Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson\u27s Disease Pathogenesis using Drosophila

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce selective loss of DA neurons is still not known. Notably, dopamine (DA) itself is a chemically labile molecule and can become oxidized to toxic by-products while induce the accumulation of harmful molecules such as Reactive Oxygen Species (ROS). Accordingly, DA toxicity has long been suspected to play a role in selective neuronal loss in PD. Vesicular Monoamine Transporter (VMAT) is essential for proper vesicular storage of monoamines such as DA and their regulated release. Increasing evidence have linked VMAT dysfunction with Parkinson’s disease. In this study, we re-examine the gain- and loss-of-function phenotypes of the sole VMAT homologue in Drosophila. Our results suggest that the C-terminal sequences in the two encoded VMAT isoforms not only determine their differential subcellular localizations, but also their activities in content release. In particular, VMAT2 orthologue potentially poses a unique, previously unexplored activity in promoting DA release. On the other hand, by examining DA distribution in wildtype and VMAT mutant animals, we find that there exists intrinsic difference in the dynamics of intracellular DA handling among DA neurons clustered in different brain regions. Furthermore, loss of VMAT causes severe loss of total DA levels and a redistribution of DA in Drosophila brain. Lastly, removal of both VMAT and another PD gene parkin, which is also conserved in Drosophila, results in the selective loss of DA neurons, primarily in the protocerebral anterior medial (PAM) clusters of the brain. Our results suggest a potential involvement of cytoplasmic DA in selective degeneration of DA neurons and also implicating a role for a differential intracellular DA handling mechanism underlying the regional specificity of neuronal loss in PD patients

THE EXPRESSION PROFILE OF A GWAS DETECTED GENE (NINJ2) IN THE BRAIN OF A MOUSE MODEL OF ISCHEMIC STROKE

Stroke is the third leading cause of death and a major debilitating disease in the United States. Multiple factors, including genetic factors, contribute to the development of the disease. Genome-wide association studies (GWAS) have contributed to the identification of genetic loci influencing risk for complex diseases, such as stroke. In 2010, a GWAS of incident stroke was performed in four large prospective cohorts from the USA and Europe and identified an association of two Single Nucleotide Polymorphisms (SNPs) on chromosome 12p13 with a greater risk of ischemic stroke in individuals of European and African-American ancestry. These SNPs are located 11 Kb upstream of the nerve injury-induced gene 2, Ninjurin2 (NINJ2), suggesting that this gene may be involved in stroke pathogenesis. NINJ2 is a cell adhesion molecule induced in the distal glial cells from a sciatic-nerve injury at 7-days after injury. In an effort to ascribe a possible role of NINJ2 in stroke, we have assessed changes in the level of gene and protein expression of NINJ2 following a time-course from a transiently induced middle cerebral artery ischemic stroke in mice brains. We report an increase in the gene expression of NINJ2 in the ischemic and peri-infarct (ipsilateral) cortical tissues at 7 and 14-days after stroke. We also report an increase in the protein expression of NINJ2 in the cortex of both the ipsilateral and contralateral cortical tissues at the same time-points. We conclude that the expression of NINJ2 is regulated by an ischemic stroke in the cortex and is consistent with NINJ2 being involved in the recovery time-points of stroke

Pay for performance risks discouraging motivated employees

They dislike the effort needed for measuring performance; some change jobs, even at a pay cut, write Antonio Cordella and Tito Cordell

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma

The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens. To this end we first assessed that miR-21-5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly upregulated in 38 urine specimens collected from two independent cohorts of ccRCC patients at the time of surgery compared to healthy donors samples. Of note, miR- 210-3p levels resulted significantly reduced in follow-up samples. These results point to miR-210-3p as a potential non-invasive biomarker useful not only for diagnosis but also for the assessment of complete resection or response to treatment in ccRCC management

Hernia of Foramen of Morgagni in Adult: Case Report of Laparoscopic Repair

The videolaparoscopic repair of a diaphragmatic hernia of Morgagni by external knot tying technique is described. A 69-year-old woman with subocclusive symptoms by intrathoracic migration of abdominal viscera had an immediate and complete postoperative recovery. The hernial sac was not excised. A four-year follow-up shows no hernia recurrence. This case indicated that the laparoscopic approach can be considered a suitable and safe procedure for treatment of Morgagni's hernia

Arco de intrusión de Burstone para la corrección de la mordida profunda. Reporte de caso

Deep overbite is defined as a vertical malocclusion, where there is an increase of the overlap of the upper incisors over the lower incisors, it may be due to supraeruption of the anterior upper teeth, increase of the curve of Spee or a combination of both. We present a case of a 23 years old patient, with a convex profile, increased overbite and retroinclination of the central upper incisors. A Burstone´s intrusion arch was used for simultaneous correction of the supraeruption and retroinclination of the upper incisors, achiving a stable occlusion after two years of follow-up. This case allows to demonstrate the application of biomechanical concepts proposed by Burstone for the treatment of deep bite malocclusion.La mordida profunda se define como una maloclusión vertical, donde existe un incremento del sobrepase vertical de los incisivos superiores sobre los incisivos inferiores, puede deberse a una supraerupción de los dientes anterosuperiores, incremento de la curva de Spee o una combinación de ambos. Se presenta un caso de una paciente de 23 años de edad, con perfil convexo, sobremordida aumentada y retroinclinación de los incisivos centrales superiores. Se empleó el arco de intrusión propuesto por Burstone para la corrección simultanea de la supraerupción y retroinclinación de los incisivos superiores, logrando una oclusión estable tras un seguimiento de dos años. Este caso permitió demostrar la aplicación de los conceptos biomecánicos propuestos por Burstone para el tratamiento de la mordida profunda

Motivations, monitoring technologies, and pay for performance

Monitoring technologies and pay for performance (PFP) contracts are becoming popular solutions to improve public services delivery. Their track record is however mixed. To show why this may be the case, this paper develops a principal agent model where agents’ motivations vary and so the effectiveness of monitoring technologies. In such a set-up, it shows that: (i) monitoring technologies should be introduced only if agents’ motivations are poor; (ii) optimal PFP contracts are non-linear/non-monotonic in agents’ motivations and monitoring effectiveness; (iii) investments aimed at improving agents’ motivations and monitoring quality are substitutes when agents are motivated, complements otherwise; (iv) if the agents’ “type” is private information, the more and less motivated agents could be separated through a menu of PFP/non-PFP contracts, designed in a way that only the less motivated ones choose the PFP

Displasia del desarrollo de cadera, diagnostico, factores asociados y eficacia del tratamiento en menores de 2 años atendidos en el Servicio de Traumatologia del Hospital Manuel Nuñez Butron de Puno en el periodo 2018 a 2019

Objetivo: determinar la validez diagnostica del método del Instituto Internacional de Displasia de Cadera, los factores asociados y la eficacia de los tratamientos no quirúrgicos en Displasia del Desarrollo de Cadera en niños menores de 2 años atendidos en el servicio de Traumatología del Hospital Manuel Núñez Butrón de Puno en el periodo 2018 a 2019. Metodología: el tipo de investigación será retrospectivo, transversal y analítico; será un diseño no experimental epidemiológico de casos y controles; para los casos, no se calculará tamaño de muestra, ingresaran al estudio el total de niños menores de 2 años con el diagnóstico de displasia del desarrollo de cadera, y para los controles, por cada caso se considerará un control, de los niños/as menores de 2 años atendidos en el servicio de crecimiento y desarrollo; para la recolección de datos, se revisarán las historias clínicas de los pacientes y niños/as que ingresaran al estudio, de donde se recogerá la información de las variables, así mismo se revisara las radiografías de los pacientes con displasia del desarrollo de cadera para calcular el índice acetabular; para el análisis estadístico, primero se describirá las variables en estudio, seguidamente se realizará el análisis de la asociación de los factores en estudio con la displasia del desarrollo de cadera, para lo cual se calculará el Odds Ratio (OR), el intervalo de confianza (IC) y el valor de p de Fisher; para considerarse factor asociado debe cumplirse con las tres premisas siguientes, el OR debe ser diferente de 1; el IC no debe contener el 1 y el valor de p debe ser menor de 0.05; luego se realizará la evaluación dela eficacia de los tratamientos no quirúrgicos, para lo cual se calculará el índicede efectividad acumulada (IEA) y el índice de riesgo (RR); para todo el análisisse trabajará con un nivel de confianza del 95%, un error máximo permitido de5% (valor de p=0.05); se utilizará el programa estadístico SPSS versión 21.Trabajo académic

Diseño e implementación de una plataforma Web para la gestión de solicitudes entre tres áreas internas de una empresa operadora de telecomunicaciones en el Perú

La presente tesis tiene por objetivo presentar una alternativa de solución para la comunicación y registro de información entre diferentes áreas dentro de una empresa operadora de telecomunicaciones en el Perú, con el fin de atender las solicitudes de configuración y puesta en marcha de servicios. Dichos servicios están dirigidos a clientes empresariales dentro de una operadora encargada del transporte de datos. La solución planteada busca aprovechar la infraestructura de red interna de la empresa operadora, con el fin de instalar y poner en marcha un servidor que trabaje como punto central de atención y de respaldo de información, para las solicitudes de diversas áreas involucradas en la atención de los pedidos. Asimismo, se genera estadísticas de uso y fechas de análisis por cada usuario.Tesi