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Immune and endocrine responses play a critical role in allowing animals to adjust to environmental perturbations. We measured immune and endocrine related markers in multiple samples from individuals from two managed-care care dolphin groups (n = 82 samples from 17 dolphins and single samples collected from two wild dolphin populations: Indian River Lagoon, (IRL) FL (n = 26); and Charleston, (CHS) SC (n = 19). The immune systems of wild dolphins were more upregulated than those of managed-care-dolphins as shown by higher concentrations of IgG and increases in lysozyme, NK cell function, pathogen antibody titers and leukocyte cytokine transcript levels. Collectively, managed-care care dolphins had significantly lower levels of transcripts encoding pro-inflammatory cytokine TNF, anti-viral MX1 and INFα and regulatory IL-10. IL-2Rα and CD69, markers of lymphocyte activation, were both lower in managed-care care dolphins. IL-4, a cytokine associated with TH2 activity, was lower in managed-care care dolphins compared to the free-ranging dolphins. Differences in immune parameters appear to reflect the environmental conditions under which these four dolphin populations live which vary widely in temperature, nutrition, veterinary care, pathogen/contaminant exposures, etc. Many of the differences found were consistent with reduced pathogenic antigenic stimulation in managed-care care dolphins compared to wild dolphins. Managed-care care dolphins had relatively low TH2 lymphocyte activity and fewer circulating eosinophils compared to wild dolphins. Both of these immunologic parameters are associated with exposure to helminth parasites which is uncommon in managed-care care dolphins. Less consistent trends were observed in a suite of hormones but significant differences were found for cortisol, ACTH, total T4, free T3, and epinephrine. While the underlying mechanisms are likely multiple and complex, the marked differences observed in the immune and endocrine systems of wild and managed-care care dolphins appear to be shaped by their environment.

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasis TfrcY20H/Y20H mice appear healthy and are not anaemic. However, TfrcY20H/Y20H mice infected with Plasmodium chabaudi chabaudi AS showed significantly higher peak parasitaemia and body weight loss. We found that TfrcY20H/Y20H mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead, P. chabaudi infected TfrcY20H/Y20H mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4+ T cell and B cell function. Despite the inhibited immune response and increased parasitaemia, TfrcY20H/Y20H mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria. Author summary: Malaria is a serious and potentially lethal infectious disease that affects nearly 250 million people each year. It is caused by Plasmodium species parasites that are transmitted between humans by mosquitoes. Iron deficiency is prevalent in malaria endemic areas and there is a complex and incompletely understood relationship between iron and malaria. Although iron deficiency is known be protective in malaria, little is known about how iron deficiency affects host cells other than the red blood cells where Plasmodium replicates, such as immune, liver, lung or kidney cells. To address this, we used genetically modified mice with decreased cellular iron uptake, but no anaemia, and infected them with a mouse strain of malaria. These mice had a more severe infection, characterised by more infected red blood cells and more weight loss at the peak of infection compared to wild-type mice. Interestingly, the mice had a significantly weaker immune response but also less severe liver damage upon malaria infection, indicating a trade-off between pathogen control and host health. This study highlights the key role of host iron status in malaria and may have implications for the treatment approach to both malaria and iron deficiency in malaria endemic regions. [ABSTRACT FROM AUTHOR]

Rabbits were given reinforced training of the nictitating membrane (NM) response using separate conditioned stimuli (CSs), which were a tone, light, and/or tactile vibration. Then, two CSs were compounded and given further pairings with the unconditioned stimulus (US). Evidence of both overexpectation and summation effects appeared. That is, responding to the individual CSs declined despite their continued pairing with the US on compound trials (overexpectation), and responding on the compound trials was greater than responding to the individual CSs (summation). The response loss appeared regardless of the testing regime, that is, whether the test presentations of the individual CSs were themselves reinforced (Experiment 2), not reinforced (Experiment 1), or deferred until the end of compound training (Experiment 2). The results are discussed with respect to the roles of excitatory versus inhibitory processes, elemental versus configural processes, and the possible roles of cerebellar and hippocampal pathways. (Contains 3 figures and 1 footnote.)

Polychlorinated biphenyls (PCBs) have been assessed for immunotoxicity; however, humans and wildlife are exposed to multiple PCBs environmentally. Therefore, the aim of this study was to examine the effects of a complex 37 PCB congener mixture identified in blubber specific to dolphins residing in the estuarine waters of Charleston, South Carolina. Immunotoxicity was determined in adult female B6C3F1 mice by assessing lymphocyte proliferation, splenic and thymic immunophenotypes, and IgM production. Mice were exposed via oral gavage to the PCB-mixture (0, 1.8, 3.6, 7.1, or 14.3 mg/kg/day) for 28 days to yield a targeted total administered dose (TAD) 0, 50, 100, 200, or 400 mg/kg. Significant increased liver weight occurred at the highest treatment. IgM production was suppressed compared to control for all treatments. Numbers of thymic CD4+/CD8+, CD4-/CD8-, and CD4+/CD8- cells were not altered, but numbers of thymic CD4-/CD8+ cells were significantly increased in the highest treatment. Lymphocyte proliferation was not markedly affected by any treatment. The numbers of splenic CD4/CD8 T-cells or MHCII+ cells were not significantly changed. Humoral immunity using the plaque-forming cell assay for determining the specific IgM antibody-forming cell response appeared to be the most sensitive endpoint affected. As the lowest concentration tested resulted in decreased IgM production and total and free thyroxine (T4) serum levels a NOAEL was not identified. The calculated ED50 for suppression of IgM production was 2.4 mg/kg/day. [ABSTRACT FROM AUTHOR]

Objective: The ADLQ measures the ability to perform basic and instrumental activities of daily living (ADLs). Several factors, including cognition, may play a role in someone's ability to perform ADLs. The purpose of this study was to understand how executive functioning (EF) impacts abilities measured by the ADLQ. Method: Data were retrospectively collected from a mixed sample of patients with cognitive impairment (MCI: 29; dementia: 34) who underwent neuropsychological evaluation at a private practice in the Portland, Oregon area (n = 63, mean age = 76.65, mean education = 14.92 years). Patients with a history of moderate-to-severe TBI or severe psychiatric history were excluded. Six ADLQ scales and measures of EF (phonemic fluency, DKEFS Tower, Trails B, Stroop Interference) were analyzed using nonparametric Spearman's rank correlations. A p-level of 0.01 was used to reduce likelihood of type I errors. Results: There was a negative correlation between phonemic fluency and both self-care (ρ = −0.485, p = 0.002) and shopping (ρ = −0.474, p = 0.003). There was a negative correlation between travel and performance on both Trails B (ρ = −0.490, p = 0.009) and Stroop Interference (ρ = −0.634, p = 0.000). For the above EF tests, worse performance was associated with more impairment in the associated ADLs. Other correlations were not significant. Conclusions: Performance on certain EF tests is associated with impairment in the domains of self-care, shopping, and travel. Executive dysfunction appears related to functional decline on the ADLQ, but further analysis using larger samples is warranted to better understand this relationship. [ABSTRACT FROM AUTHOR]

Objective: The Clock Drawing Test (CDT) is an effective screening tool for assessing cognitive dysfunction. Many studies have examined differences in CDT performance between individuals with dementia and normal controls. The current study expands on this research by comparing individuals with dementia and mild cognitive impairment (MCI). We utilized the ten-point scoring system created by Libon and colleagues (1996) as we were interested in looking at differences in error type. Methods: Data were retrospectively collected from a sample of patients (n = 59, mean age = 76.8, mean education = 14.8 years, 45.8% MCI, 54.2% dementia) seen at a private practice in the Portland, Oregon metropolitan area. Patients with a history of moderate-to-severe TBI, severe psychiatric history, or undergoing re-evaluation were excluded. Results: Mann–Whitney U tests did not reveal a statistically significant difference in total CDT errors between dementia and MCI groups across command and copy conditions. There was no statistically significant difference between groups on error type (graphomotor, hand/number placement, executive control) on either the command or copy condition, with one exception. The dementia group (mean rank = 32.63) made significantly more copy condition graphomotor errors than the MCI group (mean rank = 24.96), U = 296, p = 0.046, r = −0.26. Conclusion(s): Our results demonstrate that CDT scores in patients with dementia and MCI are not significantly different. As a screening tool, CDT errors are suggestive of cognitive impairment, however, to achieve greater clarity in degree of impairment and presumed etiology, additional comprehensive cognitive assessment is needed. [ABSTRACT FROM AUTHOR]

Abstract Fish consumption is an important route of exposure to persistent organic pollutants (POPs) in dolphins as well as humans. In order to assess the potential risks associated with these contaminants, 39 whole fish and 37 fillets from fish representing species consumed by dolphins and humans captured from Charleston Harbor and tributaries, South Carolina, USA, were measured for a suite of POPs. Polychlorinated biphenyls (PCBs) were the predominant contaminant with concentrations ranging from 5.02 to 232.20 ng/g in whole fish and 5.42–131.95 ng/g in fillets (weight weight ww) followed by total organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). Total POPs levels varied by location and species with general trends indicating significantly higher levels in fish from the Cooper (93.4 ng/g ww) and Ashley Rivers (56.2 ng/g ww) compared to Charleston Harbor (31.6 ng/g ww). Mullet and spot were found to have significantly higher PCBs, OCPs and total POPs, 2–3 times higher than red drum; mullet were also significantly higher in OCPs compared to seatrout. PCB concentrations in whole fish and fillets exceeded EPA human screening values for cancer risk in all fish sampled. For PCBs in fillets, all samples had values of maximum allowable meals per month that were less than the EPA, FDA guidelines for recommended fish meals per month, suggesting lower (more stringent) allowable fish meals per month. All fish exceeded PBDE wildlife values and all fish except two exceeded the level where 95% of the dolphin population would have tissue levels below the health effect threshold. Considering that POP concentrations in fish potentially consumed by humans exceed human health effect thresholds levels, consumption advisories should be considered as a prudent public health measure. Graphical abstract fx1 Highlights • Higher contaminant levels in fish from Cooper/Ashley Rivers than Charleston Harbor. • Mullet and spot were significantly higher in PCBs and pesticides than red drum. • PCBs were the predominant contaminant in whole fish and fillets from Charleston SC. • PCBs in all fillets exceed EPA human health values, consumption advisories warranted. • Whole fish PCBs, PBDEs exceed wildlife screening values, a concern for local dolphins. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been associated with immunotoxicity in epidemiologic studies and experimental rodent models. Lengthy half-lives and resistance to environmental degradation result in bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate (PFOS), the most prevalent PFAA detected within the environment, is found at high levels in occupationally exposed humans. We have monitored the environmental exposure of dolphins in the Charleston, SC region for over 10 years and levels of PFAAs, and PFOS in particular, were significantly elevated. As dolphins may serve as large mammal sentinels to identify the impact of environmental chemical exposure on human disease, we sought to assess the effect of environmental PFAAs on the cellular immune system in highly exposed dolphins. Herein, we utilized a novel flow cytometry-based assay to examine T cell-specific responses to environmental PFAA exposure ex vivo and to exogenous PFOS exposure in vitro. Baseline PFOS concentrations were associated with significantly increased CD4+ and CD8+ T cell proliferation from a heterogeneous resident dolphin population. Further analysis demonstrated that in vitro exposure to environmentally relevant levels of PFOS promoted proinflammatory cytokine production and proliferation in a dose-dependent manner. Collectively, these findings indicate that PFOS is capable of inducing proinflammatory interferon-gamma, but not immunoregulatory interleukin-4 production in T cells, which may establish a state of chronic immune activation known to be associated with susceptibility to disease. These findings suggest that PFOS directly dysregulates the dolphin cellular immune system and has implications for health hazards. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Deepwater Horizon oil spill was one of the worst environmental disasters on record in the United States. Response efforts to reduce the magnitude of the oil slick included the use of thousands of gallons of the chemical dispersant Corexit™ in surface and deep-water environments. The immunotoxicity of Louisiana sweet crude oil and the chemical dispersant Corexit was examined using lymphocyte proliferation (LP) and natural killer cell (NK) assays as measures of impact on the adaptive (LP) and innate (NK) immune response in bottlenose dolphins. Study results show that both high-energy media-accommodated fractions (MAF) and chemically enhanced MAF (CEMAF) mixtures modulate immune function. Following exposure to Louisiana sweet crude, both B- and T-cell proliferation of white blood cells was increased for all exposure concentrations, compared to control; however, this increase was only significant for the 50% and 100% treatments. In contrast, exposure of white blood cells to the CEMAF mixture significantly decreased both T- and B-cell proliferation in the 25%, 50% and 100% treatments. NK cell activity was enhanced significantly by CEMAF mixtures for the 50% and 100% treatments. The immunosuppression of LP at environmentally relevant concentrations of oil and dispersant suggests that marine mammals may be unable to mount an adequate defense against xenobiotic threats following exposure to oil and dispersant, leaving them more susceptible to disease. In contrast, NK cell activity was significantly enhanced, which may increase an organism's tumor or viral surveillance ability by mounting an enhanced immune response. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article focuses on assess a natural plant-based dietary supplement comprised of Lemon verbena (Lippia citriodora) extract (LVE) in alleviating stress and improve quality of sleep. Topics include considered a double-blind, placebo-controlled study was conducted for eight weeks, followed by a four-week washout period.

Urban areas are sources of perfluoroalkyl substances (PFASs) in the environment, although little is known about specific point sources and distribution of PFASs. Sentinel species, like bottlenose dolphins, are important indicators of environmental perturbations. The high PFAS levels found in dolphins inhabiting Charleston, South Carolina prompted investigation of these chemicals in this area. This study provides further evidence on the extent of contamination and potential sources of PFASs. In this study, concentrations of 11 PFASs measured in estuarine sediments collected in 2012 from the Charleston Harbor and the Ashley and Cooper Rivers (n = 36) in South Carolina revealed higher levels than those reported in any other U.S. urban areas. Detectable levels were found in all sample locations with mean total PFAS concentrations of 3.79 ng g − 1 (range 0.22 to 19.2 ng g − 1 d.w.). Dominant compounds were perfluorooctane sulfonate (PFOS) (mean 1.52 ng g − 1 ; range 0.09–7.37 ng g − 1 d.w.), followed by perfluorodecanoate (PFDA) (mean 0.83 ng g − 1 ; range 0.06–4.76 ng g − 1 d.w.) and perfluorooctanoate (PFOA) (mean 0.42 ng g − 1 ; range 0.02–2.52 ng g − 1 d.w.). PFOS levels in sediments at 19 of 36 sites (representing 52% of the study area) exceeded the published global median PFOS sediment concentration of 0.54 ng g − 1 . [ABSTRACT FROM AUTHOR]

ABSTRACT Polybrominated diphenyl ethers (PBDEs) are an emerging contaminant of concern with low level exposures demonstrating toxicity in laboratory animals and wildlife, although immunotoxicity studies have been limited. Bottlenose dolphin peripheral blood leukocytes (PBLs) and mouse splenocytes were exposed to environmentally relevant DE-71 (a penta-PBDE mixture) concentrations (0-50 µg ml−1) in vitro. Natural killer (NK) cell activity and lymphocyte (B and T cell) proliferation were evaluated using the parallelogram approach for risk assessment. This study aimed to substantiate results from field studies with dolphins, assess the sensitivities between the mouse model and dolphins, and to evaluate risk using the parallelogram approach. In mouse cells, NK cell activity increased at in vitro doses 0.05, 0.5 and 25 µg DE-71 ml−1, whereas proliferation was not modulated. In dolphin cells, NK cell activity and lymphocyte proliferation was not altered after in vitro exposure. In vitro exposure of dolphin PBLs to DE-71 showed similar results to correlative field studies; NK cell activity in mice was more sensitive to in vitro exposure than dolphins, and the parallelogram approach showed correlation with all three endpoints to predict risk in bottlenose dolphins. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The past year has seen attention directed, both in policy discourse and the media, towards the implication of Central African non-state armed groups in poaching and ivory trafficking. Engaging with both mainstream political economy analyses and work on the "geographies of resource wars," this paper turns to the case of ivory as a "conflict resource," through the case study of the Lord's Resistance Army. It begins by outlining the contextual specificities and conditions of access, before assessing the compatibility of the resource's biophysical, spatial and material characteristics with the needs of regional armed groups and the LRA in particular. Though the direction of causality is difficult to untangle, the paper finds that poaching and the trade in ivory by armed groups in Central Africa appears to incur low opportunity costs for relatively high potential gains. Moreover, that ivory qualifies as a "conflict resource" under Le Billon's (2008) definition in the extent to which it is likely to be implicated in the duration of conflict in the region, both financing and benefitting from a context of insecurity. Future research would benefit from more accessible and robust data; interesting avenues would include an evaluation of the effects of the increasing militarization of poaching strategies - including shoot-to-kill policies - and the potential of igniting grievance-based conflict. [ABSTRACT FROM AUTHOR]

ABSTRACT Previous studies in our lab have shown that perfluorooctane sulfonate (PFOS) modulates immune function in mice and correlates with many immune parameters in bottlenose dolphins ( Tursiops truncatus). In this study, bottlenose dolphin peripheral blood leukocytes (PBLs) and adult female B6C3F1 mouse splenocytes were exposed to environmentally relevant PFOS concentrations (0-5 µg ml-1) in vitro; and natural killer (NK) cell activity and lymphocyte proliferation (T and B cell) were assessed using the parallelogram approach for risk assessment. The objectives were: to corroborate results from the correlative studies in bottlenose dolphins with in vitro PFOS exposures; to evaluate the sensitivity of the mouse model as compared with bottlenose dolphins; and to assess risk using the parallelogram approach. In mouse cells, NK cell activity was decreased at in vitro doses of 0.01, 0.5, 0.1, 0.5 and 1 µg PFOS ml-1 and increased at 5 µg ml-1. Additionally, B cell proliferation was not altered, but T cell proliferation was decreased at all in vitro PFOS exposures. In dolphin cells, NK cell activity and T cell proliferation were not altered by in vitro PFOS exposure, but B cell proliferation exhibited a positive association in relation to PFOS dose. Overall, the data indicates that: the in vitro exposures of bottlenose dolphin PBLs exhibited results similar to reported correlative fields studies; that mice were generally more sensitive (for these selected endpoints) than were dolphins; and that the parallelogram approach could be used two-thirds of the time to predict the effects in bottlenose dolphins. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses the technology fund usage scheme that the University of Central Florida (UCF) employed in order to augment funds for the acquisition of library materials. An overview of the process wherein it starts with the selected library departments submitting a proposal which is to be approved by each university college is discussed. A list of winning proposals that have been funded by the technology fee is also presented.

The article discusses how a 2007 Florida state law permitting state universities to collect technology fees from students impacted the library collection process at the University of Central Florida (UCF). It examines how a review committee is established each year to determine how the funds should be distributed, with over $1.2 million in funding dedicated to purchasing library materials since 2009. According to the authors, the fee process has influenced how the UCF libraries select online materials as well as how content is acquired and delivered. Specific attention is given to the acquisition of electronic books (eBooks).

Abstract Concentrations of 11 PFASs were determined in muscle and whole fish for six species collected from Charleston, South Carolina (SC) for the assessment of potential health risks to humans and wildlife. Across all species and capture locations, total PFAS levels in whole fish were significantly higher than fillets by a factor of two- to three-fold. Mean ∑PFAS concentrations varied from 12.7 to 33.0 ng/g wet weight (ww) in whole fish and 6.2–12.7 ng/g ww in fillets. For individual whole fish, ∑PFASs ranged from 12.7 ng/g ww in striped mullet to 85.4 ng/g ww in spotted seatrout, and in fillets individual values ranged from 6.2 ng/g ww in striped mullet to 27.9 ng/g ww in spot. The most abundant compound in each species was perfluorooctane sulfonate (PFOS), comprising 25.5–69.6% of the ∑PFASs. Striped mullet had significantly lower relative amounts of PFOS compared to all other species and higher relative amounts of PFUnDA compared to Atlantic croaker, spotted seatrout, and spot. Unlike whole fish, PFAS levels in fillets varied significantly by location with higher ∑PFOS from the Ashley River than the Cooper River and Charleston Harbor, which reflects the levels of PFASs contamination in these systems. In whole fish, differences in relative concentrations of PFOS, PFNA, and PFDA occurred by capture location, suggestive of different sources. PFOS concentrations for southern flounder and spotted seatrout fillets were within the advisory range to limit fish consumption to 4 meals a month. PFOS levels exceeded screening values to protect mammals in 83% of whole fish examined and represent a potential risk to wildlife predators such as dolphins. Graphical abstract fx1 Highlights • Accumulation of PFASs in wild fish was investigated in a highly urbanized southeast U.S. region. • PFOS was predominant PFAS compound in fish muscle and whole fish. • ∑PFAS concentrations were higher in whole fish than fillets by 2–3X. • Frequent consumption of wild fish may pose health risks to local population. • PFOS levels exceeded wildlife protective guidelines in 83% of whole fish, a concern for dolphins. [ABSTRACT FROM AUTHOR]

Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes, or dendritic cells. Neutrophil rebound after anti-Gr-1-induced neutropenia was blunted during hypoferremia but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically stimulated granulopoiesis mediated by granulocyte colony-stimulating factor and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial reactive oxygen species-dependent NETosis associated with chronic inflammation. Notably, antagonizing endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system.

Polychlorinated biphenyls (PCBs) have been assessed for immunotoxicity; however, humans and wildlife are exposed to multiple PCBs environmentally. Therefore, the aim of this study was to examine the effects of a complex 37 PCB congener mixture identified in blubber specific to dolphins residing in the estuarine waters of Charleston, South Carolina. Immunotoxicity was determined in adult female B 6 C 3 F 1 mice by assessing lymphocyte proliferation, splenic and thymic immunophenotypes, and IgM production. Mice were exposed via oral gavage to the PCB-mixture (0, 1.8, 3.6, 7.1, or 14.3 mg/kg/day) for 28 days to yield a targeted total administered dose (TAD) 0, 50, 100, 200, or 400 mg/kg. Significant increased liver weight occurred at the highest treatment. IgM production was suppressed compared to control for all treatments. Numbers of thymic CD4+/CD8+, CD4-/CD8-, and CD4+/CD8- cells were not altered, but numbers of thymic CD4-/CD8+ cells were significantly increased in the highest treatment. Lymphocyte proliferation was not markedly affected by any treatment. The numbers of splenic CD4/CD8 T-cells or MHCII+ cells were not significantly changed. Humoral immunity using the plaque-forming cell assay for determining the specific IgM antibody-forming cell response appeared to be the most sensitive endpoint affected. As the lowest concentration tested resulted in decreased IgM production and total and free thyroxine (T 4 ) serum levels a NOAEL was not identified. The calculated ED 50 for suppression of IgM production was 2.4 mg/kg/day.

Objectives: To review how disasters introduce unique challenges to conducting population-based research and community-based participatory research (CBPR)., Methods: From 2007-2009, we conducted the Head-off Environmental Asthma in Louisiana (HEAL) Study in the aftermath of Hurricane Katrina in a Gulf Coast community facing an unprecedented triple burden: Katrina's and other disasters' impact on the environment and health, historic health disparities, and persistent environmental health threats., Results: The unique triple burden influenced every research component; still, most existing CBPR principles were applicable, even though full adherence was not always feasible and additional tailored principles govern postdisaster settings., Conclusions: Even in the most challenging postdisaster conditions, CBPR can be successfully designed, implemented, and disseminated while adhering to scientific rigor.

The chemokine, stromal-derived factor-1/CXCL12, is expressed by normal and neoplastic tissues and is involved in tumor growth, metastasis, and modulation of tumor immunity. T cell-mediated tumor immunity depends on the migration and colocalization of CTL with tumor cells, a process regulated by chemokines and adhesion molecules. It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis. We proposed that repulsion of tumor Ag-specific T cells from a tumor expressing high levels of CXCL12 allows the tumor to evade immune control. Murine B16/OVA melanoma cells (H2b) were engineered to constitutively express CXCL12. Immunization of C57BL/6 mice with B16/OVA cells lead to destruction of B16/OVA tumors expressing no or low levels of CXCL12 but not tumors expressing high levels of the chemokine. Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100. Memory OVA-specific CD8+ T cells demonstrated antitumor activity against B16/OVA tumors but not B16/OVA.CXCL12-high tumors. Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner. The repulsion of tumor Ag-specific T cells away from melanomas expressing CXCL12 confirms the chemorepellent activity of high concentrations of CXCL12 and may represent a novel mechanism by which certain tumors evade the immune system.

Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both S1P-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62L(high) and CD69(low) recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4 signaling was only partially overcome by the addition of the extrathymic chemoattractant S1P and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus.