scholarly journals Ultrasensitive analysis of genetic instability related to chemical exposure

2021 ◽  
Author(s):  
Tomasz Domoradzki ◽  
Piotr Grochowski ◽  
Anna Jaśkiewicz ◽  
Beata Pająk
Keyword(s):  
Prolonged Exposure ◽  
Genome Instability ◽  
Chemical Exposure ◽  
Molecular Techniques ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Lung Carcinogenesis ◽  
Explosive Properties ◽  
Genetic Profiles

AbstractOur concerns have been raised about whether prolonged exposure to ammunition-related chemicals could correlate with genomic instability predisposing to lung carcinogenesis. The group of professional soldiers engaged in routine ammunition analysis and its explosive properties testing. To assess the presence of an innate genetic profile, DNA isolated from swabs was analyzed with LungCarta and HS Lung Panels and MassARRAY Analyzer 4 mass spectrometry. The presence of new somatic single nucleotide polymorphisms (SNPs) was detected with liquid biopsy technique and circulating cell-free DNA (ccfDNA) isolation, which was further analyzed with UltraSeek Lung Panel. Both genetic profiles obtained for each individual were compared. Genetic analysis revealed that in professional soldiers with long-term exposure to ammunition-related toxic chemicals, new SNPs in genes related to lung carcinogenesis are present. The preliminary data indicate that using modern molecular techniques could be a valuable tool for monitoring the genome instability in context of occupational risk of harmful volatile toxic compounds and improving personnel safety. The analyzed group will be further enlarged, and follow-up studies will be continued.

scholarly journals Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 464
Author(s):  
Ming-Ling Chang ◽  
Su-Wei Chang ◽  
Shiang-Chi Chen ◽  
Rong-Nan Chien ◽  
Chia-Lin Hsu ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Mixed Cryoglobulinemia ◽  
Hcv Rna ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Short And Long Term ◽  
Male Sex ◽  
Genetic Profiles ◽  
Post Therapy

Genetic profiles of hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) in Asians remain elusive. A 10-year prospective cohort study was conducted with 1043 consecutive HCV Ab-positive Taiwanese surveyed with 13 single nucleotide polymorphisms (SNPs). Of 1043, 589 (56.5%) had baseline MC, 934 (89.5%) had positive HCV RNA, 796 completed anti-HCV therapy, and 715 had sustained virological responses (SVRs). SNP associations were surveyed withgenotypic, allelic, trend, permutation and multivariate analyses. At baseline, higher male sex and MC rates were noted in HCV RNA-positive than RNA-negative patients; higher female sex and positive HCV RNA rates but lower HCV RNA levels were noted in patients with than those without MC. Baseline associations were: HLA II-rs9461776 A allele, IFNL3-rs12979860 T allele, SERPINE1-rs6976053 C allele and MC with HCV RNA positivity; IFNL3-rs12979860 C allele, ARNTL-rs6486122 T allele and HCV RNA positivity with baseline MC. In SVR patients, RETN-rs1423096 C allele and SERPINE1-rs6976053 T allele were associated with 24-week and 10-year post-therapy MC, respectively. Conclusions: HCV RNA, IFNL3-rs12979860 and ARNTL-rs6486122 were associated with baseline MC; RETN-rs1423096 and SERPINE1-rs6976053 were associated with short- and long-term post-therapy MC in SVR patients, respectively. Links with HCV RNA and immune-associated SNPs suggest MC an immune reaction to expel HCV.

scholarly journals Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Melisa Intan Barliana ◽  
Arif Satria Wira Kusuma ◽  
Widya Norma Insani ◽  
Sofa Dewi Alfian ◽  
Ajeng Diantini ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Drug Transport ◽  
Population Data ◽  
Cross Sectional Study ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Hardy Weinberg Equilibrium ◽  
Tuberculosis Therapy ◽  
Genetic Profiles

Abstract Objective The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively. Result The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

scholarly journals Impact of Prolonged Exposure of Eleven Years to Hot Seawater on the Degradation of a Thermoset Composite

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2154
Author(s):  
Amir Hussain Idrisi ◽  
Abdel-Hamid I. Mourad ◽  
Muhammad M. Sherif
Keyword(s):  
Exposure Time ◽  
Prolonged Exposure ◽  
Mechanical Performance ◽  
Matrix Cracking ◽  
Pull Out ◽  
Strength Based ◽  
Different Temperatures ◽  
River Line ◽  
Composite Samples

This paper presents a long-term experimental investigation of E-glass/epoxy composites’ durability exposed to seawater at different temperatures. The thermoset composite samples were exposed to 23 °C, 45 °C and 65 °C seawater for a prolonged exposure time of 11 years. The mechanical performance as a function of exposure time was evaluated and a strength-based technique was used to assess the durability of the composites. The experimental results revealed that the tensile strength of E-glass/epoxy composite was reduced by 8.2%, 29.7%, and 54.4% after immersion in seawater for 11 years at 23 °C, 45 °C, and 65 °C, respectively. The prolonged immersion in seawater resulted in the plasticization and swelling in the composite. This accelerated the rate of debonding between the fibers and matrix. The failure analysis was conducted to investigate the failure mode of the samples. SEM micrographs illustrated a correlation between the fiber/matrix debonding, potholing, fiber pull-out, river line marks and matrix cracking with deterioration in the tensile characteristics of the thermoset composite.

scholarly journals Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 151-151
Author(s):  
Stephen R. Marder ◽  
Jean-Pierre Lindenmayer ◽  
Chirag Shah ◽  
Tara Carmack ◽  
Angel S. Angelov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Suicidal Behavior ◽  
Prolonged Exposure ◽  
First Occurrence ◽  
Balance Disorder ◽  
Clinical Interest ◽  
Post Hoc

AbstractObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

scholarly journals Characterization of metabolic responses, genetic variations, and microsatellite instability in ammonia-stressed CHO cells grown in fed-batch cultures

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dylan G. Chitwood ◽  
Qinghua Wang ◽  
Kathryn Elliott ◽  
Aiyana Bullock ◽  
Dwon Jordana ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Microsatellite Loci ◽  
Cho Cells ◽  
Genome Stability ◽  
De Novo ◽  
Genome Instability ◽  
Chinese Hamster ◽  
Functional Genes ◽  
Nucleotide Polymorphisms ◽  
De Novo Mutations

Abstract Background As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10’s of milligrams to over 10’s of grams per liter. Most of these gains in productivity can be attributed to increasing cell densities within bioreactors. As such, strategies have been developed to minimize accumulation of metabolic wastes, such as lactate and ammonia. Unfortunately, neither cell growth nor biopharmaceutical production can occur without some waste metabolite accumulation. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a suboptimal culture environment, little is known about the genotoxic properties of these compounds that may lead to global genome instability. In this study, we examined the effects of high and moderate extracellular ammonia on the physiology and genomic integrity of Chinese hamster ovary (CHO) cells. Results Through whole genome sequencing, we discovered 2394 variant sites within functional genes comprised of both single nucleotide polymorphisms and insertion/deletion mutations as a result of ammonia stress with high or moderate impact on functional genes. Furthermore, several of these de novo mutations were found in genes whose functions are to maintain genome stability, such as Tp53, Tnfsf11, Brca1, as well as Nfkb1. Furthermore, we characterized microsatellite content of the cultures using the CriGri-PICR Chinese hamster genome assembly and discovered an abundance of microsatellite loci that are not replicated faithfully in the ammonia-stressed cultures. Unfaithful replication of these loci is a signature of microsatellite instability. With rigorous filtering, we found 124 candidate microsatellite loci that may be suitable for further investigation to determine whether these loci may be reliable biomarkers to predict genome instability in CHO cultures. Conclusion This study advances our knowledge with regards to the effects of ammonia accumulation on CHO cell culture performance by identifying ammonia-sensitive genes linked to genome stability and lays the foundation for the development of a new diagnostic tool for assessing genome stability.

scholarly journals Molecular Epidemiology of Tuberculosis: Current Insights

2006 ◽  
Vol 19 (4) ◽  
pp. 658-685 ◽  
Author(s):  
Barun Mathema ◽  
Natalia E. Kurepina ◽  
Pablo J. Bifani ◽  
Barry N. Kreiswirth
Keyword(s):  
Vaccine Development ◽  
Epidemiologic Studies ◽  
Molecular Techniques ◽  
Tb Control ◽  
Molecular Approaches ◽  
Accuracy And Precision ◽  
Outbreak Investigations ◽  
Short And Long Term ◽  
Exogenous Reinfection

SUMMARY Molecular epidemiologic studies of tuberculosis (TB) have focused largely on utilizing molecular techniques to address short- and long-term epidemiologic questions, such as in outbreak investigations and in assessing the global dissemination of strains, respectively. This is done primarily by examining the extent of genetic diversity of clinical strains of Mycobacterium tuberculosis. When molecular methods are used in conjunction with classical epidemiology, their utility for TB control has been realized. For instance, molecular epidemiologic studies have added much-needed accuracy and precision in describing transmission dynamics, and they have facilitated investigation of previously unresolved issues, such as estimates of recent-versus-reactive disease and the extent of exogenous reinfection. In addition, there is mounting evidence to suggest that specific strains of M. tuberculosis belonging to discrete phylogenetic clusters (lineages) may differ in virulence, pathogenesis, and epidemiologic characteristics, all of which may significantly impact TB control and vaccine development strategies. Here, we review the current methods, concepts, and applications of molecular approaches used to better understand the epidemiology of TB.

Adaptation of greater plantain, Plantago major L., to long-term radiation and chemical exposure

2016 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
V. N. Pozolotina ◽  
E. V. Antonova ◽  
N. S. Shimalina
Keyword(s):  
Chemical Exposure ◽  
Plantago Major

scholarly journals Evaluation of Two Supplemented Culture Media for Long-Term, Room-Temperature Preservation ofStreptococcus pneumoniaeStrains

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Beatriz Quintero Moreno ◽  
María Araque ◽  
Evelyn Mendoza
Keyword(s):  
Survival Time ◽  
Room Temperature ◽  
Culture Media ◽  
Skim Milk ◽  
Extended Period ◽  
Phenotypic Characteristics ◽  
Genetic Profiles ◽  
Sequence Types ◽  
Over Time

Objective. To produce two supplemented agar types in order to store pneumococci for several months at room temperature.Methods. Todd-Hewitt/Hemoglobin/Yeast/Charcoal/Agar (TH-HYC) and Todd-Hewitt/Skim-Milk/Yeast/Charcoal/Agar (TH-SYC) were used to prepare two supplemented agar types. Nineteen pneumococci isolated from patients or asymptomatic carriers displaying diverse serotypes and multilocus sequence types (MLST) were subcultured and stored onto supplemented agar types, in four different tests, at room temperature.Findings. At the end of all tests (4–6 months) all noncontaminated subcultures were viable and maintained all phenotypic characteristics. Survival-time curves revealed a slow decrease of viable CFU over time on agar types, but at the end the number of viable CFU was satisfactory (≥2+ of growth). Decreasing of CFU was significantly higher for clinical versus nasopharyngeal isolates. Subcultures contamination rates were 6.25% and 14.58% after 2 and 6 months of storage, respectively.Conclusion. TH-HYC and TH-SYC agar types allowed the viability of pneumococci with several serotypes, MLST, and genetic profiles, after 6 months of storage at room temperature. We consider that these agar types are a valid alternative to preserve pneumococci over an extended period, especially when methods as cryopreservation or lyophilization are not available, and are useful for transporting strains between laboratories.

scholarly journals The phosphoproteome of rice leaves responds to water and nitrogen supply

2021 ◽  
Author(s):  
Sara Hamzelou ◽  
Vanessa J. Melino ◽  
Darren C. Plett ◽  
Karthik Shantharam Kamath ◽  
Arkadiusz Nawrocki ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Water Channel ◽  
Nitrogen Supply ◽  
Nitrogen Fertilizers ◽  
Label Free ◽  
Limited Information ◽  
Irrigated Rice ◽  
Post Translational Modifications ◽  
Growth Adaptation

The scarcity of freshwater is an increasing concern in flood-irrigated rice, whilst excessive use of nitrogen fertilizers is both costly and contributes to environmental pollution. To co-ordinate growth adaptation under prolonged exposure to limited water or excess nitrogen supply, plants have processes for signalling and regulation of metabolic processes. There is limited information on the involvement of one of the most important post-translational modifications (PTMs), protein phosphorylation, on plant adaptation to long-term changes in resource supply. Oryza sativa cv. Nipponbare was grown under two regimes of nitrogen from the time of germination to final harvest. Twenty-five days after germination, water was withheld from half the pots in each nitrogen treatment and low water supply continued for an additional 26 days, while the remaining pots were well watered. Leaves from all four groups of plants were harvested after 51 days in order to test whether phosphorylation of leaf proteins responded to prior abiotic events. The dominant impact of these resources is exerted in leaves, where PTMs have been predicted to occur. Proteins were extracted and phosphopeptides were analysed by nanoLC-MS/MS analysis, coupled with label-free quantitation. Water and nitrogen regimes triggered extensive changes in phosphorylation of proteins involved in membrane transport, such as the aquaporin OsPIP2-6, a water channel protein. Our study reveals phosphorylation of several peptides belonging to proteins involved in RNA-processing and carbohydrate metabolism, suggesting that phosphorylation events regulate the signalling cascades that are required to optimize plant response to resource supply.

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