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Maintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not hinder the cell cycle, but similarly to RBR silencing, result in hyperplasia. Contrary to the growth arrest that occurs when exit from proliferation to differentiation is inhibited upon RBR silencing, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.
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Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/genética , Divisão Celular , Ciclo Celular/genética , Desenvolvimento VegetalRESUMO
Background: ATP-binding cassette membrane transporter G2 (ABCG2) gene is one of transporter family and well characterized for their association with chemoresistance. Promoter methylation is a mechanism for regulation of gene expression. O6-Methyl guanine DNA methyl transferase (MGMT) gene plays a fundamental role in DNA repair. MGMT has the ability to remove alkyl adducts from DNA at the O6 position of guanine. Alkylating agents exert their function through adding these alkyls adducts to DNA leading to cell death unless it is repaired by MGMT. MGMT promoter was found to be methylated in several malignancies. The aim of the present work is to study the relation of MGMT and ABCG2 promoter methylation status in advanced breast cancer patients to response to cyclophosphamide-doxorubicin (AC) based therapeutic regime. Methods: This retrospective study included Forty-two female patients with advanced breast cancer assessed before receiving chemotherapy and after the completion of regimens. They were grouped into responders and non-responders according to RECIST criteria. Methylation analysis of MGMT and ABCG2 genes were performed on breast cancer tissues. Results: MGMT promoter was methylated in 40.5% of the cases. ABCG2 promoter was methylated in 14.3% of cases. There was no statistically significant association between MGMT and ABCG2 promoter methylation status and clinicopathological parameters. There was statistically significant association between methylation status of both promoters and response to AC when followed by Taxane. Conclusion: Methylation of MGMT and ABCG2 promoters combined could be a potential predictive factor for response to cyclophosphamide-doxorubicin based therapeutic regime.
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Background and Aim: The value of the pet food industry, which is majorly the prescribed diet, exponentially increased over the years due to increased awareness among pet owners to provide a healthy lifestyle for their pets. However, several factors such as aroma, flavor, texture, and shape of prescribed diets greatly influenced the palatability in cats. Therefore, this study aimed to determine the palatability of the prescribed diet for domestic shorthair (DSH) cats. Materials and Methods: The two-bowl method was employed to determine the palatability of prescribed diets on five DSH cats for 6 days. Furthermore, the four types of prescribed diet assessed in this study were struvite, renal, hypersensitivity, and intestinal. Furthermore, the pet food palatability was analyzed using "First Approached," "First Consumed," "Total Consumption," and "Intake ratios." Results: Our findings revealed that "Total Consumption" and "Intake Ratios" were significantly different in struvite, renal, and intestinal diets compared to the hypersensitivity diet. In addition, this result indicates that the hypersensitivity diet is the most unpalatable compared with other diets. Conclusion: A detailed investigation of the diet ingredients showed that a hypersensitivity diet lacks herbs and spices than the other diets. Therefore, these ingredients lacking in the hypersensitivity diet influence the palatability of pet foods.
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Conjoined twining is one of the most fascinating and challenging situations which a pediatric surgeon may face in his career. Only few surgeons may have the opportunity to share in separation of such cases. In this report, we aim to share our experience with the successful separation of ventrally fused male conjoined twins (omphaloischiopagus). The case was thoroughly studied via preoperative cross-sectional imaging modalities (magnetic resonance imaging [MRI] and computed tomography [CT] angiography), complemented by data obtained from reviewing similar cases in the literature. A clear delineation of the complex anatomy was achieved preoperatively which proved to be well consistent with the operative findings. A detailed description of the operative procedure to divide/redistribute the shared abdominal/pelvic organs between both twins is provided. To the best of our knowledge, this is the first report to describe the detailed and unique internal anatomy of a common central phallus associating ischiopagus conjoined twins. The penis was centrally located in the perineum in between both twins with an open urethral plate. This common phallus had a peculiar configuration with four crura anchoring ischial bones of both twins together.
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The DNA of all organisms is constantly damaged by physiological processes and environmental conditions. Upon persistent damage, plant growth and cell proliferation are reduced. Based on previous findings that RBR1, the only Arabidopsis homolog of the mammalian tumor suppressor gene retinoblastoma, plays a key role in the DNA damage response in plants, we unravel here the network of RBR1 interactors under DNA stress conditions. This led to the identification of homologs of every DREAM component in Arabidopsis, including previously not recognized homologs of LIN52. Interestingly, we also discovered NAC044, a mediator of DNA damage response in plants and close homolog of the major DNA damage regulator SOG1, to directly interact with RBR1 and the DREAM component LIN37B. Consistently, not only mutants in NAC044 but also the double mutant of the two LIN37 homologs and mutants for the DREAM component E2FB showed reduced sensitivities to DNA-damaging conditions. Our work indicates the existence of multiple DREAM complexes that work in conjunction with NAC044 to mediate growth arrest after DNA damage.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Dano ao DNA/genética , Fatores de Transcrição E2F/metabolismo , Proteínas Mutantes/metabolismo , Transdução de Sinais/genética , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Pontos de Checagem do Ciclo Celular/genética , Reparo do DNA/genética , Fatores de Transcrição E2F/genética , Regulação da Expressão Gênica de Plantas , Proteínas Mutantes/genética , Mutação , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Transativadores/genéticaRESUMO
Complete colonic duplication is rare, and usually occurs as a part of the caudal duplication syndrome. In such cases, the diagnosis is clinically evident by the presence of two ani arranged side by side in the perineum, which is commonly associated with duplication of the external genitalia as well (double phallus or double vestibule). In this report, we present a special case of anorectal anomaly that was associated with complete tubular colonic duplication. The diagnosis was initially missed due to the uncommon sagittal arrangement of duplicated rectum: one rectum was ending externally into the perineum by rectoperineal fistula, while the other was hidden by its internal termination into the vagina. Our final diagnosis for this case was a variant of anorectal anomaly in the female, which was associated with complete colonic duplication. One colon (which was in the free mesenteric border) terminated anteriorly into the vagina as a part of a "short common channel" cloaca, while the other colon terminated by rectoperineal fistula. Although the anomaly seems to be rather complex and confusing, yet our case was associated with an excellent outcome due to the benign type of anorectal anomalies (rectoperineal fistula and "short common channel" cloaca) and absence of significant sacral dysplasia; in addition to adequate identification of the abnormal anatomy by appropriate investigations and the staged approach for surgical reconstruction.
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Objective: The present study aimed to determine peptidome patterns in breast cancer (BC). Methods: We analyzed the plasma proteomic proï¬ling of 80 BC patients and 50 healthy controls, using hydrophobic interaction chromatography magnetic beads (MB-HIC8) separation followed by Matrix assisted laser desorption ionization/ time of flight mass spectrometry (MALDI-TOF MS). Results: ClinProTools software identiï¬ed 92 peaks that differed among the analyzed groups, 33 peaks were signiï¬cantly different (P < 0.05). Of those, 22 peaks were up-regulated while 11 peaks were down-regulated in BC patients compared with the healthy controls. Three peptide ion signatures (m/z 1,570.31, 1,897.4 and 2,568.17) were provided by the Quick Classifier model to discriminate BC patients from healthy control subjects with 96.4% accuracy. External validation was performed by an independent group and this achieved a sensitivity of 100% and a specificity of 76.9%. Conclusion: MALDI-TOF MS has good analytical performance in distinguishing BC patients from healthy controls.
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Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Peptídeos/sangue , Proteoma/metabolismo , Estudos de Casos e Controles , Fracionamento Químico/métodos , Regulação para Baixo/fisiologia , Egito , Feminino , Humanos , Pessoa de Meia-Idade , Proteômica , Sensibilidade e Especificidade , Software , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Regulação para Cima/fisiologiaRESUMO
Digital evolution is a computer-based instantiation of Darwinian evolution in which short self-replicating computer programs compete, mutate, and evolve. It is an excellent platform for addressing topics in long-term evolution and paleobiology, such as mass extinction and recovery, with experimental evolutionary approaches. We evolved model communities with ecological interdependence among community members, which were subjected to two principal types of mass extinction: a pulse extinction that killed randomly, and a selective press extinction involving an alteration of the abiotic environment to which the communities had to adapt. These treatments were applied at two different strengths, along with unperturbed control experiments. We examined how stability in the digital communities was affected from the perspectives of division of labor, relative shift in rank abundance, and genealogical connectedness of the community's component ecotypes. Mass extinction that was due to a Strong Press treatment was most effective in producing reshaped communities that differed from the pre-treatment ones in all of the measured perspectives; weaker versions of the treatments did not generally produce significant departures from a Control treatment; and results for the Strong Pulse treatment generally fell between those extremes. The Strong Pulse treatment differed from others in that it produced a slight but detectable shift towards more generalized communities. Compared to Press treatments, Pulse treatments also showed a greater contribution from re-evolved ecological doppelgangers rather than new ecotypes. However, relatively few Control communities showed stability in any of these metrics over the whole course of the experiment, and most did not represent stable states (by some measure of stability) that were disrupted by the extinction treatments. Our results have interesting, broad qualitative parallels with findings from the paleontological record, and show the potential of digital evolution studies to illuminate many aspects of mass extinction and recovery by addressing them in a truly experimental manner.
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Biota , Simulação por Computador , Extinção Biológica , Evolução Biológica , Modelos Biológicos , PaleontologiaRESUMO
Corrosion of reinforced concrete (RC) structures has been one of the major causes of structural failure. Early detection of the corrosion process could help limit the location and the extent of necessary repairs or replacement, as well as reduce the cost associated with rehabilitation work. Non-destructive testing (NDT) methods have been found to be useful for in-situ evaluation of steel corrosion in RC, where the effect of steel corrosion and the integrity of the concrete structure can be assessed effectively. A complementary study of NDT methods for the investigation of corrosion is presented here. In this paper, acoustic emission (AE) effectively detects the corrosion of concrete structures at an early stage. The capability of the AE technique to detect corrosion occurring in real-time makes it a strong candidate for serving as an efficient NDT method, giving it an advantage over other NDT methods.
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BACKGROUND: The aim of this study is to estimate the epidemiological features of epilepsy in a representative governorate of Upper Egypt. MATERIALS AND METHODS: A door-to-door community-based survey study was performed using a sample of 10 areas among various districts of the Qena governorate in Upper Egypt. Six were classified as rural areas, and the remaining four were classified as urban areas, with a total population of 8027 inhabitants. The population was screened using an epilepsy-screening questionnaire. Positive cases with suspected epilepsy were referred to Qena University Hospital to be further evaluated by a qualified neurologist and for further investigations, such as neuroimaging and electroencephalography. RESULTS: One hundred patients had a confirmed diagnosis of epilepsy, with a lifetime prevalence of 12.46/1000. The active prevalence rate of epilepsy was 2.12/1000, while the incidence rate was 123/100000. Seventy-six percent of the patients had idiopathic epilepsies, while 24% had symptomatic epilepsy. Generalized epilepsies were more common (70.1%) than partial epilepsy (26.3%), meanwhile epilepsies with mixed seizure types were 2.6%. The most common seizure type was generalized tonic clonic seizures (51.8%). The age-specific prevalence rate of epilepsy was much higher in infancy and early childhood (62.5 and 37.04/1000, respectively), which regressed steadily with age. Idiopathic epilepsies were significantly more common in urban areas than in rural areas (P=0.01), while symptomatic epilepsies were more common in rural areas than in urban areas (P<0.005). CONCLUSION: Upper Egypt is characterized by a relatively high incidence and prevalence of epilepsy and epilepsy-related medical service, and more cultural education should be directed to those areas in Egypt.
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Epilepsia/epidemiologia , Características de Residência , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Consanguinidade , Estudos Transversais , Egito/epidemiologia , Epilepsia/classificação , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória , Fatores de Risco , Adulto JovemRESUMO
Thermal structure and water quality in a large and shallow lake in Malaysia were studied between January 2012 and June 2013 in order to understand variations in relation to water level fluctuations and in-stream mining activities. Environmental variables, namely temperature, turbidity, dissolved oxygen, pH, electrical conductivity, chlorophyll-A and transparency, were measured using a multi-parameter probe and a Secchi disk. Measurements of environmental variables were performed at 0.1 m intervals from the surface to the bottom of the lake during the dry and wet seasons. High water level and strong solar radiation increased temperature stratification. River discharges during the wet season, and unsustainable sand mining activities led to an increased turbidity exceeding 100 NTU, and reduced transparency, which changed the temperature variation and subsequently altered the water quality pattern.
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Lagos/química , Mineração , Qualidade da Água/normas , Clorofila/análise , Clorofila A , Meio Ambiente , Monitoramento Ambiental , Malásia , Estações do Ano , Dióxido de Silício , TemperaturaRESUMO
Psoriasis is a common chronic autoimmune skin disorder with T-cell mediated multifunctional complex pathogenesis along with genetic predisposition. Conventionally, many therapies are available for the management of psoriasis, but they have limited efficacy due to higher side effects. Over the last decade, one of the major efforts in psoriasis research has been made for the development of drug molecules by understanding the potential biomolecules/biomarkers associated with psoriasis. This approach aims to provide selective immunologically directed intervention with fewer side effects than conventional therapies. The present review aims to give an exhaustive account on various biomarkers including oxidative stress, peptide, biochemical and gene markers responsible for keratocyte hyper proliferation, inflammatory responses and abnormal differentiation in psoriasis. Effective targeting of these over expressed biomarkers can serve as the novel tool for anti-psoriatic drug development. In addition, this review also gives insights into several novel biomarkers targeted drugs under pre-clinical and clinical investigation or have been registered by FDA for psoriasis management.
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Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Psoríase/tratamento farmacológico , Biomarcadores/metabolismo , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Descoberta de Drogas/métodos , Marcadores Genéticos , Humanos , Psoríase/genética , Psoríase/fisiopatologiaRESUMO
The kinetics and mechanism of the reaction of hydrogen peroxide with some Fe(II) Schiff base complexes were investigated spectrophotometrically in aqueous solution at pH 8 and 35 degrees C under pseudo-first-order conditions. The used ligands were derived from salicylaldehyde or o-hydroxynaphthaldehyde and some amino acids (l-leucine, l-iso-leucine, l-serine, l-methionine and dl-tryptophan). It was found that the formation of the purple interaperoxo complex appears only above pH 7.5. The reaction consists of two steps. The first step involves reversible formation of the intraperoxo intermediate which renders irreversible at pH 8. The second step consists of inner-sphere electron transfer. The suggested scheme illustrated first-order kinetics at low [H(2)O(2)] and zero-order at high [H(2)O(2)]. Moreover, the activation parameters of the reaction were evaluated.