Genetic and epigenetic heterogeneity in cancer: A genome‐centric perspective

Genetic and epigenetic heterogeneity (the main form of non‐genetic heterogeneity) are key elements in cancer progression and drug resistance, as they provide needed population diversity, complexity, and robustness. Despite drastically increased evidence of multiple levels of heterogeneity in cancer, the general approach has been to eliminate the “noise” of heterogeneity to establish genetic and epigenetic patterns. In particular, the appreciation of new types of epigenetic regulation like non‐coding RNA, have led to the hope of solving the mystery of cancer that the current genetic theories seem to be unable to achieve. In this mini‐review, we have briefly analyzed a number of mis‐conceptions regarding cancer heterogeneity, followed by the re‐evaluation of cancer heterogeneity within a framework of the genome‐centric concept of evolution. The analysis of the relationship between gene, epigenetic and genome level heterogeneity, and the challenges of measuring heterogeneity among multiple levels have been discussed. Further, we propose that measuring genome level heterogeneity represents an effective strategy in the study of cancer and other types of complex diseases, as emphasis on the pattern of system evolution rather than specific pathways provides a global and synthetic approach. Compared to the degree of heterogeneity, individual molecular pathways will have limited predictability during stochastic cancer evolution where genome dynamics (reflected by karyotypic heterogeneity) will dominate. J. Cell. Physiol. 220: 538–547, 2009. © 2009 Wiley‐Liss, Inc.     

英国脱欧后基因技术监管趋势及对中国的启示*——基于英国《基因技术报告》的分析

英国脱欧后加快了生物技术领域的立法进程,迫切希望通过革新原先欧盟的保守监管模式,在保障技术安全的前提下充分发挥基因技术的应用价值。为实现该目标,英国发布了《基因技术报告》,旨在重新构建更加全面的基因技术监管体系。这一报告不仅分析了既有基因技术治理实践的不足,还指明了未来英国基因技术监管的方向。当前基因编辑、合成生物学等新型基因技术正处于高速发展时期,英国的报告也为这些技术的应用提供了一条可供参考的治理路径。     

Implementation of field detection devices for antimalarial quality screening in Lao PDR—A cost-effectiveness analysis

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens.     

The “Basqueness” of the Basques of Alava: A reappraisal from a multidisciplinary perspective

The genetic and linguistic peculiarity of the Basque population is well known. Analysis of the studies published to date on the Basque population reveals that these studies refer basically to the provinces of Vizcaya and Labourd, both in the Northern part of the Basque Country. Multidisciplinary information indicates that the landscape differences of the Basque Country could have conditioned differential population biodynamics in the Atlantic and Mediterranean parts of the Basque area. In order to evaluate this possibility, this study focuses on the genetic constitution of the Basque population of Alava (in the South of the Basque Country) through the analysis of several red-cell systems. The data obtained in this genetic study and those from archaeology, linguistics, ethnography, and skeletal biology suggest that within the “Basque population” there may be at least two distinct groups: an “Atlantic” group and a “Mediterranean” one, divided mainly by the watershed. This geographical feature could have led to a greater genetic isolation of the Northern slopes, with the South more open to population contact. This is reflected nowadays in the different cline distribution detected for most systems in the Alava Basques in comparison with other Basque and Iberian Peninsula series studied to date. © 1996 Wiley-Liss, Inc.     

多学科视角下的野生动物消费需求和消费行为研究进展

全球持续扩张的野生动物消费需求和相关非法贸易是生物多样性保护的重要威胁之一。近期新冠肺炎疫情暴发, 野生动物贸易和食用的公共卫生安全风险也引起了社会各界的关注。本文从社会学、心理学、行为科学等多学科的视角分析和理解我国野生动物消费的需求动因, 提出科学的行为改变对策。从我国野生动物消费现状来看, 功能性、社会性和体验性等非生活必需性需求凸显, 并受复杂因素影响。基于对需求动因的理解, 运用合适的行为改变框架, 以及宣传教育、社会影响、法律规范和行为助推等多种行为改变方法, 通过科学系统的阶段和步骤, 可有效地影响和改变野生动物消费行为。行为改变对策的实施需在具体情境下加强合作, 重视多学科运用、多主体合作和多尺度考虑。     

RosettaSurf—A surface-centric computational design approach

Proteins are typically represented by discrete atomic coordinates providing an accessible framework to describe different conformations. However, in some fields proteins are more accurately represented as near-continuous surfaces, as these are imprinted with geometric (shape) and chemical (electrostatics) features of the underlying protein structure. Protein surfaces are dependent on their chemical composition and, ultimately determine protein function, acting as the interface that engages in interactions with other molecules. In the past, such representations were utilized to compare protein structures on global and local scales and have shed light on functional properties of proteins. Here we describe RosettaSurf, a surface-centric computational design protocol, that focuses on the molecular surface shape and electrostatic properties as means for protein engineering, offering a unique approach for the design of proteins and their functions. The RosettaSurf protocol combines the explicit optimization of molecular surface features with a global scoring function during the sequence design process, diverging from the typical design approaches that rely solely on an energy scoring function. With this computational approach, we attempt to address a fundamental problem in protein design related to the design of functional sites in proteins, even when structurally similar templates are absent in the characterized structural repertoire. Surface-centric design exploits the premise that molecular surfaces are, to a certain extent, independent of the underlying sequence and backbone configuration, meaning that different sequences in different proteins may present similar surfaces. We benchmarked RosettaSurf on various sequence recovery datasets and showcased its design capabilities by generating epitope mimics that were biochemically validated. Overall, our results indicate that the explicit optimization of surface features may lead to new routes for the design of functional proteins.     

Genetic Architecture Underlying Nascent Speciation—The Evolution of Eurasian Pigs under Domestication

Speciation is a process whereby the evolution of reproductive barriers leads to isolated species. Although many studies have addressed large-effect genetic footprints in the advanced stages of speciation, the genetics of reproductive isolation in nascent stage of speciation remains unclear. Here, we show that pig domestication offers an interesting model for studying the early stages of speciation in great details. Pig breeds have not evolved the large X-effect of hybrid incompatibility commonly observed between “good species.” Instead, deleterious epistatic interactions among multiple autosomal loci are common. These weak Dobzhansky–Muller incompatibilities confer partial hybrid inviability with sex biases in crosses between European and East Asian domestic pigs. The genomic incompatibility is enriched in pathways for angiogenesis, androgen receptor signaling and immunity, with an observation of many highly differentiated cis-regulatory variants. Our study suggests that partial hybrid inviability caused by pervasive but weak interactions among autosomal loci may be a hallmark of nascent speciation in mammals.     

Henipaviruses—A constant threat to livestock and humans

In this review, we highlight the risk to livestock and humans from infections with henipaviruses, which belong to the virus family Paramyxoviridae. We provide a comprehensive overview of documented outbreaks of Nipah and Hendra virus infections affecting livestock and humans and assess the burden on the economy and health systems. In an increasingly globalized and interconnected world, attention must be paid to emerging viruses and infectious diseases, as transmission routes can be rapid and worldwide.