Functional genomics does not have to be limited to a few select organisms

A response to Whither genomics by Andrew W Murray, Genome Biology 2000, 1:comment003.1-003.

Variation in tissue-specific gene expression among natural populations

BACKGROUND: Variation in gene expression is extensive among tissues, individuals, strains, populations and species. The interactions among these sources of variation are relevant for physiological studies such as disease or toxic stress; for example, it is common for pathologies such as cancer, heart failure and metabolic disease to be associated with changes in tissue-specific gene expression or changes in metabolic gene expression. But how conserved these differences are among outbred individuals and among populations has not been well documented. To address this we examined the expression of a selected suite of 192 metabolic genes in brain, heart and liver in three populations of the teleost fish Fundulus heteroclitus using a highly replicated experimental design. RESULTS: Half of the genes (48%) were differentially expressed among individuals within a population-tissue group and 76% were differentially expressed among tissues. Differences among tissues reflected well established tissue-specific metabolic requirements, suggesting that these measures of gene expression accurately reflect changes in proteins and their phenotypic effects. Remarkably, only a small subset (31%) of tissue-specific differences was consistent in all three populations. CONCLUSIONS: These data indicate that many tissue-specific differences in gene expression are unique to one population and thus are unlikely to contribute to fundamental differences between tissue types. We suggest that those subsets of treatment-specific gene expression patterns that are conserved between taxa are most likely to be functionally related to the physiological state in question

Wolves: Behavior, Ecology, and Conservation: Photo Section I

Wolves in Yellowstone National Park\u27s restored population often must compete with grizzly bears at the carcasses of their kills. Especially after their first feeding at a kill, wolves tend to relinquish their kills to bears. Photograph by Doug Smith. Elk are one of the most common prey of wolves in the northern Rocky Mountains of North America, primarily because in most areas they tend to outnumber other prey. This large bull standing his ground escaped this pack. Photograph by Doug Smith

Brief communication: Thwaites Glacier cavity evolution

Between 2014 and 2017, ocean melt eroded a large cavity beneath and along the western margin of the fast-flowing core of Thwaites Glacier. Here we show that from2017 to the end of 2020 the cavity persisted but did not ex-pand. This behaviour, of melt concentrated at the groundingline within confined sub-shelf cavities, fits with prior observations and modelling studies. We also show that acceleration and thinning of Thwaites Glacier grounded ice continued, with an increase in speed of 400 m a−1and a thinning rate of at least 1.5 m a−1, between 2012 and 2020

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen

Boundary Crossing: Networked Policing and Emergent “Communities of Practice” in Safeguarding Children

Child safeguarding has come to the forefront of public debate in the UK in the aftermath of a series of highly publicised incidents of child sexual exploitation and abuse. These have exposed the inadequacies and failings of inter-organisational relations between police and key partners. While the discourse of policing partnerships is now accepted wisdom, progress has been distinctly hesitant. This paper contributes to understanding both the challenges and opportunities presented through working across organisational boundaries in the context of safeguarding children. It draws on a study of relations within one of the largest Safeguarding Children partnerships in England, developing insights from Etienne Wenger regarding the potential of ‘communities of practice’ that innovate on the basis of everyday learning through ‘boundary work’. We demonstrate how such networked approaches expose the differential power relations and sites of conflict between organisations but also provide possibilities to challenge introspective cultures and foster organisational learning. We argue that crucial in cultivating effective ‘communities of practice’ are: shared commitment and purpose; relations of trust; balanced exchange of information and resources; mutual respect for difference; and an open and mature dialogue over possible conflicts. Boundary crossing can open opportunities to foster increased reflexivity among policing professionals, prompting critical self-reflection on values, ongoing reassessment of assumptions and questioning of terminology. Yet, there is an inherent tension in that the learning and innovative potential afforded by emergent ‘communities of practice’ derives from the coexistence and interplay between both the depth of knowledge within practices and active boundaries across practices

Levels of Analysis in Comprehensive River Basin Planning

Since nearly every water resource managment choice has two or more sides, differences must be resolved in decision making. Equitable resolution requires an understanding of the reasons for the differences. These reasons originate in the implemented plans have physical-environmental, economic, social, cultural, and political impacts at levels ranging from local to national or international in scope. Decisions are made by individuals and groups impacted in all of these dimensions and at all of these levels; the decisions generate additional impacts; and the entire interactive process changes water management practice in ways outside the control of any one decision point or even dicision dimension. The objective of this study is to conceptualize this process in a way that will help in establishing institutional mechanisms for reconciling differences among levels of analysis. The conceptualization used viewed differences in choices being made at the various levels of analysis as associated with perspective differences having value, jurisdiction, action, and temporal elements. The possible combinations of differences within and between these elements were used to identify ten categories of institutional obstacles to efficient water planning (differences in values, conflicts between value and jurisdiction, etc.). The history of water resources planning on the Colorado River basin was then examined to identify 17 specific institutional obstacles, and a computerized policy simulation was applied to levels of analysis in the Uintah basin of Utah to identify three more. These 20 obstacles were shown to be broadly distributed over the ten categories, and the nature of the obstacles defined provides valuable insight into the common characteristics of the major institutional obstacles to water management. The priciples of logic as applicable to rationality in decision making were then used to identify two root causes of levels\u27 conflicts. If alternatives are evaluated from a single perspective, the ostensible causal relationships commonly used lead to estimates of the sum of the consequences from the parts of a water management program being far more than the total consequences of the entire program. Looked at another way, since available water resources planning tools do not properly allocate consequences from interactive processes to individual causal sources, decisions made to acheive a desired impact are not based on reliable information. In fact, different decisions made over time from a single perspective have conflicting impacts. When multiple perspectices are considered, one finds that individual values do not aggregate linearly in forming social values, many actions are not efficient in achieving preferred values, and decision makers are not able to implement their plans as desired. Real world situations combine interacting perspectives and partial contributions. Nine recommendations are made on what to do next in improving water resources planning in an interactive, nonlinear world

FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression

BACKGROUND: While studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes. RESULTS: We describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P < 0.001) enrichment in genes associated with amine metabolism. CONCLUSION: The methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at . Data and source code are available by request at [email protected]

Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses

beta-hexosaminidase is an enzyme responsible for the degradation of gangliosides, glycans, and other glycoconjugates containing beta-linked hexosamines that enter the lysosome. GM2 gangliosidoses, such as Tay-Sachs and Sandhoff, are lysosomal storage disorders characterized by beta-hexosaminidase deficiency and subsequent lysosomal accumulation of its substrate metabolites. These two diseases result in neurodegeneration and early mortality in children. A significant difference between these two disorders is the accumulation in Sandhoff disease of soluble oligosaccharide metabolites that derive from N- and O-linked glycans. In this paper we describe our results from a longitudinal biochemical study of a feline model of Sandhoff disease and an ovine model of Tay-Sachs disease to investigate the accumulation of GM2/GA2 gangliosides, a secondary biomarker for phospholipidosis, bis-(monoacylglycero)-phosphate, and soluble glycan metabolites in both tissue and fluid samples from both animal models. While both Sandhoff cats and Tay-Sachs sheep accumulated significant amounts of GM2 and GA2 gangliosides compared to age-matched unaffected controls, the Sandhoff cats having the more severe disease, accumulated larger amounts of gangliosides compared to Tay-Sachs sheep in their occipital lobes. For monitoring glycan metabolites, we developed a quantitative LC/MS assay for one of these free glycans in order to perform longitudinal analysis. The Sandhoff cats showed significant disease-related increases in this glycan in brain and in other matrices including urine which may provide a useful clinical tool for measuring disease severity and therapeutic efficacy. Finally, we observed age-dependent increasing accumulation for a number of analytes, especially in Sandhoff cats where glycosphingolipid, phospholipid, and glycan levels showed incremental increases at later time points without signs of peaking. This large animal natural history study for Sandhoff and Tay-Sachs is the first of its kind, providing insight into disease progression at the biochemical level. This report may help in the development and testing of new therapies to treat these disorders