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71.
72.
Sheila Unger Maria?W. Górna Antony Le?Béchec Sonia Do?Vale-Pereira Maria?Francesca Bedeschi Stefan Geiberger Giedre Grigelioniene Eva Horemuzova Faustina Lalatta Ekkehart Lausch Cinzia Magnani Sheela Nampoothiri Gen Nishimura Duccio Petrella Francisca Rojas-Ringeling Akari Utsunomiya Bernhard Zabel Sylvain Pradervand Keith Harshman Belinda Campos-Xavier Luisa Bonafé Giulio Superti-Furga Brian Stevenson Andrea Superti-Furga 《American journal of human genetics》2013,92(6):990-995
Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth. 相似文献
73.
Keisuke Maruyama Masaharu Nakamura Shusuke Tomoshige Kazuyuki Sugita Makoto Makishima Yuichi Hashimoto Minoru Ishikawa 《Bioorganic & medicinal chemistry letters》2013,23(14):4031-4036
Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ERα/ERβ subtype selectivity. Among the compounds examined, 18 was found to be a potent ERα-antagonist with high selectivity over ERβ and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ERα. ERα-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. 相似文献
74.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
75.
Tomohisa Nagasaki Masanori Sugita Hideaki Fukawa Hsin-Tung Lin 《Bioscience, biotechnology, and biochemistry》2013,77(2):363-369
Taxonomical investigation was performed on the bacterium, strain NB 320 isolated from soil, and it was identified as Enterobacter cloacae. This bacterium produced the enzyme which catalyzed the transamination reaction between 3,4-dihydroxyphenyl pyruvate and an amino acid to form l-Dopa.The optimum culture conditions for the enzyme production were studied along with the characteristics of the enzyme. The enzyme of the strain was different in some properties from that of Alcaligenes faecalis IAM 1015 which had been already studied. The former utilized glutamate as an amino donor best among the amino acids tested for transamination and was induced by the addition of glutamine and asparagine. Intact cells of the strain did not catalyze the reaction unless they were treated with sonication or with a detergent. 相似文献
76.
Tomohisa Nagasaki Masanori Sugita Hideaki Fukawa 《Bioscience, biotechnology, and biochemistry》2013,77(7):1701-1706
Some enzymatic properties were examined on the transaminase (DOPA transaminase) which catalyzes the reaction between 3,4-dihydroxy phenyl pyruvate (DOPP) and certain amino acids to form 3,4-dihydroxyphenyl-L-alanine (DOPA). The cell-free extract from Alcaligenes faecalis IAM 1015 was used as the DOPA transaminase. L-Aspartate, L-glutamate, and L-phenylalanine were utilized efficiently as amino donor. The occurrence of three kinds of transaminase—aspartate-DOPP transaminase (ADT), glutamate-DOPP transaminase (GDT), and phenylalanine-DOPP transaminase (PDT)—was postulated.The pH optima of these enzymes were observed in the alkaline pH range. The enzymes were unstable in the acidic range and inactivated above 60°C. Ca2+, Mg2+, and Mn2+ protected PDT from heat denaturation. Fe2+, Cu2+, and Al3+ remarkably inhibited the enzyme reaction. 相似文献
77.
Yasuo Noda Yoshiki Ida Shinichi Tanaka Taku Toyama Murilo Felix Roggia Yasuhiro Tamaki Naohiko Sugita Mamoru Mitsuishi Takashi Ueta 《PloS one》2013,8(1)
Purpose
To elucidate the merits of robotic application for vitreoretinal maneuver in comparison to conventional manual performance using an in-vitro eye model constructed for the present study.Methods
Capability to accurately approach the target on the fundus, to stabilize the manipulator tip just above the fundus, and to perceive the contact of the manipulator tip with the fundus were tested. The accuracies were compared between the robotic and manual control, as well as between ophthalmologists and engineering students.Results
In case of manual control, ophthalmologists were superior to engineering students in all the 3 test procedures. Robotic assistance significantly improved accuracy of all the test procedures performed by engineering students. For the ophthalmologists including a specialist of vitreoretinal surgery, robotic assistance enhanced the accuracy in the stabilization of manipulator tip (from 90.9 µm to 14.9 µm, P = 0.0006) and the perception of contact with the fundus (from 20.0 mN to 7.84 mN, P = 0.046), while robotic assistance did not improve pointing accuracy.Conclusions
It was confirmed that telerobotic assistance has a potential to significantly improve precision in vitreoretinal procedures in both experienced and inexperienced hands. 相似文献78.
79.
Norimasa Sugita 《PloS one》2016,11(11)
A recent focus of interest has been on the functional significance of genital licking (fellatio and cunnilingus) in relation to sexual selection in Pteropodid bats. In the present paper, a form of fellatio in wild Bonin flying foxes, Pteropus pselaphon, performed between adult males has been reported. During the mating season, adult flying foxes roost in same-sex groups, forming ball-shaped clusters which provide warmth. The female clusters may also contain a few males. Unassociated with allogrooming, same-sex genital licking occurred among males in the all male clusters. As such, male-male fellatio can be considered as homosexual behavior, two functional explanations could account for this behavior; the social bonding and the social tension regulation hypotheses suggested in a previous review. Given that neither the simpler alternative that in all male groups such fellatio may represent misdirected sexual behavior, nor the two previously proposed functional hypotheses were supported by the data, I propose another functional hypothesis. Homosexual fellatio in this species could help males solve inconsistent situations in the roost when there are conflicts between cooperative behavior for social thermoregulation and competition for mating. 相似文献
80.
Belma Zengin Kurt Çiğdem Bilen Adem Ergun Nahit Gençer Oktay Arslan 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):991-998
New secondary benzenesulphonamide-substituted coumarylthiazole derivatives were synthesized and their inhibitory effects on purified carbonic anhydrase I and II were evaluated using CO2 as a substrate. The result showed that all the synthesized compounds exhibited inhibitory activity on both hCA I and hCA II with N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)naphthalene-2-sulphonamide (5f, IC50 value of 5.63 and 8.48?µM, against hCA I and hCA II, respectively) as the strongest inhibitor revealed from this study. Structure–activity relationship revealed that the inhibitory activity of the synthesized compounds is related to the type of the halogen and bulky substituent on the phenyl ring. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were assayed. 4-methoxy-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)benzenesulphonamide (5e) exhibited the strongest ABTS and CUPRAC activity with IC50 value of 48.83?µM and A0.50 value of 23.29?µM, respectively. 相似文献