Cellular iron governs the host response to malaria.

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.

Ancient genomic linkage couples metabolism with erythroid development.

Generation of mature cells from progenitors requires tight coupling of differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material and enucleate to produce erythrocytes. has remained in synteny with the α-globin genes for >500 million years, and harbours the majority of the α-globin enhancers.

Plasma iron controls neutrophil production and function.

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.

IMPACT OF RETINAL ISCHEMIA ON FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN PATIENTS WITH RETINAL VEIN OCCLUSION.

Purpose: To compare the impact of the classification of retinal vein occlusion (RVO) into ischemic or nonischemic forms on outcomes after anti-vascular endothelial growth factor therapy.

Methods: Retrospective review of consecutive patients with RVO evaluated at the Belfast Health and Social Care Trust between July 1, 2014, and December 31, 2015. Outcomes, including gain of ≥10 and ≥15 letters at 12 months, mean change in best-corrected visual acuity from baseline to 12 months, resolution of macular edema at 12 months, and development of neovascular complications and epiretinal membrane after anti-vascular endothelial growth factor therapy, were compared between ischemic and nonischemic eyes using regression models.

Perfluoroalkyl substances (PFASs) in edible fish species from Charleston Harbor and tributaries, South Carolina, United States: Exposure and risk assessment.

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.

Persistent organic pollutants in fish from Charleston Harbor and tributaries, South Carolina, United States: A risk assessment.

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.

The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus).

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.

Environmental perfluorooctane sulfonate exposure drives T cell activation in bottlenose dolphins.

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.

Elevated levels of perfluoroalkyl substances in estuarine sediments of Charleston, SC.

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.

In vitro exposure of DE-71, a penta-PBDE mixture, on immune endpoints in bottlenose dolphins (Tursiops truncatus) and B6C3F1 mice.

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.

In vitro PFOS exposure on immune endpoints in bottlenose dolphins (Tursiops truncatus) and mice.

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.

Murine B16 melanomas expressing high levels of the chemokine stromal-derived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control.

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.

A CXCR4-dependent chemorepellent signal contributes to the emigration of mature single-positive CD4 cells from the fetal thymus.

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.

Overexpectation: response loss during sustained stimulus compounding in the rabbit nictitating membrane preparation.

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.

Extinction revisited: similarities between extinction and reductions in US intensity in classical conditioning of the rabbit's nictitating membrane response.

The mechanisms of extinction were examined by reducing the intensity of the unconditioned stimulus (US) after acquisition training to determine whether such reductions lie on a continuum with CS-alone extinction. The experiments revealed that reductions in US intensity yielded extinction-like effects. Specifically, there were proportional reductions in the daily mean level of responding across sessions.