Genome Wide Analysis of Inbred Mouse Lines Identifies a Locus Containing Ppar-γ as Contributing to Enhanced Malaria Survival

The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-γ in malaria infection

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype–phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype–phenotype mapping using the power of Drosophila genetics

A model integrating social-cultural concepts of nature into frameworks of interaction between social and natural systems

Existing frameworks for analysing interactions between social and natural systems (e.g. Social-Ecological Systems framework, Ecosystem Services concept) do not sufficiently consider and operationalize the dynamic interactions between people\u27s values, attitudes and understandings of the human-nature relationship at both individual and collective levels. We highlight the relevance of individual and collective understandings of the human-nature relationship as influencing factors for environmental behaviour, which may be reflected in natural resource management conflicts, and review the diversity of existing social-cultural concepts, frameworks and associated research methods. Particular emphasis is given to the context-sensitivity of social-cultural concepts in decision-making. These aspects are translated into a conceptual model aiming not to replace but to expand and enhance existing frameworks. Integrating this model into existing frameworks provides a tool for the exploration of how social-cultural concepts of nature interact with existing contexts to influence governance of social-ecological systems

A model integrating social-cultural concepts of nature into frameworks of interaction between social and natural systems

Existing frameworks for analysing interactions between social and natural systems (e.g. Social-Ecological Systems framework, Ecosystem Services concept) do not sufficiently consider and operationalize the dynamic interactions between people's values, attitudes and understandings of the human-nature relationship at both individual and collective levels. We highlight the relevance of individual and collective understandings of the human-nature relationship as influencing factors for environmental behaviour, which may be reflected in natural resource management conflicts, and review the diversity of existing social-cultural concepts, frameworks and associated research methods. Particular emphasis is given to the context-sensitivity of social-cultural concepts in decision-making. These aspects are translated into a conceptual model aiming not to replace but to expand and enhance existing frameworks. Integrating this model into existing frameworks provides a tool for the exploration of how social-cultural concepts of nature interact with existing contexts to influence governance of social-ecological systems.</p

Prolactin and the skin: A dermatological perspective on an ancient pleiotropic peptide hormone

The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator of lactation and reproduction. However, based on the almost ubiquitous distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary PRL-expressing tissues, a vast range of PRL actions “beyond the mammary horizon” has now been documented or claimed. For example, PRL modulates hair growth in domestic animals with seasonal hair growth changes (“PRL–pelage axis”). Given that the mammary gland is an epidermal derivative, it is not surprising that the pilosebaceous unit, another epidermal derivative, has also surfaced as a prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact that murine and human hair follicles even synthesize PRL strongly invites one to explore fully the dermatological dimensions of this multifunctional, cytokine-like neuroendocrine bioregulator, which remain insufficiently charted. After describing the relevant essentials of general PRL/PRLR biology, we summarize clinical observations that provide insights into how PRL may impact on the skin, and define important research frontiers and controversies in the quest to better characterize the complex role of PRL in human skin biology and pathology. Focusing on psoriasis, alopecia, and stress-related dermatoses, we then discuss the possible role of PRL/PRLR in cutaneous pathology, and identify potential therapeutic targets for the management of these skin disorders. We close by delineating major open questions at this emerging frontier of basic and clinical cutaneous neuroendocrinology, and argue that systematic exploration of the “PRL–skin connection” will fertilize the development of previously unreported neuroendocrinological strategies for managing selected skin disorders