RSL Class II Transcription Factors Guide the Nuclear Localization of RHL1 to Regulate Root Hair Development.

Root hairs are important for absorption of nutrients and water from the rhizosphere. The Root Hair Defective-Six Like (RSL) Class II family of transcription factors is expressed preferentially in root hairs and has a conserved role in root hair development in land plants. We functionally characterized the seven members of the RSL Class II subfamily in the rice (Oryza sativa) genome. In root hairs, six of these genes were preferentially expressed and four were strongly expressed. Phenotypic analysis of each mutant revealed that Os07g39940 plays a major role in root hair formation, based on observations of a short root hair phenotype in those mutants. Overexpression (OX) for each of four family members in rice resulted in an increase in the density and length of root hairs. These four members contain a transcription activation domain and are targeted to the nucleus. They interact with rice Root Hairless1 (OsRHL1), a key regulator of root hair development. When heterologously expressed in epidermal cells of Nicotiana benthamiana leaves, OsRHL1 was predominantly localized to the cytoplasm. When coexpressed with each of the four RSL Class II members, however, OsRLH1 was translocated to the nucleus. Transcriptome analysis using Os07g39940-OX plants revealed that 86 genes, including Class III peroxidases, were highly up-regulated. Furthermore, reactive oxygen species levels in the root hairs were increased in Os07g39940-OX plants but were drastically reduced in the os07g39940 and rhl1 mutants. Our results demonstrate that RSL Class II members function as essential regulators of root hair development in rice.

MRI features and texture analysis for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy and tumor recurrence of locally advanced rectal cancer.

OBJECTIVES: This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). METHODS: Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. RESULTS: In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). CONCLUSIONS: Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. KEY POINTS: • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.

Structural Study of Monomethyl Fumarate-Bound Human GAPDH.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a core enzyme of the aerobic glycolytic pathway with versatile functions and is associated with cancer development. Recently, Kornberg et al . published the detailed correlation between GAPDH and di- or monomethyl fumarate (DMF or MMF), which are well-known GAPDH antagonists in the immune system. As an extension, herein, we report the crystal structure of MMF-bound human GAPDH at 2.29 Å. The MMF molecule is covalently linked to the catalytic Cys152 of human GAPDH, and inhibits the catalytic activity of the residue and dramatically reduces the enzymatic activity of GAPDH. Structural comparisons between NAD+bound GAPDH and MMF-bound GAPDH revealed that the covalently linked MMF can block the binding of the NAD+ cosubstrate due to steric hindrance of the nicotinamide portion of the NAD+ molecule, illuminating the specific mechanism by which MMF inhibits GAPDH. Our data provide insights into GAPDH antagonist development for GAPDH-mediated disease treatment.