SRF Phosphorylation by Glycogen Synthase Kinase-3 Promotes Axon Growth in Hippocampal Neurons

The growth of axons is an intricately regulated process involving intracellular signaling cascades and gene transcription. We had previously shown that the stimulus-dependent transcription factor, serum response factor (SRF), plays a critical role in regulating axon growth in the mammalian brain. However, the molecular mechanisms underlying SRF-dependent axon growth remains unknown. Here we report that SRF is phosphorylated and activated by GSK-3 to promote axon outgrowth in mouse hippocampal neurons. GSK-3 binds to and directly phosphorylates SRF on a highly conserved serine residue. This serine phosphorylation is necessary for SRF activity and for its interaction with MKL-family cofactors, MKL1 and MKL2, but not with TCF-family cofactor, ELK-1. Axonal growth deficits caused by GSK-3 inhibition could be rescued by expression of a constitutively active SRF. The SRF target gene and actin-binding protein, vinculin, is sufficient to overcome the axonal growth deficits of SRF-deficient and GSK-3-inhibited neurons. Furthermore, short hairpin RNA-mediated knockdown of vinculin also attenuated axonal growth. Thus, our findings reveal a novel phosphorylation and activation of SRF by GSK-3 that is critical for SRF-dependent axon growth in mammalian central neurons.

Reservoir Operation with Fuzzy State Variables for Irrigation of Multiple Crops

This paper presents the development and application of a stochastic dynamic programming model with fuzzy state variables for irrigation of multiple crops. A fuzzy stochastic dynamic programming (FSDP) model is developed in which the reservoir storage and soil moisture of the crops are considered as fuzzy numbers, and the reservoir inflow is considered as a stochastic variable. The model is formulated with an objective of minimizing crop yield deficits, resulting in optimal water allocations to the crops by maintaining storage continuity and soil moisture balance. The standard fuzzy arithmetic method is used to solve all arithmetic equations with fuzzy numbers, and the fuzzy ranking method is used to compare two or more fuzzy numbers. The reservoir operation model is integrated with a daily-based water allocation model, which results in daily temporal variations of allocated water, soil moisture, and crop deficits. A case study of an existing Bhadra reservoir in Karnataka, India, is chosen for the model application. The FSDP is a more realistic model because it considers the uncertainty in discretization of state variables. The results obtained using the FSDP model are found to be more acceptable for the case study than those of the classical stochastic dynamic model and the standard operating model, in terms of 10-day releases from the reservoir and evapotranspiration deficit. (C) 2015 American Society of Civil Engineers.

Of plants and pikas: evidence for a climate-mediated decline in forage and cache quality

Background: Animals that hoard food to mediate seasonal deficits in resource availability might be particularly vulnerable to climate-mediated reductions in the quality and accessibility of food during the caching season. Central-place foragers might be additionally impacted by climatic constraints on their already restricted foraging range. Aims: We sought evidence for these patterns in a study of the American pika (Ochotona princeps), a territorial, central-place forager sensitive to climate. Methods: Pika food caches and available forage were re-sampled using historical methods at two long-term study sites, to quantify changes over two decades. Taxa that changed in availability or use were analysed for primary and secondary metabolites. Results: Both sites trended towards warmer summers, and snowmelt trended earlier at the lower latitude site. Graminoid cover increased at each site, and caching trends appeared to reflect available forage rather than primary metabolites. Pikas at the lower latitude site preferred species higher in secondary metabolites, known to provide higher-nutrient winter forage. However, caching of lower-nutrient graminoids increased in proportion with graminoid availability at that site. Conclusions: If our results represent trends in climate, cache quality and available forage, we predict that pikas at the lower latitude site will soon face nutritional deficiencies.

Fiscal Policy and Economic Stability: Does PIGS stand for Procyclicality In Government Spending?

The Financial Crisis has hit particularly hard countries like Ireland or Spain. Procyclical fiscal policy has contributed to a boom-bust cycle that undermined fiscal positions and deepened current account deficits during the boom. We set up an RBC model of a small open economy, following Mendoza (1991), and introduce the effect of fiscal policy decisions that change over the cycle. We calibrate the model on data for Ireland, and simulate the effect of different spending policies in response to supply shocks. Procyclical fiscal policy distorts intertemporal allocation decisions. Temporary spending boosts in booms spur investment, and hence the need for external finance, and so generates very volatile cycles in investment and the current account. This economic instability is also harmful for the steady state level of output. Our model is able to replicate the relation between the degree of cyclicality of fiscal policy, and the volatility of consumption, investment and the current account observed in OECD countries.

Sediment budget: principals and applications

The framework of sediment budget concepts provides a formalized procedure to account for the various components of sediment flux and the changes of volume that occur within a given region. Sediment budget methodology can be useful in a number of coastal engineering and research applications, including: inferring the amount of onshore sediment transport for a nearshore system that contains an "excess of sediment", determining sediment deficits to downdrift beaches as a result of engineering works at navigational entrances, evaluating the performance of a beach nourishment project, inferring the distribution of longshore sediment transport across the surf zone, etc. This chapter reviews briefly the governing equations for sediment budget calculations, considers various measurement and other bases for determining the sediment flux components necessary to apply the sediment budget concept and finally for illustration purposes, applies the sediment budget concept to several examples. (PDF contains 52 pages.)

Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

11 p.

Extreme events and ecological forecasting

Almost all extreme events lasting less than several weeks that significantly impact ecosystems are weather related. This review examines the response of estuarine systems to intense short-term perturbations caused by major weather events such as hurricanes. Current knowledge concerning these effects is limited to relatively few studies where hurricanes and storms impacted estuaries with established environmental monitoring programs. Freshwater inputs associated with these storms were found to initially result in increased primary productivity. When hydrographic conditions are favorable, bacterial consumption of organic matter produced by the phytoplankton blooms and deposited during the initial runoff event can contribute to significant oxygen deficits during subsequent warmer periods. Salinity stress and habitat destruction associated with freshwater inputs, as well as anoxia, adversely affect benthic populations and fish. In contrast, mobile invertebrate species such as shrimp, which have a short life cycle and the ability to migrate during the runoff event, initially benefit from the increased primary productivity and decreased abundance of fish predators. Events studied so far indicate that estuaries rebound in one to three years following major short-term perturbations. However, repeated storm events without sufficient recovery time may cause a fundamental shift in ecosystem structure (Scavia et al. 2002). This is a scenario consistent with the predicted increase in hurricanes for the east coast of the United States. More work on the response of individual species to these stresses is needed so management of commercial resources can be adjusted to allow sufficient recovery time for affected populations.

Understanding Tariff Deficit and its Challenges

Regulators and market participants have become increasingly concerned about the Spanish electricity tariff deficit due to its size and the difficulties to control its growth. The deficit can be traced to inefficiencies in market organization and solutions should be designed to mitigate those inefficiencies. Tariff deficits have allowed for the transfer of part of the present costs of electricity services to future consumers, but this situation has reached a limit and a deep revision of regulation in this market cannot be postponed. In general, solutions that interfere with market prices and signals are not appropriate.

Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Lambda beta (amyloid beta-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to A beta accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere. Palabras clave

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

Background: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE). A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon 4 allele, increasing the risk of AD (OR = 5.96, 95% CI 2.74-12.94, p < 0.001 and OR = 6.71, 95% CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women. In MCI patients such as synergistic effect was only found between AG and APOE epsilon 4 allele (OR = 3.21 95% CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95% CI 1.69-20.42, p < 0.01). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)

Macaque lateral intraparietal area and oculomotor behaviors

Neurons in the primate lateral intraparietal area (area LIP) carry visual, saccade-related and eye position activities. The visual and saccade activities are anchored in a retinotopic framework and the overall response magnitude is modulated by eye position. It was proposed that the modulation by eye position might be the basis of a distributed coding of target locations in a head-centered space. Other recording studies demonstrated that area LIP is involved in oculomotor planning. These results overall suggest that area LIP transforms sensory information for motor functions. In this thesis I further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. Macaque monkeys were trained to do visually guided and memory saccades and a double saccade task to examine the use of eye position signal. Finally, by intermixing visual saccades with trials in which two targets were presented at opposite sides of the fixation point, I examined the behavior of visual extinction.

In chapter 2, I will show that lesion of area LIP results in increased latency of contralesional visual and memory saccades. Contralesional memory saccades are also hypometric and slower in velocity. Moreover, the impairment of memory saccades does not vary with the duration of the delay period. This suggests that the oculomotor deficits observed after inactivation of area LIP is not due to the disruption of spatial memory.

In chapter 3, I will show that lesion of area LIP does not severely affect the processing of spontaneous eye movement. However, the monkeys made fewer contralesional saccades and tended to confine their gaze to the ipsilesional field after inactivation of area LIP. On the other hand, lesion of area LIP results in extinction of the contralesional stimulus. When the initial fixation position was varied so that the retinal and spatial locations of the targets could be dissociated, it was found that the extinction behavior could best be described in a head-centered coordinate.

In chapter 4, I will show that inactivation of area LIP disrupts the use of eye position signal to compute the second movement correctly in the double saccade task. If the first saccade steps into the contralesional field, the error rate and latency of the second saccade are both increased. Furthermore, the direction of the first eye movement largely does not have any effect on the impairment of the second saccade. I will argue that this study provides important evidence that the extraretinal signal used for saccadic localization is eye position rather than a displacement vector.

In chapter 5, I will demonstrate that in parietal monkeys the eye drifts toward the lesion side at the end of the memory saccade in darkness. This result suggests that the eye position activity in the posterior parietal cortex is active in nature and subserves gaze holding.

Overall, these results further support the view that area LIP neurons encode spatial locations in a craniotopic framework and is involved in processing voluntary eye movements.

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)