Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

<p>Abstract</p> <p>Background</p> <p>Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy.</p> <p>Methods</p> <p>To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC.</p> <p>Results</p> <p>The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression.</p> <p>Conclusion</p> <p>This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.</p

Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

<p>Abstract</p> <p>Background</p> <p>Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.</p> <p>Methods</p> <p>By using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.</p> <p>Results</p> <p>There were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).</p> <p>Conclusions</p> <p>The present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.</p

The global abundance of tree palms

Aim: Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location: Tropical and subtropical moist forests. Time period: Current. Major taxa studied: Palms (Arecaceae). Methods: We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results: On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions: Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

S-nitrosothiols regulate nitric oxide production and storage in plants through the nitrogen assimilation pathway

Nitrogen assimilation plays a vital role in plant metabolism. Assimilation of nitrate, the primary source of nitrogen in soil, is linked to the generation of the redox signal nitric oxide (NO). An important mechanism by which NO regulates plant development and stress responses is through S-nitrosylation, that is, covalent attachment of NO to cysteine residues to form S-nitrosothiols (SNO). Despite the importance of nitrogen assimilation and NO signalling, it remains largely unknown how these pathways are interconnected. Here we show that SNO signalling suppresses both nitrate uptake and reduction by transporters and reductases, respectively, to fine tune nitrate homeostasis. Moreover, NO derived from nitrate assimilation suppresses the redox enzyme S-nitrosoglutathione Reductase 1 (GSNOR1) by S-nitrosylation, preventing scavenging of S-nitrosoglutathione, a major cellular bio-reservoir of NO. Hence, our data demonstrates that (S)NO controls its own generation and scavenging by modulating nitrate assimilation and GSNOR1 activity.5540

Active Packaging of Immobilized Zinc Oxide Nanoparticles Controls Campylobacter jejuni in Raw Chicken Meat

Zinc oxide nanoparticles (ZnO NPs) are regarded as a safe and stable antimicrobial that can inactivate bacteria by several potential working mechanisms. We aimed to incorporate ZnO NPs into packaging material to control Campylobacter in raw chicken meat. ZnO NPs were first incorporated into three-dimensional (3D) paper tubes to identify the lethal concentration against Campylobacter jejuni, which was selected as the working concentration to develop 2D functionalized absorbing pads by an ultrasound-assisted dipping technique. The functionalized pad was placed underneath raw chicken meat to inactivate C. jejuni and the predominant chicken microbiota at 4&deg;C within 8 days of storage. Immobilized ZnO NPs at 0.856&thinsp;mg/cm2 reduced C. jejuni from &sim;4 log CFU/25 g raw chicken meat to an undetectable level after 3 days of storage. Analysis by inductively coupled plasma-optical emission spectroscopy showed that the Zn level increased from 0.02 to 0.17&thinsp;mg/cm2 in treated raw chicken meat. Scanning electron microscopy validated the absence of nanoparticle migration onto raw chicken meat after treatment. Inactivation of C. jejuni was associated with the increase of lactic acid produced by Lactobacillus in raw chicken meat in a pH-dependent manner. Less than 5% of Zn2+ was released from ZnO NPs at neutral pH, while up to 88% was released when the pH was &lt;3.5 within 2 days. Whole-transcriptome sequencing (RNA-Seq) analysis demonstrated a broad effect of ZnO NPs on genes involved in various cellular developmental processes as annotated by gene ontology. Taken together, the results indicate that functionalized absorbing pads inactivated C. jejuni in raw chicken meat by immobilized ZnO NPs along with the controllable released Zn2+.IMPORTANCE Prevalence of Campylobacter in raw poultry remains a major food microbiological safety challenge. Novel mitigation strategies are required to ensure the safety and quality of poultry products. Active food packaging can control pathogens without directly adding antimicrobials into the food matrix and extend the food&rsquo;s shelf life. The functionalized absorbing pad with ZnO NPs developed in this study was able to inactivate C. jejuni in raw chicken meat and keep the meat free from C. jejuni contamination during shelf life without any observed migration of nanoparticles. The controllable conversion of immobilized ZnO NPs to free Zn2+ makes this approach safe and eco-friendly and paves the way for developing a novel intervention strategy for other high-risk foods. Our study applied nanotechnology to exploit an effective approach for Campylobacter control in raw chicken meat products.</jats:p