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To help ensure the fidelity
2024-03-22
To help ensure the fidelity of mitosis and cytokinesis cells monitor these processes and delay cell cycle progression in response to certain defects. The spindle assembly checkpoint (SAC) is a surveillance system which delays CEP-18770 onset until a bipolar spindle has been correctly assembled (Lara
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Several structural classes of ASK inhibitors mostly from ind
2024-03-22
Several structural Paxilline of ASK1 inhibitors, mostly from industry but also from academia, have been identified over the last decade. In 2012, Terao et al. (Takeda) reported imidazo[1,2-α]pyridine () as a potent ASK1 inhibitor derived from structure-based drug design. GSK, Merck and Gilead revea
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Many coumarin derivatives can be found in nature There
2024-03-22
Many coumarin derivatives can be found in nature. There are more than 1300 types of those purely derived from plants, and if synthetic products are included, their number is immeasurable. According to the earliest existing records extant, herbs containing Psoralen-type compounds, e.g., methoxsalen,
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br Materials and methods br
2024-03-22
Materials and methods Results A first series of experiments explored whether the Ampkα1 isoform is involved in the regulation of cardiac Pkcζ. To this end, HL-1 cardiomyocytes were transfected with a construct encoding constitutively active Prkaa1T183D (CAα1) or with the empty vector as contro
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CCT129202 Although little is known about the
2024-03-22
Although little is known about the etiopathogenesis of preeclampsia, this syndrome has a major impact on maternal and fetal health worldwide, since it is responsible for 10–15% of maternal deaths [16], [17], preterm births, intrauterine growth restriction (IUGR), and fetal deaths [2]. In developing
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br Acknowledgments br Introduction Angiotensin II AngII is a
2024-03-22
Acknowledgments Introduction Angiotensin II (AngII) is among the most potent vasoactive substances produced in humans. Its effects are numerous, from vasoconstriction to control of fluid and electrolytes balances. Many of the physiological and pathological effects of AngII are mediated by the
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There is a growing body of evidence showing that
2024-03-22
There is a growing body of evidence showing that pentobarbital causes memory disorders [3], [4], [5]. Our results that a single injection of pentobarbital into bilateral hippocampus significantly impaired hippocampus-dependent spatial memory retrieval (Fig. 1) add support to that evidence. Previous
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Cell surface metalloproteases coordinate signaling
2024-03-22
Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. A disintegrin and metalloprotease 17 (ADAM17) is a well-characterized member among ADAM family, which mediates the cleavage of various cell surface proteins (Black, 2002, Black et al., 1997, Dello
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The excellent potencies selectivities and improved PK associ
2024-03-21
The excellent potencies, selectivities and improved PK associated with the piperazine class triggered more extensive off-target screenings of the highlighted compounds. A screen of more than 100 enzymes, receptors, and ion channels resulted in activity at the norepinephrine transporter (NET). This
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Based on the observation that
2024-03-21
Based on the observation that antipsychotic drugs increase 5-HT1A–D2 heteromerization level (Łukasiewicz et al., 2016), we set out to compare the effect of paroxetine to that of risperidone. Paroxetine, a potent SSRI, is very effective in the treatment of depression and anxiety disorders, e.g., gene
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In order to investigate their effects in
2024-03-21
In order to investigate their effects in vitro, therefore, we first used TE671 cells, which have provided a useful source of human AChR for in vitro and radioimmunoassay studies. We found no marked effect of either MuSK-MG or SNMG sera on AChR numbers or on AChR subunit expression. This appears to c
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On the basis of the above information we
2024-03-21
On the basis of the above information, we designed a new series of benzothiazole–piperazine derivatives (–) that have the aforementioned structural requirements (). Benzothiazole is an important ring system in the drug discovery studies of AD. There are several benzothiazole compounds that show pote
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Acetylcholinesterase AChE activity and expression level can
2024-03-21
Acetylcholinesterase (AChE) activity and expression level can be down regulated by TCDD in neuronal cells [3], [6]. Thus AChE could be considered as a target of the neuronal toxicity of dioxin. AChE has several types of transcripts by alternative splicing in the 3′ region of primary transcripts [7],
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A similar circuit between pyramidal neurons
2024-03-21
A similar circuit between pyramidal neurons and SST interneurons is also prevalent in layers 2/3 of the cortex. The synapses onto SST interneurons, however, are functionally weak, raising questions about their computational power. In the first set of experiments, Urban-Ciecko et al. (2018) show that
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Previously several genes such as cytokine
2024-03-21
Previously, several genes such as cytokine (Lyu and Park, 2007), cell motility-associated genes (Schotterl et al., 2017), transforming growth factor-β (TGF-β), TGF-β receptor II which is a cell surface receptor with serine/threonine kinase activity (Jiang et al., 2014, Schotterl et al., 2017), cell
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