Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually (...) impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co‐opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction. (shrink)

This study examines the mediating role of rumination, state anger, and blame attribution, and the moderating role of trait forgiveness in the relationship between workplace harassment intensity and revenge among employed students at a medium-sized Midwestern U.S. university and full-time employees from various industries in Shanghai, China. We tested the proposed model using techniques described by Hayes. Results within both samples suggested that workplace harassment intensity is positively associated with both major and minor revenge. Results of multiple mediation tests showed (...) that state anger and blame attribution mediated the relationships between workplace harassment intensity and both types of revenge behavior. Furthermore, trait forgiveness moderated the relationship between blame attribution and major revenge. (shrink)

Background: Freezing of gait is a common symptom in Parkinson’s disease and can be difficult to treat with dopaminergic medications or with deep brain stimulation. Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation delivers current in various frequencies of bursts, while maintaining an intra-burst frequency identical to conventional DBS.Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG.Methods: Ten PD subjects with STN or GPi DBS (...) and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state.Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS.Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy. (shrink)

Strong reciprocity has recently been subject to heated debate. In this debate, the “West camp” :231–262, 2011), which is critical of the case for SR, and the “Laland camp” :1512–1516, 2011, Biol Philos 28:719–745, 2013), which is sympathetic to the case of SR, seem to take diametrically opposed positions. The West camp criticizes advocates of SR for conflating proximate and ultimate causation. SR is said to be a proximate mechanism that is put forward by its advocates as an ultimate explanation (...) of human cooperation. The West camp thus accuses advocates of SR for not heeding Mayr’s original distinction between ultimate and proximate causation. The Laland camp praises advocates of SR for revising Mayr’s distinction. Advocates of SR are said to replace Mayr’s uni-directional view on the relation between ultimate and proximate causes by the bi-directional one of reciprocal causation. The paper argues that both the West camp and the Laland camp misrepresent what advocates of SR are up to. The West camp is right that SR is a proximate cause of human cooperation. But rather than putting forward SR as an ultimate explanation, as the West camp argues, advocates of SR believe that SR itself is in need of ultimate explanation. Advocates of SR tend to take gene-culture co-evolutionary theory as the correct meta-theoretical framework for advancing ultimate explanations of SR. Appearances notwithstanding, gene-culture coevolutionary theory does not imply Laland et al.’s notion of reciprocal causation. “Reciprocal causation” suggests that proximate and ultimate causes interact simultaneously, while advocates of SR assume that they interact sequentially. I end by arguing that the best way to understand the debate is by disambiguating Mayr’s ultimate-proximate distinction. I propose to reserve “ultimate” and “proximate” for different sorts of explanations, and to use other terms for distinguishing different kinds of causes and different parts of the total causal chain producing behavior. (shrink)

Although Gene Sharp was a pacifist, he was also, in the last few decades of the 20th century, the initial framer of a new methodology of political and social struggle, which is now often referred to as civil resistance. Organizers of successful people’s movements in Poland, Czechoslovakia, South Africa, Mali, Ukraine, Tunisia and a score of other countries in the last thirty years pushed out rights-violating rulers and did so without resort to violence.

The decade-long debate over ownership of living human materials has recently intensified with the ability of biomedical research to isolate, purify, and use human genes and gene products as therapeutics, factories for the production of therapeutics, and targets for the identification of therapeutic pharmaceuticals. Indeed, advances in genomic research have resulted in the identification of hundreds of thousands of DNA fragments and hundreds of genes. Many within the scientific and business communities believe genes and gene fragments have commercial (...) value and have filed patent applications on the nucleic acid sequences. This commercialization has amplified the discussion surrounding the ethics of patenting genes and the ownership of the human genome. (shrink)

Approach–avoidance generally describes appetitive motivation and fear of punishment. In a social context approach motivation is, however, also expressed as social aggression and dominance. We therefore link approach–avoidance to dominance–submissiveness, and provide a neural framework that describes how the steroid hormone testosterone shifts reflexive as well as deliberate behaviors towards dominance and promotion of social status. Testosterone inhibits acute fear at the level of the basolateral amygdala and hypothalamus and promotes reactive dominance through upregulation of vasopressin gene expression in (...) the central-medial amygdala. Finally, the hormone can, depending on social context and prenatal hormone exposure, promote both pro- and antisocial behaviors and decisions through its effects on prefrontal–amygdala interactions. All these effects of testosterone, however, serve to increase and maintain social status. (shrink)

The lantibiotics are a rapidly expanding group of biologically active peptides produced by a variety of Gram‐positive bacteria, and are so‐called because of their content of the thioether amino acids lanthionine and β‐methyllanthionine. These amino acids, and indeed a number of other unusual amino acids found in the lantibiotics, arise following post‐translational modification of a ribosomally synthesised precursor peptide. A number of genes involved in the biosynthesis of these highly modified peptides have been identified, including genes encoding the precursor peptide, (...) enzymes responsible for specific amino acid modifications, proteases able to remove the leader peptide, ABC‐superfamily transport proteins involved in lantibiotic translocation, regulatory proteins controlling lantibiotic biosynthesis and proteins that protect the producing strain from the action of its own lantibiotic. Analysis of these genes and their products is allowing greater understanding of the complex mechanism(s) of the biosynthesis of these unique peptides. (shrink)

UV‐radiation‐induced lesions in DNA result in the formation of: (1) excision gaps (i.e. a lesion is excised, leaving a gap), (2) daughter‐strand gaps (i.e. a lesion can be skipped during replication, leaving a gap), and (3) double‐strand breaks (i.e. the DNA strand opposite a gap can be cut). In Escherichia coli, the recA gene product is involved in repairs of all three types of lesions – repair of daughter‐strand gaps (2) and double‐strand breaks (3) constitutes post‐replication repair. The evidence (...) suggests, furthermore, that recA‐dependent repair of excision gaps (1) produced in DNA replicated prior to UV irradiation (pre‐replication repair) appears to occur by similar mechanisms. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit with a (...) known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit with a (...) known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

From the viewpoint of an evolutionary biologist, carcinogenesis should be looked upon as a protective mechanism against destruction of DNA. Because genes expressed in embryonic cells are covered and protected by heterochromatinization, they are the most appropriate ‘alternate genes’ compared to genes that are expressed already in somatic cells. When DNA-damage occurs, the embryonic genes can be activated. Some somatic cells exhibit some features of embryonic cells.

Transposable elements are no longer considered to be “junk” DNA. Here, we review how TEs can impact gene regulation systematically. TEs encode various regulatory elements that enables them to regulate gene expression. RJ Britten and EH Davidson hypothesized that TEs can integrate the function of various transcriptional regulators into gene regulatory networks. Uniquely TEs can deposit regulatory sites across the genome when they transpose, and thereby bring multiple genes under control of the same regulatory logic. Several studies (...) together have robustly established that TEs participate in embryonic development and oncogenesis. We discuss the regulatory characteristics of TEs in context of evolution to understand the extent of their impact on gene networks. Understanding these features of TEs is central to future investigations of TEs in cellular processes and phenotypic presentations, which are applicable to development and disease studies. We re-visit the Britten–Davidson “gene-battery” model and understand the genetic and transcriptional impact of TEs in innovating gene regulatory networks. Transposable elements are exogenous sequences that have either been co-opted or repurposed for host functions. The vast amounts of TE sequence in the genome provides raw material for gene expression regulation, and still remains to be fully understood; the “gene-battery” model provides the basis for understanding this. (shrink)

Résumé: O design cultural integra o conteúdo cultural no processo de design. É um meio importante para perceber a inovação da cultura tradicional na herança. O comportamento do design cultural é sutilmente influenciado pela filosofia cultural. Especificamente, a análise do ambiente cultural, a associação semântica cultural e a extração de imagens culturais, na perspectiva da filosofia cultural, ajudam a perceber a explicitação do conhecimento implícito no processo de codificação e decodificação de genes culturais. Selecionamos Ningbo como uma amostra, aprofundamos os (...) genes culturais regionais, exploramos o modelo de geração de design cultural e ainda propusemos a estrutura para a construção de um sistema de serviços de conhecimento de design cultural para fornecer orientação metodológica, para a prática de design cultural regional, a fim de construir capacidades de design cultural sustentável. (shrink)

When relating genomic data to survival outcomes, there are three main challenges that are the censored survival outcomes, the high-dimensionality of the genomic data, and the non-normality of data. We propose a method to tackle these challenges simultaneously and obtain a robust estimation of detecting significant genes related to survival outcomes based on Accelerated Failure Time model. Specifically, we include a general loss function to the AFT model, adopt model regularization and shrinkage technique, cope with parameters tuning and model selection, (...) and develop an algorithm based on unified Expectation–Maximization approach for easy implementation. Simulation results demonstrate the advantages of the proposed method compared with existing methods when the data has heavy-tailed errors and correlated covariates. Two real case studies on patients are provided to illustrate the application of the proposed method. (shrink)

N6‐methyladenine (6mA) is one of the most abundant types of DNA methylation, and plays an important role in bacteria; however, its roles in higher eukaryotes, such as plants, insects, and mammals, have been considered less important. Recent studies highlight that 6mA does indeed occur, and that it plays an important role in eukaryotes, such as worm, fly, and green algae, and thus the regulation of 6mA has emerged as a novel epigenetic mechanism in higher eukaryotes. Despite this intriguing development, a (...) number of important issues regarding its biological roles are yet to be addressed. In this review, we focus on the 5mC and 6mA modifications in terms of their production, distribution, and the erasure of 6mA in higher eukaryotes including mammals. We perform an analysis of the potential functions of 6mA, hence widening understanding of this new epigenetic mark in higher eukaryotes, and suggesting future studies in this field. (shrink)

During development one mechanism for generating different cell types is asymmetric cell division, by which a cell divides and contributes different factors to each of its daughter cells. Asymmetric cell division occurs through out the eukaryotic kingdom, from yeast to humans. Many asymmetric cell divisions occur in a defined orientation. This implies a cellular mechanism for sensing direction, which must ultimately lead to differences in gene expression between two daughter cells. In this review, we describe two classes of molecules: (...) regulatory factors that are differentially expressed upon asymmetric cell division, and components of a signal transduction pathway that may define cell polarity. The lin‐11 and mec‐3 genes of C. elegans, the Isl‐1 gene of mammals and the HO gene of yeast, encode regulatory factors that determine cell type of one daughter after asymmetric cell division. The CDC24 and CDC42 genes of yeast affect both bud positioning and orientation of mating projections, and thus may define a general cellular polarity. We speculate that molecules such as Cdc24 and Cdc42 may regulate expression of genes such as lin‐11, mec‐3, Isl‐1 and HO upon asymmetric cell division. (shrink)

During the COVID-19 public health crisis, market failures such as shortage of supplies and soaring prices of anti-epidemic materials – with masks as the core – have occurred. In essence, such anti-epidemic materials have the dual nature of necessities with low elasticity of demand and private products with positive externalities. This research explores the understanding of anti-pandemic materials and how different initiatives, and evaluation to increase availability of necessary resources can be effective in curbing a pandemic. Market regulation results in (...) a non-Pareto optimal allocation of resources and the difficulty of exerting the positive externalities of products. However, in China, the market failure of anti-epidemic materials was quickly resolved, due to the institutional advantages of socialism with Chinese characteristics, the social responsibility drive of domestic enterprises, and cultural genes that focus on equity and concern for the disadvantaged. The optimal allocation of anti-epidemic materials gave access to exerting efficiency and fairness effects, positive external effects, and public effects. (shrink)

Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic “junk yard”, functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest (...) has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone. (shrink)

The genetic basis for animal social organization is poorly understood. Fire ants provide one of the rare cases where variation in social organization has been demonstrated to be under genetic control, which amazingly, segregates as a single Mendelian locus. A recent genetic, genomic, and cytological analysis revealed that this locus actually consists of over 600 genes locked together in a supergene that possesses many characteristics of sex chromosomes. The fire ant social supergene also behaves selfishly, and an interesting evolutionary question (...) is whether the genes incorporated first into the social supergene were those for social adaptation, selfish genetic drive, or something else. In depth, functional molecular genetic analysis in fire ants and comparative genomics in other closely related socially polymorphic species will be required to resolve this question.Editor's suggested further reading in BioEssays Social supergenes of superorganisms: Do supergenes play important roles in social evolution? Abstract. (shrink)

The explosion of multiomics data poses new challenges to existing data mining methods. Joint analysis of multiomics data can make the best of the complementary information that is provided by different types of data. Therefore, they can more accurately explore the biological mechanism of diseases. In this article, two forms of joint nonnegative matrix factorization based on the sparse and graph Laplacian regularization method are proposed. In the method, the graph regularization constraint can preserve the local geometric structure of data. (...) L 2,1 -norm regularization can enhance the sparsity among the rows and remove redundant features in the data. First, SG-jNMF1 projects multiomics data into a common subspace and applies the multiomics fusion characteristic matrix to mine the important information closely related to diseases. Second, multiomics data of the same disease are mapped into the common sample space by SG-jNMF2, and the cluster structures are detected clearly. Experimental results show that SG-jNMF can achieve significant improvement in sample clustering compared with existing joint analysis frameworks. SG-jNMF also effectively integrates multiomics data to identify co-differentially expressed genes. SG-jNMF provides an efficient integrative analysis method for mining the biological information hidden in heterogeneous multiomics data. (shrink)

The development of culture-independent strategies to study microbial diversity and function has led to a revolution in microbial ecology, enabling us to address fundamental questions about the distribution of microbes and their influence on Earth’s biogeochemical cycles. This article discusses some of the progress that scientists have made with the use of so-called “omic” techniques (metagenomics, metatranscriptomics, and metaproteomics) and the limitations and major challenges these approaches are currently facing. These ‘omic methods have been used to describe the taxonomic structure (...) of microbial communities in different environments and to discover new genes and enzymes of industrial and medical interest. However, microbial community structure varies in different spatial and temporal scales and none of the ‘omic techniques are individually able to elucidate the complex aspects of microbial communities and ecosystems. In this article we highlight the importance of a spatiotemporal sampling design, together with a multilevel ‘omic approach and a community analysis strategy (association networks and modeling) to examine and predict interacting microbial communities and their impact on the environment. (shrink)

Accumulating research has identified the interactive effects of catechol-O-methyltransferase gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who are more affected by environmental conditions and has been challenged for the low power of analyses on gene–environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions in a (...) sample of 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene–environment interaction using a mixed design. (shrink)

The increasing importance of computational techniques in post-genomic life science research calls for new forms and combinations of expertise that cut across established disciplinary boundaries between computing and biology. These are most marked in large scale gene sequencing facilities. Here new ways of organising knowledge production, drawing on industrial models, have been perceived as pursuing efficiency and control to the potential detriment of academic autonomy and scientific quality. We explore how these issues are played out in the case of (...) BGI (Beijing Genomics Institute prior to 2008). BGI (in Pinyin, Hua Da Jiyin– Big China Genome) is today the world’s largest centre for gene sequencing research. Semi-detached from traditional academic institutions, BGI has developed distinctive models for organising research and for developing expertise, informed by practices in US Information Technology and Life Science Laboratories, that differ from existing models of interdisciplinary research in academic institutions. (shrink)

The process of gene expression is affected by many extracellular stimulus signals, and the stochasticity of these signals reshapes gene expression. To adapt the fluctuation of the extracellular environment, genes have many strategies for augmenting their survival probability, frequency modulation, and amplitude modulation. However, it is unclear how genes utilize the stochasticity of signals to regulate gene expression and which strategy will be chosen to maximize cellular function. Here, we analyze a simple mechanistic model to clarify the (...) effect of extracellular random input on gene expression and burst kinetics at different timescales. We can see that in different contexts, extracellular noise has different effects on downstream gene expression, effects which include the following: extracellular noise will make the ON-OFF-state dwell time drift, which will influence the burst frequency and burst size of downstream gene expression under different modulation paradigms; comparing the burst parameter or gene expression products under different modulation paradigms, we can see that the amplitude signal is more sensitive in the case of extracellular noise input, whereas the signal in noiseless conditions is more sensitive when the random input is a fast process, which indicates that the amplitude signal is a superior and common signal in gene expression; and extracellular random input will change the bimodality for gene expression, but its influence is different for gene expression products under different modulation paradigms. These qualitative results reveal that extracellular random input can prompt the gene to achieve its function quickly under different modulation paradigms. (shrink)

Gene expression network is also a type of complex network. It is challenging to analyze the gene expression network through relevant knowledge and algorithms of a complex network. In this paper, the existing characteristics of genes are analyzed from various indexes of the gene expression network to analyze key genes and TOP genes. Firstly, gene chip data are screened, gene data with obvious characteristics are selected, and relevant clustering characteristics are analyzed. Then, the complex (...) class='Hi'>gene network structure is established, and gene networks with different threshold shapes and different sizes are selected. Finally, the relevant indexes and PR values after the PageRank algorithm are analyzed for complex networks under different thresholds, thus establishing the TOP gene and PR sequence. (shrink)

Research has indicated that microRNAs (miRNAs), a special class of non-coding RNAs (ncRNAs), can perform important roles in different biological and pathological processes. miRNAs’ functions are realized by regulating their respective target genes (targets). It is thus critical to identify and analyze miRNA-target interactions for a better understanding and delineation of miRNAs’ functions. However, conventional knowledge discovery and acquisition methods have many limitations. Fortunately, semantic technologies that are based on domain ontologies can render great assistance in this regard. In our (...) previous investigations, we developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), to provide the community with common data elements and data exchange standards in the miRNA research. This paper describes (1) our continuing efforts in the OMIT ontology development and (2) the application of the OMIT to enable a semantic approach for knowledge capture of miRNA-target interactions. (shrink)

Graphical AbstractCRISPR activation (CRISPRa) in bacteria is an attractive method for programmable gene activation. In article number 1900252, Yang Liu and Baojun Wang summarize the current state-of-the-art in this area of high potential, and present the powerful features and capabilities of a newly reported eukaryote-like, σ54-dependent CRISPRa system. The eukaryote-like bacterial CRISPRa enables novel designs in synthetic gene regulation and promotes research in the σ54-dependent gene networks with broad applications envisioned.

CRISPR (clustered regularly interspaced short palindromic repeats) activation (CRISPRa) in bacteria is an attractive method for programmable gene activation. Recently, a eukaryote‐like, σ54‐dependent CRISPRa system has been reported. It exhibits high dynamic ranges and permits flexible target site selection. Here, an overview of the existing strategies of CRISPRa in bacteria is presented, and the characteristics and design principles of the CRISPRa system are introduced. Possible scenarios for applying the eukaryote‐like CRISPRa system is discussed with corresponding suggestions for performance optimization (...) and future functional expansion. The authors envision the new eukaryote‐like CRISPRa system enabling novel designs in multiplexed gene regulation and promoting research in the σ54‐dependent gene regulatory networks among a variety of biotechnology relevant or disease‐associated bacterial species. (shrink)

In the big data era, sequencing technology has produced a large number of biological sequencing data. Different views of the cancer genome data provide sufficient complementary information to explore genetic activity. The identification of differentially expressed genes from multiview cancer gene data is of great importance in cancer diagnosis and treatment. In this paper, we propose a novel method for identifying differentially expressed genes based on tensor robust principal component analysis, which extends the matrix method to the processing of (...) multiway data. To identify differentially expressed genes, the plan is carried out as follows. First, multiview data containing cancer gene expression data from different sources are prepared. Second, the original tensor is decomposed into a sum of a low-rank tensor and a sparse tensor using TRPCA. Third, the differentially expressed genes are considered to be sparse perturbed signals and then identified based on the sparse tensor. Fourth, the differentially expressed genes are evaluated using Gene Ontology and Gene Cards tools. The validity of the TRPCA method was tested using two sets of multiview data. The experimental results showed that our method is superior to the representative methods in efficiency and accuracy aspects. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The form of higher plants is largely dependent upon cell division and expansion patterns. Taking a genetic approach, Takahashi et al.(1) have identified a regulatory molecule in Arabidopsis thaliana called DIMINUTO (DIM), which is involved in determining the degree and direction of plant cell expansion. Their extensive characterization of a dim mutant suggested a direct involvement of the DIM gene in regulating cell elongation, perhaps by modulating the expression of structural genes which determine the orientation and elasticity of the (...) cell wall. (shrink)

AimTo examine the relative cost-effectiveness of predictive genetic tests for familial breast and ovarian cancer provided by Genetic Services of Western Australia.MethodsThe relative cost-effectiveness was assessed using a decision analytic model.ResultsThe cost and outcomes of genetic testing was compared in first-degree relatives of known BRCA1/2 mutation-carriers who have a 50% risk of carrying the mutated gene (intervention group) to individuals with the same a priori risk but who do not undergo a genetic test (control subjects).Since genetic testing enables the (...) restriction of intensive surveillance to individuals with an identified BRCA1/2 gene mutation, net savings in the period observed (age 25-70) were $980-$1008 per woman in the ovarian intervention group and $1681-$1795 per woman in the breast intervention group, and delayed the onset of breast cancer (6mths BRCA1, 3mths BRCA2).Compared to control subjects undergoing population surveillance, it was estimated the onset of breast cancer could be delayed at a total net cost of $3055 (5.1yrs) to $3389 (3.2yrs) for women in the breast intervention group with BRCA1/2 mutations. Since population surveillance is not currently recommended for ovarian cancer, control subjects undergoing no surveillance were compared with the intervention group. The onset of ovarian cancer was delayed at a net cost of $1630 (3.5yrs) to $2509 (1.2years) for women with BRCA1/2 mutations.ConclusionsTesting allows targeted high-level surveillance for gene mutation carriers, which ensures the cost-effective use of resources and reduces cancer-related morbidity if clinical recommendations for intervention are adopted. (shrink)

Plasmids are a major type of mobile genetic elements (MGEs) that mediate horizontal gene transfer. The stable maintenance of plasmids plays a critical role in the functions and survival for microbial populations. However, predicting and controlling plasmid persistence and abundance in complex microbial communities remain challenging. Computationally, this challenge arises from the combinatorial explosion associated with the conventional modeling framework. Recently, a plasmid‐centric framework (PCF) has been developed to overcome this computational bottleneck. This framework enables the derivation of a (...) simple metric, the persistence potential, to predict plasmid persistence and abundance. Here, we discuss how PCF can be extended to account for plasmid interactions. We also discuss how such model‐guided predictions of plasmid fates can benefit from the development of new experimental tools and data‐driven computational methods. (shrink)

This study aims to develop a robust metalearning system for rapid classification on a large number of tasks. The model-agnostic metalearning with the CACTUs method is improved as EW-CACTUs-MAML after integrated with the entropy weight method. Few-shot mechanisms are introduced in the deep network for efficient learning of a large number of tasks. The process of implementation is theoretically interpreted as “gene intelligence.” Validation of EW-CACTUs-MAML on a typical dataset indicates an accuracy of 97.42%, performing better than CACTUs-MAML. At (...) the end of this paper, the availability of our thoughts to improve another metalearning system is also preliminarily discussed based on a cross-validation on another typical dataset. (shrink)

The fast advancing RNA‐seq technology has unveiled an unexpected diversity and expression specificity of 3′ untranslated regions (3′UTRs) of mRNAs. In particular, neural mRNAs seem to express significantly longer 3′UTRs, some of which are over 10 kb in length. The extensive elongation of 3′UTRs in neural tissues provides intriguing possibilities for cell type‐specific regulations that are governed by miRNAs, RNA‐binding proteins and ribonucleoprotein aggregates. In this article, we review recent progress in the characterization of mRNA 3′UTRs and discuss their implications (...) in the understanding of 3′UTR‐mediated gene regulation. (shrink)

How to interpret the “molecular gene” concept is discussed in this paper. I argue that the architecture of biological systems is hierarchical and multi-layered, exhibiting striking similarities to that of modern computers. Multiple layers exist between the genotype and system level property, the phenotype. This architectural complexity gives rise to the intrinsic complexity of the genotype-phenotype relationships. The notion of a gene being for a phenotypic trait or traits lacks adequate consideration of this complexity and has limitations in (...) explaining the genotype-phenotype relationships. I explore ways toward an integrative interpretation of the gene in the context of multi-layered biological systems. A gene, I argue, should be interpreted as a functional unit that is responsible for the trans-generation passage of the capacity to dynamically produce a biochemical activity or biochemical activities. At the molecular level, a gene is a genetic unit, a stretch of DNA sequence, which dictates the behavior and the dynamic production of the encoded cellular component(s). Embedded in a gene’s quadruple DNA code are the regulatory signals, such as those for RNA splicing and/or editing, as well as for transcription factor binding. A regulatory signal can be recognized by the gene expression machinery in one state, but not in another. The confusion caused by RNA splicing, editing, and a gene’s selective tissue distribution pattern is addressed. Instead of a context-dependent definition of the gene, I argue for the view that it is the same gene displaying multiple meanings, subject to differential interpretation by the cellular machinery in different states. In other words, the same gene gives rise to different products and expression levels under different conditions. (shrink)

The fact that genes and environment contribute differentially to variation in human behaviors, traits and attitudes is central to the field of behavior genetics. Perceptions about these differential contributions may affect ideas about human agency. We surveyed two independent samples (N = 301 and N = 740) to assess beliefs about free will, determinism, political orientation, and the relative contribution of genes and environment to 21 human traits. We find that lay estimates of genetic influence on these traits cluster into (...) four distinct groups, which differentially predict beliefs about human agency, political orientation, and religiosity. Despite apparent ideological associations with these beliefs, the correspondence between mean lay estimates and published heritability estimates for the surveyed traits is large (r = .77). Belief in genetic determinism emerges as a modest predictor of accuracy in these lay estimates. Additionally, educated mothers with multiple children emerge as particularly accurate in their estimates of the genetic contribution to these traits. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

Recent studies have revealed an astonishing diversity of sex chromosomes in many vertebrate lineages, prompting questions about the mechanisms of sex chromosome turnover. While there is considerable population genetic theory about the evolutionary forces promoting sex chromosome replacement, this theory has not yet been integrated with our understanding of the molecular and developmental genetics of sex determination. Here, we review recent data to examine four questions about how the structure of gene networks influences the evolution of sex determination. We (...) argue that patterns of epistasis, arising from the structure of genetic networks, may play an important role in regulating the rates and patterns of sex chromosome replacement. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)