Equatorial Pacific coral geochemical records show recent weakening of the Walker Circulation

Equatorial Pacific ocean-atmosphere interactions affect climate globally, and a key component of the coupled system is the Walker Circulation, which is driven by sea surface temperature (SST) gradients across the equatorial Pacific. There is conflicting evidence as to whether the SST gradient and Walker Circulation have strengthened or weakened over the late twentieth century. We present new records of SST and sea surface salinity (SSS) spanning 1959–2010 based on paired measurements of Sr/Ca and δ18O in a massive Porites coral from Butaritari atoll in the Gilbert Islands, Republic of Kiribati, in the central western equatorial Pacific. The records show 2–7 year variability correlated with the El Niño–Southern Oscillation (ENSO) and corresponding shifts in the extent of the Indo-Pacific Warm Pool, and decadal-scale signals related to the Pacific Decadal Oscillation and the Pacific Warm Pool Index. In addition, the Butaritari coral records reveal a small but significant increase in SST (0.39°C) from 1959 to 2010 with no accompanying change in SSS, a trend that persists even when ENSO variability is removed. In contrast, larger increases in SST and SSS are evident in coral records from the equatorial Pacific Line Islands, located east of Butaritari. Taken together, the equatorial Pacific coral records suggest an overall reduction in the east-west SST and SSS gradient over the last several decades, and a recent weakening of the Walker Circulation. © 2014, American Geophysical Union. All Rights Reserved

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Predicting negative health outcomes in older general practice patients with chronic illness: Rationale and development of the PROPERmed harmonized individual participant data database.

The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process

Predicting negative health outcomes in older general practice patients with chronic illness: Rationale and development of the PROPERmed harmonized individual participant data database.

The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process

Astrocyte-Derived Tissue Transglutaminase Interacts with Fibronectin: A Role in Astrocyte Adhesion and Migration?

An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar. Astroglial scar formation is facilitated by the interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there is evidence indicating that glial scars strongly inhibit both axon growth and (re)myelination in brain lesions, it is important to understand the factors that contribute to the interaction between astrocytes and ECM proteins. Tissue Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate cell adhesion and migration and it binds fibronectin with high affinity. We therefore hypothesized that TG2 is involved in astrocyte-fibronectin interactions. Our studies using primary rat astrocytes show that intracellular and cell surface expression and activity of TG2 is increased after treatment with pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is involved in stimulating focal adhesion formation which is necessary for the interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived TG2 contributes to the interaction between astrocytes and fibronectin. It might thereby regulate ECM remodeling and possibly glial scarring

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

When visual contrast changes, retinal ganglion cells adapt by adjusting their sensitivity as well as their temporal filtering characteristics. The latter has classically been described by contrast-induced gain changes that depend on temporal frequency. Here, we explored a new perspective on contrast-induced changes in temporal filtering by using spike-triggered covariance analysis to extract multiple parallel temporal filters for individual ganglion cells. Based on multielectrode-array recordings from ganglion cells in the isolated salamander retina, we found that contrast adaptation of temporal filtering can largely be captured by contrast-invariant sets of filters with contrast-dependent weights. Moreover, differences among the ganglion cells in the filter sets and their contrast-dependent contributions allowed us to phenomenologically distinguish three types of filter changes. The first type is characterized by newly emerging features at higher contrast, which can be reproduced by computational models that contain response-triggered gain-control mechanisms. The second type follows from stronger adaptation in the Off pathway as compared to the On pathway in On-Off-type ganglion cells. Finally, we found that, in a subset of neurons, contrast-induced filter changes are governed by particularly strong spike-timing dynamics, in particular by pronounced stimulus-dependent latency shifts that can be observed in these cells. Together, our results show that the contrast dependence of temporal filtering in retinal ganglion cells has a multifaceted phenomenology and that a multi-filter analysis can provide a useful basis for capturing the underlying signal-processing dynamics

Equatorial pacific coral ceochemical records show recent weakening of the Walker Circulation

Equatorial Pacific ocean-atmosphere interactions affect climate globally, and a key component of the coupled system is the Walker Circulation, which is driven by sea surface temperature (SST) gradients across the equatorial Pacific. There is conflicting evidence as to whether the SST gradient and Walker Circulation have strengthened or weakened over the late twentieth century. We present new records of SST and sea surface salinity (SSS) spanning 1959–2010 based on paired measurements of Sr/Ca and δ18O in a massive Porites coral from Butaritari atoll in the Gilbert Islands, Republic of Kiribati, in the central western equatorial Pacific. The records show 2–7 year variability correlated with the El Niño–Southern Oscillation (ENSO) and corresponding shifts in the extent of the Indo-Pacific Warm Pool, and decadal-scale signals related to the Pacific Decadal Oscillation and the Pacific Warm Pool Index. In addition, the Butaritari coral records reveal a small but significant increase in SST (0.39°C) from 1959 to 2010 with no accompanying change in SSS, a trend that persists even when ENSO variability is removed. In contrast, larger increases in SST and SSS are evident in coral records from the equatorial Pacific Line Islands, located east of Butaritari. Taken together, the equatorial Pacific coral records suggest an overall reduction in the east-west SST and SSS gradient over the last several decades, and a recent weakening of the Walker Circulation.© 2014, American Geophysical Union