The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a

The inhibitor cystine knot (ICK) is an unusual three-disulfide architecture in which one of the disulfide bonds bisects a loop formed by the two other disulfide bridges and the intervening sections of the protein backbone. Peptides containing an ICK motif are frequently considered to have high levels of thermal, chemical and enzymatic stability due to cross-bracing provided by the disulfide bonds. Experimental studies supporting this contention are rare, in particular for spider-venom toxins, which represent the largest diversity of ICK peptides. We used ω-hexatoxin-Hv1a (Hv1a), an insecticidal toxin from the deadly Australian funnel-web spider, as a model system to examine the contribution of the cystine knot to the stability of ICK peptides. We show that Hv1a is highly stable when subjected to temperatures up to 75 °C, pH values as low as 1, and various organic solvents. Moreover, Hv1a was highly resistant to digestion by proteinase K and when incubated in insect hemolymph and human plasma. We demonstrate that the ICK motif is essential for the remarkable stability of Hv1a, with the peptide’s stability being dramatically reduced when the disulfide bonds are eliminated. Thus, this study demonstrates that the ICK motif significantly enhances the chemical and thermal stability of spider-venom peptides and provides them with a high level of protease resistance. This study also provides guidance to the conditions under which Hv1a could be stored and deployed as a bioinsecticide.     

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19–55) y, and mean body mass index was 22.43 (17.3–30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p?=?0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r?=?0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.     

Exact Solution of a Constraint Optimization Problem for the Thermoelectric Figure of Merit

In the classical theory of thermoelectricity, the performance integrals for a fully self-compatible material depend on the dimensionless figure of merit zT. Usually these integrals are evaluated for constraints z =  const. and zT =  const., respectively. In this paper we discuss the question from a mathematical point of view whether there is an optimal temperature characteristics of the figure of merit. We solve this isoperimetric variational problem for the best envelope of a family of curves z(T)T.     

IgG subclass deficiencies in children: Facts and fiction

The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey¹. Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children.     

Pulmonary perfusion quantification with flow‐sensitive inversion recovery (FAIR) UTE MRI in small animal imaging

Blood perfusion in lung parenchyma is an important property for assessing lung function. In small animals, its quantitation is limited even with radioactive isotopes or dynamic contrast‐enhanced MRI techniques. In this study, the feasibility flow‐sensitive alternating inversion recovery (FAIR) for the quantification of blood flow in lung parenchyma in free breathing rats at 7 T has been investigated. In order to obtain sufficient signal from the short T₂* lung parenchyma, a 2D ultra‐short echo time (UTE) Look‐Locker read‐out has been implemented. Acquisitions were segmented to maintain acquisition time within an acceptable range. A method to perform retrospective respiratory gating (DC‐SG) has been applied to investigate the impact of respiratory movement. Reproducibilities within and between sessions were estimated, and the ability of FAIR‐UTE to identify the decrease of lung perfusion under hyperoxic conditions was tested. The implemented technique allowed for the visualization of lung parenchyma with excellent SNR and no respiratory artifact even in ungated acquisitions. Lung parenchyma perfusion was obtained as 32.54 ± 2.26 mL/g/min in the left lung, and 34.09 ± 2.75 mL/g/min in the right lung. Application of retrospective gating significantly but minimally changes the perfusion values, implying that respiratory gating may not be necessary with this center‐our acquisition method. A decrease of 10% in lung perfusion was found between normoxic and hyperoxic conditions, proving the feasibility of the FAIR‐UTE approach to quantify lung perfusion changes.