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In root-nodule symbiosis, rhizobial invasion and nodule organogenesis is host controlled. In most legumes, rhizobia enter through infection threads and nodule primordium in the cortex is induced from a distance. But in dalbergoid legumes like Arachis hypogaea, rhizobia directly invade cortical cells through epidermal cracks to generate the primordia. Herein, we report the transcriptional dynamics with the progress of symbiosis in A. hypogaea at 1 day postinfection (dpi) (invasion), 4 dpi (nodule primordia), 8 dpi (spread of infection in nodule-like structure), 12 dpi (immature nodules containing rod-shaped rhizobia), and 21 dpi (mature nodules with spherical symbiosomes). Expression of putative ortholog of symbiotic genes in 'crack entry' legume A. hypogaea was compared with infection thread-adapted model legumes. The contrasting features were i) higher expression of receptors like LYR3 and EPR3 as compared with canonical Nod factor receptors, ii) late induction of transcription factors like NIN and NSP2 and constitutive high expression of ERF1, EIN2, bHLH476, and iii) induction of divergent pathogenesis-responsive PR-1 genes. Additionally, symbiotic orthologs of SymCRK, ROP6, RR9, SEN1, and DNF2 were not detectable and microsynteny analysis indicated the absence of a RPG homolog in diploid parental genomes of A. hypogaea. The implications are discussed and a molecular framework that guides crack-entry symbiosis in A. hypogaea is proposed.
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Arachis , Perfilación de la Expresión Génica , Rhizobium , Simbiosis , Adaptación Fisiológica/genética , Arachis/genética , Arachis/microbiología , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Nódulos de las Raíces de las Plantas/genética , TranscriptomaRESUMEN
Silver ions, because of its recognised antimicrobial activity are reported in several regions for the very long time while ergosterol, apart from its role as a secondary metabolite, structural component of the fungal cell membranes, also turns out to be activating defence response in plants. Silver ions biosynthesized by terpene ergosterol producing Trichoderma harzianum could be used against other plant pathogenic fungi. In this work, possible interaction of the silver ions with ergosterol enzyme has been investigated using a computational approach. Protein model construction via prior knowledge of sequences and molecular ligand docking experiments as well as structural and sequence comparisons were executed to identify potential active-site in ergosterol enzyme. Moldock score of -48.5747 with the reranking score of -40.0228 has been reported by Molegro Virtual Docker(MVD) at ergosterol enzyme's active site positions for silver ion. Apart from the core of the active site, four other positions have been occupied by silver ion. The interacting site surrounded by Cys339, Arg343, Lue365, Leu336 and Trp371 formed hydrophobic bonds with silver. The anti-microbial activity against phytopathogens is believed to increase synergistically when combined with ergosterol enzyme. Thus the computational analysis of silver ion in conjugation with ergosterol enzyme provided additional strategies to improve the ability of the Trichoderma strains in biocontrol of pathogenic fungi. In the present study, silver ion based formulations which are produced by strong bio-control fungi as shown were estimated in response to different plant pathogen in further studies.
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Enzimas/metabolismo , Ergosterol/metabolismo , Nanopartículas/metabolismo , Plata/metabolismo , Trichoderma/metabolismo , Sitios de Unión , Simulación del Acoplamiento Molecular , Unión ProteicaRESUMEN
OBJECTIVES: Globally, disease surveillance systems are playing a significant role in outbreak detection and response management of Infectious Diseases (IDs). However, in developing countries like Pakistan, epidemic outbreaks are difficult to detect due to scarcity of public health data and absence of automated surveillance systems. Our research is intended to formulate an integrated service-oriented visual analytics architecture for ID surveillance, identify key constituents and set up a baseline for easy reproducibility of such systems in the future. STUDY DESIGN: This research focuses on development of ID-Viewer, which is a visual analytics decision support system for ID surveillance. It is a blend of intelligent approaches to make use of real-time streaming data from Emergency Departments (EDs) for early outbreak detection, health care resource allocation and epidemic response management. METHODS: We have developed a robust service-oriented visual analytics architecture for ID surveillance, which provides automated mechanisms for ID data acquisition, outbreak detection and epidemic response management. Classification of chief-complaints is accomplished using dynamic classification module, which employs neural networks and fuzzy-logic to categorize syndromes. Standard routines by Center for Disease Control (CDC), i.e. c1-c3 (c1-mild, c2-medium and c3-ultra), and spatial scan statistics are employed for detection of temporal and spatio-temporal disease outbreaks respectively. Prediction of imminent disease threats is accomplished using support vector regression for early warnings and response planning. Geographical visual analytics displays are developed that allow interactive visualization of syndromic clusters, monitoring disease spread patterns, and identification of spatio-temporal risk zones. RESULTS: We analysed performance of surveillance framework using ID data for year 2011-2015. Dynamic syndromic classifier is able to classify chief-complaints to appropriate syndromes with high classification accuracy. Outbreak detection methods are able to detect the ID outbreaks in start of epidemic time zones. Prediction model is able to forecast dengue trend for 20 weeks ahead with nominal normalized root mean square error of 0.29. Interactive geo-spatiotemporal displays, i.e. heat-maps, and choropleth are shown in respective sections. CONCLUSION: The proposed framework will set a standard and provide necessary details for future implementation of such a system for resource-constrained regions. It will improve early outbreak detection attributable to natural and man-made biological threats, monitor spatio-temporal epidemic trends and provide assurance that an outbreak has, or has not occurred. Advanced analytics features will be beneficial in timely organization/formulation of health management policies, disease control activities and efficient health care resource allocation.
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Control de Enfermedades Transmisibles , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades/prevención & control , Vigilancia de la Población/métodos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Humanos , Pakistán/epidemiología , Reproducibilidad de los ResultadosRESUMEN
Colorectal surgery is a treatment for colorectal lesions. Technological advancements have given the rise to robotic colorectal surgery, a procedure that limits excessive blood loss via 3D pin-point precision capabilities during surgeries. The aim of this study is to review robotic surgery in colorectal treatment procedures in order to dictate its ultimate merits. This is a literature review utilising PubMed and Google Scholar; it only includes case studies and case reviews related to robotic colorectal surgeries. Literature reviews are excluded. We incorporated abstracts from all articles and full publications were examined to compare the benefits of robotic surgery in colorectal treatments. The number of articles reviewed was 41 literature spanning from 2003 to 2022. We found that robotic surgeries yielded finer marginal resections, greater amounts of lymph node resections and earlier recovery of bowel functions. The patients also spent less time in hospital after surgery. The obstacles on the other hand are it costs longer operative hours and further training, which is expensive. Studies show robotic approach is a choice for treating rectal cancer. However further studies would be needed to conclude the best approach. This is especially true with patients treated for anterior colorectal resections. Based on the evidence it's safe to say that the upsides outweigh the downsides, but advancements and further research in robotic colorectal surgeries are still necessary to reduce operative hours and cost. Surgical societies should also take the initiative and set up effective training programmes for colorectal robotic surgeries, as trained physicians result in better treatment outcomes.
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PURPOSE: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with proven efficacy in patients with ALK-rearranged lung cancer previously treated with first- and second-generation ALK inhibitors. Beside compound mutations in the ALK kinase domain, other resistance mechanisms driving lorlatinib resistance remain unknown. We aimed to characterize the mechanisms of resistance to lorlatinib occurring in patients with ALK-rearranged lung cancer and design new therapeutic strategies in this setting. EXPERIMENTAL DESIGN: Resistance mechanisms were investigated in 5 patients resistant to lorlatinib. Longitudinal tumor biopsies were studied using high-throughput next-generation sequencing. Patient-derived models were developed to characterize the acquired resistance mechanisms, and Ba/F3 cell mutants were generated to study the effect of novel ALK compound mutations. Drug combinatory strategies were evaluated in vitro and in vivo to overcome lorlatinib resistance. RESULTS: Diverse biological mechanisms leading to lorlatinib resistance were identified. Epithelial-mesenchymal transition (EMT) mediated resistance in two patient-derived cell lines and was susceptible to dual SRC and ALK inhibition. We characterized three ALK kinase domain compound mutations occurring in patients, L1196M/D1203N, F1174L/G1202R, and C1156Y/G1269A, with differential susceptibility to ALK inhibition by lorlatinib. We identified a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors. CONCLUSIONS: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.
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Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/genética , Lactamas Macrocíclicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Aminopiridinas , Animales , Línea Celular Tumoral , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Femenino , Reordenamiento Génico , Humanos , Lactamas , Lactamas Macrocíclicas/uso terapéutico , Estudios Longitudinales , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Mutación , Neurofibromina 2/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Replication in herpesvirus genomes is a major concern of public health as they multiply rapidly during the lytic phase of infection that cause maximum damage to the host cells. Earlier research has established that sites of replication origin are dominated by high concentration of rare palindrome sequences of DNA. Computational methods are devised based on scoring to determine the concentration of palindromes. In this paper, we propose both extraction and localization of rare palindromes in an automated manner. Discrete Cosine Transform (DCT-II), a widely recognized image compression algorithm is utilized here to extract palindromic sequences based on their reverse complimentary symmetry property of existence. We formulate a novel approach to localize the rare palindrome clusters by devising a Minimum Quadratic Entropy (MQE) measure based on the Renyi's Quadratic Entropy (RQE) function. Experimental results over a large number of herpesvirus genomes show that the RQE based scoring of rare palindromes have higher order of sensitivity, and lesser false alarm in detecting concentration of rare palindromes and thereby sites of replication origin.
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Algoritmos , Biología Computacional/métodos , Genoma Viral/genética , Herpesviridae/genética , Secuencias Invertidas Repetidas/genética , Origen de Réplica/genética , Análisis por Conglomerados , EntropíaRESUMEN
Selection of synonymous codons for an amino acid is biased in protein translation process. This biased selection causes repetition of synonymous codons in structural parts of genome that stands for high N/3 peaks in DNA spectrum. Period-3 spectral property is utilized here to produce a 3-phase network model based on polyphase filterbank concepts for derivation of codon bias spectra (CBS). Modification of parameters in this model can produce GC, GC3, and AT3 bias spectra. Complete schematic in LabVIEW platform is presented here for efficient and parallel computation of GC, GC3, and AT3 bias spectra of genomes alongwith results of CBS patterns. We have performed the correlation coefficient analysis of GC, GC3, and AT3 bias spectra with codon bias patterns of CBS for biological and statistical significance of this model.
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It is known that disseminated intravascular coagulation (DIC) can contribute towards blood loss after transurethral resection of the prostate because of the absorption of various prostatic substances. The aim of the present study was to establish whether simple coagulation tests (prothrombin time/activated partial thromboplastin time) carried out immediately after surgery would be useful in predicting those patients who bleed excessively after prostatic resection due to DIC. Criteria to determine significant post-operative haemorrhage were defined. Of 110 patients entered into the study, 34.5% had significant post-operative bleeding and 74% of these had an abnormal prothrombin time (> or = 15 s) immediately after surgery. An abnormal prothrombin time was associated with the resection of large prostates but could also predict the risk of bleeding independent of the resected weight; 18% of patients with an abnormal prothrombin time were also found to have an abnormal activated partial thromboplastin time and all of these had significant blood loss. A group of patients with an abnormal prothrombin time and a resected dry weight > or = 35 g was identified as a high risk group.
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Coagulación Intravascular Diseminada/etiología , Hematuria/etiología , Prostatectomía/efectos adversos , Enfermedades de la Próstata/cirugía , Anciano , Anciano de 80 o más Años , Coagulación Intravascular Diseminada/prevención & control , Hematuria/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Periodo Posoperatorio , Estudios Prospectivos , Próstata/patología , Enfermedades de la Próstata/patología , Tiempo de ProtrombinaRESUMEN
This study presents a review of 519 of 553 unselected patients with carcinoma of the caecum presenting in the Plymouth Health District between 1975 and 1987. A large proportion of the patients were elderly and the median age increased throughout the study period to 76 years. One third of cases presented as an emergency and a small number was discovered at autopsy. Bowel obstruction accounted for over half the emergencies and chronic anaemia for half the elective cases. At presentation many tumours were advanced and only 5% were Dukes' A. One quarter of patients had synchronous tumours. Resection was performed in most cases, and this was attempted even in the presence of local invasion and liver metastases. Morbidity following resection was low and only six anastomotic leaks were clinically apparent. The mortality rate following resection was 2.6% and was higher for emergency procedures. The age-adjusted 5-year survival rate was 37% and rose to 64% for those undergoing 'curative' surgery. These results suggest that future improvements in the management of right colon cancer may lie with early referral and diagnosis. This study further highlights the importance of good perioperative care in the increasingly elderly patient.
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Neoplasias del Ciego , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ciego/diagnóstico , Neoplasias del Ciego/mortalidad , Neoplasias del Ciego/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones PosoperatoriasRESUMEN
A total of 519 patients presenting with carcinoma of the caecum in the Plymouth Health District between 1975 and 1987 were reviewed. The clinical course was determined in relation to patients with and without a history of previous appendicectomy. There was no difference in the incidence of previous appendicectomy between patients with carcinoma of the caecum and an age and sex matched control group. The presence of synchronous carcinomas and/or adenomas was unrelated to previous appendicectomy. Ten patients presented with appendicitis and 11 with a mucocele of the appendix as the first sign of carcinoma of the caecum. Previous appendicectomy was associated with a higher incidence of local fixity, invasion of the abdominal wall, metastatic spread and poor differentiation. These differences were reflected in a significantly lower resection rate for carcinomas in patients who had previously undergone appendicectomy. The survival of patients who had previously had appendicectomy was significantly reduced. Four independent prognostic factors for survival were identified using multivariate discriminant analysis. These were Dukes' classification, local invasion, tumour differentiation and previous appendicectomy. Local recurrence was more common in patients who had previously had appendicectomy and was often in the old appendicectomy wound itself. Appendicectomy does not increase the risk of carcinogenesis in the caecum. In this study a history of appendicectomy was an independent risk factor for survival and significantly worsened the prognosis for patients who subsequently developed carcinoma of the caecum.