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1.
Sci Rep ; 13(1): 21415, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38049427

RESUMO

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.


Assuntos
Carpa Dourada , Oxigênio , Animais , Teorema de Bayes , Carpa Dourada/fisiologia , Temperatura , Água
2.
Front Microbiol ; 14: 1196101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465020

RESUMO

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.

3.
Materials (Basel) ; 15(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35806552

RESUMO

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.

4.
Surg Neurol Int ; 13: 198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35673661

RESUMO

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.

5.
Mol Biol Rep ; 49(5): 4107-4114, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35359235

RESUMO

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.


Assuntos
Tigres , Animais , Conservação dos Recursos Naturais/métodos , DNA , Patrimônio Genético , Variação Genética , Endogamia , Tigres/genética
6.
Spinal Cord Ser Cases ; 8(1): 45, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474303

RESUMO

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.


Assuntos
Radiculopatia , Ferimentos por Arma de Fogo , Criança , Pré-Escolar , Descompressão Cirúrgica , Humanos , Laminectomia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiculopatia/cirurgia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/cirurgia
7.
J Orthop Case Rep ; 12(12): 109-113, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37056591

RESUMO

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.

8.
J Genet Eng Biotechnol ; 19(1): 146, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596780

RESUMO

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.

9.
Environ Monit Assess ; 192(6): 388, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32440902

RESUMO

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.


Assuntos
Pradaria , Hyptis , Biomassa , Monitoramento Ambiental , Índia , Chuva
10.
J Med Imaging (Bellingham) ; 4(2): 027503, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28680911

RESUMO

Ziehl-Neelsen stained microscopy is a crucial bacteriological test for tuberculosis detection, but its sensitivity is poor. According to the World Health Organization (WHO) recommendation, 300 viewfields should be analyzed to augment sensitivity, but only a few viewfields are examined due to patient load. Therefore, tuberculosis diagnosis through automated capture of the focused image (autofocusing), stitching of viewfields to form mosaics (autostitching), and automatic bacilli segmentation (grading) can significantly improve the sensitivity. However, the lack of unified datasets impedes the development of robust algorithms in these three domains. Therefore, the Ziehl-Neelsen sputum smear microscopy image database (ZNSM iDB) has been developed, and is freely available. This database contains seven categories of diverse datasets acquired from three different bright-field microscopes. Datasets related to autofocusing, autostitching, and manually segmenting bacilli can be used for developing algorithms, whereas the other four datasets are provided to streamline the sensitivity and specificity. All three categories of datasets were validated using different automated algorithms. As images available in this database have distinctive presentations with high noise and artifacts, this referral resource can also be used for the validation of robust detection algorithms. The ZNSM-iDB also assists for the development of methods in automated microscopy.

11.
Sci Rep ; 6: 27437, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27272679

RESUMO

Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed "duon mutations" due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.


Assuntos
Genoma , Mutação de Sentido Incorreto , Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Humanos
12.
Nucleic Acids Res ; 44(5): 2075-84, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26883632

RESUMO

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.


Assuntos
Envelhecimento/genética , Exoma , Neoplasias/genética , Fases de Leitura Aberta , Seleção Genética , Microambiente Tumoral/genética , Feminino , Genoma Humano , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Modelos Genéticos , Taxa de Mutação , Mutação de Sentido Incorreto , Neoplasias/patologia , Especificidade de Órgãos
13.
Brief Bioinform ; 16(2): 232-41, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24562872

RESUMO

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.


Assuntos
Biologia Computacional/métodos , Neoplasias/genética , Neoplasias/patologia , Perfilação da Expressão Gênica/estatística & dados numéricos , Genoma Humano , Genômica/estatística & dados numéricos , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Humanos , Software
14.
Nucleic Acids Res ; 42(18): 11589-600, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25249619

RESUMO

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.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Vinculina/genética , Animais , Linhagem Celular Tumoral , Progressão da Doença , Adesões Focais/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Camundongos Nus , Regiões Promotoras Genéticas , Transcrição Gênica , Vinculina/biossíntese , Peixe-Zebra
15.
Nucleic Acids Res ; 42(15): 9602-11, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25081206

RESUMO

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.


Assuntos
Nucleossomos/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Transcrição Gênica , Sítios de Ligação , Linhagem Celular Tumoral , Genoma Humano , Humanos , Neoplasias Pulmonares/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo
16.
Mol Cancer Ther ; 13(10): 2264-75, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25125675

RESUMO

Endoglin, a 180-kDa disulfide-linked homodimeric transmembrane receptor protein mostly expressed in tumor-associated endothelial cells, is an endogenous binding partner of GAIP-interacting protein, C terminus (GIPC). Endoglin functions as a coreceptor of TßRII that binds TGFß and is important for vascular development, and consequently has become a compelling target for antiangiogenic therapies. A few recent studies in gastrointestinal stromal tumor (GIST), breast cancer, and ovarian cancer, however, suggest that endoglin is upregulated in tumor cells and is associated with poor prognosis. These findings indicate a broader role of endoglin in tumor biology, beyond angiogenic effects. The goal of our current study is to evaluate the effects of targeting endoglin in pancreatic cancer both in vitro and in vivo. We analyzed the antiproliferative effect of both RNAi-based and peptide ligand-based inhibition of endoglin in pancreatic cancer cell lines, the latter yielding a GIPC PDZ domain-targeting lipopeptide with notable antiproliferative activity. We further demonstrated that endoglin inhibition induced a differentiation phenotype in the pancreatic cancer cells and sensitized them against conventional chemotherapeutic drug gemcitabine. Most importantly, we have demonstrated the antitumor effect of both RNAi-based and competitive inhibitor-based blocking of endoglin in pancreatic cancer xenograft models in vivo. To our knowledge, this is the first report exploring the effect of targeting endoglin in pancreatic cancer cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Receptores de Superfície Celular/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antígenos CD/metabolismo , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Endoglina , Humanos , Ligantes , Masculino , Camundongos , Camundongos SCID , Terapia de Alvo Molecular , Neoplasias Pancreáticas/patologia , Peptídeos/farmacologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Distribuição Aleatória , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina , Neoplasias Pancreáticas
18.
Nucleic Acids Res ; 42(2): 764-73, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24157835

RESUMO

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.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Genes Supressores de Tumor , Neoplasias/genética , Engenharia Celular , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Humanos , Mesoderma/metabolismo , Metástase Neoplásica , Neoplasias/metabolismo
19.
J Carcinog ; 12: 3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23599685

RESUMO

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.

20.
Nucleic Acids Res ; 41(1): 76-89, 2013 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-23161683

RESUMO

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.


Assuntos
Deinococcus/genética , Quadruplex G , Regiões Promotoras Genéticas , Tolerância a Radiação/genética , Metabolismo dos Carboidratos/genética , DNA Bacteriano/química , Deinococcus/efeitos da radiação , Genes Bacterianos , Genoma Bacteriano , Guanina/química , Ligantes , Motivos de Nucleotídeos , Especificidade da Espécie
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