A genome-wide association study reveals the quantitative trait locus and candidate genes that regulate phosphate efficiency in a Vietnamese rice collection.

The crucial role of phosphate (Pi) for plant alongside the expected depletion of non-renewable phosphate rock have created an urgent need for phosphate-efficient rice varieties. In this study, 157 greenhouse-grown Vietnamese rice landraces were treated under Pi-deficient conditions to discover the genotypic variation among biochemical traits, including relative efficiency of phosphorus use (REP), relative root to shoot weight ratio (RRSR), relative physiological phosphate use efficiency (RPPUE), and relative phosphate uptake efficiency (RPUpE). Plants were grown in Yoshida nutrient media with either a full (320 µM) or a low Pi supply (10 µM) over six weeks. This genome-wide association study led to the discovery of 31 significant single nucleotide polymorphisms, 18 quantitative trait loci (QTLs), and 85 candidate genes. A common QTL named qRPUUE9.16 was found among the three investigated traits. Some interesting candidate genes, such as PLASMA MEMBRANE PROTEIN1 (OsPM1), CALMODULIN-RELATED CALCIUM SENSOR PROTEIN 15 (OsCML15), phosphatases 2C (PP2C), STRESS-ACTIVATED PROTEIN KINASE (OsSAPK2), and GLYCEROPHOSPHORYL DIESTER PHOSPHODIESTERASES (GDPD13), were found strongly correlated to the Pi starvation. RNA sequencing transcriptomes revealed that 45 out of 85 candidate genes were significantly regulated under Pi starvation. Furthermore, nearly two-thirds of genotypes did not possess the OsPsTOL1 gene; however, no significant difference was observed in response to Pi deficiency between genotypes with or without this gene, suggesting that other QTLs in rice may resist Pi starvation. These results provide new information on the genetics of nutrient use efficiency in rice and may potentially assist with developing more phosphate-efficient rice plants.

Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit.

Mitochondria continually undergo fusion and fission, and these dynamic processes play a major role in regulating mitochondrial function. Studies of several genes associated with familial Parkinson's disease (PD) have implicated aberrant mitochondrial dynamics in the disease pathology, but the importance of these processes in dopaminergic neurons remains poorly understood. Because the mitofusins Mfn1 and Mfn2 are essential for mitochondrial fusion, we deleted these genes from a subset of dopaminergic neurons in mice. Loss of Mfn2 results in a movement defect characterized by reduced activity and rearing. In open field tests, Mfn2 mutants show severe, age-dependent motor deficits that can be rescued with L-3,4 dihydroxyphenylalanine. These motor deficits are preceded by the loss of dopaminergic terminals in the striatum. However, the loss of dopaminergic neurons in the midbrain occurs weeks after the onset of these motor and striatal deficits, suggesting a retrograde mode of neurodegeneration. In our conditional knockout strategy, we incorporated a mitochondrially targeted fluorescent reporter to facilitate tracking of mitochondria in the affected neurons. Using an organotypic slice culture system, we detected fragmented mitochondria in the soma and proximal processes of these neurons. In addition, we found markedly reduced mitochondrial mass and transport, which may contribute to the neuronal loss. These effects are specific for Mfn2, as the loss of Mfn1 yielded no corresponding defects in the nigrostriatal circuit. Our findings indicate that perturbations of mitochondrial dynamics can cause nigrostriatal defects and may be a risk factor for the neurodegeneration in PD.

Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients.

Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59-3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14-2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07-2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13-2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54-4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.