Characterization of an aryl hydrocarbon receptor from a cetacean : an approach for assessing contaminant susceptibility in protected species

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2000Some cetaceans bioaccumulate substantial concentrations of halogenated aromatic hydrocarbons (HAH) in their tissues, but little is known about the effects of such burdens on cetacean health. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related HAH cause toxicity via activation of the aryl hydrocarbon receptor (AHR), a member of the bHLH-PAS family of transcription factors. Differences in AHR structure and function are known to contribute to species-specific differences in susceptibility to HAH toxicity, and targets for HAH toxicity are related to the tissue-specific expression of AHR. The goal of these studies was to ascertain the potential for HAH effects in cetaceans by characterizing the AHR from the beluga, Delphinapterus leucas. The beluga AHR was characterized by its molecular structure, capacity for ligand binding, structure-binding relationships with various classes of HAH, as well as tissue-specific expression. These results show that: 1) in an in vitro system, the beluga AHR possesses binding affinities similar to AHRs of other mammals that are considered sensitive to toxic effects of HAH, 2) Structure-activity relationships are consistent with a common mechanism of coplanar HAH action among cetaceans and rodent species, and 3) the AHR protein is expressed in many tissues of the beluga, and is present at high levels in lymphoid organs, liver and lung. Together, these data suggest that cetaceans can be considered sensitive to the action of coplanar HAH. Further, using in vitro expressed proteins is a promising approach for addressing molecular and biochemical questions about PHAH toxicity in endangered and protected species where logistical and ethical concerns preclude testing in live animals.This work was supported by NIH Grant No. ES06272, NOAA National Sea Grant College Program Grant Nos. NA46RG0470, (WHO! Sea Grant Project No. R/B-137), NA86RG0075 (WHO! Sea Grant Project No. R/B-15l), NA86RG0075 (WHOI Sea Grant Project No. R/P-64) and the Ocean Ventures Fund

Engagement in Behavioral Parent Training: Review of the Literature and Implications for Practice

Engagement in behavioral parent training (BPT), including enrollment, attrition, attendance, within-session engagement, and homework completion, has long been a critical issue in the literature. Several estimates of various aspects of engagement have been suggested in the literature, but a systematic review of the available literature has never been accomplished. This review examines engagement data across 262 studies of BPT. Recruitment attrition, program attrition, attendance, and within-session engagement are examined across studies, with particular emphasis on the impact that SES, study purpose (efficacy vs. effectiveness), treatment format (individual vs. group), and age of child may have on those rates. Results of this review suggest that the significant amount of attrition occurs prior to enrollment in BPT, with at least 25 % of those identified as appropriate for BPT not enrolling in such programs. An additional 26 % begin, but drop out before completing treatment. Still the combined dropout rate of at least 51 % leaves at best half of identified parents completing treatment. While SES status had a small effect on attrition, other variables were not found to meaningfully impact engagement. Information on within-session engagement (homework and ratings of participation) was not often reported in studies. Key issues in this literature (e.g., varying definitions of engagement, limited attention to reporting key aspects of engagement) are discussed, and recommendations are made to further improve this important area of research and clinical practice

Pennsylvania Folklife Vol. 34, No. 4

• Coverlets • Sign Painting • Reverse Painting on Glass • Kites • Snake Lore • Horncraft • Weathervanes and Country Signs • Festival Focus • Sheep Shearing & Natural Knits • Bread Baking Among the Pennsylvania Dutch • The Craft of Rushing • Toy Soldier Casting • Pennsylvania Dutch Humor • Fireside Brooms and Whirligigs • Springerlehttps://digitalcommons.ursinus.edu/pafolklifemag/1108/thumbnail.jp

Trans-Arctic asymmetries, melting pots and weak species cohesion in the low-dispersal amphiboreal seaweed Fucus distichus

Amphiboreal taxa are often composed of vicariant phylogroups and species complexes whose divergence and phylogeographic affinities reflect a shared history of chronic isolation and episodic trans-Arctic dispersal. Ecological filters and shifting selective pressures may also promote selective sweeps, niche shifts and ecological speciation during colonization, but these are seldom considered at biogeographical scales. Here we integrate genetic data and Ecologic Niche Models (ENMs) to investigate the historical biogeography and cohesion of the polymorphic rockweed Fucus distichus throughout its immense amphiboreal range, focusing on trans-Arctic asymmetries, glacial/interglacial dynamics, and integrity of sympatric eco-morphotypes. Populations were sampled throughout the Pacific and the Atlantic, from southern rear-edges to the high-Arctic. They were genotyped for seven microsatellites and an mtDNA spacer, and genetic diversity and structure were assessed from global to local scales. ENMs were used to compare niche divergence and magnitude of post-glacial range shifts in Pacific versus Atlantic sub-ranges. Haplotypic and genotypic data revealed distinct and seemingly isolated Pacific vs Arctic/Atlantic gene-pools, with finer-scale regional sub-structuring pervasive in the Pacific. MtDNA diversity was highly structured and overwhelmingly concentrated in the Pacific. Regionally, Alaska showed the highest intra-population diversity but the lowest levels of endemism. Some sympatric/parapatric ecotypes exhibited distinct genotypic/ haplotypic compositions. Strikingly, niche models revealed higher Pacific tolerance to maximum temperatures and predicted a much more consolidated presence in the NE Atlantic. Glacial and modern ranges overlapped extensively in the Pacific, whereas the modern Atlantic range was largely glaciated or emerged during the Last Glacial Maximum. Higher genetic and ecogeographic diversity supports a primary Pacific diversification and secondary Atlantic colonization, also likely reflecting the much larger and more stable climatic refugia in the Pacific. The relic distribution and reduced ecological/morphological plasticity in the NE Atlantic are hypothesized to reflect functional trans-Arctic bottlenecks, recent colonization or competition with congeners. Within the Pacific, Alaska showed signatures of a post-glacial melting pot of eastern and southern populations. Genetic/ecotypic variation was generally not sufficiently discontinuous or consistent to justify recognizing multiple taxonomic entities, but support a separate species in the eastern Pacific, at the southern rear-edge. We predict that layered patterns of phylogeographic structure, incipient speciation and niche differences might be common among widespread low-dispersal amphiboreal taxa

Phocine distemper Virus: Current knowledge and future directions

Phocine distemper virus (PDV) was first recognized in 1988 following a massive epidemic in harbor and grey seals in north-western Europe. Since then, the epidemiology of infection in North Atlantic and Arctic pinnipeds has been investigated. In the western North Atlantic endemic infection in harp and grey seals predates the European epidemic, with relatively small, localized mortality events occurring primarily in harbor seals. By contrast, PDV seems not to have become established in European harbor seals following the 1988 epidemic and a second event of similar magnitude and extent occurred in 2002. PDV is a distinct species within the Morbillivirus genus with minor sequence variation between outbreaks over time. There is now mounting evidence of PDV-like viruses in the North Pacific/Western Arctic with serological and molecular evidence of infection in pinnipeds and sea otters. However, despite the absence of associated mortality in the region, there is concern that the virus may infect the large Pacific harbor seal and northern elephant seal populations or the endangered Hawaiian monk seals. Here, we review the current state of knowledge on PDV with particular focus on developments in diagnostics, pathogenesis, immune response, vaccine development, phylogenetics and modeling over the past 20 years

The global meningitis genome partnership.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Insights into hominid evolution from the gorilla genome sequence.

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution