Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.

Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in relatively high concentration in human plasma. Erythrocytes, endothelial cells, and activated platelets are the main sources of circulating S1P. The majority of plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In recent years, HDL-bound S1P attracted much attention due to its cardioprotective and anti-atherogenic properties. We have previously found that endurance-trained athletes are characterized by higher plasma S1P concentration compared to untrained individuals. This finding prompted us to examine the effect of endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male subjects completed an 8-week training program on a rowing ergometer. Three days before the first, and 3 days after the last training session, blood samples were drawn from an antecubital vein. We found that total plasma S1P concentration was increased after the training. Further analysis of different plasma fractions showed that the training selectively elevated HDL-bound S1P. This effect was associated with activation of sphingosine kinase in erythrocytes and platelets and enhanced S1P release from red blood cells. We postulate that increase in HDL-bound S1P level is one of the mechanisms underlying beneficial effects of regular physical activity on cardiovascular diseases.

Probing the Interlayer Exciton Physics in a MoS2/MoSe2/MoS2 van der Waals Heterostructure.

Stacking atomic monolayers of semiconducting transition metal dichalcogenides (TMDs) has emerged as an effective way to engineer their properties. In principle, the staggered band alignment of TMD heterostructures should result in the formation of interlayer excitons with long lifetimes and robust valley polarization. However, these features have been observed simultaneously only in MoSe2/WSe2 heterostructures. Here we report on the observation of long-lived interlayer exciton emission in a MoS2/MoSe2/MoS2 trilayer van der Waals heterostructure. The interlayer nature of the observed transition is confirmed by photoluminescence spectroscopy, as well as by analyzing the temporal, excitation power, and temperature dependence of the interlayer emission peak. The observed complex photoluminescence dynamics suggests the presence of quasi-degenerate momentum-direct and momentum-indirect bandgaps. We show that circularly polarized optical pumping results in long-lived valley polarization of interlayer exciton. Intriguingly, the interlayer exciton photoluminescence has helicity opposite to the excitation. Our results show that through a careful choice of the TMDs forming the van der Waals heterostructure it is possible to control the circular polarization of the interlayer exciton emission.

A fluorescent HTS assay for phosphohydrolases based on nucleoside 5'-fluorophosphates: its application in screening for inhibitors of mRNA decapping scavenger and PDE-I.

Several nucleotide-specific phosphohydrolases can cleave P-F bonds in substrate analogues containing a fluorophosphate moiety to release fluoride ions. In this work, by employing a fluoride-sensitive molecular sensor, we harnessed this cleavage reaction to develop a fluorescence assay to screen for phosphohydrolase inhibitors. The assay is rapid, sensitive, and based on simple and synthetically available reagents. The assay was adapted to the high-throughput screening (HTS) format and its utility was demonstrated by screening an 'in-house' library of small nucleotides against two enzymes: DcpS, a metal-independent mRNA decapping pyrophosphatase of the histidine triad (HIT) family; and PDE-I, a divalent cation-dependent nuclease. Our screening results agreed with the known specificities of DcpS and PDE-I, and led to the selection of several inhibitors featuring low-micromolar IC50 values. For DcpS, we also verified the results by using an alternative method with the natural substrate. Notably, the assay presented here is the first fluorescence-based HTS-adaptable assay for DcpS, an established therapeutic target for spinal muscular atrophy. The assay should be useful for phosphohydrolase specificity profiling and inhibitor discovery, particularly in the context of DcpS and other HIT-family enzymes, which play key roles in maintaining cellular functions and have been linked to disease development.

The Lipari-Szabo Model-Free Analysis as a Method for Study of Molecular Motion in Solid State Heteronuclear Systems Using NMR Off-Resonance.

In the present work, a new method for measuring motional parameters using the off-resonance technique was described. The Lipari-Szabo model-free formalism was used to analyze molecular dynamics in a heteronuclear system [1, 2]. Cross-relaxation solid state nuclear magnetic resonance off-resonance experiments were performed on a homebuilt pulse spectrometer operating at the frequency of 30.2 MHz for protons at temperature 173 K. The proton spins were spin-locked in the effective field [Formula: see text] while 19F spins were continuously saturated for a long time. It was possible to carry out these experiments because a uniquely designed probe was able to produce three slightly differing frequencies on and off-resonance for protons and the frequency of 28.411 MHz for fluorine [3-6]. The off-resonance frequencies can be changed within the range of 30.2-30.6 MHz.

Analysis of Uniformity of Magnetic Field Generated by the Two-Pair Coil System.

In this paper we use a simple analysis based on properties of the axial field generated by symmetrical multipoles to reveal all possible distributions of two coaxial pairs of circular windings, which result in systems featuring zero octupole and 32 pole magnetic moments (six-order systems). Homogeneity of magnetic field of selected systems is analyzed. It has been found that one of the derived systems generates homogenous magnetic field whose volume is comparable to that yielded by the eight-order system. The influence of the current distribution and the windings placement on the field homogeneity is considered. The table, graphs and equations given in the paper facilitate the choice of the most appropriate design for a given problem. The systems presented may find applications in low field electron paramagnetic resonance imaging, some functional f-MRI (nuclear magnetic resonance imaging) and bioelectromagnetic experiments requiring the access to the working space from all directions.

Change in blood gelsolin concentration in response to physical exercise.

Plasma gelsolin (pGSN) produced by muscle is an abundant protein of extracellular fluids capable of severing actin filaments and eliminating actin from the circulation. Additionally, pGSN modulates the cellular effects of some bioactive lipids. In this study we test the hypothesis that hormonal and metabolic adaptations to exercise are associated with changes in gelsolin concentration in blood. Plasma samples were collected from twenty healthy males recruited from untrained (UT, n=10) and endurance trained (ET, n=10) groups that performed 30-60 minutes of exercise on a cycloergometer at a workload corresponding to 70% of VO2max. Gelsolin concentration was determined by quantitative Western blot analysis with an anti-human gelsolin antibody. The gelsolin concentration in UT and ET subjects before starting exercise ranged from 104 to 330 and 163 to 337 µg · ml(-1) respectively. After 30 minutes of exercise we observed a significant decrease of plasma gelsolin in the UT group (p<0.05) while the gelsolin concentration in the ET group rose on average from 244 to 271 µg · ml(-1). However, this increase did not reach statistical significance. Endurance training might increase the ability of muscle tissue to express plasma gelsolin as part of an adaptive mechanism.

Ceramide metabolism is affected by obesity and diabetes in human adipose tissue.

Ceramide is involved in development of insulin resistance. However, there are no data on ceramide metabolism in human adipose tissue. The aim of our study was to examine sphingolipid metabolism in fat tissue from obese nondiabetic (n = 11), obese diabetic (n = 11), and lean nondiabetic (n = 8) subjects. The content of ceramide (Cer), dihydroceramide (dhCer), sphingosine (SPH), sphinganine (SPA), sphingosine-1-phosphate (S1P; pmol/mg of protein), the expression (mRNA) and activity of key enzymes responsible for Cer metabolism: serine palmitoyltransferase (SPT), neutral and acidic sphingomyelinase (nSMase and aSMase, respectively), and neutral and acidic ceramidase (nCDase and aCDase, respectively) were examined in human adipose tissue. The contents of SPA and Cer were significantly lower whereas the content of dhCer was higher in both obese groups than the respective values in the lean subjects. The expression of examined enzymes was elevated in both obese groups. The SPT and CDases activity increased whereas aSMase activity deceased in both obese groups. We have found correlation between adipose tissue Cer content and plasma adiponectin concentration (r = 0.69, P < 0.001) and negative correlation between total Cer content and HOMA-IR index (homeostasis model of insulin resistance) (r = -0.67, P < 0.001). We have found that both obesity and diabetes affected pathways of sphingolipid metabolism in the adipose tissue.

The Faraday effect of natural and artificial ferritins.

Measurements of the Faraday rotation at room temperature over the light wavelength range of 300-680 nm for horse spleen ferritin (HSF), magnetoferritin with different loading factors (LFs) and nanoscale magnetite and Fe(2)O(3) suspensions are reported. The Faraday rotation and the magnetization of the materials studied present similar magnetic field dependences and are characteristic of a superparamagnetic system. The dependence of the Faraday rotation on the magnetic field is described, excluding HSF and Fe(2)O(3), by a Langevin function with a log-normal distribution of the particle size allowing the core diameters of the substances studied to be calculated. It was found that the specific Verdet constant depends linearly on the LF. Differences in the Faraday rotation spectra and their magnetic field dependences allow discrimination between magnetoferritin with maghemite and magnetite cores which can be very useful in biomedicine.

The Instrument Set for Generating Fast Adiabatic Passage.

The design and construction of a high-performance, low-cost, and easy to assemble adiabatic extension set for homebuilt and commercial spectrometers is described. Described apparatus set was designed for the fast adiabatic passage generation and is based on direct digital synthesizer DDS. This solution gives generator high signal to noise ratio, phase stability even during frequency change which is only possible in expansive commercial high-end hardware. Critical synchronization and timing issues are considered and solutions are discussed. Different experimental conditions and techniques for the measurements are briefly discussed. The proposed system is very flexible and might be used for the measurement of low-frequency nuclear magnetic resonance.

Interlayer excitons in MoSe2/2D perovskite hybrid heterostructures - the interplay between charge and energy transfer.

van der Waals crystals have opened a new and exciting chapter in heterostructure research, removing the lattice matching constraint characteristics of epitaxial semiconductors. They provide unprecedented flexibility for heterostructure design. Combining two-dimensional (2D) perovskites with other 2D materials, in particular transition metal dichalcogenides (TMDs), has recently emerged as an intriguing way to design hybrid opto-electronic devices. However, the excitation transfer mechanism between the layers (charge or energy transfer) remains to be elucidated. Here, we investigate PEA2PbI4/MoSe2 and (BA)2PbI4/MoSe2 heterostructures by combining optical spectroscopy and density functional theory (DFT) calculations. We show that band alignment facilitates charge transfer. Namely, holes are transferred from TMDs to 2D perovskites, while the electron transfer is blocked, resulting in the formation of interlayer excitons. Moreover, we show that the energy transfer mechanism can be turned on by an appropriate alignment of the excitonic states, providing a rule of thumb for the deterministic control of the excitation transfer mechanism in TMD/2D-perovskite heterostructures.

The carcinogenic effects of benzoquinones produced by the flour beetle.

Humans and animals come into contact with various compounds in their natural environment. Most of the encountered substances are neutral, yet some may carry adverse health effects. The ingested food may be a source of harmful substances, including benzoquinones which, as shown by research results cited in this paper, demonstrate toxic, carcinogenic and enterotoxic activity. This group of compounds is inclusive of 2-methyl-1,4-benzoquinone (MBQ) and 2-ethyl-1,4-benzoquinone (EBQ), defensive secretions of the confused flour beetle (Tribolium confusum J. du V) and the red flour beetle (Tribolium castaneum Herbst). Benzoquinones have a carcinogenic effect, they are inhibitors of growth of various microorganisms, they produce a self-defense mechanism in threat situations and affect population aggregation. As noted by the referenced authors, the properties of benzoquinones have not been fully researched to this date.

Effects of streptozotocin-induced diabetes and elevation of plasma FFA on ceramide metabolism in rat skeletal muscle.

Ceramide is likely to mediate in induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin-diabetes and treatment with heparin on ceramide metabolism in skeletal muscles. The experiments were performed on Wistar rats divided into three groups: 1) control, 2) treated with streptozotocin, and 3) treated with heparin. Assays were carried out on three types of muscle: slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic, and fast-twitch glycolytic (red and white section of the gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), and neutral and alkaline ceramidase (nCDase and alCDase) was examined. The content of ceramide, sphinganine, sphingosine, and sphingosine-1-phosphate was also measured. Both streptozotocin-diabetes and treatment with heparin increased the activity of SPT in each type of muscle. Heparin inhibits the activity of aSMase and concomitantly induces the activity of nSMase in each studied muscle. Streptozotocin decreased aSMase activity in each muscle and increased nSMase activity in the soleus and red section of the gastrocnemius. Heparin induced, whereas streptozotocin inhibited the activity of n-CDase in the soleus and the red section of the gastrocnemius. Heparin increased the activity of alCDase in the red gastrocnemius. In the soleus and the white gastrocnemius the activity of alCDase decreased. Streptozotocin significantly increased the content of ceramide in each muscle studied and heparin did it only in the soleus. It is concluded that insulin deficiency is accompanied by alterations in ceramide metabolism in skeletal muscles. Increased concentration of the plasma free fatty acids may mediate certain effects of insulin deficiency.

n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet.

AIMS/HYPOTHESIS: Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators of peroxisome proliferator-activated receptor gamma, which improve whole-body insulin sensitivity. We hypothesised that a combined treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms, impairments of lipid and glucose homeostasis in obesity. METHODS: Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone (10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as on liver and muscle gene expression and metabolism were analysed. Euglycaemic-hyperinsulinaemic clamps were used to characterise the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose tolerance (IGT). RESULTS: DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, low-grade adipose tissue inflammation, dyslipidaemia and insulin resistance, while inducing adiponectin, suppressing hepatic lipogenesis and decreasing muscle ceramide concentration. The improvement in glucose tolerance reflected a synergistic stimulatory effect of the combined treatment on muscle glycogen synthesis and its sensitivity to insulin. The combination treatment also reversed dietary obesity, dyslipidaemia and IGT. CONCLUSIONS/INTERPRETATION: DHA/EPA and rosiglitazone can be used as complementary therapies to counteract dyslipidaemia and insulin resistance. The combination treatment may reduce dose requirements and hence the incidence of adverse side effects of thiazolidinedione therapy.

Effect of acute exercise on mRNA and protein expression of main components of the lipolytic complex in different skeletal muscle types in the rat.

Adipose triglyceride lipase (ATGL) hydrolyses the first bond of triacylglycerols. The activity of the enzyme is elevated by comparative gene identification 58 (CGI-58), and reduced by G0/G1 switch gene 2 (G0S2) protein. There are no data on the effect of acute exercise on the behavior of particular components of the lipolytic complex in different skeletal muscle types, therefore, the aim of the present study was to examine that topic. The experiments were carried out on four groups of male Wistar rats: 1) control 2) rats running on a treadmill at the speed of 18 m/min for 30 min, 3) at the speed of 18 m/min for 120 min, 4) for 30 min at the speed of 28 m/min. We found that each exercise bout induced numerous changes in the expression of mRNA and protein ATGL, hormone-sensitive lipase, CGI-58 and G0S2 in the investigated muscles. These changes, depended to a large extent on a muscle type. In general, the strongest pro-lipolytic response was observed in the soleus, followed by the red section of the gastrocnemius (RG). On the other hand, in the white section of the gastrocnemius protein expression of the components of the lipolytic complex was reduced in response to exercise. These changes were not accompanied by alterations in muscle triacylglycerol content, with the exception of a reduction observed in the RG following 2-hour run. We conclude that a single bout of exercise induces significant effect on the expression of components of the lipolytic complex in skeletal muscle, and that the magnitude of this effect depends on muscle oxidative capacity, as well as the duration and intensity of exercise.

Histological estimation of the small intestine wall after administration of feed containing deoxynivalenol, T-2 toxin and zearalenone in the pig.

Fusarium spp. moulds are common in moderate climate regions of North America, Asia and Europe. They produce hepatotoxic and nephrotoxic mycotoxins, acting like estrogens, impairing hemopoesis and immunosuppressing. Actively dividing skin cells, lymphatic tissue, haemopoetic tissue and gastrointestinal tissue are the most sensitive for these trichothecenes action. The mucosal membrane of the gastrointestinal tract is the first barrier of the organism contacting with foreign antigens like feed proteins, natural toxins, saprophytic and pathogenic microflora and mycotoxins. The aim of this study was to perform histological estimation of the porcine small intestine after short term intoxication with low doses of deoxynivalenol (DON), T-2 toxin (T-2) and zearalenone (ZEA) obtained from wheat naturally contaminated with Fusarium moulds. Experimental pigs (n=5) were fed for 14 days feed containing DON, T-2 and ZEA (28.9, 11.5 and 33.2 microg kg(-1) of feed). On the last day of the experiment, the animals were euthanised and samples of the jejunum were collected for histological examination. In the experimental pigs, normally developed intestinal villi and crypts were found. However, number of acidophilic granulocytes in the mucous membrane and decreased numbers of goblet cells, increased numbers of endothelial lymphocytes and numerous plasma cells in intestinal epithelium was observed. On the surface of the intestinal epithelium the glycocalyx was poorly developed. The results obtained suggest that short term intoxication with low doses of DON, T-2 and ZEA does not cause significant changes in the histological structure of the small intestine in the pig. However, low concentrations of DON, T-2 and ZEA probably influence enterocytes metabolism and evoke inflammation of the mucous membrane of the small intestine.

PPARalpha agonist induces the accumulation of ceramide in the heart of rats fed high-fat diet.

It was shown that high-fat feeding of mice with cardiac-specific overexpression of peroxisome proliferator-activated receptor (PPAR) alpha but not wild type animals leads to the accumulation of ceramide (an important mediator of lipotoxicity) in the heart [Finck et al. 2003 Proc Natl Acad Sci USA]. To investigate the mechanism of this phenomenon we examined the effects of PPARalpha activation on ceramide metabolism in the myocardium. Male Wistar rats were fed either a standard chow or a high-fat diet. Each group was divided into two subgroups: control and treated with selective PPARalpha activator - WY-14643. In the rats fed on the standard diet WY-14643 did not affect the myocardial content of sphingomyelin and ceramide but reduced the content of sphinganine and sphingosine. It also inhibited the activity of neutral sphingomyelinase and increased the activity of acid sphingomyelinase, whereas the activity of ceramidases and serine palmitoyltransferase (SPT) remained stable. High-fat diet itself did not affect the content of the examined sphingolipids. However, it reduced the activity of sphingomyelinases and ceramidases having no effect on the activity of SPT. Administration of WY-14643 to this group significantly increased the content of myocardial free palmitate, ceramide, sphingomyelin and the activity of SPT. Our results demonstrated that PPARalpha activation modulates myocardial ceramide metabolism and leads to the accumulation of ceramide in the heart of the high-fat fed rats due to its increased synthesis de novo.

Multicolor emission from intermediate band semiconductor ZnO1-xSex.

Photoluminescence and photomodulated reflectivity measurements of ZnOSe alloys are used to demonstrate a splitting of the valence band due to the band anticrossing interaction between localized Se states and the extended valence band states of the host ZnO matrix. A strong multiband emission associated with optical transitions from the conduction band to lower E- and upper E+ valence subbands has been observed at room temperature. The composition dependence of the optical transition energies is well explained by the electronic band structure calculated using the kp method combined with the band anticrossing model. The observation of the multiband emission is possible because of relatively long recombination lifetimes. Longer than 1 ns lifetimes for holes photoexcited to the lower valence subband offer a potential of using the alloy as an intermediate band semiconductor for solar power conversion applications.

Observation of A Raman mode splitting in few layer black phosphorus encapsulated with hexagonal boron nitride.

We investigate the impact of encapsulation with hexagonal boron nitride (h-BN) on the Raman spectrum of few layer black phosphorus. The encapsulation results in a significant reduction of the line width of the Raman modes of black phosphorus, due to a reduced phonon scattering rate. We observe a so far elusive peak in the Raman spectra ∼4 cm-1 above the A mode in trilayer and thicker flakes, which had not been observed experimentally. The newly observed mode originates from the strong black phosphorus inter-layer interaction, which induces a hardening of the surface atom vibration with respect to the corresponding modes of the inner layers. The observation of this mode suggests a significant impact of h-BN encapsulation on the properties of black phosphorus and can serve as an indicator of the quality of its surface.

Adiabatic fast passage application in solid state NMR study of cross relaxation and molecular dynamics in heteronuclear systems.

The paper presents the benefits of using fast adiabatic passage for the study of molecular dynamics in the solid state heteronuclear systems in the laboratory frame. A homemade pulse spectrometer operating at the frequency of 30.2MHz and 28.411MHz for protons and fluorines, respectively, has been enhanced with microcontroller direct digital synthesizer DDS controller [1-4]. This work briefly describes how to construct a low-cost and easy-to-assemble adiabatic extension set for homemade and commercial spectrometers based on recently very popular Arduino shields. The described set was designed for fast adiabatic generation. Timing and synchronization problems are discussed. The cross-relaxation experiments with different initial states of the two spin systems have been performed. Contrary to our previous work [5] where the steady-state NOE experiments were conducted now proton spins (1)H are polarized in the magnetic field B0 while fluorine spins (19)F are perturbed by selective saturation for a short time and then the system is allowed to evolve for a period in the absence of a saturating field. The adiabatic passage application leads to a reversal of magnetization of fluorine spins and increases the amplitude of the signal.

Unified Model of Nanosecond Charge Recombination in Closed Reaction Centers from Rhodobacter sphaeroides: Role of Protein Polarization Dynamics.

Ongoing questions surround the influence of protein dynamics on rapid processes such as biological electron transfer. Such questions are particularly addressable in light-activated systems. In Rhodobacter sphaeroides reaction centers, charge recombination or back electron transfer from the reduced bacteriopheophytin, HA(-), to the oxidized dimeric bacteriochlorophyll, P(+), may be monitored by both transient absorption spectroscopy and transient fluorescence spectroscopy. Signals measured with both these techniques decay in a similar three-exponential fashion with lifetimes of ∼0.6-0.7, ∼2-4, and ∼10-20 ns, revealing the complex character of this electron transfer reaction. In this study a single kinetic model was developed to connect lifetime and amplitude data from both techniques. The model took into account the possibility that electron transfer from HA(-) to P(+) may occur with transient formation of the state P(+)BA(-). As a result it was possible to model the impact of nanosecond protein relaxation on the free energy levels of both P(+)HA(-) and P(+)BA(-) states relative to that of the singlet excited state of P, P*. Surprisingly, whereas the free energy gap between P* and P(+)HA(-) increased with time in response to protein reorganization, the free energy gap between P* and P(+)BA(-) decreased. This finding may be accounted for by a gradual polarization of the protein environment which stabilizes the state P(+)HA(-) and destabilizes the state P(+)BA(-), favoring productive charge separation over unproductive charge recombination.