502 resultados para Expansions


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Oxygen isotope records show a major climatic reversal at 8.2 ka in Greenland and Europe. Annually laminated sediments from two lakes in Switzerland and Germany were sampled contiguously to assess the response of European vegetation to climate change ca. 8.2 ka with time resolution and precision comparable to those of the Greenland ice cores. The pollen assemblages show pronounced and immediate responses (0–20 yr) of terrestrial vegetation to the climatic change at 8.2 ka. A sudden collapse of Corylus avellana (hazel) was accompanied by the rapid expansion of Pinus (pine), Betula (birch), and Tilia (linden), and by the invasion of Fagus silvatica (beech) and Abies alba (fir). Vegetational changes suggest that climatic cooling reduced drought stress, allowing more drought-sensitive and taller growing species to out-compete Corylus avellana by forming denser forest canopies. Climate cooling at 8.2 ka and the immediate reorganization of terrestrial ecosystems has gone unrecognized by previous pollen studies. On the basis of our data we conclude that the early Holocene high abundance of C. avellana in Europe was climatically caused, and we question the conventional opinion that postglacial expansions of F. silvatica and A. alba were controlled by low migration rates rather than by climate. The close connection between climatic change and vegetational response at a subcontinental scale implies that forecasted global warming may trigger rapid collapses, expansions, and invasions of tree species.

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The Out-of-Africa (OOA) dispersal ∼50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

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Expanding populations incur a mutation burden – the so-called expansion load. Previous studies of expansion load have focused on codominant mutations. An important consequence of this assumption is that expansion load stems exclusively from the accumulation of new mutations occurring in individuals living at the wave front. Using individual-based simulations, we study here the dynamics of standing genetic variation at the front of expansions, and its consequences on mean fitness if mutations are recessive. We find that deleterious genetic diversity is quickly lost at the front of the expansion, but the loss of deleterious mutations at some loci is compensated by an increase of their frequencies at other loci. The frequency of deleterious homozygotes therefore increases along the expansion axis, whereas the average number of deleterious mutations per individual remains nearly constant across the species range. This reveals two important differences to codominant models: (i) mean fitness at the front of the expansion drops much faster if mutations are recessive, and (ii) mutation load can increase during the expansion even if the total number of deleterious mutations per individual remains constant. We use our model to make predictions about the shape of the site frequency spectrum at the front of range expansion, and about correlations between heterozygosity and fitness in different parts of the species range. Importantly, these predictions provide opportunities to empirically validate our theoretical results. We discuss our findings in the light of recent results on the distribution of deleterious genetic variation across human populations and link them to empirical results on the correlation of heterozygosity and fitness found in many natural range expansions.

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Hexanucleotide repeat expansions in the C9ORF72 gene are causally associated with frontotemporal lobar dementia (FTLD) and/or amyotrophic lateral sclerosis (ALS). The physiological function of the normal C9ORF72 protein remains unclear. In this study, we characterized the subcellular localization of C9ORF72 to processing bodies (P-bodies) and its recruitment to stress granules (SGs) upon stress-related stimuli. Gain of function and loss of function experiments revealed that the long isoform of C9ORF72 protein regulates SG assembly. CRISPR/Cas9-mediated knockdown of C9ORF72 completely abolished SG formation, negatively impacted the expression of SG-associated proteins such as TIA-1 and HuR, and accelerated cell death. Loss of C9ORF72 expression further compromised cellular recovery responses after the removal of stress. Additionally, mimicking the pathogenic condition via the expression of hexanucleotide expansion upstream of C9ORF72 impaired the expression of the C9ORF72 protein, caused an abnormal accumulation of RNA foci, and led to the spontaneous formation of SGs. Our study identifies a novel function for normal C9ORF72 in SG assembly and sheds light into how the mutant expansions might impair SG formation and cellular-stress-related adaptive responses.

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A small, but growing, body of literature searches for evidence of non-Keynesian effects of fiscal contractions. That is, some evidence exists that large fiscal contractions stimulate short-run economic activity. Our paper continues this research effort by systematically examining the effects, if any, of unusual fiscal events - either non-Keynesian results within a Keynesian model or Keynesian results within a neoclassical model -- on short-run economic activity. We examine this issue within three separate models -- a St. Louis equation, a Hall-type consumption equation, and a growth accounting equation. Our empirical findings are mixed, and do not provide strong systematic support for the view that unusually large fiscal contractions/expansions reverse the effects of normal fiscal events. Moreover, we find only limited evidence that trigger points are empirically important.

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Standard macroeconomic models that assume an exogenous stochastic process for multifactor productivity offer the interpretation that recessions are the result of ''bad news'' (technological regress) and expansions are the result of ''good news'' (technological advancement). The view taken here is that both expansions and recessions are the result of ''good news'' in the sense that in both cases, aggregate production possibilities have increased. Recessions can be thought of as the transition from one technological frontier to the next.

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The molecular mechanisms responsible for the expansion and deletion of trinucleotide repeat sequences (TRS) are the focus of our studies. Several hereditary neurological diseases including Huntington's disease, myotonic dystrophy, and fragile X syndrome are associated with the instability of TRS. Using the well defined and controllable model system of Escherichia coli, the influences of three types of DNA incisions on genetic instability of CTG•CAG repeats were studied: DNA double-strand breaks (DSB), single-strand nicks, and single-strand gaps. The DNA incisions were generated in pUC19 derivatives by in vitro cleavage with restriction endonucleases. The cleaved DNA was then transformed into E. coli parental and mutant strains. Double-strand breaks induced deletions throughout the TRS region in an orientation dependent manner relative to the origin of replication. The extent of instability was enhanced by the repeat length and sequence (CTG•CAG vs. CGG•CCG). Mutations in recA and recBC increased deletions, mutations in recF stabilized the TRS, whereas mutations in ruvA had no effect. DSB were repaired by intramolecular recombination, versus an intermolecular gene conversion or crossover mechanism. 30 nt gaps formed a distinct 30 nt deletion product, whereas single strand nicks and gaps of 15 nts did not induce expansions or deletions. Formation of this deletion product required the CTG•CAG repeats to be present in the single-stranded region and was stimulated by E. coli DNA ligase, but was not dependent upon the RecFOR pathway. Models are presented to explain the DSB induced instabilities and formation of the 30 nucleotide deletion product. In addition to the in vitro creation of DSBs, several attempts to generate this incision in vivo with the use of EcoR I restriction modification systems were conducted. ^

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There are many diseases associated with the expansion of DNA repeats in humans. Myotonic dystrophy type 2 is one of such diseases, characterized by expansions of a (CCTG)•(CAGG) repeat tract in intron 1 of zinc finger protein 9 (ZNF9) in chromosome 3q21.3. The DM2 repeat tract contains a flanking region 5' to the tract that consists of a polymorphic repetitive sequence (TG)14-25(TCTG)4-11(CCTG) n. The (CCTG)•(CAGG) repeat is typically 11-26 repeats in persons without the disease, but can expand up to 11,000 repeats in affected individuals, which is the largest expansion seen in DNA repeat diseases to date. This DNA tract remains one of the least characterized disease-associated DNA repeats, and mechanisms causing the repeat expansion in humans have yet to be elucidated. Alternative, non B-DNA structures formed by the expanded repeats are typical in DNA repeat expansion diseases. These sequences may promote instability of the repeat tracts. I determined that slipped strand structure formation occurs for (CCTG)•(CAGG) repeats at a length of 42 or more. In addition, Z-DNA structure forms in the flanking human sequence adjacent to the (CCTG)•(CAGG) repeat tract. I have also performed genetic assays in E. coli cells and results indicate that the (CCTG)•(CAGG) repeats are more similar to the highly unstable (CTG)•(CAG) repeat tracts seen in Huntington's disease and myotonic dystrophy type 1, than to those of the more stable (ATTCT)•(AGAAT) repeat tracts of spinocerebellar ataxia type 10. This instability, however, is RecA-independent in the (CCTG)•(CAGG) and (ATTCT)•(AGAAT) repeats, whereas the instability is RecA-dependent in the (CTG)•(CAG) repeats. Structural studies of the (CCTG)•(CAGG) repeat tract and the flanking sequence, as well as genetic selection assays may reveal the mechanisms responsible for the repeat instability in E. coli, and this may lead to a better understanding of the mechanisms contributing to the human disease state. ^

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Preventable Hospitalizations (PHs) are hospitalizations that can be avoided with appropriate and timely care in the ambulatory setting and hence are closely associated with primary care access in a community. Increased primary care availability and health insurance coverage may increase primary care access, and consequently may be significantly associated with risks and costs of PHs. Objective. To estimate the risk and cost of preventable hospitalizations (PHs); to determine the association of primary care availability and health insurance coverage with the risk and costs of PHs, first alone and then simultaneously; and finally, to estimate the impact of expansions in primary care availability and health insurance coverage on the burden of PHs among non-elderly adult residents of Harris County. Methods. The study population was residents of Harris County, age 18 to 64, who had at least one hospital discharge in a Texas hospital in 2008. The primary independent variables were availability of primary care physicians, availability of primary care safety net clinics and health insurance coverage. The primary dependent variables were PHs and associated hospitalization costs. The Texas Health Care Information Collection (THCIC) Inpatient Discharge data was used to obtain information on the number and costs of PHs in the study population. Risk of PHs in the study population, as well as average and total costs of PHs were calculated. Multivariable logistic regression models and two-step Heckman regression models with log-transformed costs were used to determine the association of primary care availability and health insurance coverage with the risk and costs of PHs respectively, while controlling for individual predisposing, enabling and need characteristics. Predicted PH risk and cost were used to calculate the predicted burden of PHs in the study population and the impact of expansions in primary care availability and health insurance coverage on the predicted burden. Results. In 2008, hospitalized non-elderly adults in Harris County had 11,313 PHs and a corresponding PH risk of 8.02%. Congestive heart failure was the most common PH. PHs imposed a total economic burden of $84 billion at an average of $7,449 per PH. Higher primary care safety net availability was significantly associated with the lower risk of PHs in the final risk model, but only in the uninsured. A unit increase in safety net availability led to a 23% decline in PH odds in the uninsured, compared to only a 4% decline in the insured. Higher primary care physician availability was associated with increased PH costs in the final cost model (β=0.0020; p<0.05). Lack of health insurance coverage increased the risk of PH, with the uninsured having 30% higher odds of PHs (OR=1.299; p<0.05), but reduced the cost of a PH by 7% (β=-0.0668; p<0.05). Expansions in primary care availability and health insurance coverage were associated with a reduction of about $1.6 million in PH burden at the highest level of expansion. Conclusions. Availability of primary care resources and health insurance coverage in hospitalized non-elderly adults in Harris County are significantly associated with the risk and costs of PHs. Expansions in these primary care access factors can be expected to produce significant reductions in the burden of PHs in Harris County.^

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Primary motor cortex (M1) is involved in the production of voluntary movement and contains a complete functional representation, or map, of the skeletal musculature. This functional map can be altered by pathological experiences, such as peripheral nerve injury or stroke, by pharmacological manipulation, and by behavioral experience. The process by which experience-dependent alterations of cortical function occur is termed plasticity. In this thesis, plasticity of M1 functional organization as a consequence of behavioral experience was examined in adult primates (squirrel monkeys). Maps of movement representations were derived under anesthesia using intracortical microstimulation, whereby a microelectrode was inserted into the cortex to electrically stimulate corticospinal neurons at low current levels and evoke movements of the forelimb, principally of the hand. Movement representations were examined before and at several times after training on behavioral tasks that emphasized use of the fingers. Two behavioral tasks were utilized that dissociated the repetition of motor activity from the acquisition of motor skills. One task was easy to perform, and as such promoted repetitive motor activity without learning. The other task was more difficult, requiring the acquisition of motor skills for successful performance. Kinematic analysis indicated that monkeys used a consistent set of forelimb movements during pellet extractions. Functional mapping revealed that repetitive motor activity during the easier task did not produce plastic changes in movement representations. Instead, map plasticity, in the form of selective expansions of task-related movement representations, was only produced following skill acquisition on the difficult task. Additional studies revealed that, in general, map plasticity persisted without further training for up to three months, in parallel with the retention of task-related motor skills. Also, extensive additional training on the small well task produced further improvements in performance, and further changes in movement maps. In sum, these experiments support the following three conclusions regarding the role of M1 in motor learning. First, behaviorally-driven plasticity is learning-dependent, not activity-dependent. Second, plastic changes in M1 functional representations represent a neural correlate of acquired motor skills. Third, the persistence of map plasticity suggests that M1 is part of the neural substrate for the memory of motor skills. ^

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A knowledge of rock stress is fundamental for improving our understanding of oceanic crustal mechanisms and lithospheric dynamic processes. However, direct measurements of stress in the deep oceans, and in particular stress magnitudes, have proved to be technically difficult. Anelastic strain recovery measurements were conducted on 15 basalt core samples from Sites 765 and 766 during Leg 123. Three sets of experiments were performed: anelastic strain recovery monitoring, dynamic elastic property measurements, and thermal azimuthal anisotropy observations. In addition, a range of other tests and observations were recorded to characterize each of the samples. One common feature of the experimental results and observations is that apparently no consistent orientation trend exists, either between the different measurements on each core sample or between the same sets of measurements on the various core samples. However, some evidence of correspondence between velocity anisotropy and anelastic strain recovery exists, but this is not consistent for all the core samples investigated. Thermal azimuthal anisotropy observations, although showing no conclusive correlations with the other results, were of significant interest in that they clearly exhibited anisotropic behavior. The apparent reproducibility of this behavior may point toward the possibility of rocks that retain a "memory" of their stress history, which could be exploited to derive stress orientations from archived core. Anelastic strain recovery is a relatively new technique. Because use of the method has extended to a wider range of rock types, the literature has begun to include examples of rocks that contracted with time. Strong circumstantial evidence exists to suggest that core-sample contractions result from the slow diffusion of pore fluids from a preexisting microcrack structure that permits the rock to deflate at a greater rate than the expansion caused by anelastic strain recovery. Both expansions and contractions of the Leg 123 cores were observed. The basalt cores have clearly been intersected by an abundance of preexisting fractures, some of which pass right through the samples, but many are intercepted or terminate within the rock matrix. Thus, the behavior of the core samples will be influenced not only by the properties of the rock matrix between the fractures, but also by how these macro- and micro-scale fractures mutually interact. The strain-recovery curves recorded during Leg 123 for each of the 15 basalt core samples may reflect the result of two competing time dependent processes: anelastic strain recovery and pore pressure recovery. Were these the only two processes to influence the gauge responses, then one might expect that given the additional information required, established theoretical models might be used to determine consistent stress orientations and reliable stress magnitudes. However, superimposed upon these competing processes is their respective interaction with the preexisting fractures that intersect each core. Evidence from our experiments and observations suggests that these fractures have a dominating influence on the characteristics of the recovery curves and that their effects are complex.

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Detailed analyses of the Lake Van pollen, Ca/K ratio and stable oxygen isotope record allow the identification of millennial-scale vegetation and environmental changes in eastern Anatolia throughout the last glacial (~75-15 ka BP). The climate within the last glacial was cold and dry, with low arboreal pollen (AP) levels. The driest and coldest period corresponds to Marine Isotope Stage (MIS) 2 (~28-14.5 ka BP) dominated by the highest values of xerophytic steppe vegetation. Our high-resolution multi proxy record shows rapid expansions and contractions of tree populations that reflects variability in temperature and moisture availability. This rapid vegetation and environmental changes can be linked to the stadial-interstadial pattern of the Dansgaard-Oeschger (DO) events as recorded in the Greenland ice cores. Periods of reduced moisture availability were characterized by enhanced xerophytic species and high terrigenous input from the Lake Van catchment area. Furthermore, comparison with the marine realm reveals that the complex atmosphere-ocean interaction can be explained by the strength and position of the westerlies, which is responsible for the supply of humidity in eastern Anatolia. Influenced by diverse topography of the Lake Van catchment, larger DO interstadials (e.g. DO 19, 17-16, 14, 12 and 8) show the highest expansion of temperate species within the last glacial. However, Heinrich events (HE), characterized by highest concentrations of ice-rafted debris (IRD) in marine sediments, are identified in eastern Anatolia by AP values not lower and high steppe components not more abundant than during DO stadials. In addition, this work is a first attempt to establish a continuous microscopic charcoal record over the last glacial in the Near East, which documents an initial immediate response to millennial-scale climate and environmental variability and enables us to shed light on the history of fire activity during the last glacial.

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En el presente trabajo buscamos contextualizar la situación del sector hidroeléctrico en América Latina, los principales argumentos que se presentan por parte de diferentes actores para la implementación de estos proyectos y la realidad que esto ofrece para las economías locales impactadas. En primer lugar, se presenta la configuración en América Latina de las principales iniciativas de expansión del sector eléctrico, reflejada en la acción de empresas y gobiernos en esta región. Posteriormente, se delimita el artículo a partir del estudio de caso de la hidroeléctrica El Quimbo en Colombia, que muestra la forma de acción del Estado colombiano al impulsar estos proyectos de expansión. Dentro de los procedimientos legales para la implementación de estos proyectos, guarda especial importancia el análisis de la Licencia Ambiental, que refleja en su proceso de concesión diferentes disputas entre los actores relacionados: la empresa Endesa-Enel, los afectados que constituyen diferentes grupos, las diferentes instituciones del Estado y el movimiento social. Metodológicamente, el estudio se basa en una serie de autores que buscan rescatar las contradicciones y los intereses de los afectados por la implementación de este tipo de proyectos (Sigaud 1992, 1995, Vianna 2009, Borralho, 1988) a partir de una muestra de argumentación cualitativa. De este modo, el estudio se sustentó en una revisión bibliográfica y de prensa sobre el funcionamiento de la expansión eléctrica en América Latina y posteriormente sobre el contexto colombiano a partir de sus proyectos de expansión hidroeléctrica y la legislación acerca del funcionamiento de la Licencia Ambiental en este país. Finalmente, se sitúa en el caso concreto de El Quimbo, donde se realizaron diversos trabajos de campo con campesinos localizados en el área de afectación y se recolectó material de prensa y material emitido tanto por Emgesa como por la Asociación de Afectados por la hidroeléctrica El Quimbo-Asoquimbo. El trabajo investigativo refleja el panorama sobre la expansión de grandes proyectos de infraestructura y el consenso que existe sobre su implementación tanto por el sector privado como por los gobiernos nacionales, materializados a través de marcos legales del Estado y figuras como las licencias ambientales. A partir de este caso, se muestra cómo estas decisiones del Estado generan cambios en las condiciones previas de vida de poblaciones rurales, que reaccionan a partir de protestas y de la conformación de grupos con diferentes intereses y tiempos de resistencia y negociación.

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En el presente trabajo buscamos contextualizar la situación del sector hidroeléctrico en América Latina, los principales argumentos que se presentan por parte de diferentes actores para la implementación de estos proyectos y la realidad que esto ofrece para las economías locales impactadas. En primer lugar, se presenta la configuración en América Latina de las principales iniciativas de expansión del sector eléctrico, reflejada en la acción de empresas y gobiernos en esta región. Posteriormente, se delimita el artículo a partir del estudio de caso de la hidroeléctrica El Quimbo en Colombia, que muestra la forma de acción del Estado colombiano al impulsar estos proyectos de expansión. Dentro de los procedimientos legales para la implementación de estos proyectos, guarda especial importancia el análisis de la Licencia Ambiental, que refleja en su proceso de concesión diferentes disputas entre los actores relacionados: la empresa Endesa-Enel, los afectados que constituyen diferentes grupos, las diferentes instituciones del Estado y el movimiento social. Metodológicamente, el estudio se basa en una serie de autores que buscan rescatar las contradicciones y los intereses de los afectados por la implementación de este tipo de proyectos (Sigaud 1992, 1995, Vianna 2009, Borralho, 1988) a partir de una muestra de argumentación cualitativa. De este modo, el estudio se sustentó en una revisión bibliográfica y de prensa sobre el funcionamiento de la expansión eléctrica en América Latina y posteriormente sobre el contexto colombiano a partir de sus proyectos de expansión hidroeléctrica y la legislación acerca del funcionamiento de la Licencia Ambiental en este país. Finalmente, se sitúa en el caso concreto de El Quimbo, donde se realizaron diversos trabajos de campo con campesinos localizados en el área de afectación y se recolectó material de prensa y material emitido tanto por Emgesa como por la Asociación de Afectados por la hidroeléctrica El Quimbo-Asoquimbo.

El trabajo investigativo refleja el panorama sobre la expansión de grandes proyectos de infraestructura y el consenso que existe sobre su implementación tanto por el sector privado como por los gobiernos nacionales, materializados a través de marcos legales del Estado y figuras como las licencias ambientales. A partir de este caso, se muestra cómo estas decisiones del Estado generan cambios en las condiciones previas de vida de poblaciones rurales, que reaccionan a partir de protestas y de la conformación de grupos con diferentes intereses y tiempos de resistencia y negociación.

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En el presente trabajo buscamos contextualizar la situación del sector hidroeléctrico en América Latina, los principales argumentos que se presentan por parte de diferentes actores para la implementación de estos proyectos y la realidad que esto ofrece para las economías locales impactadas. En primer lugar, se presenta la configuración en América Latina de las principales iniciativas de expansión del sector eléctrico, reflejada en la acción de empresas y gobiernos en esta región. Posteriormente, se delimita el artículo a partir del estudio de caso de la hidroeléctrica El Quimbo en Colombia, que muestra la forma de acción del Estado colombiano al impulsar estos proyectos de expansión. Dentro de los procedimientos legales para la implementación de estos proyectos, guarda especial importancia el análisis de la Licencia Ambiental, que refleja en su proceso de concesión diferentes disputas entre los actores relacionados: la empresa Endesa-Enel, los afectados que constituyen diferentes grupos, las diferentes instituciones del Estado y el movimiento social. Metodológicamente, el estudio se basa en una serie de autores que buscan rescatar las contradicciones y los intereses de los afectados por la implementación de este tipo de proyectos (Sigaud 1992, 1995, Vianna 2009, Borralho, 1988) a partir de una muestra de argumentación cualitativa. De este modo, el estudio se sustentó en una revisión bibliográfica y de prensa sobre el funcionamiento de la expansión eléctrica en América Latina y posteriormente sobre el contexto colombiano a partir de sus proyectos de expansión hidroeléctrica y la legislación acerca del funcionamiento de la Licencia Ambiental en este país. Finalmente, se sitúa en el caso concreto de El Quimbo, donde se realizaron diversos trabajos de campo con campesinos localizados en el área de afectación y se recolectó material de prensa y material emitido tanto por Emgesa como por la Asociación de Afectados por la hidroeléctrica El Quimbo-Asoquimbo. El trabajo investigativo refleja el panorama sobre la expansión de grandes proyectos de infraestructura y el consenso que existe sobre su implementación tanto por el sector privado como por los gobiernos nacionales, materializados a través de marcos legales del Estado y figuras como las licencias ambientales. A partir de este caso, se muestra cómo estas decisiones del Estado generan cambios en las condiciones previas de vida de poblaciones rurales, que reaccionan a partir de protestas y de la conformación de grupos con diferentes intereses y tiempos de resistencia y negociación.