A plasma inhibitor of the renin-antirenin reaction and the in vitro generation of angiotensin I

In the course of studies designed to develop a radioimmunoassay system for the detection of renin, we have identified in human plasma a potent inhibitor that interferes with the renin-antirenin reaction. Utilizing gel filtration, this renin-antirenin inhibitory activity was found to have the same molecular size as renin substrate. However, it could be separated from renin substrate by ion-exchange chromatography. When fractions containing this activity were tested in an in vitro system containing renin and renin substrate, they were found to inhibit the generation of angiotensin I.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22129/1/0000557.pd

Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay

Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was supported by grants from GenePOC, now part of Meridian Biosciences.published version, accepted versio

Vision-based real-time position control of a semi-automated system for robot-assisted joint fracture surgery

Purpose: Joint fracture surgery quality can be improved by robotic system with high-accuracy and high-repeatability fracture fragment manipulation. A new real-time vision-based system for fragment manipulation during robot-assisted fracture surgery was developed and tested. Methods: The control strategy was accomplished by merging fast open-loop control with vision-based control. This two-phase process is designed to eliminate the open-loop positioning errors by closing the control loop using visual feedback provided by an optical tracking system. Evaluation of the control system accuracy was performed using robot positioning trials, and fracture reduction accuracy was tested in trials on ex vivo porcine model.Results: The system resulted in high fracture reduction reliability with a reduction accuracy of 0.09mm (translations) and of (Formula presented.) (rotations), maximum observed errors in the order of 0.12mm (translations) and of (Formula presented.) (rotations), and a reduction repeatability of 0.02mm and (Formula presented.). Conclusions: The proposed vision-based system was shown to be effective and suitable for real joint fracture surgical procedures, contributing a potential improvement of their quality

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs

How a slow-ovipositing parasitoid can succed as a biological control agent of the invasive mealybug Phenacoccus peruvianus: implications for future classical and conservation biological control programs

[EN] Phenaccocus peruvianus Granara de Willink (Hemiptera: pseudococcidae) is an invasive mealybug that has become a pest of ornamental plants in Europe and has recently been detected in California, USA. In this work, we studied the tritrophic interaction among this mealybug, its main parasitoid Acerophagus n. sp. near coccois (Hymenoptera: Encyrtidae) and tending ants to disclose the success of this parasitoid controlling P. peruvianus. Acerophagus n. sp. near coccois accepted mealybugs for parasitism regardless of their size but did not hostfeed. We recorded three active defenses of P. peruvianus. Host handling time-consuming process that required more than 30 min. Tending ants, Lasius grandis (Hymenoptera: Encyrtidae), reduced the time spent by parasitoids in a patch and disrupted oviposition attempts. The low numbers of ants tending mealybugs colonies in Spain and France could explain why this parasitoid, with a long handling time, is an efficient biological control agent for P. peruvianus.Beltrà Ivars, A.; Soto Sánchez, AI.; Tena Barreda, A. (2015). How a slow-ovipositing parasitoid can succed as a biological control agent of the invasive mealybug Phenacoccus peruvianus: implications for future classical and conservation biological control programs. BioControl. 60(4):473-484. https://doi.org/10.1007/s10526-015-9663-6S473484604Arakelian G (2013) Bougainvillea mealybug (Phenacoccus peruvianus). Factsheet 2013. County of Los Angeles. Department of agricultural commissioner/weights and measures, USABartlett BR (1961) The influence of ants upon parasites, predators, and scale insects. Ann Entomol Soc Am 54:543–551Bartlett BR (1978) Pseudococcidae. In: Clausen CP (ed) Introduced parasites and predators of arthropod pests and weeds: a world review, 1st edn. Agricultural Research Service USDA, Washington, USA, pp 137–170Barzman MS, Daane KM (2001) Host-handling behaviors in parasitoids of black scale, Saissetia oleae (Homoptera: Coccidae): a case for ant-mediated evolution. J Anim Ecol 70:237–247Beltrà A, Soto A, Germain JF, Matile-Ferrero D, Mazzeo G, Pellizzari G, Russo A, Franco JC, Williams DJ (2010) The Bougainvillea mealybug Phenacoccus peruvianus, a rapid invader from South America to Europe. Entomol Hell 19:137–143Beltrà A, Garcia-Marí F, Soto A (2013a) Seasonal phenology, spatial distribution, and sampling plan for the invasive mealybug Phenacoccus peruvianus (Hemiptera: Pseudococcidae). J Econ Entomol 106:1486–1494Beltrà A, Tena A, Soto A (2013b) Fortuitous biological control of the invasive mealybug Phenacoccus peruvianus in Southern Europe. BioControl 58:309–317Beltrà A, Tena A, Soto A (2013c) Reproductive strategies and food sources used by Acerophagus n. sp. near coccois, a new successful parasitoid of the invasive mealybug Phenacoccus peruvianus. J Pest Sci 86:253–259Berlinger MJ, Golberg AM (1978) The effect of the fruit sepals on the citrus mealybug population and on its parasite. Entomol Exp Appl 24:238–243Blumstein DT, Daniel JC (2007) Quantifying behavior the JWatcher way. Sinauer Associates Inc., Sunderland, UKBoavida C, Ahounou M, Vos M, Neuenschwander P, van Alphen JJM (1995) Host stage selection and sex allocation by Gyranusoidea tebygi (Hymenoptera: Encyrtidae), a parasitoid of the mango mealybug, Rastrococcus invadens (Homoptera: Pseudococcidae). Biol Control 5:487–496Bokonon-Ganta AH, Neuenschwander P, van Alphen JJM, Vos M (1995) Host stage selection and sex allocation by Anagyrus mangicola (Hymenoptera: Encyrtidae), a parasitoid of the mango mealybug, Rastrococcus invadens (Homoptera: Pseudococcidae). Biol Control 5:479–486Bugila AAA, Franco JC, Borges da Silva E, Branco M (2014a) Defense response of native and alien mealybugs (Hemiptera: Pseudococcidae) against the solitary parasitoid Anagyrus sp. nr. pseudococci (Girault) (Hymenoptera: Encyrtidae). J Insect Behav 27:439–453Bugila AAA, Branco M, Borges da Silva E, Franco JC (2014b) Host selection behavior and specificity of the solitary parasitoid of mealybugs Anagyrus sp. nr. pseudococci (Girault) (Hymenoptera, Encyrtidae). Biocontrol Sci Techn 24:22–38Bynum EK (1937) Pseudococcobius terryi Fullaway, a Hawaiian parasite of Gray Sugarcane mealybug in the United States. J Econ Entomol 30:756–761Cadée N, van Alphen JJM (1997) Host selection and sex allocation in Leptomastidea abnormis, a parasitoid of the citrus mealybug Planococcus citri. Entomol Exp Appl 83:277–284Clausen CP (1924) The parasites of Pseudococcus maritimus (Ehrhorn) in California (Hymenoptera, Chalcidoidea). Part II. Biological studies and life histories. UC Pub Entomol 3:253–288Daane KM, Barzman MS, Caltagirone LE, Hagen KS (2000) Metaphycus anneckei and Metaphycus hageni: two discrete species parasitic on black scale, Saissetia oleae. BioControl 45:269–284Daane KM, Bentley WJ, Walton VM, Malakar-Kuenen R, Millar JC, Ingels CA, Weber EA, Gispert C (2006) New controls investigated for vine mealybug. Calif Agric 60:31–38Daane KM, Sime KR, Fallon J, Cooper ML (2007) Impacts of Argentine ants on mealybugs and their natural enemies in California’s coastal vineyards. Ecol Entomol 32:583–596De Farias AM, Hopper KR (1999) Oviposition behavior of Aphelinus asychis (Hymenoptera: Aphelinidae) and Aphidius matricariae (Hymenoptera: Aphidiidae) and defense behavior of their host Diuraphis noxia (Homoptera: Aphididae). Environ Entomol 28:858–862Dorn B, Mattiacci L, Bellotti AC, Dorn S (2001) Host specificity and comparative foraging behavior of Aenasius vexans and Acerophagus coccois, two endo-parasitoids of the cassava mealybug. Entomol Exp Appl 99:331–339Eisner T, Silberglied RE (1988) A chrysopid larva that cloaks itself in mealybug wax. Psyche 95:15–20Flanders SE (1963) Predation by parasitic Hymenoptera, the basis of ant-induced outbreaks of a host species. J Econ Entomol 56:116Foldi I (1983) Structure et fonctions des glandes tégumentaires de cochenilles Pseudococcines et de leurs secretions. Ann Soc Entomol Fr 19:155–156Foldi I (1997) Defense strategies in scale insects: phylogenetic inference and evolutionary scenarios (Hemiptera, Coccoidea). In: Grandcolas P (ed) The origin of biodiversity in insects: phylogenetic tests of evolutionary scenarios, 1st edn. Muséum National d’Histoire Naturelle, Paris, France, pp 203–230Godfray HCJ (1994) Parasitoids: behavioral and evolutionary ecology. Princeton University Press, Princeton, USAGonzález-Hernández H, Johnson MW, Reimer NJ (1999) Impact of Pheidole megacephala (F.) (Hymenoptera: Formicidae) on the biological control of Dysmicoccus brevipes (Cockerell) (Homoptera: Pseudococcidae). Biol Control 15:145–152Gross P (1993) Insect behavioral and morphological defenses against parasitoids. Annu Rev Entomol 38:251–273Gullan PJ (1997) Relationships with ants. In: Ben-Dov Y, Hodgson CJ (eds) Soft scale insects—their biology natural enemies and control, 1st edn. Elsevier, Amsterdam, The Netherlands, pp 351–373Gullan PJ, Kosztarab M (1997) Adaptations in scale insects. Annu Rev Entomol 42:23–50Hcidari M, Jahan M (2000) A study of ovipositional behavior of Anagyrus pseudococci a parasitoid of mealybugs. J Agric Sci Technol 2:49–53Honda JY, Luck RF (1995) Scale morphology effects on feeding behavior and biological control potential of Rhyzobius lophanthae (Coleoptera: Coccinellidae). Ann Entomol Soc Am 88:441–450Joyce AL, Hoddle MS, Bellows TS, Gonzalez D (2001) Oviposition behavior of Coccidoxenoides peregrinus, a parasitoid of Planococcus ficus. Entomol Exp Appl 98:49–57Karamaouna F (1999) Biology of the parasitoids Leptomastix epona (Walker) and Pseudaphycus flavidulus (Brèthes) and behavioural interactions with the host mealybug Pseudococcus viburni (Signoret). Ph.D. Thesis, University of London, UK, p 333Karamaouna F, Copland MJ (2000) Oviposition behavior, influence of experience on host size selection, and niche overlap of the solitary Leptomastix epona and the gregarious Pseudaphycus flavidulus, two endoparasitoids of the mealybug Pseudococcus viburni. Entomol Exp Appl 97:301–308Klotz JH, Hansen L, Pospischil R, Rust M (2008) Urban ants of North America and Europe. Cornell University Press, Ithaca, USAMailleux AC, Deneubourg JL, Detrain C (2003) Regulation of ants foraging to resource productivity. P R Soc Lond B Bio 270:1609–1616Majerus ME, Sloggett JJ, Godeau JF, Hemptinne JL (2007) Interactions between ants and aphidophagous and coccidophagous ladybirds. Popul Ecol 49:15–27Mgocheki N, Addison P (2009) Interference of ants (Hymenoptera: Formicidae) with biological control of the vine mealybug Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae). Biol Control 49:180–185Moore D (1988) Agents used for biological control of mealybugs (Pseudococcidae). Biocontrol News Inf 9:209–225Paris CI, Espadaler X (2009) Honeydew collection by the invasive garden ant Lasius neglectus versus the native ant L grandis. Arthropod Plant Interact 3:75–85Pekas A, Tena A, Aguilar A, Garcia-Marí F (2011) Spatio-temporal patterns and interactions with honeydew-producing Hemiptera of ants in a Mediterranean citrus orchard. Agric Forest Entomol 13:89–97Pennacchio F, Strand MR (2006) Evolution of developmental strategies in parasitic Hymenoptera. Annu Rev Entomol 51:233–258Pijls JW, Hofker KD, Staalduinen MJ, van Alphen JJM (1995) Interspecific host discrimination and competition in Apoanagyrus (Epidinocarsis) lopezi and A(E) diversicornis parasitoids of the cassava mealybug Phenacoccus manihoti. Ecol Entomol 20:326–332Robert Y (1987) Dispersion and migration. In: Minks AK, Harrewijn P (eds) Aphids—their biology, natural enemies and control, 1st edn. Elsevier, Amsterdam, The Netherlands, pp 299–313Sandanayaka WRM, Charles JG, Allan DJ (2009) Aspects of the reproductive biology of Pseudaphycus maculipennis (Hym: Encyrtidae), a parasitoid of obscure mealybug, Pseudococcus viburni (Hem: Pseudococcidae). Biol Control 48:30–35Sarkar D (2008) Lattice: multivariate data visualization with R. Springer, New York, USASime KR, Daane KM (2014) Rapid, non-discriminatory oviposition behaviors are favored in mealybug parasitoids when Argentine ants are present. Environ Entomol 43:995–1002Tena A, Garcia-Marí F (2008) Suitability of citricola scale Coccus pseudomagnoliarum (Hemiptera: Coccidae) as host of Metaphycus helvolus (Hymenoptera: Encyrtidae): Influence of host size and encapsulation. Biol Control 46:341–347Tena A, Hoddle CD, Hoddle MS (2013) Competition between honeydew producers in an ant–hemipteran interaction may enhance biological control of an invasive pest. Bull Entomol Res 103:714–723The R Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austriavan Driesche RG, Belloti A, Herrera CJ, Castello JA (1987a) Host preferences of two encyrtid parasitoids for the Columbian Phenacoccus spp. of cassava mealybugs. Entomol Exp Appl 43:261–266van Driesche RG, Belloti A, Herrera CJ, Castello JA (1987b) Host feeding and ovipositor insertion as sources of mortality in the mealybug Phenacoccus herreni caused by two encyrtids Epidinocarsis diversicornis and Acerophagus coccois. Entomol Exp Appl 44:97–100Vet LE, Dicke M (1992) Ecology of infochemical use by natural enemies in a tritrophic context. Annu Rev Entomol 37:141–172Völkl W, Woodring J, Fischer M, Lorenz MW, Hoffmann KH (1999) Ant-aphid mutualisms: the impact of honeydew production and honeydew sugar composition on ant preferences. Oecologia 118:483–491Wajnberg E (1989) Analysis of variations of handling-time in Trichogramma maidis. Entomophaga 34:397–407Way MJ (1963) Mutualism between ants and honeydew-producing Homoptera. Annu Rev Entomol 8:307–344Weiss MR (2006) Defecation behavior and ecology of insects. Annu Rev Entomol 51:635–661Wyckhuys KAG, Stone L, Desneux N, Hoelmer KA, Hopper KR, Heimpel GE (2008) Parasitism of the soybean aphid Aphis glycines by Binodoxys communis: the role of aphid defensive behavior and parasitoid reproductive performance. Bull Entomol Res 98:361–370Zain-ul-Abdin, Arif MJ, Suhail A, Gogi MD, Arshad M, Wakil W, Abbas SK, Altaf A, Shaina H, Manzoor A (2012) Molecular analysis of the venom of mealybug parasitoid Aenasius bambawalei Hayat (Hymenoptera: Encyrtidae). Pak Entomol 34:189–193Zinna G (1959) Specializzazione entomoparassitica negli Encyrtidae: studio morfologico etologico e fisiologico del Leptomastix dactylopii. Howard Boll Lab agr Filippo Silvestri 18:1–14

Towards standardized measurement of adverse events in spine surgery: conceptual model and pilot evaluation

BACKGROUND: Independent of efficacy, information on safety of surgical procedures is essential for informed choices. We seek to develop standardized methodology for describing the safety of spinal operations and apply these methods to study lumbar surgery. We present a conceptual model for evaluating the safety of spine surgery and describe development of tools to measure principal components of this model: (1) specifying outcome by explicit criteria for adverse event definition, mode of ascertainment, cause, severity, or preventability, and (2) quantitatively measuring predictors such as patient factors, comorbidity, severity of degenerative spine disease, and invasiveness of spine surgery. METHODS: We created operational definitions for 176 adverse occurrences and established multiple mechanisms for reporting them. We developed new methods to quantify the severity of adverse occurrences, degeneration of lumbar spine, and invasiveness of spinal procedures. Using kappa statistics and intra-class correlation coefficients, we assessed agreement for the following: four reviewers independently coding etiology, preventability, and severity for 141 adverse occurrences, two observers coding lumbar spine degenerative changes in 10 selected cases, and two researchers coding invasiveness of surgery for 50 initial cases. RESULTS: During the first six months of prospective surveillance, rigorous daily medical record reviews identified 92.6% of the adverse occurrences we recorded, and voluntary reports by providers identified 38.5% (surgeons reported 18.3%, inpatient rounding team reported 23.1%, and conferences discussed 6.1%). Trained observers had fair agreement in classifying etiology of 141 adverse occurrences into 18 categories (kappa = 0.35), but agreement was substantial (kappa ≥ 0.61) for 4 specific categories: technical error, failure in communication, systems failure, and no error. Preventability assessment had moderate agreement (mean weighted kappa = 0.44). Adverse occurrence severity rating had fair agreement (mean weighted kappa = 0.33) when using a scale based on the JCAHO Sentinel Event Policy, but agreement was substantial for severity ratings on a new 11-point numerical severity scale (ICC = 0.74). There was excellent inter-rater agreement for a lumbar degenerative disease severity score (ICC = 0.98) and an index of surgery invasiveness (ICC = 0.99). CONCLUSION: Composite measures of disease severity and surgery invasiveness may allow development of risk-adjusted predictive models for adverse events in spine surgery. Standard measures of adverse events and risk adjustment may also facilitate post-marketing surveillance of spinal devices, effectiveness research, and quality improvement

Transgenerational Stress Memory Is Not a General Response in Arabidopsis

Adverse conditions can trigger DNA damage as well as DNA repair responses in plants. A variety of stress factors are known to stimulate homologous recombination, the most accurate repair pathway, by increasing the concentration of necessary enzymatic components and the frequency of events. This effect has been reported to last into subsequent generations not exposed to the stress. To establish a basis for a genetic analysis of this transgenerational stress memory, a broad range of treatments was tested for quantitative effects on homologous recombination in the progeny. Several Arabidopsis lines, transgenic for well-established recombination traps, were exposed to 10 different physical and chemical stress treatments, and scored for the number of somatic homologous recombination (SHR) events in the treated generation as well as in the two subsequent generations that were not treated. These numbers were related to the expression level of genes involved in homologous recombination and repair. SHR was enhanced after the majority of treatments, confirming previous data and adding new effective stress types, especially interference with chromatin. Compounds that directly modify DNA stimulated SHR to values exceeding previously described induction rates, concomitant with an induction of genes involved in SHR. In spite of the significant stimulation in the stressed generations, the two subsequent non-treated generations only showed a low and stochastic increase in SHR that did not correlate with the degree of stimulation in the parental plants. Transcripts coding for SHR enzymes generally returned to pre-treatment levels in the progeny. Thus, transgenerational effects on SHR frequency are not a general response to abiotic stress in Arabidopsis and may require special conditions

CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo