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Psoriasis is one of the most prevalent and chronic inflammatory disease of the skin, associated with disrupted barrier function. Currently, a widely accepted, generally usable cell culture model has not been developed yet. In the present work, we aimed to establish a co-culture model with human keratinocyte (HaCaT) and human monocyte cells (THP-1) induced by Imiquimod (IMQ), which acts on the TLR7 receptor. The role of TLR7 expressed on THP-1 cells was confirmed by immunofluorescence staining of NF-κB activation. Chloroquine (CH) was used as a receptor inhibitor, in the presence or absence of which the NF-κB pathway was activated. We determined the most effective proliferation-stimulating IMQ concentration by RTCA method and the hyperproliferative effect was investigated by wound-healing test. The effect of IMQ was compared with the effects of the anthocyanin (AC) components from the anti-inflammatory sour cherry extract that we have already studied. We found that IMQ significantly increased the migration rate however, the combined treatment resulted in a decreased migration rate compared to the IMQ treatment alone. Inflammatory cytokines were measured from the supernatant of co-culture by ELISA. During the development of the co-culture intended to model psoriasis, we confirmed the induction effect of IMQ and in the case of AC treatment, we supported the stabilizing effect of the barrier., Competing Interests: Declaration of competing interest We wish to confirm that there is no conflict of interest associated with this publication., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

If severe cervical spinal cord injury or severe cervical vertebral fracture, subluxation or luxation is confirmed, 20-40% of the cases have vertebral artery dissection or occlusion. These can be asymptomatic, but can cause additional neurological damage in addition to cervical myelon and cervical nerve root symptoms. Vertebral artery dissection can be caused by direct injuries, stab wounds or gunshot wounds. Indirect vertebral artery dissection can occur at the same time as subluxation, luxation, or complex fractures of the cervical vertebra. CTA is the examination procedure of choice. In many cases, digital subtaction angiography examination and, if necessary, neurointerventional treatment must precede open neurosurgery. In our report, in the first patient, complete luxation of the C.VI vertebra caused unilateral vertebral artery 2-segment dissection-occlusion, while in our second patient, a stab injury caused direct vertebral artery compression and dissection. The occlusion of the vertebral artery did not cause neurological symptoms in any of the cases. In both of our cases, parent vessel occlusion was performed at the level of the vertebral artery injury before the neurosurgical operation.

Background: Since the publication of the major research on adverse childhood experiences (ACE) at the turn of the millennium, our knowledge about the prevalence and physical and mental consequences of childhood adversities has increased substantially. In parallel, research on metacognition, which plays an important role in understanding our mental functioning, has also been on the rise. Although the adverse effects of ACEs on mental processes and the role of metacognitive deficits in the development of mental disorders are widely known, hardly any research into the interaction between these two areas has been conducted; this is what triggered our investigation., Methods: Our research was carried out as a cross-sectional study on a sample of 304 members of the general population. We measured ACEs with the 10-item Adverse Childhood Experiences Questionnaire and maladaptive metacognitions-positive and negative metacognitive beliefs, cognitive confidence, cognitive self-consciousness, and need to control thoughts- using the Meta-Cognitions Questionnaire. The closeness of the relationship between the ACE score and metacognitions was measured using Pearson's linear correlation coefficient, while the association of ACE accumulation with metacognitive beliefs was assessed using generalized linear models., Results: The most common ACE in our sample turned out to be emotional neglect (44.74%). All the examined maladaptive metacognitive beliefs correlate mildly to moderately with the number of suffered ACEs (r = 0.13-0.34), with an increase in the ACE score leading to a rise in the salience of maladaptive metacognitive beliefs. Moreover, a dose-response relationship was seen between increases in ACE scores and the overall values of metacognition, negative metacognitive beliefs, and the maladaptive metacognitive belief of the need to control thoughts., Conclusions: Our results suggest that the more ACEs were experienced in childhood, the more pronounced the dysfunctional metacognitive beliefs are. Therefore, our findings emphasize the importance of further research into the topic., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic subdural hematoma is one of the most common diseases requiring a neurosurgical operation that affect elderly and fragile patients. In addition to standard neurosurgical operations (trepanation and craniotomy), embolization of the meningeal artery media is an alternative solution. Several review aerticles have confirmed the very high rate of success and safety of the endovascular treatment. We present the technical details and results of our 10 consecutive selective media meningeal artery embolization procedures for residual chronic subdural hematomas. Our interventions were performed without complications and all resulted in complete recovery.

The treatment of acute epidural haematoma is surgery as soon as possible, elimination of the source of bleeding and evacuation of the haematoma. In case of small epidural haematoma, strict neurological and radiological follow-up is necessary. In a significant percentage of cases, open surgery must also be performed within a few days. In case of small epidural haematomas, embolization of the middle meningeal artery is considered as an alternative solution. We review the literature on middle meningeal artery embolization and present our first treatment. Our case report is the first European report about an acute epidural haematoma which was treated by embolization of middle meningeal artery. Our case study is the first report in which a patient was treated with both open surgery and endovascular treatment for acute epidural haematoma within a year.

Introduction: Academic motivation (AM), motivation in relation to formal studies that as a construct of the self-determination theory (SDT), is frequently assessed by the Academic Motivation Scale (AMS). However, the scoring of AMS in itself is not fully consistent with the SDT theory as only scores of the subscales can be calculated resulting in seven different score means instead of positioning the individual on the self-determination continuum. There have been few attempts at a person-centered approach to AMS scoring, especially among medical students. Our study aimed to find distinct academic motivation profiles and demonstrate their concurrent criterion validity with mental health variables (psychological distress, life satisfaction) among medical students., Methods: The AMS-28 college version, the General Health Questionnaire (GHQ-12), and the Single-Item Measure of Life Satisfaction were administered among medical freshmen. Academic motivation profiles were generated by two methods: 1) two-step cluster analysis, and 2) quantile analysis., Results: The sample consisted of 189 participants (mean age = 19.38 ± 2.03 years, 72% females). The cluster analyses revealed three fairly distinct profiles of self-determination: 'High' ( n  = 59; mean im = 5.48 ± 0.60; mean em = 6.07 ± 0.41; mean am = 1.57 ± 0.95), 'Moderate' ( n  = 111; mean im = 4.5 ± 1.06; mean em = 4.41 ± 0.87; mean am = 1.25 ± 0.36), and 'Low' ( n  = 19; mean im = 4.22 ± 1.02; mean em = 4.03 ± 1.16; mean am = 3.07 ± 1.30). The creation of deciles allowed the identification of those who were most intrinsically ( n  = 14, 7.4%), extrinsically ( n  = 10, 5.3%), and least motivated (amotivated) ( n  = 18, 9.5%). 'Low' self-determination/amotivation was associated with increased psychological distress and decreased life satisfaction., Conclusion: Our results provide means to position medical students on the SDT continuum based on 'Low', 'Moderate', or 'High' levels of self-determination toward their studies. These AM profiles predict the mental health of medical freshmen, which supports the validity of the outcomes and highlight the risks of amotivation for psychological morbidity. The limitations and implications are discussed.

Introduction: Multiple evidence suggests that the vast majority of children in the Child Welfare System (CWS) are victims of early, chronic, and multiple adverse childhood experiences. However, the 10-item version of the Adverse Childhood Experiences Questionnaire (ACE-10) has never been tested in such a particularly vulnerable population as adolescents living in the CWS. We aimed to assess the psychometric properties of the ACE-10 in a community sample of 240 Hungarian adolescents placed in family style group care (FGC) setting., Methods: Demographic data, the 10-item version of the Adverse Childhood Experiences Questionnaire (ACE-10), the Strengths and Difficulties Questionnaire (SDQ), and the HBSC Bullying Measure were used., Results: Our results showed acceptable internal consistency (α = 0.701) and item-total correlations ( r pb  = 0.25-0.65, p  < 0.001). However, our results also reflect that item 6 ("Parental separation/divorce") is weakly correlated with both the cumulative ACE score and the rest of the questionnaire items. When item 6 is removed, the 9-item version of the ACE produces more favorable consistency results (α = 0.729). Strong and significant associations of the cumulative ACE score with emotional and behavioral symptoms and bully victimization confirm the concurrent criterion validity of both versions of the instrument., Discussion: Our findings suggest that ACE-9 and ACE-10 are viable screening tools for adverse childhood experiences in the CWS contributing to the advancement of trauma-informed care. We recommend considering the use of either the 9-item or the 10- item version in the light of the characteristics of the surveyed population. The implications and limitations are discussed., 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 © 2023 Oláh, Fekete, Kuritárné Szabó and Kovács-Tóth.)

Several types of gluten-related disorders are known, in which the common starting point is gluten-induced zonulin release. Zonulin results in varying degrees of increased permeability in certain gluten-related disorders but is largely responsible for the development of further pathogenic processes and symptoms. Therefore, it is important to know the barrier-modulating role of individual nutritional components and to what extent the antioxidant substance supports the protection of gliadin-induced membrane damage with its radical scavenging capacity. We investigated the pH dependence of the gliadin-anthocyanin interaction using UV photometry, during which a concentration-dependent interaction was observed at pH 6.8. The barrier modulatory effect of the anthocyanin-rich sour cherry extract (AC) was analyzed on Caco-2 cell culture with pepsin-trypsin-resistant gliadin (PT-gliadin) exposure by TEER measurement, zonula occludens-1 (ZO-1), and Occludin immunohistochemistry. In addition to the TEER-reducing and TJ-rearranging effects of PT-gliadin, NF-κB activation, an increase in cytokine (TNF-α, IFN-γ, and IL-8) release, and mitochondrial ROS levels were observed. We confirmed the anti-inflammatory, stabilizing, and restoring roles of AC extract during gliadin treatment on the Caco-2 monolayer. The extract was able to significantly reduce cytokine and ROS levels despite the known interaction of the main components of the extract with PT-gliadin.

Background: Roma are the largest and most disadvantaged minority in Europe, but there is few research on how mental health and social support of Roma people living in segregated settlements compares to the majority population. Our aim was to compare the subjective well-being, life satisfaction, mental status, and social support of representative samples of adults living in segregated settlements (colonies) and identifying as Roma with those of the general population in Hungary., Methods: A cross-sectional study was conducted with random samples of 417 individuals from the general Hungarian adult population (55.6% female, mean age = 43.89 ± 12.61 years) and 394 adults living in segregated settlements (colonies) (73.9% female, mean age = 42.37 ± 12.39 years). Demographic questions were used as well as the WHO Well-Being Index (WBI-5), the single item Life Satisfaction Scale, the 12-item version of the General Health Questionnaire (GHQ-12), and the Oslo Social Support Scale (OSSS-3)., Results: Residents of colonies reported significantly lower levels of subjective well-being and life satisfaction than the general population. The proportion of individuals at high risk for mental morbidity was more than twice as high among colony dwellers (16.4%) as in non-colony dwellers (7.6%). Similar unfavorable differences were seen at the expense of self-identified Roma compared to self-identified Hungarians but no difference was found in terms of social support either by type of residence or ethnicity. 32.2% of colony-dwellers self-identified themselves as Hungarian. Mental health assessed by principal component was directly determined by settlement type of permanent residence, age, educational attainment, employment, financial status, and social support but not ethnic identity., Conclusion: The study based on representative data shows that residents of segregated settlements are in worse mental health than those not living in colonies; that housing segregation is not limited to Roma people, and that housing conditions and financial status are major social determinants of mental health for which data must be collected to avoid using self-reported Roma identity as a proxy measure of socioeconomic deprivation., 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 © 2023 Oláh, Bíró and Kósa.)

Excessive use of azole fungicides in agriculture poses a potential threat to honeybees and other pollinator insects; however, the detailed effects of these molecules remain largely unclear. Hence, in the present study it was aimed to investigate the acute sublethal effects of tebuconazole on the redox homeostasis and fatty acid composition in the brain of honeybees. Our findings demonstrate that tebuconazole decreased total antioxidant capacity, the ratio of reduced to oxidized glutathione and disturbed the function of key antioxidant defense enzymes along with the induction of lipid peroxidation indicated by increased malondialdehyde levels, while it also altered the fatty acid profile of the brain. The present study highlights the negative impact of tebuconazole on honeybees and contributes to the understanding of potential consequences related to azole exposure on pollinator insects' health, such as the occurrence of colony collapse disorder., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Although a number of studies have been conducted since the 1995 initiation of the ACE study to map the effects of adverse childhood experiences, few studies have examined the psychometric properties of the individual versions of the ACE questionnaire., Aims: The Adverse Childhood Experiences Questionnaire 10 item version (ACE-10) has only been tested in a single study in an adult population, while its applicability in a particularly vulnerable population, the adolescents, has not been investigated yet. Our present study aims to address this gap in an adolescent sample of 792 subjects from a non-representative general population., Methods: Besides demographic data, the Adverse Childhood Experiences Questionnaire 10 item version (ACE-10), the Strengths and Difficulties Questionnaire (SDQ), and the HBSC Symptom Checklist (HBSC-SCL) were employed., Results: Our results showed acceptable internal consistency (ɵ = 0.86, α = 0.64) and adequate internal validity (r = 0.28-0.70, p < 0.001). In addition, proper concurrent criterion validity of the questionnaire was found when tested along the SDQ and HBSC-SCL items., Conclusion: Our results demonstrate that the ACE-10 is suitable for assessing intrafamilial adverse childhood experiences in adolescents., 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 © 2023 Kovács-Tóth, Oláh, Kuritárné Szabó and Fekete.)

Purpose: Traumatic events often feature prominently in eating disorders. A questionnaire survey to assess the relation of eating disorder risk to the frequency of adverse childhood experiences (ACEs) and the possible association of eating disorder risk with a particular type of ACE was conducted in a community sample of Hungarian adolescents., Methods: Demographic and anthropometric data, risk for eating disorders (by SCOFF questionnaire), and ACEs (by ACE score calculator) were collected from 432 adolescents aged 12-17 years., Results: Adolescents who had undergone four or more ACEs were 5.7 times more likely to be in the high eating disorder risk group than those who did not report any ACEs. Cumulative maltreatment showed a greater association with overall risk for eating disorders than cumulative family dysfunction. There is an increased risk of eating disorders from emotional maltreatment ( OR  = 3.475), physical maltreatment ( OR  = 3.440), sexual maltreatment ( OR  = 10.973), and emotional neglect ( OR  = 3.331). Dysfunctional family circumstances revealed an association with household mental illness ( OR  = 3.401)., Conclusion: Our study of the connection between eating disorder risk and ACE is the first of its kind in Central and Eastern Europe. Maltreatments had a greater role than family dysfunctions in increasing the risk of eating disorders. Our findings contribute to a more precise understanding of the role that ACEs play in eating disorders. It is important to bring to clinicians' attention the importance of ACEs in the diagnosis and therapy of eating disorders and their potentially fundamental significance for therapy., 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 Kovács-Tóth, Oláh, Kuritárné Szabó and Túry.)

The high risk of mental health problems among medical students has been compounded by the COVID-19 pandemic, which greatly reduced social contact. The mental health support service of the medical school of one Hungarian university was transferred to the online learning management system and was expanded by self-help materials in three domains: Improving study skills, stress management techniques, and reducing stress related to the COVID-19 pandemic. We wanted to understand the preferences of medical students for psychological self-help techniques by investigating the pattern of access to online self-help materials and the characteristics of the users. Access to the online materials between April 2020 and April 2021 among Hungarian and international medical students was analyzed using the logging data of the system. Of all the students who logged in during the examination period ( n = 458), 36.6-40.4% viewed materials to improve study skills and 23-29% viewed stress management materials, of which short-duration audio format techniques were preferred. The access rate of content targeting coping with the mental health effects of COVID-19 was 9.5-24%. Support to improve study skills is significantly more preferred than interventions targeting distress-reduction. The pattern of access can be used for the development of interventions that are of most interest to medical students.

Arabidopsis NODULIN HOMEOBOX (NDX) is a nuclear protein described as a regulator of specific euchromatic genes within transcriptionally active chromosome arms. Here we show that NDX is primarily a heterochromatin regulator that functions in pericentromeric regions to control siRNA production and non-CG methylation. Most NDX binding sites coincide with pericentromeric het-siRNA loci that mediate transposon silencing, and are antagonistic with R-loop structures that are prevalent in euchromatic chromosomal arms. Inactivation of NDX leads to differential siRNA accumulation and DNA methylation, of which CHH/CHG hypomethylation colocalizes with NDX binding sites. Hi-C analysis shows significant chromatin structural changes in the ndx mutant, with decreased intrachromosomal interactions at pericentromeres where NDX is enriched in wild-type plants, and increased interchromosomal contacts between KNOT-forming regions, similar to those observed in DNA methylation mutants. We conclude that NDX is a key regulator of heterochromatin that is functionally coupled to het-siRNA loci and non-CG DNA methylation pathways., (© 2022. The Author(s).)

Over the past decades, a number of complementary treatments for schizophrenia have emerged. One of these is metacognitive training (MCT), which combines the principles of cognitive-behavioral therapies, cognitive remediation, and psychoeducation into a hybrid approach placing emphasis on increasing metacognitive awareness. The aim of our study was to investigate the efficacy of MCT on symptom severity, and neurocognitive and social cognitive functioning in schizophrenia; also, attention was paid to the assessment of subjective acceptability. Forty-six patients diagnosed with schizophrenia were included in our single-blind randomized controlled trial, who were assigned to the intervention or control group. The intervention group was provided standard MCT, while the control group received treatment as usual. We assessed symptom severity and cognitive functions before and after the training, as well as after a 6-month follow-up period. Compared to the control group, the intervention group showed improvement in overall symptom severity, and positive and disorganized symptoms. Training participans showed further improvement at the follow-up assessment. Regarding neurocognitive functions, improvement in visuospatial functions was observed between pre- and post-intervention assessments compared to the control group. Patients showed excellent adherence, and evaluated the training as useful and interesting. In line with the results of previous studies, our results demonstrate the efficacy of MCT on symptom severity in schizophrenia. Improvements in cognitive functions that are closely related to the onset and prevalence of symptoms of schizophrenia were also found., (© 2022 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Medical students are at increased risk for psychological morbidity but the majority of those with mental health problems do not seek professional care. We aimed to uncover the viewpoints of medical students regarding barriers and facilitators to using university mental health services and their attitudes and preferences towards online counselling. Four semi-structured focus groups were conducted ( n = 26, mean age = 21.8, ±1.88, 73% males). After reaching data saturation, interviews were audio-recorded, transcribed and content-analysed by two independent coders. Intrapersonal barriers emerged to be perceived low risk, excessive self-reliance, lack of belief in the effectiveness of service, lack of openness. Interpersonal factors were the following: assumed long waiting list, insufficient provision of service information, fear of exposure, and not being familiar with the counsellor and the process. Extrapersonal barriers such as insurance problems, the number of available sessions, adverse sociocultural attitudes, fear of stigmatisation were identified. Students suggested that the university should provide psychoeducation and routine screening, apply social marketing and stigma reduction campaigns, improve information flow, and offer not only personal but also online video counselling to target removing these barriers. The results provide a reference for the redesign of mental health services to facilitate their access by students. Implications and limitations are discussed.

Studies show that a significant proportion of children in the Child Welfare System (CWS) have suffered adverse childhood experiences (ACEs), which have led to well documented serious consequences. This study assessed and compared the ACE status of adolescents aged 12 to 17 placed in a family style group care (FGC) setting ( n = 240) to the ACE status of adolescents living with their biological parents ( n = 516). The ACE Score Calculator was employed. The populational differences in ACE scores and in the prevalence of ACEs were assessed using generalized linear and logistic regression models. Adolescents living in FGC settings reported more than five times as many multiple adverse experiences (≥4 types of ACEs) as those living with their biological parents. Adolescents living in FGC settings seem to be more willing to report family dysfunction rather than their maltreatment history and are less willing to report maltreatment. In the FGC group, a surprisingly high proportion of adolescents reported having experienced no maltreatment, which is probably highly underreported and/or unrecognised in the CWS. In fact, a high ACE score will not identify the children who have experienced direct maltreatment but will highlight the consequences of the unfavourable factors inherent in disadvantaged social situation instead.

Background: Adverse Childhood Experiences (ACEs) can have lifelong adverse impacts; they can play a role in the development of subsequent emotional, cognitive, and social impairments leading to somatic and mental difficulties, as well as health damaging behaviours. Unfortunately, there are currently no research data available in Hungary regarding the frequency of ACEs among adolescents., Aims: A cross sectional questionnaire survey was conducted in a community sample of Hungarian adolescents to assess the frequency of ACEs and analyse their association with current social, emotional, and behavioural symptoms (SEB), and subjective health complaints (SHC)., Methods: Demographic data, ACEs, SEB and SHC status of 516 adolescents aged 12 to 17 were collected. ACEs were assessed using the ACE Score Calculator; for SEB the Strengths and Difficulties Questionnaire, and for SHC some specific items from the Health Behaviour of School Children questionnaire were employed. To analyse the relationship of ACEs to SEB and SHC logistic regression was performed., Results: Our results showed that the frequency of ACEs, SEB and SHC is high among adolescents. One-fourth of the students reported ≥ 2 categories of childhood exposures, and 7.4% reported having experienced ≥ 4 types of ACEs. The most prevalent forms of child maltreatment were emotional neglect (15.5%) and emotional abuse (14.5%). The most frequent dysfunctional household condition was parental divorce or separation (23.8%), followed by household substance abuse (8.9%) and household mental illness (8.1%). Almost one-fifth of students (17.5%) reported SEB symptoms (peer relationship problems in 21.7%, emotional symptoms in 14.6%, conduct problems in 18.3%, hyperactivity in 15%). The prevalence of SHC was also high: more than half of the students experienced at least one subjective health complaint multiple times a week. Significant associations were found between ACEs and the SEB/SHC reported by students., Conclusions: Adverse childhood experiences, social, emotional, and behavioural symptoms, and SHC are common among Hungarian adolescents. The cumulation of ACEs is associated with a higher number of SEB and SHC symptoms. Therefore, prevention programmes, early recognition, risk reduction, and therapy are needed.

Introduction: the purpose of our study was to investigate the link between specific traits that determine muscle dysmorphia in bodybuilders and the parental behaviours which play a role in developing these schemata, as well as the eating-disorder-specific traits which differentiate bodybuilders from the normal population., Aim: conceptualising the similarities of personality traits in case of muscle dysmorphia and eating disorders, as well as their etiology based on the schema theory., Method: to measure muscle dysmorphia was used the Muscle Appearance Satisfaction Scale. We explored its connec - tion with eating disorders applying the Eating Disorder Inventory and thereof with the parental behaviours was used the Young Parental Inventory., Results: a number of eating-disorder-specific traits differentiate persons with muscle dysmorphic traits from the normal population. These are Drive for thinness, Body dissatisfaction, Feeling of inadequacy, Interoceptive awareness and Perfectionism. Regarding the perceived parental behaviour the father violated the child's need of autonomy, compe - tence and self-identity and the mother violated the need of boundaries and self-control., Conclusions: Based on several personality characteristics, muscle dysmorphia may be related to anorexia nervosa and bulimia nervosa. In its etiology parental care can have a role, as the father is disposed to detain the autonomy, and the expression of personal needs, while the mother demonstrates insufficient control functions, and the detention of the autonomy and the need for competency.

Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Spp1 is the H3K4me3 reader subunit of the Set1 complex (COMPASS/Set1C) that contributes to the mechanism by which meiotic DNA break sites are mechanistically selected. We previously proposed a model in which Spp1 interacts with H3K4me3 and the chromosome axis protein Mer2 that leads to DSB formation. Here we show that spatial interactions of Spp1 and Mer2 occur independently of Set1C. Spp1 exhibits dynamic chromatin binding features during meiosis, with many de novo appearing and disappearing binding sites. Spp1 chromatin binding dynamics depends on its PHD finger and Mer2-interacting domain and on modifiable histone residues (H3R2/K4). Remarkably, association of Spp1 with Mer2 axial sites reduces the effective turnover rate and diffusion coefficient of Spp1 upon chromatin binding, compared with other Set1C subunits. Our results indicate that "chromosomal turnover rate" is a major molecular determinant of Spp1 function in the framework of meiotic chromatin structure that prepares recombination initiation sites for break formation., (© 2018 Karányi et al.)

Lysine 27 to methionine (K27 M) mutation of the histone variant H3.3 drives the formation of an aggressive glioblastoma multiforme tumor in infants. Here we analyzed how the methionine substitution alters the stability of H3.3 nucleosomes in vitro and modifies its kinetic properties in live cells. We also determined whether the presence of mutant nucleosomes perturbed the mobility of the PRC2 subunit Ezh2 (enhancer-of-zeste homolog 2). We found that K27 M nucleosomes maintained the wild-type molecular architecture both at the level of bulk histones and single nucleosomes and followed similar diffusion kinetics to wild-type histones in live cells. Nevertheless, we observed a remarkable differential recovery of Ezh2 in response to transcriptional stress that was accompanied by a faster diffusion rate of the mobile fraction of Ezh2 and a significantly increased immobile fraction, suggesting tighter chromatin binding of Ezh2 upon transcription inhibition. The differential recovery of Ezh2 was dependent on transcription, however, it was independent from K27 M mutation status. These biophysical characteristics shed more light on the mechanism of histone H3.3 K27M in glioma genesis in relation to the kinetic properties of Ezh2., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Methods to estimate density of soil-dwelling arthropods efficiently, accurately and continuously are critical for investigating soil biological activity and evaluating soil management practices. Soil-dwelling arthropods are currently monitored manually. This method is invasive, and time- and labor-consuming. Here we describe an infrared opto-electronic sensor for detection of soil microarthropods in the size range of 0.4-10 mm. The sensor is built in a novel microarthropod trap designed for field conditions. It allows automated, on-line, in situ detection and body length estimation of soil microarthropods. In the opto-electronic sensor the light source is an infrared LED. Two plano-convex optical lenses are placed along the virtual optical axis. One lens on the receiver side is placed between the observation space at 0.5-1 times its focal length from the sensor, and another emitter side lens is placed between the observation space and the light source in the same way. This paper describes the setup and operating mechanism of the sensor and the control unit, and through basic tests it demonstrates its potential in automated detection of soil microarthropods. The sensor may be used for monitoring activities, especially for remote observation activities in soil and insect ecology or pest control., Competing Interests: The authors declare no conflict of interest.

The impact of R-loops on the physiology and pathology of chromosomes has been demonstrated extensively by chromatin biology research. The progress in this field has been driven by technological advancement of R-loop mapping methods that largely relied on a single approach, DNA-RNA immunoprecipitation (DRIP). Most of the DRIP protocols use the experimental design that was developed by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping. To assess the accuracy and utility of this technology, we pursued an analytical approach to estimate inherent biases and errors in the DRIP protocol. By performing DRIP-sequencing, qPCR, and receiver operator characteristic (ROC) analysis, we tested the effect of formaldehyde fixation, cell lysis temperature, mode of genome fragmentation, and removal of free RNA on the efficacy of RNA-DNA hybrid detection and implemented workflows that were able to distinguish complex and weak DRIP signals in a noisy background with high confidence. We also show that some of the workflows perform poorly and generate random answers. Furthermore, we found that the most commonly used genome fragmentation method (restriction enzyme digestion) led to the overrepresentation of lengthy DRIP fragments over coding ORFs, and this bias was enhanced at the first exons. Biased genome sampling severely compromised mapping resolution and prevented the assignment of precise biological function to a significant fraction of R-loops. The revised workflow presented herein is established and optimized using objective ROC analyses and provides reproducible and highly specific RNA-DNA hybrid detection., (© 2017 Halász et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: The apopto-phagocytic gene expression patterns during clearance of dying cells in the retina and the effect of triamcinolone (TC) upon these processes have relevance to development of age-related macular degeneration (AMD)., Methods: ARPE-19 cells and primary human retinal pigment epithelium (hRPE) were induced to undergo cell death by anoikis and the clearance of these cells by living hRPE/ARPE-19 or human monocyte-derived macrophages (HMDMs) in the presence or absence of TC was quantified by flow cytometry. TaqMan low-density gene expression array determining known markers of phagocytosis and loss-of-function studies on selected apopto-phagocytic genes was carried out in HMDM engulfing anoikic cells., Results: The glucocorticoid TC had a profound phagocytosis-enhancing effect on HMDM engulfing anoikic ARPE-19 or hRPE cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and thrombospondin-1 (THSB-1). The key role of the MERTK could be demonstrated in HMDM engulfing dying cells using gene silencing as well as blocking antibodies. Similar pathways were found upregulated in living ARPE-19 engulfing anoikic ARPE-19 cells. Gas6 treatment enhanced phagocytosis in TC-treated HMDMs., Conclusions: Specific agonists of the Mertk receptor may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy., General Significance: The use of Gas6 as enhancer of retinal phagocytosis via the MerTK receptor, alone or in combination with other specific ligands of the tyrosine kinase receptors' family may have a potential role in AMD therapy., (Copyright © 2014. Published by Elsevier B.V.)

The symbiotic nitrogen-fixing soil bacterium Sinorhizobium meliloti carries a large number of toxin-antitoxin (TA) modules both on the chromosome and megaplasmids. One of them, the vapBC-5 module that belongs to the type II systems was characterized here. It encodes an active toxin vapC-5, and was shown to be controlled negatively by the complex of its own proteins. Different mutants of the vapBC-5 genes exhibited diverse effects on symbiotic efficiency during interaction with the host plant Medicago sativa. The absence of the entire vapBC-5 region had no influence on nodule formation and nitrogen fixation properties. The strain carrying an insertion in the antitoxin gene showed a reduced nitrogen fixation capacity resulting in a lower plant yield. In contrast, when the toxin gene was mutated, the strain developed more efficient symbiosis with the host plant. The nitrogen fixing root nodules had a delayed senescent phenotype and contained elevated level of plant-derived molecules characteristic of later steps of nodule development. The longer bacteroid viability and abundance of active nitrogen fixing zone resulted in increased production of plant material. These data indicate that modification of the toxin/antitoxin production may influence bacteroid metabolism and may have an impact on the adaptation to changing environmental conditions., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The architectural high mobility group box 1 (Hmgb1) protein acts as both a nuclear and an extracellular regulator of various biological processes, including skeletogenesis. Here we report its contribution to the evolutionarily conserved, distinctive regulation of the matrilin-1 gene (Matn1) expression in amniotes. We previously demonstrated that uniquely assembled proximal promoter elements restrict Matn1 expression to specific growth plate cartilage zones by allowing varying doses of L-Sox5/Sox6 and Nfi proteins to fine-tune their Sox9-mediated transactivation. Here, we dissected the regulatory mechanisms underlying the activity of a conserved distal promoter element 1. We show that this element carries three Sox-binding sites, works as an enhancer in vivo, and allows promoter activation by the Sox5/6/9 chondrogenic trio. In early steps of chondrogenesis, declining Hmgb1 expression overlaps with the onset of Sox9 expression. Unlike repression in late steps, Hmgb1 overexpression in early chondrogenesis increases Matn1 promoter activation by the Sox trio, and forced Hmgb1 expression in COS-7 cells facilitates induction of Matn1 expression by the Sox trio. The conserved Matn1 control elements bind Hmgb1 and SOX9 with opposite efficiency in vitro. They show higher HMGB1 than SOX trio occupancy in established chondrogenic cell lines, and HMGB1 silencing greatly increases MATN1 and COL2A1 expression. Together, these data thus suggest a model whereby Hmgb1 helps recruit the Sox trio to the Matn1 promoter and thereby facilitates activation of the gene in early chondrogenesis. We anticipate that Hmgb1 may similarly affect transcription of other cartilage-specific genes., (© 2013.)

A homologue of the adenylyl cyclase (AC) gene of Neurospora crassa, named Fpacy1 was cloned from the genomic library of Fusarium proliferatum ITEM 2287 by screening the library with a DNA fragment amplified by using PCR primers designed from conserved sequences of the catalytic domain of AC genes from other fungi. The deduced FPACY1 protein had 53-77% identity with the AC proteins of other fungi. DeltaFpacy1 mutants obtained by targeted gene disruption showed retarded vegetative growth, increased conidiation and delayed conidial germination. Colonization capability of the mutants, assessed on maize seedlings and tomato fruits also was adversely affected. In sexual crosses the AC mutants retained full male fertility, but their female fertility decreased significantly. Disruption of Fpacy1 abolished vegetative self-incompatibility, suggesting that the AC gene is involved in multiple developmental processes related to vegetative growth, as well as sexual and parasexual events. The elevated thermo- and H(2)O(2)-tolerance of the DeltaFpacy1 mutants was coupled to an increased sensitivity towards Cd and Cu, indicating that the cAMP signaling pathway may have both negative and positive regulatory roles on the stress response mechanisms of fungal cells. When grown under nitrogen limitation conditions, the DeltaFpacy1 mutants produced an average of approximately 274 microg g(-1) bikaverin, whereas only traces of this metabolite was detected in the wild type. This finding provides further evidence of the role of the cAMP-PKA pathway in regulating bikaverin production.

The formation of a nitrogen-fixing nodule requires the coordinated development of rhizobial colonization and nodule organogenesis. Based on its mutant phenotype, lumpy infections (lin), LIN functions at an early stage of the rhizobial symbiotic process, required for both infection thread growth in root hair cells and the further development of nodule primordia. We show that spontaneous nodulation activated by the calcium- and calmodulin-dependent protein kinase is independent of LIN; thus, LIN is not necessary for nodule organogenesis. From this, we infer that LIN predominantly functions during rhizobial colonization and that the abortion of this process in lin mutants leads to a suppression of nodule development. Here, we identify the LIN gene in Medicago truncatula and Lotus japonicus, showing that it codes for a predicted E3 ubiquitin ligase containing a highly conserved U-box and WD40 repeat domains. Ubiquitin-mediated protein degradation is a universal mechanism to regulate many biological processes by eliminating rate-limiting enzymes and key components such as transcription factors. We propose that LIN is a regulator of the component(s) of the nodulation factor signal transduction pathway and that its function is required for correct temporal and spatial activity of the target protein(s).

For two fungal strains to be vegetatively compatible and capable of forming a stable vegetative heterokaryon they must carry matching alleles at a series of loci variously termed het or vic genes. Cloned het/vic genes from Neurospora crassa and Podospora anserina have no obvious functional similarity and have various cellular functions. Our objective was to identify the homologue of the Neurospora het-c gene in Fusarium proliferatum and to determine if this gene has a vegetative compatibility function in this economically important and widely dispersed fungal pathogen. In F. proliferatum and five other closely related Fusarium species we found a few differences in the DNA sequence, but the changes were silent and did not alter the amino acid sequence of the resulting protein. Deleting the gene altered sexual fertility as the female parent, but it did not alter male fertility or existing vegetative compatibility interactions. Replacement of the allele-specific portion of the coding sequence with the sequence of an alternate allele in N. crassa did not result in a vegetative incompatibility response in transformed strains of F. proliferatum. Thus, the fphch gene in Fusarium appears unlikely to have the vegetative compatibility function associated with its homologue in N. crassa. These results suggest that the vegetative compatibility phenotype may result from convergent evolution. Thus, the genes involved in this process may need to be identified at the species level or at the level of a group of species and could prove to be attractive targets for the development of antifungal agents.

Legumes form two different types of intracellular root symbioses, with fungi and bacteria, resulting in arbuscular mycorrhiza and nitrogen-fixing nodules, respectively. Rhizobial signalling molecules, called Nod factors, play a key role in establishing the rhizobium-legume association and genes have been identified in Medicago truncatula that control a Nod factor signalling pathway leading to nodulation. Three of these genes, the so-called DMI1, DMI2 and DMI3 genes, are also required for formation of mycorrhiza, indicating that the symbiotic pathways activated by both the bacterial and the fungal symbionts share common steps. To analyse possible cross-talk between these pathways we have studied the effect of treatment with Nod factors on mycorrhization in M. truncatula. We show that Nod factors increase mycorrhizal colonization and stimulate lateral root formation. The stimulation of lateral root formation by Nod factors requires both the same structural features of Nod factors and the same plant genes (NFP, DMI1, DMI2, DMI3 and NSP1) that are required for other Nod factor-induced symbiotic responses such as early nodulin gene induction and cortical cell division. A diffusible factor from arbuscular mycorrhizal fungi was also found to stimulate lateral root formation, while three root pathogens did not have the same effect. Lateral root formation induced by fungal signal(s) was found to require the DMI1 and DMI2 genes, but not DMI3. The idea that this diffusible fungal factor might correspond to a previously hypothesized mycorrhizal signal, the 'Myc factor', is discussed.

To assess the potential for mating in several Fusarium species with no known sexual stage, we developed degenerate and semidegenerate oligonucleotide primers to identify conserved mating type (MAT) sequences in these fungi. The putative alpha and high-mobility-group (HMG) box sequences from Fusarium avenaceum, F. culmorum, F. poae, and F. semitectum were compared to similar sequences that were described previously for other members of the genus. The DNA sequences of the regions flanking the amplified MAT regions were obtained by inverse PCR. These data were used to develop diagnostic primers suitable for the clear amplification of conserved mating type sequences from any member of the genus Fusarium. By using these diagnostic primers, we identified mating types of 122 strains belonging to 22 species of Fusarium. The alpha box and the HMG box from the mating type genes are transcribed in F. avenaceum, F. culmorum, F. poae, and F. semitectum. The novelty of the PCR-based mating type identification system that we developed is that this method can be used on a wide range of Fusarium species, which have proven or expected teleomorphs in different ascomycetous genera, including Calonectria, Gibberella, and Nectria.

The glutathione (GSH) S-conjugation of 1,2-epoxy-3-(4'-nitrophenoxy)propane was catalysed predominantly by microsomal glutathione S-transferase (mGST) in Penicillium chrysogenum. The specific mGST activity unlike the cytosolic GST (cGST) activity increased substantially when the penicillin side-chain precursor phenoxyacetic acid (POA) was included in the culture medium. Therefore, a microsomal monooxygenase (causing possible release of epoxide intermediates) and mGST-dependent detoxification pathway may exist for the side-chain precursors as an alternative to microsomal activation to acyl-CoA and subsequent transfer to beta-lactam molecules. The P. chrysogenum pahA and Aspergillus nidulans phacA gene products, which are cytochrome p450 monooxygenases and are able to hydroxylate phenylacetic acid (PA) at position 2 on the aromatic ring, are unlikely to release toxic epoxide intermediates but epoxidation of PA and POA due to the action of other microsomal monooxygenases cannot be excluded. The GSH-dependent detoxification of POA was provoked by a well-controlled transient lowering of pH (down to 5.0) at the beginning of the production phase in a fed-batch fermentation system. Both the specific GST and gammaGT activities were increased but the intracellular GSH concentrations remained unaltered unless the pH of the feed was transiently lowered below 5.0. At pH 4.6, the GSH pool was depleted rapidly but no antibiotic production was observed. Although sucrose was taken up effectively by the cells, cell death and autolysis were progressing. Therefore, the industrial exploitation of the GSH-dependent detoxification of penicillin side-chain precursors to reduce intracellular GSH-levels in order to avoid the GSH inhibition of the beta-lactam biosynthetic enzymes seems to be rather unlikely. P. chrysogenum mGST and cGST were separated using GSH-Sepharose 6B affinity chromatography. The purified cGST possessed a homodimer (alpha(2)) tertiary structure with M(r) (, alpha) = 29500.

In specific plant organs, namely the root nodules of alfalfa, fixed nitrogen (ammonia) produced by the symbiotic partner Sinorhizobium meliloti supports the growth of the host plant in nitrogen-depleted environment. Here, we report that a derivative of S. meliloti carrying a mutation in the chromosomal ntrR gene induced nodules with enhanced nitrogen fixation capacity, resulting in an increased dry weight and nitrogen content of alfalfa. The efficient nitrogen fixation is a result of the higher expression level of the nifH gene, encoding one of the subunits of the nitrogenase enzyme, and nifA, the transcriptional regulator of the nif operon. The ntrR gene, controlled negatively by its own product and positively by the symbiotic regulator syrM, is expressed in the same zone of nodules as the nif genes. As a result of the nitrogen-tolerant phenotype of the strain, the beneficial effect of the mutation on efficiency is not abolished in the presence of the exogenous nitrogen source. The ntrR mutant is highly competitive in nodule occupancy compared with the wild-type strain. Sequence analysis of the mutant region revealed a new cluster of genes, termed the "ntrPR operon," which is highly homologous to a group of vap-related genes of various pathogenic bacteria that are presumably implicated in bacterium-host interactions. On the basis of its favorable properties, the strain is a good candidate for future agricultural utilization.

The results of the environmental toxicological investigations and their results of a new hungarian acaricide molecule (SZI-121) developed by the CHINOIN were summarized. The toxicological effects of the test item on different ecotoxicological test systems were investigated in the following tests: Bacterium, alga, and plant growth inhibition tests, acute immobilization and 21 days reproduction tests on Daphnia magna, acute fish test, closed bottle test, mobility, aerob degradation and adsorption/desorption tests on three different soils. No toxic effect was found in the bacterium, alga, plant growth inhibition and acute fish tests in the highest concentrations used. In the Daphnia immobilization test 0.14 mg/l LC50 value was established in the concentration range of 0.0128-40 mg/l applied. The test item showed similar characteristics as the reference item during the mobility test in soils, the adsorption/desorption study and the degradation investigations. In order to determine the environmental degradation rate further degradation investigations, as well as the nitrogen mineralization test and the model of concentration change in natural waters were performed.

Are plants generally less sensitive to toxicity than aquatic animals as indicated by some authors (1)? The use of phytotoxicity (higher plant) tests as a part of ecotoxicology is relatively underdeveloped. The objective of this study was to compare the results of the OECD Lemna Growth Inhibition Test with other mainly used test systems. Three toxicants were tested applying the Alga Growth Inhibition Test (Seleneastrum capricornutum), the Daphnia Immobilization Test (Daphnia magna) and the MICROTOX-test (Photobacterium phosphoreum). Duckweed plants were found to be sensitive to the chemicals tested, with nearly 100% inhibition of frond production occurring in the highest concentrations. The plants in some samples showed lesions (break up of the colony structure) and loss of green pigments (chlorosis), others showed localized dead tissues (necrosis). In addition to the morphological deviations (appearance) there is a wide range of characteristics to be observed on the test plants: number of fronds, number of plants, biomass, dry weight, mortality, CO2 and O2 exchange, concentration of chlorophyll a and chlorophyll b. It is consistent that the number of fronds is slightly more sensitive than or the same as the number of plants and that the biomass tend to be somewhat more tolerant than those for the number of plants (2). Applying the simplest way of observation, changes in the frond number were recorded. As Lemna minor show a characteristical sensitivity to the different kind of chemicals, it is a promising indicator of aquatic toxicity.

In the present study 4 hazardous wastes originated from 4 different typical industrial activities (leachates of waste oil, waste stockpiles of aluminium factory, sewage of leather industry and of the chemical industry) were examined with several Toxkit microbiotests: the Algaltoxkit, the Protoxkit, the Daphtoxkit and the Thamnotoxkit. The data obtained with the microbiotests were compared to those obtained with the standard conventional acute toxicity tests. The goal of the study was to try out the reproducibility of the tests on the same samples, prepared in the same laboratory and provided to all the participants of the interlaboratory exercise. The first reproducibility evaluation of the tests was made with the reference toxicant potassium dichromate (K2Cr2O7). The outcome was that the lowest coefficients of variation were found at the Thamnotoxkit and highest with Algaltoxkit. The same findings were observed with the industrial waste samples. Different responses were obtained depending on the preparation and the character of the waste. For example, whereas a strong (and highest) toxic effect was found with the Thamnotoxkit, the algal cells in the Algaltoxkit test grew better than in the controls, when exposed to the same waste sample. The sensitivity of the Protoxkit ciliates was the lowest for all the wastes examined. In conclusion of this study, the experience gained and data obtained indicate that the Toxkit microbiotests are suited for routine monitoring after modification of some technical aspects.

Methyl-chrysanthemate is one of the intermediates of pyrethroid type insecticides. The acute toxicity of the test item was investigated in rats after single oral, dermal and inhalation applications. The irritation effect was determined by Draize method. Buehler method was applied to evaluate the sensitization potential of the test item. The mutagenic effect was assessed on Salmonella typhimurium strains. Furthermore metaphase chromosome aberration assay was performed on CHO cell line to check the structural chromosome aberrations.

Ecotoxicological characteristics of a new insecticide synergist, MBB-599 (proposed common name: Verbutin) was investigated. The studies included the determination of the hydrolysis, the biodegradability, the adsorption and desorption characteristics in soil and the effects on living systems (bacterium, alga, Daphnia, and fish) as well.

Plant organs develop mostly post-embryonically from persistent or newly formed meristems. After cell division arrest, differentiation frequently involves endoreduplication and cell enlargement. Factors controlling transition from mitotic cycles to differentiation programmes have not been identified yet in plants. Here we describe ccs52, a plant homologue of APC activators involved in mitotic cyclin degradation. The ccs52 cDNA clones were isolated from Medicago sativa root nodules, which exhibit the highest degree of endopolyploidy in this plant. ccs52 represents a small multigenic family and appears to be conserved in plants. Overexpression of ccs52 in yeast triggered mitotic cyclin degradation, cell division arrest, endoreduplication and cell enlargement. In Medicago, enhanced expression of ccs52 was found in differentiating cells undergoing endoreduplication. In transgenic M.truncatula plants, overexpression of the ccs52 gene in the antisense orientation resulted in partial suppression of ccs52 expression and decreased the number of endocycles and the volume of the largest cells. Thus, the ccs52 product may switch proliferating cells to differentiation programmes which, in the case of endocycles, result in cell size increments.

Trends of certain mastitis markers were studied in udder quarters (n = 201) showing clinical symptoms of acute mastitis. Besides the clinical examination, before the first treatment (baseline sample), and about 3 weeks later, 17 to 24 days following the last treatment (control sample) milk samples were collected for bacteriological identification of the mastitis pathogens and for the determination of certain inflammatory markers: somatic cell count (SCC), N-acetyl-beta-D-glucosaminidase (NAGase) and alpha 1-antitrypsin (ATR) activities, as well as bovine serum albumin (BSA) and chloride (Cl-) concentrations. Based upon the clinical and bacteriological status as well as the SCC recorded at the control investigations, 6 groups were established (recovered, latently infected, subclinical mastitis: bacteriologically positive and negative, as well as clinical mastitis: bacteriologically positive and negative). As compared to the baseline samples, all parameters decreased in the case of recovered udder quarters, as well as in those with abated latent infection or subclinical mastitis at the time of control examination. Comparing the control samples of the different categories, characteristic differences were found in NAGase activity, indicating the grade of cytodamaging effect of mastitis. Of the other markers, ATR and Cl- proved to be more adequate for the differentiation than BSA. It can be concluded that, in addition to SCC, first of all NAGase can be recommended for use as an inflammatory parameter in pharmacodynamic studies. Besides these two parameters, ATR and Cl- can also be chosen as a possible third marker.