scholarly journals Expression of 1L-myo-Inositol -1-Phosphate Synthase (EC 5.5.1.4) is Deregulated in the Cerebellum of Curly Tail Mutant Mice

Author(s):  
Hana Dawood Alebous ◽  
Erika M. Steele ◽  
Margaret Dean Johnson

Previous research, defining spatial control of inositol phosphate biosynthesis in the developing brain of CBA (normal) and CT [curly tail (ct-CT) and straight tail (st-CT)] mutant mice implicated a role for 1l-myo-inositol 1-phosphate synthase (MIP) in normal functioning of the central nervous system. Biochemical research indicated that MIP enzymatic activity, conversion of glucose 6-phosphate into inositol phosphate, is highest in the cerebellum of ct-CT and lowest in st-CT, when compared to that of CBA mice. Here, we utilized microscopic and biochemical investigations to analyze and extend previous findings of MIP expression in the cerebellum. Results of this research indicated that MIP expression correlates, well, with its enzymatic activity in the cerebellum of CBA and CT mutant mice. Statistical analyses of fluorescent micrographs detected a significant difference in fluorescence intensity between MIP from ct-CT, st-CT, and CBA mice. These data support vital links between inositol phosphate biosynthesis, MIP expression, and normal functioning of the cerebellum. Moreover, published data, identifying significant behavioral differences in the CT mutant, as well as data linking motor and non-motor cerebellar functions to abnormal levels of inositol, support the conclusion that aspects of normal cerebellar functions require temporal and spatial control of inositol phosphate biosynthesis, MIP expression.

2017 ◽  
Vol 34 (3) ◽  
pp. 335-351 ◽  
Author(s):  
Fang Liu ◽  
Cunmei Jiang ◽  
Tom Francart ◽  
Alice H. D. Chan ◽  
Patrick C. M. Wong

Congenital amusia is a lifelong disorder of musical processing for which no effective treatments have been found. The present study aimed to treat amusics’ impairments in pitch direction identification through auditory training. Prior to training, twenty Chinese-speaking amusics and 20 matched controls were tested on the Montreal Battery of Evaluation of Amusia (MBEA) and two psychophysical pitch threshold tasks for identification of pitch direction in speech and music. Subsequently, ten of the twenty amusics undertook 10 sessions of adaptive-tracking pitch direction training, while the remaining 10 received no training. Post training, all amusics were retested on the pitch threshold tasks and on the three pitch-based MBEA subtests. Trained amusics demonstrated significantly improved thresholds for pitch direction identification in both speech and music, to the level of non-amusic control participants, although no significant difference was observed between trained and untrained amusics in the MBEA subtests. This provides the first clear positive evidence for improvement in pitch direction processing through auditory training in amusia. Further training studies are required to target different deficit areas in congenital amusia, so as to reveal which aspects of improvement will be most beneficial to the normal functioning of musical processing.


2004 ◽  
Vol 279 (27) ◽  
pp. 28539-28552 ◽  
Author(s):  
Manoj Majee ◽  
Susmita Maitra ◽  
Krishnarup Ghosh Dastidar ◽  
Sitakanta Pattnaik ◽  
Anirban Chatterjee ◽  
...  

1979 ◽  
Vol 25 (1) ◽  
Author(s):  
Fritz Pittner ◽  
IrinaI. Tovarova ◽  
ElenaYa. Kornitskaya ◽  
AleksanderS. Khokhlov ◽  
Otto Hoffmann-Ostenhof

1987 ◽  
Vol 85 (3) ◽  
pp. 611-614 ◽  
Author(s):  
Jukta Adhikari ◽  
Asima Lahiri Majumder ◽  
Tirtha Jyoti Bhaduri ◽  
Sarmila DasGupta ◽  
Arun Lahiri Majumder

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Stephen J D’Auria ◽  
Filip Istvanic ◽  
Francois Yu ◽  
Xucai Chen ◽  
John Pacella

Introduction: Microvascular obstruction (MVO) occurs frequently during successful PCI for acute myocardial infarction. Our previous work has demonstrated the potential of using ultrasound targeted microbubbles (MBs) cavitation to relieve MVO, termed sonoreperfusion (SRP). Hypothesis: In the present study, we aim to develop a tPA loaded MB in order to utilize the thrombolytic effects of locally delivered tPA to enhance SRP, with a decreased tPA dose to limit the bleeding risk. Methods: tPA (1 mg/mL) was first modified via a maleimide linkage using BMCC-biotin, leading to a biotinylated protein. The biotinylated tPA (0.87 mg/mL) was then mixed with streptavidin labeled lipid shelled MB (1х10^9MB/mL) via biotin-streptavidin bridging. The enzymatic activity of the tPA in these tPA loaded MBs were was tested with whole porcine blood thrombus and with a tPA chromogenic activity kit. The loading capability of tPA onto the MBs was determined by BCA protein assay. The SRP efficacy of the loaded tPA MB was tested in an in vitro model of MVO and compared with full dose systemic tPA as well as modified MB. Results: tPA loaded MB showed successful lysis of whole porcine blood clot in vitro , as evidenced by decreased thrombus weight. Subsequent analysis of tPA activity showed that there was no significant difference in the activity of stock tPA when compared to the BMCC labeled tPA (42.0±3.4 IU vs 44.7±1.1 IU, p =0. 17). tPA was loaded onto MB at volumetric ratios of 3 units of tPA at 0.87 mg/mL to 1 unit (3:1) of MB at 1e9 MB/mL (43.5±2.2 IU, p =0.38) and 6:1 (39.3±1.5 IU, p =0.15). There was decreased activity in the 1:1 group. The loading capability of tPA for the 3:1 tPA loaded MB was 6.2e-7 μg per MB, with a loading efficiency of 10.4% of the stock tPA. Early in vitro work showed the tPA loaded MB to be non-inferior at relieving MVO with SRP when compared to infusion of full dose tPA and SRP with standard unmodified tPA. Conclusions: We successfully loaded tPA onto the surface of a lipid encapsulated MB, with retention of the enzymatic activity of tPA. The loading efficiency was 10.4% of the stock tPA. The tPA loaded MB demonstrated similar reperfusion efficacy to full systemic dose tPA. Thus, this approach of targeted local delivery of tPA may provide a means to mitigate bleeding risk without sacrificing drug efficacy.


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