In the eye of the storm: T cell behavior in the inflammatory microenvironment.

Coordinated unfolding of innate and adaptive immunity is key to the development of protective immune responses. This functional integration occurs within the inflamed tissue, a microenvironment enriched with factors released by innate and subsequently adaptive immune cells and the injured tissue itself. T lymphocytes are key players in the ensuing adaptive immunity and their proper function is instrumental to a successful outcome of immune protection. The site of inflammation is a "harsh" environment in which T cells are exposed to numerous factors that might influence their behavior. Low pH and oxygen concentration, high lactate and organic acid content as well as free fatty acids and reactive oxygen species are found in the inflammatory microenvironment. All these components affect T cells as well as other immune cells during the immune response and impact on the development of chronic inflammation. We here overview the effects of a number of factors present in the inflammatory microenvironment on T cell function and migration and discuss the potential relevance of these components as targets for therapeutic intervention in autoimmune and chronic inflammatory diseases

Polyunsaturated fatty acid-derived lipid mediators and T cell function

Copyright © 2014 Nicolaou, Mauro, Urquhart and Marelli-Berg . This is an open- access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Polyunsaturated fatty acid-derived lipid mediators and T cell function

Copyright © 2014 Nicolaou, Mauro, Urquhart and Marelli-Berg . This is an open- access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Metabolic syndrome and the immunological affair with the blood-brain barrier

Copyright © 2015 Mauro, De Rosa, Marelli-Berg and Solito. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

A Fourier transform for sheaves on Lagrangian families of real tori

We systematically develop a transform of the Fourier-Mukai type for sheaves on symplectic manifolds $X$ of any dimension fibred in Lagrangian tori. One obtains a bijective correspondence between unitary local systems supported on Lagrangian submanifolds of $X$ and holomorphic vector bundles with compatible unitary connections supported on complex submanifolds of the relative Jacobian of $X$ (suitable conditions being verified on both sides).Comment: Latex, 30 pages (in a4wide format), no figures. v2: Minor expository changes, typos corrected. v3: Final version to appear in two parts in J. Geom. Phy

dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism

Congenital hypothyroidism (CH) is the most frequent endocrinopathy in newborn. If not promptly treated lead to a severe impairment of psychomotor development. The etiophatogenesis of CH is still poorly understood; although several causative genes are identified, they can explain only a small portion of the pathological phenotypes. This scenario is further complicated if we focused on the incidence of CH in different context. In fact, epidemiological data indicate that children born prematurely have a 3-5 fold higher risk of CH. In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report that aberrant methylation patterns are associated with prematurity, intrauterine fetal development and the onset of some diseases. This project is focused on the study of DNA methylation, as predisposing factor to permanent thyroid dysfunction with neonatal onset. Using the Illumina Infinium-HumanMethylation27 technology we analyzed the global DNA methylation patterns (AVG\uf062) and selected the differentially methylated genes (DMGs) between 31 CH-cases born premature, AGA or SGA, and 28 term or preterm controls. To better understand the relationship between the DNA methylation and the premature birth, the intrauterine growth and the thyroid defect, the following groups were selected according to the gestational age at birth: 12 CH-with very preterm birth (CH-VPB37wks). The same subjects were then analyzed according to intrauterine growth (20 CH-SGA, 11 CH-AGA than 6 C-SGA and 20 C-AGA) or the degree of CH: 19 with overt CH (OH, TSH>10 \uf06dU/L) and 12 with mild CH (MH, TSH<10 \uf06dU/L) than 16 CPB and 12 CTB. The global methylation analysis showed that infants born prematurely and SGA have a significant hypomethylation than term-controls. These data were confirmed by the gene-specific methylation analysis, through which we selected a large group of differentially methylated genes (DMGs) in CH-cases than term controls. Interestingly, the 95% of the DMGs are hypomethylated and the 70% of them are represented by CpG sites located in DNA non-coding regions. The gene ontology analysis revealed that genes involved in fetal growth and thyroid hormone metabolism were included among DMGs. The analysis of nine maternal genomic DNA for polymorphisms at the MTHFR revealed the possible association with folate deficiency during pregnancy and the global hypomethylation status of affected newborns. This is the first work exploring the role of epigenetic influences in the predisposition to congenital hypothyroidism. Our results suggest that genomic instability caused by global hypomethylation of non-coding regions may be related to premature birth and fetal growth delay. Under these conditions, thyroid defects are more frequent than expected and could result from the increased expression of predisposing genes, rather than from the reduced expression of protective genes. The role of maternal conditions during pregnancy seems to be a key factor to determine a proper DNA methylation pattern on fetus. Based on the Developmental Origin of Health and Disease Theory, we can assume that adverse condition during pregnancy, such as folate deficiency, may produce a fetal epigenetic reprogramming and the adaptation of preterm neonate to the extrauterine life includes among other dysfunctions a thyroid functional impairment. If this data will be confirmed by further experiments, this could represent a new predisposing factor to take into account during pregnancy to prevent and improve the prenatal screening of CH

Large Binocular Telescope observations of PSR J2043+2740

We present the results of deep optical imaging of the radio/$\gamma$-ray pulsar PSR J2043+2740, obtained with the Large Binocular Telescope (LBT). With a characteristic age of 1.2 Myr, PSR J2043+2740 is one of the oldest (non recycled) pulsars detected in $\gamma$-rays, although with still a quite high rotational energy reservoir ($\dot{E}_{\rm rot} = 5.6 \times 10^{34}$ erg s$^{-1}$). The presumably close distance (a few hundred pc), suggested by the hydrogen column density ($N_{\rm H} \lesssim 3.6 \times 10^{20}$ cm$^{-2}$), would make it a viable target for deep optical observations, never attempted until now. We observed the pulsar with the Large Binocular Camera of the LBT. The only object (V=25.44$\pm$0.05) detected within ~3" from the pulsar radio coordinates is unrelated to it. PSR J2043+2740 is, thus, undetected down to V~26.6 (3-$\sigma$), the deepest limit on its optical emission. We discuss the implications of this result on the pulsar emission properties.Comment: 4 pages, 3 figures, accepted for publication on MNRA

X-ray pulsations from the radio-quiet gamma-ray pulsar in CTA 1

Prompted by the Fermi LAT discovery of a radio-quiet gamma-ray pulsar inside the CTA 1 supernova remnant, we obtained a 130 ks XMM-Newton observation to assess the timing behavior of this pulsar. Exploiting both the unprecedented photon harvest and the contemporary Fermi LAT timing measurements, a 4.7 sigma single peak pulsation is detected, making PSR J0007+7303 the second example, after Geminga, of a radio-quiet gamma-ray pulsar also seen to pulsate in X-rays. Phase-resolved spectroscopy shows that the off-pulse portion of the light curve is dominated by a power-law, non-thermal spectrum, while the X-ray peak emission appears to be mainly of thermal origin, probably from a polar cap heated by magnetospheric return currents, pointing to a hot spot varying throughout the pulsar rotation.Comment: 19 pages, 4 figures. Accepted for publication in ApJ Letter