Hippocampal long-term depression and depotentiation are defective in mice carrying a targeted disruption of the gene encoding the RI beta subunit of cAMP-dependent protein kinase.

The cAMP-dependent protein kinase (PKA) has been shown to play an important role in long-term potentiation (LTP) in the hippocampus, but little is known about the function of PKA in long-term depression (LTD). We have combined pharmacologic and genetic approaches to demonstrate that PKA activity is required for both homosynaptic LTD and depotentiation and that a specific neuronal isoform of type I regulatory subunit (RI beta) is essential. Mice carrying a null mutation in the gene encoding RI beta were established by use of gene targeting in embryonic stem cells. Hippocampal slices from mutant mice show a severe deficit in LTD and depotentiation at the Schaffer collateral-CA1 synapse. This defect is also evident at the lateral perforant path-dentate granule cell synapse in RI beta mutant mice. Despite a compensatory increase in the related RI alpha protein and a lack of detectable changes in total PKA activity, the hippocampal function in these mice is not rescued, suggesting a unique role for RI beta. Since the late phase of CA1 LTP also requires PKA but is normal in RI beta mutant mice, our data further suggest that different forms of synaptic plasticity are likely to employ different combinations of regulatory and catalytic subunits.

Homeostatic plasticity induced by brief activity deprivation enhances long-term potentiation in the mature rat hippocampus

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Long-term in vivo biostability of poly(dimethylsiloxane) / poly(hexamethylene oxide) mixed macrodiol-based polyurethane elastomers

The long-term biostability of a novel thermoplastic polyurethane elastomer (Elast-Eon(TM) 2 80A) synthesized using poly(hexamethylene oxide) (PHMO) and poly(dimethylsiloxane) (PDMS) macrodiols has been studied using an in vivo ovine model. The material's biostability was compared with that of three commercially available control materials, Pellethane(R) 2363-80A, Pellethane(R) 2363-55D and Bionate(R) 55D, after subcutaneous implantation of strained compression moulded flat sheet dumbbells in sheep for periods ranging from 3 to 24 months. Scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to assess changes in the surface chemical structure and morphology of the materials. Gel permeation chromatography, differential scanning calorimetry and tensile testing were used to examine changes in bulk characteristics of the materials. The results showed that the biostability of the soft flexible PDMS-based test polyurethane was significantly better than the control material of similar softness, Pellethane(R) 80A, and as good as or better than both of the harder commercially available negative control polyurethanes. Pellethane(R) 55D and Bionate(R) 55D. Changes observed in the surface of the Pellethane(R) materials were consistent with oxidation of the aliphatic polyether soft segment and hydrolysis of the urethane bonds joining hard to soft segment with degradation in Pellethane(R) 80A significantly more severe than that observed in Pellethane(R) 55D. Very minor changes were seen on the surfaces of the Elast-Eon(TM) 2 80A and Bionate(R) 55D materials. There was a general trend of molecular weight decreasing with time across all polymers and the molecular weights of all materials decreased at a similar relative rate. The polydispersity ratio, M-w/M-n, increased with time for all materials. Tensile tests indicated that UTS increased in Elast-Eon(TM) 2 80A and Bionate(R) 55D following implantation under strained conditions. However, ultimate strain decreased and elastic modulus increased in the explanted specimens of all three materials when compared with their unimplanted unstrained counterparts. The results indicate that a soft, flexible PDMS-based polyurethane synthesized using 20% PHMO and 80% PDMS macrodiols has excellent long-term biostability compared with commercially available polyurethanes. (C) 2004 Elsevier Ltd. All rights reserved.

The immediate and long term effects of singing on the mood states of people with traumatic brain injury

Mood changes in four male participants with traumatic brain injury (TBI) were observed following their participation in a 15-session song-singing programme. An analysis of the song material was undertaken to categorise the songs according to the predominant mood they portrayed. Results showed significant differences between participants for all moods (p

Long-term outcome of a school-based, universal approach to prevention of depression in adolescents

In this study. the authors examined the 2-, 3-, and 4-year outcomes of a school-based, universal approach to the prevention of adolescent depression. Despite initial short-term positive effects, these benefits were not maintained over time. Adolescents who completed the teacher-administered cognitive-behavioral intervention did not differ significantly from adolescents in the monitoring-control condition in terms of changes in depressive symptoms, problem solving, attributional style, or other indicators of psychopathology from preintervention to 4-year follow-up. Results were equivalent irrespective of initial level of depressive symptoms.

Community and cluster centre residential services for adults with intellectual disability: long-term results from an Australian-matched sample

Changes in residential accommodation models for adults with intellectual disability (ID) over the last 20 years in Australia, the United Kingdom and the United States have involved relocation from institutions primarily into dispersed homes in the community. But an evolving alternative service style is the cluster centre. This paper reports on the relocation of a matched group of 30 pairs of adults with moderate and severe IDs and challenging behaviour who were relocated from an institution into either dispersed housing in the community or cluster centres but under the same residential service philosophy. Adaptive and maladaptive behaviour, choice-making and objective life quality were assessed prior to leaving the institution and then after 12 and 24 months of living in the new residential model. Adaptive behaviour, choice-making and life quality increased for both groups and there was no change in level of maladaptive behaviour compared with levels exhibited in the institution. However, there were some significant differences between the community and cluster centre group as the community group increased some adaptive skills, choice-making and objective life quality to a greater extent than the cluster centre group. Both cluster centre and dispersed community living offer lifestyle and skill development advantages compared with opportunities available in large residential institutions. Dispersed community houses, however, offer increased opportunities for choice-making, acquisition of adaptive behaviours and improved life quality for long-term institutionalized adults with IDs.

Long-term loading inhibits ERK1/2 phosphorylation and increases FGFR3 expression in MC3T3-E1 osteoblast cells

Bone tissue homeostasis relies upon the ability of cells to detect and interpret extracellular signals that direct changes in tissue architecture. This study utilized a four-point bending model to create both fluid shear and strain forces (loading) during the time-dependent progression of MC3T3-E1 preosteoblasts along the osteogenic lineage. Loading was shown to increase cell number, alkaline phosphatase (ALP) activity, collagen synthesis, and the mRNA expression levels of Runx2, osteocalcin (OC), osteopontin, and cyclo-oxygenase-2. However, mineralization in these cultures was inhibited, despite an increase in calcium accumulation, suggesting that loading may inhibit mineralization in order to increase matrix deposition. Loading also increased fibroblast growth factor receptor-3 (FGFR3) expression coincident with an inhibition of FGFR1, FGFR4, FGF1, and extracellular signal-related kinase (ERK)1/2 phosphorylation. To examine whether these loading-induced changes in cell phenotype and FGFR expression could be attributed to the inhibition of ERK1/2 phosphorylation, cells were grown for 25 days in the presence of the MEK1/2 inhibitor, U0126. Significant increases in the expression of FGFR3, ALP, and OC were observed, as well as the inhibition of FGFR1, FGFR4, and FGF1. However, U0126 also increased matrix mineralization, demonstrating that inhibition of ERK1/2 phosphorylation cannot fully account for the changes observed in response to loading. in conclusion, this study demonstrates that preosteoblasts are mechanoresponsive, and that long-term loading, whilst increasing proliferation and differentiation of preosteoblasts, inhibits matrix mineralization. In addition, the increase in FGFR3 expression suggests that it may have a role in osteoblast differentiation.

Long-term dynamic patterns and diversity of phytoplankton communities in a large eutrophic river (the case of River Danube, Hungary)

In this paper we present the composition, seasonal dynamics and fluctuations in diversity of the phytoplankton in the Danube River over 24 years. Weekly samplings were conducted at one section of the river at Göd, in the 1669 river kilometer segment. The change in the phytoplankton community structure was analyzed in relation of water temperature and discharge means. Our findings support the opinion that the Danube is very rich in species, although many of the species are rare and could be described only as coloring species. Results indicate trends in the phytoplankton abundance, which are only detectable in long-term studies. By the help of diversity indices we have observed an increase in the phytoplankton community diversity. With the relevant information, an explanation of the significant changes in diversity and richness was formed. Our goals were a construction of a solid database of the phytoplankton, examining the seasonal dynamics of the phytoplankton through a 24 year long study and to see the most important changing factors of the community. The results of this study are to assist and help future model developments to predict the phytoplankton seasonal dynamic patterns.

Pressure ulcers and nutritional deficits in elderly long-term care patients: Effects of a comprehensive nutritional program on pressure ulcer healing, length of hospital stay and charges to patients

The elderly are at the highest risk of developing pressure ulcers that result in prolonged hospitalization, high health care costs, increased mortality, and decreased quality of life. The burden of pressure ulcers will intensify because of a rapidly increasing elderly population in the United States (US). Poor nutrition is a major predictor of pressure ulcer formation. The purpose of this study was to examine the effects of a comprehensive, interdisciplinary nutritional protocol on: (1) pressure ulcer wound healing (2) length of hospital stays, and (3) charges for pressure ulcer management. Using a pre-intervention/post intervention quasi-experimental design the study sample was composed of 100 patients 60 years or older, admitted with or acquiring a pressure ulcer. A pre-intervention group (n= 50) received routine pressure ulcer care (standard diet, dressing changes, and equipment). A post-intervention group received routine care plus an interdisciplinary nutrition intervention (physical therapy, speech therapy, occupational therapy, added protein and calories to the diet). Research questions were analyzed using descriptive statistics, frequencies, Chi-Square Tests, and T-tests. Findings indicated that the comprehensive, interdisciplinary nutritional protocol had a significant effect on the rate of wound healing in Week3 and Week4, total hospital length of stay (pre-intervention M= 43.2 days, SD=31.70 versus M=31.77, SID-12.02 post-intervention), and pressure ulcer length of stay (pre-intervention 25.28 days, SD5.60 versus 18.40 days, SD 5.27 post-intervention). Although there was no significant difference in total charges for the pre-intervention group ($727,245.00) compared to the post-intervention group ($702,065.00), charges for speech (m=$5885.12, SD=$332.55), pre albumin (m=$808.52,SD= $332.55), and albumin($278 .88, SD=55.00) were higher in the pre-intervention group and charges for PT ($5721.26, SD$3655.24) and OT($2544 .64, SD=1712.863) were higher in the post-intervention group. Study findings indicate that this comprehensive nutritional intervention was effective in improving pressure ulcer wound healing, decreasing both hospital length of stay for treatment of pressure ulcer and total hospital length of stay while showing no significant additional charges for treatment of pressure ulcers.

Surprises and Insights from Long-Term Aquatic Data Sets and Experiments

long-term research on freshwater ecosystems provides insights that can be difficult to obtain from other approaches. Widespread monitoring of ecologically relevant water-quality parameters spanning decades can facilitate important tests of ecological principles. Unique long-term data sets and analytical tools are increasingly available, allowing for powerful and synthetic analyses across sites. long-term measurements or experiments in aquatic systems can catch rare events, changes in highly variable systems, time-lagged responses, cumulative effects of stressors, and biotic responses that encompass multiple generations. Data are available from formal networks, local to international agencies, private organizations, various institutions, and paleontological and historic records; brief literature surveys suggest much existing data are not synthesized. Ecological sciences will benefit from careful maintenance and analyses of existing long-term programs, and subsequent insights can aid in the design of effective future long-term experimental and observational efforts. long-term research on freshwaters is particularly important because of their value to humanity.

Pressure ulcers and nutritional deficits in elderly long-term care patients : effects of a comprehensive nutritional program on pressure ulcer healing, length of hospital stay and charges to patients

The elderly are at the highest risk of developing pressure ulcers that result in prolonged hospitalization, high health care costs, increased mortality, and decreased quality of life. The burden of pressure ulcers will intensify because of a rapidly increasing elderly population in the United States (US). Poor nutrition is a major predictor of pressure ulcer formation. The purpose of this study was to examine the effects of a comprehensive, interdisciplinary nutritional protocol on: 1) pressure ulcer wound healing 2) length of hospital stays, and 3) charges for pressure ulcer management. Using a pre-intervention/post intervention quasi-experimental design the study sample was composed of 100 patients 60 years or older, admitted with or acquiring a pressure ulcer. A pre-intervention group (n= 50) received routine pressure ulcer care (standard diet, dressing changes, and equipment). A post-intervention group received routine care plus an interdisciplinary nutrition intervention (physical therapy, speech therapy, occupational therapy, added protein and calories to the diet). Research questions were analyzed using descriptive statistics, frequencies, Chi-Square Tests, and T-tests. Findings indicated that the comprehensive, interdisciplinary nutritional protocol had a significant effect on the rate of wound healing in Week3 and Week4, total hospital length of stay (pre-intervention M= 43.2 days, SD=31.70 versus M=31.77, SD=12.02 post-intervention), and pressure ulcer length of stay (pre-intervention 25.28 days, SD5.60 versus 18.40 days, SD 5.27 post-intervention). Although there was no significant difference in total charges for the pre-intervention group ($727,245.00) compared to the post-intervention group ($702,065.00), charges for speech (m=$5885.12, SD=$332.55), pre albumin (m=$808.52,SD= $332.55), and albumin($278 .88, SD=55.00) were higher in the pre-intervention group and charges for PT ($5721.26, SD$3655.24) and OT($2544 .64, SD=1712.863) were higher in the post-intervention group. Study findings indicate that this comprehensive nutritional intervention was effective in improving pressure ulcer wound healing, decreasing both hospital length of stay for treatment of pressure ulcer and total hospital length of stay while showing no significant additional charges for treatment of pressure ulcers.

(Appendix A) Pigment content, microbial biomass and activity, and grain size characteristics in caged and control sites of the Arctic long-term observatory HAUSGARTEN

Present theories of deep-sea community organization recognize the importance of small-scale biological disturbances, originated partly from the activities of epibenthic megafaunal organisms, in maintaining high benthic biodiversity in the deep sea. However, due to technical difficulties, in situ experimental studies to test hypotheses in the deep sea are lacking. The objective of the present study was to evaluate the potential of cages as tools for studying the importance of epibenthic megafauna for deep-sea benthic communities. Using the deep-diving Remotely Operated Vehicle (ROV) "VICTOR 6000", six experimental cages were deployed at the sea floor at 2500 m water depth and sampled after 2 years (2y) and 4 years (4y) for a variety of sediment parameters in order to test for caging artefacts. Photo and video footage from both experiments showed that the cages were efficient at excluding the targeted fauna. The cage also proved to be appropriate to deep-sea studies considering the fact that there was no fouling on the cages and no evidence of any organism establishing residence on or adjacent to it. Environmental changes inside the cages were dependent on the experimental period analysed. In the 4y experiment, chlorophyll a concentrations were higher in the uppermost centimeter of sediment inside cages whereas in the 2y experiment, it did not differ between inside and outside. Although the cages caused some changes to the sedimentary regime, they are relatively minor compared to similar studies in shallow water. The only parameter that was significantly higher under cages at both experiments was the concentration of phaeopigments. Since the epibenthic megafauna at our study site can potentially affect phytodetritus distribution and availability at the seafloor (e.g. via consumption, disaggregation and burial), we suggest that their exclusion was, at least in part, responsible for the increases in pigment concentrations. Cages might be suitable tools to study the long-term effects of disturbances caused by megafaunal organisms on the diversity and community structure of smaller-sized organisms in the deep sea, although further work employing partial cage controls, greater replication, and evaluating faunal components will be essential to unequivocally establish their utility.

Long-term biogenic particle fluxes in the Bering Sea and the central subarctic Pacific Ocean

Time-series sediment traps were deployed for five consecutive years in two distinctively different subarctic marine environments. The centrally located subarctic pelagic Station SA (49°N, 174°W; water depth 5406 m) was simultaneously studied along with the marginal sea Station AB (53.5°N, 177°W; water depth 3788 m) in the Aleutian Basin of the Bering Sea. A mooring system was tethered to the sea-floor with a PARFLUX type trap with 13 sample bottles, which was placed at 600 m above the sea-floor at each of the two stations. Sampling intervals were synchronized at the stations, and they were generally set for 20 days during highly productive seasons, spring through fall, and 56 days during winter months of low productivity. Total mass fluxes, which consisted of mainly biogenic phases, were significantly greater at the marginal sea Station AB than at the pelagic Station SA for the first four years and moderately greater for the last year of the observations. This reflects the generally recognized higher productivity in the Bering Sea. Temporal excursion patterns of the mass fluxes at the two stations generally were in parallel, implying that temporal changes in their biological productivity are strongly governed by a large-scale seasonal climatic variability over the region rather than local phenomena. The primary reason for the difference in total mass flux at the two stations stems mainly from varying contributions of siliceous and calcareous planktonic assemblages. A significantly higher opal contribution at Station AB than at Station SA was mainly due to diatoms. Diatom fluxes at the marginal sea station were about twice those observed at the pelagic station, resulting in a very high opal contribution at Station AB. In contrast to the opal fluxes, CaCO3 fluxes at Station AB were slightly lower than at Station SA. The ratios of Corg/Cinorg were usually significantly greater than one in both regions, suggesting that preferentially greater organic carbon from cytoplasm than skeletal inorganic carbon was exported from the surface layers. Such a process, known as the biological pump, leads to a carbon sink which effectively lowers p CO2 in the surface layers and then allows a net flux of atmospheric CO2 into the surface layer. The efficiency of the biological pump is greater in the Bering Sea than at the open-ocean station.

Long-term modifications of coastal defences enhance marine biodiversity

Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity.