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Following the publication, in 2018, of a consistent part of Sylvia Plath’s correspondence, scholars interested in her complex biographical and literary story found new opportunities to read the American poet in a new light. I shall explore the letters she sent to her psychiatrist, Dr. Ruth Beuscher, while also critically observing their relevance in understanding Plath’s oeuvre.

Dorothea Tanning’s longstanding interest in the maternal element completes the artist’s complex relationship to femininity and the female experience, turning them into essential themes in her oeuvre. I shall explore the particular manner in which the American Surrealist integrates and transforms the notion of motherhood in her art. I shall also argue that Tanning’s works as a writer offer an original insight into this cardinal theme in western art, as she dismantles common tropes and refashions them into a new, unusual language.

Little girls and young women are Dorothea Tanning’s recurrent archetypes, defining and structuring her conceptual archive concerning gender and the feminine. A celebrated painter and sculptor who shaped her artistic vision in the proximity of the historical avant-gardes, Tanning was also a writer who revealed the mystery and estrangement of family ties in Chasm: A weekend, a novel she started writing in 1943 and published six decades later, in 2004. This singular book offers a privileged dialogue between literature and art, as several episodes revisit and translate the high tension of some of her most representative paintings. From within a feminist framework, the article will discuss aspects of female authority and control in Tanning’s novel as dominant forms of female empowerment, present throughout her visual Surrealist oeuvre. I argue that examining these allegories reveals their role as connectors between the literary and the visual arts, between Dorothea Tanning’s fiction and her painting.

I intend to explore Philip Roth’s representation of aging in his 1997 novel, American Pastoral, and in the allegorical, medical life story of his generic hero, Everyman (2006). My arguments connect the writer’s constant preoccupation with the biological life of the body and the cultural significance of aging, divergently projected in these two novels.

Organophosphate insecticides are known to inhibit the activity of enzyme acetylcholinesterase. They affect olfactory learning and memory formation in honeybees. These insecticides cause mushroom body inactivation in honeybees, but their influence on other brain regions involved in olfactory perception and memory is unknown. The goal of this study was to study the effects of organophosphate insecticide diazinon on carnolian honeybee (Apis mellifera carnica) acetylcholinesterase activity in the olfactory brain regions of antennal lobe, mushroom body and lateral procerebrum (lateral horn). The lamina, medulla and lobula of optic lobes were also analyzed. The level of acetylcholinesterase activity was visualized using the histochemical staining method. Densitometric analysis of histochemical signals indicated that diazinon inhibited acetylcholinesterase activity only in the lip of calyces of mushroom body, but not in other analyzed olfactory regions, antennal lobe and lateral procerebrum. The visual brain system optic lobes were also unaffected. This is in accordance with the literature reporting that mushroom body is the main brain center for olfactory learning and memory formation in honeybees.

Although one of the most influential figures of Romanian Communism, Elena Ceaușescu has been the subject of a rather limited literature exploring her historical figure. I intend to revisit the political humour of Romanian communism in order to reveal the manners and strategies employed by this type of folklore in affirming the hyperbolized clichés that defined the dictator’s wife in the public mind of that age. I also intend to bring into discussion the common traditional prejudice that blamed Elena Ceaușescu for her husband’s catastrophic politics that impoverished and isolated Romania in the Eastern Bloc.

From Philip Roth’s characater Merry Levov in American Pastoral to real-life figures such as the perpetrators of the Columbine massacre, the young domestic terrorist has become the archetype of a dramatic and unpredictable social and political climate. This paper intends to explore the real and fictional avatars of this contemporary anti-hero, its dynamics and specific place in contemporary imagination.

A Surrealist painter whose artistic vision is equally visible in her literary works, Dorothea Tanning established a solid dialogue between literature and the plastic arts. The corpus of her literary oeuvre is rather small, consisting of a novel, a volume of poetry and her memoir, Between Lives. This paper argues that Tanning can be regarded as an exemplary author of a creative transfer between verbal and plastic imagination. It also explores the tension between the two means of expression, most visible in her novel Chasm: A Weekend. Here, the imagery and enigmatic symbolism of her painting come to life in the story of a strange little girl called Destina Meridian.

American Pastoral is not only an elegiac fictional biography, but an in-depth analysis of the demise of the American dream in the context of post-war social and cultural mutations. The loss of innocence echoes the tragic mythical Fall from Paradise and the novel’s main characters, Seymour “Swede” Levov and his daughter, Merry, mirror this process in a complex and meaningful way.

Soft magnetoactive elastomers (MAEs) are currently considered to be promising materials for actuators in soft robotics. Magnetically controlled actuators often operate in the vicinity of a bias point. Their dynamic properties can be characterized by the piezomagnetic strain coefficient, which is a ratio of the time-harmonic strain amplitude to the corresponding magnetic field strength. Herein, the dynamic strain response of a family of MAE cylinders to the time-harmonic (frequency of 0.1-2.5 Hz) magnetic fields of varying amplitude (12.5 kA/m-62.5 kA/m), superimposed on different bias magnetic fields (25-127 kA/m), is systematically investigated for the first time. Strain measurements are based on optical imaging with sub-pixel resolution. It is found that the dynamic strain response of MAEs is considerably different from that in conventional magnetostrictive polymer composites (MPCs), and it cannot be described by the effective piezomagnetic constant from the quasi-static measurements. The obtained maximum values of the piezomagnetic strain coefficient (∼102 nm/A) are one to two orders of magnitude higher than in conventional MPCs, but there is a significant phase lag (35-60°) in the magnetostrictive response with respect to an alternating magnetic field. The experimental dependencies of the characteristics of the alternating strain on the amplitude of the alternating field, bias field, oscillation frequency, and aspect ratio of cylinders are given for several representative examples. It is hypothesized that the main cause of observed peculiarities is the non-linear viscoelasticity of these composite materials.

Honey bees are important plant pollinators and honey producers. Contamination of the environment with metals can lead to a decline in honey bee populations. Copper (Cu) and zinc (Zn) salts are commonly used as fungicides and foliar fertilizers. In this study, we investigated the effects of 10-day chronic oral exposure to different concentrations of Cu (CuSO4) and Zn (ZnCl2) on survival and feeding rates of Carniolan honey bees in laboratory conditions. We found that mortality in honey bee workers increased in a concentration-dependent manner and that Cu (lethal concentration [LC50] = 66 mg/l) was more toxic than Zn (LC50 = 144 mg/l). There was no difference in the feeding rate of Cu-treated bees for the different concentrations tested, but the feeding rate decreased with the increase in Zn concentration. To determine feeding preference or avoidance for Cu and Zn, we conducted 2-choice 24-h feeding experiments. We demonstrated that honey bees preferred Zn-containing solutions compared to the control diet. A two-choice experiment with Cu showed a tendency for honey bees to be deterred by Cu at high concentrations; however, it was not statistically significant. In summary, our results suggest that honey bee workers may suffer adverse effects when exposed to ecologically relevant concentrations of Cu and Zn., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Significant deformations of bodies made from compliant magnetoactive elastomers (MAE) in magnetic fields make these materials promising for applications in magnetically controlled actuators for soft robotics. Reported experimental research in this context was devoted to the behaviour in the quasi-static magnetic field, but the transient dynamics are of great practical importance. This paper presents an experimental study of the transient response of apparent longitudinal and transverse strains of a family of isotropic and anisotropic MAE cylinders with six different aspect ratios in time-varying uniform magnetic fields. The time dependence of the magnetic field has a trapezoidal form, where the rate of both legs is varied between 52 and 757 kA/(s·m) and the maximum magnetic field takes three values between 153 and 505 kA/m. It is proposed to introduce four characteristic times: two for the delay of the transient response during increasing and decreasing magnetic field, as well as two for rise and fall times. To facilitate the comparison between different magnetic field rates, these characteristic times are further normalized on the rise time of the magnetic field ramp. The dependence of the normalized characteristic times on the aspect ratio, the magnetic field slew rate, maximum magnetic field values, initial internal structure (isotropic versus anisotropic specimens) and weight fraction of the soft-magnetic filler are obtained and discussed in detail. The normalized magnetostrictive hysteresis loop is introduced, and used to explain why the normalized delay times vary with changing experimental parameters.

Several pathogens are important causes of the observed pollinator decline, some of which could be transmitted between different pollinator species. To determine whether honeybee viruses can be transmitted to butterflies, a total of 120 butterflies were sampled at four locations in Slovenia. At each location, butterflies from three families (Pieridae, Nymphalidae, Hesperiidae/Lycenidae) and Carniolan honeybees ( Apis mellifera carnica ) were collected. The RNA of six honeybee viruses, i.e., acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus A (DWV-A), Sacbrood bee virus (SBV), and Lake Sinai virus 3 (LSV3), was detected by a specific quantitative method (RT-PCR). The presence of ABPV, BQCV, LSV3, and SBV was detected in both butterflies and honeybees. All butterfly and bee samples were negative for CBPV, while DWV-A was detected only in honeybees. The viral load in the positive butterfly samples was much lower than in the positive bee samples, which could indicate that butterflies are passive carriers of bee viruses. The percentage of positive butterfly samples was higher when the butterflies were collected at sampling sites with a higher density of apiaries. Therefore, we believe that infected bees are a necessary condition for the presence of viruses in cohabiting butterflies. This is the first study on the presence of pathogenic bee viruses in butterflies.

In this work, multiferroic cantilevers comprise a layer of a magnetoactive elastomer (MAE) and a commercially available piezoelectric polymer-based vibration sensor. The structures are fixed at one end in the horizontal plane and the magnetic field is applied vertically. First, the magnetoelectric (ME) response to uniform, triangle-wave magnetic fields with five different slew rates is investigated experimentally. Time and field dependences of the generated voltage, electric charge, and observed mechanical deflection are obtained and compared for four different thicknesses of the MAE layer. The ME responses to triangular and sinusoidal wave excitations are examined in contrast. Second, the ME response at low frequencies (≤3 Hz) is studied by the standard method of harmonic magnetic field modulation. The highest ME coupling coefficient is observed in the bias magnetic field strength of ≈73 kA/m and it is estimated to be about 3.3 ns/m (ME voltage coefficient ≈ 25 V/A) at theoretically vanishing modulation frequency (f→0 Hz). Presented results demonstrate that the investigated heterostructures are promising for applications as magnetic-field sensors and energy harvesting devices.

A surface relief grating with a period of 30 µm is embossed onto the surface of magnetoactive elastomer (MAE) samples in the presence of a moderate magnetic field of about 180 mT. The grating, which is represented as a set of parallel stripes with two different amplitude reflectivity coefficients, is detected via diffraction of a laser beam in the reflection configuration. Due to the magnetic-field-induced plasticity effect, the grating persists on the MAE surface for at least 90 h if the magnetic field remains present. When the magnetic field is removed, the diffraction efficiency vanishes in a few minutes. The described effect is much more pronounced in MAE samples with larger content of iron filler (80 wt%) than in the samples with lower content of iron filler (70 wt%). A simple theoretical model is proposed to describe the observed dependence of the diffraction efficiency on the applied magnetic field. Possible applications of MAEs as magnetically reconfigurable diffractive optical elements are discussed. It is proposed that the described experimental method can be used as a convenient tool for investigations of the dynamics of magnetically induced plasticity of MAEs on the micrometer scale.

Current farm systems rely on the use of Plant Protection Products (PPP) to secure high productivity and control threats to the quality of the crops. However, PPP use may have considerable impacts on human health and the environment. A study protocol is presented aiming to determine the occurrence and levels of PPP residues in plants (crops), animals (livestock), humans and other non-target species (ecosystem representatives) for exposure modelling and impact assessment. To achieve this, we designed a cross-sectional study to compare conventional and organic farm systems across Europe. Environmental and biological samples were/are being/will be collected during the 2021 growing season, at 10 case study sites in Europe covering a range of climate zones and crops. An additional study site in Argentina will inform the impact of PPP use on growing soybean which is an important European protein-source in animal feed. We will study the impact of PPP mixtures using an integrated risk assessment methodology. The fate of PPP in environmental media (soil, water and air) and in the homes of farmers will be monitored. This will be complemented by biomonitoring to estimate PPP uptake by humans and farm animals (cow, goat, sheep and chicken), and by collection of samples from non-target species (earthworms, fish, aquatic and terrestrial macroinvertebrates, bats, and farm cats). We will use data on PPP residues in environmental and biological matrices to estimate exposures by modelling. These exposure estimates together with health and toxicity data will be used to predict the impact of PPP use on environment, plant, animal and human health. The outcome of this study will then be integrated with socio-economic information leading to an overall assessment used to identify transition pathways towards more sustainable plant protection and inform decision makers, practitioners and other stakeholders regarding farming practices and land use policy., Competing Interests: The authors have declared that no competing interests exist.

The voltage response to pulsed uniform magnetic fields and the accompanying bending deformations of laminated cantilever structures are investigated experimentally in detail. The structures comprise a magnetoactive elastomer (MAE) slab and a commercially available piezoelectric polymer multilayer. The magnetic field is applied vertically and the laminated structures are customarily fixed in the horizontal plane or, alternatively, slightly tilted upwards or downwards. Six different MAE compositions incorporating three concentrations of carbonyl iron particles (70 wt%, 75 wt% and 80 wt%) and two elastomer matrices of different stiffness are used. The dependences of the generated voltage and the cantilever's deflection on the composition of the MAE layer and its thickness are obtained. The appearance of the voltage between the electrodes of a piezoelectric material upon application of a magnetic field is considered as a manifestation of the direct magnetoelectric (ME) effect in a composite laminated structure. The ME voltage response increases with the increasing total quantity of the soft-magnetic filler in the MAE layer. The relationship between the generated voltage and the cantilever's deflection is established. The highest observed peak voltage around 5.5 V is about 8.5-fold higher than previously reported values. The quasi-static ME voltage coefficient for this type of ME heterostructures is about 50 V/A in the magnetic field of ≈100 kA/m, obtained for the first time. The results could be useful for the development of magnetic field sensors and energy harvesting devices relying on these novel polymer composites.

Aegerolysin proteins ostreolysin A6 (OlyA6), pleurotolysin A2 (PlyA2) and erylysin A (EryA) produced by the mushroom genus Pleurotus bind strongly to an invertebrate-specific membrane sphingolipid, and together with a protein partner pleurotolysin B (PlyB), form transmembrane pore complexes. This pore formation is the basis for the selective insecticidal activity of aegerolysin/PlyB complexes against two economically important coleopteran pests: the Colorado potato beetle and the western corn rootworm. In this study, we evaluated the toxicities of these aegerolysin/PlyB complexes using feeding tests with two ecologically important non-target arthropod species: the woodlouse and the honey bee. The mammalian toxicity of the EryA/PlyB complex was also evaluated after intravenous administration to mice. None of the aegerolysin/PlyB complexes were toxic against woodlice, but OlyA6/PlyB and PlyA2/PlyB were toxic to honeybees, with 48 h mean lethal concentrations (LC 50 ) of 0.22 and 0.39 mg/mL, respectively, in their food. EryA/PlyB was also tested intravenously in mice up to 3 mg/kg body mass, without showing toxicity. With no toxicity seen for EryA/PlyB for environmentally beneficial arthropods and mammals at the tested concentrations, these EryA/PlyB complexes are of particular interest for development of new bioinsecticides for control of selected coleopteran pests.

Neuroinflammation is an important factor in the pathogenesis of neurodegenerative diseases. Microglia-derived lysosomal cathepsins have been increasingly recognized as important inflammatory mediators that trigger signaling pathways that aggravate neuroinflammation. In vitro , a contribution to neuroinflammation processes has been shown for cathepsin X: however, the expression patterns and functional role of cathepsin X in neuroinflammatory brain pathology remain elusive. In this study we analyzed the expression, activity, regional distribution and cellular localization of cathepsin X in the rat brain with neuroinflammation-induced neurodegeneration. The unilateral injection of lipopolysaccharide (LPS) induced a strong upregulation of cathepsin X expression and its activity in the ipsilateral striatum. In addition to the striatum, cathepsin X overexpression was detected in other brain areas such as the cerebral cortex, corpus callosum, subventricular zone and external globus pallidus, whereas the upregulation was mainly restricted to activated microglia and reactive astrocytes. Continuous administration of the cathepsin X inhibitor AMS36 indicated protective effects against LPS-induced striatal degeneration, as seen by the attenuated LPS-mediated dilation of the lateral ventricles and partial decreased extent of striatal lesion. Taken together, our results indicate that cathepsin X plays a role as a pathogenic factor in neuroinflammation-induced neurodegeneration and represents a potential therapeutic target for neurodegenerative diseases associated with neuroinflammation., (Copyright © 2020 Pišlar, Tratnjek, Glavan, Zidar, Živin and Kos.)

The parasitic mite Varroa destructor is a threat to beekeeping colonies. Among naturally derived acaricides, the monoterpenoid essential oil compound thymol is used in beekeeping for varroa mite control, but adverse impacts on honeybees has been already documented. Carvacrol, another monoterpenoid, also has a high acaricidal potential and could thus be promising for regular use in beekeeping, but information is scarce regarding the effects of prolonged systemic administration of carvacrol on honeybees. In this study, we evaluate and compared the sublethal effects of long term consumption of carvacrol and thymol on Carnolian honeybee workers (Apis mellifera carnica). Survival and feeding rate were determined preliminary to assess sublethal concentrations. The sublethal effects were analysed by the activity of the acetylcholinesterase (AChE), enzyme involved in the control of neurotransmission, and the activity of detoxifying enzyme glutathione S-transferase (GST) in heads and thoraces. We found that, thymol and carvacrol, caused mortality only at the highest concentrations tested, 1% and 5% respectively. As demonstrated by others, both substances could be effective against varroa at concentrations ten times lower than those causing significant honeybee mortality. However, we demonstrated sublethal effects at the 0.05% carvacrol and thymol exposure concentrations evidenced as increased activity of AChE and GST in the honeybee heads. In conclusion, prolonged treatment with thymol and carvacrol affects bee nervous system and induce detoxification processes possibly resulting in a limited use for acaricidal purposes. We postulate that under the same chronic exposure conditions carvacrol and thymol will have similar sublethal effects on honeybees., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objectives: Rheumatoid arthritis (RA) is a severe autoimmune disease characterized by chronic inflammation of the joints accompanied by the progressive deformation and destruction of cartilage and joint bones. This study aims to gain insight into the outcomes related to adherence in patients with rheumatoid arthritis. Predicting the medication adherence in RA patients is a key point to improve the treatment outcome. Materials and Methods : A number of 119 Romanian patients with RA were included and divided into two groups: first group included 79 patients treated with conventional therapy and second group included 40 patients treated with biologic therapy. A CQR-9 (compliance questionnaire rheumatology with nine items) and PDSQ (psychiatric diagnostic screening questionnaire) were performed to assess correlations between medication adherence, patient sociodemographic variables, 11 psychiatric scales (major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, psychosis, agoraphobia, social phobia, drug abuse/dependence, generalized anxiety disorder, somatization disorder, hypochondriasis) and lifestyle (bulimia, alcohol intake). Results : Whilst modelling factors associated with adherence, it was found that women and patients with higher education are more adherent. From the psychiatric indicators, only major depressive disorder and post-traumatic stress disorder were found to be positively correlated with therapeutic adherence. None of the assessed lifestyle factors influenced the adherence of RA patients. Conclusion : The knowledge of factors that impact on treatment adherence can be useful for clinicians to guide patient-centred care., Competing Interests: The authors declare no conflict of interest.

We investigate the applicability of polymer-ionic liquid composites as optical elements for light, as well as for slow neutrons. The gratings are recorded using two-beam mixing and are characterized experimentally based on their diffraction properties. We produced a set of samples differing in their thickness, ranging from 10 m - 100 m . We demonstrate that it is possible to prepare transmission gratings with a lattice constant of Λ = 480 n m , resulting in thick gratings for light, as well as neutrons. The presented samples show low optical losses in the Vis-UV spectrum and exhibit refractive index modulations of about 10 - 3 at λ = 543 n m . However, further improvements have to be made to obtain efficient neutron optical components.

We investigated magnetic-field-induced modifications of the surface roughness of magnetoactive elastomers (MAEs) with four material compositions incorporating two concentrations of ferromagnetic microparticles (70 wt% and 80 wt%) and exhibiting two shear storage moduli of the resulting composite material (about 10 kPa and 30 kPa). The analysis was primarily based on spread optical reflection measurements. The surfaces of all four materials were found to be very smooth in the absence of magnetic field (RMS roughness below 50 nm). A maximal field-induced roughness modification (approximately 1 μm/T) was observed for the softer material with the lower filler concentration, and a minimal modification (less than 50 nm/T) was observed for the harder material with the higher filler concentration. All four materials showed a significant decrease in the total optical reflectivity with an increasing magnetic field as well. This effect is attributed to the existence of a distinct surface layer that is depleted of microparticles in the absence of a magnetic field but becomes filled with particles in the presence of the field. We analyzed the temporal response of the reflective properties to the switching on and off of the magnetic field and found switching-on response times of around 0.1 s and switching-off response times in the range of 0.3⁻0.6 s. These observations provide new insight into the magnetic-field-induced surface restructuring of MAEs and may be useful for the development of magnetically reconfigurable elastomeric optical surfaces., Competing Interests: The authors declare no conflicts of interest.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc). In vitro , a contribution to neuroinflammation and neurotoxicity has been shown for the lysosomal protease cathepsin X; however, its expression and its role in PD remain unknown. Therefore, the current study was designed to address the regional, cellular, and subcellular localization and activity of cathepsin X in hemi-parkinsonian rats with 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in the unilateral medial forebrain bundle (MFB) lesion. We report for the first time that cathepsin X expression and activity are rapidly increased in the ipsilateral SNc after injection of 6-OHDA into the MFB reaching a maximum after 12 h but seem to stay strongly upregulated after 4 weeks after injection. At early time points of 6-OHDA injection into the MFB, the increased cathepsin X is localized in the lysosomes in the neuronal, predominantly tyrosine hydroxylase-positive dopaminergic cells. After 12 h of 6-OHDA induced lesion, only a few activated microglial cells are positive for cathepsin X whereas, in 4 weeks post-lesion accompanied with complete loss of dopaminergic neurons, there is persistent cathepsin X upregulation restricted to activated glia cells. Taken together, our results demonstrate that cathepsin X upregulation in the lesioned dopaminergic system may play a role as a pathogenic factor in PD. Moreover, inhibition of cathepsin X expression or activity may be useful in protecting the nigrostriatal dopaminergic projection in the PD.

Organophosphate pesticide diazinon is a specific inhibitor of acetylcholinesterase (AChE), which is a common neurotoxicity biomarker in environmental studies. In honeybees, AChE exists in two forms having different physiological roles, one existing as a soluble form and the other as membrane-bound. In most studies AChE activity has been analysed without paying considerable attention to different forms of AChE. In this study, we exposed honeybees Apis mellifera carnica for 10days to diazinon via oral exposure and analysed the total AChE activities in salt soluble (SS) and detergent soluble (DS) fractions. We assumed that SS fraction would preferentially contain the soluble AChE, but the DS fraction would contain only membrane AChE. On the contrary, our results showed that SS and DS fractions both contain soluble and membrane AChE and the latter has considerably higher activity. Despite this we obtained a differential response of AChE activity in SS and DS fractions when exposed to diazinon. The head/thorax AChE activity in DS fraction decreased, while the head/thorax AChE activity in SS fraction increased at sublethal concentrations. The AChE activity in honeybee hemolymph shown here for the first time is a salt soluble enzyme. Its activity remained unaltered after diazinon treatment. In conclusion, we provide evidence that varying results regarding AChE activity alterations upon stressor exposure are obtained when extracted through different procedures. In further environmental studies with honeybees this differential response of AChE activity should be given considerable attention because this affects the outcome of ecotoxicity study., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Varroa destructor is one of the most common parasites of honey bee colonies and is considered as a possible co-factor for honey bee decline. At the same time, the use of pesticides in intensive agriculture is still the most effective method of pest control. There is limited information about the effects of pesticide exposure on parasitized honey bees. Larval ingestion of certain pesticides could have effects on honey bee immune defense mechanisms, development and metabolic pathways. Europe and America face the disturbing phenomenon of the disappearance of honey bee colonies, termed Colony Collapse Disorder (CCD). One reason discussed is the possible suppression of honey bee immune system as a consequence of prolonged exposure to chemicals. In this study, the effects of the neonicotinoid thiamethoxam on honey bee, Apis mellifera carnica, pupae infested with Varroa destructor mites were analyzed at the molecular level. Varroa-infested and non-infested honey bee colonies received protein cakes with or without thiamethoxam. Nurse bees used these cakes as a feed for developing larvae. Samples of white-eyed and brown-eyed pupae were collected. Expression of 17 immune-related genes was analyzed by real-time PCR. Relative gene expression in samples exposed only to Varroa or to thiamethoxam or simultaneously to both Varroa and thiamethoxam was compared. The impact from the consumption of thiamethoxam during the larval stage on honey bee immune related gene expression in Varroa-infested white-eyed pupae was reflected as down-regulation of spaetzle, AMPs abaecin and defensin-1 and up-regulation of lysozyme-2. In brown-eyed pupae up-regulation of PPOact, spaetzle, hopscotch and basket genes was detected. Moreover, we observed a major difference in immune response to Varroa infestation between white-eyed pupae and brown-eyed pupae. The majority of tested immune-related genes were upregulated only in brown-eyed pupae, while in white-eyed pupae they were downregulated.

The extensive production of zinc oxide (ZnO) nanomaterials (NMs) may result in high environmental zinc burdens. Honeybees need to have special concern due to their crucial role in pollination. Our previous study indicated that low concentrations of ZnO NMs, corresponding to 0.8 mg Zn/mL, have a neurotoxic potential for honeybees after a 10-day oral exposure. Present study was designed to investigate the effect of a short, dietary exposure of honeybees to ZnO NMs at concentrations 0.8-8 mg Zn/mL on consumption rate, food preference, and two enzymatic biomarkers-a stress-related glutathione S-transferase (GST) and the neurotoxicity biomarker acetylcholinesterase (AChE). Consumption rate showed a tendency toward a decrease feeding with the increasing concentrations of ZnO NMs. None of Zn NMs concentrations caused alterations in mortality rate and in the activities of brain GST and AChE. To investigate if there is an avoidance response against Zn presence in food, 24-h two-choice tests were performed with control sucrose diet versus sucrose suspensions with different concentrations of ZnO NMs added. We demonstrated that honeybees prefer ZnO NMs ZnO NMs containing suspensions, even at highest Zn concentrations tested, compared with the control diet. This indicates that they might be able to perceive the presence of ZnO NMs in sucrose solution. Because honeybees feed frequently the preference towards ZnO NMs might have a high impact on their survival when exposed to these NMs.

Synaptotagmin 7 (SYT7) is ubiquitously expressed calcium sensor, involved in neuronal membrane trafficking. Immunoprecipitation experiments demonstrated that SYT7 interacts with Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP). SYNCRIP is a component of mRNA granules, which are transported to dendrites and are prerequisite for synaptic plasticity. Given the potential significance of SYT7 regulation in processes of neurodegeneration, which are characterized by high level of synaptic vulnerability, we aimed to analyse and compare the distribution of SYT7 and SYNCRIP proteins in the adult rat striatum, hippocampus, cerebral and cerebellar cortex. We investigated the degree of SYT7-SYNCRIP co-localization in order to examine possible functional interaction of these two proteins. We found that SYT7 is abundantly distributed in neuropil of all examined anatomical areas of the brain, most prominently in axons. On the contrary, SYNCRIP had cytoplasmic somatodendritic pattern of expression, which was most prominent in the hippocampus and cerebellum. In the striatum, hippocampus and cerebral cortex SYT7 and SYNCRIP immunofluorescent signals were mutually excluded, thus diminishing the probability for their physiological interaction. In somata of Purkinje neurons in the cerebellar cortex, both SYT7 and SYNCRIP were expressed and partially co-localized suggesting possible functional connection between SYT7 and SYNCRIP proteins in Purkinje neurons., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A detailed investigation of the recording, as well as the readout of transmission gratings in composites of poly(ethylene glycol) dimethacrylate (PEGDMA) and ionic liquids is presented. Gratings with a period of about 5.8 micrometers were recorded using a two-wave mixing technique with a coherent laser beam of a 355-nm wavelength. A series of samples with grating thicknesses d 0 = 10 … 150 micrometers, each for two different exposure times, was prepared. The recording kinetics, as well as the post-exposure properties of the gratings were monitored by diffracting a low intensity probe beam at a wavelength of 633 nm for Bragg incidence. To obtain a complete characterization, two-beam coupling experiments were conducted to clarify the type and the strength of the recorded gratings. Finally, the diffraction efficiency was measured as a function of the readout angle at different post-exposure times. We found that, depending on the parameters, different grating types (pure phase and/or mixed) are generated, and at elevated thicknesses, strong light-induced scattering develops. The measured angular dependence of the diffraction efficiency can be fitted using a five-wave coupling theory assuming an attenuation of the gratings along the thickness. For grating thicknesses larger than 85 microns, light-induced scattering becomes increasingly important. The latter is an obstacle for recording thicker holograms, as it destroys the recording interference pattern with increasing sample depth. The obtained results are valuable in particular when considering PEGDMA-ionic liquid composites in the synthesis of advanced polymer composites for applications, such as biomaterials, conductive polymers and holographic storage materials.

Synaptotagmin-IV (Syt-IV) may function as a regulator of Ca(2+) -dependent synaptic transmission. In the hemi-parkinsonian rats with unilateral lesions of dopaminergic nigrostriatal neurons Syt-IV and substance-P (SP) mRNAs could be upregulated within the dopaminergically hypersensitive striatum of the lesioned brain hemisphere via the stimulation of striatal dopamine D1 (D1-R), but not D2 receptors. The hypersensitive D1-R-mediated transmission may be the culprit for the undesired expression of levodopa-induced dyskinesia, implying the involvement of Syt-IV and SP in the process. First, striatal cellular phenotypes expressing Syt-IV were determined. It was found to be expressed in all striatal neurons and a small population of astrocytes. Then it was examined, if the D1-R-mediated upregulation of Syt-IV mRNA may result in the upregulation of the translated protein. It was found that, after acute stimulation with a selective D1 agonist, (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-82958), Syt-IV was elevated within the SP-expressing striatal neurons of the lesioned side. This was followed by the upregulation of Syt-IV, but not of its mRNA, within the ipsilateral target nuclei of the direct-pathway medium spiny neurons, indicating axonal transport of de novo synthesized protein to their SP-positive synaptic terminals. However, despite the striatal upregulation of SP and Syt-IV following a similar time-course, their subcellular co-localization within the axonal terminals was not found. It was therefore suggested that Syt-IV may regulate the hypersensitive striatal synaptic transmission, although via a SP-independent mechanism., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The Carniolan honey bee, Apis mellifera carnica, is a Slovenian autochthonous subspecies of honey bee. In recent years, the country has recorded an annual loss of bee colonies through mortality of up to 35%. One possible reason for such high mortality could be the exposure of honey bees to xenobiotic residues that have been found in honey bee and beehive products. Acaricides are applied by beekeepers to control varroosis, while the most abundant common agricultural chemicals found in honey bee and beehive products are fungicides, which may enter the system when applied to nearby flowering crops and fruit plants. Acaricides and fungicides are not intrinsically highly toxic to bees but their action in combination might lead to higher honey bee sensitivity or mortality. In the present study we investigated the molecular immune response of honey bee workers at different developmental stages (prepupa, white-eyed pupa, adult) exposed to the acaricide coumaphos and the fungicide prochloraz individually and in combination. Expression of 17 immune-related genes was examined by quantitative RT-PCR. In treated prepupae downregulation of most immune-related genes was observed in all treatments, while in adults upregulation of most of the genes was recorded. Our study shows for the first time that negative impacts of prochloraz and a combination of coumaphos and prochloraz differ among the different developmental stages of honey bees. The main effect of the xenobiotic combination was found to be upregulation of the antimicrobial peptide genes abaecin and defensin-1 in adult honey bees. Changes in immune-related gene expression could result in depressed immunity of honey bees and their increased susceptibility to various pathogens., (Copyright © 2015 Elsevier Inc. All rights reserved.)

STAM2 (signal transducing adaptor molecule 2), a subunit of the ESCRT-0 complex, is an endosomal protein acting as a regulator of receptor signaling and trafficking. To analyze STAM2 in the nervous system, its gene expression and protein localization in the mouse brain were identified using three methods: mRNA in situ hybridization, immunohistochemistry, and via lacZ reporter in frame with Stam2 gene using the gene trap mouse line Stam2(Gt1Gaj). STAM2 intracellular localization was analyzed by subcellular fractionation and co-immunofluorescence using confocal microscopy. Stam2 was strongly expressed in the cerebral and cerebellar cortex, hippocampal formation, olfactory bulb, and medial habenula. The majority of STAM2-positive cells co-stained with the neuronal markers. In neurons STAM2 was found in the early endosomes and also in the nucleus. The other members of the ESCRT-0 complex co-localized with STAM2 in the cytoplasm, but they were not present in the nucleus. The newly identified neuron-specific nuclear localization of STAM2, together with its high expression in the brain indicated that STAM2 might have a specific function in the mouse nervous system., (Copyright © 2015. Published by Elsevier Inc.)

The honey bee is among most important pollinators threatened by environmental pollution, pest control and potentially, by products of nanotechnologies. The aim of the current study was an analysis of the neurotoxic potential of ingested zinc oxide nanomaterials (ZnO NMs) or zinc ions (Zn(2+)) on honey bees. We analysed a variety of biomarkers, including metabolic impairment, feeding rate, and survival, as well as the activities of a stress-related enzyme glutathione S-transferase, and the neurotoxicity biomarker acetylcholinesterase. Acetylcholinesterase activity was found to be elevated in bees exposed to either of the tested substances. In addition, we observed increased feeding rate in the group treated with Zn(2+) but not with ZnO NMs or control group. The observed effects we relate primarily to Zn(2+) ions. Here we provide evidence that zinc ions either originating from Zn salt or Zn-based NPs have a neurotoxic potential and thus might contribute to colony survival., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To investigate the involvement of the vesicular membrane trafficking regulator Synaptotagmin IV (Syt IV) in Alzheimer's disease pathogenesis and to define the cell types containing increased levels of Syt IV in the β-amyloid plaque vicinity., Methods: Syt IV protein levels in wild type (WT) and Tg2576 mice cortex were determined by Western blot analysis and immunohistochemistry. Co-localization studies using double immunofluorescence staining for Syt IV and markers for astrocytes (glial fibrillary acidic protein), microglia (major histocompatibility complex class II), neurons (neuronal specific nuclear protein), and neurites (neurofilaments) were performed in WT and Tg2576 mouse cerebral cortex., Results: Western blot analysis showed higher Syt IV levels in Tg2576 mice cortex than in WT cortex. Syt IV was found only in neurons. In plaque vicinity, Syt IV was up-regulated in dystrophic neurons. The Syt IV signal was not up-regulated in the neurons of Tg2576 mice cortex without plaques (resembling the pre-symptomatic conditions)., Conclusions: Syt IV up-regulation within dystrophic neurons probably reflects disrupted vesicular transport or/and impaired protein degradation occurring in Alzheimer's disease and is probably a consequence but not the cause of neuronal degeneration. Hence, Syt IV up-regulation and/or its accumulation in dystrophic neurons may have adverse effects on the survival of the affected neuron.

γ-Enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C-terminal end of the molecule. We have investigated the expression and colocalization of γ-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of γ-enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C-terminally cleaved form of γ-enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of γ-enolase in microglial cells in response to amyloid-β peptide (Aβ) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with γ-enolase proved to be neuroprotective against Aβ toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of γ-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-β-related neurodegeneration., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)

MicroRNAs (miRNAs) form a large class of non-coding RNAs that function in repression of gene expression in eukaryotes. By recognizing short stretches of nucleotides within the untranslated regions of mRNAs, miRNAs recruit partner proteins to individual transcripts, leading to mRNA cleavage or hindering of translation. Bioinformatic predictions and a wealth of data from wet laboratory studies indicate that miRNAs control expression of a large proportion of protein-coding genes, implying involvement of miRNAs in regulation of most biologic processes. In this review we discuss the biology of miRNAs and present examples of how manipulation of miRNA expression or activity can be exploited to attain the desired phenotypic traits in cell engineering as well as achieve therapeutic outcomes in treatment of a diverse set of diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Previous studies in rat models of neurodegenerative disorders have shown disregulation of striatal synaptotagmin7 mRNA. Here we explored the expression of synaptotagmin7 mRNA in the brains of rats with seizures triggered by the glutamatergic agonist kainate (10 mg/kg) or by the muscarinic agonist pilocarpine (30 mg/kg) in LiCl (3 mEq/kg) pre-treated (24 h) rats, in a time-course experiment (30 min-1 day). After kainate-induced seizures, synaptotagmin7 mRNA levels were transiently and uniformly increased throughout the dorsal and ventral striatum (accumbens) at 8 and 12 h, but not at 24 h, followed at 24 h by somewhat variable upregulation within different parts of the cerebral cortex, amigdala and thalamic nuclei, the hippocampus and the lateral septum. By contrast, after LiCl/pilocarpine-induced seizures, there was a more prolonged increase of striatal Synaptotagmin7 mRNA levels (at 8, 12 and 24 h), but only in the ventromedial striatum, while in some other of the aforementioned brain regions there was a decline to below the basal levels. After systemic post-treatment with muscarinic antagonist scopolamine in a dose of 2 mg/kg the seizures were either extinguished or attenuated. In scopolamine post-treated animals with extinguished seizures the striatal synaptotagmin7 mRNA levels (at 12 h after the onset of seizures) were not different from the levels in control animals without seizures, while in rats with attenuated seizures, the upregulation closely resembled kainate seizures-like pattern of striatal upregulation. In the dose of 1 mg/kg, scopolamine did not significantly affect the progression of pilocarpine-induced seizures or pilocarpine seizures-like pattern of striatal upregulation of synaptotagmin7 mRNA. In control experiments, equivalent doses of scopolamine per se did not affect the expression of synaptotagmin7 mRNA. We conclude that here described differential time course and pattern of synaptotagmin7 mRNA expression imply regional differences of pathophysiological brain activation and plasticity in these two models of seizures.

Synaptotagmins (Syts) are transmembrane proteins involved in the regulation of membrane trafficking. Here, we summarize literature data that provide growing evidence that several Syts are involved in the pathophysiological mechanisms of temporal lobe epilepsy and Parkinson's disease, as well as few reports related to brain ischemia and Alzheimer's disease (AD). We also report new data from our laboratories, showing changes of the expression of several Syts in Tg2576 mouse model of AD that may be related to neuroinflammation surrounding the beta-amyloid plaques. Furthermore, we demonstrate N-methyl-D-aspartate receptor-mediated upregulation of Syt 4 mRNA in a model of excitotoxic striatal lesion induced by unilateral striatal injection of quinolinic acid, associating the upregulation of Syt 4 with mechanisms of excitotoxicity. We propose that pharmacological manipulation of Syt expression in animal models of neurodegeneration should be further explored, as it may help to clarify the role of individual Syt isoforms in the regulation of membrane trafficking in neurodegeneration., ((c) 2009 Wiley-Liss, Inc.)

Long-term use of L-DOPA in Parkinson's disease (PD) is frequently associated with side effects that are reflected in changed neurotransmitter/neuropeptide secretion in basal ganglia. These side effects could be connected with synaptotagmins (syts) because syts are involved in regulation of membrane trafficking. We have previously reported that acute L-DOPA treatment upregulated the expression of Syt 4 and Syt 7 mRNAs in hypersensitive striatum of 6-OHDA rat model for PD. Here we investigate whether intermittent L-DOPA treatment that produces behavior sensitization affects the Syt 1, Syt 2, Syt 4, Syt 7 and Syt 10 mRNAs in striatum of 6-OHDA rats killed 4 and 12 h after the last L-DOPA injection. We verified behavioral sensitization by increased intensity of contralateral turning. 6-OHDA lesion caused Syt 2 mRNA downregulation and Syt 10 mRNA upregulation in striatum, but failed to alter Syt 4, Syt 7 and Syt 1 mRNAs. Acute l-DOPA induced an increase of Syt 4 and Syt 7 mRNAs in the denervated striatum leaving the levels of Syt 1, Syt 2 and Syt 10 mRNAs unaffected. Intermittent L-DOPA treatment did not alter Syt 1, Syt 2 and Syt 10 mRNA striatal levels, suggesting that 6-OHDA-induced Syt 2 and Syt 10 mRNA changes reflect a persistent striatal abnormality caused by dopamine depletion. On contrary, intermittent L-DOPA treatment downregulated Syt 4 mRNA and prolonged the elevation of Syt 7 mRNA in the denervated striatum. We conclude that Syt 4 and Syt 7 might be specifically involved in striatal plasticity caused by repeated L-DOPA administration that accompanies sensitization.

Synaptotagmin 7 (Syt 7) is a Ca2+ sensor implicated in the regulation of membrane fusion in vesicular transport, but its precise role in neurons is still a matter of controversy. Dopaminergic drugs have been shown to modulate its expression in the striatum. Here we investigate whether dopamine receptor agonist-up-regulation of Syt 7 mRNA is specifically involved in the pathophysiological adaptations of hypersensitive striatum by analyzing other dopaminergic neurons containing brain regions. We treated rats with systemic reserpine injections that rapidly depletes dopamine throughout the brain, but leaves dopaminergic neurons spared from destruction. We analyzed the effects of apomorphine, a D1 and D2 receptor agonist on Syt 7 mRNA expression in caudate putamen, nucleus accumbens, cingulate cortex, substantia nigra compacta, ventral tegmental area and hippocampus. The treatment with reserpine resulted in akinesia, catalepsy and rigidity and up-regulation of proenkephalin and down-regulation of preprotachykinin mRNA in caudate putamen, indicating a severe depletion. By acute treatment with apomorphine proenkephalin mRNA was down-regulated and preprotachykinin mRNA up-regulated in the caudate putamen of reserpinized rats. Apomorphine increased Syt 7 mRNA levels only in striatum (caudate putamen and nucleus accumbens) of reserpinized rats, while in other brain regions it did not have such effect. The reserpinization and/or apomorphine treatment had no effect on Syt 1 mRNA expression in caudate putamen. It may be concluded, that in the striatum depleted of biogene amines, such as occurs after reserpine treatment, the up-regulation of Syt 7 could play a specific role as part of hypersensitive response to dopaminergic agonists.

Synaptotagmin IV is a product of immediate early-response gene. It is involved in the regulated neurosecretion in the brain. Its putative role, however, in vesicular transport and localization in secretor y vesicles is still a matter of debate. Here we followed the spatiotemporal pattern of synaptotagmin IV protein upregulation in the hippocampus, caudate putamen, nucleus accumbens, nucleus amygdalae, piriform and entorhinal cortices of rats with kainate-induced seizures. We found that upregulation pattern paralleled the direction of depolarization through the hippocampus and also reflecting seizure activity spreading to other brain regions. We speculate that synaptotagmin IV may have a role in the vesicular transport of the upregulated peptides and proteins involved in the plasticity and/or neurodegeneration provoked by the kainate.

Parkinsonism, a common unwanted side effect of typical antipsychotic (neuroleptic) drugs, is induced by the blockade of striatal dopamine D2 receptors. In rats with hemi-parkinsonism induced by unilateral lesion of dopaminergic nigrostriatal neurons with 6-hydroxydopamine, D2 antagonists inhibit contralateral turning induced by D2 agonists and augment the levels of neurotensin mRNA in dopaminergically intact striatum. By contrast, D1 agonists induce contralateral turning and augment neurotensin mRNA levels in dopamine-depleted striatum. These effects could be inhibited by D1 but not by D2 antagonists. Here we used a hemi-parkinsonian model to investigate the effects of putative D1 agonist/D2 antagonist LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate), an experimental antipsychotic, on turning behavior and the expression of striatal neurotensin, preprotachykinin and neurotransmitter-induced early gene protein 4 (ania-4) mRNAs. We found that LEK-8829 inhibited contralateral turning induced by D2 agonist quinpirole, but only if the rats were cotreated with D1 antagonist SCH-23390. In situ hybridization showed that LEK-8829 induced the expression of neurotensin and ania-4 mRNAs in dopamine-intact striatum that could be completely blocked only by the combined treatment with SCH-23390 and quinpirole. In addition, LEK-8829 augmented the expression of neurotensin, preprotachykinin and ania-4 mRNAs in dopamine-depleted striatum that could be completely blocked by SCH-23390. This study clearly demonstrates that in hemi-parkinsonian rats D1 agonistic activity of LEK-8829 confers its anti-parkinsonian drug-like properties and modulates its neuroleptic drug-like properties, which are dependent on the blockade of dopamine D2 receptors. These findings imply that atypical antipsychotics with D1 intrinsic activity might have a reduced propensity for the induction of extrapyramidal syndrome.

Synaptotagmins (Syts) I and IV are synaptic proteins involved in the regulation of neurosecretion. Dopaminergic drugs have been shown to modulate their expression. Here we investigate whether dopaminergic regulation of syt I and syt IV expression could play a role in the hypersensitive striatum of rats with unilateral lesions of dopaminergic nigrostriatal neurons with 6-hydroxydopamine. We show that chronic dopaminergic denervation resulted in a small down-regulation of striatal syt I mRNA, whereas acute treatment with SKF-82958, a dopamine D1 receptor agonist, induced a massive syt IV mRNA upregulation in the striatum on the lesioned side. We conclude that chronic lack of dopamine and treatment with dopamine D1 receptor agonists alter the synaptic plasticity in dopamine depleted basal ganglia.