公开(公告)号：US20090292111A1

公开(公告)日：2009-11-26

申请号：US11909058

申请日：2006-03-27

申请人： Takuro Yamamoto ,  Takayoshi Mamine ,  Toru Takumi ,  Makoto Akashi

发明人： Takuro Yamamoto ,  Takayoshi Mamine ,  Toru Takumi ,  Makoto Akashi

IPC分类号： C07K16/00 ,  C07K14/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： A61K31/7105 ,  A61K31/7088 ,  C07K14/4702 ,  C07K14/70567 ,  G01N33/743 ,  G01N2333/70567 ,  G01N2500/00

摘要： An object of the present invention is to clarify unelucidated aspects in the control mechanism of circadian rhythms. The present inventors have newly found that RORα (retinoic acid binding-receptor alpha; the same shall apply hereinafter) stimulates an induction of Bmal1 expression and also that the induction of Bmal1 expression is promoted under hypoxia. These findings strongly suggest the existence of a control mechanism of circadian rhythms that, when RORα expression is promoted under hypoxia or the like, an induction of Bmal1 expression is stimulated and, when the induction of Bmal1 expression is stimulated, binding between BMAL1 and CLOCK is stimulated and an induction of Per gene or Cry gene expression is stimulated. The present invention, therefore, has applicability as jet-lag regulating agents and anticancer agents.

摘要翻译： 本发明的目的是澄清昼夜节律控制机制中的未消化方面。 本发明人新发现，RORalpha（视黄酸结合受体α，以下相同）将刺激Bmal1表达的诱导，并且在缺氧下促进Bmal1表达的诱导。 这些发现强烈地表明存在昼夜节律的控制机制，当在缺氧等下促进RORalpha表达时，刺激Bmal1表达的诱导，并且当刺激Bmal1表达的诱导时，BMAL1和CLOCK之间的结合是 刺激并诱导Per基因或Cry基因表达。 因此，本发明作为喷射滞后调节剂和抗癌剂具有适用性。

公开(公告)号：US20060154268A1

公开(公告)日：2006-07-13

申请号：US11174992

申请日：2005-07-05

申请人： Takuro Yamamoto ,  Haruhiko Soma ,  Takayoshi Mamine ,  Toru Takumi ,  Yasukazu Nakahata

发明人： Takuro Yamamoto ,  Haruhiko Soma ,  Takayoshi Mamine ,  Toru Takumi ,  Yasukazu Nakahata

IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12M1/34

CPC分类号： C07K14/4702

摘要： A circadian rhythm control gee cluster (Bmal1 gene, Npas2 gene, Rev-erbα, Dbp gene, Per3 gene, Per2 gene and Per1 gene) having a given expression timing and expression sequence under normal conditions is provided along with a DNA chip having, at least, the circadian control gene group sequentially arranged. There are also provided a method for predicting modulation in expression timing of the circadian rhythm control gene cluster, a method for detecting a circadian rhythm modulation, a method for selecting a circadian rhythm regulator, a method for screening a circadian rhythm regulator, and screening of a substance involving modulation of a circadian rhythm as a side effect, each using the DNA chip.

摘要翻译： 在正常条件下具有给定表达时间和表达序列的昼夜节律控制gee簇（Bmal1基因，Npas2基因，Rev-erbalpha，Dbp基因，Per3基因，Per2基因和Per1基因）与DNA芯片一起提供， 至少，昼夜节律控制基因组顺序排列。 还提供了一种用于预测昼夜节律控制基因簇的表达定时中的调制的方法，用于检测昼夜节律调节的方法，选择昼夜节律调节剂的方法，筛选昼夜节律调节剂的方法，以及筛选 一种涉及调节昼夜节律作为副作用的物质，每种都使用DNA芯片。

公开(公告)号：US20060073495A1

公开(公告)日：2006-04-06

申请号：US11174272

申请日：2005-07-01

申请人： Takuro Yamamoto ,  Toru Takumi

发明人： Takuro Yamamoto ,  Toru Takumi

IPC分类号： C12Q1/68 ,  C12M1/34

CPC分类号： G01N33/6845 ,  B01J2219/00536 ,  B01J2219/00693 ,  B01J2219/00722 ,  B01J2219/00725 ,  C12Q2600/158

摘要： A method for inspecting a quality of a sensor chip using either of (1) and (2) indicated below as a judgment index is provided: (1) interrelations of a plurality of circadian rhythm control genes in respect of expression level thereof; and (2) time-lapse patterns of specified circadian rhythm control genes in respect of expression level thereof. A method of evaluating whether sampling and preparation of a sample to be subjected to detection of interaction between substances is proper is also provided wherein (1) or (2) defined above is used as a judgment index. DNA and protein chips useful for the methods are also provided.

摘要翻译： 提供了使用以下（1）和（2）中任一项作为判断指标来检测传感器芯片的质量的方法：（1）多个昼夜节律控制基因在其表达水平上的相互关系; 和（2）指定的昼夜节律控制基因在其表达水平方面的延时模式。 还提供了评估是否对要进行物质之间的相互作用的检测的样品的取样和制备是适当的方法，其中使用上述定义的（1）或（2）作为判断指标。 还提供了可用于该方法的DNA和蛋白质芯片。

公开(公告)号：US20120093807A1

公开(公告)日：2012-04-19

申请号：US13234273

申请日：2011-09-16

申请人： Takuro Yamamoto ,  Takayoshi Mamine ,  Toru Takumi ,  Makoto Akashi

发明人： Takuro Yamamoto ,  Takayoshi Mamine ,  Toru Takumi ,  Makoto Akashi

IPC分类号： A61K39/395 ,  A61P25/24 ,  A61P25/20 ,  A61P35/00 ,  A61P25/00

CPC分类号： A61K31/7105 ,  A61K31/7088 ,  C07K14/4702 ,  C07K14/70567 ,  G01N33/743 ,  G01N2333/70567 ,  G01N2500/00

摘要： An object of the present invention is to clarify unelucidated aspects in the control mechanism of circadian rhythms. The present inventors have newly found that RORα (retinoic acid binding-receptor alpha; the same shall apply hereinafter) stimulates an induction of Bmal1 expression and also that the induction of Bmal1 expression is promoted under hypoxia. These findings strongly suggest the existence of a control mechanism of circadian rhythms that, when RORα expression is promoted under hypoxia or the like, an induction of Bmal1 expression is stimulated and, when the induction of Bmal1 expression is stimulated, binding between BMAL1 and CLOCK is stimulated and an induction of Per gene or Cry gene expression is stimulated. The present invention, therefore, has applicability as jet-lag regulating agents and anticancer agents.

摘要翻译： 本发明的目的是澄清昼夜节律控制机制中的未消化方面。 本发明人新发现RORα（视黄酸结合受体α，以下同样适用）刺激Bmal1表达的诱导，并且在缺氧下促进Bmal1表达的诱导。 这些发现强烈地表明存在昼夜节律的控制机制，当在缺氧等下促进RORα表达时，刺激Bmal1表达的诱导，并且当刺激Bmal1表达的诱导时，BMAL1和CLOCK之间的结合是 刺激并诱导Per基因或Cry基因表达。 因此，本发明具有作为喷射滞后调节剂和抗癌剂的适用性。

公开(公告)号：US20070099217A1

公开(公告)日：2007-05-03

申请号：US11543774

申请日：2006-10-06

申请人： Takuro Yamamoto ,  Haruhiko Soma ,  Toru Takumi ,  Yasukazu Nakahata

发明人： Takuro Yamamoto ,  Haruhiko Soma ,  Toru Takumi ,  Yasukazu Nakahata

IPC分类号： C12Q1/68 ,  G01N33/567 ,  C07H21/04 ,  C12P21/06 ,  C07K14/705 ,  C07K16/28

CPC分类号： C12Q1/6883 ,  C12Q2600/158

摘要： The molecular reaction mechanism that associates the clock gene with stress is elucidated based on the finding that stress is accompanied by an increase in the expression level of Per1 gene in peripheral tissues, stress response does not change the circadian rhythm in peripheral tissues, and Per1 gene increases in its expression level dependently on the responsive element of glucocorticoid existing in its promoter region. This finding is used for stress evaluation. That is, stress can be evaluated for its presence or absence or degree by detection and determination of an increase in the transcript (mRNA) of Per1 gene in peripheral tissues (an increase in the protein coded by Per1 gene).

摘要翻译： 基于应激伴随着外周组织中每1基因表达水平的增加，应激反应不改变周围组织中的昼夜节律，并且Per 1基因的表达水平依赖于存在于其启动子区域的糖皮质激素的反应元件。 这个发现用于压力评估。 也就是说，可以通过检测和测定外周组织中每1基因的转录物（mRNA）的增加（通过Per 1基因编码的蛋白质的增加）来评估其存在或不存在或程度的压力。