An Old Story Retold: Loss of G1 Control Defines A Distinct Genomic Subtype of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma(ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration(CNA) and loss of heterozygosity(LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations(NSSMs) in102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology(GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B(30.9%), amplification of 11q13.3 covering CCND1(30.9%), and TP53 point mutation(50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC.Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes.These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.     

Two new species of Neosartorya isolated from soil in Xinjiang, China

Two new species, Neosartorya shendaweii and N. tsunodae, isolated from soil in Xinjing, China and in Pernambuco, Brazil, are described and illustrated. The first species is characterized by its ascospores with two widely separated equatorial crests and tuberculate to verrucose convex surfaces. This species has affinities with several known species of the genus, bearing ascospores with a similar ornamentation, but can be distinguished from these species by other morphological characteristics such as smaller cleistothecia and conidiophores, spathulate vesicles and rather ellipsoidal conidia. The second species is characterized by its unique ascospores with two low equatorial crests, an evident furrow as a deep depression, and finely reticulate convex surfaces. The validation of these new species is supported further by analyses of the β-tubulin, calmodulin and actin gene sequences.     

Overlapping Genes May Control Reprogramming of Mouse Somatic Cells into Induced Pluripotent Stem Cells (iPSCs) and Breast Cancer Stem Cells

Recent findings suggest the possibility that tumors originate from cancer cells with stem cell properties. The cancer stem cell (CSC) hypothesis provides an explanation for why existing cancer therapies often fail in eradicating highly malignant tumors and end with tumor recurrence. Although normal stem cells and CSCs both share the capacity for self-renewal and multi-lineage differentiation, suggesting that CSC may be derived from normal SCs, the cellular origin of transformation of CSCs is debatable. Research suggests that the tightly controlled balance of self-renewal and differentiation that characterizes normal stem cell function is dis-regulated in cancer. Additionally, recent evidence has linked an embryonic stem cell (ESC)-like gene signature with poorly differentiated high-grade tumors, suggesting that regulatory pathways controlling pluripotency may in part contribute to the somatic CSC phenotype. Here, we introduce expression profile bioinformatic analyses of mouse breast cells with CSC properties, mouse embryonic stem (mES) and induced pluripotent stem (iPS) cells with an emphasis on how study of pluripotent stem cells may contribute to the identification of genes and pathways that facilitate events associated with oncogenesis. Global gene expression analysis from CSCs and induced pluripotent stem cell lines represent an ideal model to study cancer initiation and progression and provide insight into the origin cancer stem cells. Additionally, insight into the genetic and epigenomic mechanisms regulating the balance between self-renewal and differentiation of somatic stem cells and cancer may help to determine whether different strategies used to generate iPSCs are potentially safe for therapeutic use.     

Economic costs of invasive alien ants worldwide

Biological Invasions - Invasive ants are amongst the most destructive and widespread invaders across the globe; they can strongly alter invaded ecosystems and are responsible for the loss of native...     

New and interesting species ofEurotium from Chinese soil

Eurotium taklimakanense, a new species isolated from desert soil in the Taklimakan desert, Xinjiang Province, China, is described and illustrated. It is characterized by light yellow to reddish yellow colonies on Czapek's agar with 70% (w/v) sucrose, yellow ascomata, broadly lenticular ascospores with conspicuously irregular equatorial crests and tuberculate or verrucose convex surfaces, and anAspergillus anamorph.Eurotium cristatum is also described as a new record from China. It is characterized by light yellow colonies on Czapek's agar with 70% sucrose, yellow ascomata, broadly lenticular ascospores with two equatorial crests and echinulate convex surfaces, and small tuberculate conidia.     

Neosartorya takakii, a new species from soil in Brazil

Among the isolates from soil of grassland in Roraima State, Brazil, a new species ofNeosartorya, N. takakii is described and illustrated.Neosartorya takakii differs from the other known species of the genus in having lenticular ascospores with two distinct equatorial crests and with roughly circularly arranged projections on the convex walls. A comparative SEM view of ascospores from six relatedNeosartorya species is also provided.     

Two new heterothallicNeosartorya from African soil

Neosartorya nishimurae andN. otanii, two new heterothallic species isolated from African forest soil, are described and illustrated.Neosartorya nishimurae is characterized by its rapid growth on Czapek and malt extract agras, white cleistothecia, lenticular ascospores with two broad equatorial crests and echinulate convex surfaces, and large ellipsoidal conidia with a lobate-reticulate wall.Neosartorya otanii is characterized by its rapid growth on Czapek and malt extract agars, lenticular ascospores with two widely separated equatorial crests and tuberculate or lobate-reticulate convex surfaces, and globose to broadly ellipsoidal conidia with a micro-tuberculate wall.     

Human pathogenic fungus Trichophytonschoenleinii activates the NLRP3 inflammasome

The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1β. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1β production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1β secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1β secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K⁺ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.