1,060 research outputs found

    Thermal reaction norms and the scale of temperature variation: latitudinal vulnerability of intertidal Nacellid limpets to climate change

    Get PDF
    The thermal reaction norms of 4 closely related intertidal Nacellid limpets, Antarctic (Nacella concinna), New Zealand (Cellana ornata), Australia (C. tramoserica) and Singapore (C. radiata), were compared across environments with different temperature magnitude, variability and predictability, to test their relative vulnerability to different scales of climate warming. Lethal limits were measured alongside a newly developed metric of “duration tenacity”, which was tested at different temperatures to calculate the thermal reaction norm of limpet adductor muscle fatigue. Except in C. tramoserica which had a wide optimum range with two break points, duration tenacity did not follow a typical aerobic capacity curve but was best described by a single break point at an optimum temperature. Thermal reaction norms were shifted to warmer temperatures in warmer environments; the optimum temperature for tenacity (Topt) increased from 1.0°C (N. concinna) to 14.3°C (C. ornata) to 18.0°C (an average for the optimum range of C. tramoserica) to 27.6°C (C. radiata). The temperature limits for duration tenacity of the 4 species were most consistently correlated with both maximum sea surface temperature and summer maximum in situ habitat logger temperature. Tropical C. radiata, which lives in the least variable and most predictable environment, generally had the lowest warming tolerance and thermal safety margin (WT and TSM; respectively the thermal buffer of CTmax and Topt over habitat temperature). However, the two temperate species, C. ornata and C. tramoserica, which live in a variable and seasonally unpredictable microhabitat, had the lowest TSM relative to in situ logger temperature. N. concinna which lives in the most variable, but seasonally predictable microhabitat, generally had the highest TSMs. Intertidal animals live at the highly variable interface between terrestrial and marine biomes and even small changes in the magnitude and predictability of their environment could markedly influence their future distributions

    SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

    Get PDF
    DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex

    Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    Get PDF
    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

    Comparative biometrics of British marsh tits Poecile palustris and willow tits P. montana

    Get PDF
    Biometrics are commonly used to compare bird species. For Marsh Tits and Willow Tits in Britain there are few biometric data from birds of known age and sex, despite their value for population analyses in estimating the proportion of males and females in samples. Comparing measurements between the two species could also aid identification and the monitoring of these declining species in Britain. We present biometrics for a large sample of Marsh Tits of known age and sex, and new data for Willow Tits, which act as reliable reference material. Overall, adults of both species were larger than first-years and males were larger than females, but not among first-year Willow Tits. Marsh Tits were slightly larger and heavier than Willow Tits, but Willow Tits had proportionately longer tails. Discriminant analyses produced new equations for separating the species based on wing length and the measurement between the shortest and longest tail feathers. Probabilities were generated for estimating Marsh Tit population structure from samples of ringing data, but there was a greater overlap between sexes in Willow Tit measurements. We conclude by discussing issues of measurement accuracy and consistency in the collection and analysis of biometric data

    Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains

    Get PDF
    PDE4 family cAMP phosphodiesterases play a pivotal role in determining compartmentalised cAMP signalling through targeted cAMP breakdown. Expressing the widely found PDE4D5 isoform, as both bait and prey in a yeast 2-hybrid system, we demonstrated interaction consistent with the notion that long PDE4 isoforms form dimers. Four potential dimerization sites were uncovered using a scanning peptide array approach, where a recombinant purified PDE4D5 fusion protein was used to probe a 25-mer library of overlapping peptides covering the entire PDE4D5 sequence. Key residues involved in PDE4D5 dimerization were defined using a site-directed mutagenesis programme directed by an alanine scanning peptide array approach. Critical residues stabilising PDE4D5 dimerization were defined within the regulatory UCR1 region found in long, but not short, PDE4 isoforms, namely the Arg173, Asn174 and Asn175 (DD1) cluster. Disruption of the DD1 cluster was not sufficient, in itself, to destabilise PDE4D5 homodimers. Instead, disruption of an additional interface, located on the PDE4 catalytic unit, was also required to convert PDE4D5 into a monomeric form. This second dimerization site on the conserved PDE4 catalytic unit is dependent upon a critical ion pair interaction. This involves Asp463 and Arg499 in PDE4D5, which interact in a trans fashion involving the two PDE4D5 molecules participating in the homodimer. PDE4 long isoforms adopt a dimeric state in living cells that is underpinned by two key contributory interactions, one involving the UCR modules and one involving an interface on the core catalytic domain. We propose that short forms do not adopt a dimeric configuration because, in the absence of the UCR1 module, residual engagement of the remaining core catalytic domain interface provides insufficient free energy to drive dimerization. The functioning of PDE4 long and short forms is thus poised to be inherently distinct due to this difference in quaternary structure

    CDtoolX, a downloadable software package for processing and analyses of Circular Dichroism Spectroscopic Data

    Get PDF
    Circular dichroism (CD) spectroscopy is a highly-used method for the examination and characterisation of proteins, including, amongst other features, their secondary and tertiary structures, thermal stability, comparisons of wildtype and mutant proteins, and monitoring the binding of small molecules, folding/unfolding pathways, and formation of macromolecular complexes. This paper describes CDtoolX, a new, user-friendly, free-to-download-and-use software program that enables processing, displaying, archiving, calibrating, comparisons, and analyses of circular dichroism and synchrotron radiation circular dichroism (SRCD) spectroscopic data

    Managing in an economic crisis: The role of market orientation in an international law firm

    Get PDF
    This research paper contributes to the understanding of the relationship between market orientation and performance in the context of a law firm during a time of economic crisis. The contribution is twofold, adding to the fairly limited research on market orientation within law firms, and to the limited research on the role of market orientation in times of economic crisis. The findings, from the questionnaire survey and semi-structured interviews within practice groups of a large multinational law firm, conclude that market orientation is important during an economic crisis. Those practice groups with higher market orientation scores withstand the increased turbulence and outperform those practice groups with lower market orientation scores

    The SPAIR method: Isolating incident and reflected directional wave spectra in multidirectional wave basins

    Get PDF
    Wave tank tests aiming to reproduce realistic or site specific conditions will commonly involve using directionally spread, short-crested sea states. The measurement of these directional characteristics is required for the purposes of calibrating and validating the modelled sea state. Commonly used methods of directional spectrumreconstruction, based on directional spreading functions, have an inherent level of uncertainty associated with them. In this paper we aim to reduce the uncertainty in directional spectrum validation by introducing the SPAIR (Single-summation PTPD Approach with In-line Reflections) method, in combination with a directional wave gauge array. A variety of wave conditions were generated in the FloWave Ocean Energy Research Facility, Edinburgh, UK, to obtain a range of sea state and reflection scenarios. The presented approach is found to provide improved estimates of directional spectra over standardmethods, reducing the mean apparent directional deviation down to below 6% over the range of sea states. Additionally, the method isolates incident and reflected spectra in both the frequency and time domain, and can separate these wave systems over 360°. The accuracy of themethod is shown to be only slightly sensitive to the level of in-line reflectionpresent,but at present cannot dealwithoblique reflections. The SPAIRmethod, as presented or with slightmodification, will allow complex directional sea states to be validated more effectively, enabling multidirectional wave basins to simulate realistic wave scenarios with increased confidence

    Illness Beliefs Predict Mortality in Patients with Diabetic Foot Ulcers

    Get PDF
    Background - Patients’ illness beliefs have been associated with glycaemic control in diabetes and survival in other conditions. Objective - We examined whether illness beliefs independently predicted survival in patients with diabetes and foot ulceration. Methods - Patients (n = 169) were recruited between 2002 and 2007. Data on illness beliefs were collected at baseline. Data on survival were extracted on 1st November 2011. Number of days survived reflected the number of days from date of recruitment to 1st November 2011. Results - Cox regressions examined the predictors of time to death and identified ischemia and identity beliefs (beliefs regarding symptoms associated with foot ulceration) as significant predictors of time to death. Conclusions - Our data indicate that illness beliefs have a significant independent effect on survival in patients with diabetes and foot ulceration. These findings suggest that illness beliefs could improve our understanding of mortality risk in this patient group and could also be the basis for future therapeutic interventions to improve survival
    corecore