RESUMO
OBJECTIVE: Absence rates remain high in UK schools, with negative implications for attainment, life chances and inequality. Reasons for non-attendance are complex but include psychosocial factors. Few UK-based studies have evaluated psychosocial interventions for school attendance outcomes or its moderators. This pre-post evaluation examined the potential influence of school-based one-to-one counselling on school attendance and possible moderators. DESIGN AND SETTING: Secondary analysis of routine data, collected by a national mental health provider in primary and secondary schools. PARTICIPANTS: 7405 pupils aged 4-19 years, with complete school attendance records at Time1 (pre-counselling term) and Time2 (the term when counselling ended). INTERVENTION: All participants received school-based one-to-one counselling with a trained counsellor between August 2016 and December 2019. OUTCOMES: Percentage of school sessions attended (continuous) and persistent absence (binary; attending ≤90% of sessions) in a term. Potential moderators included sociodemographics, mental health and school engagement/enjoyment. RESULTS: Median Time1 attendance was 96%. 23.6% of participants were persistently absent. The intervention was not associated with improved percentage attendance (0.028%, 95% CI -0.160-0.216%) but was associated with 18.5% reduced odds of persistent absence (OR=0.815, 95% CI 0.729-0.911). We identified five moderators of change in attendance (interaction terms p<0.05): age group (improvements for 4-9 s; worsening for 15-19 s), improvement for some ethnicities and lower parent/carer education. Mental health and school engagement/enjoyment co-varied with attendance in expected directions. CONCLUSIONS: One-to-one counselling may improve school attendance among persistently absent pupils, particularly at younger ages. Improving mental health and pupil engagement/enjoyment are potential intervention targets. Our hypotheses require confirmation with controlled designs.
RESUMO
Common variable immunodeficiency (CVID) is an immune defect characterized by hypogammaglobulinemia and impaired development of B cells into plasma cells. As follicular helper T cells (TFH) play a central role in humoral immunity, we examined TFH cells in CVID, and investigated whether an inducible T cell co-stimulator (ICOS) agonist, vopratelimab, could modulate TFH, B cell interactions and enhance immunoglobulin production. CVID subjects had decreased TFH17 and increased TFH1 subsets; this was associated with increased transitional B cells and decreased IgG+ B and IgD-IgM-CD27+ memory B cells. ICOS expression on CVID CD4+ T cells was also decreased. However, ICOS activation of CD4+ T cells by vopratelimab significantly increased total CVID TFH, TFH2, cell numbers, as well as IL-4, IL-10 and IL-21 secretion in vitro. Vopratelimab treatment also increased plasma cells, IgG+ B cells, reduced naïve & transitional B cells and significantly increased IgG1 secretion by CVID B cells. Interestingly, vopratelimab treatment also restored IgA secretion in PBMCs from several CVID patients who had a complete lack of endogenous serum IgA. Our data demonstrate the potential of TFH modulation in restoring TFH and enhancing B cell maturation in CVID. The effects of an ICOS agonist in antibody defects warrants further investigation. This biologic may also be of therapeutic interest in other clinical settings of antibody deficiency.
Assuntos
Linfócitos B , Imunodeficiência de Variável Comum , Proteína Coestimuladora de Linfócitos T Induzíveis , Células T Auxiliares Foliculares , Humanos , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/tratamento farmacológico , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Células T Auxiliares Foliculares/imunologia , Células T Auxiliares Foliculares/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Imunoglobulina G/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Idoso , Adulto JovemRESUMO
BACKGROUND: The study examined the impact of varying the concentrations of zinc (Zn) on plant responses, particularly on photosynthetic and oxidative metabolic processes. This investigation aimed to distinguish between the beneficial and harmful effects of Zn on plants, highlighting significant nutrient supply concerns. METHODS: The investigation methods were centered around non-invasive methods, such as biophoton emission (delayed fluorescence-DF, ultra-weak bioluminescence-UWLE), fluorescence induction (Fv/Fm) measurements, chlorophyll content estimation (SPAD) and vegetation index (NDVI) determination. Furthermore, the analytical determination of lipid oxidation (MDA level) and antioxidant capacity (FRAP) as well as gene expression studies of the antioxidative enzymes glutathione reductase (GR), glutathione S-transferase (GST) and lipoxygenase (LOX) for essential Zn and nonessential cadmium (Cd) were also carried out in order to clarify toxic symptoms through different Zn investigation approaches. RESULTS: It was possible to identify a metabolic enhancement from 1000 µM; however, stress symptoms from the 2000 µM Zn treatment were noted for both the investigated photosynthetic and oxidative processes. The outcomes of this research contribute to the improvement of Zn mineral-supplementation technology, which is essential for maize growth, and the optimization of agricultural practices.
RESUMO
Varroa destructor is one of the most destructive enemies of the honey bee, Apis mellifera all around the world. Several control methods are known to control V. destructor, but the efficacy of several alternative control methods remains unexplored. Irradiation can be one of these unknown solutions but before practical application, the effectiveness, and the physiological effects of ionizing radiation on the host and the parasite are waiting to be tested. Therefore, the objective of our study was to investigate the effects of different doses (15, 50, 100, and 150 Gy) of high-energy X-ray irradiation through mortality rates and hemocyte composition changes in A. mellifera workers and record the mortality rates of the parasite. The mortality rate was recorded during short-term (12, 24, and 48 h) and long-term periods (3, 6, 12, 18, and 24d). The sensitivity of the host and the parasite in case of the higher doses of radiation tested (50, 100, and 150 Gy) been demonstrated by total mortality of the host and 90 % of its parasite has been observed on the 18th day after the irradiation. V. destructor showed higher sensitivity (1.52-times higher than the adult honey bee workers) at the lowest dose (15 Gy). A. mellifera hemocytes were influenced significantly by radiation dosage and the elapsed time after treatment. The higher radiation doses increased plasmatocyte numbers in parallel with the decrease in prohemocyte numbers. On the contrary, the numbers of granulocytes and oencoytes increased in the treated samples, but the putative effects of the different dosages on the recorded number of these hemocyte types could not be statistically proven. In summary, based on the outcome of our study X-ray irradiation can be deemed an effective tool for controlling phoretic V. destructor. However, further research is needed to understand the physiological response of the affected organisms.
Assuntos
Hemócitos , Hemolinfa , Varroidae , Animais , Abelhas/parasitologia , Abelhas/efeitos da radiação , Abelhas/imunologia , Varroidae/efeitos da radiação , Raios X , Hemolinfa/efeitos da radiação , Hemolinfa/parasitologia , Hemócitos/efeitos da radiação , Hemócitos/imunologia , Interações Hospedeiro-Parasita/efeitos da radiaçãoAssuntos
Neurociências , Sinapses , Neurociências/história , História do Século XX , Sinapses/fisiologia , História do Século XXI , Humanos , AnimaisRESUMO
Synapses preferentially respond to particular temporal patterns of activity with a large degree of heterogeneity that is informally or tacitly separated into classes. Yet, the precise number and properties of such classes are unclear. Do they exist on a continuum and, if so, when is it appropriate to divide that continuum into functional regions? In a large dataset of glutamatergic cortical connections, we perform model-based characterization to infer the number and characteristics of functionally distinct subtypes of synaptic dynamics. In rodent data, we find five clusters that partially converge with transgenic-associated subtypes. Strikingly, the application of the same clustering method in human data infers a highly similar number of clusters, supportive of stable clustering. This nuanced dictionary of functional subtypes shapes the heterogeneity of cortical synaptic dynamics and provides a lens into the basic motifs of information transmission in the brain.
Assuntos
Cristalino , Lentes , Animais , Humanos , Camundongos , Animais Geneticamente Modificados , Encéfalo , Análise por ConglomeradosRESUMO
The objective of this study was to characterize the effects of barley powdery mildew infection on wheat via the evolution and dynamics of chloroplasts and oxidative processes based on in vivo measurements of ultra-weak photon emission, parallel measurement of chlorophyll and ascorbic acid content, and molecular identification of the pathogen. The results showed the temporal dynamics of the evolution of ultra-weak photon emission signals that were evidently different for healthy and powdery mildew-infested wheat leaves. In the dark, the ceasing of delayed fluorescence signal made it possible to visualize the ultra-weak luminescence signal as well. Both delayed fluorescence and ultra-weak luminescence signals were characteristic of stress symptoms induced by powdery mildew that was further strengthened by the changes of chlorophyll and ascorbic acid content as typical stress analytical parameters. The presented data and parameterization enabled the identification of stress induction due to powdery mildew infestation in wheat, which should be investigated in detail in the future for fine-tuning our measurements, even by using other species and increasing the length of the measurement in order to increase its specificity. The changes in R2 values are suitable for monitoring the changes of plant stress response. The measurement of fluorescence and luminescence leads to a greater comprehension of the underlying photon emission-related processes, both in general and in the case of powdery mildew infestation.
Assuntos
Hordeum , Triticum , Ácido Ascórbico , Clorofila , Doenças das Plantas , Resistência à DoençaRESUMO
The occurrence and regularity of macrofungal fruitbody formation are influenced by meteorological conditions; however, there is a scarcity of data about the use of machine-learning techniques to estimate their occurrence based on meteorological indicators. Therefore, we employed an artificial neural network (ANN) to forecast fruitbody occurrence in mycorrhizal species of Russula and Amanita, utilizing meteorological factors and validating the accuracy of the forecast of fruitbody formation. Fungal data were collected from two locations in Western Hungary between 2015 and 2020. The ANN was the commonly used algorithm for classification problems: feed-forward multilayer perceptrons with a backpropagation algorithm to estimate the binary (Yes/No) classification of fruitbody appearance in natural and undisturbed forests. The verification indices resulted in two outcomes: however, development is most often studied by genus level, we established a more successful, new model per species. Furthermore, the algorithm is able to successfully estimate fruitbody formations with medium to high accuracy (60-80%). Therefore, this work was the first to reliably utilise the ANN approach of estimating fruitbody occurrence based on meteorological parameters of mycorrhizal specified with an extended vegetation period. These findings can assist in field mycological investigations that utilize sporocarp occurrences to ascertain species abundance.
Assuntos
Agaricales , Micorrizas , Redes Neurais de Computação , Algoritmos , Aprendizado de MáquinaRESUMO
BACKGROUND: Bilberry (Vaccinium myrtillus L.) is one of the most important economic and natural resources in Northern Europe. Despite its importance, the endophytic fungal community of the fruits has rarely been investigated. Biogeographic patterns and determinants of the fungal diversity in the bilberry fruit are poorly understood, albeit fungal endophytes can have a close relationship with the host plants. Here, we investigated the effect of climatic regions, and their weather conditions within growth season and soil properties on fungal endophytic communities of bilberry fruits collected from northern and southern regions of Finland using high-throughput sequencing technology targeting the internal transcribed spacer 2 ribosomal DNA region for fungi. RESULTS: Species richness and beta diversity (variation in community structure) were higher in the southern compared to the studied northern region. The weather condition of the growth season drove both fungal richness and community structure. Furthermore, abundance of the genera Venturia, Cladosporium, and Podosphaera was influenced by the weather, being different between the south and north regions. CONCLUSIONS: We conclude that diversity and assembly structure of the fungal endophytes in bilberry fruits follow similar patterns as for foliar fungal endophytes, being shaped by various environmental factors, such as the climate and surrounding vegetation.
RESUMO
Gene expression is controlled via complex regulatory mechanisms involving transcription factors, chromatin modifications, and chromatin regulatory factors. Histone modifications, such as H3K27me3, H3K9ac, and H3K27ac, play an important role in controlling chromatin accessibility and transcriptional output. In vertebrates, the Transcriptional Intermediary Factor 1 (TIF1) family of proteins play essential roles in transcription, cell differentiation, DNA repair, and mitosis. Our study focused on Bonus, the sole member of the TIF1 family in Drosophila, to investigate its role in organizing epigenetic modifications. Our findings demonstrated that depleting Bonus in ovaries leads to a mild reduction in the H3K27me3 level over transposon regions and alters the distribution of active H3K9ac marks on specific protein-coding genes. Additionally, through mass spectrometry analysis, we identified novel interacting partners of Bonus in ovaries, such as PolQ, providing a comprehensive understanding of the associated molecular pathways. Furthermore, our research revealed Bonus's interactions with the Polycomb Repressive Complex 2 and its co-purification with select histone acetyltransferases, shedding light on the underlying mechanisms behind these changes in chromatin modifications.
Assuntos
Cromatina , Histonas , Animais , Feminino , Drosophila/metabolismo , Código das Histonas , Histonas/metabolismo , Ovário/metabolismoRESUMO
The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus's repressive activity. SUMOylation influences Bonus's subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2-10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression.
Assuntos
Cromatina , Proteínas de Drosophila , Animais , Feminino , Cromatina/metabolismo , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Células Germinativas/metabolismo , Mamíferos/genética , Análise de Mediação , SumoilaçãoRESUMO
Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of - 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying - 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.
Assuntos
Antipsicóticos , Citocromo P-450 CYP1A2 , Humanos , Olanzapina/efeitos adversos , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Antipsicóticos/efeitos adversos , Genótipo , RNA MensageiroRESUMO
The existing plant trait databases' applicability is limited for studies dealing with the flora and vegetation of the eastern and central part of Europe and for large-scale comparisons across regions, mostly because their geographical data coverage is limited and they incorporate records from several different sources, often from regions with markedly different climatic conditions. These problems motivated the compilation of a regional dataset for the flora of the Pannonian region (Eastern Central Europe). PADAPT, the Pannonian Dataset of Plant Traits relies on regional data sources and collates data on 54 traits and attributes of the plant species of the Pannonian region. The current version covers approximately 90% of the species of the region and consists of 126,337 records on 2745 taxa. By including species of the eastern part of Europe not covered by other databases, PADAPT can facilitate studying the flora and vegetation of the eastern part of the continent. Although data coverage is far from complete, PADAPT meets the longstanding need for a regional database of the Pannonian flora.
Assuntos
Plantas , Bases de Dados Factuais , Europa (Continente) , GeografiaRESUMO
PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.
Assuntos
Proteínas de Drosophila , RNA de Interação com Piwi , Animais , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Herança Materna , Drosophila/genética , Cromatina/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Elementos de DNA Transponíveis/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismoRESUMO
When a neuron breaks silence, it can emit action potentials in a number of patterns. Some responses are so sudden and intense that electrophysiologists felt the need to single them out, labelling action potentials emitted at a particularly high frequency with a metonym - bursts. Is there more to bursts than a figure of speech? After all, sudden bouts of high-frequency firing are expected to occur whenever inputs surge. The burst coding hypothesis advances that the neural code has three syllables: silences, spikes and bursts. We review evidence supporting this ternary code in terms of devoted mechanisms for burst generation, synaptic transmission and synaptic plasticity. We also review the learning and attention theories for which such a triad is beneficial.
Assuntos
Neurônios , Transmissão Sináptica , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Plasticidade Neuronal/fisiologiaRESUMO
Various specialized structural/functional properties are considered essential for contextual memory encoding by hippocampal mossy fiber (MF) synapses. Although investigated to exquisite detail in model organisms, synapses, including MFs, have undergone minimal functional interrogation in humans. To determine the translational relevance of rodent findings, we evaluated MF properties within human tissue resected to treat epilepsy. Human MFs exhibit remarkably similar hallmark features to rodents, including AMPA receptor-dominated synapses with small contributions from NMDA and kainate receptors, large dynamic range with strong frequency facilitation, NMDA receptor-independent presynaptic long-term potentiation, and strong cyclic AMP (cAMP) sensitivity of release. Array tomography confirmed the evolutionary conservation of MF ultrastructure. The astonishing congruence of rodent and human MF core features argues that the basic MF properties delineated in animal models remain critical to human MF function. Finally, a selective deficit in GABAergic inhibitory tone onto human MF postsynaptic targets suggests that unrestrained detonator excitatory drive contributes to epileptic circuit hyperexcitability.
Assuntos
Fibras Musgosas Hipocampais , Sinapses , Animais , Humanos , Fibras Musgosas Hipocampais/fisiologia , Sinapses/fisiologia , Potenciação de Longa Duração/fisiologia , Transdução de SinaisRESUMO
Strawberry is a typical spring fruit, for which consumer demand is particularly high; however, information is scarce on the comparison of quality traits of strawberries of local and imported origin during household refrigeration storage. That is why we sought to answer the question of to what extent the quality of strawberries changes during 5 days of household refrigeration storage. The choice of methods was focused on fast and at the same time informative analytical methods: pH, total antioxidant capacity, and lipid oxidation. Furthermore, a non-invasive imaging technique: ultra-weak bioluminescence measurement was carried out along with the determination of fruit morphological (weight, height, width, and color) and analytical (antioxidant capacity and lipid oxidation) traits. The data indicate that the longer strawberries are cultivated in the same plantation, the smaller their fruit weight and the lower their fruit quality become. In addition, the results cast light on a controversial fact: despite the fact that the sample from the store had the finest appearance, as determined, its antioxidant capacity was the lowest for the duration of home refrigeration storage, indicating the lowest nutritional value.This was validated by the lipid oxidation levels, which were defined by the amount of malondialdehyde as well as by the rate of ultra-weak bioluminescence. The research underlines the exceptional value of local fruits over importand provides valuable information to customers, encouraging them to purchase strawberries from local farms in order to not only support the local economy but also to adopt a more health-conscious attitude. In addition, ultra-weak bioluminescence testing offers a non-invasive method for assessing fruit quality.
RESUMO
The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus's repressive activity. SUMOylation influences Bonus's subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2-10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression.