RESUMEN
Two distinct nonapeptide systems, vasotocin- and oxytocin-related peptides, evolved in vertebrates. Their role in male zebrafish reproduction has not been formally investigated. We hypothesized that the teleost nonapeptides vasotocin and isotocin stimulate male zebrafish reproductive physiology and success by affecting central neuronal and/or peripheral endocrine pathways. Pharmacological inhibition experiments revealed that both vasotocin and isotocin contribute significantly to male reproductive success, which in the case of vasotocin correlated significantly with indices of male courtship behavior. Interestingly, co-administration of vasotocin and isotocin antagonists completely abolished male reproductive success without affecting male courtship behavior and endocrine indices, possibly linked to a synergistic action of nonapeptides on male pheromone release. To further probe the nonapeptides' role in male zebrafish reproduction, we subsequently tested whether male zebrafish nonapeptide systems were acutely activated by the female releaser pheromone PGF2α, a strong chemoattractant and important reproductive cue in males which stimulates courtship behavior. Male zebrafish attracted to PGF2α in a choice assay exhibited acute increases in neuronal activation marker p-ERK immunoreactivity in the ventral glomerulus of the olfactory bulb and the preoptic area, however no co-localization with isotocin was observed. Conversely, PGF2α time-dependently stimulated whole brain isotocin mRNA abundance, suggesting secondary longer-term effects of PGF2α exposure on the central isotocinergic system. While the current lack of vasotocin-specific antibodies for zebrafish does not allow to probe acute activation of vasotocinergic neurons, whole brain vasotocin mRNA was not significantly affected by PGF2α exposure. Together, our results identify a role for nonapeptides in male zebrafish reproductive physiology and success.
Asunto(s)
Encéfalo/metabolismo , Oxitocina/análogos & derivados , Reproducción/fisiología , Vasotocina/biosíntesis , Proteínas de Pez Cebra/biosíntesis , Pez Cebra/metabolismo , Animales , Masculino , Neuronas/metabolismo , Oxitocina/biosíntesis , Oxitocina/genética , Vasotocina/genética , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research
Asunto(s)
Humanos , Pancreatitis , Pancreatitis/diagnóstico , Pancreatitis/terapiaRESUMEN
Hepatitis C virus (HCV) infection has become a major public health issue in Canada, and especially in Saskatchewan First Nations (FNs) communities. One of the challenges in eliminating hepatitis C in Canada is accessing hard-to-reach populations, such as FNs people living on reserves. In Canada, HCV is a notifiable disease but complete and timely surveillance of HCV data is not always possible in remote communities. In addition, national surveillance data are insufficient for determining the number of cases of hepatitis C among FNs populations, because many provinces do not collect information according to ethnicity. Statistics for FN communities are available federally through the First Nations and Inuit Health Branch (FNIHB) in partnership with the communities and the province. There are multiple factors associated with the high rates of HCV in FNs communities, including barriers in accessing preventive services, early diagnosis and treatment. These access issues are largely attributable to issues with geographical remoteness, transportation, education and awareness, and a health care system designed around urban health. New and innovative ways of delivering information and services, such as the mobile hepatitis C clinic (Liver Health Days) and the community-driven Sexually Transmitted Bloodborne Infections (STBBI) Know Your Status program, are proving invaluable in remote FNs communities. Extending these in-community and community-driven programs to other FNs communities and to the prison population could be invaluable in working towards the World Health Organization elimination goals of hepatitis C virus for all.
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Paratuberculosis is a chronic and contagious enteric disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This disease of worldwide distribution is responsible for significant economic losses and the bacteria itself has been linked to human Crohn's disease. Paratuberculosis control programs focus on reducing MAP transmission by implementing better management practices that target infection routes. In Québec, a Voluntary Paratuberculosis Prevention and Control Program (QVPPCP) was launched in 2007. The objectives of this prospective cohort study were threefold. The first was to describe the changes in the incidence of fecal excretion of MAP in cows born before and after farm enrolment in the QVPPCP. The second was to estimate the impact of the risk of within-herd transmission of MAP (measured by the risk assessment score (RAS)) on the incidence of fecal excretion of MAP. And the third was to evaluate the impact of calf rearing practices on the incidence of fecal excretion of MAP. Eighteen MAP-positive herds were visited annually from 2011 to 2015. At each visit, individual fecal samples from all adult cows were collected. MAP was cultured using liquid media and an automated system. A risk assessment questionnaire was completed upon enrolment in the QVPPCP and at each visit. The RAS of the farm was attributed to each cow according to its birthdate. Cox proportional hazards models were used to estimate the hazard ratios (HR) for the exposure variables. Herd clustering was taken into account using robust standard errors. A total of 2158 cows were included (cohort born before n=919; cohort born after n=1239). The incidence and hazard of fecal excretion were significantly lower for the cohort-after than the cohort-before (incidence rate ratio=0.38; 95% CI: 0.18-0.78 and HR=0.48; 95% CI: 0.23-0.98). The HR of fecal excretion for cows exposed to a high RAS was 2.20 times (95% CI: 1.21-3.99) that of cows exposed to a low RAS. Poor calving cow hygiene (HR=3.41; 95% CI: 1.40-8.31) and contact between pre-weaned heifers and adult cows or their feces were significantly associated with an increased hazard of fecal excretion of MAP (HR=2.66; 95% CI: 1.08-6.56). Our results suggest that enrolment in the QVPPCP reduces the risk of MAP fecal excretion. They support the hypothesis that contact between calves and adult cows or their feces increases MAP transmission. The incidence results also suggest that MAP prevalence could be reduced to low levels regardless of initial MAP prevalence.
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Enfermedades de los Bovinos/epidemiología , Mycobacterium avium subsp. paratuberculosis/aislamiento & purificación , Paratuberculosis/epidemiología , Programas Voluntarios , Crianza de Animales Domésticos/métodos , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/prevención & control , Control de Enfermedades Transmisibles/métodos , Heces/microbiología , Femenino , Incidencia , Paratuberculosis/microbiología , Paratuberculosis/prevención & control , Prevalencia , Estudios Prospectivos , Quebec/epidemiologíaRESUMEN
Blood, saliva, mucus, sweat, sputum, and other biological fluids are often hindered in their ability to be used in point-of-care (POC) diagnostics because their assays require some form of off-site sample pre-preparation to effectively separate biomarkers from larger components such as cells. The rapid isolation, identification, and quantification of proteins and other small molecules circulating in the blood plasma from larger interfering molecules are therefore particularly important factors for optical blood diagnostic tests, in particular, when using optical approaches that incur spectroscopic interference from hemoglobin-rich red blood cells (RBCs). In this work, a sequential spiral polydimethylsiloxane (PDMS) microfluidic device for rapid (â¼1 min) on-chip blood cell separation is presented. The chip utilizes Dean-force induced migration via two 5-loop Archimedean spirals in series. The chip was characterized in its ability to filter solutions containing fluorescent beads and silver nanoparticles and further using blood solutions doped with a fluorescent protein. Through these experiments, both cellular and small molecule behaviors in the chip were assessed. The results exhibit an average RBC separation efficiency of â¼99% at a rate of 5.2 × 106 cells per second while retaining 95% of plasma components. This chip is uniquely suited for integration within a larger point-of-care diagnostic system for the testing of blood plasma, and the use of multiple filtering spirals allows for the tuning of filtering steps, making this device and the underlying technique applicable for a wide range of separation applications.
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The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution.
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Envejecimiento/genética , Evolución Biológica , Drosophila/genética , Genes Mitocondriales/genética , Variación Genética , Fosforilación Oxidativa , Animales , Femenino , Masculino , Mitocondrias/genética , Factores SexualesRESUMEN
Actinides determination in urine samples is part of the analyses performed to monitor internal contamination in case of an accident or a terrorist attack involving nuclear matter. Mineralisation is the first step of any of these analyses. It aims at reducing the sample volume and at destroying all organic compounds present. The mineralisation protocol is usually based on a wet ashing step, followed by actinides co-precipitation and a furnace ashing step, before redissolution and the quantification of the actinides by the appropriate techniques. Amongst the existing methods to perform the actinides co-precipitation, alkali-earth (typically calcium) precipitation is widely used. In the present work, the extraction of uranium(VI), plutonium(IV) and americium(III) from the redissolution solutions (called "mineralised urines") on calix[6]arene columns bearing hydroxamic groups was investigated as such an extraction is a necessary step before their determination by ICP-MS or alpha spectrometry. Difficulties were encountered in the transfer of uranium(VI) from raw to mineralised urines, with yield of transfer ranging between 0% and 85%, compared to about 90% for Pu and Am, depending on the starting raw urines. To understand the origin of such a difficulty, the speciation of uranium (VI) in mineralised urines was investigated by computer simulation using the MEDUSA software and the associated HYDRA database, compiled with recently published data. These calculations showed that the presence of phosphates in the "mineralised urines" leads to the formation of strong uranyl-phosphate complexes (such as UO2HPO4) which compete with the uranium (VI) extraction by the calix[6]arene bearing hydroxamic groups. The extraction constant of uranium (VI) by calix[6]arene bearing hydroxamic groups was determined in a 0.04 mol L(-1) sodium nitrate solution (logK=4.86±0.03) and implemented in an extraction model taking into account the speciation in the aqueous phase. This model allowed to simulate satisfactorily the experimental uranium extraction data and to support the preliminary conclusions about the role of the phosphates present in mineralised urines. These calculations also showed that the phosphate/calcium ratio is a key parameter as far as the efficiency of the uranium (VI) extraction by the calix[6]arene columns is concerned. It predicted that the addition of CaCl2 in mineralised urines would release uranium (VI) from phosphates by forming calcium (II)-phosphate complexes and thus facilitate the uranium (VI) extraction on calix[6]arene columns. These predictions were confirmed experimentally as the addition of 0.1 mol L(-1) CaCl2 to a mineralised urine containing naturally a high concentration of phosphate (typically 0.04 mol L(-1)) significantly increased the percentage of uranium (VI) extraction on the calix[6]arene columns.
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Calixarenos/química , Fraccionamiento Químico/métodos , Cromatografía/métodos , Minerales/química , Fenoles/química , Uranio/aislamiento & purificación , Uranio/orina , Urinálisis/métodos , Cloruro de Calcio/química , Precipitación Química , Ácidos Hidroxámicos/química , Resinas Sintéticas/química , Uranio/químicaRESUMEN
Nuclear accidents occurred in latest years highlighted the difficulty to achieve, in a short time, the quantification of alpha and beta emitters. Indeed, most of the existing methods, though displaying excellent performances, can be very long, taking up to several weeks for some radioisotopes, such as (90)Sr. This study focuses on alpha and beta radioisotopes which could be accidentally released from nuclear installations and which could be measured by inductively coupled plasma mass spectrometer (ICP-MS). Indeed, a new and rapid separation method was developed for (234,235,236,238)U, (230,232)Th, (239,240)Pu, (237)Np, (241)Am and (90)Sr. The main objective was to minimize the duration of the separation protocol by the development of a unique radiochemical procedure with elution media compatible with ICP-MS measurements. Excellent performances were obtained with spiked river water samples. These performances are characterized by total yields exceeding 80% for all monitored radionuclides, as well as good reproducibility (RSD≤10%, n=12). The proposed radiochemical separation (including counting time) required less than 7h for a batch of 8 samples.
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Elementos de Series Actinoides/análisis , Espectrometría de Masas/métodos , Ríos/química , Radioisótopos de Estroncio/análisis , Contaminantes Radiactivos del Agua/análisis , Elementos de Series Actinoides/aislamiento & purificación , Límite de Detección , Espectrometría de Masas/economía , Reproducibilidad de los Resultados , Radioisótopos de Estroncio/aislamiento & purificación , Factores de Tiempo , Contaminantes Radiactivos del Agua/aislamiento & purificaciónRESUMEN
UNLABELLED: Francisella tularensis is ubiquitous in the Northern Hemisphere. Yet, little is known about the disease and its ecology within Canada as few serological studies have shown exposure to the disease and fewer case studies have been reported. This report is the first to describe the molecular subtyping of F. tularensis isolates within eastern Canada using multiple-locus variable-number tandem-repeat analysis. From 1998 to 2011, a total of 73 specimens were isolated from unique human and animal sources. As expected, F. tularensis subsp. tularensis AI and F. tularensis subsp. holarctica subtypes were observed, corresponding to the known geographical division within this species. The majority of human isolates (78%) and all animal (hare) isolates were of the more virulent, AI type. Half of the B isolates were isolated from patients living in a region of Quebec where muskrat densities are known to be high. A relatively high level of marker diversity was found, suggestive of multiple introductions of the organism to the region, or more likely ongoing endemicity. There was no evidence of ongoing outbreaks or transmission, and the bulk of cases were likely due to interaction between human activity and the environment (e.g. hunting/trapping activities). SIGNIFICANCE AND IMPACT OF THE STUDY: This study reveals the diversity of Francisella tularensis in eastern Canada using multiple-locus variable-number tandem-repeat analysis. It was initiated to further the understanding of the species within North America as previous studies elucidating the diversity and phylogeography of the species have consisted mostly of specimens from the United States. Type A tularaemia, the most life-threatening subtype of the species and a Category A biothreat agent, is restricted to North America, and this study serves to broaden the knowledge of the epidemiology and diversity of the organism.
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Francisella tularensis/genética , Francisella tularensis/aislamiento & purificación , Liebres/microbiología , Secuencias Repetidas en Tándem/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Arvicolinae/microbiología , Niño , Francisella tularensis/clasificación , Variación Genética/genética , Humanos , Persona de Mediana Edad , Tipificación Molecular , Filogeografía , Quebec , Tularemia/microbiología , Adulto JovenRESUMEN
BACKGROUND: Antisocial personality disorder (ASPD) is characterised by elevated impulsive aggression and increased risk for criminal behaviour and incarceration. Deficient activity of the monoamine oxidase A (MAOA) gene is suggested to contribute to serotonergic system dysregulation strongly associated with impulsive aggression and antisocial criminality. AIMS: To elucidate the role of epigenetic processes in altered MAOA expression and serotonin regulation in a population of incarcerated offenders with ASPD compared with a healthy non-incarcerated control population. METHOD: Participants were 86 incarcerated participants with ASPD and 73 healthy controls. MAOA promoter methylation was compared between case and control groups. We explored the functional impact of MAOA promoter methylation on gene expression in vitro and blood 5-HT levels in a subset of the case group. RESULTS: Results suggest that MAOA promoter hypermethylation is associated with ASPD and may contribute to downregulation of MAOA gene expression, as indicated by functional assays in vitro, and regression analysis with whole-blood serotonin levels in offenders with ASPD. CONCLUSIONS: These results are consistent with prior literature suggesting MAOA and serotonergic dysregulation in antisocial populations. Our results offer the first evidence suggesting epigenetic mechanisms may contribute to MAOA dysregulation in antisocial offenders.
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Trastorno de Personalidad Antisocial/genética , Criminales/psicología , Metilación de ADN , Regulación hacia Abajo , Monoaminooxidasa/genética , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Adulto , Trastorno de Personalidad Antisocial/sangre , Estudios de Casos y Controles , Genotipo , Humanos , Masculino , Serotonina/sangre , Adulto JovenRESUMEN
Psychophysiological insomnia is characterized by acquired sleep difficulties and/or a state of hypervigilance when going to bed. This mental and physiological condition prevents sleep onset regardless of the presence of anxious or depressive disorders. Despite the fact that cognitive behavioural therapies have been shown to be effective for this disorder, some people are not responding to this treatment. It is therefore important to explore new ways of increasing the effectiveness of current treatments. Approaches based on mindfulness, which promote a non-judgemental acceptance of the living experience, are increasingly reported in the literature to be effective in the treatment of various physical and psychological health conditions, being particularly efficient in reducing the stress and discomfort associated with these problems. This article focuses on some cognitive factors associated with maintaining insomnia and suggests that approaches based on mindfulness, through certain action mechanisms, may help to improve sleep. A review of recent studies on the application of mindfulness-based approaches to treat insomnia is hereby presented. Avenues for future research to improve insomnia treatment protocols based on mindfulness are suggested.
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Atención Plena , Trastornos Psicofisiológicos/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Atención , Actitud Frente a la Salud , Terapia Cognitivo-Conductual/métodos , Condicionamiento Clásico , Depresión/fisiopatología , Depresión/terapia , Disomnias/psicología , Disomnias/terapia , Humanos , Juicio , Distancia Psicológica , Trastornos Psicofisiológicos/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/psicologíaRESUMEN
BACKGROUND: The major limitation to the success of chemotherapy in osteosarcoma is the development of multidrug resistance (MDR). Preventing the emergence of MDR during chemotherapy treatment has been a high priority of clinical and investigational oncology, but it remains an elusive goal. The NSC23925 has recently been identified as a novel and potent MDR reversal agent. However, whether NSC23925 can prevent the development of MDR in cancer is unknown. Therefore, this study aims to evaluate the effects of NSC23925 on prevention of the development of MDR in osteosarcoma. METHODS: Human osteosarcoma cell lines U-2OS and Saos were exposed to increasing concentrations of paclitaxel alone or in combination with NSC23925 for 6 months. Cell sublines selected at different time points were evaluated for their drug sensitivity, drug transporter P-glycoprotein (Pgp) expression and activity. RESULTS: We observed that tumour cells selected with increasing concentrations of paclitaxel alone developed MDR with resistance to paclitaxel and other Pgp substrates, whereas cells cultured with paclitaxel-NSC23925 did not develop MDR and cells remained sensitive to chemotherapeutic agents. Paclitaxel-resistant cells showed high expression and activity of the Pgp, whereas paclitaxel-NSC23925-treated cells did not express Pgp. No changes in IC50 and Pgp expression and activity were observed in cells grown with the NSC23925 alone. CONCLUSIONS: Our findings suggest that NSC23925 may prevent the development of MDR by specifically preventing the overexpression of Pgp. Given the significant incidence of MDR in osteosarcoma and the lack of effective agents for prevention of MDR, NSC23925 and derivatives hold the potential to improve the outcome of cancer patients with poor prognosis due to drug resistance.
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Neoplasias Óseas/tratamiento farmacológico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Piperidinas/farmacología , Quinolinas/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Paclitaxel/farmacologíaRESUMEN
Psychiatric staff perceptions of aggression by psychiatric patients may affect the therapeutic relationship between care providers and patients in institutions. Attitudes to and the subjective experience of violence may also differ substantially between members of a single care team. This study seeks to validate the French versions of scales of staff attitudes to and subjective experience of institutional violence: a new, modified version of the Overt Aggression Scale (MOAS) to measure the subjective perception of the frequency of aggression in the ward; and the Perception of Aggression Scale (POAS) to assess attitudes to the expression of violence by psychiatric patients. Frontline staff (n = 362) from eight French-language psychiatric institutions in the province of Quebec were surveyed. Factor analyses were performed to determine the validity of the French-language MOAS and POAS. As expected, a four-factor structure emerged for the MOAS. For the 12-item POAS, a three-factor structure was found: (1) 'Aggression as a dysfunctional/undesirable phenomenon'; (2) 'Aggression as a positive expression'; and (3) 'Aggression as a protective measure'. This study supports use of the French MOAS and POAS in assessing staff attitudes to and subjective experience of aggression in future projects to explore the perception and management of inpatient violence.
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Agresión/psicología , Actitud del Personal de Salud , Pacientes Internos/psicología , Enfermería Psiquiátrica/normas , Encuestas y Cuestionarios/normas , Violencia/psicología , Análisis Factorial , Humanos , Psicometría/instrumentación , Quebec , Percepción SocialRESUMEN
BACKGROUND: Paratuberculosis has a worldwide distribution and many countries have implemented control programs to prevent transmission among and within herds. For these programs to be efficient, knowledge of the risk factors involved in transmission is essential. OBJECTIVES: Systematically review the scientific literature concerning risk factors associated with Mycobacterium avium subsp. paratuberculosis (MAP) transmission to dairy calves. STUDY DESIGN: Systematic review. METHODS: An electronic search was done in PubMed and CAB to retrieve references relevant to answer at least 1 of the 5 questions concerning neonatal environment, colostrum, milk, housing of calves, and contact of calves with adult cow feces as risk factors in MAP transmission. A 1st screening was done using titles only, then abstracts, and finally full-length articles were reviewed for relevance. From the articles selected, risk factors and presence of a significant association between these risk factors and MAP transmission were recorded. RESULTS: Twenty-three articles from 11 different countries and published in 12 different journals were reviewed. The most common study design was cross-sectional (n = 16). The case definition and diagnostic tests used were very variable among studies, but serum ELISA was used in most studies (n = 14). The study unit was the herd in 18 studies. CONCLUSIONS AND CLINICAL IMPORTANCE: The contact of calves with adult cow feces is the most important risk factor in MAP transmission. The 5 categories of risk factors are linked to one another.
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Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/transmisión , Mycobacterium avium subsp. paratuberculosis/aislamiento & purificación , Paratuberculosis/microbiología , Paratuberculosis/transmisión , Animales , Animales Recién Nacidos , Bovinos , Factores de RiesgoRESUMEN
The phosphatidylinositol-3-OH kinase (PI3K)-Akt pathway is activated in cancer by genetic or epigenetic events and efforts are under way to develop targeted therapies. phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is the major brake of the pathway and a common target for inactivation in glioblastoma, one of the most aggressive and therapy-resistant cancers. To achieve potent inhibition of the PI3K-Akt pathway in glioblastoma, we need to understand its mechanism of activation by investigating the interplay between its regulators. We show here that PTEN modulates the PI3K-Akt pathway in glioblastoma within a tumor suppressor network that includes Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) and pleckstrin-homology domain leucine-rich repeat protein phosphatases 1 (PHLPP1). The NHERF1 adaptor, previously characterized by our group as a PTEN ligand and regulator, shows also PTEN-independent Akt-modulating effects that led us to identify the PHLPP1/PHLPP2 Akt phosphatases as NHERF1 ligands. NHERF1 interacts via its PDZ domains with PHLPP1/PHLPP2 and scaffolds heterotrimeric complexes with PTEN. Functionally, PHLPP1 requires NHERF1 for membrane localization and growth-suppressive effects. PHLPP1 loss boosts Akt phosphorylation only in PTEN-negative cells and cooperates with PTEN loss for tumor growth. In a panel of low-grade and high-grade glioma patient samples, we show for the first time a significant disruption of all three members of the PTEN-NHERF1-PHLPP1 tumor suppressor network in high-grade tumors, correlating with Akt activation and patient's abysmal survival. We thus propose a PTEN-NHERF1-PHLPP PI3K-Akt pathway inhibitory network that relies on molecular interactions and can undergo parallel synergistic hits in glioblastoma.
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Neoplasias Encefálicas/etiología , Glioblastoma/etiología , Proteínas Nucleares/fisiología , Fosfohidrolasa PTEN/fisiología , Fosfoproteínas Fosfatasas/fisiología , Fosfoproteínas/fisiología , Intercambiadores de Sodio-Hidrógeno/fisiología , Proteínas Supresoras de Tumor/fisiología , Anciano , Humanos , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de SeñalRESUMEN
The genetic structure and the phylogenetic relationships among five Balkan populations of trout Salmo trutta that have been classified earlier into five different taxa were studied, using microsatellite and mitochondrial DNA (mtDNA) analyses. The pattern of population differentiation observed at microsatellites differed to that depicted by mtDNA variation, yet both methods indicated a very strong partitioning of the genetic variation among sampling locations. Results thus suggest that conservation strategies should be directed towards preserving the genetic integrity and uniqueness of each population.
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ADN Mitocondrial/genética , Variación Genética , Repeticiones de Microsatélite/genética , Trucha/genética , AnimalesRESUMEN
Following implantation of a biosensor, adhesion of proteins and cells and eventual fibrous encapsulation will limit analyte diffusion and impair sensor performance. A thermoresponsive nanocomposite hydrogel was developed as a self-cleaning biosensor membrane to minimize the effect of the host response and its utility for an optical glucose sensor, demonstrated here. It was previously reported that thermoresponsive nanocomposite hydrogels prepared from photopolymerization of an aqueous solution of N-isopropylacrylamide (NIPAAm) and polysiloxane colloidal nanoparticles released adhered cells with thermal cycling. However, poly(N-isopropylacrylamide) hydrogels exhibit a volume phase transition temperature (VPTT) of approximately 33-34 degrees C, which is below body temperature. Thus, the hydrogel would be in a collapsed state in vivo, which would ultimately limit diffusion of the target analyte (e.g., glucose) to the encapsulated sensor. In this study, the VPTT of the nanocomposite hydrogel was increased by introducing N-vinylpyrrolidone (NVP) as a comonomer, so that the hydrogel was in the swollen state in vivo. This thermoresponsive nanocomposite hydrogel was prepared by the photopolymerization of an aqueous solution of NIPAAm, NVP, and polysiloxane colloidal nanoparticles. In addition to a VPTT a few degrees above body temperature, the hydrogel also exhibited good mechanical strength, glucose diffusion, and in vitro cell release upon thermal cycling. Thus, this nanocomposite hydrogel may be useful as a biosensor membrane to minimize biofouling and extend the lifetime and efficiency of implantable glucose sensors and other biosensors.
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Técnicas Biosensibles/métodos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Ensayo de Materiales/métodos , Membranas Artificiales , Nanocompuestos/química , Prótesis e Implantes , Temperatura de Transición , Células 3T3 , Animales , Adhesión Celular , Difusión , Módulo de Elasticidad , Glucosa/metabolismo , Cinética , Ratones , Nanocompuestos/ultraestructura , Resistencia a la TracciónRESUMEN
Optimizing wavelength selection for monitoring perfusion during liver transplant requires an in-depth characterization of liver optical properties. With these, the impact of liver absorption and scattering properties can be investigated to select optimal wavelengths for perfusion monitoring. To accomplish this, we are developing a single integrating-sphere-based technique using a unique spatially resolved diffuse reflectance system for multispectral optical properties determination for thick samples. We report early results using a monochromatic source to measure the optical properties of well characterized tissue phantoms made from polystyrene spheres and Trypan blue. The presented results demonstrate the feasibility of using this unique system to measure optical properties of tissue phantoms. We are currently in the process of implementing an automated Levenberg-Marquardt diffuse-reflectance-profile fitting algorithm to enable near realtime robust computation of sample optical properties. Future work will focus on the incorporation of multispectral capability to provide needed data to facilitate development of more realistic liver tissue phantoms.
Asunto(s)
Trasplante de Hígado/instrumentación , Trasplante de Hígado/métodos , Fenómenos Ópticos , Prótesis e Implantes , Animales , Difusión , Hemoglobinas/metabolismo , Hígado/diagnóstico por imagen , Ratones , Oxígeno/metabolismo , Perfusión , Tomografía Computarizada por Rayos XRESUMEN
Following psychiatric deinstitutionalization and changes in involuntary civil commitment laws, many individuals with severe mental disorders have been receiving mental health services through the back door, that is, the criminal justice system. Significant changes to the section of Criminal Code of Canada dealing with individuals with mental disorders have led to significant annual increases in the number of individuals declared Not criminally responsible on account of mental disorder (NCRMD), many of whom are directed to civil psychiatric settings. The goal of the present study was to describe the psychosociocriminological and risk characteristics of individuals found NCRMD remanded to civil psychiatric hospitals (CPH) compared to a forensic psychiatric hospital (FPH). This study was conducted between October 2004 and August 2006 in the sole FPH of the province of Québec and two large CPH in the Montréal metropolitan area. The final sample for the current study consisted of 96 men: 60 from the FPH and 36 from the two CPH. Results indicate that individuals in both settings have similar psychosociocriminal profiles, including PCL-R scores, but that individuals in CPH have higher scores in the Risk subscale of the HCR-20 than do their counterparts in the FPH. This difference is due to a higher score on two items: exposure to destabilizing factors and noncompliance with remediation attempts. Results are discussed in terms of the need for civil psychiatric settings to implement risk assessment and management programs into their services, and the need for further research into forensic mental health services.