CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses

CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response

Zinc in plants

Zinc (Zn) is an essential component of thousands of proteins in plants, although it is toxic in excess. In this review, the dominant fluxes of Zn in the soil-root-shoot continuum are described, including Zn inputs to soils, the plant availability of soluble Zn2+ at the root surface, and plant uptake and accumulation of Zn. Knowledge of these fluxes can inform agronomic and genetic strategies to address the widespread problem of Zn-limited crop growth. Substantial within-species genetic variation in Zn composition is being used to alleviate human dietary Zn deficiencies through biofortification. Intriguingly, a meta-analysis of data from an extensive literature survey indicates that a small proportion of the genetic variation in shoot Zn concentration can be attributed to evolutionary processes whose effects manifest above the family level. Remarkable insights into the evolutionary potential of plants to respond to elevated soil Zn have recently been made through detailed anatomical, physiological, chemical, genetic and molecular characterizations of the brassicaceous Zn hyperaccumulators Thlaspi caerulescens and Arabidopsis halleri

Molecular imaging of depressive disorders

This chapter summarizes findings of a large number of molecular imaging studies in the field of unipolar and bipolar depression (BD). Brain metabolism in depressed unipolar and bipolar patients is generally hypoactive in the middle frontal gyri, the pregenual and posterior anterior cingulate, the superior temporal gyrus, the insula, and the cerebellum, while hyperactivity exists in subcortical (caudate nucleus, thalamus), limbic (amygdala, anterior hippocampus), and medial and inferior frontal regions. Interestingly, after depletion of serotonin or noradrenalin/dopamine in vulnerable (recovered) major depressive disorder (MDD) patients, a similar response pattern in metabolism occurs. Findings on the pre-and postsynaptic dopaminergic system show indications that, at least in subgroups of retarded MDD patients, presynaptic dopaminergic markers may be decreased, while postsynaptic markers may be increased. The findings regarding serotonin synthesis, pre-and postsynaptic imaging can be integrated to a presumable loss of serotonin in MDD, while this remains unclear in BD. This reduction of serotonin and dopamine in MDD was recently summarized in a revised version of the monoamine hypothesis, which focuses more on a dysfunction at the level of the MAO enzyme. This should be addressed further in future studies. Nevertheless, it should be acknowledged that the serotonergic and dopaminergic systems appear adaptive; therefore, it remains difficult to distinguish state and trait abnormalities. Therefore, future longitudinal molecular imaging studies in the same subjects at different clinical mood states (preferably with different tracers and imaging modalities) are needed to clarify whether the observed changes in transporters and receptors are compensatory reactions or reflect different, potentially causal mechanisms. Several suggestions for future developments are also provided at the end of this chapter