Project description:Sinorhizobium meliloti establishes symbiotic relationship with compatible leguminous plants by inducing root nodule formation, colonizing such nodules, and fixing molecular nitrogen for the host in exchange for carbon compounds. This mutualistic process requires complex communication and tight regulation to allow yet constrain infection to specific tissues. Production of succinoglycan, or exopolysaccharide-I (EPS-I), enables S. meliloti to invade the root cortex via infection threads. A previous genetic screen identified jspA (SMc03872), encoding an extracytoplasmic protease, as a regulator of EPS-I production. To elucidate its molecular role, we performed transcriptome analyses of strains overexpressing wild-type or mutant alleles of jspA. We observed changes in gene expression suggesting that JspA contributes to symbiosis efficiency by modulating the critical ExoR-ExoS-ChvI signaling pathway.
Project description:The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), characterized by aneuploidy and poor outcome, is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two major subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations (88%), almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia. Gene expression profiling was performed on 117 single diagnosis tumor samples and one relapse sample [SJHYPO117]. No control or reference samples were included.
Project description:The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), characterized by aneuploidy and poor outcome, is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two major subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations (88%), almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.
Project description:In the present study, we hypothesized that C/EBPa (CCAAT/enhancer-binding protein alpha) plays a role in cell regeneration in response to bronchiolar epithelial cell injury. C/EBPa mediated ciliated cell regeneration after naphthalene bronchiolar epithelial cell injury in vivo. Furthermore, we demonstrated that C/EBPa regulates protease/anti-protease balance after lung injury, and intratracheal treatment with anti-protease (BPTI) restored ciliated cell regeneration after naphthalene injury in CebpaD/D mice.