No relationship between 2',3'-cyclic nucleotide 3'-phosphodiesterase and schizophrenia in the Chinese Han population: an expression study and meta-analysis

<p>Abstract</p> <p>Background</p> <p>2',3'-Cyclic nucleotide 3'-phosphodiesterase (<it>CNP</it>), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. The present study aims to investigate the relationship between <it>CNP </it>and schizophrenia in the Chinese population and the effect of different factors on the expression level of <it>CNP </it>in schizophrenia.</p> <p>Methods</p> <p>Five <it>CNP </it>single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. The results were included in the following meta-analysis. Quantitative real-time polymerase chain reaction (PCR) was conducted to examine <it>CNP </it>expression levels in peripheral blood lymphocytes.</p> <p>Results</p> <p>Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the <it>CNP </it>gene in schizophrenia. Our meta-analysis produced similar negative results.</p> <p>Conclusion</p> <p>The results suggest that the <it>CNP </it>gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population.</p

New Strategy for Rapid Diagnosis and Characterization of Fungal Infections: The Example of Corneal Scrapings

PURPOSE: The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM) that a) detects yeasts and filamentous Fungi, b) differentiates yeasts from filamentous Fungi, and c) discriminates among relevant species of yeasts. METHODS: PCR-HRM detection limits and specificity were assessed with a) isolated strains; b) human blood samples experimentally infected with Fungi; c) blood experimentally infected with other infectious agents; d) corneal scrapings from patients with suspected fungal keratitis (culture positive and negative) and e) scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctor® HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC) and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT) and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT) and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. RESULTS: PCR-HRM detected 0.1 Colony Forming Units (CFU)/µl of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. CONCLUSIONS: PCR-HRM appears as a new, sensitive, specific and inexpensive test that detects Fungi and differentiates filamentous Fungi from yeasts. It allows direct fungal detection from clinical samples and experimentally infected blood in less than 2.30 h after DNA extraction

Natural radionuclide of Po210 in the edible seafood affected by coal-fired power plant industry in Kapar coastal area of Malaysia

<p>Abstract</p> <p>Background</p> <p>Po²¹⁰can be accumulated in various environmental materials, including marine organisms, and contributes to the dose of natural radiation in seafood. The concentration of this radionuclide in the marine environment can be influenced by the operation of a coal burning power plant but existing studies regarding this issue are not well documented. Therefore, the aim of this study was to estimate the Po²¹⁰concentration level in marine organisms from the coastal area of Kapar, Malaysia which is very near to a coal burning power plant station and to assess its impact on seafood consumers.</p> <p>Methods</p> <p>Concentration of Po²¹⁰was determined in the edible muscle of seafood and water from the coastal area of Kapar, Malaysia using radiochemical separation and the Alpha Spectrometry technique.</p> <p>Results</p> <p>The activities of Po²¹⁰in the dissolved phase of water samples ranged between 0.51 ± 0.21 and 0.71 ± 0.24 mBql^-1whereas the particulate phase registered a range of 50.34 ± 11.40 to 72.07 ± 21.20 Bqkg^-1. The ranges of Po²¹⁰activities in the organism samples were 4.4 ± 0.12 to 6.4 ± 0.95 Bqkg^-1dry wt in fish (<it>Arius maculatus</it>), 45.7 ± 0.86 to 54.4 ± 1.58 Bqkg^-1dry wt in shrimp (<it>Penaeus merguiensis</it>) and 104.3 ± 3.44 to 293.8 ± 10.04 Bqkg^-1dry wt in cockle (<it>Anadara granosa</it>). The variation of Po²¹⁰in organisms is dependent on the mode of their life style, ambient water concentration and seasonal changes. The concentration factors calculated for fish and molluscs were higher than the recommended values by the IAEA. An assessment of daily intake and received dose due to the consumption of seafood was also carried out and found to be 2083.85 mBqday^-1person^-1and 249.30 μSvyr^-1respectively. These values are comparatively higher than reported values in other countries. Moreover, the transformation of Po²¹⁰in the human body was calculated and revealed that a considerable amount of Po²¹⁰can be absorbed in the internal organs. The calculated values of life time mortality and morbidity cancer risks were 24.8 × 10^-4and 34 × 10^-4respectively which also exceeded the recommended limits set by the ICRP.</p> <p>Conclusions</p> <p>The findings of this present study can be used to evaluate the safety dose uptake level of seafood as well as to monitor environmental health. However, as the calculated dose and cancer risks were found to cross the limit of safety, finding a realistic way to moderate the risk is imperative.</p

Overexpression of Akt1 Enhances Adipogenesis and Leads to Lipoma Formation in Zebrafish

<div><h3>Background</h3><p>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the <em>Akt1</em> gene.</p> <h3>Methodology/Principal Findings</h3><p><em>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1</em>)^cy18 displays severely obese phenotypes at the adult stage. In Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.</p> <h3>Conclusion/Significance</h3><p>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.</p> </div

The atmospheric entry of fine-grained micrometeorites: The role of volatile gases in heating and fragmentation

The early stages of atmospheric entry are investigated in four large (250–950 lm) unmelted micrometeorites (three fine-grained and one composite), derived from the Transantarctic Mountain micrometeorite collection. These particles have abundant, interconnected, secondary pore spaces which form branching channels and show evidence of enhanced heating along their channel walls. Additionally, a micrometeorite with a doublewalled igneous rim is described, suggesting that some particles undergo volume expansion during entry. This study provides new textural data which links together entry heating processes known to operate inside micrometeoroids, thereby generating a more comprehensive model of their petrographic evolution. Initially, flash heated micrometeorites develop a melt layer on their exterior; this igneous rim migrates inwards. Meanwhile, the particle core is heated by the decomposition of low-temperature phases and by volatile gas release. Where the igneous rim acts as a seal, gas pressures rise, resulting in the formation of interconnected voids and higher particle porosities. Eventually, the igneous rim is breached and gas exchange with the atmosphere occurs. This mechanism replaces inefficient conductive rim-to-core thermal gradients with more efficient particle-wide heating, driven by convective gas flow. Interconnected voids also increase the likelihood of particle fragmentation during entry and, may therefore explain the rarity of large fine-grained micrometeorites among collections.Copyright © 2018, Suttle, M.D. et al. This document is the author’s final accepted version of the journal article. You are advised to consult the published version if you wish to cite from it

Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival