scholarly journals Genetic variations in AURORA cell cycle kinases are associated with glioblastoma multiforme

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aner Mesic ◽  
Marija Rogar ◽  
Petra Hudler ◽  
Nurija Bilalovic ◽  
Izet Eminovic ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
In Silico Analysis ◽  
Aurora Kinase ◽  
Bioinformatic Analysis ◽  
Mitotic Checkpoint ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Homogeneous Population ◽  
Aurora Kinase B ◽  
Significant Difference

AbstractGlioblastoma multiforme (GBM) is the most frequent type of primary astrocytomas. We examined the association between single nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC) and Polo-like kinase 1 (PLK1) mitotic checkpoint genes and GBM risk by qPCR genotyping. In silico analysis was performed to evaluate effects of polymorphic biological sequences on protein binding motifs. Chi-square and Fisher statistics revealed a significant difference in genotypes frequencies between GBM patients and controls for AURKB rs2289590 variant (p = 0.038). Association with decreased GBM risk was demonstrated for AURKB rs2289590 AC genotype (OR = 0.54; 95% CI = 0.33–0.88; p = 0.015). Furthermore, AURKC rs11084490 CG genotype was associated with lower GBM risk (OR = 0.57; 95% CI = 0.34–0.95; p = 0.031). Bioinformatic analysis of rs2289590 polymorphic region identified additional binding site for the Yin-Yang 1 (YY1) transcription factor in the presence of C allele. Our results indicated that rs2289590 in AURKB and rs11084490 in AURKC were associated with a reduced GBM risk. The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results.

Distribution and pathogenicity of nsSNPs in receptor tyrosine kinases (RTKs) in patients with colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15012-e15012
Author(s):  
Matthew K Stein ◽  
Saradasri Karri ◽  
Lindsay Kaye Morris ◽  
Srishti Sareen ◽  
Kruti Patel ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tyrosine Kinases ◽  
Transmembrane Domain ◽  
Hot Spot ◽  
In Silico Analysis ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Nucleotide Polymorphisms ◽  
Significant Difference ◽  
Carboxy Terminal

e15012 Background: Non-synonymous single nucleotide polymorphisms (nsSNPs) occur along the entire sequence of RTKs and can promote oncogenic activity. As prior “hot-spot” testing was limited to the tyrosine kinase domain (TKD), next-generation sequencing (NGS) allows the discovery of novel extra-TKD variants. Methods: We analyzed all nsSNPs in 29 RTKs of colon cancer patients (pts) who received tumor profiling (2013-2015) with Caris NGS. Mutations were classified by location including the TKD, extracellular domain (ECD), transmembrane domain (TM), juxtamembrane domain (JM) and carboxy-terminal (CT) regions. nsSNPs underwent in silico analysis using PolyPhen-2 (Harvard) to predict if damaging (pnsSNP). Results: 110 pts were identified with a median age of 58 years (range 37-86); 55% male; 57% white, 41% black. 51 were KRAS+, 12 BRAF+, 5 NRAS+ and 5 were microsatellite unstable (MSI-H); 67 were left-sided, 31 right-sided, 10 transverse and 2 unknown. A total of 171 nsSNPs and 7 pathogenic mutations (Pmut) were detected: ERBB2 (ECD S310F, TKD V777L and TKD V842I), ERBB3 (ECD A232V and TKD Q809R), FGFR2 (ECD S252L) and RET (TKD L790F). 83/110 (76%) pts had ≥1 RTK mutation (median 1; range 0-9). 72/171 (42%) variants were pnsSNPs and found in 50 (45%) pts; 14% of pts had ≥2. All 29 RTKs had nsSNPs with median 6 (range 2-12); 24/29 RTKs had a Pmut or pnsSNP (median 2; range 0-8). RTKs with the most nsSNPs were EPHA5 (8/10 were pnsSNPs), PDGFA (7/8), ALK (6/8), ERBB4 (5/8), NTRK3 (5/6), cKIT (4/9), ROS1 (3/12), PDGFRB (3/6) and FGFR1 (3/6). nsSNPs were distributed across all RTK domains: 50% were ECD (30/86 pnsSNPs), 27% TKD (28/46), 13% CT (7/22), 5% JM (6/9) and 5% TM (1/8). No significant difference was seen between pnsSNP incidence and sidedness or KRAS/BRAF/NRAS status. In MSI-H pts, 13/22 variants were pnsSNPs (median 2; 1-5); 4/5 MSI-H were right-sided (Fisher’s exact p < 0.01). Conclusions: > 70% colon cancer pts had ≥1 mutation in 29 RTKs with > 70% outside the TKD, and > 40% pnsSNPs. MSI-H had a higher incidence of pnsSNPs; further study is warranted to determine their significance and actionability.

scholarly journals The Deubiquitinating Enzyme USP14 Regulates Leukemic Chemotherapy Drugs-Induced Cell Apoptosis by Suppressing Ubiquitination of Aurora Kinase B

2017 ◽  
Vol 42 (3) ◽  
pp. 965-973 ◽  
Author(s):  
Chunge Song ◽  
Ruojin Ma ◽  
Xiaoyu Yang ◽  
Sulei Pang
Keyword(s):  
Cell Apoptosis ◽  
Aurora Kinase ◽  
Mitotic Checkpoint ◽  
Leukemia Cells ◽  
Aurora B ◽  
Deubiquitinating Enzyme ◽  
Chemotherapeutic Drugs ◽  
Aurora Kinase B ◽  
Chemotherapy Drugs ◽  
Induced Apoptosis

Background/Aims: Aurora kinase B is a mitotic checkpoint kinase that plays a pivotal role in mitosis by ensuring correct chromosome segregation and normal progression through mitosis. Aurora B has been found to be amplified and overexpressed in several types of leukemia. The deubiquitinating enzyme USP14 is one of three proteasome-associated deubiquitinating enzymes and plays critical roles in diverse biological processes including cancer. However, whether USP14 has a role in leukemia cells remains elusive. Methods: Leukemic U937, NB4 and Jurkat cells were treated with diverse apoptosis-inducing drugs. The interaction between USP14 and Aurora B were determined by Western blot. The effect of USP14 in the regulation of Aurora B was detected by cycloheximide (CHX) and deubiquitination assays. FACS assay was used to determine the apoptosis ratio of cells after treatments. Results: We found that Aurora B was ubiquitinated and degraded during leukemic chemotherapy drugs-induced cell apoptosis. FBXW7 mediated Aurora B ubiquitination and degradation during chemotherapeutic drugs-induced apoptosis. USP14 associated with Aurora B and prevented Aurora B degradation. Functionally, overexpression of USP14 inhibits chemotherapeutic drugs-induced apoptosis in leukemia cells. On the contrary, administration of b-AP15, a specific inhibitor of USP14, significantly increased leukemia cells apoptosis in a dose-dependent manner. Conclusion: Thus, our data suggest that USP14 plays a novel critical role of in leukemia cells apoptosis through Aurora B stabilization and USP14 could be a potential therapeutic target for leukemia.

scholarly journals miR-155 T/A (rs767649) and miR-146a A/G (rs57095329) single nucleotide polymorphisms as risk factors for chronic hepatitis B virus infection among Egyptian patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256724
Author(s):  
Enas M. Hefzy ◽  
Noha A. Hassuna ◽  
Olfat G. Shaker ◽  
Mohamed Masoud ◽  
Tebyan A. Abelhameed ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis B ◽  
Disease Risk ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Egyptian Population ◽  
Increased Risk ◽  
Chronic Hepatitis B Virus ◽  
Significant Difference ◽  
Potential Risk Factors

Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009–8.970), p<0.0001) and AOR = 10.583 (95%CI 4.012–27.919), p<0.0001, respectively)]. The rs767649 A allele was associated with an increased risk of developing CHBV (AOR = 2.777 (95%CI 1.847–4.175), p<0.0001). There was a significant difference in the frequency of rs57095329 AG and GG genotypes in CHBV patients compared to controls. AG and GG genotypes showed an increase in the risk of developing CHBV by about three and six folds respectively [AOR = 2.610 (95%CI 1.362–5.000), p = 0.004] and [AOR = 5.604 (95%CI 2.157–14.563), p<0.0001].We concluded that rs57095329 and rs767649 SNPs can act as potential risk factors for the development of CHBV in the Egyptian population.

scholarly journals Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment

2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Miriam Cerván-Martín ◽  
Lara Bossini-Castillo ◽  
Rocío Rivera-Egea ◽  
Nicolás Garrido ◽  
Saturnino Luján ◽  
...  
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Control Group ◽  
Testicular Sperm Extraction ◽  
Binding Motif ◽  
Obstructive Azoospermia ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Significant Difference

Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffected controls to evaluate whether five single-nucleotide polymorphisms (SNPs), previously associated with reduced fertility in Hutterites, are also involved in the genetic susceptibility to idiopathic SpF and specific clinical entities. A significant difference in the allele frequencies of USP8-rs7174015 was observed under the recessive model between the NOA group and both the control group (p = 0.0226, OR = 1.33) and the SO group (p = 0.0048, OR = 1.78). Other genetic associations for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO and between TUSC1-rs10966811 and testicular sperm extraction (TESE) success in the context of NOA were observed. In silico analysis of functional annotations demonstrated cis-eQTL effects of such SNPs likely due to the modification of binding motif sites for relevant transcription factors of the spermatogenic process. The findings reported here shed light on the molecular mechanisms leading to severe phenotypes of idiopathic male infertility, and may help to better understand the contribution of the common genetic variation to the development of these conditions.

Personal Audio System: Hearing Symptoms, Habits, and Sound Pressure Levels Measured in Real Ear and a Manikin

2020 ◽  
Vol 63 (6) ◽  
pp. 2016-2026
Author(s):  
Tamara R. Almeida ◽  
Clayton H. Rocha ◽  
Camila M. Rabelo ◽  
Raquel F. Gomes ◽  
Ivone F. Neves-Lobo ◽  
...  
Keyword(s):  
Sound Pressure ◽  
Daily Basis ◽  
Cross Sectional Study ◽  
Normal Hearing ◽  
Chi Square ◽  
Cross Sectional ◽  
The Real ◽  
Significant Difference ◽  
Sound Pressure Levels ◽  
Audio System

Purpose The aims of this study were to characterize hearing symptoms, habits, and sound pressure levels (SPLs) of personal audio system (PAS) used by young adults; estimate the risk of developing hearing loss and assess whether instructions given to users led to behavioral changes; and propose recommendations for PAS users. Method A cross-sectional study was performed in 50 subjects with normal hearing. Procedures included questionnaire and measurement of PAS SPLs (real ear and manikin) through the users' own headphones and devices while they listened to four songs. After 1 year, 30 subjects answered questions about their usage habits. For the statistical analysis, one-way analysis of variance, Tukey's post hoc test, Lin and Spearman coefficients, the chi-square test, and logistic regression were used. Results Most subjects listened to music every day, usually in noisy environments. Sixty percent of the subjects reported hearing symptoms after using a PAS. Substantial variability in the equivalent music listening level (Leq) was noted ( M = 84.7 dBA; min = 65.1 dBA, max = 97.5 dBA). A significant difference was found only in the 4-kHz band when comparing the real-ear and manikin techniques. Based on the Leq, 38% of the individuals exceeded the maximum daily time allowance. Comparison of the subjects according to the maximum allowed daily exposure time revealed a higher number of hearing complaints from people with greater exposure. After 1 year, 43% of the subjects reduced their usage time, and 70% reduced the volume. A volume not exceeding 80% was recommended, and at this volume, the maximum usage time should be 160 min. Conclusions The habit of listening to music at high intensities on a daily basis seems to cause hearing symptoms, even in individuals with normal hearing. The real-ear and manikin techniques produced similar results. Providing instructions on this topic combined with measuring PAS SPLs may be an appropriate strategy for raising the awareness of people who are at risk. Supplemental Material https://doi.org/10.23641/asha.12431435

The Influence of Age and Gender on Mandibular Indices among the Libyan Population

2019 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Negative Correlation ◽  
Bone Mineralization ◽  
Age Groups ◽  
T Test ◽  
Chi Square ◽  
Age And Gender ◽  
Significant Difference ◽  
Chi Square Test ◽  
And Gender ◽  
Libyan Population

Radiographic Mandibular Indices serve as easy and relatively cheap tools for evaluating bone mineralization. Objectives: To examine the effect of age and gender on three mandibular indices: the panoramic mandibular index (PMI), the mandibular ratio (MR) and the mandibular cortical index (MCI), among Libyan population. Methods: The three indices were measured on 317 digital (OPGs) of adult humans (155 males, 162 females). The sample was divided into six age groups (from 18-25 years through 56-65 years). The measurements were analyzed for interactions with age and sex, using SPSS (Statistical Package for Social Studies) software version no. 22. The tests employed were two way ANOVA, the unpaired T-test and chi-square test. Results: The mean PMI fluctuated between 0.37 s.d. 0.012 and 0.38 s.d. 0.012. among the sixth age groups. One-way ANOVA statistical test revealed no significant of age on PMI. On the other hand gender variation has effect on PMI, since independent sample t-test disclosed that the difference between the male and female PMI means statistically significant. ANOVA test showed that the means of MR among age groups showed a negative correlation i.e. MR mean declined from 3.01 in 18-25 age groups to 2.7 in 55-65 age groups. In contrary, the gender showed no effect on MR according two sample t-test at p> 0.05. In regards with MCI, statistical analysis showed that it affected by age that is C1 was decreasing by age while C2 and C3 were increased by age. Using chi square test the result indicated that there is a significant difference among the different age group and the two genders in MCI readings. Conclusion: PMI was influenced significantly by age but minimally by the gender. MR is not affected by gender but has a negative correlation with age. MCI is affected by both age and gender

Nomophobia: An emerging fear

2020 ◽  
Vol 11 (01) ◽  
Author(s):  
Madhu Bala ◽  
Neetu Chaudhary
Keyword(s):  
Cell Phones ◽  
Administrative Authority ◽  
Chi Square ◽  
Current Time ◽  
Gender And Age ◽  
Significant Difference ◽  
Minimum Age ◽  
Multiple Cell ◽  
Negative Face ◽  
Agra City

In the current time, the use of technologies has become propensity more than necessity. Nobody has gotten away from them nor left youth or old. It's totally relying upon us How to utilize it? One such live innovation is a Smartphone. At only one touch we approach any data about the entire world. It is very easy to carry in our pocket so everyone can use it anytime whenever. Smartphone has some constructive as well as some cynical aspects too. Nomophobia is a negative face of the smartphone. Nomophobia is the irrational dread of being without cell phones or being not able to utilize phones (situational phobia) for some reason such as some signal or battery issues. Theprimary point of the current research is to find out the proportion of Nomophobia among understudies with regardof gender and age in Agra city. For this purpose, a total number of 300 students were selected by randomization (150 males and 150 females) from the age scope of 15-20 years. The data was taken by using a self-administered questionnaire NMP-Q developed by Yilidirim and Correia. The obtained data were analyzed using descriptive statistics, Mean and Chi-square. Results revealed that there is a significant difference between male and female score on nomophobia. The other result indicates that early adolescents positively related to Nomophobia as compare to late adolescents. In India, one person can use multiple cell phones. There is no minimum age to use mobile phones. It is adding fuel to the pre-existing problem of Nomophobia. Telecom Administrative Authority of India (TRAI) should assume a functioning job by making an arrangement/law that "setting based methodology" on cell phone limitations among individuals ought to be followed. A demonstration will be detailed, under this demonstration. There ought to choose the least age for portable use. It will assist a great deal with curbing the circumstance.

Fecundity and Gonado-somatic Index of Trichiurus lepturus (Linnaeus, 1758) Along the Zamboanga del Norte Coast

2018 ◽  
Vol 6 (7) ◽  
pp. 120
Author(s):  
Ma. Dulce C. Guillena
Keyword(s):  
Sex Ratio ◽  
Stock Assessment ◽  
Chi Square ◽  
Moon Phases ◽  
Ovary Weight ◽  
Moment Coefficient ◽  
Trichiurus Lepturus ◽  
Significant Difference ◽  
The Relationship ◽  
Somatic Index

Gonado-somatic index and fecundity are tools for measuring the sexual maturity and ability of animals to reproduce.  This study investigates the reproduction of Trichiurus lepturus. Specifically, this aimed to determine the sex ratio, the GSI, the relationship between fecundity and total length, fecundity and total weight, fecundity and ovary weight. The Descriptive Method of research was used.  Percentage and chi-square was utilized in determining the percentage of occurrence and sex ratio respectively.   Pearson r Product Moment Coefficient of Correlation was used to determine the relationships of the parameters. The study revealed that females outnumbered males and the sex ratio for different month showed significant difference.  Spawning season was observed to occur in November and December as revealed in its GSI values and it synchronized with the full and new moon phases.  Fecundity is positively correlated with body weight, body size, and ovary weight where ovary weight is observed to be the best index for fecundity.  The results of this study could be used further for formal stock assessment of cutlassfish fishery.

Association of Rugae Pattern with Skeletal Malocclusion in Orthodontic Patients Visiting Tertiary Care Hospital

2020 ◽  
Author(s):  
Sarwat Memon
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Care Hospital ◽  
Class Iii ◽  
Chi Square ◽  
Cross Sectional ◽  
Skeletal Malocclusion ◽  
Palatal Rugae ◽  
Significant Difference ◽  
Orthodontic Patients

Background: The palatal rugae are special constructions that are inalterable in their position and pattern during the lifestyles of an individual. This imparts them an exceptional role in the forensic dentistry and may play potential role in malocclusion identification. This study was aimed to see association of rugae pattern with sagittal skeletal malocclusion in orthodontic patients visiting tertiary care hospital. Methods: This cross-sectional examination was completed on pretreatment records (lateral Cephalometric radiographs and maxillary dental casts) of 384 subjects at the orthodontic department of Ziauddin Dental Hospital, Karachi. The study duration was from January to July 2019. The samples were sub-divided into three sagittal skeletal groups based on ANB angle proposed by Steiner’s on lateral Cephalometric radiographs (Class I with ANB angle between 0° to 4°; Class II: ANB angle greater than 5°; Class III: ANB angle less than 0°). The shapes of three most-anterior primary rugae were then evaluated bilaterally using Kapali et al., Classification. Chi Square test was applied to find association of rugae pattern among sagittal skeletal malocclusions groups. Results: Circular and curved rugae shapes were the most prevalent in all skeletal malocclusions. The primary palatal rugae pattern was seen to be significantly different among three skeletal malocclusion groups (p<0.05). The right and left sided palatal rugae pattern showed significant difference in all three skeletal malocclusion groups (p<0.05). Conclusion: The present study showed no specific palatal rugae pattern associated with sagittal skeletal malocclusion. Further studies on larger sample and use of modern 3D technologies to scan the maxillary casts are required for results that are more precise.

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