Home About us Contact
|
Home About us Contact | ||
|
|
||
Long Form (long + form)
Selected AbstractsUse of the Bruininks,Oseretsky Test of Motor Proficiency for identifying children with motor impairmentDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2007Fotini Venetsanou MSc This study compared the consistency of the Short Form (SF) and the Long Form (LF) of the Bruininks,Oseretsky Test of Motor Proficiency (BOTMP) in identifying preschool children with motor impairment (MI). One hundred and forty-four Greek preschool children participated (74 males, 70 females; mean age 5y 2mo [SD 5mo], range 4y 6mo-5y 6mo). Although total SF and LF scores were highly correlated (r=0.85), paired t -tests indicated significant differences (t=-27.466, p=0.001). SF total scores (mean 58.72 [SD 7.28]) were higher than LF total scores (mean 47.38 [SD 9.43]). SF had low sensitivity (13.6%) and negative predictive value (72.5%) for identifying MI. The BOTMP-SF does not appear to be a valid test for the identification of MI in 5-year-old children. [source] BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtinEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010Rebecca Leon Abstract Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the N-terminus of the huntingtin protein. It is characterized by a selective loss of medium spiny neurons in the striatum. It has been suggested that impaired proteasome function and endoplasmic reticulum (ER) stress play important roles in mutant huntingtin (mHtt)-induced cell death. However, the molecular link involved is poorly understood. In the present study, we identified the essential role of the extra long form of Bim (Bcl-2 interacting mediator of cell death), BimEL, in mHtt-induced cell death. BimEL protein expression level was significantly increased in cell lines expressing the N-terminus of mHtt and in a mouse model of HD. Although quantitative RT-PCR analysis indicated that BimEL mRNA was increased in cells expressing mHtt, we provided evidence showing that, at the post-translational level, phosphorylation of BimEL played a more important role in regulating BimEL expression. Up-regulation of BimEL facilitated the translocation of Bax to the mitochondrial membrane, which further led to cytochrome c release and cell death. On the other hand, knocking down BimEL expression prevented mHtt-induced cell death. Taken together, these findings suggest that BimEL is a key element in regulating mHtt-induced cell death. A model depicting the role of BimEL in linking mHtt-induced ER stress and proteasome dysfunction to cell death is proposed. [source] The structure of the TGF-, latency associated peptide region determines the ability of the proprotein convertase furin to cleave TGF-,sJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2008Makoto Kusakabe Abstract The TGF-, family members are generated as latent pre-pro-polypeptides. The active mature peptides are cleaved from the latent forms by cellular proteases. TGF-,1, for instance, is predominantly processed by a substilisin-like proprotein convertase, furin. TGF-,2 has a consensus cleavage site for furin and therefore has been presumed to be cleaved by furin. However, TGF-,2 is often secreted as the latent form, which appears to be inconsistent with its postulated sensitivity to furin. We report here that both the regular (short) form of TGF-,2 and its spliced variant with an additional exon (long form) are insensitive to furin. NIH 3T3 and CHO cells were transfected with expression vectors containing the short or long form of TGF-,2 or a chimeric TGF-, consisting of the TGF-,1 LAP region, the TGF-,2 cleavage site and the TGF-,2 mature peptide. The constructs included a c- myc epitope tag in the N-terminal region of the mature peptide. The TGF-,s produced by the transfected cells were analyzed with Western blots and immunocytochemistry. The intracellular proteins harvested from these cells were incubated with furin. Furin only inefficiently cleaved both the long and short forms of TGF-,2, but efficiently processed the chimeric TGF-,. This indicates that the insensitivity of both forms of TGF-,2 to furin is a consequence of the tertiary structure of their LAP regions rather than their cleavage site. This differential processing of TGF-,1 and -,2 may be part of the mechanism that generates isoform-specific functions of the TGF-,s. J. Cell. Biochem. 103: 311,320, 2008. © 2007 Wiley-Liss, Inc. [source] Hypothalamic Suppressor-of-Cytokine-Signalling 3 mRNA is Elevated and Pro-Opiomelanocortin mRNA is Reduced During Pregnancy in Brandt's Voles (Lasiopodomys brandtii,)JOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2008G.-B. Tang Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles (Lasiopodomys brandtii), both circulating leptin levels and food intake are elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food intake. Diminished hypothalamic leptin receptors and impaired leptin signal transduction are characteristic of central leptin resistance. The present study aimed to determine whether these characteristic modulations of leptin sensitivity occurred in pregnant Brandt's voles. The mRNA expression of the long form of the leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3), neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to controls, there was no significant change in hypothalamic Ob-Rb mRNA during the pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no differences were found in the mRNA expression of NPY, AgRP and CART in pregnant voles compared to controls. The elevation of SOCS3 mRNA together with disrupted leptin regulation of neuropeptides in the hypothalamus suggests that leptin resistance may develop in pregnant Brandt's voles. [source] Role of Protein Kinases in the Prolactin-Induced Intracellular Calcium Rise in Chinese Hamster Ovary Cells Expressing the Prolactin ReceptorJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2000B. Sorin Abstract There is still only limited understanding of the early steps of prolactin signal transduction in target cells. It has been shown that prolactin actions are associated with cell protein phosphorylation, Ca2+ increases, and so on. However, the link between the activation of kinases and calcium influx or intracellular Ca2+ mobilization has not yet been clearly established. Chinese hamster ovary (CHO) cells, stably transfected with the long form of rabbit mammary gland prolactin receptor (PRL-R) cDNA were used for PRL-R signal transduction studies. Spectrofluorimetric techniques were used to measure intracellular calcium ([Ca2+]i) in cell populations with Indo1 as a calcium fluorescent probe. We demonstrate that, although protein kinase C activation (PMA or DiC8) caused a calcium influx in CHO cells, prolactin-induced PKC activation was not responsible for the early effect of prolactin on [Ca2+]i. Activation of protein kinase A (PKA) or protein kinase G did not modify [Ca2+]i and inhibition of PKA pathway did not affect the prolactin response. In the same way, phosphatidylinositol-3 kinaseinhibition had no effect on the prolactin-induced Ca2+ increase. On the other hand, tyrosine kinase inhibitors (herbimycin A, lavendustin A, and genistein) completely blocked the effect of prolactin on [Ca2+]i (influx and release). W7, a calmodulin-antagonist, and a specific inhibitor of calmodulin kinases (KN-62), only blocked prolactin-induced Ca2+ influx but had no significant effect on Ca2+ release. Using pharmacological agents, we present new data concerning the involvement of protein phosphorylations in the early effects of prolactin on ionic channels in CHO cells expressing the long form of PRL-R. Our results suggest that, at least in the very early steps of prolactin signal transduction, serine-threonine phosphorylation does not participate in the prolactin-induced calcium increase. On the other hand, tyrosine phosphorylation is a crucial, very early step, since it controls K+ channel activation, calcium influx, and intracellular calcium mobilization. Calmodulin acts later, since its inhibition only blocks the prolactin-induced Ca2+ influx. [source] Changes in expression of anti-apoptotic protein, cflip, in granulosa cells during follicular atresia in porcine ovariesMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2005Fuko Matsuda-Minehata Follicular selection is performed in mammalian ovaries, as most follicles undergo atresia during follicular development and growth. Follicular regression is indicated to begin with granulosa cell apoptosis. To reveal the molecular mechanisms of the selection, we examined the changes in the levels of cellular-Flice like inhibitory protein (cFLIP) expression in porcine granulosa cells. cFLIP is the homologue of intracellular apoptosis inducer (procaspase-8/Flice), and has two alternative splicing isoforms: cFLIP short form (cFLIPS) and long form (cFLIPL). By competing with caspase-8, cFLIP inhibits apoptosis initiated by death receptors. The changes in the levels of cFLIPS and cFLIPL mRNA and protein expression in granulosa cells were determined by RT-PCR and Western blotting, respectively. cFLIPL mRNA and protein were highly expressed in granulosa cells of healthy follicles and decreased during atresia. cFLIPS mRNA levels in granulosa cells were low and showed no change among the stages of follicular development, and its protein level was extremely low. We examined the changes in the localization of cFLIP mRNAs in pig ovaries by in situ hybridization and found that cFLIPL is abundant in granulosa cells of healthy follicles in comparison with those of atretic follicles. Immunohistochemical analyses demonstrated that the cFLIP protein is highly expressed in the granulosa cell of healthy follicles but weakly expressed in that of atretic follicles. We presumed that cFLIP, especially cFLIPL, plays an anti-apoptotic role in the granulosa cells of healthy follicles of pig ovaries, and that cFLIP could be a major survival factor that determines whether growth or atresia occurs in porcine follicles. © 2005 Wiley-Liss, Inc. [source] Urinary incontinence symptom scores and urodynamic diagnosesNEUROUROLOGY AND URODYNAMICS, Issue 1 2002Mary P. FitzGerald Abstract The aim of this study was to determine whether scores on two validated urinary incontinence symptom scales predicted eventual urodynamic diagnoses. Two hundred ninety-three patients undergoing multi-channel urodynamic testing rated their symptoms of urinary incontinence and/or pelvic organ prolapse (POP), using the Incontinence Impact Questionnaire, the Urogenital Distress Inventory, and an obstructive symptom subscale from the long form of the Incontinence Impact Questionnaire. Among the 202 (69%) patients without advance-stage POP, increasing scores on scale items related to stress and urge incontinence predicted increasing frequency of the diagnoses of genuine stress incontinence (GSI) and detrusor instability, respectively. Among the 91 (31%) patients with advance-stage POP, there was no association. Among all patients with GSI, the presence of intrinsic sphincter deficiency could not be predicted by responses to the symptom scales. Scores on the symptom scales were inadequate predictors of eventual urodynamic diagnoses, especially among women with advance-stage POP. Neurourol. Urodynam. 21:30,35, 2002. © 2002 Wiley-Liss, Inc. [source] Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortexJOURNAL OF PINEAL RESEARCH, Issue 4 2004Debomoy K. Lahiri Abstract:, Melatonin levels decrease with aging in mice. Dietary supplementation with melatonin has recently been shown to result in a significant rise in levels of endogenous melatonin in the serum and all other tissue samples tested. Herein, the effects of dietary melatonin on brain levels of nitric oxide synthase, synaptic proteins and amyloid beta-peptides (A,) were determined in mice. Melatonin supplementation did not significantly change cerebral cortical levels of nitric oxide synthase or synaptic proteins such as synaptophysin and SNAP-25. Increased brain melatonin concentrations however, led to a significant reduction in levels of toxic cortical A, of both short and long forms which are involved in amyloid depositions and plaque formation in Alzheimer's diseases. Thus, melatonin supplementation may retard neurodegenerative changes associated with brain aging. Depletion of melatonin in the brain of aging mice may in part account for this adverse change. [source] | |||||||||||||