Bumble bees regulate their intake of essential protein and lipid pollen macronutrients.

Bee population declines are linked to the reduction of nutritional resources due to land-use intensification, yet we know little about the specific nutritional needs of many bee species. Pollen provides bees with their primary source of protein and lipids, but nutritional quality varies widely among host-plant species. Therefore, bees might have adapted to assess resource quality and adjust their foraging behavior to balance nutrition from multiple food sources. We tested the ability of two bumble bee species, Bombus terrestris and Bombus impatiens, to regulate protein and lipid intake. We restricted B. terrestris adults to single synthetic diets varying in protein:lipid ratios (P:L). The bees over-ate protein on low-fat diets and over-ate lipid on high-fat diets to reach their targets of lipid and protein, respectively. The bees survived best on a 10:1 P:L diet; the risk of dying increased as a function of dietary lipid when bees ate diets with lipid contents greater than 5:1 P:L. Hypothesizing that the P:L intake target of adult worker bumble bees was between 25:1 and 5:1, we presented workers from both species with unbalanced but complementary paired diets to determine whether they self-select their diet to reach a specific intake target. Bees consumed similar amounts of proteins and lipids in each treatment and averaged a 14:1 P:L for B. terrestris and 12:1 P:L for B. impatiens These results demonstrate that adult worker bumble bees likely select foods that provide them with a specific ratio of P:L. These P:L intake targets could affect pollen foraging in the field and help explain patterns of host-plant species choice by bumble bees.

Caffeine in floral nectar enhances a pollinator's memory of reward.

Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

Synchronous x-ray and radio mode switches: a rapid global transformation of the pulsar magnetosphere.

Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.

The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT.

Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI) and micro-computed tomography (CT) are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection); micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF) in the tumor rim and blood vessel density (rBVD) over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R = 0.90). rBVF in the tissue of a VX2 tumor measured by MRI in vivo was qualitatively consistent with the rBVD demonstrated by micro-CT in vitro (R = 0.97). The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively.

LBM-EP: Lattice-Boltzmann method for fast cardiac electrophysiology simulation from 3D images.

Current treatments of heart rhythm troubles require careful planning and guidance for optimal outcomes. Computational models of cardiac electrophysiology are being proposed for therapy planning but current approaches are either too simplified or too computationally intensive for patient-specific simulations in clinical practice. This paper presents a novel approach, LBM-EP, to solve any type of mono-domain cardiac electrophysiology models at near real-time that is especially tailored for patient-specific simulations. The domain is discretized on a Cartesian grid with a level-set representation of patient's heart geometry, previously estimated from images automatically. The cell model is calculated node-wise, while the transmembrane potential is diffused using Lattice-Boltzmann method within the domain defined by the level-set. Experiments on synthetic cases, on a data set from CESC'10 and on one patient with myocardium scar showed that LBM-EP provides results comparable to an FEM implementation, while being 10 - 45 times faster. Fast, accurate, scalable and requiring no specific meshing, LBM-EP paves the way to efficient and detailed models of cardiac electrophysiology for therapy planning.

Inter-model consistency and complementarity: learning from ex-vivo imaging and electrophysiological data towards an integrated understanding of cardiac physiology.

Computational models of the heart at various scales and levels of complexity have been independently developed, parameterised and validated using a wide range of experimental data for over four decades. However, despite remarkable progress, the lack of coordinated efforts to compare and combine these computational models has limited their impact on the numerous open questions in cardiac physiology. To address this issue, a comprehensive dataset has previously been made available to the community that contains the cardiac anatomy and fibre orientations from magnetic resonance imaging as well as epicardial transmembrane potentials from optical mapping measured on a perfused ex-vivo porcine heart. This data was used to develop and customize four models of cardiac electrophysiology with different level of details, including a personalized fast conduction Purkinje system, a maximum a posteriori estimation of the 3D distribution of transmembrane potential, the personalization of a simplified reaction-diffusion model, and a detailed biophysical model with generic conduction parameters. This study proposes the integration of these four models into a single modelling and simulation pipeline, after analyzing their common features and discrepancies. The proposed integrated pipeline demonstrates an increase prediction power of depolarization isochrones in different pacing conditions.

In-vivo MRI and in-vivo electro-anatomical voltage map characteristics of infarct heterogeneity in a swine model.

The arrhythmogenic substrate in patients with prior myocardial infarct (MI) is located at the border zone, BZ. In this study we correlated the BZ identified by two methods: electro-anatomical voltage mapping (EAVM) and a novel MRI method, multi-contrast late enhancement (MCLE). A pre-clinical porcine model with chronic MI was used to characterize BZ via MRI and EAVM. Results focus on the comparison between scar percentage and BZ percentage identified by each method. The correlation coefficient for BZ percentage between the two methods was 0.74 with a p-value of less the 0.0001. Bland-Altman plots were also used to compare between the two methods (slope of 0.83 ± 0.045). For a case of subtle infarct, there was only 1.3% infarct identified on EAVM compared to 22.2% on the corresponding slice on MCLE. The percentage of infarct on MCLE in subtle infarct does not relate to percentage of infarct in EAVM. Future registration between T(1) maps and EAVM will permit a quantitative comparison of MRI and EAVM measures.

Role of artificial liver support in hepatic encephalopathy.

Hepatic encephalopathy (HE) refers to the reversible neuropsychiatric disorders observed in acute liver failure and as a complication of cirrhosis and/or portal hypertension. This review aims to describe the pathophysiology of HE, the rationale for the use of artificial liver support in the treatment of HE, the different concepts of artificial liver support and the results obtained. Ammonia has been considered central to its pathogenesis but recently an important role for its interaction with inflammatory responses and auto-regulation of cerebral hemodynamics has been suggested. Artificial liver support might be able to decrease ammonia and modulate inflammatory mediators and cerebral hemodynamics. Bioartificial liver support systems use hepatocytes in an extracorporeal device connected to the patient's circulation. Artificial liver support is intended to remove protein-bound toxins and water-soluble toxins without providing synthetic function. Both systems improve clinical and biochemical parameters and can be applied safely to patients. Clinical studies have shown that artificial liver support, especially albumin dialysis, is able to improve HE in acute and acute-on-chronic liver failure. Further studies are required to better understand the mechanism, however, artificial liver support can be added to the therapeutic bundle in treating HE.

Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis.

Neutrophil dysfunction in alcoholic hepatitis is associated with endotoxemia and an increased incidence of infection, but the mechanism is unclear. We aimed to investigate the role of Toll-like-receptors (TLR)2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis. Neutrophils from healthy volunteers were incubated with alcoholic hepatitis patients' plasma (n = 12) with and without TLR2, 4, or 9 antagonists and with and without human albumin. TLR2, 4, and 9 expression, neutrophil oxidative burst, phagocytosis, and CXCR1+2 expression were measured by FACS analysis. Patients' plasma increased oxidative burst, decreased CXCR1+2 expression, and decreased phagocytosis of normal neutrophils in association with increased expression of TLR2, 4, and 9 and depletion of ATP. Inhibition of TLR2, 4, and 9 prevented the increase in oxidative burst and the decrease in CXCR1 and CXCR2 expression but did not prevent phagocytic dysfunction. Incubation with albumin completely prevented the patient plasma induced neutrophil dysfunction. Increased expression of TLR2, 4, and 9 is associated with neutrophil dysfunction, endotoxemia, and energy depletion. TLR2, 4, and 9 inhibition does not improve phagocytosis, indicating that TLR overexpression may be the result and not the cause of neutrophil activation. Albumin, an endotoxin scavenger, prevents the deleterious effect of patients' plasma on neutrophil phagocytosis, resting burst, and TLR expression.

Cardiac electrophysiology model adjustment using the fusion of MR and optical imaging.

Despite important recent efforts in cardiac electrophysiology modelling, there is still a strong need for validating macroscopic models, that are well suited for diagnosis and treatment planning. In this paper we present a method to adjust the parameters of a macroscopic electrophysiology model on depolarisation and repolarisation maps obtained ex-vivo from optical imaging. With this imaging technique, optical fluorescence data are recorded with high spatial and temporal resolution on a large healthy porcine heart. A model of the myocardium is built from the MR images of the same heart, which also integrates the myocardial fibre orientation measured with DTI. We then present the first quantitative adjustment of a personalised volumetric model of the myocardium.

Inversion-recovery-prepared SSFP for cardiac-phase-resolved delayed-enhancement MRI.

Delayed-enhancement magnetic resonance imaging (DE-MRI) can be used to visualize myocardial infarction (MI). DE-MRI is conventionally acquired with an inversion-recovery gradient-echo (IR-GRE) pulse sequence that yields a single bright-blood image. IR-GRE imaging requires an accurate estimate of the inversion time (TI) to null the signal from the myocardium, and a separate cine acquisition is required to visualize myocardial wall motion. Simulations were performed to examine the effects of a steady-state free precession (SSFP) readout after an inversion pulse in the setting of DE-MRI. Using these simulations, a segmented IR-SSFP sequence was optimized for infarct visualization. This sequence yields both viability and wall motion images over the cardiac cycle in a single breath-hold. Viability images at multiple effective TIs are produced, providing a range of image contrasts. In a study of 11 patients, IR-SSFP yielded infarct sizes and left ventricular ejection fractions (LVEFs) similar to those obtained by IR-GRE and standard SSFP, respectively. IR-SSFP images yielded improved visualization of the infarct-blood border because of the simultaneous nulling of healthy myocardium and blood. T(1) (*) recovery curves were extracted from IR-SSFP images and showed excellent qualitative agreement with theoretical simulations.

MRI relaxation fluctuations in acute reperfused hemorrhagic infarction.

MRI evaluations of intramyocardial hemorrhage in acute infarction have relied on T(2) and T(2)(*) shortening only. We propose a more comprehensive evaluation of hemorrhagic infarction based on the concept that fluctuations in T(2) and T(1) relaxation in acute reperfused infarction will reflect transient edema and hemoglobin oxidative denaturation to uncompartmentalized methemoglobin. Anteroapical infarction was created via percutaneous balloon in young swine (22-25 kg, N = 12). T(2), T(1), diastolic wall thickness (DWT), and the Gd-DTPA partition coefficient (lambda) were measured on days 0, 2, and 7. DWT was elevated at 1 hr postreperfusion (128% +/- 53%, P = 0.0001), and alleviated on days 2 and 7 (48% +/- 10%, P = 0.008; 53% +/- 24%, P = 0.003). T(2) and T(1) elevations were coincident with early edema (DeltaT(2) = 55% +/- 24%, P < 0.0001; DeltaT(1) = 27% +/- 18%, P < 0.04). T(2) and T(1) were nearly normal on day 2 (DeltaT(2) = 8% +/- 8%, P = 0.27; DeltaT(1) = 0% +/- 1%, P = 0.65). On day 7, T(2) increased while T(1) decreased (DeltaT(2) = 27% +/- 16%, P = 0.005; DeltaT(1) = -14% +/- 10%, P = 0.02). Lambda was elevated by >150% at all time points (P < or = 0.002). Histology verified hemorrhagic injury. T(1) and T(2) fluctuations are consistent with transient edema, as well as hemoglobin oxidative denaturation to decompartmentalized methemoglobin. This methodological development may broaden our understanding of hemorrhagic microvascular injury and improve its detection in clinical populations.

T2 fluctuations in ischemic and post-ischemic viable porcine myocardium in vivo.

T2 relaxation can augment delayed-enhancement viability imaging because it is sensitive to tissue edema and microcirculatory oxygen state. We demonstrate the T2 'signatures' of sub-lethal ischemia and stunning in porcine myocardium perfused by the distal left anterior descending artery, by imaging during percutaneous balloon occlusion for 25 minutes and subsequent reperfusion (n = 9). Muscle displayed ischemic dysfunction and partial post-ischemic functional recovery (p < or = 0.0004), concommitant with an elevated post-ischemic T2 (deltaT2 = 27 +/- 18%, p = 0.005). TTC staining verified muscle viability. The T2 fluctuations may reflect hyperemia and tissue cellular edema in accord with the known pathophysiology of ischemic and post-ischemic yet viable muscle.

Natriuretic peptides as a prognostic marker and therapeutic target in heart failure.

Natriuretic peptides may have an increasing role in assisting clinicians to target treatment in patients with chronic heart failure.

Application of MCBEND to PBMR shielding analysis.

Shielding analysis of an early design of Pebble Bed Modular Reactor (PBMR) has been carried out by using the Monte Carlo code MCBEND. The issues of concern were damage to the core barrel and the reactor pressure vessel (RPV), activation of the core barrel, RPV, top plate and bottom plate, and also burn-up of boron in the control layer underneath the core. The analysis below the core was complicated due to the presence of the de-fuelling chute, which meant that multiplication had to be taken into account. The analysis of boron burn-up was particularly challenging and was tackled using a combination of MCBEND and the criticality code MONK in the depletion mode. The application of MCBEND to the shielding analysis of the PBMR is described, with particular attention being paid to the regions below the core.

In vitro generation and stability of the lactokinin beta-lactoglobulin fragment (142-148).

The objectives of this study were to investigate the generation of beta-lactoglobulin fragment (142-148) (beta-LG f(142-148) during the hydrolysis of whey proteins, and the in vitro stability of this fragment upon incubation with gastrointestinal and serum proteinases and peptidases. An enzyme immunoassay (EIA) protocol was developed for the quantification of beta-LG f(142-148) in whey protein hydrolysates and in human blood serum. The minimum detection limit was 3 ng/mL. The level of the peptide in whey protein hydrolysates was influenced by the degree of hydrolysis (DH). As expected, highest levels of this peptide were found in hydrolysates generated with trypsin. Sequential incubation of hydrolysates at different DH values with pepsin and Corolase PP, to simulate gastrointestinal digestion, generally resulted in the degradation of beta-LG f(142-148) as determined by EIA. Reversed-phase HPLC and angiotensin-I-converting enzyme (ACE) activity assays demonstrated that synthetic beta-LG f(142-148) was rapidly degraded upon incubation with human serum. Furthermore, beta-LG f(142-148) could not be detected by EIA in the sera of 2 human volunteers following its oral ingestion or in sera from these volunteers subsequently spiked with beta-LG f(142-148). These in vitro results indicate that beta-LG f(142-148) is probably not sufficiently stable to gastrointestinal and serum proteinases and peptidases to act as an hypotensive agent in humans following oral ingestion. The in vitro methodology described herein has general application in evaluating the hypotensive potential of food protein-derived ACE inhibitory peptides.

A comparison of nutritional regulation in solitarious- and gregarious-phase nymphs of the desert locust Schistocerca gregaria.

Nutritional regulatory responses were compared for the cryptic 'solitarious' and the conspicuously coloured, aggregating 'gregarious' phases of the desert locust Schistocerca gregaria. The desert locust has the genetic potential to exist in either phase, changing between them within a lifetime and epigenetically across generations. Our aim was to compare final-instar nymphs of the two phases with respect to key nutritional variables, including (i) points of regulated intake (the 'intake target') for protein and carbohydrate, (ii) the nature of trade-offs between over-eating nutrients in excess and under-eating those in deficit when fed nutritionally unbalanced foods, (iii) diet-related patterns of nutrient utilisation, and (iv) the performance consequences of eating nutritionally unbalanced diets. When provided with pairs of nutritionally unbalanced but complementary foods, both phases regulated their intake of protein and carbohydrate to a similar point. However, when confined to foods that were of unbalanced protein to carbohydrate ratio, gregarious nymphs ate more than solitarious insects. Both phases regulated protein growth, but gregarious insects did so to a lower adult body protein content and converted ingested protein to growth less efficiently. When fed a food high in carbohydrate and low in protein, gregarious nymphs deposited more body lipid and survived less well than did solitarious insects. Solitarious nymphs developed more quickly than gregarious nymphs except on the two most extremely unbalanced diets, on which development time was similar. The results are discussed with respect to the different nutritional ecologies of the two phases and used to develop the hypothesis that animals have evolved to trade-off the cost of eating excess of a nutritionally unbalanced diet against the probability of encountering foods of complementary composition in the future.