ABSTRACT
BACKGROUND: Genetics driven interventions if adopted in conservation breeding projects may enhance the overall success by prioritizing breeding among genetically most competent individuals and delaying or completely diminishing the ill effects of inbreeding. METHODS AND RESULTS: In the present study, we investigated genetic make-up of 15 tigers housed at five different captive facilities of West Bengal in India and report the moderate level of genetic variation. We identified five tigers based on individual genetic attributes that may be prioritized for future breeding or animal exchange programmes. The occurrence of first and second order related individuals in captivity require management attention and they should be paired considering their immediate genetic background. CONCLUSION: Considering tiger as a case study, we highlight the use of genetic assessment and necessity to validate the studbook records in formulating adaptive management strategies for long-term conservation and management of species of interest.
Subject(s)
Tigers , Animals , Conservation of Natural Resources/methods , DNA , Genetic Background , Genetic Variation , Inbreeding , Tigers/geneticsABSTRACT
Hyptis suaveolens is considered one of the most potent invaders in the eastern part of Uttar Pradesh, India. Climate change especially precipitation variability along with invasion has enormous consequences. To understand how an invasive plant (H. suaveolens) performs and interacts with precipitation variability, particularly in tropical monsoon climate, is vital. To assess the above, three rainout shelters with simulated rainfall of 1600 mm (60% more rainfall than ambient), 1100 mm (average rainfall) and 800 mm (20% less rainfall than ambient) along with one unsheltered plot (open C) were established. Three invaded grassland (IG) and three uninvaded grasslands (NIG) patches of 1 × 1 m2 size were established randomly in each sheltered and unsheltered plot. Among the studied physiological properties and growth measurements, photosynthetic rate, height, diameter and biomass varied significantly with precipitation, in general, the maximum value of these in plots receiving maximum precipitation. Also, the aboveground biomass of H. suaveolens was found to be more sensitive towards precipitation treatment than belowground biomass. H. suaveolens biomass was linearly related to soil moisture (R2 = 0.73), and a linear combination of SM and soil pH increased the R2 value by 19%. The results indicate that H. suaveolens mediates certain soil properties especially related to N-mineralisation, to maintain a constant supply of nutrient, for faster growth under the favourable condition of enhanced precipitation. These findings suggest that the population of H. suaveolens has not evolved drought tolerance, so it is likely that H. suaveolens will not spread in the part of the world which is drier either naturally or due to climate change.
Subject(s)
Grassland , Hyptis , Biomass , Environmental Monitoring , India , RainABSTRACT
Mutations acquired during development and aging lead to inter- and intra-tissue genetic variations. Evidence linking such mutations to complex traits and diseases is rising. We detected somatic mutations in protein-coding regions in 140 benign tissue samples representing nine tissue-types (bladder, breast, liver, lung, prostate, stomach, thyroid, head and neck) and paired blood from 70 donors. A total of 80% of the samples had 2-39 mutations detectable at tissue-level resolution. Factors such as age and smoking were associated with increased burden of detectable mutations, and tissues carried signatures of distinct mutagenic processes such as oxidative DNA damage and transcription-coupled repair. Using mutational signatures, we predicted that majority of the mutations in blood originated in hematopoietic stem and early progenitor cells. Missense to silent mutations ratio and the persistence of potentially damaging mutations in expressed genes carried signatures of relaxed purifying selection. Our findings have relevance for etiology, diagnosis and treatment of diseases including cancer.
Subject(s)
Aging/genetics , Exome , Neoplasms/genetics , Open Reading Frames , Selection, Genetic , Tumor Microenvironment/genetics , Female , Genome, Human , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/pathology , High-Throughput Nucleotide Sequencing , Humans , Male , Models, Genetic , Mutation Rate , Mutation, Missense , Neoplasms/pathology , Organ SpecificityABSTRACT
Solid tumor samples typically contain multiple distinct clonal populations of cancer cells, and also stromal and immune cell contamination. A majority of the cancer genomics and transcriptomics studies do not explicitly consider genetic heterogeneity and impurity, and draw inferences based on mixed populations of cells. Deconvolution of genomic data from heterogeneous samples provides a powerful tool to address this limitation. We discuss several computational tools, which enable deconvolution of genomic and transcriptomic data from heterogeneous samples. We also performed a systematic comparative assessment of these tools. If properly used, these tools have potentials to complement single-cell genomics and immunoFISH analyses, and provide novel insights into tumor heterogeneity.
Subject(s)
Computational Biology/methods , Neoplasms/genetics , Neoplasms/pathology , Gene Expression Profiling/statistics & numerical data , Genome, Human , Genomics/statistics & numerical data , High-Throughput Nucleotide Sequencing/statistics & numerical data , Humans , SoftwareABSTRACT
Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.
Subject(s)
Drug Resistance, Neoplasm/genetics , Genes, Tumor Suppressor , Neoplasms/genetics , Cell Engineering , Cell Line, Tumor , Epithelial Cells/metabolism , Gene Expression Profiling , Humans , Mesoderm/metabolism , Neoplasm Metastasis , Neoplasms/metabolismABSTRACT
Previous studies have analyzed patterns of transcription, transcription factor (TF) binding or mapped nucleosome occupancy across the genome. These suggest that the three aspects are genetically connected but the cause and effect relationships are still unknown. For example, physiologic TF binding studies involve many TFs, consequently, it is difficult to assign nucleosome reorganization to the binding site occupancy of any particular TF. Therefore, several aspects remain unclear: does TF binding influence nucleosome (re)organizations locally or impact the chromatin landscape at a more global level; are all or only a fraction of TF binding a result of reorganization in nucleosome occupancy and do all TF binding and associated changes in nucleosome occupancy result in altered gene expression? With these in mind, following characterization of two states (before and after induction of a single TF of choice) we determined: (i) genomic binding sites of the TF, (ii) promoter nucleosome occupancy and (iii) transcriptome profiles. Results demonstrated that promoter-proximal TF binding influenced expression of the target gene when it was coupled to nucleosome repositioning at or close to its binding site in most cases. In contrast, only in few cases change in target gene expression was found when TF binding occurred without local nucleosome reorganization.
Subject(s)
Nucleosomes/metabolism , Promoter Regions, Genetic , Transcription Factors/metabolism , Transcription, Genetic , Binding Sites , Cell Line, Tumor , Genome, Human , Humans , Lung Neoplasms/genetics , NM23 Nucleoside Diphosphate Kinases/metabolismABSTRACT
Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n=382), survival data (n=530) and lymph node metastases (n=100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis.
Subject(s)
Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Lung Neoplasms/genetics , Lung Neoplasms/secondary , NM23 Nucleoside Diphosphate Kinases/metabolism , Vinculin/genetics , Animals , Cell Line, Tumor , Disease Progression , Focal Adhesions/genetics , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Mice, Nude , Promoter Regions, Genetic , Transcription, Genetic , Vinculin/biosynthesis , ZebrafishABSTRACT
A remarkable number of guanine-rich sequences with potential to adopt non-canonical secondary structures called G-quadruplexes (or G4 DNA) are found within gene promoters. Despite growing interest, regulatory role of quadruplex DNA motifs in intrinsic cellular function remains poorly understood. Herein, we asked whether occurrence of potential G4 (PG4) DNA in promoters is associated with specific function(s) in bacteria. Using a normalized promoter-PG4-content (PG4(P)) index we analysed >60,000 promoters in 19 well-annotated species for (a) function class(es) and (b) gene(s) with enriched PG4(P). Unexpectedly, PG4-associated functional classes were organism specific, suggesting that PG4 motifs may impart specific function to organisms. As a case study, we analysed radioresistance. Interestingly, unsupervised clustering using PG4(P) of 21 genes, crucial for radioresistance, grouped three radioresistant microorganisms including Deinococcus radiodurans. Based on these predictions we tested and found that in presence of nanomolar amounts of the intracellular quadruplex-binding ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was attenuated by ~60%. In addition, important components of the RecF recombinational repair pathway recA, recF, recO, recR and recQ genes were found to harbour promoter-PG4 motifs and were also down-regulated in presence of NMM. Together these results provide first evidence that radioresistance may involve G4 DNA-mediated regulation and support the rationale that promoter-PG4s influence selective functions.
Subject(s)
Deinococcus/genetics , G-Quadruplexes , Promoter Regions, Genetic , Radiation Tolerance/genetics , Carbohydrate Metabolism/genetics , DNA, Bacterial/chemistry , Deinococcus/radiation effects , Genes, Bacterial , Genome, Bacterial , Guanine/chemistry , Ligands , Nucleotide Motifs , Species SpecificityABSTRACT
Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.
Subject(s)
NM23 Nucleoside Diphosphate Kinases/metabolism , Telomerase/metabolism , Telomere/metabolism , Cell Line, Tumor , Chromatin Immunoprecipitation , High-Throughput Nucleotide Sequencing , Humans , Nucleotide Motifs , Repetitive Sequences, Amino Acid , Telomere/chemistry , Telomere Homeostasis , Telomeric Repeat Binding Protein 2/metabolismABSTRACT
Non-canonical guanine quadruplex structures are not only predominant but also conserved among bacterial and mammalian promoters. Moreover recent findings directly implicate quadruplex structures in transcription. These argue for an intrinsic role of the structural motif and thereby posit that single nucleotide polymorphisms (SNP) that compromise the quadruplex architecture could influence function. To test this, we analysed SNPs within quadruplex motifs (Quad-SNP) and gene expression in 270 individuals across four populations (HapMap) representing more than 14,500 genotypes. Findings reveal significant association between quadruplex-SNPs and expression of the corresponding gene in individuals (P < 0.0001). Furthermore, analysis of Quad-SNPs obtained from population-scale sequencing of 1000 human genomes showed relative selection bias against alteration of the structural motif. To directly test the quadruplex-SNP-transcription connection, we constructed a reporter system using the RPS3 promoter-remarkable difference in promoter activity in the 'quadruplex-destabilized' versus 'quadruplex-intact' promoter was noticed. As a further test, we incorporated a quadruplex motif or its disrupted counterpart within a synthetic promoter reporter construct. The quadruplex motif, and not the disrupted-motif, enhanced transcription in human cell lines of different origin. Together, these findings build direct support for quadruplex-mediated transcription and suggest quadruplex-SNPs may play significant role in mechanistically understanding variations in gene expression among individuals.
Subject(s)
G-Quadruplexes , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Transcription, Genetic , Alleles , Animals , Base Sequence , Cell Line, Tumor , Evolution, Molecular , Humans , Molecular Sequence Data , Pan troglodytes/geneticsABSTRACT
Lung cancer is one of the deadliest cancers worldwide, with the highest incidence and mortality amongst all cancers. While the prognosis of lung cancer is generally grim, with 5-year survival rates of only 15%, there is hope, and evidence, that early detection of lung cancer can reduce mortality. Today, only computed tomography screening has shown to lead to early detection and reduction in mortality, but is limited by being anatomic in nature, unable to differentiate between inflammatory and neoplastic pathways, and therefore, susceptible to false positives. There is increasing interest in biomarkers for lung cancer, especially those that predict metastatic risk. Some biomarkers like DNA mutations and epigenetic changes potentially require tissue from the at-risk site; some like serum proteins and miRNAs are minimally invasive, but may not be specific to the lung. In comparison, emerging biomarkers from exhaled breath, like volatile organic compounds (VOC), and exhaled breath condensate, e.g., small molecules and nucleic acids, have the potential to combine the best of both. This mini review is intended to provide an overview of the field, briefly discussing the potential of what is known and highlighting the exciting recent developments, particularly with miRNAs and VOCs.
ABSTRACT
Function of non-B DNA structures are poorly understood though several bioinformatics studies predict role of the G-quadruplex DNA structure in transcription. Earlier, using transcriptome profiling we found evidence of widespread G-quadruplex-mediated gene regulation. Herein, we asked whether potential G-quadruplex (PG4) motifs associate with transcription factors (TF). This was analyzed using 220 position weight matrices [designated as transcription factor binding sites (TFBS)], representing 187 unique TF, in >75,000 genes in human, chimpanzee, mouse and rat. Results show binding sites of nine TFs, including that of AP-2, SP1, MAZ and VDR, occurred significantly within 100 bases of the PG4 motif (P < 1.24E-10). PG4-TFBS combinations were conserved in 'orthologously' related promoters across all four organisms and were associated with >850 genes in each genome. Remarkably, seven of the nine TFs were zinc-finger binding proteins indicating a novel characteristic of PG4 motifs. To test these findings, transcriptome profiles from human cell lines treated with G-quadruplex-specific molecules were used; 66 genes were significantly differentially expressed across both cell-types, which also harbored conserved PG4 motifs along with one/more of the nine TFBS. In addition, genes regulated by PG4-TFBS combinations were found to be co-regulated in human tissues, further emphasizing the regulatory significance of the associations.
Subject(s)
G-Quadruplexes , Promoter Regions, Genetic , Transcription Factors/metabolism , Zinc Fingers , Animals , Base Sequence , Binding Sites , Chromatin Immunoprecipitation , Conserved Sequence , Gene Expression Profiling , Gene Expression Regulation , Genome , Guanine/analysis , Humans , Mice , Nucleotide Motifs , Pan troglodytes/genetics , RatsABSTRACT
Ornamental fish keeping is the second most preferred hobby in the world and it provides a great opportunity for entrepreneurship development and income generation. Controlling the environment in ornamental fish farm is a considerable challenge because it is affected by a variety of parameters like water temperature, dissolved oxygen, pH, and disease occurrences. One particular interesting ornamental fish species is goldfish (Carassius auratus). Machine learning (ML) and deep learning technique have significant potential in analysing voluminous data collected from fish farm. Through this technique, the fish farmers can get insight on feeding behaviour, fish growth patterns, predict diseases/stress, and environmental factors affecting fish health. The aim of the study is to analyze the behavioural changes in goldfish due to alterations in environmental parameters (water temperature and dissolved oxygen). Decision tree, Naïve Bayes classifier, K-nearest neighbour (KNN), and linear discriminant analysis (LDA) were used to analyse the behavioural change data. To compare the performance between all four classifiers, cross validation and confusion matrix used. The cross-validation error of LDA, Naïve Bayes classification, KNN and decision tree was 19.86, 28.08, 30.14 and 13.78 respectively. Decision tree was proved to be the most accurate and effective classifier. Different temperature and DO range were taken to predict fish behaviour. Some findings are, the behaviour of fish was rest between temperature 37.85 °C and 40.535 °C, erratic when temperature was greater than or equal to 40.535 °C, gasping when temperature was between 37.85 and 40.535 °C and when DO concentration was less than 6.58 mg/L. Blood parameter analysis has been done to validate the change in external behaviours with change in physiological parameters.
Subject(s)
Goldfish , Oxygen , Animals , Bayes Theorem , Goldfish/physiology , Temperature , WaterABSTRACT
Population explosions, environmental deprivation, and industrial expansion led to an imbalanced agricultural system. Non-judicial uses of agrochemicals have decreased agrodiversity, degraded agroecosystems, and increased the cost of farming. In this scenario, a sustainable agriculture system could play a crucial role; however, it needs rigorous study to understand the biological interfaces within agroecosystems. Among the various biological components with respect to agriculture, mycorrhizae could be a potential candidate. Most agricultural crops are symbiotic with arbuscular mycorrhizal fungi (AMF). In this study, beetroot has been chose to study the effect of different AMFs on various parameters such as morphological traits, biochemical attributes, and gene expression analysis (ALDH7B4 and ALDH3I1). The AMF Gm-Funneliformis mosseae (Glomus mosseae), Acaulospora laevis, and GG-Gigaspora gigantean were taken as treatments to study the effect on the above-mentioned parameters in beetroot. We observed that among all the possible combinations of mycorrhizae, Gm+Al+GG performed best, and the Al-alone treatment was found to be a poor performer with respect to all the studied parameters. This study concluded that the more the combinations of mycorrhizae, the better the results will be. However, the phenomenon depends on the receptivity, infectivity, and past nutrient profile of the soil.
ABSTRACT
Introduction: Dislocation of the carpometacarpal (CMC) joint is a rare injury that results following high-velocity trauma. Although there are a few anecdotal reports of isolated CMC joint dislocations, there is scarce literature concerning dislocations involving multiple joints, especially those that are neglected and present late after injury. The injury is often missed when the patient presents to the surgeon since the swelling obscures the characteristic deformity, and the fracture may not be apparent on radiographs. When missed at the initial presentation, they can frequently result in pain, swelling, reduced grip strength, and arthritis. Such injuries require surgical management, along with prompt post-operative physiotherapy to enable the patient to regain satisfactory grip strength and range of motion. Case Report: We retrospectively analyzed four cases of multiple CMC joint dislocations that were managed surgically at our tertiary apex center. The average duration between injury and presentation to our center was five weeks. We used the quick disabilities of the arm, shoulder, and hand (DASH) scores and the maximum handgrip strength to assess the functional outcomes and the visual analog scale (VAS) to assess the pain at regular intervals. All patients showed an improvement in the Quick DASH scores, VAS scores, and the handgrip strength at the latest follow-up. All patients were able to return to their occupation. Conclusion: Early diagnosis and stabilization followed by early mobilization is the key to managing multiple CMC dislocations. The cases that present late are generally associated with contracted soft-tissue structures that prevent the relocation of the injury. Such cases require open reduction, along with a release of the contracted structures and internal fixation. Supervised physiotherapy in the post-operative period is essential to regain a satisfactory range of motion and grip strength.
ABSTRACT
Background: We analyzed the clinical and radiological parameters influencing functional outcomes and neurological recovery in patients with cervicothoracic junctional tuberculosis (TB). Methods: This was a retrospective analysis of 16 cases of cervicothoracic junction (CTJ) spinal TB; 11 patients were managed operatively, while five were managed conservatively. Patients' outcomes were assessed at 1 month, 1 year, and yearly thereafter and included an analysis of multiple outcome scores, various radiographic parameters, and sensitivity or resistance to anti-tubercular therapy. Results: Patients averaged 25.94 years of age, and typically had three-level vertebral involvement. They were followed for a mean duration of 24 months, and the duration of anti-tubercular therapy averaged 17 months. Patients demonstrated clinical improvement on Japanese Orthopedic Association score and Neck disability index (P < 0.005) starting from 1 month following initiation of treatment which continued in subsequent follow-up, along with change in radiological parameters consisting of mean segmental kyphotic angle from 18.98° to 15.13°, C2-C7 SVA from 16.13 mm to 22.61 mm, T1 slope from 22.80° to 14.66°, thoracic inlet angle from 75.35° to 63.25°, neck tilt from 51.81° to 48.33°, and cervical lordosis from 4.66° to -0.44° (P > 0.05) at the end of 1 year. Conclusion: Tuberculous affection of the dynamic CTJ is a challenging scenario in clinical practice and its management involves consideration of disease extent, neurological status, and effort toward restoration of normal alignment of spine in sagittal and coronal plane to get favorable clinical outcomes.
ABSTRACT
The output of the latent heat storage devices (LHSDs), based on some phase change materials (PCMs), depends upon the thermophysical properties of the phase change material used. In this study, a paraffin-based nanofluid, blended with aluminum oxide (Al2O3) nanoparticles, is used as PCM for performance evaluation. A three-dimensional (3D) numerical model of regenerative type shell-and-tube LHSD is prepared using COMSOL Multiphysics® 4.3a software to estimate the percentage of melt and the average temperature of the analyzed nanofluids. The results of this study are in close agreement with those reported in the literature, thereby ensuring the validation of the numerically predicted results. The effects of adding the nanoparticles on the rate of melting, as well as solidification and rate of stored/liberated energy, are studied. The results revealed that, by adding 10% nanoparticles of Al2O3, the melting rate of pure-paraffin-based LHSD improved by about 2.25 times. In addition, the rate of solidification was enhanced by 1.8 times. On the other hand, the heat of fusion and specific heat capacities were reduced, which, in turn, reduced the latent and sensible heat-storing capabilities. From the outcomes of the present research, it can be inferred that combining LHSD with a solar water heater may be used in technologies such as biogas generation.
ABSTRACT
INTRODUCTION: There exists sparse literature on Gunshot injuries (GSI) to the pediatric spine, its natural course, management protocols and outcomes following surgical intervention. Here, we present a projectile injury to the paediatric lumbar spine without any osseous disruption in a 5-year-old child requiring surgical management. CASE PRESENTATION: A 5-year-old child presented with a gunshot injury to the pediatric lumbar spine. On radiological imaging, there was no osseous disruption and an intraspinal canal projectile was embedded in an organised infected complex, compressing onto the left-sided L5 traversing nerve root with resultant grade 4 motor power of the left Extensor Hallucis Longus (EHL). Under fluoroscopic guidance using two separate mini-open incisions, the pellets were extracted. One from the spinal canal through left-sided L4 laminotomy and the other from the right paraspinal region. Post-surgical decompression and pellet retrieval there was gradual recovery to grade 5 motor power of Left EHL and improvement in the general condition of the child. CONCLUSION: The absence of osseous disruption can be attributed to the size of the projectile, widely spaced interlaminar spaces in the lumbar spine due to the absence of lumbar lordosis in the pediatric group and flexibility of the pediatric spine owing to its ligamentous laxity.
Subject(s)
Radiculopathy , Wounds, Gunshot , Child , Child, Preschool , Decompression, Surgical , Humans , Laminectomy , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Radiculopathy/surgery , Wounds, Gunshot/complications , Wounds, Gunshot/diagnostic imaging , Wounds, Gunshot/surgeryABSTRACT
Guanine-rich DNA of a particular sequence adopts four-stranded structural forms known as G-quadruplex or G4 DNA. Though in vitro formation of G4 DNA is known for several years, in vivo presence of G4 DNA was only recently noted in eukaryote telomeres. Recent bioinformatics analyses showing prevalence of G4 DNA within promoters of human and related species seems to implicate G4 DNA in a genome-wide cis-regulatory role. Herein we demonstrate that G4 DNA may present regulatory sites on a genome-wide scale by showing widespread effect on gene expression in response to the established intracellular G4 DNA-binding ligands. This is particularly relevant to genes that harbor conserved potential G4 DNA (PG4 DNA) forming sequence across human, mouse and rat promoters of orthologous genes. Genes with conserved PG4 DNA in promoters show co-regulated expression in 79 human and 61 mouse normal tissues (z-score > 3.5; P < 0.0001). Conservation of G4 DNA across related species also emphasizes the biological importance of G4 DNA and its role in transcriptional regulation of genes; shedding light on a relatively novel mechanism of regulation of gene expression in eukaryotes.
Subject(s)
DNA, Neoplasm/chemistry , G-Quadruplexes , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , Animals , Base Sequence , Cell Line, Tumor , Conserved Sequence , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Genome, Human , Humans , Ligands , Mice , Porphyrins/pharmacology , Tissue DistributionABSTRACT
BACKGROUND: Chromobacterium species, through their bioactive molecules, help in combating biotic and abiotic stresses in plants and humans. The present study was aimed to identify, characterize and preserve in natural gums the violet-pigmented bacterial isolate TRFM-24 recovered from the rhizosphere soil of rice collected from Tripura state. RESULTS: Based on morphological, biochemical and 16S rRNA gene sequencing, the isolate TFRM-24 was identified as Chromobacterium violaceum (NAIMCC-B-02276; MCC 4212). The bacterium is saprophytic, free living and Gram negative. The strain was found positive for production of IAA, cellulase, xylanase and protease, and showed tolerance to salt (2.5%) and drought (-1.2 MPa). However, it showed poor biocontrol activity against soil-borne phytopathogens and nutrient-solubilizing abilitiets. C. violaceum strain TRFM-24 did not survive on tryptic soya agar (TSA) beyond 12 days between 4 and 32 °C temperature hence a method of preservation of this bacterium was attempted using different natural gums namely Acacia nilotica (babul), Anogeissus latifolia (dhavda), Boswellia serrata (salai) and Butea monosperma (palash) under different temperature regime (6-32 °C). The bacterium survived in babul gum (gum acacia), dhavda and salai solution at room temperature beyond a year. CONCLUSION: Based on polyphasic approach, a violet-pigmented isolate TRFM-24 was identified as Chromobacterim violaceum which possessed some attributes of plant and human importance. Further, a simple and low-cost preservation method of strain TRFM-24 at room temperature was developed using natural gums such as babul, dhavda and salai gums which may be the first report to our knowledge.