Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction

PURPOSE: AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size. METHODS: Perfused rat hearts were subjected to 35 min ischaemia and 120 min reperfusion. Metformin (50 microM) or AICAR (0.5 mM) were added for 15 min at the onset of reperfusion alone or with Compound C (CC, 10 microM), an AMPK inhibitor. Infarct size and alpha-AMPK phosphorylation were measured. RESULTS: Metformin significantly reduced infarct size from 47.8 +/- 1.7% in control to 31.4 +/- 2.9%, an effect abolished by CC when the drugs were given concomitantly. Similarly, AICAR also induced a significant reduction in infarct size to 32.3 +/- 4.8%, an effect also abrogated by CC. However, metformin's protection was not abolished if CC was administered later in reperfusion. In addition, alpha-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion. CONCLUSIONS: Our data demonstrated that, in our ex vivo model of myocardial ischaemia-reperfusion injury, AMPK activation in early reperfusion is associated with a reduction in infarct size

Effect of sieving on ex-situ soil respiration of soils from three land use types

This study aims to investigate the effect of sieving on ex situ soil respiration (CO2 flux) measurements from different land use types. We collected soils (0–10 cm) from arable, grassland and woodland sites, allocated them to either sieved (4-mm mesh, freshly sieved) or intact core treatments and incubated them in gas-tight jars for 40 days at 10 °C. Headspace gas was collected on days 1, 3, 17, 24, 31 and 38 and CO2 analysed. Our results showed that sieving (4 mm) did not significantly influence soil respiration measurements, probably because micro aggregates (< 0.25 mm) remain intact after sieving. However, soils collected from grassland soil released more CO2 compared with those collected from woodland and arable soils, irrespective of sieving treatments. The higher CO2 from grassland soil compared with woodland and arable soils was attributed to the differences in the water holding capacity and the quantity and stoichiometry of the organic matter between the three soils. We conclude that soils sieved prior to ex situ respiration experiments provide realistic respiration measurements. This finding lends support to soil scientists planning a sampling strategy that better represents the inhomogeneity of field conditions by pooling, homogenising and sieving samples, without fear of obtaining unrepresentative CO2 flux measurements caused by the disruption of soil architecture

The grinch who stole wisdom

Dr. Seuss is wise. How the Grinch Stole Christmas (Seuss, 1957) could serve as a parable for our time. It can also be seen as a roadmap for the development of contemplative wisdom. The abiding popularity of How the Grinch Stole Christmas additionally suggests that contemplative wisdom is more readily available to ordinary people, even children, than is normally thought. This matters because from the point of view of contemplatives in any of the world's philosophies or religions, people are confused about wisdom. The content of the nascent field of wisdom studies, they might say, is largely not wisdom at all but rather what it's like to live in a particular kind of prison cell, a well appointed cell perhaps, but not a place that makes possible either personal satisfaction or deep problem solving. I believe that what the contemplative traditions have to say is important; they offer a different orientation to what personal wisdom is, how to develop it, and how to use it in the world than is presently contained in either our popular culture or our sciences. In order to illustrate this I will examine, in some detail, one contemplative path within Buddhism. Buddhism is particularly useful in this respect because its practices are nontheistic and thus avoid many of the cultural landmines associated with the contemplative aspects of Western religions

An evaluation of enteral nutrition practices and nutritional provision in children during the entire length of stay in critical care

&lt;b&gt;Background&lt;/b&gt; Provision of optimal nutrition in children in critical care is often challenging. This study evaluated exclusive enteral nutrition (EN) provision practices and explored predictors of energy intake and delay of EN advancement in critically ill children.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Data on intake and EN practices were collected on a daily basis and compared against predefined targets and dietary reference values in a paediatric intensive care unit. Factors associated with intake and advancement of EN were explored.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Data were collected from 130 patients and 887 nutritional support days (NSDs). Delay to initiate EN was longer in patients from both the General Surgical and congenital heart defect (CHD) Surgical groups [Median (IQR); CHD Surgical group: 20.3 (16.4) vs General Surgical group: 11.4 (53.5) vs Medical group: 6.5 (10.9) hours; p &lt;= 0.001]. Daily fasting time per patient was significantly longer in patients from the General Surgical and CHD Surgical groups than those from the Medical group [% of 24 h, Median (IQR); CHD Surgical group: 24.0 (29.2) vs General Surgical group: 41.7 (66.7) vs Medical group: 9.4 (21.9); p &lt;= 0.001]. A lower proportion of fluids was delivered as EN per patient (45% vs 73%) or per NSD (56% vs 73%) in those from the CHD Surgical group compared with those with medical conditions. Protein and energy requirements were achieved in 38% and 33% of the NSDs. In a substantial proportion of NSDs, minimum micronutrient recommendations were not met particularly in those patients from the CHD Surgical group. A higher delivery of fluid requirements (p &lt; 0.05) and a greater proportion of these delivered as EN (p &lt; 0.001) were associated with median energy intake during stay and delay of EN advancement. Fasting (31%), fluid restriction (39%) for clinical reasons, procedures requiring feed cessation and establishing EN (22%) were the most common reasons why target energy requirements were not met.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Provision of optimal EN support remains challenging and varies during hospitalisation and among patients. Delivery of EN should be prioritized over other "non-nutritional" fluids whenever this is possible.&lt;p&gt;&lt;/p&gt

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Loss of PINK1 Increases the Heart's Vulnerability to Ischemia-Reperfusion Injury.

Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction

In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells

α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178