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High‐quality information on predator–prey relationships is fundamental in understanding food webs, community assembly and ecosystem functioning. Recent analytical advances have made it possible to develop new trait‐based approaches to study trophic relationships and evaluate trait matching between predators and prey.Here, we develop a novel analytical approach based on generalized linear mixed‐effects models (GLMM) to test the importance of prey availability and to identify the set of prey traits that best explain the occurrence and number of prey in the predator's diet.We demonstrate that the approach by using an extensive dataset on prey availability, prey traits and gut content collected in all known populations of Vipera graeca, a little‐known, endangered snake of alpine grasslands in the Pindos Mountains of the Balkan Peninsula.We show that V. graeca is a unique, venomous snake specialized on bush‐crickets and grasshoppers (Orthoptera). Prey selection GLMMs showed that the ideal prey of V. graeca is abundant, large‐bodied, has poor escape abilities (flightless, slow‐moving and bad jumper) and prefers loose grasslands (as opposed to bare ground/rock or closed sward). Vipers restrict their feeding to periods of high Orthoptera abundance in the late summer and need to reach a certain body size to become able to catch large‐sized prey.Our analytical approach provides a framework for trait matching between predators and prey and unprecedented fine‐scale information on the importance of prey traits in prey selection by a specialist predator. The narrow trophic niche of V. graeca likely increases the vulnerability of this cold‐adapted snake to extinction. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Ducks and geese are little studied dispersal vectors for plants lacking a fleshy fruit, and our understanding of the traits associated with these plants is limited. We analyzed 507 faecal samples of mallard (Anas platyrhynchos) and Canada goose (Branta canadensis) from 18 natural and urban wetlands in England, where they are the dominant resident waterfowl. We recovered 930 plant diaspores from 39 taxa representing 18 families, including 28 terrestrial and five aquatic species and four aliens. Mallards had more seeds and seed species per sample than geese, more seeds from barochory and hydrochory syndromes, and seeds that on average were larger and from plants with greater moisture requirements (i.e., more aquatic). Mallards dispersed more plant species than geese in natural habitats. Plant communities and traits dispersed were different between urban (e.g., more achenes) and natural (e.g., more capsules) habitats. Waterfowl can readily spread alien species from urban into natural environments but also allow native terrestrial and aquatic plants to disperse in response to climate heating or other global change. Throughout the temperate regions of the Northern Hemisphere, the mallard is accompanied by a goose (either the Canada goose or the greylag goose) as the most abundant waterfowl in urbanized areas. This combination provides a previously overlooked seed dispersal service for plants with diverse traits. [ABSTRACT FROM AUTHOR]

Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of − 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying − 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage. [ABSTRACT FROM AUTHOR]

Alterations of sensory processing in migraine are well known. There is some evidence to suggest that multisensory processing is altered in migraine as well, but the area is underexplored, especially regarding pediatric migraine. A visual and an audiovisual version of the Rutgers Acquired Equivalence Test paradigm was administered to pediatric patients with migraine without aura (aged 7–17.5 years) and to age- and sex-matched controls. The application of audiovisual stimuli significantly facilitated associative pair learning in migraine-free children and adolescents, but not in pediatric migraine patients. The results of this study corroborate the hypothesis that multisensory processing is altered in pediatric migraine without aura. [ABSTRACT FROM AUTHOR]

Resistance to anticancer agents is a major obstacle to efficacious tumour therapy and responsible for high cancer-related mortality rates. Some resistance mechanisms are associated with pharmacokinetic variability in anticancer drug exposure due to genetic polymorphisms of drug-metabolizing cytochrome P450 (CYP) enzymes, whereas variations in tumoural metabolism as a consequence of CYP copy number alterations are assumed to contribute to the selection of resistant cells. A high-throughput quantitative polymerase chain reaction (qPCR)-based method was developed for detection of CYP copy number alterations in tumours, and a scoring system improved the identification of inappropriate reference genes that underwent deletion/multiplication in tumours. The copy numbers of both the target (CYP2C8, CYP3A4) and the reference genes (ALB, B2M, BCKDHA, F5, CD36, MPO, TBP, RPPH1) established in primary lung adenocarcinoma by the qPCR-based method were congruent with those determined by next-generation sequencing (for 10 genes, slope = 0.9498, r2 = 0.72). In treatment naïve adenocarcinoma samples, the copy number multiplication of paclitaxel-metabolizing CYP2C8 and/or CYP3A4 was more prevalent in non-responder patients with progressive disease/exit than in responders with complete remission. The high-throughput qPCR-based method can become an alternative approach to next-generation sequencing in routine clinical practice, and identification of altered CYP copy numbers may provide a promising biomarker for therapy-resistant tumours. [ABSTRACT FROM AUTHOR]

Aim: Migratory waterfowl are important endozoochory vectors for a range of plants lacking fleshy fruits. Our aim was to study the critical question of how endozoochory rates change throughout the annual cycle, and how this relates to plant life‐form and phenology. Location: Lake Velence, Hungary. Time period: 2017–2018. Major taxa studied: Mallard (Anas platyrhynchos), Angiospermae, Charophyta. Methods: We studied waterfowl endozoochory, quantifying seeds and other diaspores dispersed by mallards by collecting faecal samples monthly (ntotal = 670) at a Hungarian lake. We tested the germinability of all seeds recovered from the faecal samples. Main conclusions: We extracted 5,760 seeds representing 35 plant taxa from mallard faecal samples, and 40% of these seeds germinated successfully following gut passage. We found major differences between seasons in the species composition of the seeds recovered. The peak in species diversity and in abundance of terrestrial seeds coincided with the spring migration of mallards. Importantly, endozoochory was only strongly synchronized with seed production in submerged, but not in emergent or terrestrial plants, illustrating the potential for endozoochory of seeds ingested from the soil seed bank. Overall, our results suggest that endozoochory by migratory waterfowl is a strong and underestimated driver of plant distributions, and is likely to facilitate plant range shifts under climate change, and after introduction of alien species. [ABSTRACT FROM AUTHOR]

• Stimulus complexity influences the effectiveness in visual associative learning. • More complex visual stimuli could elicit more effective learning. • This more effective learning can be seen by high and low working memory load, too. • The reaction times in equivalence learning were shorter by more complex stimuli. • The retrieval and the transfer were not affected by the stimulus complexity. Visually guided equivalence learning is a special type of associative learning, which can be evaluated using the Rutgers Acquired Equivalence Test (RAET) among other tests. RAET applies complex stimuli (faces and colored fish) between which the test subjects build associations. The complexity of these stimuli offers the test subject several clues that might ease association learning. To reduce the number of such clues, we developed an equivalence learning test (Polygon), which is structured as RAET but uses simple grayscale geometric shapes instead of faces and colored fish. In this study, we compared the psychophysical performances of the same healthy volunteers in both RAET and Polygon test. Equivalence learning, which is a basal ganglia-associated form of learning, appears to be strongly influenced by the complexity of the visual stimuli. The simple geometric shapes were associated with poor performance as compared to faces and fish. However, the difference in stimulus complexity did not affect performance in the retrieval and transfer parts of the test phase, which are assumed to be mediated by the hippocampi. [ABSTRACT FROM AUTHOR]

Turkey's orchid flora is one of the richest in the Mediterranean region, but is also under threat from intensification of agriculture, land-use change, habitat loss, overgrazing and salep harvesting (tuber collection). With this study, we would like to draw attention to the importance of economic poplar plantations as orchid habitats. In six of the eight plantations surveyed in five provinces of Turkey, altogether 12 orchid species (Anacamptis elegans, A. fr agrans, A. pyramidalis, Cephalanthera longifolia, C. damasonium, Epipactis helleborine, E. persica, Himantoglossum jankae, Ophrys apifera, O. oestrifera, Ophrys sp., Serapias feldwegiana) were found. In the plantations with an average area of only 0.27 ± 0.21 hectares, the presence of 0-5 orchid species was recorded (mean ± SD = 1.88 ± 1.80). The density of orchid populations varied from 0 to 355.6 specimens per hectare. Both tuberous and rhizomatous orchids were encountered in the studied plantations, but the former ones were dominant: 8 species (67%) and 232 specimens (94%) of the studied orchids were tuberous. The average trunk diameter in poplar plantations harboring orchids ranged from 16.7 to 21.8 cm. In the surveyed plantations, there were no traces of tuber harvesting or overgrazing, which may contribute to their suitability as habitat for orchids. Considering the recent extent of poplar plantations and their expected further increase in Turkey, studying their role in orchid conservation seems important and timely. [ABSTRACT FROM AUTHOR]

The role of anthropogenically influenced habitats in conserving elements of the original wildlife has increased worldwide simultaneously with the disappearance of natural sites. Burial places are able to conserve original elements of the wildlife, and this fact has been known for at least a century. To this day, little is known about long‐time changes and the effect of long‐time management methods in cemeteries on the flora they harbor. The utility of historical maps in research focused on natural values, as well as in answering questions related to conservation was recently demonstrated, but the use of digitized historical maps in biodiversity research of the Carpathian Basin is very limited. In the present paper, we aimed to predict the conservation potential of long‐established and newly established cemeteries of Hungarian settlements with various population sizes based on the digitized maps of the 2nd Military Survey of the Austrian Empire (1819–1869), by categorizing cemeteries into 3 distinct (anthropogenic habitat, cemetery, or natural habitat) types. To build our models, we used records of the protected flora from Hungarian cemeteries, based on data of thematic botanical surveys of 991 cemeteries. Out of the surveyed cemeteries, 553 (56%) harbored protected plants, totaling 306.617 estimated individuals of 92 protected species, belonging to 28 plant families. These species represent 12% of the entire protected flora of Hungary. Hungarian cemeteries play a key role mainly in preserving steppe and dry grassland plant species. Long‐established and large cemeteries harbor more protected plant species than small and newly established ones. Human population size of the settlements correlated negatively with the number of protected species and individuals. Moreover, woodland cover and proportion of grassland also significantly positively affected the number of protected plant species in cemeteries. [ABSTRACT FROM AUTHOR]

In general, database data are a good substitution for time- and resource-consuming trait measurements; however, there is low spatial coverage for a large number of taxa (Kattge et al. [12]), and there is a severe lack of data for endemic, locally rare or red-listed species. In this paper we provide original leaf trait data of vascular plant species from the Pannonian ecoregion. Our data are well compatible with other local trait datasets (Török et al. [44], [45]; Lhotsky et al. [24]) and herbaria (Molnár et al. [31]; Takács et al. [41]; E-Vojtkó et al. [5]; Takács et al. [42]; Nótári et al. [33]) from the Pannonian ecoregion and can be amalgamated in a large plant trait and life history database in the future. [Extracted from the article]

Waterbirds disperse plant seeds within and between aquatic and terrestrial ecosystems in their faeces. However, seed dispersal distances, connectivity among habitat types, and implications for dispersal of weeds remain unquantified in agricultural landscapes. Therefore, we GPS-tagged 31 greylag geese Anser anser and collected 300 faecal samples from feeding flocks in seven agricultural habitats (four cereals, hayfields, pasture, and strawberries) across two landscapes in southern Sweden. We identified intact seeds, determined key plant traits, and tested three hypotheses: (1) geese ingest, transport, and egest seeds from a wide range of terrestrial and aquatic plants, including weeds and alien species; (2) the community and trait composition of plant seeds in faeces vary between habitat types; and (3) seed dispersal by geese is a directional dispersal mechanism that connects some habitat types more than others. We recovered 131 seeds from 41 plant species (19 families), including nine agricultural weeds and one alien species. Many seeds were from aquatic plants (45%), dispersed into terrestrial habitats. A connectivity network formed between habitat types (as nodes) and direct flights (as links) revealed that all agricultural habitats were directly connected with each other, although 66% of flights were between aquatic and agricultural habitats. Geese spent most time at lakes (34%), pastures (14%), barley (10%) and wheat (8%) fields, which were also the most interconnected habitats, with high seed species richness and seed abundance in faecal samples. Combining waterfowl movement data with faecal analysis provided support for all three hypotheses. Geese may contribute to previously overlooked agricultural conflicts through weed dispersal. Proximity to aquatic habitats suitable for roosting may increases the use of agricultural habitats, and potentially the seed dispersal into them. • Geese connect terrestrial and aquatic habitats via seed dispersal. • Functional connectivity between agricultural habitats was quantified. • Geese dispersed 41 plant species into fields, including 9 weeds. • Agricultural fields close to lakes and wetlands were used more by geese. • Geese can contribute to agricultural conflicts through weed dispersal. [ABSTRACT FROM AUTHOR]

Several important habitats have become threatened in the last few centuries in the Mediterranean Basin due to major changes adopted in land‐use practices. The consequent loss of natural and seminatural orchid habitats leads to the appreciation of small anthropogenic habitats, such as cemeteries and roadside verges. Colonization of cemeteries and roadside verges by orchids has long been known, but no study to date compared the suitability of these two anthropogenic habitats for orchids. Therefore, in this paper our aim was to survey cemeteries and roadside verges and to compare these two habitats regarding their role in conserving Mediterranean terrestrial orchids. We conducted field surveys in three Mediterranean islands, Cyprus, Crete, and Lesbos, where both cemeteries and roadside verges were sampled on a geographically representative scale. We found a total of almost 7,000 orchid individuals, belonging to 77 species in the two anthropogenic habitat types. Roadside verges hosted significantly more individuals than cemeteries in Crete and Lesbos, and significantly more species across all three islands. Our results suggest that although cemeteries have a great potential conservation value in other parts of the world, intensive maintenance practices that characterized cemeteries in these three islands renders them unable to sustain valuable plant communities. On the other hand, roadside verges play a prominent role in the conservation of Mediterranean orchids in Cyprus and Greece. The pioneer status of roadside verges facilitates their fast colonization, while roads serve as ecological corridors in fragmented landscapes. [ABSTRACT FROM AUTHOR]

In the intricate web of plant-animal interactions, granivore birds can play a dual antagonist-mutualist role as seed predators and dispersers. This study delves into the ecological significance of the house sparrow ( Passer domesticus ) as seed disperser by endozoochory. A sample of individual droppings and faecal pools were collected from a communal roost in central Spain to examine the presence of seeds. Seed viability was determined using the tetrazolium test. Our findings revealed that around 22% of the analysed droppings contained seeds, contradicting the prevalent notion of house sparrow solely as seed predator. Viability tests demonstrated that 53.9% of the defecated seeds were viable, although it varied between plant species, including those from fleshy-fruited common fig and five species of dry-fruited herbs. This study challenges the traditional perspectives on the ecological role of the house sparrow, and glimpses on their contribution to seed dispersal. Understanding the nuanced roles of granivore species like the house sparrow is crucial for developing holistic conservation and management strategies in urban and agricultural landscapes. Future studies are encouraged to unravel the actual role of this cosmopolitan species as disperser of a likely broad spectrum of wild, cultivated and exotic plants., Competing Interests: We declare we have no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

Objectives: Our aim was to characterize and compare contemporary carbapenem-resistant Enterobacterales (CRE) isolates from gulls, the River Danube, and humans in Hungary, Budapest., Methods: Multiresistant Enterobacterales were sought for in 227 gull faecal and 24 Danube water samples from 2019 to 2020. Eosin-methylene blue agar containing 2 mg/L cefotaxime and Colilert-test containing 10 mg/L cefotaxime were used for gull and water samples, respectively. Isolates were characterized by polymerase chain reactions (PCRs); acquired carbapenemase producers were further analysed by whole-genome sequencing, together with 21 Hungarian human CR Escherichia coli (CREc) isolates., Results: Gull and water samples exhibited a CRE prevalence of 7.4% (9/122) and 6.7% (7/105), none and 5/12 water samples yielded CRE from 2019 and 2020, respectively; CRE were found only in samples taken downstream of Budapest. The dominant species was Escherichia coli and the most prevalent carbapenemase was blaNDM-1. High-risk CREc clones were found both in gulls (ST224, ST372, ST744) and the Danube (ST10, ST354, ST410); the closest associations were between ST410 from humans and the Danube, among ST1437 among gulls, and between ST1437 in gulls and the Danube (46, 0, and 22-24 allelic distances, respectively). Direct links between human and gull isolates were not demonstrated., Conclusion: The study demonstrates potential epidemiological links among humans, a river crossing a city, and urbanised birds, suggesting a local transmission network. Water bodies receiving influent wastewater, together with animals using such habitats, may serve as a local reservoir system for CRE, highlighting the importance of One Health in CRE transmission, even in a country with a low CRE prevalence in humans., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Preprocessing is a mandatory step in electroencephalogram (EEG) signal analysis. Overcoming challenges posed by high noise levels and substantial amplitude artifacts, such as blink-induced electrooculogram (EOG) and muscle-related electromyogram (EMG) interference, is imperative. The signal-to-noise ratio significantly influences the reliability and statistical significance of subsequent analyses. Existing referencing approaches employed in multi-card systems, like using a single electrode or averaging across multiple electrodes, fall short in this respect. In this article, we introduce an innovative referencing method tailored to multi-card instruments, enhancing signal fidelity and analysis outcomes. Our proposed signal processing loop not only mitigates blink-related artifacts but also accurately identifies muscle activity. This work contributes to advancing EEG analysis by providing a robust solution for artifact removal and enhancing data integrity.•Removes blink•Marks muscle activity• Re -references with design specific enhancements., (© 2023 The Author(s).)

One of the most important and most easily measurable physical characteristics of plant seeds is their weight, which influences and indicates crucial ecological processes. Seed weight affects spatial and temporal dispersibility, and can also influence seed predation and the germination, growth and survival of seedlings. Providing trait data for species missing from international databases is key to promote studies that advance our understanding of the functioning of plant communities and ecosystems, which is an essential issue in the face of the global climate change and biodiversity loss. Compared to species from Western and Northwestern Europe, those with an Eastern or Central European centre of distribution are underrepresented in most international trait databases. Therefore, the creation of specific trait databases is key to help regional studies. In this respect, it is important not only to collect fresh seeds for weight measurements, but also to measure and process data of seeds preserved in collections and make them available to the broader scientific community. In this data paper we provide seed weight data to fill in missing trait data of plant species of Central and Eastern Europe. Our dataset includes weight measurement for 281 taxa of the Central European flora including also some cultivated and exotic species. The seeds were collected between 1971 and 2021 mostly in Central Europe. One part of the measured seeds was collected in the last decade, the other part is from an older seed collection, but all seeds were measured recently. For each species, we collected a minimum of 3 × 100 intact seeds, if possible. The seeds were air-dried at room temperature (approximately 21 °C and 50% relative humidity) for at least two weeks and measured with an accuracy of 0.001 g using an analytical balance. The thousand-seed weights reported here were calculated based on the measured values. Our goal for the future is to incorporate the seed weight data reported here in a regional database (Pannonian Database of Plant Traits - PADAPT) that gathers plant traits and other plant characteristics for the Pannonian flora. The data presented here will facilitate trait-based analyses of the flora and vegetation of Central Europe., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Trait-based ecology is gaining ground nowadays on species-based ecology: the number of research and publication focusing on the ecological role of taxa instead of the species themselves increased significantly in the last two decades. One great advantage of this approach is that communities with different species composition due to great geographical distances (e.g., different continents) or different environmental conditions (e.g., loess, sand, and alkaline grasslands) become comparable. Obtaining trait values is, however, labour and time consuming even in the case of so-called soft traits. It is therefore reasonable and desirable for scientists to share their data as widely as possible. Demand for such data induced the publication of data papers and the establishment of databases, which support both theoretical ecological research and practical restoration ecological projects. Although several international databases (e.g., TRY, LEDA, CLO-PLA, BiolFLOR) are available nowadays, Central and Eastern European species are either missing or underrepresented in them. Consequently, measurement and publication of the traits of species typical in the above region is necessary. This paper presents leaf trait (leaf fresh and dry weight, leaf area, specific leaf area and leaf dry matter content) data for more than 1100 species of the Central European flora., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Human CYP2B6 enzyme although constitutes relatively low proportion (1-4%) of hepatic cytochrome P450 content, it is the major catalyst of metabolism of several clinically important drugs (efavirenz, cyclophosphamide, bupropion, methadone). High interindividual variability in CYP2B6 function, contributing to impaired drug-response and/or adverse reactions, is partly elucidated by genetic polymorphisms, whereas non-genetic factors can significantly modify the CYP2B6 phenotype. The influence of genetic and phenoconverting non-genetic factors on CYP2B6-selective activity and CYP2B6 expression was investigated in liver tissues from Caucasian subjects (N = 119). Strong association was observed between hepatic S-mephenytoin N-demethylase activity and CYP2B6 mRNA expression (P < 0.0001). In less than one third of the tissue donors, the CYP2B6 phenotype characterized by S-mephenytoin N-demethylase activity and/or CYP2B6 expression was concordant with CYP2B6 genotype, whereas in more than 35% of the subjects, an altered CYP2B6 phenotype was attributed to phenoconverting non-genetic factors (to CYP2B6-specific inhibitors and inducers, non-specific amoxicillin + clavulanic acid treatment and chronic alcohol consumption, but not to the gender). Furthermore, CYP2B6 genotype-phenotype mismatch still existed in one third of tissue donors. In conclusion, identifying potential sources of CYP2B6 variability and considering both genetic variations and non-genetic factors is a pressing requirement for appropriate elucidation of CYP2B6 genotype-phenotype mismatch., (© 2022. The Author(s).)

Endozoochory by waterfowl is important for a broad range of angiosperms, most of which lack a fleshy fruit. This dispersal function contributes to the formation and maintenance of plant communities and may allow range shifts for plant species under global change. However, our current understanding of what seed or plant traits are important for this dispersal mechanism, and how they relate to variation in waterbird traits, is extremely limited. We addressed this question using a unique dataset identifying the plant species whose seeds are ingested by 31 different waterfowl species in Europe. We used RLQ and fourth-corner analyses to explore relationships between (1) bird morphological and foraging strategy traits, and (2) plant traits related to seed morphology, environmental preferences, and growth form. We then used Generalized Additive Models to identify relationships between plant/seed traits and the number of waterfowl species that disperse them. Although many waterfowl feed intentionally on seeds, available seed trait data provided little explanation for patterns compared to plant traits such as Ellenberg indicators of habitat preference and life form. Geese were associated with terrestrial plants, ingesting seeds as they graze on land. Diving ducks were associated with strictly aquatic plants, ingesting seeds as they feed at greater depths. Dabbling ducks ingest seeds from plants with high light and temperature requirements, especially shoreline and ruderal species growing in or around the dynamic and shallow microhabitats favored by these birds. Overall, the number of waterfowl vector species (up to 13 per plant species) increases for plants with greater soil moisture requirements and salinity tolerance, reflecting the inclination of most waterfowl species to feed in coastal wetlands. Our findings underline the importance of waterfowl dispersal for plants that are not strictly aquatic, as well as for plants associated with high salinities. Furthermore, our results reveal a soil moisture gradient that drives seed-bird interactions, in line with differences between waterfowl groups in their microhabitat preferences along the land-water continuum. This study provides an important advance in our understanding of the interactions that define plant dispersal in wetlands and their surroundings, and of what plants might be affected by ongoing changes in the distributions of waterfowl species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Almeida, Lukács, Lovas-Kiss, Reynolds and Green.)

During winter, a large number of rooks gather and defecate at the park of a university clinic. We investigated the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in these birds and compared recovered isolates with contemporary human isolates. In 2016, fecal samples were collected from 112 trap-captured rooks and investigated for presence of ESBL producers using eosin methylene blue agar supplemented by 2 mg/L cefotaxime; 2,455 contemporary human fecal samples of patients of the clinics sent for routine culturing were tested similarly. In addition, 42 ESBL-producing E. coli isolates collected during the same period from inpatients were also studied. ESBL genes were sought for by PCR and were characterized by sequencing; E. coli ST131 clones were identified. Epidemiological relatedness was determined by pulsed-field gel electrophoresis and confirmed using whole genome sequencing in selected cases. Thirty-seven (33%) of sampled rooks and 42 (1.7%) of human stools yielded ESBL-producing E coli . Dominant genes were bla CTX-M-55 and bla CTX-M-27 in corvid, bla CTX-M-15 and bla CTX-M-27 in human isolates. ST162 was common among rooks. Two rook-derived E. coli belonged to ST131 C1-M27, which was also predominant (10/42) among human fecal and (15/42) human clinical isolates. Another potential link between rooks and humans was a single ST744 rook isolate grouped with one human fecal and three clinical isolates. Despite possible contact, genotypes shared between rooks and humans were rare. Thus, rooks are important as long-distance vectors and reservoirs of ESBL-producing E. coli rather than direct sources of infections to humans in our setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nagy, Balázs, Benmazouz, Gyüre, Kövér, Kaszab, Bali, Lovas-Kiss, Damjanova, Majoros, Tóth, Bányai and Kardos.)

Blebbistatin, para -nitroblebbistatin (NBleb), and para -aminoblebbistatin (AmBleb) are highly useful tool compounds as they selectively inhibit the ATPase activity of myosin-2 family proteins. Despite the medical importance of the myosin-2 family as drug targets, chemical optimization has not yet provided a promising lead for drug development because previous structure-activity-relationship studies were limited to a single myosin-2 isoform. Here we evaluated the potential of blebbistatin scaffold for drug development and found that D-ring substitutions can fine-tune isoform specificity, absorption-distribution-metabolism-excretion, and toxicological properties. We defined the inhibitory properties of NBleb and AmBleb on seven different myosin-2 isoforms, which revealed an unexpected potential for isoform specific inhibition. We also found that NBleb metabolizes six times slower than blebbistatin and AmBleb in rats, whereas AmBleb metabolizes two times slower than blebbistatin and NBleb in human, and that AmBleb accumulates in muscle tissues. Moreover, mutagenicity was also greatly reduced in case of AmBleb. These results demonstrate that small substitutions have beneficial functional and pharmacological consequences, which highlight the potential of the blebbistatin scaffold for drug development targeting myosin-2 family proteins and delineate a route for defining the chemical properties of further derivatives to be developed. SIGNIFICANCE STATEMENT: Small substitutions on the blebbistatin scaffold have beneficial functional and pharmacological consequences, highlighting their potential in drug development targeting myosin-2 family proteins., (Copyright © 2021 The Author(s).)

Clozapine is effective in treatment-resistant schizophrenia; however, adverse effects often result in discontinuation of clozapine therapy. Many of the side-effects are associated with pharmacokinetic variations; therefore, the expression of major clozapine-metabolizing enzymes (CYP1A2, CYP3A4) in patients may predict development of adverse effects. In patients with schizophrenia (N = 96), development of clozapine concentration-dependent metabolic side-effects was found to be associated with pharmacokinetic variability related to CYP3A4 but not to CYP1A2 expression. In low CYP3A4 expressers, significant correlation was detected between fasting glucose level and clozapine concentration; moreover, the incidence of abnormal glucose level was associated with exaggerated clozapine concentrations (> 600 ng/ml). In low CYP3A4 expressers, exaggerated concentrations were more frequently observed than in normal/high expressers. Moderate/high risk obesity (BMI ≥ 35) more frequently occurred in low CYP3A4 expresser patients than in normal/high expressers. In patients with normal/high CYP3A4 expression and consequently with extensive clozapine-metabolizing capacity, norclozapine/clozapine ratio correlated with fasting glucose levels, triglyceride concentrations and BMI. Low CYP3A4 expression often resulting in exaggerated clozapine concentrations was considered to be as an important risk factor for some concentration-dependent adverse effects as normal/high CYP3A4 expression evoking high norclozapine/clozapine ratios. CYP3A4-status can identify patients with increased risk for metabolic side-effects and prevent their development by careful therapeutic strategy.

Background: End-stage renal disease is an irreversible status of kidney dysfunction that reduces both renal and non-renal drug clearance. Accumulation of uremic toxins seems to modify the activities of drug-metabolizing cytochrome P450 (CYP) enzymes. The aim of the present work was to refine gene expression analysis for efficient and accurate quantification of CYP mRNAs in patients' leukocytes., Methods: We compared six liquid-liquid extraction reagents for RNA isolation and five reverse transcriptase kits for RNA-to-cDNA conversion, and developed quantitative polymerase chain reaction methods for duplex measurements of CYP target genes and the reference gene. The expression of CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in patients with end-stage kidney disease (N = 105) and in organ donors with healthy kidney function (N = 110) was compared., Results: Regarding the RNA yield and purity, TRIzol, Trizolate and TRI reagents were equal; however, TRI reagent was the most advantageous in terms of financial cost. Reverse transcription using Maxima First Strand cDNA Synthesis kit appeared to be the most efficient with the widest range for quantification of the target transcript. The refined method with the detection of various CYPs and the reference gene in duplex PCR efficiently quantified even the low-level CYP expression. In leukocytes of patients with end-stage renal disease, all four CYPs were expressed at significantly lower level than in organ donors with normal kidney function (p < 0.0001)., Conclusions: Reduced CYP expression was a direct evidence of transcriptional down-regulation of CYP genes in patients with impaired kidney function.

Fish have somehow colonized isolated water bodies all over the world without human assistance. It has long been speculated that these colonization events are assisted by waterbirds, transporting fish eggs attached to their feet and feathers, yet empirical support for this is lacking. Recently, it was suggested that endozoochory (i.e., internal transport within the gut) might play a more important role, but only highly resistant diapause eggs of killifish have been found to survive passage through waterbird guts. Here, we performed a controlled feeding experiment, where developing eggs of two cosmopolitan, invasive cyprinids (common carp, Prussian carp) were fed to captive mallards. Live embryos of both species were retrieved from fresh feces and survived beyond hatching. Our study identifies an overlooked dispersal mechanism in fish, providing evidence for bird-mediated dispersal ability of soft-membraned eggs undergoing active development. Only 0.2% of ingested eggs survived gut passage, yet, given the abundance, diet, and movements of ducks in nature, our results have major implications for biodiversity conservation and invasion dynamics in freshwater ecosystems., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Interferon-beta-1a (IFN-β-1a) can diminish the symptoms of relapsing-remitting multiple sclerosis. Herein, we prepared sustained drug delivery IFN-β-1a-loaded nanoparticles by a double emulsion solvent evaporation method. Bovine serum albumin (BSA) model drug was used to optimize the preparation of nanoparticles composed of four types of poly(lactic- co -glycolic acid) (PLGA) polymers and two pegylated PLGA (PEG-PLGA) polymers. Via optimization, selected PLGA and PEG-PLGA polymers were able to entrap IFN-β-1a with high encapsulation efficiency (>95%) and low size (145 nm and 163 nm, respectively). In vitro release kinetics of BSA and IFN-β showed similar tendency for PLGA and PEG-PLGA nanoparticles, respectively. Although the drug loaded nanoparticles did not show toxicity in hepatocyte cells, mild toxic effects such as pale kidney and pyelectasis were observed in the in vivo studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The genus Pseudacronicta was erected, in the noctuid subfamily Acronictinae by Kononenko (2001) as a monotypical genus. Pseudacronicta curiosa Kononenko, 2001 (Figs 2, 3), the type species of this genus, externally resembles Acronicta pulverosa Hampson, 1909 (Fig. 7) and A. pruinosa Guenée, 1852 (Fig. 8) (subgenus Plataplecta Butler, 1878). However, its wing pattern and structure of genitalia differ (Kononenko 2001). On the basis of habitus, P. curiosa appears more similar to Acronicta jozana Matsumura, 1926 (Fig. 6) (subgenus Hyboma Hübner, [1820] sensu Kononenko 2010) than the above mentioned species, but differs from them in the reduced basal dash, linear tornal streak located between the medial and postmedial lines, occasionally continuing between the antemedial and medial lines as a broken, sometimes reduced black line and the occasionally fused basal dash and tornal streak.

The efficacy of aripiprazole therapy and the risk of adverse reactions are influenced by substantial inter-individual variability in aripiprazole metabolizing capacity. In vitro studies assigned the potential role in aripiprazole metabolism to CYP2D6 and CYP3A enzymes; therefore, the association between the steady-state aripiprazole plasma concentrations and patients' CYP2D6 and CYP3A statuses (CYP2D6, CYP3A4, and CYP3A5 genotypes, and CYP3A4 expression) and/or co-medication with CYP function modifying medications has been investigated in 93 psychiatric patients on stable aripiprazole therapy. The patients' CYP2D6 genotype had a major effect on aripiprazole plasma concentrations, whereas contribution of CYP3A genotypes and CYP3A4 expression to aripiprazole clearance were considered to be minor or negligible. The role of CYP3A4 expression in aripiprazole metabolism did not predominate even in the patients with nonfunctional CYP2D6 alleles. Furthermore, dehydroaripiprazole exposure was also CYP2D6 genotype-dependent. Dehydroaripiprazole concentrations were comparable with aripiprazole levels in patients with functional CYP2D6 alleles, and 35% or 22% of aripiprazole concentrations in patients with one or two non-functional CYP2D6 alleles, respectively. The concomitant intake of CYP2D6 inhibitors, risperidone, metoprolol, or propranolol was found to increase aripiprazole concentrations in patients with at least one wild-type CYP2D6*1 allele. Risperidone and 9-hydroxy-risperidone inhibited both dehydrogenation and hydroxylation of aripiprazole, whereas metoprolol and propranolol blocked merely the formation of the active dehydroaripiprazole metabolite, switching towards the inactivation pathways. Patients' CYP2D6 genotype and co-medication with CYP2D6 inhibitors can be considered to be the major determinants of aripiprazole pharmacokinetics. Taking into account CYP2D6 genotype and co-medication with CYP2D6 inhibitors may improve the outcomes of aripiprazole therapy.

Field studies have shown that waterbirds, especially members of the Anatidae family, are major vectors of dispersal by endozoochory for a broad range of plants lacking a fleshy fruit, yet whose propagules can survive gut passage. Widely adopted dispersal syndromes ignore this dispersal mechanism, and we currently have little understanding of what traits determine the potential of angiosperms for endozoochory by waterbirds. Results from previous experimental studies have been inconsistent as to how seed traits affect seed survival and retention time in the gut and have failed to control for the influence of plant phylogeny. Using 13 angiosperm species from aquatic and terrestrial habitats representing nine families, we examined the effects of seed size, shape, and hardness on the proportion of seeds surviving gut passage through mallards ( Anas platyrhynchos ) and their retention time within the gut. We compiled a molecular phylogeny for these species and controlled for the nonindependence of taxa due to common descent in our analyses. Intact seeds from all 13 species were egested, but seed survival was strongly determined by phylogeny and by partial effects of seed mass and hardness (wet load): species with seeds harder than expected from their size, and smaller than expected from their loading, had greater survival. Once phylogeny was controlled for, a positive partial effect of seed roundness on seed survival was also revealed. Species with seeds harder than expected from their size had a longer mean retention time, a result retained after controlling for phylogeny. Our study is the first to demonstrate that seed shape and phylogeny are important predictors of seed survival in the avian gut. Our results demonstrate that the importance of controlling simultaneously for multiple traits and relating single traits (e.g., seed size) alone to seed survival or retention time is not a reliable way to detect important patterns, especially when phylogenetic effects are ignored., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: CYP2C19 is an important drug-metabolizing enzyme, responsible for metabolism of approximately 10% of the drugs on the market. Large inter-individual differences exist in metabolic activities, which are primarily attributed to genetic polymorphism of CYP2C19 gene. Conflicting results have been published about the role of CYP2C19 polymorphisms in metabolism of CYP2C19 substrates and clinical outcomes; thus, we aimed to investigate CYP2C19 genotype-phenotype associations, and we sought to elicit potential causes of discrepancies in the genotype-based prediction by incorporating the liver donors' demographic data, drug administration events and pathological conditions., Methods: (S)-Mephenytoin was used to assess CYP2C19 activities in human liver microsomes derived from 114 Hungarian organ donors. CYP2C19 genotype was determined by SNP genotyping for CYP2C19*2, CYP2C19*3, CYP2C19*4 and CYP2C19*17 variants, and CYP2C19 mRNA levels were measured by qPCR method. Clinical data of the donors were considered in the genotype-based phenotype prediction., Results: CYP2C19 phenotype of 40% of the donors was well-predicted from the genotype data, whereas the phenotype of 13% was underestimated displaying higher activity, and of 47% was overestimated displaying lower activity than predicted from CYP2C19 genotype. Among the donors with overestimated phenotype, one was treated with CYP2C19 substrate/inhibitor, 9 were on amoxicillin-clavulanic acid therapy, 7 were chronic alcohol consumers and 9 had disease with inflammatory processes., Conclusions: CYP2C19 genotype only partially determines the CYP2C19 phenotypic appearance; co-medication, diseases with inflammatory processes and aspecific factors, such as chronic alcohol consumption and amoxicillin-clavulanic acid therapy (or any drug therapy resulting in liver injury) seem to be potential phenotype-modifying factors., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)