A Molecular Link between the Circadian Clock, DNA Damage Responses, and Oncogene Activation

Circadian clocks enhance the efficiency and survival of living things by organizing their behavior and body functions. There has been a long history of research seeking a link between circadian clock and tumorigenesis. Studies of animal models and human tumor samples have revealed that the dysregulation of circadian clocks is an important endogenous factor causing mammalian cancer development. The core circadian clock regulators have been implicated in the control of both the cell cycle and DNA damage responses (DDR). Conversely, several intracellular signaling cascades that play important roles in regulation of the cell cycle and the DDR also contribute to circadian clock regulation. This review describes selected regulatory aspects of circadian clocks, providing evidence of a molecular link of the circadian clocks with cellular DDR

Light-Dependent Regulation of Circadian Clocks in Vertebrates

Circadian clocks are intrinsic time-tracking systems that endow organisms with a survival advantage. The core of the circadian clock mechanism is a cell-autonomous and self-sustained oscillator called a cellular clock, which operates via a transcription-/translation-based negative feedback loop. Under natural conditions, circadian clocks are entrained to a 24-hour day by environmental time cues, most commonly light. In mammals, circadian clocks are regulated by cellular clocks located in the central nervous system, such as the suprachiasmatic nucleus (SCN), and in other peripheral tissues. Importantly, mammals have no photoreceptors in the peripheral tissues; therefore the effect of light on peripheral clocks is indirect. By striking contrast, zebrafish peripheral cellular clocks are directly light responsive. This characteristic of the zebrafish cellular clock has contributed to the identification of molecules and signaling pathways that are involved in the light-dependent regulation of the cellular clock. Here, selected light-dependent regulatory mechanisms of circadian clocks in mammals and zebrafish are described

Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7.

c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system

How do case presentation teaching methods affect learning outcomes?-SNAPPS and the One-Minute preceptor

Background: Various techniques have been developed to enable preceptors to teach residents effectively in outpatient settings to promote active learning, including SNAPPS and the One-Minute Preceptor (OMP). This study aimed to ascertain the differences between SNAPPS and the OMP in case presentation content and learner evaluation when used to teach residents about case presentation. Methods: From 2011 to 2013, participants were 71 junior clinical residents employed in two hospitals for clinical training. They were randomly allocated to two groups, one using SNAPPS and the other the OMP. From recorded discussions, the "differential diagnoses", "questions and uncertainties", "treatment plans", and "learning issues" were counted. Also, a self-evaluation form was distributed at the end of the study to evaluate the residents' satisfaction with the case presentation. Results: Members of the SNAPPS group used significantly more meaning units related to questions and uncertainties compared with those of the OMP group (P < 0.001). Self-evaluation sheets revealed that members of the SNAPPS group had significantly higher positive responses than those of the OMP group in terms of the following evaluations: "It was easy to bring up questions and uncertainties" (P = 0.046), "It was easy to present the case efficiently" (P = 0.002), "It was easy to present the case in the sequence given" (P = 0.029), and "I was able to give an in-depth case presentation" (P = 0.005). Conclusions: SNAPPS may induce more meaning units related to questions and uncertainties and give more satisfaction to residents than the OMP

Prehospital delay and independent/interdependent construal of self among Japanese patients with acute myocardial infarction

Reducing the time from symptom onset to reperfusion therapy is an important approach to minimizing myocardial damage and to preventing death from acute myocardial infarction (AMI). Previous studies suggest that certain ethnic or national groups, such as the Japanese, are more likely to delay in accessing care than other groups. The aims of this paper were the following; (1) to examine whether culture (defined as independent and interdependent construal of self) is associated with delay in accessing medical care in Japanese patients experiencing symptoms of AMI; (2) to determine if the relationship between independent and interdependent construal of self and prehospital delay time is mediated by cognitive responses and/or emotional responses; and (3) to determine if independent and interdependent construal of self independently predicts choice of treatment site (clinic vs. hospital). A cross-sectional study was conducted at hospitals in urban areas in Japan. One hundred and forty-five consecutive patients who were admitted with AMI within 72 h of the onset of symptoms were interviewed using the modified response to symptoms questionnaire and the independent and interdependent construal of self scale. The interdependent construal of self scores were significantly associated with prehospital delay time, controlling for demographics, medical history, and symptoms (pIndependent/interdependent construal of self Acute myocardial infarction Culture Japan Prehospital delay Care-seeking