The Common Swift Louse Fly, Crataerina pallida: An Ideal Species for Studying Host-Parasite Interactions

Little is known of the life-history of many parasitic species. This hinders a full understanding of host-parasitic interactions. The common swift louse fly, Crataerina pallida Latreille (Diptera: Hippoboscidae), an obligate haematophagous parasite of the Common Swift, Apus apus Linnaeus 1758, is one such species. No detrimental effect of its parasitism upon the host has been found. This may be because too little is known about C. pallida ecology, and therefore detrimental effects are also unknown. This is a review of what is known about the life-history of this parasite, with the aim of promoting understanding of its ecology. New, previously unreported observations about C. pallida made from personal observations at a nesting swift colony are described. Unanswered questions are highlighted, which may aid understanding of this host-parasite system. C. pallida may prove a suitable model species for the study of other host-parasite relationships

The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India

<p>Abstract</p> <p>Background</p> <p>Malaria in India has been difficult to measure. Mortality and morbidity are not comprehensively reported, impeding efforts to track changes in disease burden. However, a set of blood measures has been collected regularly by the National Malaria Control Program in most districts since 1958.</p> <p>Methods</p> <p>Here, we use principal components analysis to combine these measures into a single index, the Summary Index of Malaria Surveillance (SIMS), and then test its temporal and geographic stability using subsets of the data.</p> <p>Results</p> <p>The SIMS correlates positively with all its individual components and with external measures of mortality and morbidity. It is highly consistent and stable over time (1995-2005) and regions of India. It includes measures of both <it>vivax </it>and <it>falciparum </it>malaria, with <it>vivax </it>dominant at lower transmission levels and <it>falciparum </it>dominant at higher transmission levels, perhaps due to ecological specialization of the species.</p> <p>Conclusions</p> <p>This measure should provide a useful tool for researchers looking to summarize geographic or temporal trends in malaria in India, and can be readily applied by administrators with no mathematical or scientific background. We include a spreadsheet that allows simple calculation of the index for researchers and local administrators. Similar principles are likely applicable worldwide, though further validation is needed before using the SIMS outside India.</p

Radiolucent lines in low-contact-stress mobile-bearing total knee arthroplasty: a blinded and matched case control study

<p>Abstract</p> <p>Background</p> <p>Low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA) (Johnson & Johnson, New Brunswick, NJ; previously: DePuy, Warsawa, USA) provides excellent functional results and wear rates in long-term follow-up analyses. Radiological analysis shows radiolucent lines (RLL) appearing immediately or two years after primary implantation, indicative of poor seat. Investigations proved RLL to be more frequent in uncemented TKA, resulting in a consensus to cement the tibial plateau, but their association with clinical findings and patients discomfort and knee pain is still unknown.</p> <p>Methods</p> <p>553 patients with 566 low-contact-stress (LCS) total knee prostheses were screened for continuous moderate knee pain. We compared tibial stress shielding classified by Ewald in patients suffering from pain with a matched, pain-free control group on blinded X-rays. We hypothesized a positive correlation between pain and radiolucency and higher frequency of such radiolucent lines in the most medial and most lateral zones of the tibial plateau.</p> <p>Results</p> <p>Twenty-eight patients suffered from knee pain in total. Radiolucencies were detected in 27 of these cases and in six out of 28 matched controls without knee pain. We could demonstrate a significant correlation of knee pain and radiolucencies, which appeared significantly more frequently in the outermost zones of the tibial plateau.</p> <p>Conclusion</p> <p>Our findings suggest that radiolucent lines, representing poor implant seat, about the tibial plateau are associated with knee pain in LCS patients. Radiolucencies are observed more often in noncemented LCS, and cementing the tibial plateau might improve implant seat and reduce both radiolucent lines and associated knee pain.</p

Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques

The number of so-called new psychoactive substances (NPS) is still increasing by modification of the chemical structure of known (scheduled) drugs. As analogues of amphetamines, 2-aminopropyl-benzofurans were sold. They were consumed because of their euphoric and empathogenic effects. After the 5-(2-aminopropyl)benzofurans, the 6-(2-aminopropyl)benzofuran isomers appeared. Thus, the question arose whether the metabolic fate, the mass spectral fragmentation, and the detectability in urine are comparable or different and how an intake can be differentiated. In the present study, 6-(2-aminopropyl)benzofuran (6-APB) and its N-methyl derivative 6-MAPB (N-methyl-6-(2-aminopropyl)benzofuran) were investigated to answer these questions. The metabolites of both drugs were identified in rat urine and human liver preparations using GC-MS and/or liquid chromatography-high resolution-mass spectrometry (LC-HR-MSn). Besides the parent drug, the main metabolite of 6-APB was 4-carboxymethyl-3-hydroxy amphetamine and the main metabolites of 6-MAPB were 6-APB (N-demethyl metabolite) and 4-carboxymethyl-3-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 6-MAPB N-demethylation were CYP1A2, CYP2D6, and CYP3A4. An intake of a common users’ dose of 6-APB or 6-MAPB could be confirmed in rat urine using the authors’ GC-MS and the LC-MSn standard urine screening approaches with the corresponding parent drugs as major target allowing their differentiation. Furthermore, a differentiation of 6-APB and 6-MAPB in urine from their positional isomers 5-APB and 5-MAPB was successfully performed after solid phase extraction and heptafluorobutyrylation by GC-MS via their retention times

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

<p>Abstract</p> <p>Background</p> <p>The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of <it>KRAS </it>(3%). The aim of the correlative tumour tissue studies was to investigate the relationship between <it>EGFR </it>gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.</p> <p>Methods</p> <p>Patients included in this correlative study (<it>n </it>= 39) were a subset of patients from the clinical phase II study. The association between <it>EGFR </it>gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. <it>EGFR </it>gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene <it>CDH1 </it>was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.</p> <p>Results</p> <p>Our study showed a significant association between increased <it>EGFR </it>gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two <it>CDH1 </it>exon 9 missense mutations (A408V and D402H) were detected.</p> <p>Conclusion</p> <p>Our finding that increased <it>EGFR </it>gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.</p> <p>Trial registration</p> <p>Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.</p

A novel miniature in-line load-cell to measure in-situ tensile forces in the tibialis anterior tendon of rats.

Direct measurements of muscular forces usually require a substantial rearrangement of the biomechanical system. To circumvent this problem, various indirect techniques have been used in the past. We introduce a novel direct method, using a lightweight (~0.5 g) miniature (3 x 3 x 7 mm) in-line load-cell to measure tension in the tibialis anterior tendon of rats. A linear motor was used to produce force-profiles to assess linearity, step-response, hysteresis and frequency behavior under controlled conditions. Sensor responses to a series of rectangular force-pulses correlated linearly (R2 = 0.999) within the range of 0-20 N. The maximal relative error at full scale (20 N) was 0.07% of the average measured signal. The standard deviation of the mean response to repeated 20 N force pulses was ± 0.04% of the mean response. The step-response of the load-cell showed the behavior of a PD2T2-element in control-engineering terminology. The maximal hysteretic error was 5.4% of the full-scale signal. Sinusoidal signals were attenuated maximally (-4 dB) at 200 Hz, within a measured range of 0.01-200 Hz. When measuring muscular forces this should be of minor concern as the fusion-frequency of muscles is generally much lower. The newly developed load-cell measured tensile forces of up to 20 N, without inelastic deformation of the sensor. It qualifies for various applications in which it is of interest directly to measure forces within a particular tendon causing only minimal disturbance to the biomechanical system

Hydrophobicity and Charge Shape Cellular Metabolite Concentrations

What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108) of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ∼100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts

Limited role of spatial selfstructuring in emergent trade-offs during pathogen evolution

Pathogen transmission and virulence are main evolutionary variables broadly assumed to be linked through trade-offs. In well-mixed populations, these trade-offs are often ascribed to physiological restrictions, while populations with spatial self-structuring might evolve emergent trade-offs. Here, we reexamine a spatially-explicit, SIR model of the latter kind proposed by Ballegooijen and Boerlijst with the aim of characterising the mechanisms causing the emergence of the trade-off and its structural robustness. Using invadability criteria, we establish the conditions under which an evolutionary feedback between transmission and virulence mediated by pattern formation can poise the system to a critical boundary separating a disordered state (without emergent trade-off) from a self-structured phase (where the trade-off emerges), and analytically calculate the functional shape of the boundary in a certain approximation. Beyond evolutionary parameters, the success of an invasion depends on the size and spatial structure of the invading and invaded populations. Spatial self-structuring is often destroyed when hosts are mobile, changing the evolutionary dynamics to those of a well-mixed population. In a metapopulation scenario, the systematic extinction of the pathogen in the disordered phase may counteract the disruptive effect of host mobility, favour pattern formation and therefore recover the emergent trade-off.This work has been supported by the Spanish Ministerio de Economía, Industria y Competitividad and FEDER funds of the EU through grants ViralESS (FIS2014-57686-P and FIS2017-84256-P). The internship of VB was financed by the Severo Ochoa Centers of Excellence Program (SEV-2013-0347)

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

More than 75 percent decline over 27 years in total flying insect biomass in protected areas

Global declines in insects have sparked wide interest among scientists, politicians, and the general public. Loss of insect diversity and abundance is expected to provoke cascading effects on food webs and to jeopardize ecosystem services. Our understanding of the extent and underlying causes of this decline is based on the abundance of single species or taxonomic groups only, rather than changes in insect biomass which is more relevant for ecological functioning. Here, we used a standardized protocol to measure total insect biomass using Malaise traps, deployed over 27 years in 63 nature protection areas in Germany (96 unique location-year combinations) to infer on the status and trend of local entomofauna. Our analysis estimates a seasonal decline of 76%, and mid-summer decline of 82% in flying insect biomass over the 27 years of study. We show that this decline is apparent regardless of habitat type, while changes in weather, land use, and habitat characteristics cannot explain this overall decline. This yet unrecognized loss of insect biomass must be taken into account in evaluating declines in abundance of species depending on insects as a food source, and ecosystem functioning in the European landscape