Mutation studies including those targeting the T/t-complex—a century long project

2022 ◽  
pp. 145-160
Author(s):  
Robert Erickson
Keyword(s):  
2004 ◽  
Vol 43 (01) ◽  
pp. 43-46 ◽  
Author(s):  
J. García ◽  
G. Wagner ◽  
R. Bailón ◽  
L. Sörnmo ◽  
P. Laguna ◽  
...  

Summary Objectives: In this work we studied the temporal evolution of changes in the electrocardiogram (ECG) as a consequence of the induced ischemia during prolonged coronary angioplasty, comparing the time course of indexes reflecting depolarization and those reflecting repolarization. Methods: We considered both local (measured at specific points of the ECG) and global (obtained from the Karhunen-Loève transform) indexes. In particular, the evolution of Q, R and S wave amplitudes during ischemia was analyzed with respect to classical indexes such as ST level. As a measurement of sensitivity we used an Ischemic Changes Sensor (ICS), which reflects the capacity of an index to detect changes in the ECG. Results: The results showed that, in leads with low-amplitude ST-T complexes, the S wave amplitude was more sensitive in detecting ischemia than was the commonly used index ST60. It was found that in such leads the S wave amplitude initially exhibited a delayed response to ischemia when compared to ST60, but its performance was better from the second minute of occlusion. The global indexes describing the ST-T complex were, in terms of the ICS, superior to the S wave amplitude for ischemia detection. Conclusions: Ischemic ECG changes occur both at repolarization and depolarization, with alterations in the depolarization period appearing later in time. Local indexes are less sensitive to ischemia than global ones.


Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 675-682
Author(s):  
Victoria L Browning ◽  
Rebecca A Bergstrom ◽  
Sandra Daigle ◽  
John C Schimenti

Abstract Proper levels of gene expression are important for normal mammalian development. Typically, altered gene dosage caused by karyotypic abnormalities results in embryonic lethality or birth defects. Segmental aneuploidy can be compatible with life but often results in contiguous gene syndromes. The ability to manipulate the mouse genome allows the systematic exploration of regions that are affected by alterations in gene dosage. To explore the effects of segmental haploidy in the mouse t complex on chromosome 17, radiation-induced deletion complexes centered at the Sod2 and D17Leh94 loci were generated in embryonic stem (ES) cells. A small interval was identified that, when hemizygous, caused specific embryonic lethal phenotypes (exencephaly and edema) in most fetuses. The penetrance of these phenotypes was background dependent. Additionally, evidence for parent-of-origin effects was observed. This genetic approach should be useful for identifying genes that are imprinted or whose dosage is critical for normal embryonic development.


Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.


Genetics ◽  
1989 ◽  
Vol 121 (1) ◽  
pp. 139-151
Author(s):  
M K Uyenoyama

Abstract A quantitative model is developed to explore the effects of prezygotic and postzygotic incompatibility on the origin and maintenance of associations between the major histocompatibility complex (MHC) and the t-complex in the mouse. Incompatibility is represented by a reduction in the rate of conception or gestation of offspring derived from sperm bearing MHC antigens in common with the mother. Incompatibility encourages the evolution of associations from a state of complete independence between the two complexes by promoting the invasion of all novel antigens, including those that exhibit associations with the t-complex. Incompatibility can modify the relative numbers of antigens associated with each haplotype by actively promoting the exclusion or invasion of recombinants that bear formerly +-specific or t-specific antigens on the alternative haplotype. The results of the analysis indicate that the state of complete independence between the MHC and the t-complex is not preserved over evolutionary time in the presence of incompatibility. Further, the expression of incompatibility maintains fully associated states that include a single antigen associated with the t-haplotype and up to three to five antigens associated with the +-haplotype within a single population.


2010 ◽  
pp. n/a-n/a
Author(s):  
A. M. A. El-Sokkary ◽  
M. M. El-Naggar ◽  
A. F. Abdel-Aziz ◽  
M. M. Mostafa
Keyword(s):  

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chung-Ze Wu ◽  
Li-Chien Chang ◽  
Yuh-Feng Lin ◽  
Yi-Jen Hung ◽  
Dee Pei ◽  
...  

In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunitβ(TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1βand type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (Ccr), and kidney tissues were harvested for evaluation of TCP-1βexpression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed thatCcrand the expression of TCP-1βin kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1βwas expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1βlevel was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1βis a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.


1993 ◽  
Vol 178 (6) ◽  
pp. 2107-2113 ◽  
Author(s):  
A J da Silva ◽  
O Janssen ◽  
C E Rudd

Intracellular signaling from the T cell receptor (TCR)zeta/CD3 complex is likely to be mediated by associated protein tyrosine kinases such as p59fyn(T), ZAP-70, and the CD4:p56lck and CD8:p56lck coreceptors. The nature of the signaling cascade initiated by these kinases, their specificities, and downstream targets remain to be elucidated. The TCR-zeta/CD3:p59fyn(T) complex has previously been noted to coprecipitate a 120/130-kD doublet (p120/130). This intracellular protein of unknown identity associates directly with p59fyn(T) within the receptor complex. In this study, we have shown that this interaction with p120/130 is specifically mediated by the SH2 domain (not the fyn-SH3 domain) of p59fyn(T). Further, based on the results of in vitro kinase assays, p120/130 appears to be preferentially associated with p59fyn(T) in T cells, and not with p56lck. Antibody reprecipitation studies identified p120/130 as a previously described 130-kD substrate of pp60v-src whose function and structure is unknown. TCR-zeta/CD3 induced activation of T cells augmented the tyrosine phosphorylation of p120/130 in vivo as detected by antibody and GST:fyn-SH2 fusion proteins. p120/130 represents the first identified p59fyn(T):SH2 binding substrate in T cells, and as such is likely to play a key role in the early events of T cell activation.


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