Seed dispersal by the cosmopolitan house sparrow widens the spectrum of unexpected endozoochory by granivore birds.

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.

Visually evoked local field potential changes in the caudate nucleus are remarkably more frequent in awake, behaving cats than in anaesthetized animals.

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.

Suboptimal multisensory processing in pediatric migraine without aura: a comparative, cross-sectional study.

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.

Plant traits associated with seed dispersal by ducks and geese in urban and natural habitats.

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.

CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.

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.

Automated preprocessing of 64 channel electroenchephalograms recorded by biosemi instruments.

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.

Carbapenem-resistant Escherichia coli in Black-headed gulls, the Danube, and human clinical samples: A One Health comparison of contemporary isolates.

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.

Potential Association of Cytochrome P450 Copy Number Alteration in Tumour with Chemotherapy Resistance in Lung Adenocarcinoma Patients.

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.

Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.

Cyclophosphamide, an oxazaphosphorine prodrug is frequently used in treatment of neuroblastoma, which is one of the most prevalent solid organ malignancies in infants and young children. Cytochrome P450 2B6 (CYP2B6) is the major catalyst and CYP2C19 is the minor enzyme in bioactivation and inactivation pathways of cyclophosphamide. CYP-mediated metabolism may contribute to the variable pharmacokinetics of cyclophosphamide and its toxic byproducts leading to insufficient response to the therapy and development of clinically significant side effects. The aim of the study was to reveal the contribution of pharmacogenetic variability in CYP2B6 and CYP2C19 to the treatment efficacy and cyclophosphamide-induced side effects in pediatric neuroblastoma patients under cyclophosphamide therapy (N = 50). Cyclophosphamide-induced hematologic toxicities were pivotal in all patients, whereas only moderate hepatorenal toxicity was developed. The patients' CYP2B6 metabolizer phenotypes were associated with the occurrence of lymphopenia, thrombocytopenia, and monocytopenia as well as of liver injury, but not with kidney or urinary bladder (hemorrhagic cystitis) toxicities. Furthermore, the patients' age (< 1.5 years, P = 0.03) and female gender (P ≤ 0.02), but not CYP2B6 or CYP2C19 metabolizer phenotypes appeared as significant prognostic factors in treatment outcomes. Our results may contribute to a better understanding of the impact of CYP2B6 variability on cyclophosphamide-induced side effects.

New thousand-seed weight dataset for plant species of Central Europe.

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.

Seed Size, Not Dispersal Syndrome, Determines Potential for Spread of Ricefield Weeds by Gulls.

Recent field data suggest that migratory gulls disperse many rice field weeds by gut passage (endozoochory), most of which are dry fruited and widely assumed to have no long-distance dispersal mechanisms, except via human activity. We investigated this mechanism with a feeding experiment, in which seeds of five common rice field weeds (in order of increasing seed size: Juncus bufonius, Cyperus difformis, Polypogon monspeliensis, Amaranthus retroflexus, and the fleshy-fruited Solanum nigrum) were fed to seven individuals of lesser black-backed gulls Larus fuscus held in captivity. We quantified seed survival after collecting faeces at intervals for 33 h after ingestion, then extracting intact seeds and running germination tests, which were also conducted for control seeds. All five species showed high seed survival after gut passage, of >70%. Gut retention times averaged 2-4 h, but maxima exceeded 23 h for all species. Germinability after gut passage was 16-54%, and gut passage accelerated germination in J. bufonius and S. nigrum, but slowed it down in the other species. All species had lower germinability after gut passage compared to control seeds (likely due to stratification prior to the experiment), but the loss of germinability was higher in smaller seeds. There was no evidence that the different dispersal syndromes assigned to the five species (endozoochory, epizoochory or barochory) had any influence on our results. In contrast, mean gut retention time was strongly and positively related to seed size, likely because small seeds pass more quickly from the gizzard into the intestines. Non-classical endozoochory of dry-fruited seeds by waterbirds is a major but overlooked mechanism for potential long-distance dispersal, and more research into this process is likely essential for effective weed management.

Visual consequent stimulus complexity affects performance in audiovisual associative learning.

In associative learning (AL), cues and/or outcome events are coupled together. AL is typically tested in visual learning paradigms. Recently, our group developed various AL tests based on the Rutgers Acquired Equivalence Test (RAET), both visual and audiovisual, keeping the structure and logic of RAET but with different stimuli. In this study, 55 volunteers were tested in two of our audiovisual tests, SoundFace (SF) and SoundPolygon (SP). The antecedent stimuli in both tests are sounds, and the consequent stimuli are images. The consequents in SF are cartoon faces, while in SP, they are simple geometric shapes. The aim was to test how the complexity of the applied consequent stimuli influences performance regarding the various aspects of learning the tests assess (stimulus pair learning, retrieval, and generalization of the previously learned associations to new but predictable stimulus pairs). In SP, behavioral performance was significantly poorer than in SF, and the reaction times were significantly longer, for all phases of the test. The results suggest that audiovisual associative learning is significantly influenced by the complexity of the consequent stimuli.

Multisensory stimuli enhance the effectiveness of equivalence learning in healthy children and adolescents.

It has been demonstrated earlier in healthy adult volunteers that visually and multisensory (audiovisual) guided equivalence learning are similarly effective. Thus, these processes seem to be independent of stimulus modality. The question arises as to whether this phenomenon can be observed also healthy children and adolescents. To assess this, visual and audiovisual equivalence learning was tested in 157 healthy participants younger than 18 years of age, in both a visual and an audiovisual paradigm consisting of acquisition, retrieval and generalization phases. Performance during the acquisition phase (building of associations), was significantly better in the multisensory paradigm, but there was no difference between the reaction times (RTs). Performance during the retrieval phase (where the previously learned associations are tested) was also significantly better in the multisensory paradigm, and RTs were significantly shorter. On the other hand, transfer (generalization) performance (where hitherto not learned but predictable associations are tested) was not significantly enhanced in the multisensory paradigm, while RTs were somewhat shorter. Linear regression analysis revealed that all the studied psychophysical parameters in both paradigms showed significant correlation with the age of the participants. Audiovisual stimulation enhanced acquisition and retrieval as compared to visual stimulation only, regardless of whether the subjects were above or below 12 years of age. Our results demonstrate that multisensory stimuli significantly enhance association learning and retrieval in the context of sensory guided equivalence learning in healthy children and adolescents. However, the audiovisual gain was significantly higher in the cohort below 12 years of age, which suggests that audiovisually guided equivalence learning is still in development in childhood.

New data of plant leaf traits from Central Europe.

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.

Gulls living in cities as overlooked seed dispersers within and outside urban environments.

The yellow-legged gull is an opportunistic and generalist bird that has colonised urban areas, where it has found very favourable trophic resources but also causes disturbance to humans and damage to infrastructure. Here, we investigated the potential role that gulls play in the dispersal of plants in Barcelona, a highly populated city of north-eastern Spain. We analysed the stomach contents of 145 chicks collected in urban nests and reported the presence of seeds of 27 plant taxa. We then developed a plant dispersal model based on the movements of 20 GPS-tracked yellow-legged gulls breeding in the city of Barcelona. We estimated seed dispersal distances, seed shadows and percentage of seeds reaching habitats suitable for seeds regurgitated in pellets and those excreted in faeces. Seven of the 27 plant taxa found in the stomachs were alien taxa to Spain. Average dispersal distances of plant seeds by gulls were around 700 m, but maximum dispersal distances reached up to 35 km. Dispersal distances and seed spatial patterns did not differ between faeces and pellet models, as most strongly depended on gull movements. About 95% of the seeds were dispersed within urban environments and between 20 and 30% reached suitable habitats for seed deposition (urban woodlands, green urban parks and urban grasslands). Urban gulls frequently dispersed seeds (including alien species) within urban habitats, both via direct consumption or via secondary dispersal after consuming granivorous birds that had ingested the seeds, such as pigeons or parakeets. Urban planning for Barcelona is based on native plant species, and thus, special attention should be paid to alien plants dispersed by birds, which could pose a risk to native biodiversity in urban ecosystems.

The Influence of Stimulus Complexity on the Effectiveness of Visual Associative Learning.

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.

CYP2B6 allelic variants and non-genetic factors influence CYP2B6 enzyme function.

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.

Evaluating the effectiveness and quality of mobile applications for perinatal depression and anxiety: A systematic review and meta-analysis.

BACKGROUND: Our objectives were to assess: (1) the effectiveness of existing mHealth apps for reducing symptoms of maternal depression and/or anxiety during the prenatal period and/or the first year postpartum, and (2) the app quality of commercially available apps targeting perinatal depression and/or anxiety. METHODS: To address Objective 1, we searched five electronic databases (MEDLINE, CINAHL, PsycINFO, Web of Science, and Embase) from their inception until May 3rd, 2021. For the second objective, we searched Google Play and Apple App Stores in the United States, United Kingdom, Canada, and Australia until May 3rd, 2021. RESULTS: Our search identified 3,897 articles, seven of which were meta-analyzed. mHealth apps did not improve perinatal depression (SMD, -0.39; 95% CI, -0.80 to 0.03) or anxiety (SMD, 0.01; 95% CI, -0.13 to 0.16) within the first 3 months post-intervention or at 6 months post-intervention. Our search of app stores identified 74 commercially available apps, 37 of which were evaluated via MARS tool. Current apps for perinatal anxiety and/or depression were rated to be of moderate quality on the MARS (mean, 3.6/5). LIMITATIONS: There is a small number of overall studies in this field and the individual studies have methodological limitations. Furthermore, few apps identified in our app store search have been clinically tested. CONCLUSION: Despite their widespread availability, mHealth apps do not appear to effectively reduce perinatal depression or anxiety, and few were subjectively rated to be of high quality. There is a need to develop higher quality mHealth apps and assess their potential to improve perinatal maternal mental health.

Improved Inhibitory and Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADMET) Properties of Blebbistatin Derivatives Indicate That Blebbistatin Scaffold Is Ideal for drug Development Targeting Myosin-2.

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.

Comparison of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates From Rooks (Corvus frugilegus) and Contemporary Human-Derived Strains: A One Health Perspective.

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.