P–525 Analysis of segregation patterns of trivalent structure and the effect on genome stability in Robertsonian translocation carriers

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Dang ◽  
P Xie ◽  
L Hu ◽  
Y Tan ◽  
G Lin

Abstract Study question What are the factors that affect the separation pattern of Robertsonian translocation trivalent, and whether the structure of the trivalent affected the chromosome stability? Summary answer The meiotic segregation modes can be affected by the carrier’s sex and special chromosome, and a trivalent structure can affect the stability of the genome. What is known already Robertson translocation occurs when two proximal acrocentric chromosomes fuse at the centromere, and forms a trivalent structure during meiosis. This structure will affect the fertility of Robertsonian translocation carriers, and may destroy the stability of the genome by affecting the separation of other chromosomes, which is called Inter-Chromosomal Effect (ICE). Previous research have confirmed that the use of PGT in Robertsonian translocation carriers can effectively reduce abortion and increase live birth. But some studies dispute this conclusion and the existence of ICE. However, there is no large data study to verify these controversies. Study design, size, duration PGT results of 928 oocyte retrieval cycles in 763 couples(one of the couples is a Robertsonian translocation carrier) were analysied from December 2012 to June 2020. A total of 1492 couples who received PGT-A were collected as control group, and matched according to age and testing time stage. The study was approved by the ethics committee(LL-SC-SG–2006–008 and LL-SC-SG–2014–016). Participants/materials, setting, methods Cytogenetic analysis was performed using GTG standard method (trypsin and GiemsaG banding) to analyze the chromosomes of peripheral blood lymphocytes. Blastocysts obtained by standard IVF procedure were biopsied on the 5th or 6th morning after fertilization, and the trophoblast cells were amplified by PicoPLEX whole genome amplification kit (Rubicon Genology) or Repli-g Single Cell Kit(Qiagen). PGT-SR was performed using SNP array or NGS as previously described. Main results and the role of chance In this study, a total of 3423 blastocysts from 763 couples were analysed using SNP-array or NGS. Among them, the rate of alternate segregation of male Robertsonian translocation carriers was significantly higher than that in female carriers (82.26% vs 59.96%, P < 0.001), and meiotic segregation modes could be affected by the special chromosome such as 13 in female(P = 0.042) and 15 in male(P = 0.045) involved. A trivalent structure can affect the stability of the genome during mitosis, which is associated with an increase in the propotion of chromosome mosaic compared with the PGT-A control group(1.18% vs 0.53%, P < 0.01). In addition, we found an interesting phenomenon: in the meiotic segregation of female Robertsonian translocation carriers associated with chromosomes 21 and 22, the chromosome 21 or 22 of the two chromosomes involved in translocation are more likely to be abnormal, and according to our results, the effect of chromosome 21 seems to be greater. Limitations, reasons for caution (1) Limitations of retrospective analysis; (2) The results are not fully representative of the general population; (3) PGT-A patients always had repeated implantation failure or recurrent aboration, which may cause deviation to the results. Wider implications of the findings: This study analyzed the influencing factors of the separation patterns of trivalent, and verified the existence of ICE. This suggest that PGT-SR can have a better outcome in patients with Robertsonian translocation, especially in male carriers. These results will provide carrier couple with more appropriate genetic counseling. Trial registration number no

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Dang ◽  
P Xie ◽  
L Hu ◽  
Y Tan ◽  
G Lin

Abstract Study question What are the factors that affect the separation pattern of Robertsonian translocation trivalent, and whether the structure of the trivalent affected the chromosome stability? Summary answer The meiotic segregation modes can be affected by the carrier’s sex and special chromosome, and a trivalent structure can affect the stability of the genome. What is known already Robertson translocation occurs when two proximal acrocentric chromosomes fuse at the centromere, and forms a trivalent structure during meiosis. This structure will affect the fertility of Robertsonian translocation carriers, and may destroy the stability of the genome by affecting the separation of other chromosomes, which is called Inter-Chromosomal Effect (ICE). Previous research have confirmed that the use of PGT in Robertsonian translocation carriers can effectively reduce abortion and increase live birth. But some studies dispute this conclusion and the existence of ICE. However, there is no large data study to verify these controversies. Study design, size, duration PGT results of 928 oocyte retrieval cycles in 763 couples(one of the couples is a Robertsonian translocation carrier) were analysied from December 2012 to June 2020. A total of 1492 couples who received PGT-A were collected as control group, and matched according to age and testing time stage. The study was approved by the ethics committee(LL-SC-SG-2006-008 and LL-SC-SG-2014-016). Participants/materials, setting, methods Cytogenetic analysis was performed using GTG standard method (trypsin and GiemsaG banding) to analyze the chromosomes of peripheral blood lymphocytes. Blastocysts obtained by standard IVF procedure were biopsied on the 5th or 6th morning after fertilization, and the trophoblast cells were amplified by PicoPLEX whole genome amplification kit (Rubicon Genology) or Repli-g Single Cell Kit(Qiagen). PGT-SR was performed using SNP array or NGS as previously described. Main results and the role of chance In this study, a total of 3423 blastocysts from 763 couples were analysed using SNP-array or NGS. Among them, the rate of alternate segregation of male Robertsonian translocation carriers was significantly higher than that in female carriers (82.26% vs 59.96%, P < 0.001), and meiotic segregation modes could be affected by the special chromosome such as 13 in female(P = 0.042) and 15 in male(P = 0.045) involved. A trivalent structure can affect the stability of the genome during mitosis, which is associated with an increase in the propotion of chromosome mosaic compared with the PGT-A control group(1.18% vs 0.53%, P < 0.01). In addition, we found an interesting phenomenon: in the meiotic segregation of female Robertsonian translocation carriers associated with chromosomes 21 and 22, the chromosome 21 or 22 of the two chromosomes involved in translocation are more likely to be abnormal, and according to our results, the effect of chromosome 21 seems to be greater. Limitations, reasons for caution (1) Limitations of retrospective analysis; (2) The results are not fully representative of the general population; (3) PGT-A patients always had repeated implantation failure or recurrent aboration, which may cause deviation to the results. Wider implications of the findings This study analyzed the influencing factors of the separation patterns of trivalent, and verified the existence of ICE. This suggest that PGT-SR can have a better outcome in patients with Robertsonian translocation, especially in male carriers. These results will provide carrier couple with more appropriate genetic counseling. Trial registration number no


Author(s):  
Arda Ozdiler ◽  
suleyman dayan ◽  
Burc Gencel ◽  
Gulbahar Isık-Ozkol

This in vitro study evaluated the influence of taper angles on the internal conical connections of implant systems and of the application of chlorhexidine gel as an antibacterial agent or a polyvinyl siloxane (PVS) sealant on the reverse torque values of abutment screws after dynamic loading. The current study tested four implant systems with different taper angles (5.4°, 12°, 45°, and 60°). Specimens were divided into three groups: control (neither chlorhexidine gel filled nor silicone sealed), 2% chlorhexidine gel-filled or silicone-sealed group, and group subjected to a dynamic load of 50 N at 1 Hz for 500,000 cycles prior to reverse torque measurements. Quantitative positive correlation was observed between the taper angle degree and the percentage of tightening torque loss. However, this correlation was significant only for the 60° connection groups except in the group in which a sealant was applied ( p = 0.013 for the control group, p = 0.007 for the chlorhexidine group). Percentages of decrease in the torque values of the specimens with silicone sealant application were significantly higher compared with both the control and chlorhexidine groups ( p = 0.001, p = 0.002, p = 0.001, and p = 0.002, respectively, according to the increasing taper angles); the percentage of decrease in torque values due to chlorhexidine application was statistically insignificant when compared with the control group. The application of gel-form chlorhexidine as an antibacterial agent does not significantly affect the stability of the implant–abutment connection under dynamic loads. PVS sealants may cause screw loosening under functional loads.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sean Swetledge ◽  
Renee Carter ◽  
Rhett Stout ◽  
Carlos E. Astete ◽  
Jangwook P. Jung ◽  
...  

AbstractPolymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.


Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 12
Author(s):  
David Chavarri-Prado ◽  
Aritza Brizuela-Velasco ◽  
Ángel Álvarez-Arenal ◽  
Markel Dieguez-Pereira ◽  
Esteban Pérez-Pevida ◽  
...  

Objectives: To determine the effect of mechanical loading of bone on the stability and histomorphometric variables of the osseointegration of dental implants using an experimental test in an animal model. Materials and Methods: A total of 4 human implants were placed in both tibiae of 10 New Zealand rabbits (n = 40). A 6-week osseointegration was considered, and the rabbits were randomly assigned to two groups: Group A (Test group) included 5 rabbits that ran on a treadmill for 20 min daily during the osseointegration period; Group B (Controls) included the other 5 that were housed conventionally. The monitored variables were related to the primary and secondary stability of the dental implants (implant stability quotient—ISQ), vertical bone growth, bone to implant contact (BIC), area of regenerated bone and the percentage of immature matrix. Results: The results of the study show a greater vertical bone growth (Group A 1.26 ± 0.48 mm, Group B 0.32 ± 0.47 mm, p < 0.001), higher ISQ values (Group A 11.25 ± 6.10 ISQ, 15.73%; Group B 5.80 ± 5.97 ISQ, 7.99%, p = 0.006) and a higher BIC (Group A 19.37%, Group B 23.60%, p = 0.0058) for implants in the test group, with statistically significant differences. A higher percentage of immature bone matrix was observed for implants in the control group (20.68 ± 9.53) than those in the test group (15.38 ± 8.84) (p = 0.108). A larger area of regenerated bone was also observed for the test implants (Group A 280.50 ± 125.40 mm2, Group B 228.00 ± 141.40 mm2), but it was not statistically significant (p = 0.121). Conclusions: The mechanical loading of bone improves the stability and the histomorphometric variables of the osseointegration of dental implants.


Author(s):  
Ginette Lacoste-Royal ◽  
Martine Mathieu ◽  
Josephine Nalbantoglu ◽  
Jean-Pierre Julien ◽  
Serge Gauthier ◽  
...  

ABSTRACT:The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a Taql-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. Hindi detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.


Author(s):  
Said Yousef Swilem

The purpose of this study is to examine the efficiency of a group counseling program based on psychodrama in improving self-awareness and reducing tension among tenth grade students in Qalqilia City and examining the nature and the direction of the relationship between self-consciousness and tension, the sample of study consisted of (20) students whom were distributed randomly equally to two groups the first is an experimental contains (10) students and the second is a control group contains (10) students in light of a tension variable, they are drawn out from (152) students in governmental schools who obtained the highest stress scale for the current study, a counseling program has been built based on the principles and methodology methods of psychodrama which contained (13) sessions, the current study used a measure of self-awareness and tension before and after the program. The researcher used the semi-experimental design to verify the validity of the two instruments they were presented to a group of specialized consultants. The stability coefficient was then calculated using Cronbach Alpha, where the stability value of the self-awareness scale was 0.81 and tension scale was 0.90. The mean and standard deviations were calculated and the Shapiro-Wilk test was used to examine the normal distribution probability of the variables of self-awareness and tension. The results revealed in the non-moderate distribution of individual responses to the two variables. The Mann-Whitney test, the Wilcoxon Signed Ranks Test, and the Spearman Product-Moment Correlation Coefficient test were used. The results showed differences between the experimental and control groups in the post-test of self-awareness and stress measures and for group members this is an indication of the effectiveness of the psychodrama -based counseling program in improving self-awareness and reducing stress among tenth grade students in Qalqilia city and the absence of differences in experimental group members between the tribal and remote testing methods of self-awareness and differences in group members for testing between the two pre-test and post- test of stress. The researcher recommends that self-awareness and stress in the adolescent group should be addressed through the psychodrama -based counseling programs.    


2021 ◽  
Vol 2 (4) ◽  
pp. 196-207
Author(s):  
Emanuel Sporer ◽  
Christian B. M. Poulie ◽  
Sture Lindegren ◽  
Emma Aneheim ◽  
Holger Jensen ◽  
...  

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.


Author(s):  
Desirée Perlee ◽  
Klaas Henk van der Steege ◽  
Gijs den Besten

Abstract Objectives Transport of blood tubes is mainly by car or pneumatic transport. The transportation of blood tubes by drones is a novel approach for rapid transportation of blood tubes over long distances. However, limited data on the stability of biochemical, coagulation and hematological parameters is available after transport of blood tubes by drone. Methods To investigate the effect of drone transport on the stability of blood parameters, four test flights were performed. Blood was drawn from 20 healthy individuals and 39 of the most frequently measured blood parameters were compared between 4 groups; immediate measurement (control), late measurement, transport by car and transport by drone. Total Allowable Error (TAE) of the EFLM Biological Variation Database was used to determine the clinical relevance of significant differences. Results The majority of blood parameters were not affected by drone transport. Eight of the measured parameters showed significant differences between all the groups; glucose, phosphate, potassium, chloride, hemoglobin, platelet count, APTT and Lactate dehydrogenase (LD). A clinically relevant increase for LD after transport and a decrease for glucose values in time and after transport compared with the control group was shown. Conclusions Transportation of blood tubes from healthy individuals by drones has a limited clinically relevant effect. From the 39 investigated blood parameters only LD and glucose showed a clinically relevant effect.


2020 ◽  
Vol 9 (5) ◽  
pp. 661-668
Author(s):  
Xiumei Xing ◽  
Zhini He ◽  
Ziwei Wang ◽  
Ziying Mo ◽  
Liping Chen ◽  
...  

Abstract To explore the epigenetic alterations in response to DNA damage following polycyclic aromatic hydrocarbons (PAHs) exposure and the crosstalk between different epigenetic regulations, we examined trimethylated Lys 36 of histone H3 (H3K36me3) and methylation of ‘long interspersed element-1 (LINE-1)’ and ‘O 6-methylguanine-DNA methyltransferase (MGMT)’ in peripheral blood lymphocytes (PBLCs) of 173 coke oven workers (PAH-exposed group) and 94 non-exposed workers (control group). The PAH-exposed group showed higher internal PAH exposure level, enhanced DNA damage and increased MGMT expression (all P &lt; 0.001). Notably, the methylation of LINE-1 and MGMT decreased by 3.9 and 40.8%, respectively, while H3K36me3 level was 1.7 times higher in PBLCs of PAH-exposed group compared to control group (all P &lt; 0.001). These three epigenetic marks were significantly associated with DNA damage degree (all P &lt; 0.001) and PAH exposure level in a dose–response manner (all P &lt; 0.001). LINE-1 hypomethylation is correlated with enhanced H3K36me3 modification (β = −0.198, P = 0.002), indicating a synergistic effect between histone modification and DNA methylation at the whole genome level. In addition, MGMT expression was positively correlated with H3K36me3 modification (r = 0.253, P &lt; 0.001), but not negatively correlated with MGMT methylation (r = 0.202, P &lt; 0.05). The in vitro study using human bronchial epithelial cells treated with the organic extract of coke oven emissions confirmed that H3K36me3 is important for MGMT expression following PAH exposure. In summary, our study indicates that histone modification and DNA methylation might have synergistic effects on DNA damage induced by PAH exposure at the whole genome level and H3K36me3 is more essential for MGMT expression during the course.


2011 ◽  
Vol 81 (5) ◽  
pp. 776-782 ◽  
Author(s):  
Ki-Ho Park ◽  
Eun-Man Lee ◽  
Seung-il Shin ◽  
Seong-Hun Kim ◽  
Young-Guk Park ◽  
...  

Abstract Objective: To compare the effect of clockwise and counterclockwise torque on the primary stability of a mini-implant with a lever-arm–shaped upper structure. Materials and Methods: Twenty-four white rabbits were used for this study. Two screw-type mini-implants were placed in each tibia. In all, 96 screws were inserted. Two weeks later, a 2-N force was applied to the mini-implants without an upper structure in eight rabbits (control group). The mini-implants of the other 16 rabbits were loaded with an upper structure (experimental group). In the experimental group, the two left mini-implants were loaded in a clockwise direction (CW group) and the two right implants were loaded in a counterclockwise direction (CCW group). The rabbits were sacrificed at 1 week or 8 weeks after loading in both control and experimental groups. The removal torque value (RTV) was measured in 15 of 16 mini-implants in each group and the remaining implant was processed for histologic examination. Results: At 1 week there were no significant differences in the mean RTV between the control, CW, and CCW groups. At 8 weeks, the RTV was higher in the control and experimental groups than in the respective 1-week groups. At 8 weeks, there were no significant differences in the RTV between the control and CW groups, but the CCW group showed a lower RTV. Conclusions: CCW torque can decrease the stability of a mini-implant, whereas a CW torque has no effect.


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