N-Myc-activated microRNAs Inhibit Protein Synthesis of RUNX1 and RUNX3 in Neuroblastoma Cell Lines

　RUNX1 and RUNX3 are master transcription factors in sensory neuron lineage specifications. Protein levels of such developmental regulators are tightly controlled during carcinogenesis, in order to block differentiation and drive proliferation. Here we report that neuroblastoma specific microRNAs inhibit protein syntheses of RUNX1 and RUNX3 through 3’UTR sequences. Computational prediction identified two putative binding sequences for N-Myc-activated microRNAs both in RUNX1 and RUNX3 3’UTRs. Streptavidin RNA aptamer-tagged 3’UTR sequences pulled down miR-17, miR-18a, miR-19a, miR-20a or miR-130a from neuroblastoma cell lysate. 3’UTR target protection from N-Myc-activated microRNAs increased protein synthesis of RUNX1 or RUNX3 and induced differentiation in neuroblastoma cell lines. Together, protein levels of RUNX1 and RUNX3 are post-transcriptionally regulated by N-Myc-activated microRNAs, highlighting the mutual negative feedback between N-Myc oncogene and RUNX3 tumor suppressor in neuroblastoma

Causal Role of Neural Signals Transmitted From the Frontal Eye Field to the Superior Colliculus in Saccade Generation

The frontal eye field (FEF) and superior colliculus (SC) are major and well-studied components of the oculomotor system. The FEF sends strong projections to the SC directly, and neurons in these brain regions transmit a variety of signals related to saccadic eye movements. Electrical microstimulation and pharmacological manipulation targeting the FEF or SC affect saccadic eye movements. These data suggest the causal contribution of each region to saccade generation. To understand how the brain generates behavior, however, it is critical not only to identify the structures and functions of individual regions, but also to elucidate how they interact with each other. In this review article, we first survey previous works that aimed at investigating whether and how the FEF and SC interact to regulate saccadic eye movements using electrophysiological and pharmacological techniques. These works have reported what signals FEF neurons transmit to the SC and what roles such signals play in regulating oculomotor behavior. We then highlight a recent attempt of our own that has applied an optogenetic approach to stimulate the neural pathway from the FEF to the SC in nonhuman primates. This study has shown that optogenetic stimulation of the FEF-SC pathway is sufficiently effective not only to modulate SC neuron activity, but also to evoke saccadic eye movements. Although the oculomotor system is a complex neural network composed of numbers of cortical and subcortical regions, the optogenetic approach will provide a powerful strategy for elucidating the role of each neural pathway constituting this network

Role of piRNA biogenesis and its neuronal function in the development of neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by neuronal loss and dysfunction. Despite remarkable improvements in our understanding of these pathogeneses, serious worldwide problems with significant public health burdens are remained. Therefore, new efficient diagnostic and therapeutic strategies are urgently required. PIWI-interacting RNAs (piRNAs) are a major class of small non-coding RNAs that silence gene expression through transcriptional and post-transcriptional processes. Recent studies have demonstrated that piRNAs, originally found in the germ line, are also produced in non-gonadal somatic cells, including neurons, and further revealed the emerging roles of piRNAs, including their roles in neurodevelopment, aging, and neurodegenerative diseases. In this review, we aimed to summarize the current knowledge regarding the piRNA roles in the pathophysiology of neurodegenerative diseases. In this context, we first reviewed on recent updates on neuronal piRNA functions, including biogenesis, axon regeneration, behavior, and memory formation, in humans and mice. We also discuss the aberrant expression and dysregulation of neuronal piRNAs in neurodegenerative diseases, such as AD, PD, and ALS. Moreover, we review pioneering preclinical studies on piRNAs as biomarkers and therapeutic targets. Elucidation of the mechanisms underlying piRNA biogenesis and their functions in the brain would provide new perspectives for the clinical diagnosis and treatment of AD and various neurodegenerative diseases

Three-dimensional structure of monoanionic methionine-enkephalin: X-ray structure of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH

AbstractThe conformation of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH, as a monoanionic derivative of Met-enkephalin, was elucidated by X-ray crystal analysis. The molecule took an extended conformation which was bended at the Phe residue. The implication of the dimer formation caused by 4 intermolecular hydrogen bonds was discussed in the relation with the opiate receptor

Plasma level of D-dimer accompanying different types of gynecologic surgery and effects of prophylactic subcutaneous injection of heparin calcium

Background: The standard range of D-dimer level associated with each type of gynecologic surgery is required to note the occurrence of bleeding or thromboembolism.Methods: Plasma levels of D-dimer of patients who underwent different types of gynecologic surgery were measured on the Day of Preoperative Examination (DPE) and the first postoperative day (POD-1). Patients were classified by surgery type: hysterectomy for benign diseases or cervical intraepithelial neoplasia; hysterectomy for uterine cancer; surgery for ovarian cancer; laparoscopic surgery for a benign adnexal mass; laparotomy for a benign adnexal mass; laparotomic myomectomy; cervical conization; transcervical resection of an intrauterine mass; vaginal surgery for prolapse of a pelvic organ.Results: In each type of gynecologic surgery, plasma levels of D-dimer on POD-1 were higher than those on the DPE. Prophylactic subcutaneous injection of heparin calcium for patients who underwent surgery for endometrial cancer showed no significant difference in the plasma level of D-dimer on the sixth postoperative day (POD-6) and the plasma level of D-dimer on POD-6 was in the same level as those on POD-1.Conclusions: Plasma levels of D-dimer on POD-1 were higher than those on the DPE in each type of gynecologic surgery. The D-dimer level remained high even on POD-6, and not changed by prophylactic subcutaneous injection of heparin calcium.