Publications by authors named "Petr Heneberg"

94 Publications

The sublethal effects of neonicotinoids on spiders are independent of their nutritional status.

Sci Rep 2021 Apr 19;11(1):8496. Epub 2021 Apr 19.

Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague, Czech Republic.

Spiders were recently shown to be adversely affected by field-realistic concentrations of a broad scale of neonicotinoid insecticides. Among the reported effects of neonicotinoids on invertebrates were declines in lipid biosynthesis and upregulation of β-oxidation, while vertebrate models suggest increased adipogenesis following treatment with neonicotinoids. Therefore, we hypothesized that there exists synergy between the effects of diet and concurrent exposure to field-realistic concentrations of neonicotinoid insecticides. To address this hypothesis, we fed first instars of the large wolf spider Hogna antelucana with two types of diets and exposed them to field-realistic concentrations of three formulations of neonicotinoids (thiamethoxam, thiacloprid and acetamiprid). We then measured the growth of the tested spiders; the lipid and protein content of their bodies; and their behavior, including ballooning, rappelling, and locomotor parameters. The two tested diets consisted of casein-treated and sucrose-treated Drosophila melanogaster. The dietary treatments affected the lipid and protein content of the spiders, their body weight and carapace length but did not affect any of the measured behavioral parameters. Surprisingly, we did not find any effects of acute exposure to neonicotinoid insecticides on the lipid or protein reserves of spiders. Exposure to neonicotinoids altered the behavior of the spiders as reported previously in other spider species; however, these effects were not affected by dietary treatments. Overall, the dietary treatments did not have any major synergy with acute exposure to field-realistic concentrations of neonicotinoid insecticides.
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http://dx.doi.org/10.1038/s41598-021-87935-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055996PMC
April 2021

Cryptic speciation among Tylodelphys spp.: the major helminth pathogens of fish and amphibians.

Parasitol Res 2021 May 3;120(5):1687-1697. Epub 2021 Mar 3.

Moravian Ornithological Station, Comenius Museum, Přerov, Czechia.

Larvae of Tylodelphys Diesing, 1950 are major digenean pathogens of fish and amphibians. Tylodelphys spp. may induce mass mortality of fish and increase their susceptibility to predation. Even though Tylodelphys spp. cause substantial damage to aquaculture systems, surprisingly little is known regarding the taxonomy of this commercially important genus with a limited number of visible autapomorphic identification features. The authors obtained the DNA sequences and analyzed the molecular phylogenetics of Tylodelphys spp. adults isolated from bird hosts of Czech origin and provide comparative measurements of the analyzed species. They identified a previously unknown species complex that is subject to cryptic speciation and was previously morphologically identified as Tylodelphys excavata (Rudolphi, 1803) sensu lato. This species complex consists of three morphologically similar but genetically well-separated species. Tylodelphys excavata sensu stricto remains the dominant Tylodelphys isolated from Ciconia ciconia, which also serves as a satellite host of Tylodelphys circibuteonis Odening, 1962, which is the resurrected species for which birds of prey serve as core hosts. The authors describe Tylodelphys nigriciconis sp. n. Heneberg & Sitko as a new species identified in Ciconia nigra. By providing the first sequences of Tylodelphys podicipina Kozicka and Niewiadomska, 1960, they also show that Tylodelphys immer Dubois, 1961 is a junior synonym of T. podicipina. Further research is needed to match the provided molecular data with the DNA of larval Tylodelphys from outbreaks in commercially exploited fish species.
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http://dx.doi.org/10.1007/s00436-021-07082-2DOI Listing
May 2021

Claustral colony founding does not prevent sensitivity to the detrimental effects of azole fungicides on the fecundity of ants.

J Environ Manage 2021 Feb 4;280:111740. Epub 2020 Dec 4.

University of Hradec Králové, Faculty of Science, Hradec Králové, Czech Republic.

Azole fungicides (benzimidazoles, triazoles and imidazoles) are among the most widely used agrochemicals in the world. Unfortunately, azole fungicides are increasingly recognized for playing the role of endocrine disruptors in non-target organisms. Previously, the fecundity of ants with semi-claustral colony founding was found to be severely decreased in response to field-realistic concentrations of azole fungicides. However, during claustral colony founding, the ant queens do not feed and could therefore be protected against effects of agrochemicals applied during the colony founding. In the present study, we hypothesized that claustral colony founding is associated with a lower risk of oral exposure of ant queens to azole fungicides. We exposed queens of a common farmland ant species with claustral colony founding, Lasius niger, to four azole fungicides (epoxiconazole, flusilazole, prochloraz and thiophanate-methyl) that are commonly used in foliar applications and analyzed the differences in fecundity between fungicide-treated groups and the control water-treated group. We found that oral exposure to all four tested formulations of azole fungicides decreased the fecundity of L. niger queens. The decreases in fecundity ranged from 30.5% (epoxiconazole) to 40.3% (prochloraz), although the concentrations of fungicides used were several times lower than the minimum effective concentrations used to eliminate the target fungi by foliar applications of examined fungicides on various crops. Ants with both claustral and semi-claustral colony founding are highly vulnerable to field-realistic concentrations of azole fungicides that are sprayed in foliar applications. Azole fungicides substantially decrease the fitness of ant queens and may explain part of the recently observed decreases in farmland insect abundance and diversity.
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http://dx.doi.org/10.1016/j.jenvman.2020.111740DOI Listing
February 2021

Emerging helminthiases of song thrush (Turdus philomelos) in Central Europe.

Parasitol Res 2020 Dec 8;119(12):4123-4134. Epub 2020 Oct 8.

Charles University, Third Faculty of Medicine, Ruská 87, 100 00, Prague, Czech Republic.

Turdus philomelos is a common Western Palearctic thrush species of forests and agricultural landscapes, where it relies on the presence of hedgerows, patches of trees, and shrubs. In the present study, we address long-term changes in component communities of trematodes in T. philomelos across the timespan of over half a century. Based on our preliminary observations, we hypothesized that component communities of trematodes in T. philomelos in the study area are more diverse and species-rich compared with several decades ago. In the 1961-2019, we performed full-body necropsies of T. philomelos, which originated from the southern Czech Republic, and examined them for the presence of trematodes. We compared the trematode species richness and diversity of the analyzed component communities. The number of trematode species per host steadily increased in time in adult females and males. In juveniles, the highest numbers of trematode species per host were reached already in 1961-1990, then dropped and slowly raised up again in the latter time periods. The newly accumulated evidence suggests that trematodes with intermediate hosts previously restricted to T. philomelos wintering grounds increased in abundance in the study area. Some of them (Morishitium polonicum, Psilotornus confertus) sporadically appeared in juveniles or first-year birds, from which they were previously completely absent. Some of the spreading species, such as Lutztrema attenuatum, are present in high prevalence and high intensities of infection. Yet unknown part of observed changes could be related to changes in food composition; however, direct evidence for changes in T. philomelos diet is lacking despite clear evidence for a decline in earthworms in agricultural landscapes.
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http://dx.doi.org/10.1007/s00436-020-06911-0DOI Listing
December 2020

Neonicotinoid insecticides hinder the pupation and metamorphosis into adults in a crabronid wasp.

Sci Rep 2020 04 27;10(1):7077. Epub 2020 Apr 27.

Crop Research Institute, Functional Biodiversity Group, Prague, Czech Republic.

Neonicotinoid insecticides are associated with a decline in the diversity and distribution of bees and wasps (Hymenoptera: Aculeata). The effects of neonicotinoids on the metamorphosis of aculeates have never been addressed in detail; however, recent evidence suggests that neonicotinoids induce wing abnormalities. We hypothesized that the metamorphosis success of bees and wasps differs in response to contact exposure to field-realistic concentrations of neonicotinoid insecticides or in response to combined exposure to neonicotinoid insecticides and benzimidazole fungicides. We treated prepupae of the model crabronid wasp Pemphredon fabricii with field-realistic concentrations of four neonicotinoids, acetamiprid, imidacloprid, thiacloprid and thiamethoxam, and/or with the benzimidazole fungicide thiabendazole. Treatment with acetamiprid or imidacloprid decreased the pupation rates to only 39% and 32%, respectively. Treatment with thiacloprid or thiamethoxam did not affect the pupation rate when applied alone, but the subsequent treatment of thiacloprid- or thiamethoxam-treated prepupae with thiabendazole led to significant decreases in pupation rates. A high concentration of acetamiprid, which severely affected the pupation rates, had moderate effects on metamorphosis into adults, resulting in 53% metamorphosis success (as opposed to 95% metamorphosis success in the water-treated group). However, imidacloprid or thiamethoxam treatment resulted in only 5%-10% metamorphosis success into adults. Overall survival decreased in response to treatment with any of the neonicotinoids or benzimidazoles or their combinations, with extremely low survival (<2%) following combined treatment with imidacloprid and thiabendazole or thiamethoxam and thiabendazole. In conclusion, neonicotinoids alter insect metamorphosis success, which can be further potentiated by their combination with other agrochemicals, such as benzimidazoles.
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http://dx.doi.org/10.1038/s41598-020-63958-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184726PMC
April 2020

Neonicotinoids suppress contact chemoreception in a common farmland spider.

Sci Rep 2020 04 27;10(1):7019. Epub 2020 Apr 27.

Crop Research Institute, Biodiversity Lab, Prague, Czech Republic.

Neonicotinoid insecticides are increasingly recognized for their role as information disruptors by modifying the chemical communication system of insects and therefore decreasing the chances of reproduction in target insects. However, data from spiders are lacking. In the present study, we tested the responses of males of a common agrobiont spider, Pardosa agrestis, to the application of field-realistic concentration of acetamiprid, which was formulated as Mospilan, and trace amounts of thiacloprid, which was formulated as Biscaya. We applied fresh or 24-h-old residues of Mospilan or Biscaya to the males just prior to the experiment or treated only the surface of a tunnel containing female draglines. We evaluated the ability of the males to recognize female cues from female dragline silk in a Y-maze. The field-realistic, sublethal doses of Mospilan altered pheromone-guided behavior. The choice of the tunnel with female draglines by males was hampered by tarsal treatment of the males with 24 h-old residues of Mospilan. The mating dance display was commonly initiated in control males that came into contact with female draglines and was suppressed by the Mospilan treatments in all three experimental settings. Some males only initiated the mating dance but did not manage to complete it; this was particularly true for males that were treated tarsally with fresh Mospilan residues, as none of these males managed to complete the mating dance. All three experimental settings with Mospilan decreased the frequency of males that managed to both select the tunnel with female draglines and complete the mating dance. The responses to the low-dose Biscaya were much milder and the study was not sufficiently powered to confirm the effects of Biscaya; however, the surprisingly observed trends in responses to very low Biscaya concentrations call for further analyses of long-term effects of trace amounts of neonicotinoids on the pheromone-guided behavior of spiders. These are the first conclusive data regarding the effects of commercially available formulations of neonicotinoid insecticides on the intraspecific chemical communication of spiders.
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http://dx.doi.org/10.1038/s41598-020-63955-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184746PMC
April 2020

Systemic collapse of a host-parasite trematode network associated with wetland birds in Europe.

Parasitol Res 2020 Mar 22;119(3):935-945. Epub 2020 Feb 22.

Third Faculty of Medicine, Charles University, Ruská 87, CZ-100 00, Prague, Czech Republic.

As host community diversity decreases, parasite diversity may also decline. The life cycles of trematodes involve multiple hosts from different orders, with many trematodes displaying narrow host specialization. In the 1960s and 2010s, we performed full-body necropsies of juvenile or first-year birds of four wetland bird species, Anas platyrhynchos, Aythya fuligula, Fulica atra, and Chroicocephalus ridibundus which originated from the southern Czech Republic, and examined them for the presence of trematodes. We compared the trematode species richness and diversity of the analyzed component communities. We found complete disintegration of host-parasite networks, which led to declining populations and local extinctions of the majority of trematode species, particularly those with narrow host preferences. For example, in black-headed gulls, 67% of trematode species recorded in the 1960s were absent in gulls that were examined in the 2010s. In contrast, we did not identify any trematode species that were absent in the 1960s but present in the 2010s. This collapse provides new insight into the recent debate regarding whether human-caused extinctions should be considered a problem when locally extinct host species are replaced by an equal or even higher number of nonnative species, thus maintaining local alpha diversities but leading to biotic homogenization and consequently reducing beta diversity. By documenting the collapse of the host-parasite network, we provide a strong argument that biodiversity cannot be assessed by simple measures alone, as only local-scale conservation measures allow the preservation of host-pathogen interactions and nutrient cycles and thus prevent the loss of low-visibility species, such as helminths.
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http://dx.doi.org/10.1007/s00436-020-06624-4DOI Listing
March 2020

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma.

Transl Oncol 2020 Feb 30;13(2):383-392. Epub 2019 Dec 30.

Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a possible association of diabetes mellitus and other comorbidities and their treatment with progression of colorectal cancer.

Patients And Methods: We investigated the correlation between pathological characteristics and clinical course, including comorbidities in 1004 Czech patients diagnosed and surgically treated for colorectal adenocarcinoma (CRC) between 1999 and 2016.

Results: In our data set, CRC patients treated with metformin due to coexisting diabetes mellitus type 2 (T2DM) developed fewer distant metastases which clinically correlates with slower CRC progression. Survival in metformin subgroup was longer, particularly in men with CRC. Osteoporosis may be a negative factor of survival in CRC patients.

Conclusions: Our findings also indicate that aging, higher tumor grade and TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecular responses and with various epigenetic characteristics. More awareness and increased understanding of the mechanisms underlying the positive effect of metformin on patients' survival could offer insight into new treatment methods and permit more individualized treatment plans.
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http://dx.doi.org/10.1016/j.tranon.2019.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940647PMC
February 2020

Rapid methods for the separation of natural mixtures of beauverolides, cholesterol acyltransferase inhibitors, isolated from the fungus Isaria fumosorosea.

J Sep Sci 2020 Mar 1;43(5):962-969. Epub 2020 Jan 1.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Beauverolides (beauveriolides) are abundant, biologically active cyclodepsipeptides produced by many entomopathogenic fungi, including those that are used as biopesticides. Beauverolides act as cholesterol acyltransferase inhibitors in humans; thus, their mode of action has been the subject of pharmacological and clinical research. The cost-effective analytical methods are needed for fast, routine laboratory analysis of beauverolides. We isolated beauverolides from the fungal strain Isaria fumosorosea PFR 97-Apopka and opened the rings of the isolated beauverolides using a pyridine alkaline medium. We separated fractions of cyclic and linearized beauverolides by thin-layer chromatography, and found the chloroform-acetate (9:1, v/v) and chloroform-acetonitrile-acetate (8:1:1, v/v/v) mobile phases, respectively, to be the most efficient. We examined all the fractions by liquid chromatography-mass spectrometry using ion trap and Orbitrap high resolution mass spectrometry. For rapid screening of the contents of cyclic, and, particularly, linearized beauverolides, we developed a novel analytical method that consisted of using capillary electrophoresis coupled with contactless conductivity detection. Furthermore, we improved the separation of the peptides by applying capillary micellar electrokinetic chromatography with the N-cyclohexyl-2-aminoethanesulfonic acid:SDS:NaOH buffer, pH 9.8 as the background electrolyte. The described novel methods allow fast and cost-effective separation of chemically related groups of beauverolides.
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http://dx.doi.org/10.1002/jssc.201901084DOI Listing
March 2020

Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases.

Sci Rep 2019 12 9;9(1):18577. Epub 2019 Dec 9.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Prediction methods have become an integral part of biomedical and biotechnological research. However, their clinical interpretations are largely based on biochemical or molecular data, but not clinical data. Here, we focus on improving the reliability and clinical applicability of prediction algorithms. We assembled and curated two large non-overlapping large databases of clinical phenotypes. These phenotypes were caused by missense variations in 44 and 63 genes associated with Mendelian diseases. We used these databases to establish and validate the model, allowing us to improve the predictions obtained from EVmutation, SNAP2 and PoPMuSiC 2.1. The predictions of clinical effects suffered from a lack of specificity, which appears to be the common constraint of all recently used prediction methods, although predictions mediated by these methods are associated with nearly absolute sensitivity. We introduced evidence-based tailoring of the default settings of the prediction methods; this tailoring substantially improved the prediction outcomes. Additionally, the comparisons of the clinically observed and theoretical variations led to the identification of large previously unreported pools of variations that were under negative selection during molecular evolution. The evolutionary variation analysis approach described here is the first to enable the highly specific identification of likely disease-causing missense variations that have not yet been associated with any clinical phenotype.
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http://dx.doi.org/10.1038/s41598-019-54976-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901466PMC
December 2019

Paraphyly of Conodiplostomum Dubois, 1937.

Parasitol Int 2020 Jun 3;76:102033. Epub 2019 Dec 3.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Adult trematodes of the genera Conodiplostomum Dubois, 1937 and Neodiplostomum Railliet, 1919 (Trematoda: Diplostomidae) parasitize the intestines of birds of prey, owls and, rarely, passeriform birds. Although the family is taxonomically unsettled, molecular phylogenetics have not been applied to analyze Conodiplostomum and Neodiplostomum and the reference DNA sequences from adult Diplostomidae are scarce and limit studies of their indistinct larval forms. We analyze the Conodiplostomum and Neodiplostomum spp. found during the examination of Czech birds performed from 1962 to 2017, and we provide comparative measurements and host spectra, including prevalence and intensity; we also provide and analyze the sequences of four DNA loci from eight diplostomid species. Molecular phylogenetic analysis suggested that Conodiplostomum spathula (Creplin, 1829), the type species of this genus, is nested in Neodiplostomum. Thus, we suggest the rejection of Conodiplostomum spathula (Creplin, 1829) and the resurrection of Neodiplostomum spathula (Creplin, 1829) La Rue, 1926 and reclassification of all species of Conodiplostomum with the neodiplostomulum type of metacercariae to Neodiplostomum as well. Conodiplostomum canaliculatum (Nicoll, 1914) is reclassified as Neodiplostomum spathulaeforme (Brandes, 1888). The molecular analysis suggested that Conodiplostomum perlatum (Ciurea, 1911), the species with the neascus type of metacercariae, belongs to Crassiphialinae Sudarikov, 1960. We erect the genus Ciureatrema gen. nov. Heneberg & Sitko and reclassify Conodiplostomum perlatum (Ciurea, 1911) as Ciureatrema perlatum (Ciurea, 1911) and establish it as a type species of Ciureatrema gen. nov. Further research should focus on the evolution of the neascus and neodiplostomulum types of metacercariae, as well as the evolution of the genital cone and pseudosuckers in Diplostomidae.
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http://dx.doi.org/10.1016/j.parint.2019.102033DOI Listing
June 2020

Urticating setae of tarantulas (Araneae: Theraphosidae): Morphology, revision of typology and terminology and implications for taxonomy.

PLoS One 2019 11;14(11):e0224384. Epub 2019 Nov 11.

Biodiversity Lab, Crop Research Institute, Prague, Czechia.

Tarantula urticating setae are modified setae located on the abdomen or pedipalps, which represent an effective defensive mechanism against vertebrate or invertebrate predators and intruders. They are also useful taxonomic tools as morphological characters facilitating the classification of New World theraphosid spiders. In the present study, the morphology of urticating setae was studied on 144 taxa of New World theraphosids, including ontogenetic stages in chosen species, except for species with urticating setae of type VII. The typology of urticating setae was revised, and types I, III and IV were redescribed. The urticating setae in spiders with type I setae, which were originally among type III or were considered setae of intermediate morphology between types I and III, are newly considered to be ontogenetic derivatives of type I and are described as subtypes. Setae of intermediate morphology between that of body setae and type II urticating setae that were found in Iridopelma hirsutum and Antillena rickwesti may provide another evidence that type II urticating setae evolved from body setae. It is supposed that the fusion of barbs with the shaft may lead to the morphology of type II setae. As the type II setae of Aviculariinae evolved independently to the UrS of Theraphosinae and both subfamilies represent two non-sister groups, this should explain the differences in the morphology of body setae in Aviculariinae and Theraphosinae. The terminology of "barbs" and "reversed barbs" was revised and redefined, newly emphasizing the real direction of barbs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224384PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844489PMC
March 2020

Taxonomic comments on the validity of Echinostoma miyagawai Ischii, 1932 (Trematoda: Echinostomatidae).

Authors:
Petr Heneberg

Parasitol Int 2020 02;74:101931

Charles University, Third Faculty of Medicine, Prague, Czech Republic. Electronic address:

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http://dx.doi.org/10.1016/j.parint.2019.101931DOI Listing
February 2020

Prey contaminated with neonicotinoids induces feeding deterrent behavior of a common farmland spider.

Sci Rep 2019 11 4;9(1):15895. Epub 2019 Nov 4.

Crop Research Institute, Functional Biodiversity Group, Prague, Czech Republic.

Neonicotinoids are thought to have negligible repellent or anti-feeding effects. Based on our preliminary observations, we hypothesized that the contamination of spider prey with commonly used neonicotinoids has repellent or feeding deterrent effects on spiders. We tested this hypothesis by providing prey treated or not with field-realistic concentrations of neonicotinoids to the spiders and determining the number of (a) killed only and (b) killed and eaten prey. We exposed adult freshly molted and starved Pardosa agrestis, a common agrobiont lycosid species, to flies treated with neonicotinoids (acetamiprid, imidacloprid, thiacloprid and thiamethoxam) at field-realistic concentrations or with distilled water as a control. There were no effects of the exposure of the prey to neonicotinoids on the number of flies captured. However, the spiders consumed less of the prey treated with neonicotinoids compared to the ratio of control prey consumed, which resulted in increased overkilling (i.e., killing without feeding). In female P. agrestis, the overkilling increased from only 2.6% of control flies to 25-45% of neonicotinoid-treated flies. As the spiders avoided consuming the already captured neonicotinoid-treated prey, the sublethal effects of neonicotinoids extend beyond the simple attractivity/deterrence of the prey itself. The present study demonstrated that prey overkilling serves as a physiological response of spiders to the contact with the prey contaminated with agrochemicals. We speculate that primary contact with neonicotinoids during prey capture may play a role in this unexpected behavior.
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http://dx.doi.org/10.1038/s41598-019-52302-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828688PMC
November 2019

Neonicotinoid insecticides limit the potential of spiders to re-colonize disturbed agroecosystems when using silk-mediated dispersal.

Sci Rep 2019 08 22;9(1):12272. Epub 2019 Aug 22.

Biodiversity Lab, Crop Research Institute, Drnovská 507, Prague, CZ-16106, Czechia.

Agroecosystems are subject to regular disturbances that cause extinction or migration of much of their fauna, followed by recolonization from surrounding refuges. In small-sized aeronaut spiders, such recolonization is potentiated by their ability to rappel and balloon. These are complex behaviors that we hypothesized to be affected by neurotoxins, namely, neonicotinoids. We tested this hypothesis using two common farmland spider species, Oedothorax apicatus (Linyphiidae) and Phylloneta impressa (Theridiidae). The spiders were topically exposed by dorsal wet application or tarsal dry exposure to commercial neonicotinoid formulations Actara 25 WG, Biscaya 240 OD, Mospilan 20 SP and Confidor 200 OD at concentrations that are recommended for application in agriculture. Contact exposure to neonicotinoids suppressed the ability of spiders to produce the major ampullate fiber and anchor it to the substratum by piriform fibrils. Contact exposure to neonicotinoids also suppressed the ballooning behavior that was manifested by climbing to elevated places, adopting a tiptoe position and producing silk gossamer in the wind. Impaired ability of affected common farmland spiders to quickly recolonize disturbed agroecosystems by silk-mediated dispersal may explain their decline in multiple farmland ecosystems, in which neonicotinoids are applied.
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http://dx.doi.org/10.1038/s41598-019-48729-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706445PMC
August 2019

Identification of alkaline pH optimum of human glucokinase because of ATP-mediated bias correction in outcomes of enzyme assays.

Sci Rep 2019 08 6;9(1):11422. Epub 2019 Aug 6.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Adenosine triphosphate (ATP) is a crucial substrate and energy source commonly used in enzyme reactions. However, we demonstrated that the addition of this acidic compound to enzyme assay buffers can serve as a source of unnoticed pH changes. Even relatively low concentrations of ATP (up to 5 mM) shifted pH of reaction mixtures to acidic values. For example, Tris buffer lost buffering capacity at pH 7.46 by adding ATP at a concentration higher than 2 mM. In addition to the buffering capacity, the pH shifts differed with respect to the buffer concentration. High ATP concentrations are commonly used in hexokinase assays. We demonstrated how the presence of ATP affects pH of widely used enzyme assay buffers and inversely affected K of human hexokinase 2 and S of human glucokinase. The pH optimum of human glucokinase was never reported before. We found that previously reported optimum of mammalian glucokinase was incorrect, affected by the ATP-induced pH shifts. The pH optimum of human glucokinase is at pH 8.5-8.7. Suggested is the full disclosure of reaction conditions, including the measurement of pH of the whole reaction mixtures instead of measuring pH prior to the addition of all the components.
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http://dx.doi.org/10.1038/s41598-019-47883-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684659PMC
August 2019

Unconventional support for a raptorial niche division between Australaves and Afroaves: The distribution of helminths.

Parasitol Int 2019 Oct 21;72:101946. Epub 2019 Jun 21.

Charles University, Third Faculty of Medicine, Prague, Czech Republic. Electronic address:

Deep evolutionary relationships within raptorial niche have recently been challenged. Little is known as to whether birds of the raptorial niche share congruent or host-switching communities of parasites. Here, we analyzed the helminth component communities associated with birds of prey and owls. From 1962 to 2015, we examined 1731 birds of prey and owls in Czechia, and we provide a meta-analysis based on the available literature. Both the analysis of newly examined birds as well as the meta-analysis of previous studies suggested low similarities in the helminth component communities in Strigiformes relative to those in Accipitriformes (Sørensen similarity indices 0.380 in Czechia and 0.324 worldwide) or Falconiformes (0.341 and 0.328), as well as low similarities in the helminth component communities in Falconiformes to those in Accipitriformes (0.366 and 0.413). Globally, 59.6% of helminth species found in Accipitriformes, 39.5% of those in Falconiformes and 38.3% of those in Strigiformes were obligate specialists that were limited to a single examined bird order. Another 11.5%, 12.8% and 8.3% of species had core hosts in only a single order. Only five helminth species infected all three bird orders at a similar prevalence. The differences in prevalence cannot be explained by differences in food composition. We provide detailed information on the prevalence, seasonality, age- and sex-specificity, intensity and lethality of helminth infections. In conclusion, we provide the first systematically collected evidence on the congruence of the helminth distribution and phylogeny of the raptorial niche, which is consistent with its split into Australaves and Afroaves.
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http://dx.doi.org/10.1016/j.parint.2019.101946DOI Listing
October 2019

Characterization of the complete mitochondrial genome of Uvitellina sp., representative of the family Cyclocoelidae and phylogenetic implications.

Parasitol Res 2019 Jul 1;118(7):2203-2211. Epub 2019 Jun 1.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, People's Republic of China.

Mitochondrial (mt) DNA has been useful in revealing the phylogenetic relationship of eukaryotic organisms including flatworms. Therefore, the use of mitogenomic data for the comparative and phylogenetic purposes is needed for those families of digenetic trematodes for which the mitogenomic data are still missing. Molecular data with sufficiently rich informative characters that can better resolve species identification, discrimination, and membership in different genera is also required for members of some morphologically difficult families of trematodes bearing few autapomorphic characters among its members. Here, the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (rDNA) and the complete mt genome of the trematode Uvitellina sp. (Cyclocoelidae: Haematotrephinae) was determined and annotated. The mt genome of this avian trematode is 14,217 bp in length, containing 36 genes plus a single non-coding region. The ITS rDNA sequences were used for the pairwise sequence comparison of Uvitellina sp. with European cyclocoelid species, and the mitochondrial 12 protein-coding genes (PCGs) and two ribosomal RNA genes were used to evaluate the position of the family within selected trematodes. The ITS rDNA analysis of Uvitellina sp. showed less nucleotide differences with Hyptiasmus oculeus (16.77%) than with other European cyclocoelids (18.63-23.58%). The Bayesian inference (BI) analysis using the 12 mt PCGs and two rRNA genes supported the placement of the family Cyclocoelidae within the superfamily Echinostomatoidea (Plagiorchiida: Echinostmata). The availability of the mt genome sequences of Uvitellina sp. provides a novel resource of molecular markers for phylogenetic studies of Cyclocoelidae and other trematodes.
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http://dx.doi.org/10.1007/s00436-019-06358-yDOI Listing
July 2019

Unveiled feather microcosm: feather microbiota of passerine birds is closely associated with host species identity and bacteriocin-producing bacteria.

ISME J 2019 09 24;13(9):2363-2376. Epub 2019 May 24.

Home address: Gočárova třída 542/12, 500 02, Hradec Králové, Czech Republic.

The functional relevance of microbiota is a key aspect for understanding host-microbiota interactions. Mammalian skin harbours a complex consortium of beneficial microorganisms known to provide health and immune-boosting advantages. As yet, however, little is known about functional microbial communities on avian feathers, including their co-evolution with the host and factors determining feather microbiota (FM) diversity. Using 16S rRNA profiling, we investigated how host species identity, phylogeny and geographic origin determine FM in free-living passerine birds. Moreover, we estimated the relative abundance of bacteriocin-producing bacteria (BPB) and keratinolytic feather damaging bacteria (FDB) and evaluated the ability of BPB to affect FM diversity and relative abundance of FDB. Host species identity was associated with feather bacterial communities more strongly than host geographic origin. FM functional properties differed in terms of estimated BPB and FDB relative abundance, with both showing interspecific variation. FM diversity was negatively associated with BPB relative abundance across species, whereas BPB and FDB relative abundance was positively correlated. This study provides the first thorough evaluation of antimicrobial peptides-producing bacterial communities inhabiting the feather integument, including their likely potential to mediate niche-competition and to be associated with functional species-specific feather microbiota in avian hosts.
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http://dx.doi.org/10.1038/s41396-019-0438-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775979PMC
September 2019

Massive infection of a song thrush by Mesocestoides sp. (Cestoda) tetrathyridia that genetically match acephalic metacestodes causing lethal peritoneal larval cestodiasis in domesticated mammals.

Parasit Vectors 2019 May 14;12(1):230. Epub 2019 May 14.

Department of Biology and Wildlife Diseases, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czechia.

Background: Peritoneal larval cestodiasis induced by Mesocestoides Vaillant, 1863 (Cyclophyllidea: Mesocestoididae) is a common cause of severe infections in domestic dogs and cats, reported also from other mammals and less frequently from birds. However, there is a limited knowledge on the taxonomy of causative agents of this disease.

Results: In the present study, we investigated a massive, likely lethal, infection of a song thrush Turdus philomelos (Passeriformes: Turdidae) by Mesocestoides sp. tetrathyridia. We performed combined morphological and phylogenetic analysis of the tetrathyridia and compared them with the materials obtained previously from other birds and mammals. The metrical data fitted within the wide range reported by previous authors but confirmed the limited value of morphological data for species identification of tetrathyridia of Mesocestoides spp. The molecular analyses suggested that the isolates represented an unidentified Mesocestoides sp. that was previously repeatedly isolated and sequenced in larval and adult forms from domestic dogs and cats in Europe, the Middle East and North Africa. In contrast to the present study, which found encysted tetrathyridia, four of the five previous studies that identified the same species described infections by acephalic metacestodes only.

Conclusions: The tetrathyridia of the examined Mesocestoides sp. are described in the present study for the first time. However, the possible match with the species that were previously reported to infect birds remains uncertain. The phylogenetic analyses also suggested the rejection of two cases that were previously identified as Mesocestoides corti as they were likely caused by the same species as in the presently reported infection case. The newly provided DNA sequences should allow the assignment to species in the future, when adults of the genus Mesocestoides are more thoroughly sequenced.
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http://dx.doi.org/10.1186/s13071-019-3480-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518502PMC
May 2019

Air sac trematodes: as a newly identified cause of death in the common blackbird ().

Int J Parasitol Parasites Wildl 2019 Aug 30;9:74-79. Epub 2019 Mar 30.

Department of Veterinary Sciences, University of Pisa, Pisa, Italy.

Necropsy of two free-ranging common blackbirds () found dead in central Italy revealed the presence of a high number of cyclocoelid flukes in the coelomatic cavity. Cyclocoelid flukes primarily infect avian respiratory system. Histologically, air sac walls were covered with a fibrinous exudate containing degenerate heterophils, many trematodes and some colonies of Gram-positive cocci. The superficial bronchi and parabronchi were markedly distended, and the adjacent pulmonary parenchyma was congested and collapsed. Trematodes, surrounded by a mild suppurative to pyogranulomatous inflammatory reaction, were also observed on the pericardial, intestinal, kidney and hepatic serosal surfaces. The death of the two examined birds was likely due to the high parasite load and associated severe lesions. At parasitological examination, flukes showed a tongue-shaped elongate body, tapered anteriorly and rounded posteriorly, of 2,088-2,314 μm in width and 8,268-11,830 μm in length. The mouth was slightly oval and sub-terminal, with a small oral sucker. The oval pharynx measured 250-309 μm, and the two caeca joined posteriorly. Two large (550-702 μm × 450-520 μm) globular testes were situated obliquely to each other, whereas an oval (250 × 300 μm in mean) or round (about 334 μm in diameter) intertesticular ovary was placed in a longitudinal straight line with the testes. The ootype was about 110 μm in diameter, while the brown-yellow eggs measured 131.5 × 73.9 μm in mean. The genital pore was post-pharyngeal, while the symmetrically arranged vitelline glands were not confluent posteriorly. Morphoflogical diagnosis led to the identification of , a cyclocoelid fluke species that typically inhabits the air sacs of blackbirds. The morphological diagnosis was corroborated by molecular phylogenetic analysis of the mitochondrial (CO1, ND1) DNA loci. The present study provides the first report of pathological lesions and death caused by in birds.
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http://dx.doi.org/10.1016/j.ijppaw.2019.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463545PMC
August 2019

Comment on Mulukutla et al. Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes. Diabetes Care 2018;41:2637-2640.

Authors:
Petr Heneberg

Diabetes Care 2019 05;42(5):e81

2nd Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic

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http://dx.doi.org/10.2337/dc19-0022DOI Listing
May 2019

Contact application of neonicotinoids suppresses the predation rate in different densities of prey and induces paralysis of common farmland spiders.

Sci Rep 2019 04 5;9(1):5724. Epub 2019 Apr 5.

Crop Research Institute, Biodiversity Lab, Prague, Czech Republic.

Neonicotinoids are very effective in controlling crop pests but have adverse effects on predators and pollinators. Spiders are less sensitive to neonicotinoids compared to insects because of the different structure of their acetylcholine receptors, the binding targets of neonicotinoids. We tested whether short-term exposure to neonicotinoids affected the predation rate in different densities of prey of spiders and led to their paralysis or eventual death. To examine these effects, we topically exposed dominant epigeic, epiphytic and sheet-weaving farmland spiders to four widely used neonicotinoids (imidacloprid, thiamethoxam, acetamiprid and thiacloprid). We applied the neonicotinoids at concentrations recommended by the manufacturers for spray application under field conditions. Short-term exposure to the formulations of all four tested neonicotinoids had adverse effects on the predation rate of spiders, with imidacloprid (Confidor) associated with the most severe effects on the predation rate and exhibiting partial acute lethality after one hour (15-32%). Acetamiprid also displayed strong sublethal effects, particularly when applied dorsally to Philodromus cespitum. Day-long exposure to dorsally applied acetamiprid or thiacloprid led to paralysis or death of multiple Linyphiidae spp., with the effects particularly prominent in males. To conclude, we provided multiple lines of evidence that short-term exposure to neonicotinoids, which were applied at recommended field concentrations, caused severe health effects or death in multiple families of spiders. Even acetamiprid caused strong effects, despite being subject to less strict regulations in the European Union, compared with those for imidacloprid because of claims of its negligible off-target toxicity.
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http://dx.doi.org/10.1038/s41598-019-42258-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450932PMC
April 2019

First evidence of changes in enzyme kinetics and stability of glucokinase affected by somatic cancer-associated variations.

Biochim Biophys Acta Proteins Proteom 2019 03 24;1867(3):213-218. Epub 2018 Dec 24.

Charles University, Third Faculty of Medicine, Prague, Czech Republic. Electronic address:

Recent investigation of somatic variations of allosterically regulated proteins in cancer genomes suggested that variations in glucokinase (GCK) might play a role in tumorigenesis. We hypothesized that somatic cancer-associated GCK variations include in part those with activating and/or stabilizing effects. We analyzed the enzyme kinetics and thermostability of recombinant proteins possessing the likely activating variations and the variations present in the connecting loop I and provided the first experimental evidence of the effects of somatic cancer-associated GCK variations. Activating and/or stabilizing variations were common among the analyzed cancer-associated variations, which was in strong contrast to their low frequency among germinal variations. The activating and stabilizing variations displayed focal distribution with respect to the tertiary structure, and were present in the surroundings of the heterotropic allosteric activator site, including but not limited to the connecting loop I and in the active site region subject to extensive rearrangements upon glucose binding. Activating somatic cancer-associated variations induced a reduction of GCK's cooperativity and an increase in the affinity to glucose (a decline in the S values). The hotspot-associated variations, which decreased cooperativity, also increased the half-maximal inhibitory concentrations of the competitive GCK inhibitor, N-acetylglucosamine. Concluded, we have provided the first convincing biochemical evidence establishing GCK as a previously unrecognized enzyme that contributes to the reprogramming of energy metabolism in cancer cells. Activating GCK variations substantially increase affinity of GCK to glucose, disrupt the otherwise characteristic sigmoidal response to glucose and/or prolong the enzyme half-life. This, combined, facilitates glucose phosphorylation, thus supporting glycolysis and associated pathways.
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http://dx.doi.org/10.1016/j.bbapap.2018.12.008DOI Listing
March 2019

Autoantibodies against ZnT8 are rare in Central-European LADA patients and absent in MODY patients, including those positive for other autoantibodies.

J Diabetes Complications 2019 01 13;33(1):46-52. Epub 2018 Oct 13.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Background: Testing for autoantibodies against the zinc transporter ZnT8 (ZnTA) is becoming routine in pediatric diabetes. However, available data are inconclusive when focusing on adult-onset diabetes, including autoimmune diabetes, which does not require insulin at diagnosis (LADA).

Basic Procedures: We examined the ZnTA prevalence and titers and matched them with the clinical phenotype and PTPN22 genotypes of Czech LADA patients who were positive for GADA and/or IA2A and had a fasting C-peptide level >200 pmol/L at diagnosis as well as HNF4A-, GCK- or HNF1A-MODY patients and healthy controls.

Main Findings: Most LADA patients were negative for ZnTA, and the sensitivity of the assay was only 18-20% for patients with LADA-like progression to insulinotherapy compared to healthy controls. In LADA patients, there was no association between the ZnTA and PTPN22 risk genotypes. LADA patients positive for ZnTA had a lower BMI than those positive for other autoantibodies alone. Importantly, MODY patients were completely negative for ZnTA, and the levels of ZnTA in MODY patients were similar to those in healthy controls.

Conclusions: ZnTA quantification did not improve LADA diagnosis. However, positivity for ZnTA can be used as a negative MODY pre-diagnostic criterion even in the region of Central and East Europe, where other islet cell autoantibodies are common in MODY patients.
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http://dx.doi.org/10.1016/j.jdiacomp.2018.10.004DOI Listing
January 2019

Updates on the surface antigens of basophils: CD16 on basophils of patients with respiratory or insect venom allergy and the rejection of CD203c and CD63 externalization decoupling by bisindolylmaleimides.

Clin Exp Allergy 2019 01 30;49(1):54-67. Epub 2018 Oct 30.

Department of Immunology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: CD16 was previously suggested to be a new marker of basophils that is subject to downregulation by FcεRI crosslinking. Certain compounds, including supraoptimal concentrations of the PKC inhibitors, bisindolylmaleimides, decouple the release of granules containing CD203c, CD63 and histamine, and may thus help to identify the mechanisms related to the CD16 externalization.

Objective: We hypothesized that CD16 is differentially expressed on the surface of basophils in patients with birch pollen or insect venom allergy and is subject to a regulation in response to allergens. We also employed CD203c and CD63 externalization decoupling by bisindolylmaleimides.

Methods: We performed a basophil activation test coupled with CD16 and histamine detection using cells isolated from patients with allergy to birch pollen or insect venom and negative controls. We employed two PKC inhibitors, bisindolylmaleimide II and Ro 31-8220 at their supraoptimal concentrations and, after difficulties reproducing previously published data, we analyzed the fluorescence of these inhibitors alone. We identified the CD16 isoforms by sequencing nested RT-PCR amplicons from flow cytometry sorted basophils and by cleaving the CD16b GPI anchor using a phospholipase C.

Results: We provide the first evidence that CD16a is expressed as a surface antigen on a small subpopulation of human basophils in patients with respiratory and insect venom allergy, and this antigen shows increased surface expression following allergen challenge or FcεRI crosslinking. We rejected the apparent decoupling of the surface expression of basophil activation markers following the administration of bisindolylmaleimides.

Conclusions & Clinical Relevance: The inclusion of αCD16 in negative selection cocktails selects against a subset of basophils that are CD16 or CD16 . Using CD16 basophils and unstained leucocytes, we show that previous studies with supraoptimal concentrations of bisindolylmaleimides are likely flawed and are not associated with the differential expression of CD203c and CD63.
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http://dx.doi.org/10.1111/cea.13288DOI Listing
January 2019

Central European Strigeidae Railliet, 1919 (Trematoda: Strigeidida): Molecular and comparative morphological analysis suggests the reclassification of Parastrigea robusta Szidat, 1928 into Strigea Abildgaard, 1790.

Parasitol Int 2018 Dec 9;67(6):688-701. Epub 2018 Jul 9.

Charles University, Third Faculty of Medicine, Prague, Czech Republic.

Strigeidae Railliet, 1919 are digenean parasites of birds and mammals that are characteristic by their cup-shaped forebody and bilobed holdfast organ. Despite that the family is taxonomically unsettled, particularly due to a very limited number of visible autapomorphic identification features, molecular phylogenetics have never been applied to analyze the relationships among European members of Strigeidae except for the genus Ichthyocotylurus. Here, we analyze the Strigeidae found during the examination of Czech birds performed from 1962 to 2017, and we provide comparative measurements and host spectra, including prevalence and intensity; we also provide and analyze sequences of four DNA loci of 12 of the Strigeidae species. We suggest the reclassification of Parastrigea robusta Szidat, 1928 as Strigea robusta (Szidat, 1928) Heneberg and Sitko, 2018 comb. n. The genera Strigea Abildgaard, 1790 and Parastrigea Szidat, 1928 appear paraphyletic, and morphological diagnostic features of genera within Strigeini Dubois, 1936 are invalid. The mute swan Cygnus olor hosts two Cotylurus spp., Cotylurus syrius Dubois, 1934 and a second species with molecular identification features shared in part with Cotylurus cornutus (Rudolphi, 1808) and Cotylurus gallinulae Lutz, 1928. New host records are provided for seven species. Analyses of non-European genera of the Strigeidae are needed to provide an updated key to Strigeini.
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http://dx.doi.org/10.1016/j.parint.2018.07.003DOI Listing
December 2018

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

Int Arch Allergy Immunol 2018 12;177(1):57-68. Epub 2018 Jun 12.

Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22.

Methods: We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA.

Results: We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes).

Conclusions: The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood.
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http://dx.doi.org/10.1159/000489225DOI Listing
September 2018

Redox Regulation of Hexokinases.

Authors:
Petr Heneberg

Antioxid Redox Signal 2019 01 18;30(3):415-442. Epub 2018 Jun 18.

Third Faculty of Medicine, Charles University , Prague, Czech Republic .

Significance: Hexokinases are key enzymes that are responsible for the first reaction of glycolysis, but they also moonlight other cellular processes, including mitochondrial redox signaling regulation. Modulation of hexokinase activity and spatiotemporal location by reactive oxygen and nitrogen species as well as other gasotransmitters serves as the basis for a unique, underexplored method of tight and flexible regulation of these fundamental enzymes. Recent Advances: Redox modifications of thiols serve as a molecular code that enables the precise and complex regulation of hexokinases. Redox regulation of hexokinases is also used by multiple parasites to cause widespread and severe diseases, including malaria, Chagas disease, and sleeping sickness. Redox-active molecules affect each other, and the moonlighting activity of hexokinases provides another feedback loop that affects the cellular redox status and is hijacked in malignantly transformed cells.

Critical Issues: Several compounds affect the redox status of hexokinases in vivo. These include the dehydroascorbic acid (oxidized form of vitamin C), pyrrolidinium porrolidine-1-carbodithioate (contraceptive), peroxynitrite (product of ethanol metabolism), alloxan (a glucose analog), and isobenzothiazolinone ebselen. However, very limited information is available regarding which amino acid residues in hexokinases are affected by redox signaling. Except in cases of monogenic diabetes, direct evidence is absent for disease phenotypes that are associated with variations within motifs that are susceptible to redox signaling.

Future Directions: Further studies should address the propensity of hexokinases and their disease-associated variants to participate in redox regulation. Robust and straightforward proteomic methods are needed to understand the context and consequences of hexokinase-mediated redox regulation in health and disease.
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http://dx.doi.org/10.1089/ars.2017.7255DOI Listing
January 2019