Nuclear Deoxyribonucleic Acid Research Articles

The Nature and Origin of Plant Viruses with an Incursion into Virus Nomenclature

Eversince, the chemical nature of not only the anisometric tobacco mosaic virus (TMV) but also the crystalline viruses like bushy stunt of tomato, tobacco necrosis virus, turnip yellow mosaic virus and others have been characterized, sap transmissible viruses have been shown to be good antigens and that their antisera had group specificity aiding identification. Whilst symptomatology alone was found unreliable and of insufficient means for diagnosis and classification of viruses, serology, chemical and physical structure of viruses and the modes of transmission have played an important role in virus nomenclature. However, it is premature to think of orthodox binomial and trinomial nomenclature as practised in fungal classification playing a role in virus terminology, Anisometric and crystalline viruses are comparatively simple chemical entities (as compared with animal viruses) and are essentially nucleoproteins where the RNA (ribonucleic acid) core has a shell of protein in a helical pattern serving as a protective coating. The infectivity of the nucleic acid alone (which is hardly 6% of the nucleoproteiri) has been proved beyond doubt whereas, the protein (which is the bulk of the virus) does not count for infectivity but plays an important role in serological reactions and consequently is of immense value in grouping viruses. Nevertheless, size, shapes and structure of viruses are of considerable significance as a tool in virus classification of rodshaped particles. Spherical virus particles, however, have not lent themselves to this approach. A somewhat similar approach to classification has been made by using specific vector-virus relationships.In the speculative field of origin of viruses, the free gene or plasmagene theory of Darlington seems to find little support at present. Nonetheless, a biochemical approach is still valid and as all the ribonucleic acid (RNA) in the TMV appears to be present in a single polynucleotide chain, a break in this chain has to be transmitted intact to the recipient cell to enable reduplication. That the RNA may be replicated in the cells is, therefore, not to be regarded as a shortlived messenger carrying genetic information from nuclear deoxyribonucleic acid (DNA) to protein. Stretching this argument one could conceive of a further step to the self-perpetuating RNA molecule capable of directing protein synthetic mechanisms in recipient cells to specific products.

Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets.

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.

A Review of Numerical Models of Radiation Injury and Repair Considering Subcellular Targets and the Extracellular Microenvironment.

Astronauts in space are subject to continuous exposure to ionizing radiation. There is concern about the acute and late-occurring adverse health effects that astronauts could incur following a protracted exposure to the space radiation environment. Therefore, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models could be improved. Historically, radiobiological models focused on how radiation damages nuclear deoxyribonucleic acid (DNA) and the role DNA repair mechanisms play in resulting biological effects, building on the hypotheses of Crowther and Lea from the 1940s and 1960s, and they neglected other subcellular targets outside of nuclear DNA. The development of these models and the current state of knowledge about radiation effects impacting astronauts in orbit, as well as how the radiation environment and cellular microenvironment are incorporated into these radiobiological models, aid our understanding of the influence space travel may have on astronaut health. It is vital to consider the current tools and models used to describe the organic consequences of ionizing radiation exposure and identify where they can be further improved.

A Monte Carlo study on the impact of indirect action on neutron relative biological effectiveness.

Recent Monte Carlo studies have linked the energy-dependent risk of neutron-induced stochastic effects to the relative biological effectiveness (RBE) of neutrons in inflicting difficult-to-repair clusters of lesions in nuclear deoxyribonucleic acid (DNA). However, an investigation on the damaging effects of indirect radiation action is missing from such studies. In this work, we extended our group's existing simulation pipeline by incorporating and validating a model for indirect action. Our updated simulation pipeline was used to study the impact of indirect action and estimate neutron RBE for inflicting clustered lesions in DNA. In our results, although indirect action significantly increased the average yield of DNA damage clusters, our neutron RBE values are lower in magnitude than previous estimates due to model limitations and the greater relative impact of indirect action in lower-linear energy transfer (LET) radiation than in higher-LET radiation.

Single-cell DNA sequencing-a potential dosimetric tool.

We hypothesised that single-cell whole-genome sequencing has the potential to detect mutational differences in the genomes of the cells that are irradiated with different doses of radiation and we set out to test our hypothesis using in silico and in vitro experiments. In this manuscript, we present our findings from a Monte Carlo single-cell irradiation simulation performed in TOPAS-nBio using a custom-built geometric nuclear deoxyribonucleic acid (DNA) model, which predicts a significant dose dependence of the number of cluster damages per cell as a function of radiation dose. We also present preliminary experimental results, obtained from single-cell whole-genome DNA sequencing analysis performed on cells irradiated with different doses of radiation, showing promising agreement with the simulation results.

The Analysis of Genetic Polymorphism on Mitochondrial Hypervariable Region III in Thai Population.

Mitochondrial DNA (mtDNA) analysis is a genetic marker for human identification, especially matrilineal inheritance. Hypervariable regions (HVR) I and II of mtDNA have been currently performed for human identification worldwide. Further examination of HVRIII has been conducted with the aim of enhancing the power of discrimination. The aim of this research is to provide informative data on the polymorphisms of HVRIII in the Thai population in order to establish a national database for human identification. Thai people who were unrelated through the maternal lineage were recruited for blood collections. The mtDNA was extracted by Chelex extraction, amplified by polymerase chain reaction, and analyzed using Sequencing Analysis Software. The most common mutation in HVRIII was base substitution, followed by deletion and insertion. We discovered 40 unique haplotypes, with haplotype 489C being the most frequent. The haplotype diversity, power of discrimination, and random match probability were 0.8014, 0.7987, and 0.2013, respectively. Five-CA repeats were the most frequently observed in nucleotide positions 514-523. Our database can be employed as supplementary markers in addition to nuclear deoxyribonucleic acid (DNA) markers in forensic investigations. Moreover, the data could potentially enhance genetic identification and anthropological genetics research in Thailand.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

Systematic Review on Implication for DNA Assisted Technology into Molecular Medicine and the useful is the application of Genome Wide Studies

Objective: The aim of this study is to explore the role of molecular DNA, DNA Phenotyping and Polymerase Chain Reaction in samples relevant to genetic investigation. The Deoxyribonucleic Acid (DNA) is a macromolecule which has propelled our capacity of understanding the function of an organism at the cellular level, how organism reproduce and replicate, and pass their subjective genetic information from one generation to the other. DNA is also referred to as the genetic “Blueprint” of an organism and found to possess all information pertaining to the specific being. Nuclear DNA is present within the nucleus and is significant in developing immunity for the cell and depends on the information incorporated within its framework. Mitochondrial DNA exists in varying locations in frequencies of two to ten copies within mitochondria. The most familiar body fluids come across in molecular medicine laboratories is blood, semen and saliva and further more are vaginal fluids, urine and sweat. Bones, teeth, soft tissues etc. are also essential biomarkers for DNA-phenotyping. Methodology: The methods for research for this particular study is to demonstrate a review of relevant literature to examine the molecular genetics and the application of genome and DNA-amplification into molecular medicine investigations. To conduct a literature review a qualitative research design is the most suitable research design. It provides the rationale for assessing the human behaviour and assists to legalize and authenticate the data which is selectively collected from the secondary sources. Results: Every individual’s DNA consists of minor alterations a change in these restriction places would result in different profile of restriction fragments. Genome wide population substructure is large enough to determine ancestry with large number of Autosomal SNPs at the level of continental resolutions. Conclusion: The advances in human genomics and molecular genetics have provided success and advances by determining the cellular origin and estimating the age of sample and disposition time. The Phenotypical characteristics like hair and eye color demonstration in criminal cases has yielded better inferences however, DNA phenotyping illustrates a limited approach wherein incorporated into biological material analysis. The accuracy of DNA technology is incredibly useful for professionals like lawyers, anthropologists, homicide detectives etc. in the field of molecular medicines and is expected to improve in years to come. Key Words; Deoxyribonucleic Acid (DNA) , Polymerase Chain Reaction (PCR), Mitochondrial DNA (mtDNA) sequencing and Short Tardem Repeat (STR)

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies.

The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication with the prediction of potential targets employing in silico studies. An oral administration of different concentrations (100, 200 and 400 mg/kg body weight) of BERM before high-dose ethanol via intraperitoneal injection was performed in mice. On day 7, liver sections were dissected for histopathological examination. The ethanol intoxication caused liver injury and large areas of necrosis. The pre-BERM administration decreased the ethanol-induced liver damage marker tumor necrosis factor-alpha (TNF-α) expression, reduced hepatotoxicity revealed by nuclear deoxyribonucleic acid (DNA) fragmentation and decreased oxidative stress indicated by malondialdehyde and glutathione contents. Our in silico studies have identified BERM-derived metabolites exhibiting the highest predicted antioxidant and free radical scavenger activities. Molecular docking studies showed that most of the metabolites were predicted to be enzyme inhibitors such as carbonic anhydrase inhibitors, which were reported to stimulate the antioxidant defense system. The metabolites predominantly presented acceptable pharmacokinetics and safety profiles, suggesting them as promising new antioxidant agents. Altogether, the BERM extract exerts antioxidative activities and shows promising hepatoprotective effects against ethanol intoxication. Identification of related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis.

Sepsis is not only a threat to the health of individual patients but also presents a serious epidemiological problem. Despite intensive research, modern sepsis therapy remains based primarily on antimicrobial treatment and supporting the functions of failing organs. Finding a cure for sepsis represents a great and as yet unfulfilled need in modern medicine. Research results indicate that the activity of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) may play an important role in the inflammatory response and the cellular metabolic disorders found in sepsis. Mechanisms by which PARP-1 may contribute to inflammation and metabolic disorders include effects on the regulation of gene expression, impaired metabolism, cell death, and the release of alarmins. These findings suggest that inhibition of this enzyme may be a promising solution for the treatment of sepsis. In studies using experimental sepsis models, inhibition of PARP-1 has been shown to ameliorate the inflammatory response and increase survival. This action was described, among others, for olaparib, a PARP-1 inhibitor approved for use in oncology. While the results of current research are promising, the use of PARP inhibitors in non-oncological diseases raises some concerns, mainly related to the enzyme’s role in deoxyribonucleic acid (DNA) repair. However, the results of studies on experimental models indicate the effectiveness of even short-term PARP-1 inhibition and do not confirm concerns regarding its impact on the integrity of nuclear DNA. Current research presents PARP inhibition as a potential solution for the treatment of sepsis and indicates the need for further research.

SECONDARY MITOCHONDRIAL DYSFUNCTION

Mitochondria are the most vital organelle in the cell because of its multitask properties. They are well known for the production of energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), which involves multiple complexes and cofactors. Mitochondria in addition to ATP production, also perform other vital functions like generation of reactive oxygen species (ROS), antioxidants, apoptosis, signaling and hormone actions.
 Because of their multiple actions, it is quite expected that their dysfunction will result in the number of effects. Since most vital organs exclusively depend on ATP to perform their functions, therefore impediment in its supply resulting from mitochondrial dysfunction will be detrimental and have a widespread spectrum. Neurodegenerative disorders, Huntington’s disease, cardiovascular disease (CVD), epilepsy, aging, metabolic syndrome, diabetes, autism, muscular atrophy, lou gehrig’s disease, neoplasia, down syndrome are few instances where mitochondrial dysfunction is the basic cause in pathogenesis.
 Mitochondrial disorders are either Primary or secondary disorders. Primary mitochondrial disease or disorder (PMD) has mitochondrial or nuclear deoxyribonucleic acid (mt DNA or nDNA) mutation affecting oxidative phosphorylation (OXPHOS). While Secondary mitochondrial dysfunction (SMD) does not involve OXPHOS but is the result of mutations in non OXPHOS genes. Secondary mitochondrial dysfunction (SMD) can also be acquired secondary to adverse factors those cause oxidative stress.
 All this highlights the role of mitochondria and makes it a new therapeutic target in managing these disorders. The present review has briefly discussed the secondary mitochondrial dysfunctional disorders and the approach to tackle it.

Empowering of reproductive health of farm animals through genome editing technology

To cater the exponential growth of human population, need to improve food production and quality through modern biotechnology with limited recourses in a way that has minimal impact on the environment. The selective breeding and genomic selection have attended the momentum gain in livestock productivity. Recent advancement in genome-editing technologies offers exciting prospects for the production of healthy and prolific livestock. Genome editing involves altering genetic material by manipulation, addition, or removal of certain deoxyribonucleic acid (DNA) sequences at a specific locus in a way that does not occur naturally. The major genome editors are zinc finger nucleases, transcription-activator-like endonucleases, and clustered regularly interspaced short palindromic repeats associated protein nine systems which are proficient of cutting the nuclear DNA precisely at a predetermined position. This review provides an update on the use of genome editing systems to modify the genes related to reproduction of farm animal vis-à-vis human, update knowledge on the underlying mechanism and discusses new opportunities to produce genetically modified farm animals.

SUN-155 A Complex Case of Adrenal Insufficiency Associated with NLRP1 Gene Mutation in a Patient with Myopathy and Mitochondrial Cytopathy

Most cases of Addison’s disease are due to an autoimmune response, with the most commonly associated genes belonging to human leukocyte antigen (HLA) complex. Genome wide association studies have shown a significant association of variants of Nuclear Localization Leucine-Rich-Repeat Protein 1 (NLRP1) with Addison’s disease. NLRP1 protein is involved in the assembly of inflammasome which promotes the secretion of interleukin-1β, interleukin-18 and downstream inflammatory responses to regulate inflammation. With underlying myopathy and mitochondrial disease, coexisting adrenal insufficiency may be challenging to identify. A 36-year-old female presented for evaluation of fatigue, myalgia, and dyspnea for several years. She carried a diagnosis of asthma, myopathy, gastroparesis requiring a gastric stimulator, and recently diagnosed adrenal insufficiency secondary to long term fluticasone use. Beside low blood pressure of 91/64 millimetres of mercury, physical exam was unremarkable. Lab findings were significant for dehydroepiandrosterone-sulfate (DHEAS) of 7.0 micrograms per deciliter (mcg/dL), Adrenocorticotropic hormone (ACTH) of 7.2 picograms per milliliter and cortisol of 1.4 mcg/dL. Adrenal insufficiency was confirmed with cosyntropin stimulation test. Methacholine challenge test showed worsening asthma. She was managed with empiric stress dose steroids when indicated. Muscle fatigue progressed despite taking ubiquinol, B100 and carnitine. She was further evaluated with muscle biopsy that showed type two fiber atrophy. Muscle coenzyme Q10 was 0.08 mcg/dL, and citrate synthase was 50% of normal, insufficient for electron transport complex I. Whole exome sequencing showed mutations in NLRP1 in addition to Myosin Heavy Chain 2 (MYH2) and Sodium voltage-gated Channel alpha subunit 4 (SCN4a) both of which are associated with myopathy. She was then started on a short-acting glucocorticoid regimen. While her adrenal insufficiency was initially thought to be secondary to inhaled steroids, subsequent mutation analysis suggested that she was prone to autoimmunity. This case illustrates the association of adrenal insufficiency with NLRP1 mutation. Furthermore, the symptoms of adrenal insufficiency and myopathy can overlap making it difficult to delineate. While so far most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial deoxyribonucleic acid (DNA), a new field of investigation is that of syndromes due to mutations in the nuclear DNA.

Genotoxicity evaluation of multiwalled carbon nanotubes: in vivo studies in mice

The toxicity of carbon nanoparticles in recent years has attracted much attention due to their active use in industry, medicine and agriculture, which brings not only obvious benefits, but also potential danger to the environment and human health. Getting into the natural environment, bioaccumulating and bioconcentrating in them, carbon nanotubes pose a real threat to mammals, since due to their high migration ability they can penetrate the food chain of animals and humans. Therefore, the aim of this study was to study the genotoxicity of carbon nanotubes in in vivo experiments on laboratory mice. For this, based on the method of single cell alkaline gel electrophoresis assay, studies were conducted to determine the effect of aqueous colloidal solutions of multiwalled carbon nanotubes on genotoxicity towards various tissues in laboratory mice. During these acute and subacute in vivo experiments we have established that orally introduced multiwalled carbon nanotubes colloids damage deoxyribonucleic acid in various organs. In particular, 0.5 mg of multiwalled carbon nanotubes administered daily for 21 days have a prominent genotoxic effect. Thus, the obtained results have illustrated that multiwalled carbon nanotubes can potentially affect the genetic material in mammals, orally administered nanotubes increase the rate of nuclear deoxyribonucleic acid destruction.

Urinary cell-free mitochondrial and nuclear deoxyribonucleic acid correlates with the prognosis of chronic kidney diseases

IntroductionCell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an easily obtained and non-invasive sample source over tissue and blood. In clinical practice, it is important to identify non-invasive biomarkers of chronic kidney disease (CKD) in monitoring and surveillance of disease progression. Information is limited, however, regarding the relationship between urine and plasma cf-DNA and the renal outcome in CKD patients.MethodsOne hundred and thirty-one CKD patients were enrolled between January 2016 and September 2018. Baseline urine and plasma cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) were isolated using quantitative real-time PCR. Estimated glomerular filtration rate (eGFR) measurement was performed at baseline and 6-month follow-up. Favorable renal outcome was defined as eGFR at 6 months minus baseline eGFR> = 0. Receiver operator characteristics (ROC) curve analysis was performed to assess different samples of cf-DNA to predict favorable renal outcomes at 6 months. A multivariate linear regression model was used to evaluate independent associations between possible predictors and different samples of cf-DNA.ResultsPatients with an advanced stage of CKD has significantly low plasma cf-nDNA and high plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. Low urine cf-mtDNA, cf-nDNA levels and low plasma NGAL were significantly correlated with favorable renal outcomes at 6 months. The urine albumin-creatinine ratio (ACR) or urine protein-creatinine ratio (PCR) level is a robust predictor of cf-mtDNA and cf-nDNA in CKD patients. Baseline urine levels of cf-mtDNA and cf-nDNA could predict renal outcomes at 6 months.ConclusionsUrinary cf-mtDNA and cf-nDNA may provide novel prognostic biomarkers for renal outcome in CKD patients. The levels of plasma cf-nDNA and plasma NGAL are significantly correlated with the severity of CKD.

Ninjinyoeito for cancer treatment: A systematic review and Meta-analysis

To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery.Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital.Prospective observational study.Fifty adult patients undergoing cardiac surgery.Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated.Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors.The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury.

Feulgen Reaction as a Marker for Identifying Prostatic Hyperplasia and Prostate Cancer

Introduction: A prostate cancer case in sub-Saharan Africa is rising. In Sudan, prostate cancer ranks third at after breast cancer. The nuclear deoxyribonucleic acid content has been shown to be of great prognostic value in prostate tumors. In the present work, we focus on semi-quantification of nuclear deoxyribonucleic acid in prostate cancer compared to prostatic hyperplasia using the Feulgen reaction technique. Methods: Paraffin wax sections were selected from patients previously diagnosed with prostatic hyperplasia and prostatic cancer. Clinic pathological data of patients were collected from the records of the archive of the National Health Laboratory Khartoum Sudan. From all cases, two sections were taken. One section was stained with Hematoxylin and eosin stain to confirm the diagnosis, while the other paraffin section was used for deoxyribonucleic acid demonstration using Feulgen reaction. Results: A total of 46 patients with a clinical and pathologic diagnosis of prostatic tumors were enrolled in this study; 23 (50.1%) had high-grade prostatic adenocarcinoma, 11 (23.9%) had moderate grade prostatic adenocarcinoma, two (4.3%) had low-grade prostatic adenocarcinoma and 10 (21.7%) had benign hyperplasia. The significant differences in deoxyribonucleic acid staining intensities were observed in high-grade prostatic adenocarcinomas. The deoxyribonucleic acid staining intensities of moderate and high-grade prostatic adenocarcinomas were significantly higher than those of benign hyperplasia (P<0.000). Conclusion: Deoxyribonucleic acid detection using Feulgen reaction may provide valuable prognostic information in prostate cancer, with potential clinical implications in patient management, active research on this topic should be a high priority objective.

A potential role as a suppressor protein of Regucalcin in the development of human carcinogenesis

Regucalcin was discovered in 1978 as a calcium-binding protein. After that, regucalcin was demonstrated to play a multifunctional role as a suppressor protein in signal transduction in various types of cell and tissues. The regucalcin gene (rgn) is localized on the X chromosome. Regucalcin was found to suppress nuclear deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis in liver cells. Overexpression of endogenous regucalcin possessed suppressive effects on proliferation in the modeled rat hepatoma cells by inhibiting G1 and G2/M cell cycle arrests. Suppressed regucalcin gene expression was found to be associated with progression of hepatocarcinogenesis by proteosome analysis. Moreover, regucalcin mRNA expression was found to suppress in various human normal and tumor tissues including hepatocellular carcinoma, kidney transitional cell carcinoma, brain malignant meningioma, and lung non-small cell carcinoma of human subjects. Suppressed regucalcin gene expression may be a key in development of carcinogenesis. Development of the regucalcin gene deliver system will be expected as a novel gene therapy in clinical aspects for cancer treatment.

Nuclear DNA as Predictor of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft: A Pilot Study

To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. Prospective observational study. Fifty adult patients undergoing cardiac surgery. Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury.

Primer in Genetics and Genomics, Article 3-Explaining Human Diversity: The Role of DNA.

Genetic variation lays the foundation for diversity and enables humans to adapt to changing environments. The order of the nucleotides adenine, guanine, cytosine, and thymine on the deoxyribonucleic acid (DNA) molecules of the nuclear chromosomes and mitochondrial DNA (mtDNA) plays an important role in normal cell division, tissue development, and reproduction but is susceptible to alteration from a large number of random, inherited, or environmental events. Variations can range from a change in a single nucleotide to duplication of entire chromosomes. Single nucleotide polymorphisms are the major source of human heterogeneity. Other variations that can alter phenotypes and adversely impact growth, development, and health include copy number variations, aneuploidies, and structural alterations such as deletions, translocations, inversions, duplications, insertions, or mutations in mtDNA. In addition, DNA rearrangements in somatic cells underlie the uncontrolled cell growth found in cancer. This article explores the mechanisms by which variations in DNA arise and the impact those changes can have on human health.