Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Photocatalytic activity of exfoliated graphite-TiO2_2 nanocomposites

We investigate the photocatalytic performance of composites prepared in a one-step process by liquid-phase exfoliation of graphite in the presence of TiO2 nanoparticles (NPs) at atmospheric pressure and in water, without heating or adding any surfactant, and starting from low-cost commercial reagents. These show enhanced photocatalytic activity, degrading up to 40% more pollutants with respect to the starting TiO2-NPs, in the case of a model dye target, and up to 70% more pollutants in the case of nitrogen oxides. In order to understand the photo-physical mechanisms underlying this enhancement, we investigate the photo-generation of reactive species (trapped holes and electrons) by ultrafast transient absorption spectroscopy. We observe an electron transfer process from TiO2 to the graphite flakes within the first picoseconds of the relaxation dynamics, which causes the decrease of the charge recombination rate, and increases the efficiency of the reactive species photo-production.We acknowledge funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 785219 (GrapheneCore2), EU Neurofibres, ERC Minegrace and Hetero2D, EPSRC Grants EP/509K01711X/1, EP/K017144/1, EP/N010345/1, EP/M507799/5101, and EP/L016087/1

Discovery of permuted and recently split transfer RNAs in Archaea

Background: As in eukaryotes, precursor transfer RNAs in Archaea often contain introns that are removed in tRNA maturation. Two unrelated archaeal species display unique pre-tRNA processing complexity in the form of split tRNA genes, in which two to three segments of tRNAs are transcribed from different loci, then trans-spliced to form a mature tRNA. Another rare type of pre-tRNA, found only in eukaryotic algae, is permuted, where the 3 ’ half is encoded upstream of the 5 ’ half, and must be processed to be functional. Results: Using an improved version of the gene-finding program tRNAscan-SE, comparative analyses and experimental verifications, we have now identified four novel trans-spliced tRNA genes, each in a different species of the Desulfurococcales branch of the Archaea: tRNA Asp(GUC) in Aeropyrum pernix and Thermosphaera aggregans, and tRNA Lys(CUU) in Staphylothermus hellenicus and Staphylothermus marinus. Each of these includes features surprisingly similar to previously studied split tRNAs, yet comparative genomic context analysis and phylogenetic distribution suggest several independent, relatively recent splitting events. Additionally, we identified the first examples of permuted tRNA genes in Archaea: tRNA iMet(CAU) and tRNA Tyr(GUA) in Thermofilum pendens, which appear to be permuted in the same arrangement seen previously in red alga. Conclusions: Our findings illustrate that split tRNAs are sporadically spread across a major branch of the Archaea

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

Transmission Heterogeneity and Control Strategies for Infectious Disease Emergence

The control of emergence and spread of infectious diseases depends critically on the details of the genetic makeup of pathogens and hosts, their immunological, behavioral and ecological traits, and the pattern of temporal and spatial contacts among the age/stage-classes of susceptible and infectious host individuals.We show that failing to acknowledge the existence of heterogeneities in the transmission rate among age/stage-classes can make traditional eradication and control strategies ineffective, and in some cases, policies aimed at controlling pathogen emergence can even increase disease incidence in the host. When control strategies target for reduction in numbers those subsets of the population that effectively limit the production of new susceptible individuals, then control can produce a flush of new susceptibles entering the population. The availability of a new cohort of susceptibles may actually increase disease incidence. We illustrate these general points using Classical Swine Fever as a reference disease.Negative effects of culling are robust to alternative formulations of epidemiological processes and underline the importance of better assessing transmission structure in the design of wildlife disease control strategies

Neoadjuvant multidrug chemotherapy including High-Dose Methotrexate modifies VEGF expression in Osteosarcoma: an immunohistochemical analysis

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays a role in the progression of osteosarcoma, as well as in other mesenchymal tumors and carcinomas, and it is most commonly assessed by vascular endothelial growth factor (VEGF) expression or tumor CD31-positive microvessel density (MVD). Tumor VEGF expression is predictive of poor prognosis, and chemotherapy can affect the selection of angiogenic pattern. The aim of the study was to investigate the clinical and prognostic significance of VEGF and CD31 in osteosarcoma, both at diagnosis and after neoadjuvant chemotherapy, in order to identify a potential role of chemotherapy in angiogenic phenotype.</p> <p>Methods</p> <p>A retrospective analysis was performed on 16 patients with high grade osteosarcoma. In each case archival pre-treatment biopsy tissue and post-chemotherapy tumor specimens were immunohistochemically stained against CD31 and VEGF, as markers of angiogenic proliferation both in newly diagnosed primary osteosarcoma and after multidrug chemotherapy including high-dose methotrexate (HDMTX). The correlation between clinicopathological parameters and the degree of tumor VEGF and CD31 expression was statistically assessed using the χ²test verified with Yates' test for comparison of two groups. Significance was set at <it>p </it>< 0,05.</p> <p>Results</p> <p>Expression of VEGF was positive in 11 cases/16 of cases at diagnosis. Moreover, 8 cases/16 untreated osteosarcomas were CD31-negative, but the other 8 showed an high expression of CD31. VEGF expression in viable tumor cells after neoadjuvant chemotherapy was observed in all cases; in particular, there was an increased VEGF expression (post-chemotherapy VEGF - biopsy VEGF) in 11 cases/16. CD31 expression increased in 11 cases/16 and decreased in 3 cases after chemotherapy. The data relating to the change in staining following chemotherapy appear statistically significant for VEGF expression (<it>p </it>< 0,05), but not for CD31 (<it>p </it>> 0,05).</p> <p>Conclusions</p> <p>Even if the study included few patients, these results confirm that VEGF and CD31 expression is affected by multidrug chemotherapy including HDMTX. The expression of angiogenic factors that increase microvessel density (MVD) can contribute to the penetration of chemotherapeutic drugs into the tumor in the adjuvant stage of treatment. So VEGF could have a paradoxical effect: it is associated with a poor outcome but it could be a potential target for anti-angiogenic therapy.</p

Comparison of Epithelial Differentiation and Immune Regulatory Properties of Mesenchymal Stromal Cells Derived from Human Lung and Bone Marrow

Mesenchymal stromal cells (MSCs) reside in many organs including lung, as shown by their isolation from fetal lung tissues, bronchial stromal compartment, bronchial-alveolar lavage and transplanted lung tissues. It is still controversial whether lung MSCs can undergo mesenchymal-to-epithelial-transition (MET) and possess immune regulatory properties. To this aim, we isolated, expanded and characterized MSCs from normal adult human lung (lung-hMSCs) and compared with human bone marrow-derived MSCs (BM-hMSCs). Our results show that lung-MSCs reside at the perivascular level and do not significantly differ from BM-hMSCs in terms of immunophenotype, stemness gene profile, mesodermal differentiation potential and modulation of T, B and NK cells. However, lung-hMSCs express higher basal level of the stemness-related marker nestin and show, following in vitro treatment with retinoic acid, higher epithelial cell polarization, which is anyway partial when compared to a control epithelial bronchial cell line. Although these results question the real capability of acquiring epithelial functions by MSCs and the feasibility of MSC-based therapeutic approaches to regenerate damaged lung tissues, the characterization of this lung-hMSC population may be useful to study the involvement of stromal cell compartment in lung diseases in which MET plays a role, such as in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Characterization of highly frequent epitope-specific CD45RA(+)/CCR7(+/- )T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors

Human polyomavirus BK (BKV) has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag) to products of tumor-suppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. Peptides selected from either p53-binding region (LTag(351–450 )and LTag(533–626)) by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture. We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag(579–587); LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations. These data indicate that widespread cellular immune responses against epitopes within BKV LTag-p53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection