Protein and lipid utilization during fasting with shallow and deep hypothermia in the European hedgehog (Erinaceus europaeus)

We investigated whether the relative contributions of body protein and lipid reserves differ according to the level of energy expenditure in fasting animals. Protein and lipid utilization was therefore quantified and compared in hedgehogs which fasted with shallow and deep hypothermia, i.e. by exposure at 5 or 20 °C ambient temperature. Body composition was determined for every 150-g decrease in mass throughout the experiment, allowing the calculation of regression lines between body mass (independent variable, x) and body composition (dependent variable, y: water, protein, neutral lipids, phospholipids and cholesterol). There were highly significant (P<0.001) linear decreases in all body components with decreasing body mass in both groups of hedgehogs. Neutral lipids were the main component of the total body mass loss (54%) in fasted animals with shallow and deep hypothermia, percentages of water (26–30%) and protein (10–11%) being lower, and those of phospholipid and cholesterol negligible (<0.5%). In spite of different levels in energy expenditure (2.54 and 1.07 W·kg^-1 in shallow-and deep-hypothermal fasting hedgehogs, respectively), the energy sources were identical in both groups, neutral lipid being the main fuel (91–92%) and body protein accounting for the remainder (8–9%). Prolonged fasting with shallow and deep hypothermia were marked by low alaninemia and glycemia, while plasma free fatty acids and -hydroxybutyrate were elevated. These data therefore indicate that the relative contribution of lipid and protein is similar during prolonged fasting with shallow and deep hypothermia, i.e. there is no specific effect of deep hypothermia on body fuel utilization. The tolerance of a much longer fast in deep-hypothermal hedgehogs can simply be attributed to the lower rates of lipid and protein utilization as a result of the lower level of energy expenditure.Abbreviations bm body mass     

Activation of smooth muscle in the airway wall, force production, and airway narrowing.

Airway narrowing depends on smooth muscle force production and muscle shortening, but the structural and geometric properties exhibited by individual generations of the bronchial tree largely determine the extent and characteristics of airway narrowing. Properties of major importance include the nature and integrity of the epithelium, the structural and mechanical properties of the airway wall, as well as airway diameter. The influence of these properties on airway narrowing measured as flow or flow resistance in large and small diameter segments of airways from pig lung is described using a novel preparation, the perfused bronchial segment.     

Upper esophageal sphincter impedance as a marker of sphincter opening diameter

The measurement of the physical extent of opening of the upper esophageal sphincter (UES) during bolus swallowing has to date relied on videofluoroscopy. Theoretically luminal impedance measured during bolus flow should be influenced by luminal diameter. In this study, we measured the UES nadir impedance (lowest value of impedance) during bolus swallowing and assessed it as a potential correlate of UES diameter that can be determined nonradiologically. In 40 patients with dysphagia, bolus swallowing of liquids, semisolids, and solids was recorded with manometry, impedance, and videofluoroscopy. During swallows, the UES opening diameter (in the lateral fluoroscopic view) was measured and compared with automated impedance manometry (AIM)-derived swallow function variables and UES nadir impedance as well as high-resolution manometry-derived UES relaxation pressure variables. Of all measured variables, UES nadir impedance was the most strongly correlated with UES opening diameter. Narrower diameter correlated with higher impedance (r = -0.478, P < 0.001). Patients with <10 mm, 10-14 mm (normal), and ≥ 15 mm UES diameter had average UES nadir impedances of 498 ± 39 Ohms, 369 ± 31 Ohms, and 293 ± 17 Ohms, respectively (ANOVA P = 0.005). A higher swallow risk index, indicative of poor pharyngeal swallow function, was associated with narrower UES diameter and higher UES nadir impedance during swallowing. In contrast, UES relaxation pressure variables were not significantly altered in relation to UES diameter. We concluded that the UES nadir impedance correlates with opening diameter of the UES during bolus flow. This variable, when combined with other pharyngeal AIM analysis variables, may allow characterization of the pathophysiology of swallowing dysfunction.     

Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design

HTP (human thymidine phosphorylase), also known as PD-ECGF (platelet-derived endothelial cell growth factor) or gliostatin, has an important role in nucleoside metabolism. HTP is implicated in angiogenesis and apoptosis and therefore is a prime target for drug design, including antitumour therapies. An HTP structure in a closed conformation complexed with an inhibitor has previously been solved. Earlier kinetic studies revealed an ordered release of thymine followed by ribose phosphate and product inhibition by both ligands. We have determined the structure of HTP from crystals grown in the presence of thymidine, which, surprisingly, resulted in bound thymine with HTP in a closed dead-end complex. Thus thymine appears to be able to reassociate with HTP after its initial ordered release before ribose phosphate and induces the closed conformation, hence explaining the mechanism of non-competitive product inhibition. In the active site in one of the four HTP molecules within the crystal asymmetric unit, additional electron density is present. This density has not been previously seen in any pyrimidine nucleoside phosphorylase and it defines a subsite that may be exploitable in drug design. Finally, because our crystals did not require proteolysed HTP to grow, the structure reveals a loop (residues 406-415), disordered in the previous HTP structure. This loop extends across the active-site cleft and appears to stabilize the dimer interface and the closed conformation by hydrogen-bonding. The present study will assist in the design of HTP inhibitors that could lead to drugs for anti-angiogenesis as well as for the potentiation of other nucleoside drugs.     

Prokaryotic-Type Aspartate Aminotransferase in Sorghum Leaves: Localization,Distribution and Potential Role

Russian Journal of Plant Physiology - The first part of this work consists in the identification of a prokaryotic-type bifunctional enzyme (aspartate aminotransferase, PT-AAT) in photosynthetic...     

Investigation of Metal levels in Artemisia herba-alba Medicinal Plant and Soil Samples Collected from Different Areas in Jordan Country

ABSTRACT

The concentrations of selected heavy metals including cadmium (Cd), lead (Pb), zinc (Zn), copper (Cu), nickel (Ni) and iron (Fe) in stems and leaves of Artemisia herba-alba medicinal plant and soil samples were evaluated. Results showed that there in heavy metal concentrations of washed and unwashed parts of A. herba-alba from northern site (Irbid), Middle site (Al-Mafraq), and Souhern site (Ma’an) (P < .05). Moreover, the results of this study revealed that there is a correlation between heavy metal levels in medicinal plants and their concentrations in soil. Two standard reference materials of plant (SRM 1790a; spinach, CRM 281; ryegrass) and a standard reference material of soil (GBW 07406) were examined to validate the method used. There were good agreements between the measured values of these standard reference materials and their certified values. In addition to that high recoveries for tested elements were ranged between 91.7–97.7%, 90–96.6%, and 92.2–97.7% in (CRM281, ryegrass), (SRM1570a, spinach) and (GBW 04706, soil) respectively. It is reasonable to conclude that the variation in metal concentration from site to another site as well as from element to another element may be due to the different factors such as traf?c volumes, the wind directions, the soil nature, and the element behavior.

Based on the results obtained, the health authorities will take in consideration these useful information and direct the residents about the risk of these pollutants.     

Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design

Background  

Development of countermeasures to bioterrorist threats such as those posed by the smallpox virus (variola), include vaccination and drug development. Selective activation of nucleoside analogues by virus-encoded thymidine (dThd) kinases (TK) represents one of the most successful strategies for antiviral chemotherapy as demonstrated for anti-herpes drugs. Vaccinia virus TK is a close orthologue of variola TK but also shares a relatively high sequence identity to human type 2 TK (hTK), thus achieving drug selectivity relative to the host enzyme is challenging.