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

Ethical and pedagogical challenges of experiential learning - in different types of memorials of repression - with foreign students in Argentina

From 1976 to 1983, Argentina experienced the worst dictatorship in its history. Roughly 30,000 people were disappeared in the military junta’s clandestine system of terror. Once democracy was reinstalled in 1983 and in particular throughout the last few years, many actions have been undertaken to bring justice and initiate a process of collective memory. The study abroad program “Argentina Social Movements and Human Rights” from SIT has the challenge to teach about this period of the history to foreign students. The different types of memorials are a path by which we can bring students to the understanding of a complex process. This approach presents some challenges in order to combine ethical principles with the pedagogical objectives. In this paper we describe briefly the history of Argentina and some core concepts about collective memory. We also describe the different types of memorials visited by the students as well as the impact it has on them. We define four main challenges that should be taken into account in the debriefing process: 1. From Oversimplification to Thick Comprehension 2. From Horror to Hope, 3. From Particular to Global 4. From Foreign to Personal Our proposition is that these challenges should be faced in order to assure that foreign students are able to comprehend a complex phenomenon being compliant to ethical principles and are able to reflect about broader human rights issues that go beyond this case

The effect of aging on cervical parameters in a normative North American population

Study Design: Retrospective cohort study. Objectives: To investigate age-based changes in cervical alignment parameters in an asymptomatic population. Methods: Retrospective review of a prospective study of 118 asymptomatic subjects who underwent biplanar imaging with 3-dimensional capabilities. Demographic and health-related quality of life data was collected prior to imaging. Patients were stratified into 5 age groups: &lt;35 years, 35-44 years, 45-54 years, 55-64 years, and ≥65 years. Radiographic measurements of the cervical spine and spinopelvic parameters were compared between age groups. The normal distribution of parameters was assessed followed by analysis of variance for comparison of variance between age groups. Results: C2-C7 lordosis, C0-C7 lordosis, and T1 slope demonstrated significant increases with age. C0-C7 lordosis was significantly less in subjects &lt;35 years compared with ≥55 years. Significant differences in T1 slope were identified in patients &lt;35 versus ≥65, 35-44 versus ≥65, and 45-54 versus ≥65 years. T1 slope demonstrated a positive correlation with age. Horizontal gaze parameters did not change linearly with age and mean averages of all age groups were within 10° of one another. Cervical kyphosis was present in approximately half of subjects who were &lt;55 compared with approximately 10% of subjects ≥55 years. Differences in pelvic tilt, pelvic incidence-lumbar lordosis, and C7-S1 sagittal vertical axis were identified with age. Conclusions: C0-C7 lordosis, C2-C7 lordosis, and T1 slope demonstrate age-based changes while other cervical and horizontal gaze parameters remain relatively constant with age. </jats:sec

Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme

Purpose: Clinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered CTLs delivered directly to the tumor bed in the central nervous system. The objective of this study is to determine a suite of magnetic resonance imaging (MRI) measurements using an orthotopic xenograft murine model that can noninvasively monitor immunologically mediated tumor regression and reactive changes in the surrounding brain parenchyma. Experimental Design: Our preclinical therapeutic platform is based on CTL genetic modification to express a membrane tethered interleukin-13 (IL-13) cytokine chimeric T-cell antigen receptor. This enables selective binding and signal transduction on encountering the glioma-restricted IL-13 α2 receptor (IL-13Rα2). We used MRI to visualize immune responses following adoptive transfer of IL-13Rα2-specific CD8^+ CTL clones. Results: Based on MRI measurements, several phases following IL-13Rα2-specific T-cell adoptive transfer could be distinguished, all of which correlated well with glioblastoma regression confirmed on histology. The first detectable changes, 24 hours post-treatment, were significantly increased T_2 relaxation times and strongly enhanced signal on T_1-weighted postcontrast images. In the next phase, the apparent diffusion coefficient was significantly increased at 2 and 3 days post-treatment. In the last phase, at day 3 after IL-13Rα2-specific T-cell injection, the volume of hyperintense signal on T_1-weighted postcontrast image was significantly decreased, whereas apparent diffusion coefficient remained elevated. Conclusions: The present study indicates the feasibility of MRI to visualize different phases of immune response when IL-13Rα2-specific CTLs are administered directly to the glioma tumor bed. This will further the aim of better predicting clinical outcome following immunotherapy

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

Scaling up context-tailored clinical guidelines and training to improve childbirth care in urban, low-resource maternity units in Tanzania: A protocol for a stepped-wedged cluster randomized trial with embedded qualitative and economic analyses (The PartoMa Scale-Up Study)

While facility births are increasing in many low-resource settings, quality of care often does not follow suit; maternal and perinatal mortality and morbidity remain unacceptably high. Therefore, realistic, context-tailored clinical support is crucially needed to assist birth attendants in resource-constrained realities to provide best possible evidence-based and respectful care. Our pilot study in Zanzibar suggested that co-created clinical practice guidelines (CPGs) and low-dose, high-frequency training (PartoMa intervention) were associated with improved childbirth care and survival. We now aim to modify, implement, and evaluate this multi-faceted intervention in five high-volume, urban maternity units in Dar es Salaam, Tanzania (approximately 60,000 births annually). This PartoMa Scale-up Study will include four main steps: I. Mixed-methods situational analysis exploring factors affecting care; II. Co-created contextual modifications to the pilot CPGs and training, based on step I; III. Implementation and evaluation of the modified intervention; IV. Development of a framework for co-creation of context-specific CPGs and training, of relevance in comparable fields. The implementation and evaluation design is a theory-based, stepped-wedged cluster-randomised trial with embedded qualitative and economic assessments. Women in active labour and their offspring will be followed until discharge to assess provided and experienced care, intra-hospital perinatal deaths, Apgar scores, and caesarean sections that could potentially be avoided. Birth attendants\u27 perceptions, intervention use and possible associated learning will be analysed. Moreover, as further detailed in the accompanying article, a qualitative in-depth investigation will explore behavioural, biomedical, and structural elements that might interact with non-linear and multiplying effects to shape health providers\u27 clinical practices. Finally, the incremental cost-effectiveness of co-creating and implementing the PartoMa intervention is calculated. Such real-world scale-up of context-tailored CPGs and training within an existing health system may enable a comprehensive understanding of how impact is achieved or not, and how it may be translated between contexts and sustained.Trial registration number: NCT04685668

Overview of Spirit Microscopic Imager Results

This paper provides an overview of Mars Exploration Rover Spirit Microscopic Imager (MI) operations and the calibration, processing, and analysis of MI data. The focus of this overview is on the last five Earth years (2005-2010) of Spirit's mission in Gusev crater, supplementing the previous overview of the first 450 sols of the Spirit MI investigation. Updates to radiometric calibration using in-flight data and improvements in high-level processing are summarized. Released data products are described, and a table of MI observations, including target/feature names and associated data sets, is appended. The MI observed natural and disturbed exposures of rocks and soils as well as magnets and other rover hardware. These hand-lens-scale observations have provided key constraints on interpretations of the formation and geologic history of features, rocks, and soils examined by Spirit. MI images complement observations by other Spirit instruments, and together show that impact and volcanic processes have dominated the origin and evolution of the rocks in Gusev crater, with aqueous activity indicated by the presence of silica-rich rocks and sulfate-rich soils. The textures of some of the silica-rich rocks are similar to terrestrial hot spring deposits, and observations of subsurface cemented layers indicate recent aqueous mobilization of sulfates in places. Wind action has recently modified soils and abraded many of the rocks imaged by the MI, as observed at other Mars landing sites. Plain Language Summary The Microscopic Imager (MI) on NASA's Spirit rover returned the highest-resolution images of the Martian surface available at the time of the 2004-2010 mission. Designed to survive 90 Mars days (sols) and search for evidence of water in the past, Spirit returned data for 2210 sols, far exceeding all expectations. This paper summarizes the scientific insights gleaned from the thousands of MI images acquired during the last 5years of the mission, supplementing the summary of the first 450 sols of the Spirit MI investigation published previously (Herkenhoff et al., ). Along with data from the other instruments on Spirit, MI images guided the scientific interpretation of the geologic history of the rocks and soils observed in Gusev crater on Mars. We conclude that the geologic history of the area explored by Spirit has been dominated by impacts and volcanism, and that water, perhaps very hot water, was involved in the evolution of some of the rocks and soils. More recently, winds have moved soil particles and abraded rocks, as observed elsewhere on Mars. These results have improved our understanding of Mars' history and informed planning of future missions to Mars.National Aeronautics and Space AdministrationPublic domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]