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1
Bitar, K. N., C. Hillemeier, P. Biancani e K. J. Balazovich. "Regulation of smooth muscle contraction in rabbit internal anal sphincter by protein kinase C and Ins(1,4,5)P3". American Journal of Physiology-Gastrointestinal and Liver Physiology 260, n. 4 (1 aprile 1991): G537—G542. http://dx.doi.org/10.1152/ajpgi.1991.260.4.g537.
Testo completoAbstract (sommario):
We have examined the role of protein kinase C (PKC)-beta II and its functional relationship to inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and intracellular Ca2+ in the contraction of smooth muscle cells from the rabbit internal and sphincter (IAS). PKC-beta (0.1-100 U/ml) and Ins(1,4,5)P3 (10(-9) to 10(-6) M) caused concentration-dependent contraction of IAS smooth muscle cells permeabilized by saponin. The combination of threshold concentrations of Ins(1,4,5)P3 (10(-9) M) and PKC (0.1 U/ml) was more than additive, causing near maximal shortening (28.2 +/- 2.1% decrease in cell length from control). The response to high concentrations of Ins(1,4,5)P3 and PKC used in combination was not greater than the response to either agent alone. The calmodulin antagonist W-7 (10(-9) M) inhibited the maximal contraction induced by Ins(1,4,5)P3 but not contraction caused by PKC, whereas the PKC antagonist H-7 (10(-6) M) inhibited the maximal contraction induced by PKC but not contraction caused by Ins(1,4,5)P3. Threshold doses of the ionophores A23187 (10(-9) M) and ionomycin (0.2 ng/ml) caused little contraction by themselves, but they potentiated the response elicited by a threshold concentration of PKC (0.1 U/ml), inducing maximal contraction. Preincubation of IAS cells with 4 mM Sr2+, which inhibits the release of intracellular Ca2+, abolished the potentiating effect of Ins(1,4,5)P3 and calcium ionophores on PKC, but the calmodulin antagonist W-7 did not. These data suggest that the contractile effect of maximally effective doses of PKC is independent of the effects of Ins(1,4,5)P3. At submaximal concentrations, however, PKC-dependent contraction is potentiated by Ins(1,4,5)P3 or by ionophore-mediated release of intracellular Ca2+ without requiring calmodulin activation.
2
Barkun, A., K. Ravanbakhsh, D. Kim, G. Milky, P. Stanowski, O. Geraci, M. Martel, C. Menard e D. von Renteln. "A72 THE ENDOSCOPIC YIELD OF PRIORITIZED INDICATIONS USING A PROVINCIAL-WIDE COLONOSCOPY REFERRAL FORM". Journal of the Canadian Association of Gastroenterology 7, Supplement_1 (14 febbraio 2024): 49–50. http://dx.doi.org/10.1093/jcag/gwad061.072.
Testo completoAbstract (sommario):
Abstract Background The widespread use of a standardized and validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait time categories, has allowed for a more comprehensive assessment of routine colonoscopy practice Aims To validate the Quebec PCRF by better characterizing endoscopic finding yields according to specific clinical indications. Methods This retrospective cohort study includes consecutive adult patients with available data from the PCRF from two tertiary hospitals. The primary outcome was the diagnostic rates of colorectal cancer (CRC). Secondary outcomes assessed incidences of clinically significant lesions (CSL) on endoscopy and confirmed at pathology. These are CRC, advanced adenomas, sessile serrated polyps, polyps ≥ 5mm, colitis, colonic strictures, and miscellaneous other findings excluding hemorrhoids and diverticulosis. Descriptive and inferential statistics, and multivariable regression predictive modeling are reported. Results Overall, 14,657 patients (mean age 59.2 ± 14.0 years, 50.9% female) were included from September 2018 to August 2022. The most frequent indications for colonoscopy were polyp surveillance (IN13, 20.8%), recent change in bowel habits (IN7, 11.9%), a positive fecal immunochemical test (IN5, 8.3%), a family history of CRC or polyps (first-degree relative) (IN8, 6.4%), and suspected active inflammatory bowel disease (IBD) (IN3, 5.8%). Overall, 40.6% had CSL, including CRCs in 0.8%. CRCs were found more frequently for IN2 (19.7% vs 2.0%, pampersand:003C0.01), IN5 (29.9% vs 8.2%, pampersand:003C0.01), and an unexplained documented iron deficiency anemia (IN6) (11.8% vs 5.2%, pampersand:003C0.01). CSLs were more frequent for IN3 (1.6% vs 5.8%, p=0.04), IN7 (4.7% vs 12.0%, p=0.01), IN8 (0.8% vs 6.5%, p=0.01), IN13 (7.1% vs 20.9%, pampersand:003C0.01), IBD surveillance (IN15, 0.0% vs 4.0%, p=0.02), and surveillance for a significant family history (IN21, 0.0% vs 3.7%, p=0.02). On multivariable analysis, CRC was significantly associated with IN2 OR=31.8 (4.86; 208.7), IN5 OR=19.2 (3.86; 95.7), and IN6 OR=15.7 (2.37; 78.0) - (all are high priority PCRF referrals with a suggested shorter wait time than for most other indications). CSLs were significantly associated with age (OR=1.03 (1.02; 1.03)), IN2 (OR=2.32 (1.35; 3.99)), IN5 (OR=2.37 (1.74; 3.22)), and IN13 (OR= 1.66 (1.36; 2.02)). Conclusions This large cohort study confirms the validity of indications and corresponding prioritization of wait times of a PCRF. Funding Agencies CPAC and MSSS
3
Trevisan, Gustavo Aléssio, Everton Leonardi da Silva, Anderson Luiz de Carvalho e Rafael Messias Luiz. "EFEITOS ANESTÉSICOS DA ADMINISTRAÇÃO INTRANASAL OU INTRAMUSCULAR DA ASSOCIAÇÃO DE MIDAZOLAM E CETAMINA RACÊMICA OU S+ EM PERIQUITO AUSTRALIANO (Melopsittacus undulatus)". Ciência Animal Brasileira 17, n. 1 (marzo 2016): 126–32. http://dx.doi.org/10.1590/1089-6891v17i131271.
Testo completoAbstract (sommario):
Resumo A anestesia intranasal em aves é considerada uma técnica anestésica segura, simples e eficiente. O objetivo deste estudo foi comparar os efeitos anestésicos da associação de midazolam (5 mg.kg-1) e cetamina (15 mg.kg-1) nas formulações racêmica (R) ou S+ (S) administrados pela via intranasal (IN) ou intramuscular (IM) em periquitos australianos (Melopsittacus undulatus). Foram utilizados oito periquitos em delineamento do tipo crossover, em quatro tratamentos: INR, INS, IMR e IMS. Foram avaliados os tempos de latência, decúbito dorsal, anestesia e recuperação, grau de sedação e qualidade de recuperação. Foi observada diferença significativa no tempo de latência entre INS (40,25±10,55 seg) e IMR (74,32±21,77 seg); entre as vias de administração para o tempo de decúbito dorsal, INS (23,93±7,51 min) e INR (28,68±16,13 min), diferente de IMS (60,08±27,37 min) e IMR (74,3±21,77 min) e para tempo de anestesia, INS (45,48±17,94 min) e INR (39,24±15,62 min), diferentes de IMS (75,84±20,20 min) e IMR (79,4±20,73 min). O tempo de recuperação foi significativamente maior em INS (21,55±18,43 min) comparado a IMR (5,1±3,56 min). Pode-se concluir que as duas vias de administração avaliadas podem ser utilizadas em procedimentos de curta duração e não invasivos e a via intranasal é preferível para procedimentos rápidos.
4
A.V, Raveendran. "Inhalational Steroids and Iatrogenic Cushing’s Syndrome". Open Respiratory Medicine Journal 8, n. 1 (31 dicembre 2014): 74–84. http://dx.doi.org/10.2174/1874306401408010074.
Testo completoAbstract (sommario):
Bronchial asthma (BA) and Allergic rhinitis (AR) are common clinical problems encountered in day to day practice, where inhalational corticosteroids (ICS) or intranasal steroids (INS) are the mainstay of treatment. Iatrogenic Cushing syndrome (CS) is a well known complication of systemic steroid administration. ICS /INS were earlier thought to be safe, but now more and more number of case reports of Iatrogenic Cushing syndrome have been reported, especially in those who are taking cytochrome P450 (CYP 450) inhibitors. Comparing to the classical clinical features of spontaneous Cushing syndrome, iatrogenic Cushing syndrome is more commonly associated with osteoporosis, increase in intra-ocular pressure, benign intracranial hypertension, aseptic necrosis of femoral head and pancreatitis, where as hypertension, hirsuitisum and menstrual irregularities are less common. Endocrine work up shows low serum cortisol level with evidence of HPA (hypothalamo-pituitary-adrenal) axis suppression. In all patients with features of Cushing syndrome with evidence of adrenal suppression always suspect iatrogenic CS. Since concomitant administration of cytochrome P450 inhibitors in patients on ICS/INS can precipitate iatrogenic CS, avoidance of CYP450 inhibitors, its dose reduction or substitution of ICS are the available options. Along with those, measures to prevent the precipitation of adrenal crisis has to be taken. An update on ICS-/INS- associated iatrogenic CS and its management is presented here.
5
Fossataro, Claudia, Pia Clara Pafundi, Roberta Mattei, Valentina Cima, Francesca De Rossi e Gustavo Savino. "Infantile nystagmus syndrome: An observational, retrospective, multicenter study". Optometry and Vision Science 101, n. 4 (aprile 2024): 211–23. http://dx.doi.org/10.1097/opx.0000000000002131.
Testo completoAbstract (sommario):
SIGNIFICANCE This multicenter study assessed clinical and psychological aspects of infantile nystagmus syndrome (INS) focusing on its management and nonsurgical treatment. PURPOSE This study aimed to assess clinical features, management, relationship life, and psychological impact in a group of patients with nystagmus onset in pediatric age. METHODS This observational study included patients diagnosed with INS referred to two Italian centers from January 1, 2017, to December 31, 2020. Ophthalmologic and orthoptic features and impact of visual function on quality of life, according to nystagmus-specific nystagmus quality of life questionnaire, were analyzed within the overall sample and in any of INS subgroups. RESULTS Forty-three patients were included; 65.1% of them had idiopathic INS (IINS), and 34.9% had INS associated with ocular diseases (INSOD). The median age was 15.4 years (interquartile range [IQR], 10.4 to 17.3 years), significantly different between groups (median, 15.8 years among those with IINS vs. 12.3 years among those with INSOD; p<0.001). In the INSOD subgroup, strabismus was significantly more prevalent (93.3 vs. 57.1%; p=0.017). Binocular distance best-corrected visual acuity in primary position was significantly higher in the IINS subsample (p<0.001). Such behavior was further confirmed at anomalous head position evaluation (p<0.001). At near best-corrected visual acuity assessment, differences between groups were more remarkable in primary position (p<0.001) than in anomalous head position. Contrast sensitivity showed significantly higher values in the IINS subgroup (p<0.001). The nystagmus quality of life questionnaire disclosed a significantly lower score in IINS as compared with INSOD (median total score, 90.5 [IQR, 84 to 97] vs. 94 [IQR, 83.0 to 96.5]; p<0.001). CONCLUSIONS The IINS group showed significantly better ophthalmologic and orthoptic outcomes than the INSOD group. The psychological and quality-of-life impact was instead significantly greater in the IINS group. To the best of our knowledge, this is the first multicenter study investigating the clinical features of IIN and comparing the two main subgroups, IINS and INSOD.
6
Timofeev, E. A., e G. S. Tsekhanovich. "INS simulator for debugging INS/GNSS data". IEEE Aerospace and Electronic Systems Magazine 24, n. 1 (gennaio 2009): 38–40. http://dx.doi.org/10.1109/maes.2009.4772753.
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Kleespies, Matthias Winfried, Tina Braun, Paul Wilhelm Dierkes e Volker Wenzel. "Measuring Connection to Nature—A Illustrated Extension of the Inclusion of Nature in Self Scale". Sustainability 13, n. 4 (6 febbraio 2021): 1761. http://dx.doi.org/10.3390/su13041761.
Testo completoAbstract (sommario):
The human-nature connection is an important factor that is frequently the subject of environmental education research and environmental psychology. Therefore, over the years, numerous measuring instruments have been established to quantitatively record a person’s connection to nature. However, there is no instrument specifically for children with cognitive limitations. For this reason, in this study, an established scale for connection to nature, the inclusion of nature in self scale (INS), was modified especially for the needs of this group. Study 1 investigated what students understand by the term “nature” in order to create an illustrated version of the INS. In study 2, the new instrument was tested on university students and compared with the original INS and the connectedness to nature scale (CNS). No significant differences between the original INS and the new developed scale were found (p = 0.247), from which it can be concluded that the illustrated INS (IINS) measures the connection to nature with similar accuracy as the original INS. In study 3, the instrument was tested together with other established nature connection instruments on the actual target group, students with disabilities. The correlation between the IINS, the CNS, and nature connectedness scale (NR) were in accordance with the expected literature values (rIINS-CNS = 0.570 & rIINS-NR = 0.605). The results of this study also prove effectiveness of the developed illustrated scale. This research thus provides a suitable measuring instrument for people with learning difficulties and can make a contribution to the investigation of human-nature connections and conservation education.
8
Azhermacheva, M., E. Therskih, K. Burkova e D. Plotnikov. "Endothelial dysfunction in smoker patients/INS; with/INS; acute isc/INS;hemic stroke". Journal of the Neurological Sciences 333 (ottobre 2013): e272. http://dx.doi.org/10.1016/j.jns.2013.07.1038.
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Haenicke, Diether H., e Helena Janeczek. "Ins Freie". World Literature Today 64, n. 4 (1990): 632. http://dx.doi.org/10.2307/40146936.
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Papachristopoulos, Ioannis. ""Ins offene..."". Die Musikforschung 61, n. 4 (22 settembre 2021): 349–67. http://dx.doi.org/10.52412/mf.2008.h4.510.
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Bernhart, Wolfgang, e Norbert Dressler. "Ins Grüne". Automotive Agenda 3, n. 3 (settembre 2010): 52–56. http://dx.doi.org/10.1007/bf03223782.
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Martin, Gerhard Marcel. "Ins Offene". Praktische Theologie 40, n. 1 (1 febbraio 2005): 73–76. http://dx.doi.org/10.14315/prth-2005-0118.
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Coulehan, Jack. "Shut-ins". JAMA 295, n. 19 (17 maggio 2006): 2225. http://dx.doi.org/10.1001/jama.295.19.2225.
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Finazzi-Agrò, Alessandro. "Prote-ins". Biotechnology and Applied Biochemistry 65, n. 1 (gennaio 2018): 5–6. http://dx.doi.org/10.1002/bab.1639.
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Parin, Alexei. "INS INNERSTE". Opernwelt 64, n. 1 (2023): 38–39. http://dx.doi.org/10.5771/0030-3690-2023-1-038.
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Mattenklott, Gert. "«Komm ins Offene, Freund!» Transit ins wilde Denken". Zeitschrift für Ideengeschichte 2, n. 4 (2008): 5–10. http://dx.doi.org/10.17104/1863-8937-2008-4-5.
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Aurangzeb, S., e Z. Zaiwalla. "Paediatric narcolepsy — /INS;A seven-/INS;year experience". Journal of the Neurological Sciences 333 (ottobre 2013): e687. http://dx.doi.org/10.1016/j.jns.2013.07.2373.
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Kovalyuk, Z. D. "Investigation of InS-InSe heterojunctions prepared using sulphurization of p-InSe". Semiconductor Physics Quantum Electronics and Optoelectronics 15, n. 1 (29 marzo 2012): 38–40. http://dx.doi.org/10.15407/spqeo15.01.038.
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YONESHIMA, Hiroyuki, Atsushi MIYAWAKI, Takayuki MICHIKAWA, Teiichi FURUICHI e Katsuhiko MIKOSHIBA. "Ca2+ differentially regulates the ligand-affinity states of type 1 and type 3 inositol 1,4,5-trisphosphate receptors". Biochemical Journal 322, n. 2 (1 marzo 1997): 591–96. http://dx.doi.org/10.1042/bj3220591.
Testo completoAbstract (sommario):
To elucidate the functional difference between type 1 and type 3 Ins(1,4,5)P3 receptors [Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 respectively] we studied the effect of Ca2+ on the ligand-binding properties of both Ins(1,4,5)P3R types. We expressed full-length human Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 from cDNA species in insect ovary Sf9 cells, and the membrane fractions were used for Ins(1,4,5)P3-binding assays. The binding of Ins(1,4,5)P3 to Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 was differentially regulated by Ca2+. With increasing concentrations of free Ca2+ ([Ca2+]), Ins(1,4,5)P3 binding to Ins(1,4,5)P3R1 decreased, whereas that to Ins(1,4,5)P3R3 increased. Alteration of Ins(1,4,5)P3 binding to Ins(1,4,5)P3R1 was observed at [Ca2+] ranging from less than 1 nM to more than 10 μM. The EC50 of Ins(1,4,5)P3 binding was 100 nM Ca2+ for Ins(1,4,5)P3R1. In contrast, Ins(1,4,5)P3 binding to Ins(1,4,5)P3R3 was changed at high [Ca2+] with an EC50 value of 872 nM, and steeply between 100 nM and 10 μM. These Ca2+-dependent alterations of Ins(1,4,5)P3 binding to both Ins(1,4,5)P3R types were reversible. Scatchard analyses revealed that Ca2+ changed the affinity of both Ins(1,4,5)P3R types but not the total number of Ins(1,4,5)P3-binding sites. The Kd values of Ins(1,4,5)P3R1 for Ins(1,4,5)P3 were 78.5 nM with 3 nM free Ca2+, and 312 nM with 1.4 μM free Ca2+. In contrast, Ins(1,4,5)P3R3 exhibited an affinity for Ins(1,4,5)P3 with Kd values of 116 nM with 3 nM free Ca2+, and 62.2 nM with 1.4 μM free Ca2+. These results indicate that (1) both Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 have at least two affinity states, (2) Ca2+ regulates interconversions between these states, and (3) Ca2+ regulates the binding of Ins(1,4,5)P3 to Ins(1,4,5)P3R1 and Ins(1,4,5)P3R3 in opposite manners.
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Astriani, Nadia, e Yulinda Adharani. "PEMBANGUNAN KERETA CEPAT JAKARTA-BANDUNG DARI SUDUT PANDANG PENEGAKAN HUKUM PENATAAN RUANG". Jurnal Rechts Vinding: Media Pembinaan Hukum Nasional 6, n. 2 (31 agosto 2017): 243. http://dx.doi.org/10.33331/rechtsvinding.v6i2.173.
Testo completoAbstract (sommario):
<p>Pembangunan infrastruktur harus dilakukan dengan mempertimbangkan pembangunan berkelanjutan serta mengedepankan instrumen pencegahan dan/atau kerusakan lingkungan<ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:37">, hal ini berlaku pula terhadap </ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">proyek </ins><ins cite="mailto:alice%20angelica" datetime="2017-08-18T15:16">i</ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">nfrast</ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">r</ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">ukt</ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">u</ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">r </ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:38">pembangunan kereta cepat Jakarta-Bandung</ins>. Jika tidak, akan merusak lingkungan dan berdampak kepada kehidupan sosial masyarakat sekitar. <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:39">Penelitian </ins>ini akan membahas pembangunan <ins cite="mailto:alice%20angelica" datetime="2017-08-18T15:16">k</ins>ereta cepat Jakarta-Bandung dalam kerangka penataan ruang serta upaya penegakan hukum penataan ruangnya <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:39">dengan </ins>menggunakan metode yuridis-normatif<ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:40">, hasil penelitian menunjukan </ins><ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:41">pembangunan p</ins>royek kereta cepat Jakarta<ins cite="mailto:alice%20angelica" datetime="2017-08-18T15:17">-</ins>Bandung <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:42">seharusnya </ins>mengikuti kaidah hukum penataan ruang, dimana sebuah rencana pemanfaatan ruang harus dicantumkan dalam Rencana Tata Ruang Wilayah (RTRW). Tidak tercantumnya proyek ini dalam RTRW Kota/Kabupaten berarti tidak menaati RTR<ins cite="mailto:TDA%20P" datetime="2017-08-15T15:45">W</ins> yang ditetapkan. Selain itu, kondisi ini juga bisa dikategorikan sebagai pemanfaatan ruang yang tidak sesuai dengan peruntukkannya<ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:43">, sehingga</ins> <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:43">m</ins>erupakan unsur pelanggaran yang dapat dikenakan sanksi administrasi dan pidana. <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:43">Oleh sebab itu d</ins>alam melaksanakan pembangunan, <ins cite="mailto:Apri%20Listiyanto" datetime="2017-08-08T09:43">P</ins>emerintah harus lebih konsisten dalam memilih proyek yang sesuai dengan rencana yang telah ditetapkan.</p>
21
Ackermann, K. E., B. G. Gish, M. P. Honchar e W. R. Sherman. "Evidence that inositol 1-phosphate in brain of lithium-treated rats results mainly from phosphatidylinositol metabolism". Biochemical Journal 242, n. 2 (1 marzo 1987): 517–24. http://dx.doi.org/10.1042/bj2420517.
Testo completoAbstract (sommario):
In cerebral cortex of rats treated with increasing doses of LiCl, the relative concentrations of Ins(1)P, Ins(4)P and Ins(5)P (when InsP is a myo-inositol phosphate) are approx. 10:1:0.2 at all doses. In rats treated with LiCl followed by increasing doses of pilocarpine a similar relationship occurs. myo-Inositol-1-phosphatase (InsP1ase) from bovine brain hydrolyses Ins(1)P, Ins(4)P and Ins(5)P at comparable rates, and these substrates have similar Km values. The hydrolysis of Ins(4)P is inhibited by Li+ to a greater degree than is hydrolysis of Ins(1)P and Ins(5)P. D-Ins(1,4,5)P3 and D-Ins(1,4)P2 are neither substrates nor inhibitors of InsP1ase. A dialysed high-speed supernatant of rat brain showed a greater rate of hydrolysis of Ins(1)P than of D-Ins(1,4)P2 and a lower sensitivity of the bisphosphate hydrolysis to LiCl, as compared with the monophosphate. That enzyme preparation produced Ins(4)P at a greater rate than Ins(1)P when D-Ins(1,4)P2 was the substrate. The amount of D-Ins(3)P [i.e. L-Ins(1)P, possibly from D-Ins(1,3,4)P3] is only 11% of that of D-Ins(1)P on stimulation with pilocarpine in the presence of Li+. DL-Ins(1,4)P2 was hydrolysed by InsP1ase to the extent of about 50%; both Ins(4)P and Ins(1)P are products, the former being produced more rapidly than the latter; apparently L-Ins(1,4)P2 is a substrate for InsP1ase. Li+, but not Ins(2)P, inhibited the hydrolysis of L-Ins(1,4)P2. The following were neither substrates nor inhibitors of InsP1ase; Ins(1,6)P2, Ins(1,2)P2, Ins(1,2,5,6)P4, Ins(1,2,4,5,6)P5, Ins(1,3,4,5,6)P5 and phytic acid. myo-Inositol 1,2-cyclic phosphate was neither substrate nor inhibitor of InsP1ase. We conclude that the 10-fold greater tissue contents of Ins(1)P relative to Ins(4)P in both stimulated and non-stimulated rat brain in vivo are the consequence of a much larger amount of PtdIns metabolism than polyphosphoinositide metabolism under these conditions.
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Al-Dhahir, W., A. Mubashir e D. S. Andole. "Total ophthalmoplegia /INS;due to giant /INS;cell arteritis". Journal of the Neurological Sciences 333 (ottobre 2013): e699. http://dx.doi.org/10.1016/j.jns.2013.07.2416.
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Narahara, Kouji. "Dir ins(9)(q34.3q22.1q31.3) or inv ins(9)(q34.3q22.3q21.2)?" Japanese journal of human genetics 32, n. 1 (marzo 1987): 49–50. http://dx.doi.org/10.1007/bf01876528.
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Benecke, R., D. Hauschke e P. Roggenkämper. "Incobotulinum /INS;toxin /INS;A demonstrated therapeutic equivalence to onabotulinum /INS;toxin /INS;A in the treatment of blepharospasm and cervical dystonia". Journal of the Neurological Sciences 333 (ottobre 2013): e120. http://dx.doi.org/10.1016/j.jns.2013.07.402.
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Kuo, Shu-Chen, Yung-Chih Wang, Mei-Chen Tan, Wei-Cheng Huang, Yih-Ru Shiau, Hui-Ying Wang, Jui-Fen Lai, I.-Wen Huang e Tsai-Ling Lauderdale. "In vitro activity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan". Journal of Antimicrobial Chemotherapy 76, n. 8 (6 maggio 2021): 2071–78. http://dx.doi.org/10.1093/jac/dkab141.
Testo completoAbstract (sommario):
Abstract Objectives To investigate the susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB) and Pseudomonas aeruginosa (INS-PA) to novel antibiotics. Methods MICs were determined using the broth microdilution method. Carbapenemase and ESBL phenotypic testing and PCR for genes encoding ESBLs, AmpCs and carbapenemases were performed. Results Zidebactam, avibactam and relebactam increased the respective susceptibility rates to cefepime, ceftazidime and imipenem of 17 INS-EC by 58.8%, 58.8% and 70.6%, of 163 INS-KP by 77.9%, 88.3% and 76.1% and of 81 INS-PA by 45.7%, 38.3% and 85.2%, respectively. Vaborbactam increased the meropenem susceptibility of INS-EC by 41.2% and of INS-KP by 54%. Combinations of β-lactams and novel β-lactamase inhibitors or β-lactam enhancers (BLI-BLE) were inactive against 136 INS-AB. In 58 INS-EC and INS-KP with exclusively blaKPC-like genes, zidebactam, avibactam, relebactam and vaborbactam increased the susceptibility of the partner β-lactams by 100%, 96.6%, 84.5% and 75.9%, respectively. In the presence of avibactam, ceftazidime was active in an additional 85% of 20 INS-EC and INS-KP with exclusively blaOXA-48-like genes while with zidebactam, cefepime was active in an additional 75%. INS-EC and INS-KP with MBL genes were susceptible only to cefepime/zidebactam. The β-lactam/BLI-BLE combinations were active against INS-EC and INS-KP without detectable carbapenemases. For INS-EC, INS-KP and INS-AB, tigecycline was more active than omadacycline and eravacycline but eravacycline had a lower MIC distribution. Lascufloxacin and delafloxacin were active in <35% of these INS isolates. Conclusions β-Lactam/BLI-BLE combinations were active in a higher proportion of INS-EC, INS-KP and INS-PA. The susceptibility of novel fluoroquinolones and tetracyclines was not superior to that of old ones.
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Salamun, Tri. "PELAKSANAAN IZIN GANGGUAN DALAM USAHA KEDAI KOPI DI KOTA BANDA ACEH". Jurnal Rechts Vinding: Media Pembinaan Hukum Nasional 7, n. 3 (17 dicembre 2018): 409. http://dx.doi.org/10.33331/rechtsvinding.v7i3.270.
Testo completoAbstract (sommario):
<p><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:57">Keberadaan kedai kopi di Kota Banda Aceh </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:58">semakin marak seiring dengan pulihnya kondisi perekonomian masyarakat pasca bencana Tsunami yang melanda Aceh pada akhir Tahun 2004.</ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:59"> Bisnis </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:56">café dan kedai kopi khususnya di Kota Banda Aceh</ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:59"> berkembang menjadi tempat berkumpulnya masyarakat dalam melakukan rutinitas kesehariannya dengan latar belakang yang beragam</ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:56">.</ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T10:00">Banyaknya kedai kop</ins>i<ins cite="mailto:Windows%20User" datetime="2018-11-06T10:00"> ini disertai juga dengan dampak buruk antara lain menimbulkan </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T09:57">terhadap lingkungan sekitar, atau kerugian-kerugian lainnya. </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T10:01">Oleh karena itu </ins>untuk mengetahui pelaksanaan Izin Gangguan bagi usaha kedai kopi, untuk menjelaskan sebab penyelenggara usaha kedai kopi yang tidak sesuai Izin Gangguan dan untuk mengetahui upaya dari Pemerintah Kota Banda Aceh dalam pengendalian Izin Gangguan dalam usaha kedai kopi<ins cite="mailto:Windows%20User" datetime="2018-11-06T10:01"> menjadi topik yang menarik untuk dibahas. Dengan pendekatan yuridis empiris terhadap permasalahan ini dihasilkan data </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T10:02"> bahwa </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T10:02">p</ins>elaksanaan ketentuan Izin Gangguan dalam usaha kedai kopi di Kota Banda Aceh belum dilaksanakan sepenuhnya. Ada yang telah melaksanakan sepenuhnya ketentuan dan ada yang belum melaksanakan sepenuhnya ketentuan. <ins cite="mailto:Windows%20User" datetime="2018-11-06T10:03">Sehingga </ins><ins cite="mailto:Windows%20User" datetime="2018-11-06T10:03">seharusnya </ins>para pelaku usaha melaksanakan kegiatan usaha sesuai ketentuan Izin Gangguan<ins cite="mailto:Windows%20User" datetime="2018-11-06T10:03">. Selain itu</ins> Pemerintah Kota Banda Aceh <ins cite="mailto:Windows%20User" datetime="2018-11-06T10:03">perlu</ins> meningkatkan pengawasan terhadap Izin Gangguan, serta segera menyelesaikan pembuatan peraturan baru tentang Izin Gangguan.</p>
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Cullen, P. J., R. F. Irvine e A. P. Dawson. "Synergistic control of Ca2+ mobilization in permeabilized mouse L1210 lymphoma cells by inositol 2,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate". Biochemical Journal 271, n. 2 (15 ottobre 1990): 549–53. http://dx.doi.org/10.1042/bj2710549.
Testo completoAbstract (sommario):
L1210 lymphoma cells were permeabilized with digitonin, and the ability of Ins(2,4,5)P3 and Ins(1,3,4,5)P4 to mobilize intracellular Ca2+ was studied. At high doses of Ins(2,4,5)P3 Ca2+ was rapidly released from intracellular stores, and prior or subsequent addition of Ins(1,3,4,5)P4 had no discernible effect. However, the Ca2(+)-mobilizing action of low (threshold or just above) concentrations of Ins(2,4,5)P3 was markedly enhanced by Ins(1,3,4,5)P4, which alone caused no mobilization of Ca2+; this phenomenon was shown not to be due to protection of Ins(2,4,5)P3 by the Ins(1,3,4,5)P4 against hydrolysis. The ability of the pre-addition of Ins(1,3,4,5)P4 to enhance subsequent Ins(2,4,5)P3-induced Ca2+ mobilization was always seen whether or not the free Ca2+ concentration was low (pCa = 7) or high (pCa = 6). However, at low Ca2+, Ins(1,3,4,5)P4 could cause a further mobilization if added after the Ins(2,4,5)P3, whereas at higher Ca2+ values Ins(1,3,4,5)P4 was only able to affect Ca2+ if added before Ins(2,4,5)P3. These effects of Ins(1,3,4,5)P4 were not, at the same concentration, mimicked by a random mixture of InsP4 isomers obtained by partial acid hydrolysis of phytic acid, by Ins(1,3,4)P3 or by Ins(1,3,4,5,6)P5, and they were shown not to be due to enzymic generation of Ins(1,4,5)P3 from Ins(1,3,4,5)P4 by (a) the absence of any detectable production of Ins(1,4,5)P3 if radiolabelled Ins(1,3,4,5)P4 was used, or (b) the observation that Ins(1,3,4,5,6)P5 could mimic Ins(1,3,4,5)P4 provided that higher doses were used; this inositol phosphate, when added radiolabelled, yielded only trace quantities of D/L-Ins(1,4,5,6)P4, which itself does not mobilize Ca2+. We interpret these results overall to mean that in these cells there is a small proportion of the Ins(2,4,5)P3-mobilizable Ca2+ pools which can only be mobilized in the presence of Ins(1,3,4,5)P4 [or at the least, Ins(1,3,4,5)P4 can help Ins(2,4,5)P3 to gain access to them]. The significance of this conclusion is discussed in the light of current concepts of the second messenger function of Ins(1,3,4,5)P4.
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Greiner, Ralf, e Nils-Gunnar Carlsson. "myo-Inositol phosphate isomers generated by the action of a phytate-degrading enzyme from Klebsiella terrigena on phytate". Canadian Journal of Microbiology 52, n. 8 (1 agosto 2006): 759–68. http://dx.doi.org/10.1139/w06-028.
Testo completoAbstract (sommario):
For the first time a dual pathway for dephosphorylation of myo-inositol hexakisphosphate by a histidine acid phytase was established. The phytate-degrading enzyme of Klebsiella terrigena degrades myo-inositol hexakisphosphate by stepwise dephosphorylation, preferably via D-Ins(1,2,4,5,6)P5, D-Ins(1,2,5,6)P4, D-Ins(1,2,6)P3, D-Ins(1,2)P2 and alternatively via D-Ins(1,2,4,5,6)P5, Ins(2,4,5,6)P4, D-Ins(2,4,5)P3, D-Ins(2,4)P2 to finally Ins(2)P. It was estimated that more than 98% of phytate hydrolysis occurs via D-Ins(1,2,4,5,6)P5. Therefore, the phytate-degrading enzyme from K. terrigena has to be considered a 3-phytase (EC 3.1.3.8). A second dual pathway of minor importance could be proposed that is in accordance with the results obtained by analysis of the dephosphorylation products formed by the action of the phytate-degrading enzyme of K. terrigena on myo-inositol hexakisphosphate. It proceeds preferably via D-Ins(1,2,3,5,6)P5, D-Ins(1,2,3,6)P4, Ins(1,2,3)P3, D-Ins(2,3)P2 and alternatively via D-Ins(1,2,3,5,6)P5, D-Ins(2,3,5,6)P4, D-Ins(2,3,5)P3, D-Ins(2,3)P2 to finally Ins(2)P. D-Ins(2,3,5,6)P4, D-Ins(2,3,5)P3, and D-Ins(2,4)P2 were reported for the first time as intermediates of enzymatic phytate dephosphorylation. A role of the phytate-degrading enzyme from K. terrigena in phytate breakdown could not be ruled out. Because of its cytoplasmatic localization and the suggestions for substrate recognition, D-Ins(1,3,4,5,6)P5 might be the natural substrate of this enzyme and, therefore, may play a role in microbial pathogenesis or cellular myo-inositol phosphate metabolism.Key words: myo-inositol phosphate isomers, phytate-degrading enzyme, phytate, phytase, Klebsiella terrigena.
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Naito, Yusuke, Kensuke Tanaka, Kento Yoshioka, Koichiro Tatsumi, Sadao Kimura e Yoshitoshi Kasuya. "Effects of selective ETB receptor antagonist on the /INS;brain of/INS; /INS;sepsis mouse model". Life Sciences 93, n. 25-26 (dicembre 2013): e76. http://dx.doi.org/10.1016/j.lfs.2014.01.055.
Testo completo
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Wilcox, R. A., R. A. Challiss, G. Baudin, A. Vasella, B. V. Potter e S. R. Nahorski. "Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization". Biochemical Journal 294, n. 1 (15 agosto 1993): 191–94. http://dx.doi.org/10.1042/bj2940191.
Testo completoAbstract (sommario):
Ins(1,3,4,5)P4 was able to mobilize the entire Ins(1,4,5)P3-sensitive intracellular Ca2+ store in saponin-permeabilized SH-SY5Y human neuroblastoma cells in a concentration-dependent manner, yielding an EC50 value of 2.05 +/- 0.45 microM, compared with 0.14 +/- 0.03 microM for Ins(1,4,5)P3. However, L-Ins(1,3,4,5)P4 [= D-Ins(1,3,5,6)P4] failed to cause mobilization of intracellular Ca2+ at concentrations up to 100 microM. Binding studies using pig cerebellar membranes as a source of both Ins(1,4,5)P3/Ins(1,3,4,5)P4-specific binding sites have revealed a marked contrast in their stereospecificity requirements. Ins(1,4,5)P3-receptors from pig cerebella exhibited stringent stereospecificity, L-Ins(1,4,5)P3 and L-Ins(1,3,4,5)P4 were > 1000-fold weaker, whereas Ins(1,3,4,5)P4 (IC50 762 +/- 15 nM) was only about 40-fold weaker than D-Ins(1,4,5)P3 (IC50 20.7 +/- 9.7 nM) at displacing specific [3H]Ins(1,4,5)P3 binding from an apparently homogeneous Ins(1,4,5)P3 receptor population. In contrast, the Ins(1,3,4,5)P4-binding site exhibited poor stereoselectivity. Ins(1,3,4,5)P4 produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding, with two-site analysis revealing KD values for high- and low-affinity sites of 2.1 +/- 0.5 nM and 918 +/- 161 nM respectively. L-Ins(1,3,4,5)P4 also produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding which was less than 10-fold weaker than with D-Ins(1,3,4,5)P4 (IC50 values for the high- and low-affinity sites of 17.2 +/- 3.7 nM and 3010 +/- 542 nM respectively). Therefore, although L-Ins(1,3,4,5)P4 appears to be a high-affinity Ins(1,3,4,5)P4-binding-site ligand in pig cerebellum, it is a very weak agonist at the Ca(2+)-mobilizing receptors of permeabilized SH-SY5Y cells. We suggest that the ability of D-Ins(1,3,4,5)P4 to access intracellular Ca2+ stores may derive from specific interaction with the Ins(1,4,5)P3- and not the Ins(1,3,4,5)P4-receptor population.
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Barker, C. J., N. S. Wong, S. M. Maccallum, P. A. Hunt, R. H. Michell e C. J. Kirk. "The interrelationships of the inositol phosphates formed in vasopressin-stimulated WRK-1 rat mammary tumour cells". Biochemical Journal 286, n. 2 (1 settembre 1992): 469–74. http://dx.doi.org/10.1042/bj2860469.
Testo completoAbstract (sommario):
1. Temporal changes in the levels of many inositol phosphates, whose structural characterization is presented in the preceding paper [Wong, Barker, Morris, Craxton, Kirk & Michell (1991) Biochem. J. 286, 459-468], have been monitored in vasopressin-stimulated WRK-1 cells. 2. Upon stimulation, Ins(1,4,5)P3 accumulated within 1 s, consistent with its role as a rapidly acting second messenger produced by receptor activation of phosphoinositidase C. Ins(1,4)P2 and Ins(1,3,4,5)P4, both of which are immediate products of Ins(1,4,5)P3 metabolism, also accumulated quickly. Ins4P, Ins(1,3,4)P3, Ins(3,4)P2, Ins(1,3)P2, Ins1P and Ins3P, which are intermediates in the metabolism of Ins(1,4)P2 and Ins(1,3,4,5)P4 to inositol, accumulated after seconds or within a few minutes, and in a temporal sequence consistent with their known metabolic interrelationships. 3. The stimulated accumulation of Ins(1,3,4,6)P4 was delayed, as expected if it is formed by phosphorylation of Ins(1,3,4)P3. 4. Ins(3,4,5,6)P4 accumulated 2-3-fold in a few minutes, and mainly before Ins(1,3,4,6)P4. 5. Using a [3H]-/[14C]-inositol double-labelling protocol, we obtained evidence that all of the compounds that accumulated upon stimulation, except Ins(3,4,5,6)P4, originated from lipid-derived Ins(1,4,5)P3, but that the newly formed Ins(3,4,5,6)P4 came from a different source. 6. There were no consistent changes in the levels of Ins(1,3,4,5,6)P5 and InsP6 during stimulation. 7. Alongside the gradual accumulation of Ins(1:2-cyclic,4,5)P3 during stimulation [Wong, Barker, Shears, Kirk & Michell (1988) Biochem. J. 252, 1-5], there was an accumulation of Ins(1:2-cyclic,4)P2 and Ins(1:2-cyclic)P, probably as either minor side products of phosphoinositidase C action or metabolites of Ins(1:2-cyclic,4,5)P3. 8. When Li+ was present during stimulation, it redirected the dephosphorylation pathways downstream of Ins(1,4,5)P3 in the manner expected from its inhibition of inositol monophosphatase and Ins(1,4)P2/Ins(1,3,4)P3 1-phosphatase: there were marked increases in the accumulation of Ins(1,4)P2 and Ins(1,3,4)P3 and of monophosphates. Moreover, Li+ shifted the Ins1P/Ins3P balance in favour of Ins1P, thus demonstrating redirection of the metabolism of the accumulated Ins(1,3,4)P3 towards Ins(1,3)P2 rather than Ins(3,4)P2.
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Afolabi, Folashade, e Oluwafemi Abayomi Olajuyigbe. "Building Resilience in Education for Academic Continuity During Disruption". International Journal of Pedagogy and Teacher Education 7, n. 1 (28 dicembre 2022): 13. http://dx.doi.org/10.20961/ijpte.v7i1.62396.
Testo completoAbstract (sommario):
<p class="p1"><ins cite="mailto:proofreader" datetime="2023-04-23T16:50">T</ins>he traditional method of learning prevailed in the educational system <ins cite="mailto:proofreader" datetime="2023-04-26T14:15">up </ins>until the <ins cite="mailto:proofreader" datetime="2023-04-23T16:46">out</ins>break<del cite="mailto:proofreader" datetime="2023-04-23T16:46"> out</del> of the COVID-19 pandemic<ins cite="mailto:proofreader" datetime="2023-04-23T16:50">,</ins> which brought a turning point by digitali<ins cite="mailto:proofreader" datetime="2023-04-23T16:47">s</ins><del cite="mailto:proofreader" datetime="2023-04-23T16:47">z</del>ing learning. <ins cite="mailto:proofreader" datetime="2023-04-26T14:16">Education </ins><del cite="mailto:proofreader" datetime="2023-04-26T14:16">Learning </del>shifted from traditional<ins cite="mailto:proofreader" datetime="2023-04-23T16:50">ly</ins> student<ins cite="mailto:proofreader" datetime="2023-04-23T16:50">-</ins><del cite="mailto:proofreader" datetime="2023-04-23T16:50">s </del>centred to digital<ins cite="mailto:proofreader" datetime="2023-04-26T14:16"> learning</ins><del cite="mailto:proofreader" datetime="2023-04-26T14:16"> education</del>. The transition made learning difficult and students <ins cite="mailto:proofreader" datetime="2023-04-26T14:16">did not </ins><del cite="mailto:proofreader" datetime="2023-04-25T11:32">could not</del><ins cite="mailto:proofreader" datetime="2023-04-25T11:32">cope</ins> easily <del cite="mailto:proofreader" datetime="2023-04-25T11:33">cope </del>with the new trend. <del cite="mailto:proofreader" datetime="2023-04-23T16:51">To this end, the</del><ins cite="mailto:proofreader" datetime="2023-04-23T16:51">This</ins> study investigated learners’ experience of <ins cite="mailto:proofreader" datetime="2023-04-23T16:51">the</ins><del cite="mailto:proofreader" datetime="2023-04-23T16:51">a</del> paradigm shift to digital learning under three stages: Anticipation<del cite="mailto:proofreader" datetime="2023-04-25T11:33"> stage</del>, <del cite="mailto:proofreader" datetime="2023-04-23T16:51">c</del><ins cite="mailto:proofreader" datetime="2023-04-23T16:51">C</ins>oping<ins cite="mailto:proofreader" datetime="2023-04-26T14:16">,</ins><del cite="mailto:proofreader" datetime="2023-04-25T11:33"> stage</del> and Adaptation<del cite="mailto:proofreader" datetime="2023-04-25T11:33"> stage</del>. Two hundred and ten (210) senior secondary school 2 students in the Eti-Osa <del cite="mailto:proofreader" datetime="2023-04-26T15:21">l</del><ins cite="mailto:proofreader" datetime="2023-04-26T15:21">L</ins>ocal <del cite="mailto:proofreader" datetime="2023-04-26T15:21">g</del><ins cite="mailto:proofreader" datetime="2023-04-26T15:21">G</ins>overnment <del cite="mailto:proofreader" datetime="2023-04-26T15:21">a</del><ins cite="mailto:proofreader" datetime="2023-04-26T15:21">A</ins>rea of Lagos State were purposively selected. <ins cite="mailto:proofreader" datetime="2023-04-23T16:52">A </ins>21-<del cite="mailto:proofreader" datetime="2023-04-23T16:52"> </del>item online questionnaire with a 4-point Likert scale was used for data collection. The instrument was validated and the reliability was confirmed using Cronbach<ins cite="mailto:proofreader" datetime="2023-04-23T16:52">’s</ins> <del cite="mailto:proofreader" datetime="2023-04-23T16:52">A</del><ins cite="mailto:proofreader" datetime="2023-04-23T16:52">a</ins>lp<ins cite="mailto:proofreader" datetime="2023-04-23T16:52">h</ins>a (0.78). <ins cite="mailto:proofreader" datetime="2023-04-23T16:52">The </ins><del cite="mailto:proofreader" datetime="2023-04-23T16:52">D</del><ins cite="mailto:proofreader" datetime="2023-04-23T16:52">d</ins>ata were analysed using descriptive statistics. From the results, <ins cite="mailto:proofreader" datetime="2023-04-23T16:52">t</ins><ins cite="mailto:proofreader" datetime="2023-04-23T16:53">h</ins><ins cite="mailto:proofreader" datetime="2023-04-23T16:52">e </ins>participants were able to identify <ins cite="mailto:proofreader" datetime="2023-04-23T16:53">the </ins>various challenges encountered during the transition and <ins cite="mailto:proofreader" datetime="2023-04-23T16:53">discover </ins>how institutions <del cite="mailto:proofreader" datetime="2023-04-23T16:53">could </del><ins cite="mailto:proofreader" datetime="2023-04-23T16:53">can </ins>be resilient during disruption<del cite="mailto:proofreader" datetime="2023-04-23T16:53"> was discovered</del>.</p>
33
Wong, N. S., C. J. Barker, A. J. Morris, A. Craxton, C. J. Kirk e R. H. Michell. "The inositol phosphates in WRK1 rat mammary tumour cells". Biochemical Journal 286, n. 2 (1 settembre 1992): 459–68. http://dx.doi.org/10.1042/bj2860459.
Testo completoAbstract (sommario):
1. A detailed structural survey has been made of the inositol phosphates of unstimulated and vasopressin-stimulated WRK-1 rat mammary tumour cells. Inositol phosphate peaks were separated by h.p.l.c., and structural assignments were made for more than 20 compounds by combinations of: (a) co-chromatography with labelled standards; (b) site-specific enzymic dephosphorylation; (c) complete and partial periodate oxidation, followed by h.p.l.c. of polyols and their stereospecific oxidation by dehydrogenases; and (d) ammoniacal hydrolysis. 2. The ‘inositol monophosphates’ fraction from unstimulated cells included an uncharacterized peak, probably containing some glycerophosphoinositol, and Ins(1:2-cyclic)P. Stimulation provoked accumulation of both Ins1P and Ins3P, of Ins2P, and of Ins5P and/or the enantiomers Ins4P and Ins6P. The proportions of Ins1P and Ins3P were determined by partial periodate oxidation and enantiomeric identification of the resulting glucitols. 3. Three inositol bisphosphate peaks were detected in unstimulated cells: Ins(1,4)P2 [this was distinguished chemically from its enantiomer Ins(3,6)P2], Ins(3,4)P2 and/or Ins(1,6)P2, and Ins(4,5)P2 and/or Ins(5,6)P2. On stimulation, Ins(1,4)P2 and Ins(3,4)P2 [and/or Ins(1,6)P2] levels increased, and Ins(1:2-cyclic,4)P2 and Ins(1,3)P2 were also formed. 4. Three inositol trisphosphate peaks were obtained from unstimulated cells: all increased during stimulation. These were Ins(1,3,4)P3 [with some Ins(1:2-cyclic,4,5)P3], Ins(1,4,5)P3 and Ins(3,4,5)P3 [and/or Ins(1,5,6)P3]. During stimulation, another compound, probably Ins(1,4,6)P3, appeared in the ‘Ins(1,4,5)P3 peak’. The ‘Ins(3,4,5)P3 peak’ contained a second trisphosphate, probably Ins(2,4,5)P3. 5. Three inositol tetrakisphosphates, namely Ins(1,3,4,6)P4, Ins(1,3,4,5)P4, were present in unstimulated cells, and all accumulated during stimulation. 6. Ins(1,3,4,5,6)P5, which is the most abundant inositol polyphosphate in these cells, a less abundant inositol pentakisphosphate and inositol hexakisphosphate were all unresponsive to stimulation.
34
Suharyo, Suharyo. "PROBLEMATIKA PENEGAKAN HUKUM PENATAAN RUANG DALAM PELAKSANAAN OTONOMI DAERAH". Jurnal Rechts Vinding: Media Pembinaan Hukum Nasional 6, n. 2 (31 agosto 2017): 171. http://dx.doi.org/10.33331/rechtsvinding.v6i2.185.
Testo completoAbstract (sommario):
<p><ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">Dalam dinamika kehidupan masyarakat yang semakin berkembang pesat dan maju dengan perekonomian yang membaik, tata ruang menjadi hal yang sangat strategis untuk menccapai ketertiban, keserasian, kesejahteraan</ins>, <ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">dan ketenteraman masyarakat. Sebagai kebijakan negara telah dikeluarkan Undang-Undang Nomor 26 </ins>T<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">ahun 2007 tentang Penataan Ruang. Dalam era otonomi daerah</ins> juga telah dikeluarkan <ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">Undang-Undang Nomor 32 </ins>T<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">ahun 2004 tentang Pemerintahan Daerah jo </ins>U<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">ndang-Undang Nomor 23 </ins>T<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">ahun 2014, dan undang-undang lainnya. Permasalahan yang diangkat dalam penelitian ini adalah bagaimana implementasi undang-undang penataan ruang serta bagaimana pula implementasi undang-undang pemerintahan daerah yang di</ins> <ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">dalamnya terdapat juga pengaturan tata ruang, </ins>serta bagaimana<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32"> strategi penegakan hukumnya. Metode yang dipakai dalam penelitian ini adalah yuridis normatif. </ins>Kesimpulan tulisan ini adalah bahwa<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32"> penataan ruang harus selaras dengan kepentingan pemerintah pusat, pemerintah daerah provinsi, dan pemerintah kabupaten kota, mengacu </ins>pada <ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">berbagai peraturan perundang-undangan yang berlaku</ins> <ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32">dan saling berkaitan</ins>.<ins cite="mailto:TDA%20P" datetime="2017-08-22T08:32"> Penegakan hukum sangat dimungkinkan melalui berbagai sanksi termasuk sanksi pidana jika terdapat/memenuhi unsur pidana. </ins></p>
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HIRATA, Masato, Hiroshi TAKEUCHI, M. Andrew RILEY, J. Stephen MILLS, Yutaka WATANABE e V. L. Barry POTTER. "Inositol 1,4,5-trisphosphate receptor subtypes differentially recognize regioisomers of D-myo-inositol 1,4,5-trisphosphate". Biochemical Journal 328, n. 1 (15 novembre 1997): 93–98. http://dx.doi.org/10.1042/bj3280093.
Testo completoAbstract (sommario):
The Ins(1,4,5)P3 regioisomers, Ins(1,4,6)P3 and Ins(1,3,6)P3, which can mimic the 1,4,5-arrangement on the inositol ring of Ins(1,4,5)P3, were examined for Ca2+ release by using four types of saponin-permeabilized cell possessing various abundances of receptor subtypes, with special reference to the relation of potency to receptor subtype. Ins(1,4,6)P3 and Ins(1,3,6)P3 were weak agonists in rat basophilic leukaemic cells (RBL cells), which possess predominantly subtype II receptors, with respective potencies of 1/200 and less than 1/500 that of Ins(1,4,5)P3 [the EC50 values were 0.2, 45 and more than 100 μM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively]. Similar rank order potencies were also evaluated for the displacement of [3H]Ins(1,4,5)P3 bound to RBL cell membranes by these regioisomers. However, they caused Ca2+ release from GH3 rat pituitary cells possessing predominantly subtype I receptors more potently; Ins(1,4,6)P3 and Ins(1,3,6)P3 evoked release at respective concentrations of only one-third and one-twentieth that of Ins(1,4,5)P3 (the EC50 values were 0.4, 1.2 and 8 μM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In COS-1 African green-monkey kidney cells, with the relative abundances of 37% of the subtype II and of 62% of the subtype III receptor, potencies of 1/40 and approx. 1/200 for Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively were exhibited relative to Ins(1,4,5)P3 (the EC50 values were 0.4, 15 and approx. 80 μM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In HL-60 human leukaemic cells, in spite of the dominant presence of subtype I receptors (71%), similar respective potencies to those seen with COS-1 cells were exhibited (the EC50 values were 0.3, 15 and approx. 100 μM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). These results indicate that these regioisomers are the first ligands that distinguish between receptor subtypes; the present observations are of significance for the future design of molecules with enhanced selectivity.
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Beinotti, F., K. Alonso, E. Azevedo e A. Cliquet Junior. "Neuromuscular electrical stimulation applied to upper limb flexor /INS;muscles of tetraplegics: Interlimb reflex /INS;response assessed by electromyography /INS;— /INS;Pilot study". Journal of the Neurological Sciences 333 (ottobre 2013): e548-e549. http://dx.doi.org/10.1016/j.jns.2013.07.1927.
Testo completo
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Shieh, W. R., e C. S. Chen. "Preparation and characterization of a d-myo-inositol 1,4,5-trisphosphate-specific antibody". Biochemical Journal 311, n. 3 (1 novembre 1995): 1009–14. http://dx.doi.org/10.1042/bj3111009.
Testo completoAbstract (sommario):
Antibodies against Ins(1,4,5)P3 were raised by immunizing rabbits with two types of InsP3-BSA conjugates which were synthesized by covalently coupling Ins(1,4,5)P3 to the carrier protein via alkyl linkages. The anti-Ins(1,4,5)P3 antibody was detected by a novel ELISA using Ins(1,4,5)P3-immobilized microtitre plates. Both antiserum preparations showed specific binding with Ins(1,4,5)P3, with titres of 1:4000. Most inositol phosphates, including Ins1P, Ins(4,5)P2, Ins(1,3,4)P3, Ins(1,5,6)P3, Ins(1,2,5,6)P1, Ins(3,4,5,6)P4, Ins(1,3,4,5,6)P5, InsP6, and PtdIns(4,5)P2, did not exhibit significant molecular interactions with the antibodies. Ins(1,3,4,5)P4, however, cross-reacted with these antibodies with one-third of the affinity as that of Ins(1,4,5)P3, in part due to the largely shared structural motifs. The differential affinity was significantly improved by affinity purification on Ins(1,4,5)P3-agarose. The affinity-purified antibody displayed IC50 values of 12 nM and 730 nM for Ins(1,4,5)P3 and Ins(1,3,4,5)P4 respectively, according to a competitive ELISA; these values are in line with those reported for the Ins(1,4,5)P3 receptor. The modes of ligand recognition at the binding sites of these two types of biomolecules are, however, different. Moreover, although the ligand binding was interfered with by multivalent anions such as ATP4-, HPO4(3-) and SO4(2-) at high concentrations, no inhibition was noted with heparin, an antagonist of the Ins(1,4,5)P3 receptor.
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ONGUSAHA, Pat P., Philip J. HUGHES, John DAVEY e Robert H. MICHELL. "Inositol hexakisphosphate in Schizosaccharomyces pombe: synthesis from Ins(1,4,5)P3 and osmotic regulation". Biochemical Journal 335, n. 3 (1 novembre 1998): 671–79. http://dx.doi.org/10.1042/bj3350671.
Testo completoAbstract (sommario):
Schizosaccharomyces pombe extracts synthesize InsP6 (myo-inositol hexaphosphate) from Ins(1,4,5)P3 plus ATP. An S. pombe soluble fraction converts Ins(1,4,5)P3 into Ins(1,4,5,6)P4 and Ins(1,3,4,5)P4, in a constant ratio of ≈ 5:1, and thence to Ins(1,3,4,5,6)P5 and InsP6. We have purified a soluble Mg2+-dependent kinase of molecular mass ≈ 41 kDa that makes Ins(1,4,5,6)P4 and Ins(1,3,4,5)P4 in the same ratio and also converts Ins(1,4,5,6)P4 or Ins(1,3,4,5)P4 into Ins(1,3,4,5,6)P5 and InsP6. Of InsP3 isomers other than Ins(1,4,5)P3, only the non-biological molecule Ins(1,4,6)P3 potently ‘competed ’ with all steps in conversion of Ins(1,4,5)P3 into InsP6. Examination of molecular graphics representations allowed us to draw tentative conclusions about the environment needed for an hydroxyl group to be phosphorylated by this kinase and to predict successfully that the purified kinase would phosphorylate the 5-hydroxyl of Ins(1,4,6)P3. S. pombe that have been cultured with [3H]inositol contains a variety of 3H-labelled inositol polyphosphates, with Ins(1,4,5)P3 and InsP6 the most prominent, and the InsP6 concentration quickly increases in hyper-osmotically stressed S. pombe. This yeast therefore contains InsP6 and Ins(1,4,5)P3 as normal constituents, makes more InsP6 when hyper-osmotically stressed and contains a versatile inositol polyphosphate kinase that synthesizes InsP6 from Ins(1,4,5)P3.
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Guse, A. H., I. Berg e G. Gercken. "Metabolism of inositol phosphates in α1-adrenoceptor-stimulated and homogenized cardiac myocytes of adult rats". Biochemical Journal 261, n. 1 (1 luglio 1989): 89–92. http://dx.doi.org/10.1042/bj2610089.
Testo completoAbstract (sommario):
Previous studies demonstrated the accumulation of inositol mono- and poly-phosphates in carbamoylcholine-stimulated cultured cardiac ventricular myocytes of adult rats [Berg, Guse & Gercken (1989) Biochim. Biophys. Acta 1010, 100-107]. Stimulation with noradrenaline (50 microM) in the presence of propranolol (10 microM) led to a time-dependent pattern of inositol mono- and poly-phosphates in cultured cardiac-ventricular myocytes. Ins(1,4,5)P3 and Ins(1,3,4,5)P4 increased in a rapid initial phase. The degradation products of Ins(1,4,5)P3, namely Ins(1,4)P2 and Ins(4)P, accumulated between 1 and 15 min. Ins(1,3,4,5)P4 was rapidly dephosphorylated to Ins(1,3,4)P3, which was then metabolized to Ins(1,3)P2 and Ins(3,4)P2. The last two InsP2 isomers and their degradation products, Ins(1)P and Ins(3)P (determined as an enantiomeric mixture), increased at extended stimulation periods. To confirm the pathway of Ins(1,3,4,5)P4 degradation, homogenates of isolated ventricular myocytes were incubated with [3H]INs(1,3,4,5)P4. The subsequent products were Ins(1,3,4)P3, Ins(3,4)P2, Ins(1,3)P2 and InsP. The effect of noradrenaline was antagonized by prazosin (0.1 microM), but not by yohimbine (0.1 microM), indicating phosphoinositidase activation via the alpha 1-adrenoceptor.
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Hirata, M., Y. Kimura, T. Ishimatsu, F. Yanaga, T. Shuto, T. Sasaguri, T. Koga, Y. Watanabe e S. Ozaki. "Synthetic inositol 1,3,4,5-tetrakisphosphate analogues". Biochemical Journal 276, n. 2 (1 giugno 1991): 333–36. http://dx.doi.org/10.1042/bj2760333.
Testo completoAbstract (sommario):
Inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] analogues were synthesized and their effects on [3H]Ins(1,3,4,5)P4 5-phosphatase, [3H]Ins(1,3,4,5)P4 3-phosphatase and [3H]inositol 1,4,5-trisphosphate [3H]Ins(1,4,5)P3] 5-phosphatase activities were examined. The Ins(1,3,4,5)P4 analogue with the aminobenzoyl group at the 2-position of Ins(1,3,4,5)P4 inhibited the hydrolysis of 5-phosphate of [3H]Ins(1,3,4,5)P4 catalysed by erythrocyte ghosts, with a lower Ki value than seen with Ins(1,3,4,5)P4, whereas the analogue with the aminocyclohexanecarbonyl group at the same position had a higher Ki value. The Ins(1,4,5)P3 analogues that we had previously synthesized were also capable of inhibiting this process, with the same tendency as Ins(1,3,4,5)P4 analogues. Such differences in the potency among Ins(1,3,4,5)P4 and Ins(1,4,5)P3 analogues were applicable to other phosphatase activities, namely [3H]Ins(1,3,4,5)P4 3-phosphatase and [3H]Ins(1,4,5)P3 5-phosphatase. These results suggest that the active sites of these enzymes may catalyse the dephosphorylation in a similar fashion.
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Wang, Shuangqing, Saige Meng, Xinlei Zhou, Zhonggao Gao e Ming Guan Piao. "pH-Responsive and Mucoadhesive Nanoparticles for Enhanced Oral Insulin Delivery: The Effect of Hyaluronic Acid with Different Molecular Weights". Pharmaceutics 15, n. 3 (2 marzo 2023): 820. http://dx.doi.org/10.3390/pharmaceutics15030820.
Testo completoAbstract (sommario):
Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA–PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA–PDM–INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA–PDM–INS, M-HA–PDM–INS, H-HA–PDM–INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA–PDM–INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA–PDM–INS was investigated. The release of INS from H-HA–PDM–INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA–PDM–INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA–PDM–INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA–PDM–INS, regardless of the MW of HA, was demonstrated using CCK-8 and live–dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA–PDM–INS, M-HA–PDM–INS, and H-HA–PDM–INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA–PDM–INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.
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Van Lookeren Campagne, M. M., C. Erneux, R. Van Eijk e P. J. M. Van Haastert. "Two dephosphorylation pathways of inositol 1,4,5-trisphosphate in homogenates of the cellular slime mould Dictyostelium discoideum". Biochemical Journal 254, n. 2 (1 settembre 1988): 343–50. http://dx.doi.org/10.1042/bj2540343.
Testo completoAbstract (sommario):
Dictyostelium discoideum homogenates contain phosphatase activity which rapidly dephosphorylates Ins(1,4,5)P3 (D-myo-inositol 1,4,5-trisphosphate) to Ins (myo-inositol). When assayed in Mg2+, Ins(1,4,5)P3 is dephosphorylated by the soluble Dictyostelium cell fraction to 20% Ins(1,4)P2 (D-myo-inositol 1,4-bisphosphate) and 80% Ins(4,5)P2 (D-myo-inositol 4,5-bisphosphate). In the particulate fraction Ins(1,4,5)P3 5-phosphatase is relatively more active than the Ins(1,4,5)P3 1-phosphatase. CaCl2 can replace MgCl2 only for the Ins(1,4,5)P3 5-phosphatase activity. Ins(1,4)P2 and Ins(4,5)P2 are both further dephosphorylated to Ins4P (D-myo-inositol 4-monophosphate), and ultimately to Ins. Li+ ions inhibit Ins(1,4,5)P3 1-phosphatase, Ins(1,4)P2 1-phosphatase, Ins4P phosphatase and L-Ins1P (L-myo-inositol 1-monophosphate) phosphatase activities; Ins(1,4,5)P3 1-phosphatase is 10-fold more sensitive to Li+ (half-maximal inhibition at about 0.25 mM) than are the other phosphatases (half-maximal inhibition at about 2.5 mM). Ins(1,4,5)P3 5-phosphatase activity is potently inhibited by 2,3-bisphosphoglycerate (half-maximal inhibition at 3 microM). Furthermore, 2,3-bisphosphoglycerate also inhibits dephosphorylation of Ins(4,5)P2. These characteristics point to a number of similarities between Dictyostelium phospho-inositol phosphatases and those from higher organisms. The presence of an hitherto undescribed Ins(1,4,5)P3 1-phosphatase, however, causes the formation of a different inositol bisphosphatase isomer [Ins(4,5)P2] from that found in higher organisms [Ins(1,4)P2]. The high sensitivity of some of these phosphatases for Li+ suggests that they may be the targets for Li+ during the alteration of cell pattern by Li+ in Dictyostelium.
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Li, Zengke, Nanshan Zheng, Jian Wang e Jingxiang Gao. "Performance Comparison among Different Precise Satellite Ephemeris and Clock Products for PPP/INS/UWB Tightly Coupled Positioning". Journal of Navigation 71, n. 3 (27 novembre 2017): 585–606. http://dx.doi.org/10.1017/s0373463317000856.
Testo completoAbstract (sommario):
To meet the requirements of different applications, the International Global Navigation Satellite System (GNSS) Service (IGS) has provided Global Positioning System (GPS) satellite ephemerides and clock products with different accuracy levels (final, rapid and ultra-rapid products). Comparison of Precise Point Positioning/Inertial Navigation System/Ultra Wideband (PPP/INS/UWB) tightly coupled positioning with different precise satellite ephemeris and clock products is made and corresponding data analysis is provided. Final, rapid and ultra-rapid products are applied in a PPP/INS/UWB integrated system. The field trajectories, position and velocity errors of the integrated system with different products are compared. The results indicate that PPP/INS/UWB tightly coupled positioning with final and rapid products achieves an accurate performance. Compared with the position resolution using final products, the position accuracy with the ultra-rapid products (observed half) is slightly reduced and the position accuracy with the ultra-rapid products (predicted half) has a 0·1–0·2 m reduction. The influence of precise satellite ephemeris and clock products is very minor for non-real-time positioning, relative to the accuracy of PPP/INS/UWB tightly coupled positioning.
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Taylor, C. W., e B. V. L. Potter. "The size of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores depends on inositol 1,4,5-trisphosphate concentration". Biochemical Journal 266, n. 1 (15 febbraio 1990): 189–94. http://dx.doi.org/10.1042/bj2660189.
Testo completoAbstract (sommario):
An explanation of the complex effects of hormones on intracellular Ca2+ requires that the intracellular actions of Ins(1,4,5)P3 and the relationships between intracellular Ca2+ stores are fully understood. We have examined the kinetics of 45Ca2+ efflux from pre-loaded intracellular stores after stimulation with Ins(1,4,5)P3 or the stable phosphorothioate analogue, Ins(1,4,5)P3[S]3, by simultaneous addition of one of them with glucose/hexokinase to rapidly deplete the medium of ATP. Under these conditions, a maximal concentration of either Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 evoked rapid efflux of about half of the accumulated 45Ca2+, and thereafter the efflux was the same as occurred under control conditions. Submaximal concentrations of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 caused a smaller rapid initial efflux of 45Ca2+, after which the efflux was similar whatever the concentration of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 present. The failure of submaximal concentrations of Ins(1,4,5)P3 and Ins(1,4,5)P3[S]3 to mobilize fully the Ins(1,4,5)P3-sensitive Ca2+ stores despite prolonged incubation was not due either to inactivation of Ins(1,4,5)P3 or to desensitization of the Ins(1,4,5)P3 receptor. The results suggest that the size of the Ins(1,4,5)P3 sensitive Ca2+ stores depends upon the concentration of Ins(1,4,5)P3.
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Gawler, D. J., B. V. L. Potter, R. Gigg e S. R. Nahorski. "Interactions between inositol tris- and tetrakis-phosphates. Effects on intracellular Ca2+ mobilization in SH-SY5Y cells". Biochemical Journal 276, n. 1 (15 maggio 1991): 163–67. http://dx.doi.org/10.1042/bj2760163.
Testo completoAbstract (sommario):
The potential Ca2(+)-releasing activity of the inositol tetrakisphosphates Ins(1,3,4,6)P4 and DL-Ins(1,4,5,6)P4 and the inositol pentakisphosphate Ins(1,3,4,5,6)P5 and their effect on Ins(1,4,5)P3- and DL-Ins (1,3,4,5)P4-mediated Ca2+ release were examined in permeabilized SH-SY5Y human neuroblastoma cells. Neither DL-Ins(1,4,5,6)P4 nor Ins(1,3,4,5,6)P5 exhibit Ca2(+)-releasing activity at concentrations up to 10 microM, but Ins(1,3,4,6)P4 releases Ca2+ dose-dependently, with an EC50 value (conen, giving half-maximal effect) of 5.92 +/- 0.47 microM. Maximal response by this tetrakisphosphate (49 +/- 2.5%) is significantly less than that seen with Ins(1,4,5)P3 (60 +/- 3%) and is achieved at a concentration of 30 microM. In the presence of this concentration of Ins(1,3,4,6)P4 the EC50 value for Ins(1,4,5)P3-mediated Ca2+ release increases from 0.12 +/- 0.02 microM to 2.11 +/- 0.51 microM, providing evidence that this naturally occurring inositol tetrakisphosphate may recognize and exhibit its Ca2(+)-releasing activity via the Ins(1,4,5)P3 receptor. DL-Ins(1,3,4,5)P4, however, at its maximally effective concentration (10 microM) does not significantly affect Ins(1,4,5)P3-mediated Ca2+ release, and therefore appears to mediate its Ca2(+)-mobilizing action through a receptor distinct from that for Ins(1,4,5)P3.
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Taylor, C. W., M. J. Berridge, A. M. Cooke e B. V. L. Potter. "Inositol 1,4,5-trisphosphorothioate, a stable analogue of inositol trisphosphate which mobilizes intracellular calcium". Biochemical Journal 259, n. 3 (1 maggio 1989): 645–50. http://dx.doi.org/10.1042/bj2590645.
Testo completoAbstract (sommario):
D-Ins(1,4,5)P3 is now recognized as an intracellular messenger that mediates the actions of many cell-surface receptors on intracellular Ca2+ pools, but its complex and rapid metabolism in intact cells has confused interpretation of its possible roles in oscillatory changes in intracellular [Ca2+] and in controlling Ca2+ entry at the plasma membrane. We now report the actions and metabolic stability of a synthetic analogue of Ins(1,4,5)P3, DL-inositol 1,4,5-trisphosphorothioate [DL-Ins(1,4,5)P3[S]3]. In permeabilized hepatocytes, DL-Ins(1,4,5)P3[S]3 and synthetic DL-Ins(1,4,5)P3 stimulated Ca2+ release from the same intracellular stores, though the concentration required for half-maximal release was 3-fold higher for DL-Ins(1,4,5)P3[S]3. Since L-Ins(1,4,5)P3 neither antagonized the effects of D-Ins(1,4,5)P3 nor itself stimulated appreciable Ca2+ release, the activity of the racemic mixture of Ins(1,4,5)P3, and presumably also of Ins(1,4,5)P3[S]3, is attributable to the D-isomer. Under conditions where there was negligible metabolism of D-[3H]Ins(1,4,5)P3, both DL-Ins(1,4,5)P3 and DL-Ins(1,4,5)P3[S]3 elicited rapid Ca2+ release from intracellular stores, and the stores remained empty during prolonged stimulation. When cells were incubated at high density, both compounds stimulated rapid Ca2+ release, but while the stores soon refilled as Ins(1,4,5)P3 was degraded to Ins(1,4)P2, there was no refilling of the pools after stimulation with DL-Ins(1,4,5)P3[S]3. When DL-Ins(1,4,5)P3 or DL-Ins(1,4,5)P3[S]3 was treated with a crude preparation of Ins(1,4,5)P3 3-kinase and ATP, and the Ca2+-releasing activity of the products subsequently assayed, DL-Ins(1,4,5)P3 was completely inactivated by phosphorylation, but there was no loss of activity of the phosphorothioate analogue. In additional experiments, DL-Ins(1,4,5)P3[S]3 (10 microM) did not affect the rate of phosphorylation of D-[3H]Ins(1,4,5)P3 (1 microM). We conclude that Ins(1,4,5)P3[S]3 is a full agonist and only 3-fold less potent than Ins(1,4,5)P3 in mobilizing intracellular Ca2+ stores, but unlike the natural messenger it is resistant to both phosphorylation and dephosphorylation. We propose that this stable analogue will allow the direct actions of Ins(1,4,5)P3 to be resolved from those that require its metabolism.
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Gawler, D. J., B. V. Potter e S. R. Nahorski. "Inositol 1,3,4,5-tetrakisphosphate-induced release of intracellular Ca2+ in SH-SY5Y neuroblastoma cells". Biochemical Journal 272, n. 2 (1 dicembre 1990): 519–24. http://dx.doi.org/10.1042/bj2720519.
Testo completoAbstract (sommario):
Inositol-polyphosphate-induced Ca2+ mobilization was investigated in saponin-permeabilized SH-SY5Y human neuroblastoma cells. Ins(1,4,5)P3 induced a dose-related release from intracellular Ca2+ stores with an EC50 (concn. giving half-maximal effect) of 0.1 microM and a maximal release of 70%. Ins(1,3,4)P3, DL-Ins(1,4,5,6)P4 and Ins(1,3,4,5,6)P5 did not evoke Ca2+ mobilization in these cells when used at concentrations up to 10 microM. However, Ins(1,3,4,5)P4 was found to release Ca2+ in a dose-related manner, but the response was dependent on the source of Ins(1,3,4,5)P4 used. When commercially available D-Ins(1,3,4,5)P4 was used, the EC50 and maximal response values were 1 microM and 50% respectively, compared with values for chemically synthesized DL-Ins(1,3,4,5)P4 of 2 microM and 25%. The enhanced maximal response of commercial D-Ins(1,3,4,5)P4 was decreased by pretreatment with rat brain crude Ins(1,4,5)P3 3-kinase and was therefore concluded to be indicative of initial Ins(1,4,5)P3 contamination of the Ins(1,3,4,5)P4 preparation. When metabolism of DL-Ins(1,3,4,5)P4 (10 microM) in these cells at 25 degrees C was investigated by h.p.l.c., substantial amounts of Ins(1,4,5)P3 (0.2 microM) and Ins(1,3,4)P3 (0.8 microM) were found to be produced within 3 min. Analysis of DL-Ins(1,3,4,5)P4 incubation with cells at 4 degrees C, however, indicated that metabolism had been arrested ([3H]Ins(1,4,5)P3 detection limits were estimated to be approx. 0.01 microM). When chemically synthesized DL-Ins(1,3,4,5)P4 and incubation conditions of low temperature were used, the Ca2(+)-releasing properties of this compound were established to be 1 microM and 19% for the EC50 and maximal response values respectively. The results obtained strongly suggest that Ins(1,3,4,5)P4 alone has the ability to release intracellular Ca2+. However, in the presence of sub-maximal concentrations of Ins(1,4,5)P3, Ca2+ release appears to be synergistic with Ins(1,3,4,5)P4, but at supramaximal concentrations not even additive effects are observed.
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Erneux, C., A. Delvaux, C. Moreau e J. E. Dumont. "The dephosphorylation pathway of d-myo-inositol 1,3,4,5-tetrakisphosphate in rat brain". Biochemical Journal 247, n. 3 (1 novembre 1987): 635–39. http://dx.doi.org/10.1042/bj2470635.
Testo completoAbstract (sommario):
Dephosphorylation of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] was measured in both the soluble and the particulate fractions of rat brain homogenates. Analysis of the hydrolysis of [4,5-32P]Ins(1,3,4,5)P4 showed that for both fractions the 5-phosphate of Ins(1,3,4,5)P4 was removed and inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] was specifically produced. In the soluble fraction, Ins(1,3,4)P3 was further hydrolysed at the 1-phosphate position to inositol 3,4-bisphosphate[Ins(3,4)P2]. DEAE-cellulose chromatography of the soluble fraction separated the phosphatase activities into three peaks. The first hydrolysed both Ins(1,3,4,5)P4 and inositol 1,4,5-trisphosphate, the second inositol 1-phosphate and the third Ins(1,3,4)P3 and inositol 1,4-bisphosphate, [Ins(1,4)P2]. Further purification of the third peak on either Sephacryl S-200 or Blue Sepharose could not dissociate these two activities [i.e. with Ins(1,4)P2 and Ins(1,3,4)P3 as substrates]. The dephosphorylation of Ins(1,3,4)P3 could be inhibited by the addition of Li+.
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Köpke, Ralf. "Ins Lee gedreht". VDI nachrichten 74, n. 43 (2020): 12. http://dx.doi.org/10.51202/0042-1758-2020-43-12.
Testo completo
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Ciupek, Martin. "Vollgefedert ins Gelände". VDI nachrichten 75, n. 05 (2021): 40. http://dx.doi.org/10.51202/0042-1758-2021-05-40-1.
Testo completo