scholarly journals The actin-modulating protein Synaptopodin mediates long-term survival of dendritic spines

2020 ◽  
Author(s):  
Kenrick Yap ◽  
Alexander Drakew ◽  
Dinko Smilovic ◽  
Michael Rietsche ◽  
Mario Vuksic ◽  
...  
Keyword(s):  
Memory Trace ◽  
Granule Cells ◽  
Time Lapse ◽  
Two Phase ◽  
Term Survival ◽  
Long Lifetime ◽  
Time Courses ◽  
Organotypic Tissue ◽  
Trace Formation

AbstractLarge spines are stable and important for memory trace formation. The majority of large spines also contains Synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using time-lapse 2-photon-imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP-positive (SP+) spines followed conditional two-phase decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single exponential decays. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines and the presence of SP indicates spines of high stability.

scholarly journals The actin-modulating protein synaptopodin mediates long-term survival of dendritic spines

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kenrick Yap ◽  
Alexander Drakew ◽  
Dinko Smilovic ◽  
Michael Rietsche ◽  
Mandy H Paul ◽  
...  
Keyword(s):  
Memory Trace ◽  
Granule Cells ◽  
Time Lapse ◽  
Term Survival ◽  
Long Lifetime ◽  
Time Courses ◽  
Organotypic Tissue ◽  
Time Lapse Imaging ◽  
Trace Formation

Large spines are stable and important for memory trace formation. The majority of large spines also contains synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using 2-photon time-lapse imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive (SP+) spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP+ spines followed conditional two-stage decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single-phase exponential decays. This was also the case following afferent denervation. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines, and the presence of SP indicates spines of high stability.

scholarly journals Mobility of B.C.T. Dental implants inserted by one and two-phase surgical method: An experimental study

2006 ◽  
Vol 63 (10) ◽  
pp. 867-872
Author(s):  
Novak Stamatovic ◽  
Smiljana Matic ◽  
Zoran Lazic ◽  
Zoran Tatic
Keyword(s):  
Dental Implants ◽  
Titanium Implants ◽  
Phase Method ◽  
Average Weight ◽  
Crucial Importance ◽  
Two Phase ◽  
Term Survival ◽  
Surgical Method ◽  
The Difference

Background/Aim. Achievement of the osseointegration of dental implants is of crucial importance for their long-term survival. One of the factors that influence the osseointegration is a surgical method of implantation. The outcome of osseointegration can be evaluated on the basis of implant mobility in bone. The aim of this study was to investigate and compare the mobility of B.C.T. dental titanium implants inserted to experimental animals using an one and two-phase method. Methods. The investigation was performed using a split-mouth design on nine dogs, male german shephards, average age of 3.5 years and average weight of 32 kg. Extractions of the third and fourth lower premolars were performed under intravenous (i.v.) anaesthesia with 5% ketamine chloride. Eight weeks after the extractions, the implants, diameter of 4.5 mm each, with four threads 13.7 mm long, were inserted. Eighteen implants were inserted one side of the jaw using a one-phase method, and another 18 implants were inserted contralaterally using a two-phase method. Three months after the implantation, the implant mobility was evaluated. Three measurements were performed with a Periotest device, and average values were calculated. The implant mobility was classified according to the Periotest scale in four groups of Periotest values (PTV) and compared. A total of 36 implants were inserted in 9 experimental dogs. The PTV ranged from -7.666 to + 50. Results. According to the Periotest scale, 14 one-phase implants (78%) were classified into the 0 group of PTV, and 4 one-phase implants (22%) in the 3rd group. Thirteen two phase implants (72%) were classified in the 0 group, and 5 implants in the 3rd group of Periotest scale. The difference in the average values of PTV between the two methods was 0.879 which was not statistically significant. Conclusion. This study showed that the method of implant insertion had no influence on the implant mobility, i.e. satisfactory osseointegration could be achieved by both methods. Further clinical parameters, as well as pathohistological and histomorphometric ones, have to be evaluated in order to assess better outcome of a particular method.

Defects in DNA repair genes and long-term survival in cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4536-4536
Author(s):  
Benjamin Miron ◽  
Eric A. Ross ◽  
Fern Anari ◽  
John O'Neill ◽  
Jean H. Hoffman-Censits ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Term Survival

4536 Background: Although cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in MIBC, only a subset of patients have pathologic complete response (pT0) at cystectomy. ATM, RB1 and FANCC mutations have shown correlation with pT0 to cisplatin-based NAC, as previously published. We now report updated OS and disease specific survival (DSS) from two phase II trials using these gene alterations as biomarkers. Methods: Patients with stage T2-T4 (N0 or N1) MIBC were enrolled in phase II trials of dose-dense NAC with MVAC (methotrexate, vinblastine, adriamycin, and cisplatin; NCT01031420) or GC (gemcitabine and cisplatin; NCT01611662). Patients were treated with NAC with plan for curative cystectomy. DNA from pretreatment tumor tissue was sequenced for coding exons of 287 cancer-related genes and analyzed for mutations. Survival in patients with one or more mutations in ATM, RB1, or FANCC genes was compared to those without mutations. Results: Of 58 pts treated, 38% (22/58 pts) had relevant mutations in the combined group of MVAC (13/34 pts) and GC (9/24 pts) trials. At a median follow-up of 56 months and minimum follow up of 16 months, patients with mutations had statistically significantly greater OS (p = 0.0043) and DSS (p = 0.0015). Median OS/DSS was not reached for patients with a mutation in any group. At 5 years post treatment, OS/DSS were greater in mutated vs non-mutated patients in all groups (see table). Conclusions: Long-term follow up reveals that previously reported improved responses to cisplatin-based NAC associated with mutations in ATM, RB1 and FANCC also confer a clinically meaningful and statistically significant survival benefit in these patients. These alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients most likely to benefit from NAC prior to radical cystectomy. [Table: see text]

Caspases and apoptosis

2002 ◽  
Vol 38 ◽  
pp. 9-19 ◽  
Author(s):  
Guy S Salvesen
Keyword(s):  
Cysteine Proteases ◽  
Signalling Pathways ◽  
Term Survival ◽  
Mature Adult ◽  
Intracellular Signalling Pathways ◽  
Adult Cell ◽  
Caspase Family ◽  
Cell Fragments ◽  
Pro Inflammatory Cytokines

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells
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