IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Tinkering with the C-Function: A Molecular Frame for the Selection of Double Flowers in Cultivated Roses

International audienc

Quantitative Control of Organ Shape by Combinatorial Gene Activity

A novel combination of molecular genetics, shape analysis, and computational modelling shows how the complex three-dimensional shape of the Snapdragon flower can arise through local gene activity

Cryptic Variation between Species and the Basis of Hybrid Performance

Studies on natural variation in gene expression and its phenotypic effects provide fresh insights into the origins of vigour and sterility in species hybrids

Dysregulated Recruitment of the Histone Methyltransferase EZH2 to the Class II Transactivator (CIITA) Promoter IV in Breast Cancer Cells

One mechanism frequently utilized by tumor cells to escape immune system recognition and elimination is suppression of cell surface expression of Major Histocompatibility Class II (MHC II) molecules. Expression of MHC II is regulated primarily at the level of transcription by the Class II Transactivator, CIITA, and decreased CIITA expression is observed in multiple tumor types. We investigate here contributions of epigenetic modifications to transcriptional silencing of CIITA in variants of the human breast cancer cell line MDA MB 435. Significant increases in histone H3 lysine 27 trimethylation upon IFN-γ stimulation correlate with reductions in transcription factor recruitment to the interferon-γ inducible CIITA promoter, CIITApIV, and with significantly increased CIITApIV occupancy by the histone methyltransferase enhancer of zeste homolog 2 (EZH2). Most compelling is evidence that decreased expression of EZH2 in MDA MB 435 variants results in significant increases in CIITA and HLA-DRA mRNA expression, even in the absence of interferon-γ stimulation, as well as increased cell surface expression of MHC II. Together, these data add mechanistic insight to prior observations of increased EZH2 expression and decreased CIITA expression in multiple tumor types

Progress Towards a Reference Genome for Sunflower

The Compositae is one of the largest and most economically important families of flowering plants and includes a diverse array of food crops, horticultural crops, medicinals, and noxious weeds. Despite its size and economic importance, there is no reference genome sequence for the Compositae, which impedes research and improvement efforts. We report on progress toward sequencing the 3.5 Gb genome of cultivated sunflower (Helianthus annuus), the most important crop in the family. Our sequencing strategy combines whole-genome shotgun sequencing using the Solexa and 454 platforms with the generation of high-density genetic and physical maps that serve as scaffolds for the linear assembly of whole-genome shotgun sequences. The performance of this approach is enhanced by the construction of a sequence-based physical map, which provides unique sequence-based tags every 5–6 kb across the genome. Thus far, our physical map covers ∼85% of the sunflower genome, and we have generated ∼80× genome coverage with Solexa reads and 15.5× with 454 reads. Preliminary analyses indicated that ∼78% of the sunflower genome consists of repetitive sequences. Nonetheless, ∼76% of contigs \u3e5 kb in size can be assigned to either the physical or genetic map or to both, suggesting that our approach is likely to deliver a highly accurate and contiguous reference genome for sunflower

Correção das deficiências transversas e ântero-posteriores da maxila em pacientes adultos Maxillary anteroposterior and transverse problems correction in adult patients

OBJETIVO: a finalidade deste trabalho é avaliar os resultados de tratamento de pacientes com desarmonias esqueléticas Classe III e discrepâncias transversas, tratados com a técnica de expansão maxilar assistida cirurgicamente, associada à mecânica de tração reversa. METODOLOGIA: Foram avaliados 10 pacientes portadores de Classe III esquelética e discrepância transversal, submetidos à expansão maxilar assistida cirurgicamente e ao uso de máscara facial. A avaliação das alterações ortodônticas e ortopédicas foram realizadas por meio dos exames clínico e radiográfico. CONCLUSÃO: os resultados clínicos e radiográficos demonstraram eficiência nestes procedimentos, evitando nova cirurgia de maxila, diminuindo a morbidade do tratamento e o seu custo.<br>AIM: The purpose of this article is to evaluate the correction of anteroposterior and transverse maxillary deficiency in adult patients with the use of facial mask and surgically assisted RME (SARME). METHODS: Reverse traction of the maxilla was applied to 10 subjects through a facial mask after a SARME. All individuals presented a Class III skeletal malocclusion. Cephalometric tracings were used to access the amount of anterior maxillary displacement during treatment. RESULTS AND CONCLUSION: The association of these procedures promoted transverse correction and anterior displacement of the maxilla. This approach avoided a two step correction - one for SARME and other for maxillary advancement, reducing morbidity and costs of treatment