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

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]

The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice

Female mice lacking ATRX in the pancreas have increased sensitivity to pancreatic cancer, whereas male mice without ATRX are protected. This study identifies such susceptibility in pancreatic cancer and highlights the need for sex-specific approaches in cancer treatment. BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for \u3e30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler.-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS\u27s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx in pancreatic acinar cells will increase susceptibility to injury and oncogenic METHODS: Mice allowing conditional loss of Atrx within pancreatic acinar cells were examined after induction of recurrent cerulein-induced pancreatitis or oncogenic KRAS (KRASG12D). Histologic, biochemical, and molecular analysis examined pancreatic pathologies up to 2 months after induction of Atrx deletion. RESULTS: Mice lacking Atrx showed more progressive damage, inflammation, and acinar-to-duct cell metaplasia in response to injury relative to wild-type mice. In combination with KRASG12D, Atrx-deficient acinar cells showed increased fibrosis, inflammation, progression to acinar-to-duct cell metaplasia, and pre-cancerous lesions relative to mice expressing only KRASG12D. This sensitivity appears only in female mice, mimicking a significant prevalence of ATRX mutations in human female PDAC patients. CONCLUSIONS: Our results indicate the absence of ATRX increases sensitivity to injury and oncogenic KRAS only in female mice. This is an instance of a sex-specific mutation that enhances oncogenic KRAS\u27s ability to promote pancreatic intraepithelial lesion formation

ExCyto PCR Amplification

ExCyto PCR cells provide a novel and cost effective means to amplify DNA transformed into competent bacterial cells. ExCyto PCR uses host E. coli with a chromosomally integrated gene encoding a thermostable DNA polymerase to accomplish robust, hot-start PCR amplification of cloned sequences without addition of exogenous enzyme.Because the thermostable DNA polymerase is stably integrated into the bacterial chromosome, ExCyto cells can be transformed with a single plasmid or complex library, and then the expressed thermostable DNA polymerase can be used for PCR amplification. We demonstrate that ExCyto cells can be used to amplify DNA from different templates, plasmids with different copy numbers, and master mixes left on ice for up to two hours. Further, PCR amplification with ExCyto cells is comparable to amplification using commercial DNA polymerases. The ability to transform a bacterial strain and use the endogenously expressed protein for PCR has not previously been demonstrated.ExCyto PCR reduces pipetting and greatly increases throughput for screening EST, genomic, BAC, cDNA, or SNP libraries. This technique is also more economical than traditional PCR and thus broadly useful to scientists who utilize analysis of cloned DNAs in their research