cancer genome medicine］, ［regular acquisition of up-to-date information on genetic medicine］, and［ genetic counseling in actual clinical settings］revealed no differences between OCNSs involved and not involved in genetic medicine. On the other hand,［ role of an OCNS in genetic medicine］, ［nursing care for patients and families with hereditary diseases］, ［systems and collaboration to incorporate genetic medicine into organizations］, ［information on genetic medicine for facilities other than urban/designated hospitals］, and［ programmed learning as a systematic approach to genetic medicine provided by academic societies］ differed between the groups in terms of descriptive contents

遺伝性腫瘍に関する遺伝カウンセリングの動向

The purpose of this study was to determine the actual situation of the genetic counseling for familial tumors in overseas literatures. We searched literatures including key words “genetic counseling” “familial tumor” “heredity” “cancer” “patients” and “genetic diseases” on PubMed published from ２００８ to ２０１８, resulting ２０９ articles extracted and ２１ of those examined. The quantitative studies were the most common type of these articles, and Certified Genetic Counselors （CGC）were the most common first author. The study contents were［factors associated with testing acceptance］,［utility of the screening system］,［utility of the genetic counseling］, and ［contents of the genetic counseling］. The analysis revealed genetic counseling for familial tumors in overseas was at present frequently provided to promote uptake of genetic testing

Application of environmental performance analysis for urban design with Computational Fluid Dynamics (CFD) and EcoTect tools: the case of Cao Fei Dian eco-city, China

This paper suggests a type of quantitative research method with the application of Computational Fluid Dynamics (CFD) and EcoTect tools for a sustainable urban design project. This paper is part of a funded research study and was completed in 2010. This study is part of the larger project for planning and development of Cao Fei Dian eco-city development in North-Eastern China; one of the first eco-city development projects in the first batch of pilot eco-cities in China. The research programme addresses the main aspects of good practice in terms of eco-design and sustainability. These aspects include wind flow analysis around buildings, insolation analysis of open spaces, pollutant dispersion in water systems and noise control on urban highways. This study aims to explore a range of research methods in order to enhance the performance of integrated design with a comprehensive planning stage. The integration in evaluation across professions and subject boundaries is emphasised to identify the key gaps between sustainability and design. The main method of this study is the application of CFD and EcoTect tools for environmental performance of a larger urban area than the common use for architectural interventions or immediate outdoor spaces of a project. This study suggests an integrated urban design model with the application of computational tools (i.e. CFD and EcoTect in here) and how these could inform, from a technical dimension, a more comprehensive approach to executing best practice in design and planning. The paper concludes by suggesting an integrated model of urban design to achieve urban sustainability

〈Case Reports〉HELLP syndrome at 22 weeks of gestation with resulting stillbirth and a favorable outcome in a subsequent pregnancy: A case report

[Abstract]HELLP syndrome, characterized by hemolysis,elevated liver enzymes, and low platelets,is one of the diseases related to hypertension in pregnancy. If the pregnancy is not terminated soon after HELLP is diagnosed, liver failure or disseminated intravascular coagulopathy (DIC)may occur. HELLP syndrome occurs in 0.2%–0.9% of all pregnancies; Onset before 24 weeks of gestation is extremely rare but is more likely to result in stillbirth. Women who have had a stillbirth often hope for another pregnancy soon after,but there is little information about the risks and outcomes for subsequent pregnancy in women who developed HELLP syndrome in early pregnancy.Thus, it is important to accumulate data on these outcomes in this population. Here, we report a case in which severe HELLP syndrome developed at 22 weeks of gestation, resulting in stillbirth, and was followed six months later by a pregnancy that with early intervention, produced a live birth

Adaptation by stochastic switching of a monostable genetic circuit in Escherichia coli

Stochastic switching of a bistable genetic circuit represents a potential cost-saving strategy for adaptation to environmental challenges. This study reports that stochastic switching of a monostable circuit can be sufficient to mediate reversible adaptation in E. coli

Global coordination in adaptation to gene rewiring

Gene rewiring is a common evolutionary phenomenon in nature that may lead to extinction for living organisms. Recent studies on synthetic biology demonstrate that cells can survive genetic rewiring. This survival (adaptation) is often linked to the stochastic expression of rewired genes with random transcriptional changes. However, the probability of adaptation and the underlying common principles are not clear. We performed a systematic survey of an assortment of gene-rewired Escherichia coli strains to address these questions. Three different cell fates, designated good survivors, poor survivors and failures, were observed when the strains starved. Large fluctuations in the expression of the rewired gene were commonly observed with increasing cell size, but these changes were insufficient for adaptation. Cooperative reorganizations in the corresponding operon and genome-wide gene expression largely contributed to the final success. Transcriptome reorganizations that generally showed high-dimensional dynamic changes were restricted within a one-dimensional trajectory for adaptation to gene rewiring, indicating a general path directed toward cellular plasticity for a successful cell fate. This finding of global coordination supports a mechanism of stochastic adaptation and provides novel insights into the design and application of complex genetic or metabolic networks