Dynamic Remodeling of the Stressed Heart: Role of Protein Degradation Pathways

The heart is a remarkable organ. In order to maintain its function, it remodels in response to a variety of environmental stresses, including pressure overload, volume overload, mechanical or pharmacological unloading and hormonal or metabolic disturbances. All these responses are linked to the inherent capacity of the heart to rebuild itself. Particularly, cardiac pressure overload activates signaling pathways of both protein synthesis and degradation. While much is known about regulators of protein synthesis, little is known about regulators of protein degradation in hypertrophy. The ubiquitin-proteasome system (UPS) selectively degrades unused and abnormal intracellular proteins. I speculated that the UPS may play an important role in both qualitative and quantitative changes in the composition of heart muscle during hypertrophic remodeling. My study hypothesized that cardiac remodeling in response to hypertrophic stimuli is a dynamic process that requires activation of highly regulated mechanisms of protein degradation as much as it requires protein synthesis. My first aim was to adopt a model of left ventricular hypertrophy and determine its gene expression and structural changes. Male Sprague-Dawley rats were submitted to ascending aortic banding and sacrificed at 7 and 14 days after surgery. Sham operated animals served as controls. Effective aortic banding was confirmed by hemodynamic assessment by Doppler flow measurements in vivo. Banded rats showed a four-fold increase in peak stenotic jet velocities. Histomorphometric analysis revealed a significant increase in myocyte size as well as fibrosis in the banded animals. Transcript analysis showed that banded animals had reverted to the fetal gene program. My second aim was to assess if the UPS is increased and transcriptionally regulated in hypertrophic left ventricular remodeling. Protein extracts from the left ventricles of the banded and control animals were used to perform an in vitro peptidase assay to assess the overall catalytic activity of the UPS. The results showed no difference between hypertrophied and control animals. Transcript analysis revealed decreases in transcript levels of candidate UPS genes in the hypertrophied hearts at 7 days post-banding but not at 14 days. However, protein expression analysis showed no difference at either time point compared to controls. These findings indicate that elements of the UPS are downregulated in the early phase of hypertrophic remodeling and normalizes in a later phase. The results provide evidence in support of a dynamic transcriptional regulation of a major pathway of intracellular protein degradation in the heart. The discrepancy between transcript levels on the one hand and protein levels on the other hand supports post-transcriptional regulation of the UPS pathway in the hypertrophied heart. The exact mechanisms and the functional consequences remain to be elucidated.

Effect of VEGF treatment on the blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced magnetic resonance imaging.

Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

Post-colonial (American?) English Presence on the North-Western Pacific Island of Kosrae: A cross-linguistic analysis of the overlaps and divergences of Kosraean English compared to standard American English

Kosrae is the most remote island of the Federated States of Micronesia (FSM), with a population of less than 7,000 inhabitants, located in the Pacific Ocean between Hawaii and Guam. FSM is an independent sovereign nation consisting of four states in total: Pohnpei, Chuuk, Yap, and Kosrae. Having passed through the hands of Spain, Germany and Japan, the United States gained administrative control of FSM after WWII, as commissioned by the UN. The FSM became an independent nation in 1986 while still retaining affiliation with the US under a ‘Compact of Free Association’. Now both Kosraean and English are considered to be the two official languages and the variety of Kosraean English which has arisen proves for an interesting comparative study. In order to obtain the relevant data, I spent three months on the island of Kosrae, interviewing 90 local speakers, ranging in age (16-70), occupation, sex and time spent off island. The 45 minute long interviews were informal but supported by participant information to capture relevant data and conversations were guided in a way that aimed to reveal language and cultural attitudes. With reference to these samples, I examine the effects of American English on the language use in Kosrae. This paper aims to present a broad analysis of phonological, morphosyntactic and pragmatic features, such as pro-dropping, discourse markers and other practices in order to demonstrate the similarities and differences between the two varieties, which are coming to shape the variety developing on Kosrae. Having transcribed conversations using the tool Elan, I will put particular focus on [h] deletion and insertion, a rare occurrence found in a variety of post-colonial American English which I believe is of particular interest. I assess the presence of English in Kosrae with reference to sociological influences, past and present. First, I discuss the extralinguistic factors which have shaped the English that is currently used on Kosrae, including migration between US and FSM, and English as a language of administration, social media usage and visual media presence. Secondly, I assess the use of English in this community in light of Schneider’s (2007) ‘Dynamic Model’, with reference to America’s contribution as an ‘exploitation colony’ as defined by Mufwene (2001). Finally, an overview of the salient linguistic characteristics of Kosraean English, based on the data collected will be presented and compared to features associated with standard American English in view of examining overlap and divergence. The overall objective is to present a cross-linguistic description of a hitherto unexamined English emerging in a postcolonial environment with a juxtaposed contact variety. Mufwene, Salikoko S. 2001. The ecology of language evolution. Cambridge: Cambridge University Press. Schneider, E. (2007). Postcolonial Englishes. Cambridge: Cambridge University Press. Segal, H.G. (1989) Kosrae, The Sleeping Lady Awakens. Kosrae: Kosrae Tourist Division, Dept. Of Conservation and Development. Keywords: American English, Global English, Pacific English, Morphosyntactic, Phonological, Variation, Discourse

Inflación, transferencias y distribución del ingreso en la Argentina post-convertibilidad : ¿Cómo se gestan y a quiénes benefician?

El trabajo analiza cómo se distribuyen las cargas y beneficios del modelo de acumulación post-convertibilidad, 2002-2007, entre las fracciones de clase. En este sentido exploramos la constitución de un sistema de transferencias de ingresos en el que convergen en un proceso dinámico la inflación, las políticas económicas y las estrategias de acumulación de los agentes económicos. Desde una perspectiva que amplía el modo de abordaje del debate sobre la distribución del ingreso, postulamos la conformación de un sistema de transferencias en base al análisis de dos núcleos vinculados: uno ligado a transferencias operadas a partir de la articulación de políticas económicas y transformaciones estructurales, y otro que es en sí mismo un mecanismo de transferencia de importante relevancia y alcance explicativo: la inflación. La evolución diferencial de los precios afecta la capacidad de apropiación, por los agentes económicos, del ingreso socialmente producido, expresando así cambios en las relaciones de fuerzas

Inflación, transferencias y distribución del ingreso en la Argentina post-convertibilidad : ¿Cómo se gestan y a quiénes benefician?

El trabajo analiza cómo se distribuyen las cargas y beneficios del modelo de acumulación post-convertibilidad, 2002-2007, entre las fracciones de clase. En este sentido exploramos la constitución de un sistema de transferencias de ingresos en el que convergen en un proceso dinámico la inflación, las políticas económicas y las estrategias de acumulación de los agentes económicos. Desde una perspectiva que amplía el modo de abordaje del debate sobre la distribución del ingreso, postulamos la conformación de un sistema de transferencias en base al análisis de dos núcleos vinculados: uno ligado a transferencias operadas a partir de la articulación de políticas económicas y transformaciones estructurales, y otro que es en sí mismo un mecanismo de transferencia de importante relevancia y alcance explicativo: la inflación. La evolución diferencial de los precios afecta la capacidad de apropiación, por los agentes económicos, del ingreso socialmente producido, expresando así cambios en las relaciones de fuerzas

Inflación, transferencias y distribución del ingreso en la Argentina post-convertibilidad : ¿Cómo se gestan y a quiénes benefician?

El trabajo analiza cómo se distribuyen las cargas y beneficios del modelo de acumulación post-convertibilidad, 2002-2007, entre las fracciones de clase. En este sentido exploramos la constitución de un sistema de transferencias de ingresos en el que convergen en un proceso dinámico la inflación, las políticas económicas y las estrategias de acumulación de los agentes económicos. Desde una perspectiva que amplía el modo de abordaje del debate sobre la distribución del ingreso, postulamos la conformación de un sistema de transferencias en base al análisis de dos núcleos vinculados: uno ligado a transferencias operadas a partir de la articulación de políticas económicas y transformaciones estructurales, y otro que es en sí mismo un mecanismo de transferencia de importante relevancia y alcance explicativo: la inflación. La evolución diferencial de los precios afecta la capacidad de apropiación, por los agentes económicos, del ingreso socialmente producido, expresando así cambios en las relaciones de fuerzas

Runtime variability for dynamic reconfiguration in wireless sensor network product lines

Runtime variability is a key technique for the success of Dynamic Software Product Lines (DSPLs), as certain application demand reconfiguration of system features and execution plans at runtime. In this emerging research work we address the problem of dynamic changes in feature models in sensor networks product families, where nodes of the network demand dynamic reconfiguration at post-deployment time.

Visions of the Spanish Revolution: identities and conflicts in post-welfare societies

This is a case study that analyzes photographic documents of the social protest in Spain between 2011 and 2013. The analysis is qualitative and considers the use of space, the visual expression of the messages and the orientation toward the causes or effects of political, economic and social changes. Visual sociology allows us to appreciate, in the case of the Spanish Revolution, a dynamic of “reflexivity” unrecognizable from other research approaches. Two successive waves of social mobilization in response to two different shocks can be appreciated. The first is given by political corruption, unemployment and the threat to consumer society. The second shock is caused by the savage cuts in the Welfare State. Social mobilization is expressed differently in each phase, and the forms taken by the protests show how the class structure in post industrial society shapes the reactions to the crisis of the Welfare State.

Forms and role of the cluster initiatives in fostering innovation in post-industrial regions: A comparative study of environmental clusters in British West Midlands and Spanish Basque country. ACES Working Paper No. 8, August 2008

The objective of this research is to present cluster initiative approaches in post industrial regions characterized by similar economic history and challenges, with additional emphasis on their role in promoting innovation among regional businesses. The research is based on a comparison study of two environmental industry clusters: Environmental Technology Cluster (ET) from British West Midlands and ACLIMA from Spanish Basque Country. The study analyzes clusters' design and their role in fostering innovation based on environment industry clusters. In both regions environmental industry clusters represent strong potential for further dynamic development with grow opportunities driven by legislation introduced at EU, national or regional levels. The paper compares clusters' heterogeneity, goals and priorities, financing schemes, management structure, types of projects, character of private-public partnerships, challenges, as well as clusters' collaboration at regional/national/international levels. Also focus is given on how the clusters enhance innovation and what types of projects are executed by the regions in this field.

Homo Jihadicus. Islam in the former USSR and the phenomenon of the post-Soviet militants in Syria and Iraq. OSW REPORT 2015-09-21

The post-Soviet area, along with the countries of the Middle East, North Africa and Western Europe, have become one of the main global exporters of Islamic militants. Currently on the territory of Syria, and to a lesser extent of Iraq, there are several thousands of foreign fighters from the post-Soviet states. The causes of the war migration from the former USSR states to the Middle East have their roots in the dynamic changes taking place inside Islam in the post-Soviet area: primarily the growth of Salafism and militant Islam, as well as the internationalisation and globalisation of the local Islam. The deep political, economic, social and ideological changes which Muslims underwent after the collapse of the USSR, led to the creation of a specific group within them, for which Islam in its radical form became the main element of their identity. Homo sovieticus, without fully eradicating his Soviet part, became Homo jihadicus who not only identifies himself with the global Ummah, but is also ready to leave his country and join jihad beyond its borders in the name of the professed ideas.

Highly dynamic host actin reorganization around developing Plasmodium inside hepatocytes

Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver.

Essays on the Analysis of Dynamic Games

Thesis (Ph.D.)--University of Washington, 2016-06

Dynamic training volume: A construct of both time under tension and volume load

The purpose of this study was to investigate the effects of three different weight training protocols, that varied in the way training volume was measured, on acute muscular fatigue. Ten resistance-trained males performed all three protocols which involved dynamic constant resistance exercise of the elbow flexors. Protocol A provided a standard for the time the muscle group was under tension (TUT) and volume load (VL), expressed as the product of the total number of repetitions and the load that was lifted. Protocol B involved 40% of the TUT but the same VL compared to protocol A; protocol C was equated with protocol A for TUT but only involved 50% of the VL. Fatigue was assessed by changes in maximum voluntary isometric force and integrated electromyography (iEMG) between the pre- and post-training protocols. The results of the study showed that, when equated for VL, greater TUT produced greater overall muscular fatigue ( p

Dynamic ocular thermography

The ability to measure ocular surface temperature (OST) with thermal imaging offers potential insight into ocular physiology that has been acknowledged in the literature. The TH7102MX thermo-camera (NEC San-ei, Japan) continuously records dynamic information about OST without sacrificing spatial resolution. Using purpose-designed image analysis software, it was possible to select and quantify the principal components of absolute temperature values and the magnitude plus rate of temperature change that followed blinking. The techniques was examined for repeatability, reproducibility and the effects of extrinsic factors: a suitable experimental protocol was thus developed. The precise source of the measured thermal radiation has previously been subject toe dispute: in this thesis, the results of a study examining the relationships between physical parameters of the anterior eye and OST, confirmed a principal role for the tear film in OST. The dynamic changes in OST were studied in a large group of young subjects: quantifying the post-blink changes in temperature with time also established a role for tear flow dynamics in OST. Using dynamic thermography, the effects of hydrogel contact lens wear on OST were investigated: a model eye for in vivo work, and both neophyte and adapted contact lens wearers for in vivo studies. Significantly greater OST was observed in contact lens wearers, particularly with silicone hydrogel lenses compared to etafilcon A, and tended to be greatest when lenses had been worn continuously. This finding is important to understanding the ocular response to contact lens wear. In a group of normal subjects, dynamic thermography appeared to measure the ocular response to the application of artificial tear drops: this may prove to be a significant research and clinical tool.

The effect of contact lens wear on dynamic ocular surface temperature

Aim: To determine the dynamic emitted temperature changes of the anterior eye during and immediately after wearing different materials and modalities of soft contact lenses. Method: A dynamic, non-contact infrared camera (Thermo-Tracer TH7102MX, NEC San-ei) was used to record the ocular surface temperature (OST) in 48 subjects (mean age 21.7 ± 1.9 years) wearing: lotrafilcon-A contact lenses on a daily wear (LDW; n = 8) or continuous wear (LCW; n = 8) basis; balafilcon-A contact lenses on a daily wear (BDW; n = 8) or continuous wear (BCW; n = 8) basis; etafilcon-A contact lenses on a daily disposable regimen (EDW; n = 8); and no lenses (controls; n = 8). OST was measured continuously five times, for 8 s after a blink, following a minimum of 2 h wear and immediately following lens removal. Absolute temperature, changes in temperature post-blink and the dynamics of temperature changes were calculated. Results: OST immediately following contact lens wear was significantly greater compared to non-lens wearers (37.1 ± 1.7 °C versus 35.0 ± 1.1 °C; p < 0.005), predominantly in the LCW group (38.6 ± 1.0 °C; p < 0.0001). Lens surface temperature was highly correlated (r = 0.97) to, but lower than OST (by -0.62 ± 0.3 °C). There was no difference with modality of wear (DW 37.5 ± 1.6 °C versus CW 37.8 ± 1.9 °C; p = 0.63), but significant differences were found between etafilcon A and silicone hydrogel lens materials (35.3 ± 1.1 °C versus 37.5 ± 1.5 °C; p < 0.0005). Ocular surface cooling following a blink was not significantly affected by contact lens wear with (p = 0.07) or without (p = 0.47) lenses in situ. Conclusions: Ocular surface temperature is greater with hydrogel and greater still with silicone hydrogel contact lenses in situ, regardless of modality of wear. The effect is likely to be due to the thermal transmission properties of a contact lens. © 2004 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.