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1.
Cell ; 174(3): 536-548.e21, 2018 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-29961578

RESUMEN

The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that, in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and they identify a potential treatment for a group of hereditary deafness cases.


Asunto(s)
Sordera/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Empalme Alternativo/genética , Animales , Línea Celular , Exones , Regulación de la Expresión Génica/genética , Células HEK293 , Células Ciliadas Auditivas/fisiología , Audición/genética , Audición/fisiología , Inhibidores de Histona Desacetilasas/metabolismo , Histona Desacetilasas/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Neuronas , Empalme del ARN/genética , Proteínas Represoras/fisiología , Factores de Transcripción , Vorinostat/farmacología
2.
Int J Mol Sci ; 24(9)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37175503

RESUMEN

Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1ß in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased ß-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic ß-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic ß-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.


Asunto(s)
Analgesia , Neuralgia , Ratas , Animales , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , betaendorfina/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Hiperalgesia/terapia , Hiperalgesia/metabolismo , Nervio Ciático/metabolismo , Ganglios Espinales/metabolismo
3.
Brain ; 144(10): 2994-3004, 2021 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-34373901

RESUMEN

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.


Asunto(s)
Dolor Crónico/terapia , Terapia por Estimulación Eléctrica/métodos , Corteza Motora/fisiología , Neuralgia/terapia , Dimensión del Dolor/métodos , Adulto , Anciano , Dolor Crónico/diagnóstico , Dolor Crónico/fisiopatología , Estudios Cruzados , Método Doble Ciego , Electrodos Implantados , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/diagnóstico , Neuralgia/fisiopatología , Método Simple Ciego
4.
J Biol Chem ; 295(45): 15328-15341, 2020 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-32868297

RESUMEN

Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G protein-coupled receptors (GPCRs) function as transducers of external signals by activating associated G proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, although their activities in tooth development remain poorly understood. The present results show that the adhesion GPCR Gpr115 (Adgrf4) is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the in vivo function of Gpr115, knockout (Gpr115-KO) mice were created and found to develop hypomineralized enamel, with a larger acidic area because of the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of Gpr115 disrupted pH homeostasis and ion transport processes in enamel formation. In addition, in vitro analyses using the dental epithelial cell line cervical loop-derived dental epithelial (CLDE) cell demonstrated that Gpr115 is indispensable for the expression of carbonic anhydrase 6 (Car6), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced Car6 expression under the regulation of Gpr115 in CLDE cells. Thus, we concluded that Gpr115 plays an important role in enamel mineralization via regulation of Car6 expression in ameloblasts. The present findings indicate a novel function of Gpr115 in ectodermal organ development and clarify the molecular mechanism of enamel formation.


Asunto(s)
Ameloblastos/metabolismo , Esmalte Dental/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Células Cultivadas , Ratones , Ratones Noqueados , Ratas , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética
5.
Environ Sci Technol ; 54(6): 3278-3287, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-32062974

RESUMEN

Floodplain restoration is popular to address excess nutrients, but its ability to enhance photolysis of emerging contaminants has not been evaluated. We used the numerical model MIKE-21 to simulate photolysis reactions within the inundated surface water of restored floodplains along a mid-size river. We examined both "high" and "low" floodplain scenarios where inundation occurs 5% (storms) and 50% (baseflow) of the year, respectively. We simulated photolysis of the pharmaceuticals morphine, codeine, and methamphetamine and, for context, compared it with nitrate removal (denitrification and plant uptake). Pollutant removal due to floodplain restoration was greater for the low floodplain (e.g., 18.8% for morphine) than for the high floodplain (5.6% for morphine) due to greater water exchange relative to channel flow. The fastest- and slowest-reacting pollutants (morphine and methamphetamine, respectively) were always transport- and reaction/kinetics-limited within floodplain surface water, respectively. Yet, those with intermediate decay-rate constants switched from reaction limitation to transport limitation as the floodplain length increased, and removal leveled off at an optimum length of ∼1000 m. However, as the floodplain width increased, the required floodplain length for 30% removal decreased. Optimal restored floodplain conditions for photolysis would maximize light exposure, which may differ from those for nutrients.


Asunto(s)
Desnitrificación , Ríos , Nitratos , Fotólisis , Agua
6.
Brain ; 142(11): 3592-3604, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31553039

RESUMEN

Deep brain stimulation of the subthalamic nucleus is an effective and established therapy for patients with advanced Parkinson's disease improving quality of life, motor symptoms and non-motor symptoms. However, there is a considerable degree of interindividual variability for these outcomes, likely due to variability in electrode placement and stimulation settings. Here, we present probabilistic mapping data from a prospective, open-label, multicentre, international study to investigate the influence of the location of subthalamic nucleus deep brain stimulation on non-motor symptoms in patients with Parkinson's disease. A total of 91 Parkinson's disease patients undergoing bilateral deep brain stimulation of the subthalamic nucleus were included, and we investigated NMSScale, NMSQuestionnaire, Scales for Outcomes in Parkinson's disease-motor examination, -activities of daily living, and -motor complications, and Parkinson's disease Questionnaire-8 preoperatively and at 6-month follow-up after surgery. Leads were localized in standard space using the Lead-DBS toolbox and individual volumes of tissue activated were calculated based on clinical stimulation settings. Probabilistic stimulation maps and non-parametric permutation statistics were applied to identify voxels with significant above or below average improvement for each scale and analysed using the DISTAL atlas. All outcomes improved significantly at follow-up. Significant spatial distribution patterns of neurostimulation were observed for NMSScale total score and its mood/apathy and attention/memory domains. For both domains, voxels associated with below average improvement were mainly located dorsal to the subthalamic nucleus. In contrast, above average improvement for mood/apathy was observed in the ventral border region of the subthalamic nucleus and in its sensorimotor subregion and for attention/memory in the associative subregion. A trend was observed for NMSScale sleep domain showing voxels with above average improvement located ventral to the subthalamic nucleus. Our study provides evidence that the interindividual variability of mood/apathy, attention/memory, and sleep outcomes after subthalamic nucleus deep brain stimulation depends on the location of neurostimulation. This study highlights the importance of holistic assessments of motor and non-motor aspects of Parkinson's disease to tailor surgical targeting and stimulation parameter settings to patients' personal profiles.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Núcleo Subtalámico , Actividades Cotidianas , Afecto , Anciano , Apatía , Atención , Mapeo Encefálico , Femenino , Humanos , Individualidad , Masculino , Memoria , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Enfermedad de Parkinson/psicología , Estudios Prospectivos , Desempeño Psicomotor , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento
7.
BMC Genomics ; 19(1): 696, 2018 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-30241496

RESUMEN

BACKGROUND: Cell type-specific ribosome-pulldown has become an increasingly popular method for analysis of gene expression. It allows for expression analysis from intact tissues and monitoring of protein synthesis in vivo. However, while its utility has been assessed, technical aspects related to sequencing of these samples, often starting with a smaller amount of RNA, have not been reported. In this study, we evaluated the performance of five library prep protocols for ribosome-associated mRNAs when only 250 pg-4 ng of total RNA are used. RESULTS: We obtained total and RiboTag-IP RNA, in three biological replicates. We compared 5 methods of library preparation for Illumina Next Generation sequencing: NuGEN Ovation RNA-Seq system V2 Kit, TaKaRa SMARTer Stranded Total RNA-Seq Kit, TaKaRa SMART-Seq v4 Ultra Low Input RNA Kit, Illumina TruSeq RNA Library Prep Kit v2 and NEBNext® Ultra™ Directional RNA Library Prep Kit using slightly modified protocols each with 4 ng of total RNA. An additional set of samples was processed using the TruSeq kit with 70 ng, as a 'gold standard' control and the SMART-Seq v4 with 250 pg of total RNA. TruSeq-processed samples had the best metrics overall, with similar results for the 4 ng and 70 ng samples. The results of the SMART-Seq v4 processed samples were similar to TruSeq (Spearman correlation > 0.8) despite using lower amount of input RNA. All RiboTag-IP samples had an increase in the intronic reads compared with the corresponding whole tissue, suggesting that the IP captures some immature mRNAs. The SMARTer-processed samples had a higher representation of ribosomal and non-coding RNAs leading to lower representation of protein coding mRNA. The enrichment or depletion of IP samples compared to corresponding input RNA was similar across all kits except for SMARTer kit. CONCLUSION: RiboTag-seq can be performed successfully with as little as 250 pg of total RNA when using the SMART-Seq v4 kit and 4 ng when using the modified protocols of other library preparation kits. The SMART-Seq v4 and TruSeq kits resulted in the highest quality libraries. RiboTag IP RNA contains some immature transcripts.


Asunto(s)
Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Análisis de Secuencia de ARN/veterinaria , Transcriptoma , Animales , Inmunoprecipitación , Ratones , Control de Calidad , ARN Mensajero/genética , ARN Mensajero/aislamiento & purificación , Ribosomas/genética
8.
J Int Neuropsychol Soc ; 22(4): 412-25, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26831638

RESUMEN

OBJECTIVES: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. METHODS: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. RESULTS: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. CONCLUSIONS: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.


Asunto(s)
Aprendizaje por Asociación/fisiología , Corteza Cerebral/diagnóstico por imagen , Señales (Psicología) , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/patología , Discapacidades para el Aprendizaje/etiología , Sistema Límbico/diagnóstico por imagen , Semántica , Adolescente , Adulto , Anciano , Análisis de Varianza , Mapeo Encefálico , Trastorno Depresivo Mayor/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Discapacidades para el Aprendizaje/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto Joven
9.
Environ Sci Technol ; 50(13): 6830-45, 2016 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-27152660

RESUMEN

While sustainability is an essential concept to ensure the future of humanity and the integrity of the resources and ecosystems on which we depend, identifying a comprehensive yet realistic way to assess and enhance sustainability may be one of the most difficult challenges of our time. We review the primary environmental sustainability assessment approaches, categorizing them as either being design-based or those that employ computational frameworks and/or indicators. We also briefly review approaches used for assessing economic and social sustainability because sustainability necessitates integrating environmental, economic, and social elements. We identify the collective limitations of the existing assessment approaches, showing that there is not a consistent definition of sustainability, that the approaches are generally not comprehensive and are subject to unintended consequences, that there is little to no connection between bottom-up and top-down approaches, and that the field of sustainability is largely fragmented, with a range of academic disciplines and professional organizations pursuing similar goals, but without much formal coordination. We conclude by emphasizing the need for a comprehensive definition of sustainability (that integrates environmental, economic, and social aspects) with a unified system-of-systems approach that is causal, modular, tiered, and scalable, as well as new educational and organizational structures to improve systems-level interdisciplinary integration.


Asunto(s)
Ecosistema , Ambiente , Conservación de los Recursos Naturales , Humanos
10.
J Neuroinflammation ; 12: 10, 2015 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-25600429

RESUMEN

BACKGROUND: Motor cortex stimulation (MCS) is an effective treatment in neuropathic pain refractory to pharmacological management. However, analgesia is not satisfactorily obtained in one third of patients. Given the importance of understanding the mechanisms to overcome therapeutic limitations, we addressed the question: what mechanisms can explain both MCS effectiveness and refractoriness? Considering the crucial role of spinal neuroimmune activation in neuropathic pain pathophysiology, we hypothesized that modulation of spinal astrocyte and microglia activity is one of the mechanisms of action of MCS. METHODS: Rats with peripheral neuropathy (chronic nerve injury model) underwent MCS and were evaluated with a nociceptive test. Following the test, these animals were divided into two groups: MCS-responsive and MCS-refractory. We also evaluated a group of neuropathic rats not stimulated and a group of sham-operated rats. Some assays included rats with peripheral neuropathy that were treated with AM251 (a cannabinoid antagonist/inverse agonist) or saline before MCS. Finally, we performed immunohistochemical analyses of glial cells (microglia and astrocytes), cytokines (TNF-α and IL-1ß), cannabinoid type 2 (CB2), µ-opioid (MOR), and purinergic P2X4 receptors in the dorsal horn of the spinal cord (DHSC). FINDINGS: MCS reversed mechanical hyperalgesia, inhibited astrocyte and microglial activity, decreased proinflammatory cytokine staining, enhanced CB2 staining, and downregulated P2X4 receptors in the DHSC ipsilateral to sciatic injury. Spinal MOR staining was also inhibited upon MCS. Pre-treatment with AM251 blocked the effects of MCS, including the inhibitory mechanism on cells. Finally, MCS-refractory animals showed similar CB2, but higher P2X4 and MOR staining intensity in the DHSC in comparison to MCS-responsive rats. CONCLUSIONS: These results indicate that MCS induces analgesia through a spinal anti-neuroinflammatory effect and the activation of the cannabinoid and opioid systems via descending inhibitory pathways. As a possible explanation for MCS refractoriness, we propose that CB2 activation is compromised, leading to cannabinoid resistance and consequently to the perpetuation of neuroinflammation and opioid inefficacy.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Corteza Motora/fisiología , Mielitis/etiología , Mielitis/terapia , Neuralgia/complicaciones , Análisis de Varianza , Animales , Antiinflamatorios/uso terapéutico , Proteínas de Unión al Calcio/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Hiperalgesia/etiología , Hiperalgesia/terapia , Masculino , Proteínas de Microfilamentos/metabolismo , Corteza Motora/efectos de los fármacos , Neuralgia/patología , Neuralgia/terapia , Neuroglía/metabolismo , Neuroglía/patología , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Piperidinas/efectos adversos , Pirazoles/efectos adversos , Ratas , Receptor Cannabinoide CB2/metabolismo , Receptores Opioides mu/metabolismo , Receptores Purinérgicos P2X4/metabolismo
12.
Epilepsia ; 56(7): 1152-61, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26146753

RESUMEN

OBJECTIVES: The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). METHODS: Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). RESULTS: All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. SIGNIFICANCE: In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts.


Asunto(s)
Agresión/psicología , Estimulación Encefálica Profunda , Hipotálamo Medio/fisiología , Hipotálamo Posterior/fisiología , Convulsiones/psicología , Convulsiones/terapia , Adolescente , Adulto , Agresión/fisiología , Estimulación Encefálica Profunda/tendencias , Epilepsia/complicaciones , Epilepsia/psicología , Epilepsia/terapia , Femenino , Humanos , Masculino , Estudios Retrospectivos , Convulsiones/complicaciones , Resultado del Tratamiento , Adulto Joven
13.
Environ Sci Technol ; 49(22): 13190-8, 2015 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-26463837

RESUMEN

Stream and river restoration activities have recently begun to emphasize the enhancement of biogeochemical processing within river networks through the restoration of river-floodplain connectivity. It is generally accepted that this practice removes pollutants such as nitrogen and phosphorus because the increased contact time of nutrient-rich floodwaters with reactive floodplain sediments. Our study examines this assumption in the floodplain of a recently restored, low-order stream through five seasonal experiments. During each experiment, a floodplain slough was artificially inundated for 3 h. Both the net flux of dissolved nutrients and nitrogen uptake rate were measured during each experiment. The slough was typically a source of dissolved phosphorus and dissolved organic matter, a sink of NO3(-), and variable source/sink of ammonium. NO3(-) uptake rates were relatively high when compared to riverine uptake, especially during the spring and summer experiments. However, when scaled up to the entire 1 km restoration reach with a simple inundation model, less than 0.5-1.5% of the annual NO3(-) load would be removed because of the short duration of river-floodplain connectivity. These results suggest that restoring river-floodplain connectivity is not necessarily an appropriate best management practice for nutrient removal in low-order streams with legacy soil nutrients from past agricultural landuse.


Asunto(s)
Restauración y Remediación Ambiental/métodos , Nitrógeno/análisis , Ríos , Agricultura , Ecosistema , Inundaciones , Nitratos/análisis , Fósforo/análisis , Estaciones del Año , Suelo , Virginia
14.
Int J Geriatr Psychiatry ; 30(11): 1120-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26251013

RESUMEN

OBJECTIVES: Studies have demonstrated an association between major depressive disorder (MDD) symptoms and fall risk in older adults, which may be at least partially mediated by executive functioning skills. There have also been observations of increased gait variability associated with fall risk and disease. This preliminary study first sought to understand whether gait variability in the context of dual task cost differs among older adults with MDD, relative to those with no history of psychiatric illness, and second, to identify relationships between gait variability measures and cognitive functioning in the context of MDD. METHODS: We recruited 15 older adults with MDD and 17 non-depressed (ND) community-dwelling older adults. All participants had impaired balance based on unipedal stance time. Assessments included neuropsychological measures and measures of gait variability using an instrumented gait mat (GAITRite© ) in the context of dual task relative to single task performance (i.e., dual task cost). RESULTS: The groups did not differ on any gait variability parameters. The MDD group demonstrated poorer performance in the psychomotor speed domain, relative to the ND group, but cognitive functioning between the groups in other domains was equivalent. In MDD, increased variability in stride time, stride velocity, and swing time during dual-tasking were associated with poorer executive functioning and visual memory. In ND, no significant relationships between gait variables and cognitive performance were observed. CONCLUSIONS: Findings suggest that unique cognitive mechanisms underlie mobility problems associated with fall risk in late-life depression.


Asunto(s)
Cognición/fisiología , Trastorno Depresivo Mayor/fisiopatología , Marcha/fisiología , Anciano , Anciano de 80 o más Años , Atención/fisiología , Estudios de Casos y Controles , Trastorno Depresivo Mayor/psicología , Femenino , Evaluación Geriátrica , Humanos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Caminata
16.
Int J Geriatr Psychiatry ; 29(11): 1104-15, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24948034

RESUMEN

OBJECTIVE: Verbal memory difficulties are common among individuals with late-life depression (LLD), though there is limited knowledge about disruptions to underlying cerebral circuitry. The purpose of this study is to examine aberrations to cerebral networks implicated in encoding novel verbal semantic material among older adults with LLD. METHODS: Twenty-four older adults with early-onset LLD and 23 non-depressed comparisons participated in the study. Participants completed a word list-learning task while undergoing functional magnetic resonance imaging. RESULTS: In the context of equivalent recall and recognition of words following scanning and similar hippocampal volumes, patients with LLD exhibited less activation in structures known to be relevant for new learning and memory, including hippocampus, parahippocampal gyrus, insula, and cingulate, relative to non-ill comparisons. An important region in which the LLD group displayed greater activation than the non-depressed comparison group was in left inferior frontal gyrus, an area involved in cognitive control and controlled semantic/phonological retrieval and analysis; this region may be critical for LLD patients to consolidate encoded words into memory. CONCLUSIONS: Functional irregularities found in LLD patients may reflect different modes of processing to-be-remembered information and/or early changes predictive of incipient cognitive decline. Future studies might consider mechanisms that could contribute to these functional differences, including hypothalamic-pituitary-adrenal axis functioning and vascular integrity, and utilize longitudinal designs in order to understand whether functional changes are predictive of incipient cognitive decline.


Asunto(s)
Corteza Cerebral/fisiología , Trastorno Depresivo/fisiopatología , Memoria a Corto Plazo/fisiología , Aprendizaje Verbal/fisiología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Recuerdo Mental/fisiología , Persona de Mediana Edad , Semántica
17.
NPJ Parkinsons Dis ; 10(1): 73, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553493

RESUMEN

Pain control after deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level. Pallidal GPi-DBS decreased bodily discomfort and beta-endorphin levels. Unexplained pain by other conditions and bodily discomfort were negatively correlated with beta-endorphin levels. Thus, DBS regulates central opioids, and prioritizing STN is important for PD patients with significant sensory complications.

18.
Am J Hum Genet ; 86(3): 378-88, 2010 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-20170899

RESUMEN

Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic DNA from an affected member of a consanguineous family segregating recessive, nonsyndromic hearing loss was used to make a library of fragments covering the DFNB79 linkage interval defined by genetic analyses of four pedigrees. Homozygosity for eight previously unreported variants in transcribed sequences was detected by evaluating a library of 402,554 sequencing reads and was later confirmed by Sanger sequencing. Of these variants, six were determined to be polymorphisms in the Pakistani population, and one was in a noncoding gene that was subsequently excluded genetically from the DFNB79 linkage interval. The remaining variant was a nonsense mutation in a predicted gene, C9orf75, renamed TPRN. Evaluation of the other three DFNB79-linked families identified three additional frameshift mutations, for a total of four truncating alleles of this gene. Although TPRN is expressed in many tissues, immunolocalization of the protein product in the mouse cochlea shows prominent expression in the taper region of hair cell stereocilia. Consequently, we named the protein taperin.


Asunto(s)
Cromosomas Humanos Par 9/genética , Sordera/genética , Mutación , Proteínas/genética , Alelos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Codón sin Sentido , Consanguinidad , Sordera/metabolismo , Femenino , Mutación del Sistema de Lectura , Genes Recesivos , Células Ciliadas Auditivas/metabolismo , Humanos , Inmunohistoquímica , Masculino , Ratones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Pakistán , Linaje , Polimorfismo de Nucleótido Simple , Proteínas/metabolismo , Distribución Tisular
19.
Environ Sci Technol ; 47(15): 8083-90, 2013 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-23713687

RESUMEN

Environmental sustainability assessment is a rapidly growing field where measures of sustainability are used within an assessment framework to evaluate and compare alternative actions. Here we argue for the importance of evaluating environmental sustainability of water at the watershed scale. We review existing frameworks in brief before reviewing watershed-relevant measures in more detail. While existing measures are diverse, overlapping, and interdependent, certain attributes that are important for watersheds are poorly represented, including spatial explicitness and the effect of natural watershed components, such as rivers. Most studies focus on one or a few measures, but a complete assessment will require use of many existing measures, as well as, perhaps, new ones. Increased awareness of the broad dimensions of environmental sustainability as applied to water management should encourage integration of existing approaches into a unified assessment framework appropriate for watersheds.


Asunto(s)
Conservación de los Recursos Naturales , Agua Dulce , Ríos
20.
ACS Omega ; 8(43): 40321-40340, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37929091

RESUMEN

In three-phase gravity separators used in gas and oil production, foaming can occur by either depressurization or injection of gas in the equipment. This formed foam can be harmful, causing various problems such as liquid carry-over, gas carry-under, decreased capacity, and difficulty in level measurement. The mechanism of foam formation by gas injection in separators motivated the present study. Thus, this work proposes the analysis of the influence of certain physical-chemical parameters such as temperature (20-40 °C), pressure (1-10 bar), and types of gases (nitrogen and methane) on the formation of the column and stability of the foam formed, in ISO14 mineral oil + sodium laureth sulfate + water, through gas injection in separator conditions. To carry out this analysis, an experimental apparatus was designed and assembled consisting of a transparent foam formation cell of 0.5 m height and 5 cm internal diameter. Parameters such as foamability, foaminess, and the collapse curve were also evaluated to characterize the foam formed. In addition, simplified models of foam formation and decay by gas injection were proposed based on models already available in the literature, which were validated with the experimentally obtained results. The experimental results showed good agreement when compared to the literature, referring to the behavior of temperature (higher temperature, lower stability), pressure (higher pressure, higher stability), and type of injected gas (dependency on solubility). In addition, maximum errors of 26% (in height) and 11% (decay phase) were obtained for the formation and decay models, respectively.

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