Search results for "KINASE"
showing 10 items of 2635 documents
Experimental and Theoretical Investigations of Structural Trends for Selenium(IV) Imides and Oxides: X-ray Structure of Se3(NAd) 2
2004
The thermal decomposition of Se(NAd)(2) (Ad = 1-adamantyl) in THF was monitored by (77)Se NMR and shown to give the novel cyclic selenium imide Se(3)(NAd)(2) as one of the products. An X-ray structural determination showed that Se(3)(NAd)(2) is a puckered five-membered ring with d(Se-Se) = 2.404(1) A and |d(Se-N)| = 1.873(4) A. On the basis of (77)Se NMR data, other decomposition products include the six-membered ring Se(3)(NAd)(3), and the four-membered rings AdNSe(micro-NAd)(2)SeO and OSe(micro-NAd)(2)SeO. The energies for the cyclodimerization of E(NR)(2) and RNEO (E = S, Se; R = H, Me, (t)Bu, SiMe(3)), and the cycloaddition reactions of RNSeO with E(NR)(2), RNSO(2) with Se(NR)(2), and S…
Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and aggregation
2021
AbstractPost-translational modifications (PTMs) have emerged as key modulators of protein phase separation and have been linked to protein aggregation in neurodegenerative disorders. The major aggregating protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the RNA-binding protein TDP-43, is hyperphosphorylated in disease on several C-terminal serine residues, which is generally believed to promote TDP-43 aggregation. Here, we show that hyperphosphorylation by Casein kinase 1δ or C-terminal phosphomimetic mutations surprisingly reduce TDP-43 phase separation and aggregation and render TDP-43 condensates more liquid-like and dynamic. Multi-scale simulations revea…
Dual effects of increased glycogen synthase kinase-3β activity on adult neurogenesis
2013
Adult neurogenesis, the generation of new neurons during the adulthood, is a process controlled by several kinases and phosphatases among which GSK3β exerts important functions. This protein is particularly abundant in the central nervous system, and its activity deregulation is believed to play a key role in chronic disorders such as Alzheimer's disease. Previously, we reported that in vivo overexpression of GSK3β (Tet/GSK3β mice) causes alterations in adult neurogenesis, leading to a depletion of the neurogenic niches. Here, we have further characterized those alterations, finding a delay in the switching-off of doublecortin marker as well as changes in the survival and death rates of imm…
Pediatric Anaplastic Large Cell Lymphoma with Concomitant Involvement of Spine and Central Nervous System: A Case Report and Review of Literature
2021
Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusio…
Clinical Course and Significance of the Novel FLT3-Y842C Mutation in a Patient with AML Treated with PKC412 Monotherapy.
2004
Abstract We recently identified a novel mutation (Y842C) within the tyrosine kinase domain of FLT3 in a patient treated with PKC410 monotherapy (ASH 2003, # 4681). Here, we present follow up studies including the clinical course of the patient and frequency analysis in 110 patients with AML. In addition, we characterized the novel mutation using overexpression of FLT3-Y842C in 32D cells. AML M2 was diagnosed in a 63 year old, male patient in 1993. After having experienced his second relapse upon standard therapy the patient was refractory to alemtuzumab treatment. Due to reduced performance status the patient was not eligible to standard chemotherapy and was enrolled into a phase II trial i…
Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour
2014
Abstract Background To explore the activity of pazopanib in solitary fibrous tumour (SFT). Patients and methods In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm3. Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure. Results In the …
Spleen Tyrosine Kinase (SYK) in the Progression of Peritoneal Fibrosis Through Activation of the TGF-β1/Smad3 Signaling Pathway.
2019
BACKGROUND Long-term exposure to hypertonic and high glucose in peritoneal dialysis fluid can result in peritoneal fibrosis. Spleen tyrosine kinase (SYK) has a role in inflammation and fibrosis. This study aimed to investigate the role of SYK in an in vivo rat model of peritoneal fibrosis and in rat peritoneal mesothelial cells (PMCs) in vitro and to investigate the underlying mechanisms. MATERIAL AND METHODS Sprague-Dawley rats (N=24) were randomized into the sham control group (N=6); the peritoneal fibrosis group (N=6) treated with intraperitoneal chlorhexidine digluconate; the SYK inhibitor group (N=6), treated with chlorhexidine digluconate and fostamatinib; and the TGF-s inhibitor grou…
Coupling of Cholesterol and Cone-shaped Lipids in Bilayers Augments Membrane Permeabilization by the Cholesterol-specific Toxins Streptolysin O and V…
2001
Abstract Vibrio cholerae cytolysin (VCC) forms oligomeric pores in lipid bilayers containing cholesterol. Membrane permeabilization is inefficient if the sterol is embedded within bilayers prepared from phosphatidylcholine only but is greatly enhanced if the target membrane also contains ceramide. Although the enhancement of VCC action is stereospecific with respect to cholesterol, we show here that no such specificity applies to the two stereocenters in ceramide; all four stereoisomers of ceramide enhanced VCC activity in cholesterol-containing bilayers. A wide variety of ceramide analogs were as effective asd-erythro-ceramide, as was diacylglycerol, suggesting that the effect of ceramide …
Light-Dependent Translocation of Arrestin in Rod Photoreceptors is Signaled through a Phospholipase C Cascade and Requires ATP
2009
Light adaptation of rod photoreceptors induces translocation of arrestin from inner segments (IS) to outer segments (OS). Our study suggests that components of the G-protein linked phosphoinositide pathway play a role in signaling the initiating events of arrestin translocation. We show that arrestin translocation can be stimulated by activators of phospholipase C (PLC) and protein kinase C (PKC) in the absence of light. Conversely, arrestin translocation to the OS is significantly slowed by inhibitors of PLC and PKC.In the second part of this study, we investigated the mechanism by which arrestin translocates in response to light. Other investigators have suggested that arrestin translocat…
EphrinB2 controls vessel pruning through STAT1-JNK3 signalling
2014
Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signalling repressing c-jun N-terminal kinase 3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessel…