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Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
Benoit, Joshua B. ; Adelman, Zach N. ; Reinhardt, Klaus ; Dolan, Amanda ; Poelchau, Monica ; Jennings, Emily C. ; Szuter, Elise M. ; Hagan, Richard W. ; Gujar, Hemant ; Shukla, Jayendra Nath ; Zhu, Fang ; Mohan, Muthugounder ; Nelson, David R. ; Rosendale, Andrew J. ; Derst, Christian ; Resnik, Valentina ; Wernig, Sebastian ; Menegazzi, Pamela ; Wegener, Christian ; Peschel, Nicolai ; Hendershot, Jacob M. ; Blenau, Wolfgang ; Predel, Reinhard ; Johnston, Paul R. ; Ioannidis, Panagiotis ; Waterhouse, Robert M. ; Nauen, Ralf ; Schorn, Corinna ; Ott, Mark-Christoph ; Maiwald, Frank ; Johnston, J. Spencer ; Gondhalekar, Ameya D. ; Scharf, Michael E. ; Peterson, Brittany F. ; Raje, Kapil R. ; Hottel, Benjamin A. ; Armisén, David ; Crumière, Antonin Jean Johan ; Refki, Peter Nagui ; Santos, Maria Emilia ; Sghaier, Essia ; Viala, Séverine ; Khila, Abderrahman ; Ahn, Seung-Joon ; Childers, Christopher ; Lee, Chien-Yueh ; Lin, Han ; Hughes, Daniel S. T. ; Duncan, Elizabeth J. ; Murali, Shwetha C. ; Qu, Jiaxin ; Dugan, Shannon ; Lee, Sandra L. ; Chao, Hsu ; Dinh, Huyen ; Han, Yi ; Doddapaneni, Harshavardhan ; Worley, Kim C. ; Muzny, Donna Marie ; Wheeler, David ; Panfilio, Kristen A. ; Vargas Jentzsch, Iris M. ; Vargo, Edward L. ; Booth, Warren ; Friedrich, Markus ; Weirauch, Matthew T. ; Anderson, Michelle A. ; Jones, Jeffery W. ; Mittapalli, Omprakash ; Zhao, Chaoyang ; Zhou, Jing-Jiang ; Evans, Jay D. ; Attardo, Geoffrey M. ; Robertson, Hugh M. ; Zdobnov, Evgeny M. ; Ribeiro, José M. C. ; Gibbs, Richard A. ; Werren, John H. ; Palli, Subba Reddy ; Schal, Coby ; Richards, Stephen
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Posch, Wilfried ; Steger, Marion ; Knackmuss, Ulla ; Blatzer, Michael ; Baldauf, Hanna-Mari ; Doppler, Wolfgang ; White, Tommy E. ; Hörtnagl, Paul ; Diaz-Griffero, Felipe ; Lass-Flörl, Cornelia ; Hackl, Hubert ; Moris, Arnaud ; Keppler, Oliver Till ; Wilflingseder, Doris
DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.
Maier, Hannes ; Lenarz, Thomas ; Agha-Mir-Salim, Parwis ; Agterberg, Martijn J. H. ; Anagiotos, Andreas ; Arndt, Susan ; Ball, Geoffrey R. ; Bance, Manohar ; Barbara, Maurizio ; Baumann, Uwe ; Baumgartner, Wolfgang ; Bernardeschi, Daniele ; Beutner, Dirk ; Bosman, Arjan ; Briggs, Robert ; Busch, Susan ; Caversaccio, Marco ; Dahm, Markus ; Dalhoff, Ernst ; Devèze, Arnaud ; Ebrahimi-Madiseh, Azadeh ; Fraysse, Bernard ; Frenzel, Henning ; Gavilán, Javier ; Ghoncheh, Mohammad ; Håkansson, Bo E. V. ; Hodgetts, William ; Hol, Myrthe Karianne Sophie ; Holland, Julian ; Holmberg, Marcus ; Huber, Alexander ; Jenkins, Herman ; Katiri, Roulla ; Kheirkhah, Kiana ; Koitschev, Assen ; Kompis, Martin ; Lanting, Cris ; Lassaletta, Luis ; Lerut, Bob ; Leuwer, Rudolf ; Linder, Thomas ; Löwenheim, Hubert Martin ; Lustig, Lawrence ; Mandavia, Rishi ; Manrique, Manuel ; Jorge Humberto, Martins ; Mertens, Griet ; Mlynski, Robert Arndt ; Mojallal, Hamidreza ; Monini, Simonetta ; Monksfield, Peter ; Müller, Alexander ; Mylanus, Emmanuel ; Nakajima, Hideko Heidi ; Neudert, Marcus ; Offeciers, Erwin ; Pfiffner, Flurin ; Pietsch, Markus ; Plontke, Stefan K.-R. ; Prenzler, Nils Kristian ; Profant, Milan ; Rahne, Torsten ; Rajan, Gunesh ; Ratuszniak, Anna ; Raufer, Stefan ; Ray, Jaydip ; Reinfeldt, Sabine ; Röösli, Christof ; Rosenbom, Tove ; Salcher, Rolf Benedikt ; Schönermark, Matthias ; Schwab, Burkard ; Skarżyński, Henryk ; Skarżyński, Piotr H. ; Snapp, Hillary ; Sprinzl, Georg ; Spearman, Michael ; Stenfelt, Stefan ; Stieger, Christof ; Tringali, Stephane ; Truy, Eric ; Tysome, James ; Van de Heyning, Paul ; Verhaert, Nicolas ; Wesarg, Thomas ; Westerkull, Patrik ; Wollenberg, Barbara ; Zahnert, Thomas ; Zarowski, Andrzej ; Snik, Ad
Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
Bekele, Selemon ; Braghin, Fabio ; Chajecki, Zbigniew ; Chung, Paul ; Cramer, John G. ; Csörgo, Tamás ; Eggers, Hans ; Gavin, Sean ; Grassi, Frédérique ; Hama, Yogiro ; Kisiel, Adam ; Ko, Che-Ming ; Koide, Tomoi ; Krein, Gastão ; Lacey, Roy Alphanso ; Lednický, Richard ; Lisa, Michael A. ; Metzger, Wesley ; Miśkowiec, Dariusz Czesław ; Morita, Kenji ; Padula, Sandra S. ; Pratt, Scott ; Qian, Wei-Liang ; Simak, Vladislav ; Sinyukov, Yuri ; Šumbera, Michal ; Tavares, Bernardo M. ; Verde, Giuseppe ; Zschiesche, Detlef
After five years of running at RHIC, and on the eve of the LHC heavy-ion program, we highlight the status of femtoscopic measurements. We emphasize the role interferometry plays in addressing fundamental questions about the state of matter created in such collisions, and present an enumerated list of measurements, analyses and calculations that are needed to advance the field in the coming years.
Mulley, Geraldine ; Beeton, Michael L. ; Wilkinson, Paul ; Vlisidou, Isabella ; Ockendon-Powell, Nina ; Hapeshi, Alexia ; Tobias, Nicholas J. ; Nollmann, Friederike I. ; Bode, Helge Björn ; Elsen, Jean van den ; ffrench-Constant, Richard H. ; Waterfield, Nicholas R.
Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.
Craig, Timothy ; Zuraw, Bruce ; Longhurst, Hilary ; Cicardi, Marco ; Bork, Konrad ; Grattan, Clive ; Katelaris, Constance ; Sussman, Gordon ; Keith, Paul K. ; Yang, William ; Hébert, Jacques ; Hanzlikova, Jana ; Staubach-Renz, Petra ; Martinez Saguer, Inmaculada ; Magerl, Markus ; Aygören-Pürsün, Emel ; Farkas, Henriette ; Reshef, Avner ; Kivity, Shmuel ; Neri, Sergio ; Crișan, Ioana ; Caballero, Teresa ; Baeza, María Luisa ; Hernandez, Maria Dolores ; Li, Henry ; Lumry, William ; Bernstein, Jonathan A. ; Hussain, Iftikar ; Anderson, John ; Schwartz, Lawrence B. ; Jacobs, Joshua ; Manning, Michael ; Levy, Donald ; Riedl, Marc A. ; Christiansen, Sandra ; Feuersenger, Henrike ; Pragst, Ingo ; Mycroft, Sarah ; Pawaskar, Dipti ; Jacobs, Iris
Background: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA®, CSL Behring) was established in the 16-week COMPACT trial.
Objective: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC).
Methods: Open-label, randomised, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naïve or who had completed the COMPACT trial, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional up-titration to optimise prophylaxis. ClinicalTrials.gov registration: NCT02316353.
Results: 126 patients with a monthly attack rate of 4.3 in 3 months prior to entry in the COMPACT program were enrolled and treated for a mean of 1·5 years; 44 patients (34·9%) had >2 years exposure. Median steady-state C1-INH functional activity increased to a maximum of 73.0% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11·3 and 8·5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualised attack rates were 1·3 and 1·0, respectively and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for >2 years, 19 (83%) were attack-free during months 25–30 of treatment.
Conclusion: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.
Yap, Kenrick ; Drakew, Alexander ; Smilovic, Dinko ; Rietsche, Michael ; Paul, Mandy H. ; Vuksic, Mario ; Del Turco, Domenico ; Deller, Thomas
Large spines are stable and important for memory trace formation. The majority of large spines also contains synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using 2-photon time-lapse imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive (SP+) spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP+ spines followed conditional two-stage decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single-phase exponential decays. This was also the case following afferent denervation. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines, and the presence of SP indicates spines of high stability.
Verkuijl, Sanne J. ; Friedmacher, Florian Michael ; Harter, Patrick Nikolaus ; Rolle, Udo ; Broens, Paul M. A.
Hirschsprung’s disease (HD) is a congenital disorder, characterized by aganglionosis in the distal part of the gastrointestinal tract. Despite complete surgical resection of the aganglionic segment, both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options. There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD, which may play a role in persistent bowel dysfunction. These abnormalities include: (1) Histopathological abnormalities of enteric neural cells; (2) Imbalanced expression of neurotransmitters and neuroproteins; (3) Abnormal expression of enteric pacemaker cells; (4) Abnormalities of smooth muscle cells; and (5) Abnormalities within the extracellular matrix. Hence, a better understanding of these previously unrecognized neuropathological abnormalities may improve follow-up and treatment in patients with HD suffering from persistent bowel dysfunction following surgical correction. In the long term, further combination of clinical and neuropathological data will hopefully enable a translational step towards more individual treatment for HD.
Introduction: Gastroesophageal reflux disease (GERD) is associated with accelerated decline in lung health in children with cystic fibrosis (CF). Thus, antireflux surgery (ARS) is offered to a selected CF cohort with refractory GERD, but outcomes remain poorly investigated. This study aimed to determine the incidence of GERD in children with CF and to evaluate complications and outcomes of ARS. Materials and Methods: A systematic literature-based search was conducted using various online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The number of GERD cases in pediatric CF cohorts who underwent diagnostic investigation(s) was recorded. Data on postoperative complications and outcomes (including symptoms, lung function, and nutritional status) following ARS were analyzed. Results: Ten articles (n = 289 patients) met the defined inclusion criteria (51% male; age range, 0.5 month–36 years). The overall incidence of GERD was 46% (range, 19–81%), derived from seven studies (n = 212 patients). Four publications (n = 82 patients) reported on ARS due to uncontrolled GERD. All ARSs were Nissen fundoplication (majority with gastrostomy placement). Major postoperative complications occurred in 15 (18%) patients, two required redo-ARS. Median follow-up time was 2 years (range, 3 months–6 years); 59% showed symptom improvement, and pulmonary exacerbations and decline in lung function were reduced. Nutritional status mainly improved in milder CF cases. There were no deaths related to ARS. Conclusion: Approximately half of pediatric CF patients have GERD. Published data for children with CF are limited and heterogeneous in terms of GERD diagnosis and outcomes following ARS. However, ARS has shown to slow the deterioration of lung function in CF.
Konopka, Paul ; Günther, Gebhard ; Müller, Rolf ; Santos, Fábio Henrique Silva dos ; Schiller, Cornelius ; Ravegnani, Fabrizio ; Ulanovsky, Alexey ; Schlager, Hans ; Volk, C.-Michael ; Viciani, Silvia ; Pan, Laura L. ; McKenna, Daniel-S. ; Riese, Martin
During the second part of the TROCCINOX campaign that took place in Brazil in early 2005, chemical species were measured on-board the high-altitude research aircraft Geophysica (ozone, water vapor, NO, NOy, CH4 and CO) in the altitude range up to 20 km (or up to 450 K potential temperature), i.e. spanning the entire TTL region roughly extending between 350 and 420 K. Here, analysis of transport across the TTL is performed using a new version of the Chemical Lagrangian Model of the Stratosphere (CLaMS). In this new version, the stratospheric model has been extended to the earth surface. Above the tropopause, the isentropic and cross-isentropic advection in CLaMS is driven by meteorological analysis winds and heating/cooling rates derived from a radiation calculation. Below the tropopause, the model smoothly transforms from the isentropic to the hybrid-pressure coordinate and, in this way, takes into account the effect of large-scale convective transport as implemented in the vertical wind of the meteorological analysis. As in previous CLaMS simulations, the irreversible transport, i.e. mixing, is controlled by the local horizontal strain and vertical shear rates. Stratospheric and tropospheric signatures in the TTL can be seen both in the observations and in the model. The composition of air above ≈350 K is mainly controlled by mixing on a time scale of weeks or even months. Based on CLaMS transport studies where mixing can be completely switched off, we deduce that vertical mixing, mainly driven by the vertical shear in the tropical flanks of the subtropical jets and, to some extent, in the the outflow regions of the large-scale convection, offers an explanation for the upward transport of trace species from the main convective outflow at around 350 K up to the tropical tropopause around 380 K.