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1.
Lett Appl Microbiol ; 74(4): 543-554, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34951701

RESUMEN

The tropical peatlands of southern Brazil are essential for the maintenance of the Atlantic Rain Forest, one of the 25 hotspots of biodiversity in the world. Although diazotrophic micro-organisms are essential for the maintenance of this nitrogen limited ecosystem, so far studies have focused only on micro-organisms involved in the carbon cycle. In this work, peat samples were collected from three tropical peatland regions during dry and rainy seasons and their chemical and microbial characteristics were evaluated. Our results showed that the structure of the diazotrophic communities in the Brazilian tropical peatlands differs in the evaluated seasons. The abundance of the genus Bradyrhizobium showed to be affected by rainfall and peat pH. Despite the shifts of the nitrogen-fixing population in the tropical peatland caused by seasonality it showed to be constantly dominated by α-Proteobacteria followed by Cyanobacteria. In addition, more than 50% of nifH gene sequences have not been classified, indicating the necessity for more studies in tropical peatland, since the reduction of N supply in the peatlands stimulates the recalcitrant organic matter decomposition performed by peatland micro-organisms, influencing the C stock.


Asunto(s)
Bosque Lluvioso , Microbiología del Suelo , Brasil , Ecosistema , Suelo/química
2.
Phys Rev Lett ; 124(14): 140503, 2020 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-32338986

RESUMEN

Entangled pairs of microwave photons are commonly produced in the narrow frequency band of a resonator, which represents a modified vacuum density of states. We generate and investigate the entanglement of a stream of photon pairs, generated in a semi-infinite broadband transmission line, terminated by a superconducting quantum interference device (SQUID). A weak pump signal modulates the SQUID inductance, resulting in a single time-varying boundary condition, and we detect all four quadratures of the microwave radiation emitted at two different frequencies separated by 0.7 GHz. Power calibration is done in situ, and we find positive logarithmic negativity and two-mode squeezing below the vacuum in the observed radiation, indicating entanglement.

3.
Public Health Nutr ; 23(14): 2494-2500, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32456727

RESUMEN

OBJECTIVE: We aimed to assess the validity of maternal recall of exclusive breastfeeding (EBF) at 3 months obtained 12 months after childbirth. DESIGN: A population-based birth cohort study. The gold standard is maternal report of EBF at the age of 3 months (yes or no) and age of introduction of other foods in the infant's diet. EBF was considered when the mother reported that no liquid, semi-solid or solid food was introduced up to that moment. The variable to be validated was obtained at 12 months after childbirth when the mother was asked about the age of food introduction. The prevalence of EBF at 3 months, and sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of 12-month recall with 95 % CI were calculated. SETTING: Pelotas, Brazil. PARTICIPANTS: 3700 mothers of participants of the Pelotas 2004 Birth Cohort. RESULTS: The prevalence of EBF at 3 months was 27·8 % (95 % CI 26·4, 29·3) and 49·0 % (95 % CI 47·4, 50·6) according to gold standard and maternal recall, respectively. The sensitivity of maternal recall at 12 months was 98·3 % (95 % CI 97·4, 99·0), specificity 70·0 % (95 % CI 68·2, 71·7), PPV 55·8 % (95 % CI 53·4, 58·1), NPV 99·1 % (95 % CI 98·6, 99·5) and accuracy 77·9 % (95 % CI 76·6, 79·2). When the analyses were stratified by maternal and infant characteristics, the sensitivity remained around 98 %, and the specificity ranged from 64·4 to 81·8 %. CONCLUSIONS: EBF recalled at the end of the first year of infant's life is a valid measure to be used in epidemiological investigations.


Asunto(s)
Lactancia Materna , Recuerdo Mental , Madres , Brasil , Estudios de Cohortes , Femenino , Humanos , Lactante , Embarazo
4.
Artículo en Inglés | MEDLINE | ID: mdl-33132403

RESUMEN

We present a simple, one-dimensional model of an atom exposed to a time-dependent intense, short-pulse EM field with the objective of teaching undergraduates how to apply various numerical methods to study the behavior of this system as it evolves in time using several time propagation schemes.In this model, the exact Coulomb potential is replaced by a soft-core interaction to avoid the singularity at the origin. While the model has some drawbacks, it has been shown to be a reasonable representation of what occurs in the fully three-dimensional hydrogen atom.The model can be used as a tool to train undergraduate physics majors in the art of computation and software development. PROGRAM SUMMARY: Program Title:: 1d hydrogen light interactionProgram Files doi:: http://dx.doi.org/10.17632/2275fmvdzc.1Code Ocean Capsule:: https://doi.org/10.24433/CO.1476487.v1Licensing provisions:: MIT licenseProgramming language:: FORTRAN90Nature of problem:: The one dimensional time dependent Schrödinger equation has been shown to be quite useful as a model to study the Hydrogen atom exposed to an intense, short pulse, electromagnetic field. We use a model potential that is cut-off near x = 0 and avoids the singularity of the true 1-D potential, but retains the characteristic Rydberg series and continuum to study excitation and ionization of the true H atom. The code employs a number of numerical methods to understand and compare the efficacy and accuracy when applied to this model problem.Solution method:: The program uses and contrasts a number of approaches; the Crank-Nicolson, Short Iterative Lanczos, various incarnations of the split-operator and the Chebychev method have been programmed. These methods have been compared using a 3-point finite difference (FD) discretization of the space coordinate. For completeness, some attention has also been given to using 5-9 FD formulas in order to show how higher order discretization affects the accuracy and efficiency of the methods but the primary focus of the method is the time propagation.Additional comments including restrictions and unusual features:: The main purpose of this code is as a teaching tool for undergraduates interested in acquiring knowledge of numerical methods and programming skills useful to a practicing computational physicist.

5.
Neoplasma ; 66(1): 109-117, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30509096

RESUMEN

Glioblastoma multiforme is a highly invasive and incurable primary brain tumor. The most frequent genetic alteration therein is amplification of the epidermal growth factor receptor (EGFR) gene, the target of current clinical trials. However, EGFR amplification is poorly represented in glioblastoma cell lines. From the 30 cultures attempted herein, we were able to establish two glioblastoma permanent cell lines. The remaining cultures showed limited life span and underwent senescence between passage numbers (PN) 8 to 15. Our newly established glioblastoma cell lines, designated 170-MG-BA and 538-MG-BA, both originated between PN 3 and 5 when areas of smaller, more rapidly proliferating cells appeared. Both cell lines showed similar rates of growth, moderate morphological differences, cytoskeletal heterogeneity and multiple chromosome rearrangements. Analysis by molecular cytogenetics and comparative genomic hybridization (aCGH) revealed two copies of a stable marker chromosome in 170-MG-BA cells effecting focal amplification at 7q11 of the EGFR locus. Comparative RqPCR analysis confirmed that EGFR was uniquely highly expressed in 170-MG-BA cells. Combined targeted expression analysis and aCGH data excluded the recurrent EGFRvIII activating mutation. In contrast, EGFR expression in 538-MG-BA cells which lacked genomic EGFR amplification was not raised. Immunofluorescent staining showed high EGFR protein expression only in the 170-MG-BA cells. Cytogenetic, genomic and transcriptional analyses then confirmed high-level genomic amplification and transcriptional upregulation of wild type EGFR in 170-MG-BA; the first conventional cell line model for investigating the biology and targeted therapy of this key alteration in glioblastoma. Both cell lines are freely available from the DSMZ cell repository.


Asunto(s)
Neoplasias Encefálicas/genética , Amplificación de Genes , Glioblastoma/genética , Línea Celular Tumoral , Hibridación Genómica Comparativa , Receptores ErbB/genética , Humanos
6.
Artículo en Inglés | MEDLINE | ID: mdl-27464353

RESUMEN

The symptom literature in cancer has primarily examined symptom severity, frequency and distress. Assessing cancer patients' perceptions of symptom importance-how important it is for them to see improvement in a symptom following an intervention-and factors influencing these judgments would also inform patient-centred care, but this analysis has not been undertaken. This qualitative study aimed to identify factors underlying perceptions of symptom importance among 25 symptomatic metastatic breast cancer (MBC) patients. Participants were recruited from a cancer centre in the Midwestern USA. Semi-structured interviews focused on patients' rationale for considering common symptoms (i.e., anxiety, sadness, sleep problems, pain or fatigue) to be important. Thematic analyses revealed five interrelated factors underlying MBC patients' perceptions of symptom importance: activity restriction, concentration difficulties, exacerbation of other physical symptoms, symptom-related long-term health concerns and negative impact on their relationships with others. Patients most frequently stated that a physical or psychological symptom was important because of the resulting activity restriction. Additionally, some patients considered pain to be important because it signalled potential long-term health concerns, such as worsening metastatic disease. Findings suggest that clinicians should take into account MBC patients' perceptions of symptom importance and factors underlying these judgments when making shared treatment decisions.


Asunto(s)
Actitud Frente a la Salud , Neoplasias de la Mama/psicología , Actividades Cotidianas , Adulto , Anciano , Ansiedad/etiología , Atención/fisiología , Emociones , Fatiga/etiología , Femenino , Humanos , Relaciones Interpersonales , Persona de Mediana Edad , Medio Oeste de Estados Unidos , Metástasis de la Neoplasia , Dolor/psicología , Percepción
7.
Psychol Med ; 47(15): 2602-2612, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28485257

RESUMEN

BACKGROUND: Most original studies and all meta-analyses conducted to date converge on the conclusion that patients with schizophrenia display rather generalized neurocognitive deficits. For the present study, we reopen this seemingly closed chapter and examine whether important influences, such as lack of motivation and negative attitudes towards cognitive assessment, result in poorer secondary neuropsychological performance. METHOD: A sample of 50 patients with an established diagnosis of schizophrenia were tested for routine neurocognitive assessment and compared to 60 nonclinical volunteers. Before and after the assessment, subjective momentary influences were examined (e.g. motivation, concerns about assessment, fear about poor outcome) for their impact on performance using a new questionnaire called the Momentary Influences, Attitudes and Motivation Impact (MIAMI) on Cognitive Performance Scale. RESULTS: As expected, patients performed significantly worse than controls on all neurocognitive domains tested (large effect size, on average). However, patients also displayed more subjective momentary impairment, as well as more fears about the outcome and less motivation than controls. Mediation analyses indicated that these influences contributed to (secondary) poorer neurocognitive performance. Differences in neurocognitive scores shrank to a medium effect size, on average, when MIAMI scores were accounted for. CONCLUSIONS: The data argue that performance on measures of neurocognition in schizophrenia are to a considerable extent due to secondary factors. Poor motivation, fears and momentary impairments distinguished patients from controls and these variables heavily impacted performance. Before concluding that neurocognitive deficits in psychiatric patients are present, clinicians should take these confounding influences into account. Although patients with schizophrenia achieved, on average, worse test scores than controls, a large subgroup displayed spared performance.


Asunto(s)
Disfunción Cognitiva/fisiopatología , Esquizofrenia/fisiopatología , Adulto , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/complicaciones , Adulto Joven
8.
Biochim Biophys Acta ; 1853(2): 299-307, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25461841

RESUMEN

The tissue micromilieu in disorders (inflammation, ischemia, tumor) often shows pronounced metabolic acidosis that may alter signaling and transcriptional activity in resident cells which can be of special importance for omnipresent fibroblasts. In the present study we investigated the impact of metabolic acidosis on rat fibroblasts with special emphasis on their role in inflammation by regulation of TNF-α, MCP-1, COX-2 and iNOS expression and the signaling pathways involved. Extracellular acidosis led to an enhanced expression of TNF-α, COX-2 and iNOS in parallel to an activation of p38 and ERK1/2 kinases that was not observed by sole intracellular acidosis. Accordingly, the protein amounts of TNF-α and COX-2 as well as the production of nitrate and nitrite were elevated. Acidosis-induced expression of COX-2 and iNOS depended on p38 kinase, but not on ERK1/2. In contrast acidosis-induced TNF-α expression was independent of both kinases. Although GPR4, GPR68 and GPR132 are expressed in fibroblasts, the involvement of these potential candidate pH sensors could be ruled out since no acidosis-induced elevation in intracellular cAMP or free calcium content was observed. Furthermore our data show that MAPK activation by an acidic micromilieu depends on Ser/Thr phosphatase activity, but not on the production of reactive oxygen species and is sensitive to cAMP antagonism by Rp-cAMPS. In conclusion, our results show that an acidic microenvironment induces a differential transcriptional program of pathological relevant genes in fibroblasts via the cAMP-phosphatase-MAPK pathway and thereby generates a parainflammatory situation that can result in tissue remodeling.


Asunto(s)
Acidosis/enzimología , Acidosis/patología , Ácidos/metabolismo , AMP Cíclico/metabolismo , Fibroblastos/enzimología , Fibroblastos/patología , Sistema de Señalización de MAP Quinasas , Acidosis/genética , Animales , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Espacio Intracelular/metabolismo , Modelos Biológicos , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Receptores Acoplados a Proteínas G/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
9.
Pharmacopsychiatry ; 49(1): 18-22, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26629642

RESUMEN

INTRODUCTION: Elevated rest heart rate (RHR) is a known risk factor of cardiovascular diseases. The aim of this study was to analyse the effects of different psychiatric disorders and psychotropic medication on RHR. METHODS: In this retrospective study, medical records of 590 inpatients with a psychiatric disorder (309 men, 281 women, mean age 42.11; SD=13.8 years) were evaluated. RHR, the psychiatric diagnosis according to ICD-10, the psychotropic medication and the use of beta blockers were assessed. RESULTS: The average RHR of all patients was 85.62 beats per minute (bpm) (SD=10.60 bpm) which is, according to the literature and the consensus of experts, to be considered as a relevant elevation of RHR. There was a significant negative correlation between age and RHR. Patients treated with monotherapy or with SSRI showed in the multiple regression analysis significant lower RHR than other subjects, whereas both polytherapy with more antipsychotics and the diagnosis of schizophrenia could be identified as an independent risk factor of elevated RHR (p<0.05, 2-tailed). The presence of hypertonia, diabetes, hypercholesterolemia or obesity has no influence on RHR. 6% of the study population received beta blocker during the hospitalization. DISCUSSION: The elevated RHR in psychiatric patients is a common phenomenon and can be observed independently of the use of psychotropic medication but more in patients with schizophrenia. An interesting additional finding could be a possible protective effect of SSRI on RHR in psychiatric patients.


Asunto(s)
Frecuencia Cardíaca/efectos de los fármacos , Psicotrópicos/efectos adversos , Psicotrópicos/farmacología , Descanso , Adolescente , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Persona de Mediana Edad , Psicotrópicos/uso terapéutico , Análisis de Regresión , Adulto Joven
10.
Appl Opt ; 55(1): 133-9, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26835632

RESUMEN

We propose using a neural network approach in conjunction with digital holographic microscopy in order to rapidly determine relevant parameters such as the core and shell diameter of coated, non-absorbing spheres. We do so without requiring a time-consuming reconstruction of the cell image. In contrast to previous approaches, we are able to obtain a continuous value for parameters such as size, as opposed to binning into a discrete number of categories. Also, we are able to separately determine both core and shell diameter. For simulated particle sizes ranging between 7 and 20 µm, we obtain accuracies of (4.4±0.2)% and (0.74±0.01)% for the core and shell diameter, respectively.


Asunto(s)
Holografía/métodos , Redes Neurales de la Computación , Simulación por Computador , Leucocitos/citología
12.
Adv Exp Med Biol ; 876: 215-220, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26782215

RESUMEN

The tumor microenvironment is characterized by hypoxia, acidosis as well as other metabolic and biochemical alterations. Its role in cancer progression is increasingly appreciated especially on invasive capacity and the formation of metastasis. The effect of acidosis on metastasis formation of two rat carcinoma cell lines was studied in the animal model. In order to analyze the pH dependency of different steps of metastasis formation, invasiveness, cell adhesion and migration of AT-1 prostate cancer cells as well as possible underlying cell signaling pathways were studied in vitro. Acidosis significantly increased the formation of lung metastases of both tumor cell lines in vivo. In vitro, extracellular acidosis neither enhanced invasiveness nor affected cell adhesion to a plastic or to an endothelial layer. However, cellular motility was markedly elevated at pH 6.6 and this effect was sustained even when extracellular pH was switched back to pH 7.4. When analyzing the underlying mechanism, a prominent role of ROS in the induction of migration was observed. Signaling through the MAP kinases ERK1/2 and p38 as well as Src family kinases was not involved. Thus, cancer cells in an acidic microenvironment can acquire enhanced motility, which is sustained even if the tumor cells leave their acidic microenvironment e.g. by entering the blood stream. This increase depended on elevated ROS production and may contribute to the augmented formation of metastases of acidosis-primed tumor cells in vivo.


Asunto(s)
Acidosis/patología , Carcinoma 256 de Walker/patología , Animales , Carcinoma 256 de Walker/metabolismo , Movimiento Celular , Femenino , Concentración de Iones de Hidrógeno , Masculino , Metástasis de la Neoplasia , Ratas , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral
13.
Plant Dis ; 100(11): 2275-2280, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30682914

RESUMEN

In Samochvalovichi, Belarus, apple and pear tree root samples were examined for the presence of phytoplasmas using a universal 16S rDNA-based PCR assay. Out of 27 tested apple trees, 23 were found to be infected by 'Candidatus Phytoplasma mali' and 46 out of 58 pear trees were positive for the presence of 'Ca. P. pyri.' Species were identified by sequence analysis of the 16S rDNA amplicons. The molecular diversity of the phytoplasma isolates was examined by analysis of an hflB gene using single-strand conformation polymorphism (SSCP) and sequence analysis. Therefore hflB gene amplicons from 'Ca. P. mali' and 'Ca. P. pyri' accessions were cloned after amplification. Screening of 640 cloned hflB fragments by SSCP analysis revealed the presence of eight different profiles for 'Ca. P. mali' and 12 different profiles for 'Ca. P. pyri.' The variants were sequenced and compared in multiple alignments. The nucleic acid homology among the hflB gene fragments ranged between 95.4 and 100.0% and 81.3 to 100.0% for 'Ca. P. mali' and 'Ca. P. pyri,' respectively, indicating a high genetic variability within the species. This is the first report on the occurrence of 'Ca. P. mali' and 'Ca. P. pyri' in Belarusian apple and pear trees and their molecular diversity.

14.
Nervenarzt ; 87(5): 488-95, 2016 May.
Artículo en Alemán | MEDLINE | ID: mdl-27056189

RESUMEN

Psychotherapy is an important therapeutic option in the treatment of suicidality. Irrespective of the different treatment settings the psychotherapeutic attitudes, strategies and techniques are presented as they were developed on the basis of cognitive behavioral therapy and psychoanalysis. Starting from the common basic attitude of an active, approachable and for the patient recognizable therapist, the cognitive behavioral attitude is defined by the concept of a "team" involving patient and therapist, which fights against suicidality. The problems that led to suicidal ideation have to be exactly defined and specific behavioral strategies should aim at a modification of the behavioral repertoire and of cognitive strategies. A psychodynamic strategy starting from the analysis of the therapist's inner reaction, the countertransference comes from a primary involvement of both patient and therapist, which the therapist has to recognize and interpret to the patient in a "digestible" way. The experience of an approachable therapist who unexpectedly behaves differently than usual or feared, enables the patient to come to insights and new relational patterns which make suicidal destruction unnecessary. Finally, empirical evidence for the effectiveness of cognitive behavioral and psychodynamic treatment of suicidality is presented.


Asunto(s)
Psicoterapia/métodos , Ideación Suicida , Prevención del Suicidio , Suicidio/psicología , Adulto , Terapia Cognitivo-Conductual/métodos , Femenino , Humanos , Masculino , Teoría Psicoanalítica , Terapia Psicoanalítica/métodos , Psicoterapia Psicodinámica/métodos , Intento de Suicidio/prevención & control , Intento de Suicidio/psicología , Resultado del Tratamiento , Adulto Joven
15.
Nanotechnology ; 26(12): 125706, 2015 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-25742057

RESUMEN

Nanocrystalline diamond (NCD) is a promising material for electronic and mechanical micro- and nanodevices. Here we introduce a versatile pick-up and drop technique that makes it possible to investigate the electrical, optical and mechanical properties of as-grown NCD films. Using this technique, NCD nanosheets, as thin as 55 nm, can be picked-up from a growth substrate and positioned on another substrate. As a proof of concept, electronic devices and mechanical resonators are fabricated and their properties are characterized. In addition, the versatility of the method is further explored by transferring NCD nanosheets onto an optical fiber, which allows measuring its optical absorption. Finally, we show that NCD nanosheets can also be transferred onto two-dimensional crystals, such as MoS2, to fabricate heterostructures. Pick-up and drop transfer enables the fabrication of a variety of NCD-based devices without requiring lithography or wet processing.

16.
Nervenarzt ; 86(9): 1120-9, 2015 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-26315646

RESUMEN

In German psychiatry suicidal behavior is seen as sign of a psychiatric crisis in a person in the context of psychopathology, psychodynamics and psychosocial situation. Psychiatric disorders are found in up to 90% of people who commit suicide and the time span following the decision to commit suicide is often very short, within 24 h. Suicide prevention is a central duty and obligation in psychiatry and psychotherapy. This article gives an overview on the current state of knowledge on suicide from a clinical point of view.


Asunto(s)
Cuidados Críticos/métodos , Servicios Médicos de Urgencia/métodos , Servicios de Urgencia Psiquiátrica/métodos , Obligaciones Morales , Prevención del Suicidio , Suicidio/psicología , Alemania , Humanos
17.
Hum Mol Genet ; 21(8): 1861-76, 2012 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-22246294

RESUMEN

Mitochondrial dysfunction and oxidative stress have been implicated in the etiology of Parkinson's disease. Therefore, pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets. Here, we explore the neuronal response to prolonged overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional regulator of mitochondrial function, both in vitro and in vivo. In neuronal primary cultures from the ventral midbrain, PGC-1α induces mitochondrial biogenesis and increases basal respiration. Over time, we observe an increasing proportion of the oxygen consumed by neurons which are dedicated to adenosine triphosphate production. In parallel to enhanced oxidative phosphorylation, PGC-1α progressively leads to a decrease in mitochondrial polarization. In the adult rat nigrostriatal system, adeno-associated virus (AAV)-mediated overexpression of PGC-1α induces the selective loss of dopaminergic markers and increases dopamine (DA) catabolism, leading to a reduction in striatal DA content. In addition, PGC-1α prevents the labeling of nigral neurons following striatal injection of the fluorogold retrograde tracer. When PGC-1α is expressed at higher levels following intranigral AAV injection, it leads to overt degeneration of dopaminergic neurons. Finally, PGC-1α overexpression does not prevent nigrostriatal degeneration in pathologic conditions induced by α-synuclein overexpression. Overall, we find that lasting overexpression of PGC-1α leads to major alterations in the metabolic activity of neuronal cells which dramatically impair dopaminergic function in vivo. These results highlight the central role of PGC-1α in the function and survival of dopaminergic neurons and the critical need for maintaining physiological levels of PGC-1α activity.


Asunto(s)
Neuronas Dopaminérgicas/fisiología , Sustancia Negra/fisiología , Transactivadores/genética , Transactivadores/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Respiración de la Célula , Supervivencia Celular , Células Cultivadas , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiología , Dependovirus/genética , Dopamina/metabolismo , Neuronas Dopaminérgicas/citología , Femenino , Regulación de la Expresión Génica , Vectores Genéticos , Humanos , Potencial de la Membrana Mitocondrial , Ratones , Mitocondrias/metabolismo , Degeneración Nerviosa , Neuronas/fisiología , Fosforilación Oxidativa , Consumo de Oxígeno , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ratas , Ratas Sprague-Dawley , Sustancia Negra/citología , Factores de Transcripción , alfa-Sinucleína/metabolismo
18.
Br J Cancer ; 111(6): 1241-8, 2014 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-25117820

RESUMEN

BACKGROUND: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. METHODS: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. RESULTS: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 × 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4). CONCLUSIONS: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials.


Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Hipertensión/inducido químicamente , Hipertensión/genética , Glicoproteínas de Membrana/genética , Proteínas del Tejido Nervioso/genética , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab , Biomarcadores , Presión Sanguínea , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple
19.
J Acoust Soc Am ; 136(4): 1797-807, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25324081

RESUMEN

Thresholds for detecting a gap between two complex tones were determined for young listeners with normal hearing and old listeners with mild age-related hearing loss. The leading tonal marker was always a 20-ms, 250-Hz complex tone with energy at 250, 500, 750, and 1000 Hz. The lagging marker, also tonal, could differ from the leading marker with respect to fundamental frequency (f0), the presence versus absence of energy at f0, and the degree to which it overlapped spectrally with the leading marker. All stimuli were presented with steeper (1 ms) and less steep (4 ms) envelope rise and fall times. F0 differences, decreases in the degree of spectral overlap between the markers, and shallower envelope shape all contributed to increases in gap-detection thresholds. Age differences for gap detection of complex sounds were generally small and constant when gap-detection thresholds were measured on a log scale. When comparing the results for complex sounds to thresholds obtained for pure-tones in a previous study by Heinrich and Schneider [(2006). J. Acoust. Soc. Am. 119, 2316-2326], thresholds increased in an orderly fashion from markers with identical (within-channel) pure tones to different (between-channel) pure tones to complex sounds. This pattern of results was true for listeners of both ages although younger listeners had smaller thresholds overall.


Asunto(s)
Envejecimiento/psicología , Umbral Auditivo , Percepción de la Altura Tonal , Presbiacusia/psicología , Detección de Señal Psicológica , Estimulación Acústica , Factores de Edad , Anciano , Audiometría de Tonos Puros , Señales (Psicología) , Femenino , Humanos , Masculino , Presbiacusia/diagnóstico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
20.
Poult Sci ; 93(12): 2970-82, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25260522

RESUMEN

The effect of commercial selection on the growth, efficiency, and yield of broilers was studied using 2 University of Alberta Meat Control strains unselected since 1957 and 1978, and a commercial Ross 308 strain (2005). Mixed-sex chicks (n = 180 per strain) were placed into 4 replicate pens per strain, and grown on a current nutritional program to 56 d of age. Weekly front and side profile photographs of 8 birds per strain were collected. Growth rate, feed intake, and measures of feed efficiency including feed conversion ratio, residual feed intake, and residual maintenance energy requirements were characterized. A nonlinear mixed Gompertz growth model was used to predict BW and BW variation, useful for subsequent stochastic growth simulation. Dissections were conducted on 8 birds per strain semiweekly from 21 to 56 d of age to characterize allometric growth of pectoralis muscles, leg meat, abdominal fat pad, liver, gut, and heart. A novel nonlinear analysis of covariance was used to test the hypothesis that allometric growth patterns have changed as a result of commercial selection pressure. From 1957 to 2005, broiler growth increased by over 400%, with a concurrent 50% reduction in feed conversion ratio, corresponding to a compound annual rate of increase in 42 d live BW of 3.30%. Forty-two-day FCR decreased by 2.55% each year over the same 48-yr period. Pectoralis major growth potential increased, whereas abdominal fat decreased due to genetic selection pressure over the same time period. From 1957 to 2005, pectoralis minor yield at 42 d of age was 30% higher in males and 37% higher in females; pectoralis major yield increased by 79% in males and 85% in females. Over almost 50 yr of commercial quantitative genetic selection pressure, intended beneficial changes have been achieved. Unintended changes such as enhanced sexual dimorphism are likely inconsequential, though musculoskeletal, immune function, and parent stock management challenges may require additional attention in future selection programs.


Asunto(s)
Cruzamiento , Pollos/crecimiento & desarrollo , Pollos/genética , Selección Genética , Tejido Adiposo , Animales , Composición Corporal/genética , Composición Corporal/fisiología , Ingestión de Alimentos , Femenino , Masculino , Aumento de Peso/genética
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