bioRxiv ScienceSearch

Biology subjects

Ohta, A.

Publications and source records attributed to Ohta, A..

3 recordsLinked to original sources

Genome analyses reveal the hybrid origin of the staple food crop white Guinea yam

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wild Dioscorea species using an improved reference genome sequence of D. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild species D. praehensilis and the savannah-adapted D. abyssinica. We identified a higher genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and an extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

evolutionary biology

High-throughput Screening with Pluripotent Stem Cells Identifies CUDC-907 as an Effective Compound for Restoring the Proinflammatory Phenotype of Nakajo-Nishimura Syndrome

Nakajo-Nishimura syndrome (NNS) is an autoinflammatory disorder caused by a homozygous mutations in PSMB8 gene. The administration of systemic corticosteroids is partially effective, but continuous treatment causes severe side effects. We previously established a pluripotent stem cell (PSC)-derived NNS disease model that reproduces several inflammatory phenotypes including the overproduction of monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein-10 (IP-10). Here we performed high-throughput compound screening (HTS) using this PSC-derived NNS model to find potential therapeutic candidates and identified CUDC-907 as an effective inhibitor of the release of MCP-1 and IP-10. CUDC-907 did not induce cell death within therapeutic concentrations and was also effective on primary patient cells. Further analysis indicated that the inhibitory effect was post-transcriptional. These findings suggest that HTS with PSC-derived disease models is useful for finding drug candidates for autoinflammatory diseases. Significance statementIn this study, we identified a histone deacetylase inhibitor CUDC-907 as a potential effective compound for ameliorating overproduction of inflammatory chemokines in an autoinflammatory disease named Nakajo-Nishimura syndrome. We performed high-throughput screening using pluripotent stem cell-derived monocytic cell lines. Our data prove the validity of screening system as a versatile platform for seeking candidate compounds for the treatment of congenital immunological disorders associated with monocytic lineage cells.

immunology

Mechanoreceptor-mediated circuit regulates cold tolerance in Caenorhabditis elegans

C. elegans mechanoreceptors located in the ASG sensoryneuron have been found to sense temperature -- a key trait for animal survival. Experimental loss of xanthine dehydrogenase (XDH-1) function in the AIN and AVJ interneurons resulted in reduced cold tolerance and atypical neuronal response to changes in temperature. These interneurons are synapse with upstream neurons such as the mechanoreceptor-expressing ASG. Ca2+ imaging revealed that ASG responsiveness to temperature change via mechanoreceptor DEG-1, a Degenerin/Epithelial Sodium Channel (DEG/ENaC), affects downstream AIN and AVJ circuits. Ectopic expression of DEG-1 in the ASE gustatory neuron resulted in acquisition of thermosensitivity, while electrophysiological analysis revealed that DEG-1 was involved in temperature sensation. Together, these results suggest that cold tolerance is regulated by mechanoreceptor-mediated circuit calculation.

genetics