The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention.

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only neurotypical adults imitated atypical biological kinematics. Adults with autism did, however, become significantly more accurate at imitating movement time. This confirmed they engaged in the task, and that sensorimotor adaptation was self-regulated. The attentional bias to movement time suggests the attenuation in imitating kinematics might be a compensatory strategy due to deficits in lower-level visuomotor processes associated with self-other mapping, or selective attention modulated the processes that represent biological kinematics

Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans

Aims Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions. Methods and results Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species. Conclusions Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI

Resource heterogeneity and community structure: A case study in Heliconia imbricata Phytotelmata

Complex or non-additive differences in the distribution and abundance of arthropod species inhabiting the water-filled bracts of Heliconia imbricata can be created by simple manipulations of resource levels. The primary resources for these assemblages are the corollas of the flowers that accumulate in the bracts. Removing or adding corollas to individual bracts changes the pattern in the abundance of arthropod species within each bract such that bracts with different treatments ultimately differ in composition and numerical associations among species. These results suggest that direct and indirect resource-mediated factors can structure or significantly affect the distribution and abundance of species in these and perhaps other assemblages. Thus, in natural communities, if resources are heterogeneous among patches (such as among the bracts in this study) structure in a given patch may be a function of the resource level of that patch and can differ significantly from neighboring patches that provide different resource levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47788/1/442_2004_Article_BF00665591.pd

Interrogating host immunity to predict treatment response in inflammatory bowel disease

IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting different aspects of the immune response. Three novel classes of drugs have emerged in the past decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so it is desirable to develop personalized strategies to identify which patients should be treated with which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and alternative modalities are now needed to deliver precision medicine in IBD. High-resolution profiling of immune response networks in individual patients is a promising approach and different technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and germline genetics, are promising tools to help predict responses to specific therapies. However, important challenges remain regarding the clinical utility of these technologies, including their scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy

GPR109A and Vascular Inflammation

GPR109A has generated expanding interest since its discovery as the receptor for niacin a decade ago, along with deorphanisation as the receptor for endogenous ligand 3-hydroxy-butyrate shortly after. This interest is generated especially because of the continuing exploration of niacin's "pleiotropic" mechanisms of action and its potential in the "cross-talk" between metabolic and inflammatory pathways. As GPR109A's primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins. However, it has become apparent that niacin also possesses lipoprotein-independent effects that influence inflammatory pathways mediated through GPR109A. In addition to its G-protein-mediated effects, recent evidence has emerged to support alternative GPR109A signalling via adaptive protein β-arrestins. In this article, we consider the role of GPR109A and its downstream effects in the context of atherosclerosis and vascular inflammation, along with insights into strategy for future drug development. © 2013 The Author(s)

Nicotinic acid and the prevention of coronary artery disease.

PURPOSE OF REVIEW: Nicotinic acid is the most potent treatment clinically available for lowering LDL cholesterol and VLDL cholesterol and raising HDL cholesterol. The strong inverse relationship between coronary heart disease risk and HDL cholesterol at all levels of LDL cholesterol has, therefore, given renewed emphasis on the therapeutic potential of niacin. The purpose of this review is to evaluate advances in the elucidation of mechanisms by which nicotinic acid affects the lipoprotein profile and, more recently, emerging evidence of nonlipid-mediated anti-inflammatory effects. RECENT FINDINGS: Niacin treatment reduces cardiovascular events and the progression of atherosclerosis. Identification of G-protein-coupled receptor 109A as the receptor for nicotinic acid has provided insights into how treatment with this compound leads to a favourable alteration in HDL cholesterol. In addition, evidence of nonlipid-mediated anti-inflammatory effects of nicotinic acid such as direct enhancement of adiponectin secretion demonstrates a novel atheroprotective role. SUMMARY: Whether nicotinic acid use becomes routine in the treatment of atherosclerosis is likely to be determined by the results of two ongoing clinical outcome trials. In addition, further research is required to explore the 'pleiotropic' effects of nicotinic acid and will ultimately provide a platform for the development of newer molecules that are potentially beneficial but without the well known side-effects

Niacin in cardiovascular disease: recent preclinical and clinical developments.

Niacin has been used for more than 50 years in the treatment of cardiovascular disease, although its use has largely been superseded by better-tolerated lipid-modulating interventions. There has been a renewed interest in the HDL-cholesterol raising properties of niacin, with the appreciation that substantial cardiovascular risk remains despite effective treatment of LDL-cholesterol. This coincides with increasing evidence that the complex functional properties of HDL are not well reflected by measurement of HDL-cholesterol alone. In addition to favorable actions on lipoproteins, it is becoming apparent that niacin may also possess lipoprotein independent or pleiotropic effects including the inhibition of inflammatory pathways mediated by its receptor GPR109A, which is expressed by adipocytes and some leukocytes. In this article we consider emerging and prior clinical trial data relating to niacin. We review recent data in respect of mechanisms of action on lipoproteins, which remain complex and incompletely understood. We discuss the recent reports of anti-inflammatory effects of niacin in adipocytes and through bone marrow derived cells and vascular endothelium. These novel observations come at an interesting time, with current imaging and outcome studies leaving outstanding questions on niacin efficacy in statin-treated patients