Energy Price Uncertainty and Investment: Firm Level Evidence from Indian Manufacturing Sector

Uncertainty whatsoever has undoubtedly been deemed to be malevolent to the interests of investors. Theories of partial irreversibility of investment argue that uncertainty at the micro level negatively impacts the firm's investment and thereby, at least, slow the process of capital accumulation. Therefore, the present study, empirically analyzes how energy price uncertainty affects investment decisions of manufacturing firms in India.  A variety of panel data models are estimated using Generalized Method of Moments (GMM) with data pertaining to  Indian manufacturing firms over the period 1992- 93 to 2013- 14. Results are consistent with irreversible investment literature on the supply side of production, which shows that energy uncertainty has a negative effect on the capital accumulation in the manufacturing sector and this effect transpires in the form of firm's inability to adjust its actual capital stock to match up to its potential desired capital stock as proposed by the investment theories. Keywords: Energy Price Uncertainty, Irreversible Investment, Energy Intensity JEL Classifications: C23, D80, E20, Q41

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model

Molecular analysis reveals heterogeneity of mouse mammary tumors conditionally mutant for Brca1

<p>Abstract</p> <p>Background</p> <p>Development of therapies for patients with BRCA1 mutations has been hampered by lack of readily available <it>in vitro </it>and <it>in vivo </it>models. We recently showed that transplantation of transgenic mammary tumors as cell suspensions into naïve recipients generates reproducible tumors with remarkable stability of gene expression profile. We examined the expression profiles of original and serially transplanted mammary tumors from <it>Brca1 </it>deficient mice, and tumor derived cell lines to validate their use for preclinical testing and studies of tumor biology.</p> <p>Methods</p> <p>Original tumors, serially transplanted and multiple cell lines derived from <it>Brca1 </it>mammary tumors were characterized by morphology, gene and protein expression, and cell surface markers.</p> <p>Results</p> <p>Gene expression among <it>Brca1 </it>tumors showed more heterogeneity than among previously characterized tumors from MMTV-<it>PyMT </it>and -<it>Wnt1 </it>models. Gene expression data segregated <it>Brca1 </it>tumors into 3 distinct types: basal, mixed luminal, and tumors with epithelial-to-mesenchymal transition (EMT). Serial transplantation of individual tumors and multiple cell lines derived from the original tumors recapitulated the molecular characteristics of each tumor of origin. One tumor had distinct features of EMT and gave rise to cell lines that contained a distinct CD44⁺/CD24^-/lowpopulation that may correlate with human breast cancer stem cells.</p> <p>Conclusion</p> <p>Although individual tumors expanded by transplantation maintain the genomic profile of the original tumors, the heterogeneity among <it>Brca1 </it>tumors limits the extent of their use for preclinical testing. However, cell lines offer a robust material for understanding tumor biology and response to therapies driven by BRCA1 deficiency.</p

Oral delivery of il-27 recombinant bacteria attenuates immune colitis in mice

BACKGROUND & AIMS: Treatment of inflammatory bowel disease (IBD) would benefit from specific targeting of therapeutics to the intestine. We developed a strategy for localized delivery of the immunosuppressive cytokine IL27, which is actively synthesized in situ by the food-grade bacterium Lactococcuslactis (LL-IL-27), and tested its ability to reduce colitis in mice. METHODS: The 2 genes encoding mouse IL27 were synthesized with optimal codon usage for L lactis and joined with a linker; a signal sequence was added to allow for secretion of the product. The construct was introduced into L lactis. Colitis was induced via transfer of CD4(+)CD45RB(hi) T cells into Rag(−/−) mice to induce colitis; 7.5 weeks later, LL-IL-27 was administered to mice via gavage. Intestinal tissues were collected and analyzed. RESULTS: LL-IL-27 administration protected mice from T-cell transfer-induced enterocolitis and death. LL-IL-27 reduced disease activity scores, pathology features of large and small bowel, and levels of inflammatory cytokines in colonic tissue. LL-IL-27 also reduced numbers of CD4(+) and IL17(+) T cells in gut-associated lymphoid tissue. The effects of LL-IL-27 required production of IL10 by the transferred T cells. LL-IL-27 was more effective than either LL-IL-10 or systemic administration of recombinant IL27 in reducing colitis in mice. LL-IL-27 also reduced colitis in mice following administration of dextran sodium sulfate. CONCLUSIONS: L lactis engineered to express IL27 (LL-IL-27) reduces colitis in mice, by increasing production of IL10. Mucosal delivery of LL-IL-27 could be a more effective and safer therapy for IBD

Toxicity of polybrominated biphenyls (Firemaster BP-6) in rodents

Pregnant rodents were fed concentrations of a mixture of polybrominated biphenyls (Firemaster BP-6) during the pregnancy. The material appears to be weakly teratogenic, causing exencephaly and cleft palate in mice. Decreasing birth weight with increasing dosage of the material was seen in both mice and rats. Nonpregnant mice fed 1000 ppm Firemaster BP-6 for 11 days had a marked increase in liver size and weight.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21936/1/0000343.pd

Gene expression evolution in pattern-triggered immunity within Arabidopsis thaliana and across Brassicaceae species

Plants recognize surrounding microbes by sensing microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). Despite their significance for microbial control, the evolution of PTI responses remains largely uncharacterized. Here, by employing comparative transcriptomics of six Arabidopsis thaliana accessions and three additional Brassicaceae species to investigate PTI responses, we identified a set of genes that commonly respond to the MAMP flg22 and genes that exhibit species-specific expression signatures. Variation in flg22-triggered transcriptome responses across Brassicaceae species was incongruent with their phylogeny, while expression changes were strongly conserved within A. thaliana. We found the enrichment of WRKY transcription factor binding sites in the 5′-regulatory regions of conserved and species-specific responsive genes, linking the emergence of WRKY-binding sites with the evolution of gene expression patterns during PTI. Our findings advance our understanding of the evolution of the transcriptome during biotic stress

Interleukin-27 is a potential rescue therapy for acute severe colitis through Interleukin-10–Dependent, T-Cell–independent attenuation of colonic mucosal innate immune responses

Background: If treatment with intravenous steroids fail, inflammatory bowel disease patients with acute severe colitis face systemic anti–tumor necrosis factor biologic rescue therapy or colectomy. Interleukin (IL)-27 is a cytokine with an immunosuppressive role in adaptive immune responses. However, the IL-27 receptor complex is also expressed on innate immune cells, and there is evidence that IL-27 can impact the function of innate cell subsets, although this particular functionality in vivo is not understood. Our aim was to define the efficacy of IL-27 in acute severe colitis and characterize novel IL-27–driven mechanisms of immunosuppression in the colonic mucosa. Methods: We assessed oral delivery of Lactococcus lactis expressing an IL-27 hyperkine on the innate immune response in vivo in a genetically intact, noninfective, acute murine colitis model induced by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid in SJL/J mice. Results: IL-27 attenuates acute severe colitis through the reduction of colonic mucosal neutrophil infiltrate associated with a decreased CXC chemokine gradient. This suppression was T cell independent and IL-10 dependent, initially featuring enhanced mucosal IL-10. IL-27 was associated with a reduction in colonic proinflammatory cytokines and induced a multifocal, strong, positive nuclear expression of phosphorylated STAT-1 in mucosal epithelial cells. Conclusion: We have defined novel mechanisms of IL-27 immunosuppression toward colonic innate immune responses in vivo. Mucosal delivery of IL-27 has translational potential as a novel therapeutic for inflammatory bowel disease, and it is a future mucosal directed rescue therapy in acute severe inflammatory bowel disease