View Of Biology Research Articles

Uncovering Pharmacological Opportunities for Cancer Stem Cells-A Systems Biology View.

Cancer stem cells (CSCs) represent a small fraction of the total cancer cell population, yet they are thought to drive disease propagation, therapy resistance and relapse. Like healthy stem cells, CSCs possess the ability to self-renew and differentiate. These stemness phenotypes of CSCs rely on multiple molecular cues, including signaling pathways (for example, WNT, Notch and Hedgehog), cell surface molecules that interact with cellular niche components, and microenvironmental interactions with immune cells. Despite the importance of understanding CSC biology, our knowledge of how neighboring immune and tumor cell populations collectively shape CSC stemness is incomplete. Here, we provide a systems biology perspective on the crucial roles of cellular population identification and dissection of cell regulatory states. By reviewing state-of-the-art single-cell technologies, we show how innovative systems-based analysis enables a deeper understanding of the stemness of the tumor niche and the influence of intratumoral cancer cell and immune cell compositions. We also summarize strategies for refining CSC systems biology, and the potential role of this approach in the development of improved anticancer treatments. Because CSCs are amenable to cellular transitions, we envision how systems pharmacology can become a major engine for discovery of novel targets and drug candidates that can modulate state transitions for tumor cell reprogramming. Our aim is to provide deeper insights into cancer stemness from a systems perspective. We believe this approach has great potential to guide the development of more effective personalized cancer therapies that can prevent CSC-mediated relapse.

Cassava Brown Streak Viruses express second 6-kilodalton (6K2) protein with varied polarity and three dimensional (3D) structures: Basis for trait discrepancy between the virus species.

Cassava Brown Streak Virus (CBSV) and Ugandan Cassava Brown Streak Virus (UCBSV) are the two among six virus species speculated to cause the most catastrophic Brown Streak Disease of Cassava (CBSD) in Africa and Asia. Cassava Brown Streak Virus (CBSV) is hard to breed resistance for compared to Ugandan Cassava Brown Streak Virus (UCBSV) species. This is exemplified by incidences of CBSV species rather than UCBSV species in elite breeding line, KBH 2006/0026 at Bagamoyo, Tanzania. It is not yet understood as to why CBSV species could breakdown CBSD-resistance in the KBH 2006/0026 unlike the UCBSV species. This marks the first in silico study conducted to understand molecular basis for the trait discrepancy between CBSV and UCBSV species from structural biology view point. Following ab initio modelling and analysis of physical-chemical properties of second 6-kilodalton (6K2) protein encoded by CBSV and UCBSV species, using ROBETTA server and Protein Parameters tool, respectively we report that; three dimensional (3D) structures and polarity of the protein differs significantly between the two virus species. (95% and 5%) and (85% and 15%) strains of 20 CBSV and 20 UCBSV species respectively, expressed the protein in homo-trimeric and homo-tetrameric forms, correspondingly. 95% and 85% of studied strain population of the two virus species expressed hydrophilic and hydrophobic 6K2, respectively. Based on findings of the curent study, we hypothesize that; (i) The hydrophilic 6K2 expressed by the CBSV species, favour its faster systemic movement via vascular tissues of cassava host and hence result into higher tissue titres than the UCBSV species encoding hydrophobic form of the protein. t and (ii) The hydrophilic 6K2 expressed byCBSV species have additional interaction advantage with Nuclear Inclusion b protease domain (NIb) and Viral genome-linked protein (VPg), components of Virus Replication Complex (VRC) and hence contributing to faster replication of viral genome than the hydrophobic 6K2 expressed by the UCBSV species. Experimental studies are needed to resolve the 3D structures of the 6K2, VPg and NIb and comprehend complex molecular interactions between them. We suggest that, the 6K2 gene should be targeted for improvement of RNA interference (RNAi)-directed transgenesis of virus-resistant cassava as a more effective way to control the CBSD besides breeding.

Olfactory receptors contribute to progression of kidney fibrosis

Olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are shown to be expressed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis. For further validation, common differentially expressed ORs resulted from reanalysis of two time-course microarray datasets were selected for experimental evaluation in a validated murine model of unilateral ureteral obstruction (UUO). Transcriptional analysis by real-time quantitative polymerase chain reaction demonstrated considerable changes in the expression pattern of Olfr433, Olfr129, Olfr1393, Olfr161, and Olfr622 during the progression of kidney fibrosis. For localization of these ORs, single-cell RNA-sequencing datasets of normal and UUO mice were reanalyzed. Results showed that Olfr433 is highly expressed in macrophages in day-2 and 7 post-injury in UUO mice and not in normal subgroups. Besides, like previous findings, Olfr1393 was shown to be expressed prominently in the proximal tubular cells of the kidney. In conclusion, our combinatorial temporal approach to the underlying mechanisms of chronic kidney disease highlighted the potential role of ORs in progression of fibrosis. The expression of Olfr433 in the macrophages provides some clue about its relation to molecular mechanisms promoted in the fibrotic kidney. The proposed ORs in this study could be the subject of further functional assessments in the future.

Uniqueness and stability of periodic solutions for an interactive wild and Wolbachia-infected male mosquito model

We investigate a mosquito population suppression model, which includes the release of Wolbachia-infected males causing incomplete cytoplasmic incompatibility (CI). The model consists of two sub-equations by considering the density-dependent birth rate of wild mosquitoes. By assuming the release waiting period T is larger than the sexual lifespan of Wolbachia-infected males, we derive four thresholds: the CI intensity threshold , the release amount thresholds and , and the waiting period threshold . From a biological view, we assume throughout the paper. When , we prove the origin is locally asymptotically stable iff , and the model admits a unique T-periodic solution iff , which is globally asymptotically stable. When , we show the origin is globally asymptotically stable iff , and the model has a unique T-periodic solution iff , which is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations.

Multi-transcriptomic analysis points to early organelle dysfunction in human astrocytes in Alzheimer's disease

The phenotypic transformation of astrocytes in Alzheimer's disease (AD) is still not well understood. Recent analyses based on single-nucleus RNA sequencing of postmortem Alzheimer's disease (AD) samples are limited by the low number of sequenced astrocytes, small cohort sizes, and low number of differentially expressed genes detected. To optimize the detection of astrocytic genes, we employed a novel strategy consisting of the localization of pre-determined astrocyte and neuronal gene clusters in publicly available whole-brain transcriptomes. Specifically, we used cortical transcriptomes from 766 individuals, including cognitively normal subjects (Controls), and people diagnosed with mild cognitive impairment (MCI) or dementia due to AD. Samples came from three independent cohorts organized by the Mount Sinai Hospital, the Mayo Clinic, and the Religious Order Study/Memory and Aging Project (ROSMAP). Astrocyte- and neuron-specific gene clusters were generated from human brain cell-type specific RNAseq data using hierarchical clustering and cell-type enrichment scoring. Genes from each cluster were manually annotated according to cell-type specific functional Categories. Gene Set Variation Analysis (GSVA) and Principal Component Analysis (PCA) were used to establish changes in these functional categories among clinical cohorts. We highlight three novel findings of the study. First, individuals with the same clinical diagnosis were molecularly heterogeneous. Particularly in the Mayo Clinic and ROSMAP cohorts, over 50% of Controls presented down-regulation of genes encoding synaptic proteins typical of AD, whereas 30% of patients diagnosed with dementia due to AD presented Control-like transcriptomic profiles. Second, down-regulation of neuronal genes related to synaptic proteins coincided, in astrocytes, with up-regulation of genes related to perisynaptic astrocytic processes (PAP) and down-regulation of genes encoding endolysosomal and mitochondrial proteins. Third, down-regulation of astrocytic mitochondrial genes inversely correlated with the disease stages defined by Braak and CERAD scoring. Finally, we interpreted these changes as maladaptive or adaptive from the point of view of astrocyte biology in a model of the phenotypical transformation of astrocytes in AD. The main prediction is that early malfunction of the astrocytic endolysosomal system, associated with progressive mitochondrial dysfunction, contribute to Alzheimer's disease. If this prediction is correct, therapies preventing organelle dysfunction in astrocytes may be beneficial in preclinical and clinical AD.

Relevance of miR-223 as Potential Diagnostic and Prognostic Markers in Cancer.

Simple SummaryMicroRNAs (miRNAs) are endogenous small non-coding RNAs that function in the regulation of gene expression and regulate a wide array of biological processes, including carcinogenesis. Several mechanisms are involved in miRNA-associated cancer development, such as amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes, and defects in miRNA biogenesis machinery. MiRNA-223 has been found to be a critical miRNA that is involved in a wide range of molecular processes. It is involved in the regulation of inflammatory cytokines, epithelial homeostasis, immune checkpoint signaling pathways, apoptosis, cell cycle, cell proliferation, invasion, and chemosensitivity. Published literature has demonstrated that miRNA-223 expression is associated with cancer development and prevention. Mir-223 functions as either a tumor suppressor or oncogene under certain circumstances, containing multiple targets or specific targets. Hence, miR-223 could be a potential candidate diagnostic biomarker, prognostic biomarker, or therapeutic target of cancer.In 1993, the discovery of microRNAs in Caenorhabditis elegans (C. elegans) altered the paradigmatic view of RNA biology and post-transcriptional gene regulation. Further study revealed the role of microRNAs in disease development and progression. In particular, this review highlights microRNA-223 (miR-223 or miRNA-223) expression in malignant neoplastic disorders. miR-223 expression controls aspects of hematopoiesis and apoptosis, and cell proliferation, migration, and invasion. miR-223 regulates a number of gene targets, including cytoplasmic activation/proliferation-associated protein-1 (Caprin-1), insulin-like growth factor-1 receptor (IGF-1R), and other cell proliferation- and cell cycle-associated genes. Several studies have proposed miR-223 as a novel biomarker for early cancer diagnosis. Here, we emphasize miR-223′s role in the development and progression of cancer.

Physics of liquid crystals in cell biology.

The past decade has witnessed a rapid growth in understanding of the pivotal roles of mechanical stresses and physical forces in cell biology. As a result, an integrated view of cell biology is evolving, where genetic and molecular features are scrutinised hand in hand with physical and mechanical characteristics of cells. Physics of liquid crystals has emerged as a burgeoning new frontier in cell biology over the past few years, fuelled by an increasing identification of orientational order and topological defects in cell biology, spanning scales from subcellular filaments to individual cells and multicellular tissues. Here, we provide an account of the most recent findings and developments, together with future promises and challenges in this rapidly evolving interdisciplinary research direction.

Multimodal retinal imaging to detect and understand Alzheimer's and Parkinson's disease.

Retinal neurodegeneration and visual dysfunctions have been reported in a majority of Alzheimer's and Parkinson's patients, and, in light of the quest for novel biomarkers for these neurodegenerative proteinopathies, the retina has been receiving increasing attention as an organ for diagnosing, monitoring, and understanding disease. Thinning of retinal layers, abnormalities in vasculature, and protein deposition can be imaged at unprecedented resolution, which offers a unique systems biology view on the cellular and molecular changes underlying these pathologies. It makes the retina not only a promising target for biomarker development, but it also suggests that novel fundamental insights into the pathophysiology of Alzheimer's and Parkinson's disease can be obtained by studying the retina-brain axis.

Branched ubiquitin code: from basic biology to targeted protein degradation.

Protein ubiquitylation regulates numerous pathways, and the diverse information encoded by various forms of ubiquitylation is known as the ubiquitin code. Recent studies revealed that branched ubiquitin chains are abundant in mammalian cells and regulate important pathways. They include proteasomal degradation of misfolded and disease-causing proteins, regulation of NF-κB signalling and apoptotic cell fate decisions. Targeted protein degradation through chemical degraders emerged as a transformative therapeutic paradigm aimed at inducing the disappearance of unwanted cellular proteins. To further improve the efficacy of target degradation and expand its applications, understanding the molecular mechanism of degraders' action from the view of ubiquitin code biology is required. In this review, I discuss the roles of the ubiquitin code in biological pathways and in chemically induced targeted protein degradation by focusing on the branched ubiquitin codes that we have characterized.

Cross-Section Resistivity Detection of Tree (Swietenia Magahoni and Gmelina) Using ERT Method

The existence of trees is very beneficial for humans’ life. There are utilizations of tree such as urban planning and reforestation. However, the tree can be dangerous when the tree is aged and decay because of several factors that might be cause fallen tree. Furthermore, the monitoring activity is needed to know the condition of the tree. One of the methods that can be used to detect hollow in living tree is Electrical Resistivity Tomography (ERT). The ERT is an efficient and nondestructive method that can be potential to estimate resistivity cross section. The measurement of ERT conducted on Swietenia mahagoni and Gmelina with unhealthy and healthy condition visually. The data processed using Res2Dinv and reconstructed for obtaining 2D resistivity cross section. The results shows that the unhealthy Swietenia mahagoni has logarithmic resistivity value range between 0.1-1 Ωm and the healthy Swietenia mahagoni has 1-4 Ωm. Meanwhile, the unhealthy and healthy Gmelina has logarithmic resistivity value range between 0.5-4.5 Ωm and 0.5-3 Ωm, respectively. It is shows that the tree indicated health visually from biological view does not mean the tree is decay. It might be influenced by phenology factor and/or the species of the tree.

My road to the ants: A model clade for eco-evo-devo.

This chapter is the story of how I pioneered ants as a system for studying eco-evo-devo, a field that integrates developmental biology with ecology and evolutionary biology. One aim of eco-evo-devo is to understand how the interactions between genes and their environments during development facilitates the origin and evolution of novel phenotypes. In a series of six parts, I review some of the key discoveries from my lab on how novel worker caste systems in ants--soldiers and supersoldiers--originated and evolved. I also discuss some of the ideas that emerged from these discoveries, including the role that polyphenisms, hidden developmental potentials, and rudimentary organs play in facilitating developmental and evolutionary change. As superorganisms, I argue that ants are uniquely positioned to reveal types of variation that are often difficult to observe in nature. In doing so, they have the potential to transform our view of biology and provide new perspectives in medicine, agriculture, and biodiversity conservation. With my story I hope to inspire the next generation of biologists to continue exploring the unknown regions of phenotypic space to solve some of our most pressing societal challenges.

The reproductive biology of oviraptorosaurs: a synthesis

Abstract Among all of the dinosaurs, the Late Cretaceous oviraptorosaurs, in addition to troodontid dinosaurs, boast the best fossil records ranging from numerous eggs and embryos, seven clutch–adult associations, highly organized egg clutches, two gravid adults and possible colonial nesting grounds, to plenty of species described from skeletons from East Asia. These well-preserved fossils provided insights into the reproductive biology, ecology, behaviour and developmental biology of oviraptorid dinosaurs, contributing to several groundbreaking palaeontological discoveries in the last decade. Some of them received further support, while the others remain controversial, indicating that a comprehensive, rigorous re-examination using all available evidence is required. In a recent review, oviraptorosaurs were considered as an intermediate stage in moving towards the modern avian reproduction, whose reproductive biology can be inferred based on the avian model. With the new insights generated from the shell histology of several embryo-containing eggs and evidence from previous studies, this study offers a synthetic view of the reproductive biology of the Late Cretaceous oviraptorosaurs, illuminating the peculiar reproductive biology of oviraptorosaurs. In conclusion, oviraptorosaurs had an essentially unique reproductive biology lacking modern analogies. Thus, simply applying either avian or reptilian models to infer the biology of extinct animals appears inappropriate in the case of oviraptorosaurs.

How advances in cryo-electron tomography have contributed to our current view of bacterial cell biology

Advancements in the field of cryo-electron tomography have greatly contributed to our current understanding of prokaryotic cell organization and revealed intracellular structures with remarkable architecture. In this review, we present some of the prominent advancements in cryo-electron tomography, illustrated by a subset of structural examples to demonstrate the power of the technique. More specifically, we focus on technical advances in automation of data collection and processing, sample thinning approaches, correlative cryo-light and electron microscopy, and sub-tomogram averaging methods. In turn, each of these advances enabled new insights into bacterial cell architecture, cell cycle progression, and the structure and function of molecular machines. Taken together, these significant advances within the cryo-electron tomography workflow have led to a greater understanding of prokaryotic biology. The advances made the technique available to a wider audience and more biological questions and provide the basis for continued advances in the near future.

Цифровая девиация как феномен современного мира

This research is devoted to the current issue of the formation of deviations on the Internet, in connection with the global digitalization taking place in the modern world. The peculiarity of this process is the fact that in virtual reality, unlike everyday reality, there are no clear laws and rules defining the norms of digital behavior, there are no criteria for deviant behavior. The process of deviant forms of behavior on the Internet, such as trolling, astroturfing, sexting, scamming, fishing, has become possible due to the anonymity on the Internet. The virtual space has thus created fertile ground for the emergence of deviant activity without fear of being held accountable. We consider the controversial issue of the impact of digitalization on personality and human behavior, provide an interpretation overview for term “deviation” from the point of view of biology, sociology, deviantology. The digital network causes the changes in humans at several levels: emotional, intellectual, physical, value, etc. These changes, in turn, generate new psychological personality traits. Behavioral changes are put forward in a special class, namely: the formation of deviant behavior in the digital network. As literature analysis on the studied issue shows, the characteristics of digital deviations are the latent nature of the manifestation, the absence of sanctions for the manifestation of deviations, the complex nature of the manifestation, etc. In addition, we provide a conditional typology of types of digital deviations by levels of human impact with such forms as “alienated in a digital crowd”, “digital dementia”, “I know everything and nothing”, etc.

Volumetric compression develops noise-driven single-cell heterogeneity

Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical microenvironments to single-cell heterogeneity remains largely unexplored. Here, we show that a homogeneous population of non-small-cell lung carcinoma develops into heterogeneous subpopulations upon application of a homogeneous physical compression, as shown by single-cell transcriptome profiling. The generated subpopulations stochastically gain the signature genes associated with epithelial-mesenchymal transition (EMT; VIM, CDH1, EPCAM, ZEB1, and ZEB2) and cancer stem cells (MKI67, BIRC5, and KLF4), respectively. Trajectory analysis revealed two bifurcated paths as cells evolving upon the physical compression, along each path the corresponding signature genes (epithelial or mesenchymal) gradually increase. Furthermore, we show that compression increases gene expression noise, which interplays with regulatory network architecture and thus generates differential cell-fate outcomes. The experimental observations of both single-cell sequencing and single-molecule fluorescent in situ hybridization agrees well with our computational modeling of regulatory network in the EMT process. These results demonstrate a paradigm of how mechanical stimulations impact cell-fate determination by altering transcription dynamics; moreover, we show a distinct path that the ecology and evolution of cancer interplay with their physical microenvironments from the view of mechanobiology and systems biology, with insight into the origin of single-cell heterogeneity.

Integrative Analysis Identifies Multi-Omics Signatures That Drive Molecular Classification of Uveal Melanoma.

Simple SummaryUveal melanoma (UM) is a heterogeneous disease driven by accumulative alterations at multi-omics levels including genomics, epigenomics and transcriptomics. It is of great clinical interest to identify UM molecular subtypes and subtype-specific biomarkers that could be used for prognosis and targeted therapy. Integrative clustering (iCluster) analysis is a new approach designed to identify cancer integrative subtypes (iSubtypes) and multi-omics signatures that drive molecular classification of cancer. In this study, we performed an iCluster analysis of UM multi-omics data and identified four UM iSubtypes, which formed two major iSubtypes (denoted by M3 and D3) with distinct multi-omics landscapes. We showed that the integrative molecular classification of UM was determined by concordant alterations at multi-omics levels including DNA copy number, DNA methylation, gene expression and somatic mutation. We further derived a gene panel that can be used to classify UM into high- or low-risk groups for metastasis.By iCluster analysis, we found that the integrative molecular classification of the UM was primarily driven by DNA copy number variation on chromosomes 3, 6 and 8, differential methylation and expression of genes involved in the immune system, cell morphogenesis, movement and migration, and differential mutation of genes including GNA11, BAP1, EIF1AX, SF3B1 and GNAQ. Integrative analysis revealed that pathways including IL6/JAK/STAT3 signaling, angiogenesis, allograft rejection, inflammatory response and interferon gamma response were hypomethylated and up-regulated in the M3 iSubtype, which was associated with a worse overall survival, compared to the D3 iSubtype. Using two independent gene expression datasets, we demonstrated that the subtype-driving genes had an excellent prognostic power in classifying UM into high- or low-risk groups for metastasis. Integrative analysis of UM multi-omics data provided a comprehensive view of UM biology for understanding the underlying mechanism leading to UM metastasis. The concordant molecular alterations at multi-omics levels revealed by our integrative analysis could be used for patient stratification towards personalized management and surveillance.

Cross-Kingdom Comparative Transcriptomics Reveals Conserved Genetic Modules in Response to Cadmium Stress.

ABSTRACTIt is known that organisms have developed various mechanisms to cope with cadmium (Cd) stress, while we still lack a system-level understanding of the functional isomorphy among them. In the present study, a cross-kingdom comparison was conducted among Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii, through toxicological tests, comparative transcriptomics, as well as conventional functional genomics. An equivalent level of Cd stress was determined via inhibition tests. Through transcriptome comparison, the three organisms exhibited differential gene expression under the same Cd stress relative to the corresponding no-treatment control. Results from functional enrichment analysis of differentially expressed genes (DEGs) showed that four metabolic pathways responsible for combating Cd stress were commonly regulated in the three organisms, including antioxidant reactions, sulfur metabolism, cell wall remodeling, and metal transport. In vivo expression patterns of 43 DEGs from the four pathways were further examined using quantitative PCR and resulted in a relatively comparable dynamic of gene expression patterns with transcriptome sequencing (RNA-seq). Cross-kingdom comparison of typical Cd stress-responding proteins resulted in the detection of 12 groups of homologous proteins in the three species. A class of potential metal transporters were subjected to cross-transformation to test their functional complementation. An ABC transporter gene in E. coli, possibly homologous to the yeast ycf1, was heterologously expressed in S. cerevisiae, resulting in enhanced Cd tolerance. Overall, our findings indicated that conserved genetic modules against Cd toxicity were commonly regulated among distantly related microbial species, which will be helpful for utilizing them in modifying microbial traits for bioremediation.IMPORTANCE Research is establishing a systems biology view of biological response to Cd stress. It is meaningful to explore whether there is regulatory isomorphy among distantly related organisms. A transcriptomic comparison was done among model microbes, leading to the identification of a conserved cellular model pinpointing the generic strategies utilized by microbes for combating Cd stress. A novel E. coli transporter gene substantially increased yeast’s Cd tolerance. Knowledge on systems understanding of the cellular response to metals provides the basis for developing bioengineering remediation technology.

Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2

Identification of transcriptional regulatory mechanisms and signaling networks involved in the response of host cells to infection by SARS-CoV-2 is a powerful approach that provides a systems biology view of gene expression programs involved in COVID-19 and may enable the identification of novel therapeutic targets and strategies to mitigate the impact of this disease. In this study, our goal was to identify a transcriptional regulatory network that is associated with gene expression changes between samples infected by SARS-CoV-2 and those that are infected by other respiratory viruses to narrow the results on those enriched or specific to SARS-CoV-2. We combined a series of recently developed computational tools to identify transcriptional regulatory mechanisms involved in the response of epithelial cells to infection by SARS-CoV-2, and particularly regulatory mechanisms that are specific to this virus when compared to other viruses. In addition, using network-guided analyses, we identified kinases associated with this network. The results identified pathways associated with regulation of inflammation (MAPK14) and immunity (BTK, MBX) that may contribute to exacerbate organ damage linked with complications of COVID-19. The regulatory network identified herein reflects a combination of known hits and novel candidate pathways supporting the novel computational pipeline presented herein to quickly narrow down promising avenues of investigation when facing an emerging and novel disease such as COVID-19.

‘There is no right or wrong answer’: Swedish preschool teachers’ reflections on the didactics of death

This study is part of a larger project with the general aim of developing the ability of preschool teachers to reflect critically on questions, topics and theories related to different understandings of death(s). The article is based on three focus-group interviews with a focus on how preschool teachers reflect on what, how, why and when they teach about death and death-related issues. The results show that preschool teachers consider that it is important in early childhood education to teach about death because death is a fundamental aspect of life in daily reality, and they consider it to be their task to comfort a child in grief, as well as care for the well-being of the group. However, much of the time, they avoid teaching about biological death relative to concrete goals that the children are to achieve in understanding what death implies. Instead, they use child-responsive, improvisational teaching that is intended to calm and comfort the children. The content of the teaching arises at the intersection of expert knowledge in talking about death as an irreversible outcome of natural processes and the preschool teachers’ own beliefs and ideas about death, dying and an afterlife. As a consequence, the biological conceptions of death coexist with the teachers’ own beliefs in an afterlife, reflecting a dualistic thinking within which culturally constructed beliefs coexist with biological views.

Oncogenic Viruses as Entropic Drivers of Cancer Evolution.

Viral infection is an indisputable causal factor for nearly 17% of all human cancers. However, the diversity and complexity of oncogenic mechanisms raises new questions as to the mechanistic role of viruses in cancer. Classical viral oncogenes have been identified for all tumor-associated viruses. These oncogenes can have multiple oncogenic activities that may or may not be utilized in a particular tumor cell. In addition, stochastic events, like viral mutation and integration, as well as heritable host susceptibilities and immune deficiencies are also implicated in tumorigenesis. A more contemporary view of tumor biology highlights the importance of evolutionary forces that select for phenotypes better adapted to a complex and changing environment. Given the challenges of prioritizing singular mechanistic causes, it may be necessary to integrate concepts from evolutionary theory and systems biology to better understand viral cancer-driving forces. Here, we propose that viral infection provides a biological “entropy” that increases genetic variation and phenotypic plasticity, accelerating the main driving forces of cancer cell evolution. Viruses can also influence the evolutionary selection criteria by altering the tumor microenvironment and immune signaling. Utilizing concepts from cancer cell evolution, population genetics, thermodynamics, and systems biology may provide new perspectives on viral oncogenesis and identify novel therapeutic strategies for treating viruses and cancer.