1,380 research outputs found

    Mexican-American Political Participation and California History

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    In this article, Laura Cazares describes her participation in the local politics of East Salinas during the recent recall election. She draws connections between the current state of Mexican-American political participation in California politics and the historical disenfranchisement that they have suffered since statehood. She also analyzes specific policies that have prevented Mexican-American political involvement and proposes ideas for overcoming them. The political project discussed in this pages stems out of a unique college course designed around the concept of Democratic Participation

    MALDI Mass Spectrometry Imaging for the Discovery of Prostate Carcinoma Biomarkers

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    The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision making. To address these questions, and to investigate the potential of MALDI-IMS for the diagnosis of prostate cancer, we have used this approach to analyze prostate tissue for the determination of the cellular origins of different protein signals to improve cancer detection and to identify specific protein markers of PCa. We found that specific protein/peptide expression changes correlated with the presence or absence of prostate cancer as well as the presence of micro-metastatic disease. Additionally, the over-expression of a single peptide (m/z = 4355) was able to accurately define primary cancer tissue from adjacent normal tissue. Tandem mass spectrometry analysis identified this peptide as a fragment of MEKK2, a member of the MAP kinase signaling pathway. Validation of MEKK2 overexpression in moderately differentiated PCa and prostate cancer cell lines was performed using immunohistochemistry and Western Blot analysis. Classification algorithms using specific ions differentially expressed in PCa tissue and a ROC cut-off value for the normalized intensity of the MEKK2 fragment at m/z 4355 were used to classify a blinded validation set. Finally, the optimization of sample processing in a new fixative which preserves macromolecules has led to improved through-put of samples making MALDI-IMS more compatible with current histological applications, facilitating its implementation in a clinical setting. This study highlights the potential of MALDI-IMS to define the molecular events involved in prostate tumorigenesis and demonstrates the applicability of this approach to clinical diagnostics as an aid to pathological decision making in prostate cancer

    Molecular Mechanisms Orchestrating the Dynamics of Secretory Vesicle Pools.

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    The secretion of chemical messengers via Ca2+-dependent exocytosis of vesicles is fundamental to a wide-range of physiological events. Rab GTPases and SNARE proteins govern the temporal and spatial precision of transmitter release. Yet, little is known about their role in specifying the size and filling kinetics of functionally defined vesicle pools, which impact the strength and efficiency of exocytosis. We first sought to delineate the distinct vs. overlapping roles of highly homologous Rab GTPase proteins, Rab3 and Rab27, which display high sequence homology, share protein-effectors, and may functionally compensate. To define their actions, we overexpressed Rab3GAP and/or EPI64A GTPase-activating protein in wild-type or Rab27-null cells to transit the Rab3 family or Rab27A to a GDP-bound inactive state. We found Rab27A is essential for generation of the functionally defined immediately releasable pool, Rab3 is essential for a kinetically rapid filling of the RRP, and both cooperate in populating the readily releasable granule pool (RRP). We conclude that while Rab3 and Rab27A cooperate to generate release-ready vesicles in β-cells, they also direct unique kinetic and functional properties of the exocytotic pathway. We also investigated how the SNARE Tomosyn1 (Tomo1) regulates the partitioning of synaptic vesicle (SV) pools in hippocampal neurons. Tomo1 inhibits SV priming at the plasma membrane. Yet, its localization to SVs and cytosol uniquely positions it to coordinate SV pool partitioning. We that find that Tomo1 controls SV transition between the Resting Pool and Total Recycling Pool (TRP), and modulates the RRP size. Tomo1’s regulation of SV distribution between pools is sensitive to neural activity and requires Cdk5. We provide novel evidence for an interaction between Tomo1 and Rab3A-GTP, and through this with Synapsin1 proteins, known regulators of SV recruitment. In addition, Tomo1 regulatory control over the TRP occurred independent of its C-terminal SNARE domain. Hence, Tomo1 actions on neurotransmission extend beyond its known inhibition of SV priming into the RRP and may involve other effector proteins. Altogether, our results advance the understanding of how Rab and Tomosyn proteins coordinate steps of the vesicle cycle that lead to functional heterogeneity among vesicles and thus may determine modes of transmitter release.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116755/1/vcazares_1.pd

    La mujer en el ejercicio de la justicia indígena. Experiencias de las mujeres kichwa saraguro - Loja

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    Una de las motivaciones de este trabajo está relacionada con la participación de la mujer en la justicia. En este sentido se pretende analizar las relaciones entre dos temas que en el marco de la interculturalidad se vuelven complejos, estos son: género y la participación. Estos conceptos serán tratados considerando siempre el aporte del pueblo Saraguro. Así, identificar cómo se concibe la participación desde las mujeres en sus comunidades resulta relevante, puesto que se reconoce un proceso histórico desde el cual se hace evidente el alcance político de la mujer desde y en la comunidad. Entre los objetivos planteados en esta investigación caben destacar: identificar el momento y los elementos en el cual la participación para las mujeres indígenas se vuelve un tema de derechos; e identificar si la participación desde la experiencia participativa de las mujeres en Saraguro, constituye un aporte a la de-construcción de los parámetros establecidos de participación y de género. Para lograr cumplir con estos objetivos se realiza un análisis respecto a lo que ha significado la participación en el contexto del Estado y la democracia que, junto con una de las propuestas desde la crítica del feminismo de-colonial, invita a una relectura de estos componentes. Vale aclarar que este trabajo, si bien presenta algunas experiencias de mujeres en el ejercicio de la justicia, no pretende ser ni debe entenderse como una generalidad aplicable a otras nacionalidades ni pueblos, precisamente por ser consecuentes con la especificidad histórica de cada uno. La información ha sido obtenida mediante entrevistas e historias de vida, donde el aporte de las personas entrevistadas ha sido de gran valía para la construcción de esta propuesta. Los resultados están organizados en tres capítulos, se inicia con una aproximación y descripción del pueblo Saraguro, continuando con una recopilación de lo que ha significado para este pueblo asumir la justicia como un derecho; posteriormente se analizan los diversos enfoques desde los cuales se discute la participación, y se expone también cómo se construye y entiende la participación desde el pueblo Saraguro; finalmente se exponen los elementos desde los cuales las mujeres construyen su identidad y reivindican desde su experiencia el alcance político de su participación

    Disability Inclusive Transportation: Assessing First Mile Last Mile Conditions in the Richmond Region

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    Accessible public transportation services are vital to promoting a healthy, livable, and thriving region. For people with physical disabilities, the inability to access services and activities can have a harmful impact. A lack of personal mobility may lead to a decreased quality of life and the inability to advocate for one’s rights. Given the region\u27s growing population, as well as increased disability rates, providing accessible public transportation services is crucial. While public transportation services are required to be accessible under Title II of the Americans with Disabilities Act of 1990, supporting infrastructure oftentimes creates additional barriers. For example, poorly maintained sidewalks leading up to designated bus stops contribute to unsafe traveling conditions for people with disabilities. The purpose of the Disability Inclusive Transportation plan is to address these barriers, often referred to as First Mile Last Mile problems, to increase accessibility for individuals with physical impairments (i.e., visual, auditory, or ambulatory). Through a three-step methodology, this plan analyzes the nine localities in the Richmond region to better understand where there is a need for improvements, what barriers look like, and how they impact people with disabilities. This analysis is important for the Richmond region as it is experiencing rapid growth and development. The recommendations provided by this plan can be used to inform how the built environment should be integrated concurrently with development to enable more inclusive transportation systems
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