A survey of pyrethroid‐resistant populations of Meligethes aeneus F. in Poland indicates the incidence of numerous substitutions in the pyrethroid target site of voltage‐sensitive sodium channels in individual beetles

The pollen beetle (Meligethes aeneus F.) is the most devastating pest of oilseed rape (Brassica napus) and is controlled by pyrethroid insecticides. However, resistance to pyrethroids in Europe is becoming widespread and predominant. Pyrethroids target the voltage‐sensitive sodium channel (VSSC), and mutations in VSSC may be responsible for pyrethroid insensitivity. Here, we analysed individual beetles that were resistant to esfenvalerate, a pyrethroid, from 14 populations that were collected from oilseed rape fields in Poland. We screened the VSSC domains that were presumed to directly interact with pyrethroids. We identified 18 heterozygous nucleic acid substitutions, amongst which six caused an amino acid change: N912S, G926S, I936V, R957G, F1538L and E1553G. Our analysis of the three‐dimensional structure of these domains in VSSC revealed that some of these changes may slightly influence the protein structure and hence the docking efficiency of esfenvalerate. Therefore, these mutations may impact the susceptibility of the sodium channel to the action of this insecticide.     

Nesfatin‐1: a novel inhibitory regulator of food intake and body weight

The protein nucleobindin 2 (NUCB2) or NEFA (DNA binding/EF‐hand/acidic amino acid rich region) was identified over a decade ago and implicated in intracellular processes. New developments came with the report that post‐translational processing of hypothalamic NUCB2 may result in nesfatin‐1, nesfatin‐2 and nesfatin‐3 and convergent studies showing that nesfatin‐1 and full length NUCB2 injected in the brain potently inhibit the dark phase food intake in rodents including leptin receptor deficient Zucker rats. Nesfatin‐1 also reduces body weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. In light of the obesity epidemic and its associated diseases, underlying new mechanisms regulating food intake may be promising targets in the drug treatment of obese patients particularly as the vast majority of them display reduced leptin sensitivity or leptin resistance while nesfatin‐1's mechanism of action is leptin independent. Although much progress on the localization of NUCB2/nesfatin‐1 in the brain and periphery as well as on the understanding of nesfatin‐1's anorexic effect have been achieved during the past three years, several important mechanisms have yet to be unraveled such as the identification of the nesfatin‐1 receptor and the regulation of NUCB2 processing and nesfatin‐1 release.     

Synthesis of S‐thiomethyl DMSA and S‐thiomethyl ECD,radiolabelling with technetium‐99m and biological evaluation

Protection of the thiolate function of dimercaptosuccinic acid (DMSA) and ethylenedi‐l ‐cysteine diethyl ester (ECD) by S‐thiomethylation allowed automatic deprotection during technetium‐99m (^99mTc) radiolabelling by direct reduction with stannous chloride dihydrate. Protection of the free thiolate group increased the stability of the ligands as well as deprotection during complexation, which resulted in the desired radiopharmaceuticals. The complexes obtained from the protected ligands were chromatographically (HPLC) and biologically compared with the corresponding ^99mTc complexes of the unprotected ligands. The results suggest that the aforementioned method of protection by S‐thiomethylation could be utilized for the development of single‐vial DMSA and ECD kit. Copyright © 2012 John Wiley & Sons, Ltd.     

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

Initial HRCT findings of novel influenza A (H1N1) infection

Please cite this paper as: Yuan et al. (2012) Initial HRCT findings of novel influenza A (H1N1) infection. Influenza and Other Respiratory Viruses 6(601), e114–e119. Objectives The aim of our study was to describe the presentation and illustrate the imaging features of chest high‐resolution computed tomography (HRCT) of patients with novel influenza A (H1N1) virus infection. Methods Data were collected from 163 hospitalized patients between November 2009 and March 2011, who fulfilled the clinical criteria for H1N1 influenza infection and underwent HRCT examinations within 24 hours of admission. Results Abnormal findings were observed in 40·5% of the patients. The patients with positive imaging findings were significantly older than patients with normal HRCT findings (P = 0·02). The most common finding was ground‐glass opacity (GGO) (n = 35). Interlobular septal thickening (n = 31) and centrilobular nodules (n = 30) were the second most frequent findings. Other common findings were consolidation, reticulation, and linear shadow. The most common imaging finding for lung involvement was GGO with a patchy pattern. Pulmonary involvement of the disease may be extensive and variable, but the total volume of affected lung was mostly <1 lobe. Conclusion The baseline HRCT may be valuable and suggestive even for non‐severe H1N1 infections. When a severe case or a evolution is suspected, chest CT could be essential both for determining the precise extent of parenchymal damage and for monitoring its evolution.