Ethnobotanical study of cowpea (Vigna unguiculata (L.) Walp.) in Senegal.

Cowpea (Vigna unguiculata) plays a key role in family farming systems in Senegal. It makes an essential contribution to economic, nutritional and food security. Although it is crucial, little is known about how farmers classify the diversity of local varieties or about the social practices associated with them. The aim of this study is to characterize the farming practices associated with growing cowpea in Senegal. Surveys were conducted involving 335 rural farmers living in 37 villages, spread across seven regions that produce cowpea. An average of ten farmers were randomly selected in each village. The results reveal that cowpea is a key feature of cropping systems in the studied area. Our findings highlight the high diversity of local cowpea varieties with 59 local names inventoried. In 75% of cases, the name refers to the seed's morphology or color. Cowpea production is more diverse in Diourbel and Louga and less diverse in the south. More than half the farmers (57%) acquired their cowpea seeds (early, semi-early and late maturity varieties) outside their village, either from markets, seed suppliers or NGOs. This new understanding of farmers' expertize in the management of cowpea and its local variability will help to valorize local diversity in breeding programs.

Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031.

Gemcitabine is a fluoropyrimidine analogue that is used as a mainstay of chemotherapy treatment for pancreatic and ovarian cancers, amongst others. Despite its widespread use, gemcitabine achieves responses in less than 10% of patients with metastatic pancreatic cancer and has a very limited impact on overall survival due to intrinsic and acquired resistance. NUC-1031 (Acelarin), a phosphoramidate transformation of gemcitabine, was the first anti-cancer ProTide to enter the clinic. We find it displays important in vitro cytotoxicity differences to gemcitabine, and a genome-wide CRISPR/Cas9 genetic screening approach identified only the pyrimidine metabolism pathway as modifying cancer cell sensitivity to NUC-1031. Low deoxycytidine kinase expression in tumour biopsies from patients treated with gemcitabine, assessed by immunostaining and image analysis, correlates with a poor prognosis, but there is no such correlation in tumour biopsies from a Phase I cohort treated with NUC-1031.

PKCθ-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration.

The AP-1 transcription factor Fra-1 is aberrantly expressed in a large number of cancers and plays crucial roles in cancer development and progression by stimulating the expression of genes involved in these processes. However, the control of Fra-1 transactivation ability is still unclear and here we hypothesized that PKCθ-induced phosphorylation could be necessary to obtain a fully active Fra-1 protein. Using MCF7 stable cells overexpressing equivalent levels of unphosphorylated Fra-1 or PKCθ-phosphorylated Fra-1, we showed that PKCθ-induced phosphorylation of Fra-1 was crucial for the stimulation of MMP1 and IL6 expression. Consistently, we found a significant positive correlation between PRKCQ (coding for PKCθ) and MMP1 mRNA expression levels in human breast cancer samples. PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors. More importantly, these phosphorylations were required for Fra-1-induced migration of breast cancer cells and phosphorylated Fra-1 expression was enriched at the invasion front of human breast tumors. Taken together, our findings indicate that PKCθ-induced phosphorylation could be important for the function of Fra-1 in cancer progression.