RESUMEN
Sweet potato starch is in high demand globally for food and industry. However, starch content is negatively correlated with fresh yield. It is urgent to uncover the genetic basis and molecular mechanisms underlying the starch yield of sweet potato. Here we systematically explore source-sink synergy-mediated sweet potato starch yield formation: the production, loading, and transport of photosynthates in leaves, as well as their unloading and allocation in storage roots, lead to starch content divergence between sweet potato varieties. Moreover, we find that six haplotypes of IbPMA1 encoding a plasma membrane H+-ATPase are significantly linked with starch accumulation. Overexpression of IbPMA1 in sweet potato results in significantly increased starch and sucrose contents, while its knockdown exhibits an opposing effect. Furthermore, a basic helix-loop-helix (bHLH) transcription factor IbbHLH49 directly targets IbPMA1 and activates its transcription. Overexpression of IbbHLH49 notably improves source-sink synergy-mediated fresh yield and starch accumulation in sweet potato. Both IbbHLH49 and IbPMA1 substantially influence sugar transport and starch biosynthesis in source and sink tissues. These findings expand our understanding of starch yield formation and provide strategies and candidate genes for high starch breeding in root and tuber crops.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Ipomoea batatas , Hojas de la Planta , Proteínas de Plantas , Raíces de Plantas , Almidón , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Ipomoea batatas/crecimiento & desarrollo , Almidón/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Plantas Modificadas Genéticamente , Haplotipos , Sacarosa/metabolismo , ATPasas de Translocación de Protón/metabolismo , ATPasas de Translocación de Protón/genéticaRESUMEN
Cell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre-transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. In this survey review, the authors interpret and highlight responses for antibody development and, where relevant, contrast complex molecule development challenges to provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line.
Asunto(s)
Cricetulus , Animales , Células CHO , Industria Farmacéutica , Células Clonales , Transfección/métodos , HumanosRESUMEN
Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230⯵M and can inhibit the proliferation of THP-1â¯cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.