Envisioning sustainable tourism futures: An evaluation of the futures wheel method

Methods for researching the future have grown both in variety and rigour, offering new opportunities for understanding sustainable tourism. This paper discusses the value of futures research as a tool for envisioning and planning sustainable tourism futures but observes that there is greater potential for the use of futures methods in tourism. The aim of this paper is to evaluate the usefulness of a particular method known as the futures wheel as a sustainable planning tool for tourism decision makers and researchers. The futures wheel method is combined with a grounded theory approach to capture and distil the tacit knowledge of three 'expert' think tanks. The evaluation suggests that the futures wheel is a useful tool for researching sustainable tourism futures but that its potential may be enhanced if it can be combined with other futures research methods

A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Postponed access: the file will be accessible after 2021-10-14Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.acceptedVersio

Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

MicroRNA (miRNA) play a major role in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with co-transcriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. While most miRNA are located within introns of protein coding genes, a substantial minority of miRNA originate from long non coding (lnc) RNA where transcript processing is largely uncharacterized. Here, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis, we show that most lnc-pri-miRNA do not use the canonical cleavage and polyadenylation (CPA) pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a novel RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment ap-proaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothy-roidism, hyperthyroidism, or thyroid cancer, are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a se-ries of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes

Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females

The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1omat-/- mouse embryos born to Dnmt1Δ1o/Δ1o female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1Δ1o/Δ1o mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation. © 2013 McGraw et al

Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet

Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable

Genomic imprinting and parent-of-origin effects on complex traits

Parent-of-origin effects occur when the phenotypic effect of an allele depends on whether it is inherited from an individual’s mother or father. Several phenomena can cause parent-of-origin effects, with the best characterized being parent-of-origin dependent gene expression associated with genomic imprinting. Imprinting plays a critical role in a diversity of biological processes and in certain contexts it structures epigenetic relationships between DNA sequence and phenotypic variation. The development of new mapping approaches applied to the growing abundance of genomic data has demonstrated that imprinted genes can be important contributors to complex trait variation. Therefore, to understand the genetic architecture and evolution of complex traits, including complex diseases and traits of agricultural importance, it is crucial to account for these parent-of-origin effects. Here we discuss patterns of phenotypic variation associated with imprinting, evidence supporting its role in complex trait variation, and approaches for identifying its molecular signatures

Processos de democracia direta: sim ou não? Os argumentos clássicos à luz da teoria e da prática

Regularmente surgem controvérsias sobre os processos de democracia direta, dos quais os mecanismos mais frequentes são a iniciativa popular, o plebiscito e o referendo. Por um lado, há autores que defendem a posição de que essas instituições tornam o jogo político mais lento, caro, confuso e ilegítimo; outros defendem a posição contrária e argumentam que processos de democracia direta são fundamentais para os cidadãos e a qualidade da democracia. O presente estudo analisa esse tema em torno de sete questões, baseadas em considerações teóricas e pesquisas empíricas: 1. A questão entre o minimalismo e o maximalismo democrático; 2. A concorrência entre maioria e minoria; 3. A concorrência entre as instituições representativas e os processos de democracia direta; 4. A questão da competência dos cidadãos; 5. A questão dos efeitos colaterais dos processos de democracia direta; 6. A questão do tamanho do eleitorado; 7. A questão dos custos dos processos de democracia direta. As sete questões são analisadas a partir de uma revisão bibliográfica que considera tanto fontes nacionais como internacionais. O estudo mostra que os processos de democracia direta podem ser um complemento para as instituições representativas em um sistema democrático. O bom desempenho dos plebiscitos, referendos e iniciativas populares depende tanto da regulamentação destes como também do desempenho das outras instituições políticas e da situação socioeconômica de um país. O estudo permite ampliar e aprofundar o debate sobre processos de democracia direta no Brasil