Recently discovered Aedes japonicus japonicus (Diptera: Culicidae) populations in The Netherlands and northern Germany resulted from a new introduction event and from a split from an existing population

BACKGROUND: Originally native to East Asia, Aedes japonicus japonicus, a potential vector of several arboviruses, has become one of the most invasive mosquito species in the world. After having established in the USA, it is now spreading in Europe, with new populations emerging. In contrast to the USA, the introduction pathways and modes of dispersal in Europe are largely obscure. METHODS: To find out if two recently detected populations of Ae. j. japonicus in The Netherlands and northern Germany go back to new importations or to movements within Europe, the genetic makeup of mosquito specimens from all known European populations was compared. For this purpose, seven microsatellite loci from a representative number of mosquito specimens were genotyped and part of their mitochondrial nad4 gene sequenced. RESULTS: A novel nad4 haplotype found in the newly discovered Dutch population of Ae. j. japonicus suggests that this population is not closely related to the other European populations but has emanated from a further introduction event. With five nad4 haplotypes, the Dutch population also shows a very high genetic diversity indicating that either the founder population was very large or multiple introductions took place. By contrast, the recently detected North German population could be clearly assigned to one of the two previously determined European Ae. j. japonicus microsatellite genotypes and shows nad4 haplotypes that are known from West Germany. CONCLUSION: As the European populations of Ae. j. japonicus are geographically separated but genetically mixed, their establishment must be attributed to passive transportation. In addition to intercontinental shipment, it can be assumed that human activities are also responsible for medium- and short-distance overland spread. A better understanding of the processes underlying the introduction and spread of this invasive species will help to increase public awareness of the human-mediated displacement of mosquitoes and to find strategies to avoid it

Cholesterol overload: contact sites to the rescue!

Delivery of low-density lipoprotein-derived cholesterol to the endoplasmic reticulum (ER) is essential for cholesterol homeostasis, yet the mechanism of this transport has largely remained elusive. Two recent reports shed some light on this process, uncovering a role for Niemann Pick type-C1 protein (NPC1) in the formation of membrane contact sites (MCS) between late endosomes (LE)/lysosomes (Lys) and the ER. Both studies identified a loss of MCS in cells lacking functional NPC1, where cholesterol accumulates in late endocytic organelles. Remarkably, and taking different approaches, both studies have made a striking observation that expansion of LE/Lys-ER MCS can rescue the cholesterol accumulation phenotype in NPC1 mutant or deficient cells. In both cases, the cholesterol was shown to be transported to the ER, demonstrating the importance of ER-LE/Lys contact sites in the direct transport of low-density lipoprotein-derived cholesterol to the ER

Determination of HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in heart failure patients

Altres ajuts: Fundació La MARATÓ de TV3 (201502, 201516).Altres ajuts: PERIS/SLT002-16-00234Altres ajuts: PERIS/SLT002-16-00209Aims: Cell therapy can be used to repair functionally impaired organs and tissues in humans. Although autologous cells have an immunological advantage, it is difficult to obtain high cell numbers for therapy. Well-characterized banks of cells with human leukocyte antigens (HLA) that are representative of a given population are thus needed. The present study investigates the HLA allele and haplotype frequencies in a cohort of heart failure (HF) patients. Methods and results: We carried out the HLA typing and the allele and haplotype frequency analysis in 247 ambulatory HF patients. We determined HLA class I (A, B, and C) and class II (DRB1 and DQB1) using next-generation sequencing technology. The allele frequencies were obtained using Python for Population Genomics (PyPop) software, and HLA haplotypes were estimated using HaploStats. A total of 30 HLA-A, 56 HLA-B, 23 HLA-C, 36 HLA-DRB1, and 15 HLA-DQB1 distinct alleles were identified within the studied cohort. The genotype frequencies of all five HLA loci were in Hardy-Weinberg equilibrium. We detected differences in HLA allele frequencies among patients when the etiological cause of HF was considered. There were a total of 494 five-loci haplotypes, five of which were present six or more times. Moreover, the most common estimated HLA haplotype was HLA-A*01:01, HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, and HLA-DQB1*02:01 (6.07% haplotype frequency per patient). Remarkably, the 11 most frequent haplotypes would cover 31.17% of the patients of the cohort in need of allogeneic cell therapy. Conclusions: Our findings could be useful for improving allogeneic cell administration outcomes without concomitant immunosuppression

Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors.

OBJECTIVE: Alcoholic steatohepatitis is a life-threatening condition with short-term mortality up to 40%. It features hepatic neutrophil infiltration and blood neutrophilia, and may evolve from ethanol-induced breakdown of the enteric barrier and consequent bacteraemia. Signalling through CXCR1/2 G-protein-coupled-receptors (GPCRs), the interleukin (IL)-8 receptors, is critical for the recruitment and activation of neutrophils. We have developed short lipopeptides (pepducins), which inhibit post-ligand GPCR activation precisely targeting individual GPCRs. DESIGN: Experimental alcoholic liver disease was induced by administering alcohol and a Lieber-DeCarli high-fat diet. CXCR1/2 GPCRs were blocked via pepducins either from onset of the experiment or after disease was fully established. Hepatic inflammatory infiltration, hepatocyte lipid accumulation and overall survival were assessed as primary outcome parameters. Neutrophil activation was assessed by myeloperoxidase activity and liver cell damage by aspartate aminotransferase and alanine aminotransferase plasma levels. Chemotaxis assays were performed to identify chemoattractant signals derived from alcohol-exposed hepatocytes. RESULTS: Here, we show that experimental alcoholic liver disease is driven by CXCR1/2-dependent activation of neutrophils. CXCR1/2-specific pepducins not only protected mice from liver inflammation, weight loss and mortality associated with experimental alcoholic liver disease, but therapeutic administration cured disease and prevented further mortality in fully established disease. Hepatic neutrophil infiltration and triglyceride accumulation was abrogated by CXCR1/2 blockade. Moreover, CXCL-1 plasma levels were decreased with the pepducin therapy as was the transcription of hepatic IL-1β mRNA. CONCLUSIONS: We propose that high circulating IL-8 in human alcoholic hepatitis may cause pathogenic overzealous neutrophil activation, and therapeutic blockade via pepducins merits clinical study.Wellcome Trust Career Re-entry Fellowship (103077/Z/13/Z) to NCK, Christian Doppler Research Society to HT and European Research Council (FP7/2007- 2013) to AKThis is the final version of the article. It first appeared from the BMJ Group via http://dx.doi.org/10.1136/gutjnl-2015-31034

Simultaneous Continuation of Infinitely Many Sinks Near a Quadratic Homoclinic Tangency

We prove that the $C^3$ diffeomorphisms on surfaces, exhibiting infinitely many sinksnear the generic unfolding of a quadratic homoclinic tangency of a dissipative saddle, can be perturbed along an infinite dimensional manifold of $C^3$ diffeomorphisms such that infinitely many sinks persist simultaneously. On the other hand, if they are perturbed along one-parameter families that unfold generically the quadratic tangencies, then at most a finite number of those sinks have continuation

Reduced plasma extracellular vesicle CD5L content in patients with acute-on-chronic liver failure: interplay with specialized pro-resolving lipid mediators.

Acute-on chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated cirrhosis (AD). It is characterized by a systemic hyperinflammatory state, leading to multiple organ failure. Our objective was to analyze macrophage anti-inflammatory protein CD5L in plasma extracellular vesicles (EVs) and assess its as yet unknown relationship with lipid mediators in ACLF. With this aim, EVs were purified by size exclusion chromatography from the plasma of healthy subjects (HS) (n=6) and patients with compensated cirrhosis (CC) (n=6), AD (n=11) and ACLF (n=11), which were defined as positive for CD9, CD5L and CD63 and their size, number, morphology and lipid mediator content were characterized by NTA, EM, and LC-MS/MS, respectively. Additionally, plasma CD5L was quantified by ELISA in 10 HS, 20 CC and 149 AD patients (69 ACLF). Moreover, macrophage CD5L expression and the biosynthesis of specialized lipid mediators (SPMs) were characterized in vitro in primary cells. Our results indicate that circulating EVs were significantly suppressed in cirrhosis, regardless of severity, and showed considerable alterations in CD5L and lipid mediator content as the disease progressed. In AD, levels of EV CD5L correlated best with those of the SPM RvE1. Analysis of total plasma supported these data and showed that, in ACLF, low CD5L levels were associated with circulatory (p<0.001), brain (p<0.008) and respiratory (p<0.05) failure (Mann-Whitney test). Functional studies in macrophages indicated a positive feedback loop between CD5L and RvE1 biosynthesis. In summary, we have determined a significant alteration of circulating EV contents in ACLF, with a loss of anti-inflammatory and pro-resolving molecules involved in the control of acute inflammation in this condition

The MAL protein is crucial for proper membrane condensation at the ciliary base, which is required for primary cilium elongation

The base of the primary cilium contains a zone of condensed membranes whose importance is not known. Here, we have studied the involvement of MAL, a tetraspanning protein that exclusively partitions into condensed membrane fractions, in the condensation of membranes at the ciliary base and investigated the importance of these membranes in primary cilium formation. We show that MAL accumulates at the ciliary base of epithelial MDCK cells. Knockdown of MAL expression resulted in a drastic reduction in the condensation of membranes at the ciliary base, the percentage of ciliated cells and the length of the cilia, but did not affect the docking of the centrosome to the plasma membrane or produce missorting of proteins to the pericentriolar zone or to the membrane of the remaining cilia. Rab8 (for which there are two isoforms, Rab8A and Rab8b), IFT88 and IFT20, which are important components of the machinery of ciliary growth, were recruited normally to the ciliary base of MAL-knockdown cells but were unable to elongate the primary cilium correctly. MAL, therefore, is crucial for the proper condensation of membranes at the ciliary base, which is required for efficient primary cilium extensionThis work was supported by the Ministerio de Economıa y Competitividad, Spain [grant numbers BFU2012-32532 and CONSOLIDER COAT CSD2009-00016 to M. A.A.]. G.A. was supported by the Amarouto Program for senior researchers from the Comunidad Autónoma de Madri

Magnetic Properties of Co(II) Complexes with Polyhedral Carborane Ligands

In this work we present a computational analysis of a new family of magnetic Co(II) single-ion complexes with large magnetic anisotropy based on icosahedral and octahedral carborane ligands. In particular, we extend our previous computational work [Alcoba et al. Inorg. Chem. 57, 7763 (2018)] on mononuclear Co(II) complexes with 1,2-(HS)2-1,2-C2B10H10 and 9,12-(HS)2-1,2-C2B10H10 icosahedral o-carborane ligands to a larger set of complexes where the Co(II) ion is doubly chelated by those ligands and by other two positional isomers belonging to the 1,2-dicarba-closo-dodecaborane family. We also describe Co(II) complexes with octahedral ligands derived from 1,2- dicarba-closo-hexaborane and study the effects of replacing a thiol group by a hydroxy one in both polyhedral geometries, as well as the influence of the position of the carbon atoms. Analyzing the results for a total of 20 complexes, our results show that carborane-based Co(II) single-ion compounds present a distorted tetrahedral geometry, high spin ground states, and high values for the magnetic anisotropy parameters. We point out which of these would be suitable candidates to be synthesized and used as molecular magnets.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada