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Abstract: Lung cancer is a complex disease, with a wide range of genetic alterations and clinical presentations. Understanding the natural and clinical history of the disease is crucial for developing effective diagnostic and treatment strategies. Omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools for understanding the molecular mechanisms underlying lung cancer and for identifying novel biomarkers and therapeutic targets. These approaches enable researchers to examine the entire genome, transcriptome, proteome, or metabolome of a cell or tissue, providing a comprehensive view of the biological processes involved in lung cancer development and progression. Targeted therapies that address specific genetic mutations and pathways hold promise for improving the diagnosis and treatment of this disease.
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Neoplasias Pulmonares , Medicina de Precisión , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Genómica , Proteómica , MetabolómicaRESUMEN
Background: Sarcomas are a relatively rare but diverse group of cancers that typically develop in the mesenchymal cells of bones and soft tissues. Occurring in more than 70 subtypes, sarcomas have broad histological presentations, posing significant challenges of prognosis and treatment. Modern multi-omics studies, which include genomics, proteomics, metabolomics, and micro-biomics, are vital to understand the underlying mechanisms of sarcoma development and progression, identify molecular biomarkers for early detection, develop personalized treatment plans, and discover drug resistance mechanisms in sarcomas to upsurge the survival rate. Aim: This study aims to highlight the genetic risk factors responsible for sarcoma-genesis, and to present a comprehensive review of multi-omics studies about sarcoma. Methods: Extensive literature research was undertaken using reliable and authentic medical journals, e-books, and online cancer research databases. Mendelian inheritance in man database (OMIM) was explored to study particular genes and their loci that are responsible to cause various sarcomas. Result: This in-depth research led to the finding out that omics studies provide a more comprehensive understanding of underlying molecular mechanisms of sarcomas. Through genomics, we can reveal genetic alterations that predispose to sarcoma, like mutation in TP53, NF1, and so on. Pharmacogenomics enable us to find molecular targets for specific drugs. Whereas, proteomic and metabolomic studies provide insights into the biological pathways involved in sarcoma development and progression. Conclusion: Future advancements in omics sciences for sarcoma are on the cutting-edge of defining precision treatment plans and improved resilience of sarcoma patients.
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Proteómica , Sarcoma , Humanos , Medicina de Precisión , Genómica , Sarcoma/tratamiento farmacológico , Sarcoma/genética , BiomarcadoresRESUMEN
Abstract: In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.
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Neoplasias de la Próstata , Proteómica , Humanos , Masculino , Proteómica/métodos , Medicina de Precisión , Genómica/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , BiomarcadoresRESUMEN
Abstract: Glioblastoma is a highly aggressive and malignant type of brain cancer with a poor prognosis, despite current treatment options of surgery, radiation therapy, and chemotherapy. These treatments have limitations due to the aggressive nature of the cancer and the difficulty in completely removing the tumor without damaging healthy brain tissue. Personalized medicine, using genomic profiling to tailor treatment to the patient's specific tumor, and immunotherapy have shown promise in clinical trials. The blood-brain barrier also poses a challenge in delivering treatments to the brain, and researchers are exploring various approaches to bypass it. More effective, personalized treatment approaches are needed to improve outcomes for glioblastoma patients. This tumor is studied using genomics, transcriptomics, and proteomics techniques, to better understand its underlying molecular mechanisms. Recent studies have used these techniques to identify potential therapeutic targets, molecular subtypes, and heterogeneity of tumor cells. Advancements in omics sciences have improved our understanding of glioblastoma biology, and precision medicine approaches have impli-cations for more accurate diagnoses, improved treatment outcomes, and personalized preventive care. Precision medicine can match patients with drugs that target specific genetic mutations, improve clinical trials, and identify individuals at higher risk for certain diseases. Precision medicine, which involves customizing medical treatment based on an individual's genetic makeup, lifestyle, and environmental factors, has shown promise in improving treatment outcomes for glioblastoma patients. Identifying biomarkers is essential for patient stratification and treatment selection in precision medicine approaches for glioblastoma, and several biomarkers have shown promise in predicting patient response to treatment. Targeted therapies are a key component of precision medicine approaches in glioblastoma, but there is still a need to improve their effectiveness. Technical challenges, such as sample quality and availability, and challenges in analyzing and interpreting large amounts of data remain significant obstacles in omics sciences and precision medicine for glioblastoma. The clinical implementation of precision medicine in glioblastoma treatment faces challenges related to patient selection, drug development, and clinical trial design, as well as ethical and legal considerations related to patient privacy, informed consent, and access to expensive treatments.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/tratamiento farmacológico , Medicina de Precisión , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Proteómica/métodos , BiomarcadoresRESUMEN
Abstract: Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.
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Neoplasias del Colon , Medicina de Precisión , Humanos , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Genómica , Pronóstico , ProteómicaRESUMEN
Background: Human breast carcinoma is a complex disease, affecting 1 in 8 women worldwide. The seriousness of the disease increases when the definite cause of the disease remains obscure, thus making prognosis challenging. Researchers are emphasizing on adapting more advanced and targeted therapeutic approaches to address the multifaceted impacts of the disease. Hence, modern multi-omics systems have gained popularity among clinicians, as they offer insights into the genomic, pharmacogenomic, metabolomic, and microbiomic factors, thus allowing researchers to develop targeted and personalized approaches for breast cancer prevention and early detection, and eventually improving patient outcomes. Aim: The primary focus of this study is to elucidate, through the integration of multi-omics research findings, the inherent molecular origins of diverse subtypes of breast cancer and to evaluate the effectiveness of these findings in reducing breast cancer-related mortalities. Methods: Thorough investigation was conducted by reviewing reputable and authoritative medical journals, e-books, and online databases dedicated to cancer research. The Mendelian inheritance in man database (OMIM) was used to scrutinize specific genes and their respective loci associated with the development of different types of breast cancer. Results: Our present research revealed the holistic picture of sundry molecular, genomic, pharmacogenomic, metabolomic, and microbiomic features of breast cancer. Such findings, like genetic alterations in highly penetrant genes, plus metabolomic and microbiomic signatures of breast cancer, unveil valuable insights and show great potential for multi-omics research in breast oncology. Conclusion: Further research in omics sciences pertaining to breast cancer are at the forefront of shaping precise treatment and bolstering patient survival.
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Neoplasias de la Mama , Neoplasias Ováricas , Femenino , Humanos , Medicina de Precisión , Genómica , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Pronóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapiaRESUMEN
Abstract: The global COVID-19 outbreak, started in December 2019, resulted in severe financial losses and extraordinary health crises. Finding a potent and secure medication candidate to treat SARS-CoV-2 infection and its symptoms is still an urgent global need. After reviewing previous studies, olive leaves, being rich in polyphenolic compounds (a large class of bioactive substances naturally found in plants), were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. It has long been known that olive tree polyphenols-such as oleuropein, hydroxytyrosol, verbascoside, as well as triterpenoids like maslinic, ursolic, and oleanolic acids-have anti-inflammatory and multitarget antiviral effects on several virus families, and they could be one of the reasons of the beneficial effects of the Mediterranean diet against COVID-19. Thus, olive tree poly-phenols were tested in silico and in vitro for preventing SARS-CoV-2 infection, claiming that they have beneficial effects. Nevertheless, there is still a small number of research studies on this topic. The aim of this scoping review is to provide more information and offer an opinion on the feasibility of using olive tree polyphenols as a springboard for the creation of innovative natural remedies against this viral illness, ultimately planning future relevant studies.
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COVID-19 , Olea , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Polifenoles/farmacología , Polifenoles/uso terapéutico , FenolesRESUMEN
OBJECTIVE: Lymphedema is a debilitating disease and may be a comorbidity of obesity. New molecules have been investigated for the treatment of lymphedema; one of the most promising molecules is hydroxytyrosol. The aim of this study was to evaluate the association between mutations in genes mutated in lymphedema and the presence of obesity and making an estimate of the quality of life in lymphedema patients. MATERIALS AND METHODS: We recruited 71 Caucasian individuals with the diagnosis of primary lymphedema, and they undertook a questionnaire to assess their quality life. For this purpose, we developed a NGS custom-made panel comprising genes associated with lymphedema. RESULTS: An obesity rate of 20% was detected. The average Lymph-ICF-LL value for patients who consume olive oil daily was 20 with a better quality of life. Twenty-three patients resulted positive to the genetic test. Genetic variants with a likely association with obesity have been identified in PROX1, FOXC2 and FLT4. CONCLUSIONS: A obesity rate, higher than that reported by ISTAT, was detected. The use of olive oil enhances the quality of life of lymphedema patients. Moreover, a diagnostic approach by a NGS panel shows an association of lymphedema with obesity.
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Linfedema/dietoterapia , Linfedema/genética , Obesidad/dietoterapia , Obesidad/genética , Aceite de Oliva/administración & dosificación , Alcohol Feniletílico/análogos & derivados , Calidad de Vida , Adulto , Antioxidantes/administración & dosificación , Índice de Masa Corporal , Estudios de Cohortes , Biología Computacional/métodos , Femenino , Pruebas Genéticas/métodos , Humanos , Linfedema/psicología , Masculino , Persona de Mediana Edad , Obesidad/psicología , Alcohol Feniletílico/administración & dosificación , Calidad de Vida/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of the study was to show the importance of developing techniques that could exploit the potential of bacteriophages as therapeutics or food supplements. MATERIALS AND METHODS: PubMed database was searched using the following combination of keywords: (bacteriophage) AND (human therapy); (natural bacteriophage) AND (application). RESULTS: The increasing antibiotic resistance of many bacterial strains is making standard antibiotic treatments less effective. Phage therapy provides a non-antibiotic alternative with greater specificity and without harmful effects on the human microbiota. Phages target their specific bacteria, replicate, and then, destroy the host pathogen. Bacteriophages may be administered by several routes, including topical, oral and intravenous. They not only destroy the host pathogen but, in some cases, increase the sensitivity of host bacteria to antibiotics. Various studies have shown that combining phage therapy and antibiotic treatment can be effective against bacterial infections. Clinical trials of phage therapy have shown promising results for various human diseases and conditions. With advances in genetic engineering and molecular techniques, bacteriophages will be able to target a wide range of bacteria. CONCLUSIONS: In the future, phage therapy promises to become an effective therapeutic option for bacterial infections. Since many potentially beneficial bacteriophages can be found in food, supplements containing bacteriophages could be designed to remodel gut microbiota and eliminate pathogenic bacteria. Remodeling of gut microbiota could correct gut dysbiosis. The order of phages known to have these promising activities is Caudovirales, especially the families Siphoviridae and Myoviridae.
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Infecciones Bacterianas/terapia , Bacteriófagos , Terapia de Fagos/métodos , Infecciones Bacterianas/fisiopatología , Infecciones Bacterianas/virología , Bacteriófagos/aislamiento & purificación , Bacteriófagos/fisiología , Técnicas de Cultivo/métodos , Técnicas de Cultivo/tendencias , Disbiosis/fisiopatología , Disbiosis/terapia , Disbiosis/virología , Microbioma Gastrointestinal/fisiología , Humanos , Terapia de Fagos/tendenciasRESUMEN
Pheromones are ectohormones that play an important role in communication and behavior. Pheromones and pheromone receptor genes are important in mice and other mammals that rely heavily on pheromone cues to survive. Although there is controversy about whether pheromones and pheromone receptor genes have the same importance or are even active in humans, there are some hints that they might have roles in sociosexual behavior and mental disorders. The aim of this qualitative review was to provide an overview of the state of the art regarding pheromones and pheromone receptors in humans and their possible implications in human physiology and pathology. An electronic search was conducted in MEDLINE, PubMed and Scopus databases for articles published in English up to December 2018. The search concerned a possible role of pheromones and pheromone receptors in humans with implications for sociosexual behavior, mental disorders, the menstrual cycle and nutrition. Pheromone communication in humans has not been definitively demonstrated. However, the potential ability of putative pheromones to activate the hypothalamus, which controls the release of many hormones, suggests they could have a role in systemic functions in humans. Future confirmation of the effects of pheromones and pheromone receptors in humans could be useful in the prevention and treatment of various human disorders.
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Feromonas/metabolismo , Receptores de Feromonas/metabolismo , Animales , Humanos , Ligandos , Ratones , Feromonas/genética , Receptores de Feromonas/genéticaRESUMEN
The aim of this study was to evaluate, during the first 4 wk of life, the involution of umbilical structures in clinically healthy calves and in calves affected by umbilical disorders, in both B-mode and color Doppler ultrasonography. The present study was carried out on 63 Holstein Friesian calves, divided into 3 different groups: group H (clinically healthy, n = 17), group A, (affected by omphaloarteritis, n = 24), and group V (affected by omphalophlebitis, n = 22). B-mode ultrasonography was performed at weekly intervals, using a portable device (LOGIQ Book XP, GE Healthcare, Little Chalfont, UK) and a linear multifrequency 7 to 10 MHz probe. In addition to the ultrasound examinations, the umbilicus of the calves was also evaluated using a color Doppler. The extra-abdominal as well as the intra-abdominal hemodynamics within the umbilical structures were evaluated using 3 different ranges of speed-flow detections (23, 14, and 7 cm/s). In healthy calves, as the age increased, the umbilical structures decreased in size and their ultrasonographic identification became more difficult. Conversely, in affected calves the umbilical structures did not show the same progressive reduction of external diameters and areas, but had an irregular trend of regression. Also the color Doppler ultrasonography showed a significant difference in frequency and percentage of speed-flow in the early days of examination between the 3 groups, with the most reliable results detected from the umbilical arteries. In our experimental study, omphaloarteritis could be detected at the d 1 color Doppler exam, with a 100% specificity and a 100% positive predictive value.
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Enfermedades de los Bovinos/diagnóstico por imagen , Ultrasonografía/veterinaria , Animales , Animales Recién Nacidos , Bovinos , Femenino , Sensibilidad y Especificidad , Ultrasonografía Doppler en Color/veterinaria , Arterias Umbilicales/diagnóstico por imagen , Ombligo/diagnóstico por imagenRESUMEN
OBJECTIVE: While next generation sequencing (NGS) has become the technology of choice for clinical diagnostics, most genetic laboratories still use Sanger sequencing for orthogonal confirmation of NGS results. Previous studies have shown that when the quality of NGS data is high, most calls are indicated by Sanger sequencing, making confirmation redundant. We aimed at establishing a set of criteria that make it possible to distinguish NGS calls that need orthogonal confirmation from those that do not would significantly decrease the amount of work necessary to reach a diagnosis. MATERIALS AND METHODS: A data set of 7976 NGS calls confirmed as true or false positive by Sanger sequencing was used to train and test different machine learning (ML) approaches. By varying the size and class balance of the training dataset, we measured the performance of the different algorithms to determine the conditions under which ML is a valid approach for confirming NGS calls in a diagnostic environment. RESULTS: Our results indicate that machine learning is a valid approach to find variant calls that need more investigation, but in order to reach the high accuracy required in a clinical environment, the training data set must include enough observations and these observations must be well-balanced between true/false positive NGS calls. CONCLUSIONS: Our results show that it is possible to integrate the diagnostic NGS validation workflow with a machine learning approach to reduce the number of Sanger confirmations of high- quality NGS calls, reducing the time and costs of diagnosis.
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Algoritmos , Secuenciación de Nucleótidos de Alto Rendimiento , Aprendizaje Automático , Análisis de Secuencia de ADN , Humanos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Familial atrial fibrillation (FAF), a not uncommon arrhythmia of the atrium, is characterized by heritability, early onset and absence of other heart defects. The molecular and genetic basis is still not completely clear and genetic diagnosis cannot be achieved in about 90% of patients. In this study, we present the results of genetic screening by next generation sequencing in affected Russian families. PATIENTS AND METHODS: Sixty subjects (18 probands and 42 relatives) with a clinical diagnosis of FAF were enrolled in the study. Since AF frequently associates with other cardiomyopathies, we included all genes that were known to be associated with these disorders at the time of our study. All probands were therefore systematically screened for 47 genes selected from the literature. RESULTS: Our study revealed that seven variants co-segregated with the clinical phenotype in seven families. Interestingly, four out of six genes and three out of seven variants have already been associated with Brugada syndrome in the literature. CONCLUSIONS: To our knowledge, this is the first report of association of the CACNA1C, CTNNA3, PKP2, ANK2 and SCN10A genes with FAF; it is also the first study in Russian families.
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Fibrilación Atrial/diagnóstico , Síndrome de Brugada/genética , Adolescente , Adulto , Ancirinas/genética , Fibrilación Atrial/genética , Síndrome de Brugada/patología , Canales de Calcio Tipo L/genética , Análisis Mutacional de ADN , Bases de Datos Genéticas , Ecocardiografía , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Canal de Sodio Activado por Voltaje NAV1.8/genética , Linaje , Fenotipo , Placofilinas/genética , Adulto Joven , alfa Catenina/genéticaRESUMEN
OBJECTIVE: We describe how to set up a custom workflow for the analysis of next generation sequencing (NGS) data suitable for the diagnosis of genetic disorders and that meets the strictest standards of quality and accuracy. Our method goes from DNA extraction to data analysis with a computational in-house pipeline. The system was extensively validated using three publicly available Coriell samples, estimating accuracy, sensitivity and specificity. Multiple runs were also made to assess repeatability and reproducibility. MATERIALS AND METHODS: Three different Coriell samples were analyzed in a single run to perform coverage, sensitivity, specificity, accuracy, reproducibility and repeatability analysis. The three samples were analyzed with a custom-made oligonucleotide probe library using Nextera Rapid Capture enrichment technique and subsequently quantified using the Qubit method. Sample quality was verified using a 4200 TapeStation and sequenced on a MiSeq personal sequencer. Analysis of NGS data was then performed with a custom pipeline. RESULTS: The workflow enabled an accurate and precise analysis of NGS data that meets all the requirements of quality and accuracy required by international standards such as ISO15189 and the Association of Molecular Pathology. CONCLUSIONS: The proposed analysis/validation workflow has high assay accuracy, precision and robustness and can, therefore, be used for clinical diagnostic applications.
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Biología Computacional/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Flujo de Trabajo , Algoritmos , Conjuntos de Datos como Asunto , Secuenciación de Nucleótidos de Alto Rendimiento/instrumentación , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis de Secuencia de ADN/instrumentaciónRESUMEN
Primary lymphedema is a rare inherited condition characterized by swelling of body tissues caused by accumulation of fluid, especially in the lower limbs. In many patients, primary lymphedema has been associated with variations in a number of genes involved in the development and maintenance of the lymphatic system. In this study, we performed a genetic screening in patients affected by primary lymphedema using a next generation sequencing (NGS) approach. With this technology, based on a custom-made oligonucleotide probe library, we were able to analyze simultaneously in each patient all the coding exons of 10 genes (FLT4, FOXC2, CCBE1, GJC2, MET, HGF, GATA2, SOX18, VEGFC, KIF11) associated with primary lymphedema. In the study population, composed of 45 familial and 71 sporadic cases, we identified the presence of rare variants with a potential pathogenic effect in 33% of subjects. Overall, we found a total of 36 different rare nucleotidic alterations, 30 of which had not been previously described. Among these, we identified 23 mutations that we considered most likely to be disease causing. Patients with an FLT4 or FOXC2 alteration accounted for the largest percentage of the sample, followed by MET, HGF, KIK11, GJC2 and GATA2. No alterations were identified in SOX18, VEGFC, and CCBE1 genes. In conclusion, we showed that NGS technology can be successfully applied to perform molecular screening of lymphedema-associated genes in large cohort of patients with a reasonable effort in terms of cost, work, and time.
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Linfedema/genética , Población Blanca/genética , Adolescente , Adulto , Proteínas de Unión al Calcio/genética , Niño , Preescolar , Estudios de Cohortes , Conexinas/genética , Femenino , Factores de Transcripción Forkhead/genética , Factor de Transcripción GATA2/genética , Pruebas Genéticas , Genotipo , Factor de Crecimiento de Hepatocito/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Italia , Cinesinas/genética , Linfedema/diagnóstico por imagen , Linfocintigrafia , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Proteínas Proto-Oncogénicas c-met/genética , Factores de Transcripción SOXF/genética , Análisis de Secuencia de ADN , Proteínas Supresoras de Tumor/genética , Factor C de Crecimiento Endotelial Vascular/genética , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genética , Adulto JovenRESUMEN
Increasing evidence points to a role for dysfunctional glutamate N-methyl-D-aspartate receptor (NMDAR) neurotransmission in schizophrenia. D-aspartate is an atypical amino acid that activates NMDARs through binding to the glutamate site on GluN2 subunits. D-aspartate is present in high amounts in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-aspartate oxidase (DDO). The agonistic activity exerted by D-aspartate on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for some of the NMDAR-related alterations observed in schizophrenia. Consistently, substantial reductions of D-aspartate and NMDA were recently observed in the postmortem prefrontal cortex of schizophrenic patients. Here we show that DDO mRNA expression is increased in prefrontal samples of schizophrenic patients, thus suggesting a plausible molecular event responsible for the D-aspartate imbalance previously described. To investigate whether altered D-aspartate levels can modulate schizophrenia-relevant circuits and behaviors, we also measured the psychotomimetic effects produced by the NMDAR antagonist, phencyclidine, in Ddo knockout mice (Ddo(-)(/-)), an animal model characterized by tonically increased D-aspartate levels since perinatal life. We show that Ddo(-/-) mice display a significant reduction in motor hyperactivity and prepulse inhibition deficit induced by phencyclidine, compared with controls. Furthermore, we reveal that increased levels of D-aspartate in Ddo(-/-) animals can significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico-hippocampal connectivity networks potentially involved in schizophrenia. Collectively, the present results suggest that altered D-aspartate levels can influence neurodevelopmental brain processes relevant to schizophrenia.
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Conducta Animal/efectos de los fármacos , D-Aspartato Oxidasa/genética , Antagonistas de Aminoácidos Excitadores/farmacología , Fenciclidina/farmacología , Corteza Prefrontal/metabolismo , Adulto , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Estudios de Casos y Controles , D-Aspartato Oxidasa/metabolismo , Metilación de ADN , Modelos Animales de Enfermedad , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Inhibición Prepulso/efectos de los fármacos , Inhibición Prepulso/genética , EsquizofreniaRESUMEN
We conducted a pilot-scale experiment to study the effects of an aided phytostabilisation on soil microbial and biological endpoints in an ore dust-contaminated soil. Soil was amended with alkaline fly ashes plus peat to reduce mobility of trace elements and vegetated with a proprietary grass/herb mixture. Results indicated that the proposed aided phytostabilization approach of Cu-Pb contaminaed soil significantly increased microbial biomass and respiration, reduced microbial stress and increased key soil enzyme activities. Further research is needed to unambiguously determine whether the soil biochemical endpoints that were studied responded more to decreased metal mobility or to general soil amelioration.
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Cobre/toxicidad , Enzimas/metabolismo , Plomo/toxicidad , Contaminantes del Suelo/toxicidad , Suelo/análisis , Biodegradación Ambiental , Biomasa , Monitoreo del Ambiente , Contaminación Ambiental , Concentración de Iones de Hidrógeno , Residuos Industriales , Consumo de Oxígeno , Proyectos Piloto , Microbiología del Suelo , Oligoelementos/toxicidadRESUMEN
A speckle technique recently developed for transient phenomena analysis is applied to the study of dynamic properties of petroleum wells. It is shown that the samples (proceeding from the Orinoco Belt, Venezuela) actually give rise to random speckle patterns when illuminated with a laser beam. Transverse displacements of the sample's surface can then be measured by classical speckle photography. When the root mean square of the phase and intensity variations in the scattered light are small with respect to the corresponding mean values, line of sight displacements of the surface can also be measured by means of a simple modification of the original technique.