Fire alters diversity, composition, and structure of dry tropical forests in the Eastern Ghats.

Fire is known to have dramatic consequences on forest ecosystems around the world and on the livelihoods of forest-dependent people. While the Eastern Ghats of India have high abundances of fire-prone dry tropical forests, little is known about how fire influences the diversity, composition, and structure of these communities. Our study aimed to fill this knowledge gap by examining the effects of the presence and the absence of recent fire on tropical dry forest communities within the Kadiri watershed, Eastern Ghats. We sampled plots with and without evidence of recent fire in the Eswaramala Reserve Forest in 2008 and 2018. Our results indicate that even though stem density increases in the recently burned areas, species richness is lower because communities become dominated by a few species with fire resistance and tolerance traits, such as thick bark and clonal sprouting. Further, in the presence of fire, the size structure of these fire-tolerant species shifts toward smaller-sized, resprouting individuals. Our results demonstrate that conservation actions are needed to prevent further degradation of forests in this region and the ecosystem services they provide.

Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells.

Human embryonal carcinoma (EC) cell lines exhibit considerable heterogeneity in their levels of pluripotency. Thus, NT2/D1 cells differentiate into neural lineages upon exposure to all-trans retinoic acid (ATRA) and non-neural epithelial lineages upon exposure to bone morphogenetic protein-2 (BMP-2). In contrast, 27X-1 cells differentiate into extra-embryonic endodermal (ExE) cells upon treatment with either morphogen. To understand the molecular basis for the differential responses of the two cell lines, we performed gene expression profiling at the undifferentiated EC cell line state to identify constitutive differences in gene expression. NT2/D1 cells preferentially expressed transcripts associated with neurectodermal development, whereas 27X-1 cells expressed high levels of transcripts associated with mesendodermal characteristics. We then determined temporal expression profiles of 27X-1 cells during ExE differentiation upon treatment with ATRA and BMP-2 and compared the data with changes in gene expression observed during BMP-2- and ATRA-induced differentiation of NT2/D1 cells. ATRA and BMP-2 induced distinct sets of transcription factors and phenotypic markers in the two EC cell lines, underlying distinct lineage choices. Although 27X-1 differentiation yielded comprehensive gene expression profiles of parietal endodermal lineages, we were able to use the combined analysis of 27X-1 data with data derived from yolk sac tumors for the identification of transcripts associated with visceral endoderm formation. Our results demonstrate constitutive differences in the levels of pluripotency between NT2/D1 and 27X-1 cells that correlate with lineage potential. This study also demonstrates that EC cells can serve as robust models to investigate early lineage choices during both embryonic and extra-embryonic human development.

Targeting von Hippel-Lindau pathway in renal cell carcinoma.

Inheritance of a defective copy of the von Hippel-Lindau (VHL) gene leads to the most common cause of inherited renal cell carcinoma (RCC). In addition, most patients with sporadic RCC have aberrant VHL. In the absence of VHL, hypoxia-inducible factor alpha accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. We review here the biology of RCC and how a combination of proximal and distal block of VHL/hypoxia-inducible factor alpha pathway by novel targeted agents, including sunitinib, sorafenib, bevacizumab, everolimus, and temsirolimus, has led to significant improvements in progression-free survival.

Transcriptional program associated with IFN-alpha response of renal cell carcinoma.

Metastatic renal cell carcinoma (RCC) is refractory to therapy; however, 10%-20% of patients respond favorably with interferon-alpha (IFN-alpha) treatment. To understand the molecular basis of response to IFN-alpha therapy, we performed global gene expression analysis of sensitive and resistant RCC cell lines in the absence and in the presence of IFN-alpha, using high-density oligonucleotide arrays to detect differentially expressed genes. In the absence of IFN-alpha, no significant differences in gene expression were observed between six sensitive and six resistant cell lines. Gene expression analysis following a time course of IFN-alpha2b treatment in one sensitive (SK-RC-17) and one resistant (SK-RC-12) cell line revealed that 484 and 354 transcripts, respectively, were modulated. A considerable number of these transcripts were similarly modulated between the two cell types that included several known targets of IFN signaling associated with antiviral and immunomodulatory activity. A further analysis of gene expression pattern in response to IFN revealed that several transcripts associated with proapoptotic function were upregulated in the sensitive cells. In the resistant cells, transcripts associated with cell survival and proliferation were induced, and key apoptotic molecules were suppressed. This study suggests that the IFN-alpha response of individual RCC tumors is determined by the expression pattern of genes in the apoptosis vs. survival and proliferation pathways rather than by alterations in expression of one or more individual genes.

Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors.

Adult male germ cell tumors (GCTs) comprise distinct groups: seminomas and nonseminomas, which include pluripotent embryonal carcinomas as well as other histologic subtypes exhibiting various stages of differentiation. Almost all GCTs show 12p gain, but the target genes have not been clearly defined. To identify 12p target genes, we examined Affymetrix (Santa Clara, CA) U133A+B microarray ( approximately 83% coverage of 12p genes) expression profiles of 17 seminomas, 84 nonseminoma GCTs, and 5 normal testis samples. Seventy-three genes on 12p were significantly overexpressed, including GLUT3 and REA (overexpressed in all GCTs) and CCND2 and FLJ22028 (overexpressed in all GCTs, except choriocarcinomas). We characterized a 200-kb gene cluster at 12p13.31 that exhibited coordinated overexpression in embryonal carcinomas and seminomas, which included the known stem cell genes NANOG, STELLA, and GDF3 and two previously uncharacterized genes. A search for other coordinately regulated genomic clusters of stem cell genes did not reveal any genomic regions similar to that at 12p13.31. Comparison of embryonal carcinoma with seminomas revealed relative overexpression of several stem cell-associated genes in embryonal carcinoma, including several core "stemness" genes (EBAF, TDGF1, and SOX2) and several downstream targets of WNT, NODAL, and FGF signaling (FGF4, NODAL, and ZFP42). Our results indicate that 12p gain is a functionally relevant change leading to activation of proliferation and reestablishment/maintenance of stem cell function through activation of key stem cell genes. Furthermore, the differential expression of core stem cell genes may explain the differences in pluripotency between embryonal carcinomas and seminomas.

Transcriptional program of bone morphogenetic protein-2-induced epithelial and smooth muscle differentiation of pluripotent human embryonal carcinoma cells.

Pluripotent human embryonal carcinoma NTera2/cloneD1 (NT2/D1) cells respond to multiple vertebrate patterning factors and offer a unique model system to investigate the signaling events associated with lineage determination and cell differentiation. Here, we define the temporal changes in global gene expression patterns in NT2/D1 cells upon treatment with bone morphogenetic protein-2 (BMP-2). Exposure to BMP-2 rapidly induced the expression of several transcription factors involved in establishing non-neural ectodermal fate followed by the appearance of epithelial-specific markers. Subsequent loss of stem cell markers was coupled to gene expression changes associated with decreased proliferative activity. Temporal clustering of gene expression patterns revealed a concurrent down-regulation of multiple transcripts involved in neurogenesis, neurite outgrowth, and axonal guidance, suggesting that the BMP-mediated differentiation process involves pro-epithelial as well as anti-neurogenic mechanisms. In addition, increased expression of smooth muscle markers both by gene expression and immunohistochemistry was detected. Several neural crest markers were induced preceding such a differentiation, compatible with a neural crest origin of NT2/D1-derived smooth muscle cells. Comparison of changes in transcript expression between BMP-2-induced epithelial versus all-trans-retinoic acid (ATRA)-induced neural differentiation revealed potential candidates for regulation of BMP-2 signaling and suppression of neural fate by BMP-2. This study suggests that BMP-2-induced differentiation of NT2/D1 cells provides a powerful assay to study early human epithelial and smooth muscle development.