Previous work established that mutations in mitogen-activated protein (MAP) kinase (CHK1) and heterotrimeric G-protein ␣ (G␣) subunit (CGA1) genes affect the development of several stages of the life cycle of the maize pathogen Cochliobolus heterostrophus. The effects of mutating a third signal transduction pathway gene, CGB1, encoding the G␤ subunit, are reported here. CGB1 is the sole G␤ subunit-encoding gene in the genome of this organism. cgb1 mutants are nearly wild type in vegetative growth rate; however, Cgb1 is required for appressorium formation, female fertility, conidiation, regulation of hyphal pigmentation, and wild-type virulence on maize. Young hyphae of cgb1 mutants grow in a straight path, in contrast to those of the wild type, which grow in a wavy pattern. Some of the phenotypes conferred by mutations in CGA1 are found in cgb1 mutants, suggesting that Cgb1 functions in a heterotrimeric G protein; however, there are also differences. In contrast to the deletion of CGA1, the loss of CGB1 is not lethal for ascospores, evidence that there is a G␤ subunit-independent signaling role for Cga1 in mating. Furthermore, not all of the phenotypes conferred by mutations in the MAP kinase CHK1 gene are found in cgb1 mutants, implying that the G␤ heterodimer is not the only conduit for signals to the MAP kinase CHK1 module. The additional phenotypes of cgb1 mutants, including severe loss of virulence on maize and of the ability to produce conidia, are consistent with CGB1 being unique in the genome. Fluorescent DNA staining showed that there is often nuclear degradation in mature hyphae of cgb1 mutants, while comparable wild-type cells have intact nuclei. These data may be genetic evidence for a novel cell death-related function of the G␤ subunit in filamentous fungi.

Human erythropoietin (EPO) is a glycoprotein hormone secreted from the kidney and controls red blood cell production. EPO has a wide clinical use in the treatment of anemia associated with renal disease, certain chronic diseases, and anemia related to chemotherapy and radiotherapy. One major issue regarding the clinical use of EPO is its relatively short half-life due to its clearance by glomerular filtration. Thus, the therapeutic protocol used in the treatment of patient-required frequent injections of EPO. To address this issue, we constructed a chimeric gene that contains the sequence of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin-beta subunit bearing four O-linked oligosaccharide recognition sites and the coding sequence of human EPO cDNA. Fusing the CTP to the carboxyl-terminal of EPO did not affect secretion, receptor binding affinity, or in vitro bioactivity. However, both in vivo potency and half-life of EPO-CTP were significantly enhanced. A single injection dose (660 IU/kg) of EPO wild-type administered once a week had no significant effect on haematocrit levels. However, EPO-CTP administered as 660 IU/kg once a week was effective as well as the same total dose of EPO wild-type administered as 220 IU/kg three times a week. This may emphasize the importance of sustained blood levels rather than total dose of administration for in vivo bioactivity. These data established the rationale for using this chimera as a long-acting EPO analog. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and human clinical trials.

The study examines the relationship between walking, cognitive, and academic skills. Students from elementary, middle, high school, and college were required to walk for 10 min prior to completing feature detection, Simon-type memory, and mathematical problem-solving tasks. Participants were counterbalanced to remove a time bias. Ten minutes of walking had a significant positive effect on Simon-type memory and critical feature-detection tasks among all age groups. Separately, with mathematical problem-solving ability, higher performing high-school students demonstrated significant positive effects on mathematical reasoning tasks based on the Bloom Taxonomy. However, poorly achieving high-school students performed significantly better than those with higher grades in mathematics on tests of mathematical problem-solving ability based on the Bloom’s Taxonomy. The study indicates that there is justification to employ relatively simple means to effect lifestyle, academic, and cognitive performance.

No abstract