Shallow groundwater irrigation in White Volta Basin: Current status, livelihood contributions, and up-scaling potential

A diversity-oriented synthesis has been developed for facile construction of a library of carbohydrate–cyclopamine conjugates. The synthetic protocol is suitable for generating cyclopamine derivatives with various structural motifs for exploring the desired activity. From this initial library, we have observed one derivative that exhibits improved activity against lung cancer cell as compared to cyclopamin

Keeping Them in Their Place: Migrant Women Workers in Spain’s Strawberry Industry

The idea of guest-worker migration has resurfaced in recent decades as the global agri-food industry has confronted a shortage of workers willing to take low-wage and often seasonal jobs. To date, there have been very few cases studies of these twenty-first century guest-worker programs and their role in managing contemporary labor migration. This article examines guest-worker migration in the strawberry industry of southern Spain. In this case, guest-worker programs at- tempt to regulate and enforce the circular migration of foreign workers in Spain. By making future work contracts contingent on migrants’ return to their country of origin, by recruiting migrant workers from various countries, and by target- ing women with dependent children, these programs help to discipline migrant workers into the rigors of circular migration. We argue that although the program has been lauded as a model of twenty-first century labor migration, it succeeds primarily by keeping foreign, low-wage, women workers ‘in their place’

Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling

The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1 and K14cre:SmoM2). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis

Additional file 1: Figure S1. of Cyclopamine tartrate, an inhibitor of Hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells

The effect of CycT treatment on NSCLC cancer cell proliferation. %live cells was calculated by dividing the number of treated cells with the number of untreated cells (seeded with the same number of cells). It shows the relative proliferative rates of treated cells (10 or 25 μM) vs. untreated cells (None). For statistical analysis, the values for treated cells were compared to the values for untreated cells, by using Welch 2-sample t-test. *, p value < 0.05; **, p value < 0.005. (JPG 270 kb

Cyclopamine: From Cyclops Lambs to Cancer Treatment

In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented