BACKGROUND: The complement component C4 gene has been identified as a strong marker for schizophrenia (SCZ) risk. The C4 gene has a complex genetic structure consisting of variable structural elements (C4A, C4B, C4L, and C4S) and compound structural forms (C4AL, C4BL, C4AS and C4BS). In addition, the variations in C4 structural forms may have a direct or indirect effect on the brain expression level of C4A and C4B proteins. Previous studies have associated C4AL with higher brain C4A expression and sex-dimorphism of C4 between males and females was observed.
METHODS: A total of 613 patients with DSM-IV SCZ or schizoaffective disorder (SCZ-AFF) were recruited to investigate the relationship between C4 gene variants and clinical characteristics of SCZ (age of onset, symptom severity, and global assessment of functioning (GAF)). This study also explored the effect of sex on the association of C4 with SCZ. 434 patients were included in the final analyses after genetic quality control.
RESULTS: We observed associations between C4 and clinical characteristics of SCZ (age of onset, symptom severity, GAF) and found significant differences when males and females were examined separately.
CONCLUSIONS: Overall, our preliminary findings encourage future investigations of C4 in SCZ-related phenotypes, including antipsychotic response and side effects. The study sample was of moderate size; therefore, further studies in larger samples are needed to extend and validate these results.

Autism Spectrum Disorder (ASD) is a heterogeneous disorder in children, and the current clinical diagnosis is accomplished using behavioral, cognitive, developmental, and language metrics. These clinical metrics can be imperfect measures as they are subject to high test-retest variability, and are influenced by assessment factors such as environment, social structure, or comorbid disorders. Advances in neuroimaging coupled with machine-learning provides an opportunity to develop methods that are more quantifiable, and reliable than existing clinical techniques. In this paper, we design and develop a deep-learning model that operates on functional magnetic resonance imaging (fMRI) data, and can classify between ASD and neurotypical brains. We introduce a novel strategy to transform time-series data extracted from fMRI signals into Gramian Angular Field (GAF) while locking in the temporal and spatial patterns in the data. Our motivation is to design and develop a novel framework that could encode the time-series, acquired from fMRI data, into images that can be used by deep-learning architectures that have been successful in computer vision. In our proposed framework called ASD-GResTM, we used a Convolutional Neural Network (CNN) to extract useful features from GAF images. We then used a Long Short-Term Memory (LSTM) layer to learn the activities between the regions. Finally, the output representations of the last LSTM layer are applied to a single-layer perceptron (SPL) to get the final classification. Our extensive experimentation demonstrates high accuracy across 4 centers, and outperforms state-of-the-art models on two centers with an increase in the accuracy of 17.58% and 6.7%, respectively as compared to the state of the art. Our model achieved the maximum accuracy of 81.78% with high degree of sensitivity and specificity. All training, validation, and testing was accomplished using openly available ABIDE-I benchmarking dataset.

Fluorine, depending on its concentration and chemical form, is essential or toxic to humans and animals. Therefore, it is crucial to be able to determine it reliably. In this study, fluorine was determined in animal feed after extraction with HCl (gastric juice simulation). The standard potentiometric method with a fluoride-selective electrode (ISE) and newly developed high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GFMAS) method was applied. Feed samples turned out to be a challenge for HR-CS GFMAS. Chemical interferences (formation of competing molecules, CaF, GaCl, and GaP, instead of the target GaF molecule) and spectral effects (including a phosphorous molecule spectrum and atomic lines) were identified. An additional difficulty was caused by reagent contamination with F and memory effects. Difficulties were eliminated/reduced. The quality of ISE analysis was multi-directionally verified (including comprehensive proficiency testing). A risk of inaccuracy at low F concentration, where the calibration relationship is nonlinear, was investigated. The results of both methods were consistent, which confirms the accuracy of the methods and informs that the extracted fluorine is in fluoride form. The results of extensive ISE tests conducted in Poland in 2021-2023 have shown that, in most cases, the fluoride content is significantly lower than the threshold values.

BACKGROUND: The COVID-19 pandemic generated uncertainty and disruption among the child and adolescent population. Multiple studies have documented a worsening of mental health following the pandemic. The main objective of this longitudinal study is to analyze the short-, medium-, and long-term evolution of the overall functioning of children and adolescents treated by a child and adolescent mental health team in the context of the COVID-19 pandemic.
METHODS: 420 patients aged 3 to 18 were assessed using the Global Assessment of Functioning (GAF) scale at three time points: during the lockdown, three months later, and three years later. Differences based on gender, diagnosis, and time were analyzed.
RESULTS: A significant improvement was observed in the short-term (three months) and long-term (three years) compared to the lockdown period. This improvement was maintained in all diagnostic subgroups except for mixed cases (severe mental pathology), which showed the least improvement. No significant differences were found between males and females.
CONCLUSIONS: The child and adolescent population showed a greater capacity for adaptation to the lockdown than expected. Family support, decreased stress, and therapeutic intervention appear to have played an important role in improving mental health.

Since their initial discovery some 30 years ago, heme-based O2 sensors have been extensively studied. Among many other lessons, we have learned that they have adapted a wide variety of folds to bind heme for O2 sensing, and they can couple those sensory domains to transducer domains with many different activities. There is no question that we have learned a great deal about those systems by solving X-ray structures of the truncated pieces of larger multi-domain proteins. All of the studies have, for example, hinted at the importance of protein residues, which were further investigated, usually by site-directed mutagenesis of the full-length proteins together with physico-chemical measurements and enzymatic studies. The biochemistry has suggested that the sensing functions of heme-based O2 sensors involve not only the entire proteins but also, and quite often, their associated regulatory partners and targets. Here we critically examine the state of knowledge for some well-studied sensors and discuss outstanding questions regarding their structures. For the near future, we may foresee many large complexes with sensor proteins being solved by cryo-EM, to enhance our understanding of their mechanisms.

Research on the effects of fish oil on clinical symptoms and psychosocial functioning in people with psychosis has been inconsistent. We conducted this systematic review and meta-analysis to summarize the available data on the effects of oral intake of fish oil on psychological functioning in patients with psychosis. Three online databases including PubMed, Scopus, and Web of Science were searched to identify relevant studies published by April 2021. The exposure was oral fish-oil supplementation. The Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Global Assessment of Functioning (GAF) were our outcome measures. Seventeen randomized clinical trials involving 1390 patients were included. No change in PANSS was observed following oral fish-oil intake [weighted mean difference (WMD): -0.87; 95% CI: -16.99, 15.26; P = 0.92]. In a nonlinear dose-response analysis, a significant inverse association was observed between <10 wk of fish-oil supplementation and PANSS (WMD: -10; P-nonlinearity = 0.02). Although analysis of 4 studies showed a nonsignificant reduction in BPRS after fish-oil intake (WMD: -2.990; 95% CI: -6.42, 0.44; P = 0.08), a nonlinear dose-response analysis revealed significant inverse associations between dose (>2200 mg/d) and duration of fish-oil supplementation (<15 wk) with BPRS score (WMD: -8; P-nonlinearity = 0.04). Combined effect sizes from 6 randomized clinical trials showed significant increases in GAF after oral administration of fish oil (WMD: 6.66; 95% CI: 3.39, 9.93; P < 0.001). In conclusion, we did not find any significant changes in PANSS and BPRS scores following fish-oil supplementation. Nevertheless, oral fish-oil intake significantly contributed to improvement in GAF scores. This is the first meta-analysis to examine the effects of fish oil on the psychological functioning scores of PANSS, BPRS, and GAF simultaneously.

Polycomb group (PcG) repressors and Trithorax group (TrxG) activators of transcription are essential for the proper development and maintenance of gene expression profiles in multicellular organisms. In Drosophila, PcG/TrxG proteins interact with DNA elements called PRE (Polycomb response elements). We have previously shown that the repressive activity of inactive PRE in transgenes can be induced by architectural protein-binding sites. It was shown that the induction of repression is associated with the recruitment of PcG/TrxG proteins, including the DNA-binding factors Pho and Combgap. In the present study, we tested the association of the two other PRE DNA-binding factors, GAF and Psq, with bxdPRE in the presence and absence of sites for architectural proteins. As a result, it was shown that both factors can be efficiently recruited to the bxdPRE only in the presence of adjacent binding sites for architectural proteins Su(Hw), CTCF, or Pita.

Research on the effects of fish oil on clinical symptoms and psychosocial functioning in people with psychosis has been inconsistent. We conducted this systematic review and meta-analysis to summarize the available data on the effects of oral intake of fish oil on psychological functioning in patients with psychosis. Three online databases including PubMed, Scopus, and Web of Science were searched to identify relevant studies published by April 2021. The exposure was oral fish-oil supplementation. The Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Global Assessment of Functioning (GAF) were our outcome measures. Seventeen randomized clinical trials involving 1390 patients were included. No change in PANSS was observed following oral fish-oil intake [weighted mean difference (WMD): -0.87; 95% CI: -16.99, 15.26; P = 0.92]. In a nonlinear dose-response analysis, a significant inverse association was observed between <10 wk of fish-oil supplementation and PANSS (WMD: -10; P-nonlinearity = 0.02). Although analysis of 4 studies showed a nonsignificant reduction in BPRS after fish-oil intake (WMD: -2.990; 95% CI: -6.42, 0.44; P = 0.08), a nonlinear dose-response analysis revealed significant inverse associations between dose (>2200 mg/d) and duration of fish-oil supplementation (<15 wk) with BPRS score (WMD: -8; P-nonlinearity = 0.04). Combined effect sizes from 6 randomized clinical trials showed significant increases in GAF after oral administration of fish oil (WMD: 6.66; 95% CI: 3.39, 9.93; P < 0.001). In conclusion, we did not find any significant changes in PANSS and BPRS scores following fish-oil supplementation. Nevertheless, oral fish-oil intake significantly contributed to improvement in GAF scores. This is the first meta-analysis to examine the effects of fish oil on the psychological functioning scores of PANSS, BPRS, and GAF simultaneously.

Inflammatory phenomena such as hyperinflammation or hemophagocytic lymphohistiocytosis are a frequent yet paradoxical accompaniment to virus susceptibility in patients with impairment of type I interferon (IFN-I) signaling caused by deficiency of signal transducer and activator of transcription 2 (STAT2) or IFN regulatory factor 9 (IRF9).
We hypothesized that altered and/or prolonged IFN-I signaling contributes to inflammatory complications in these patients.
We explored the signaling kinetics and residual transcriptional responses of IFN-stimulated primary cells from individuals with complete loss of one of STAT1, STAT2, or IRF9 as well as gene-edited induced pluripotent stem cell-derived macrophages.
Deficiency of any IFN-stimulated gene factor 3 component suppressed but did not abrogate IFN-I receptor signaling, which was abnormally prolonged, in keeping with insufficient induction of negative regulators such as ubiquitin-specific peptidase 18 (USP18). In cells lacking either STAT2 or IRF9, this late transcriptional response to IFN-α2b mimicked the effect of IFN-γ.
Our data suggest a model wherein the failure of negative feedback of IFN-I signaling in STAT2 and IRF9 deficiency leads to immune dysregulation. Aberrant IFN-α receptor signaling in STAT2- and IRF9-deficient cells switches the transcriptional output to a prolonged, IFN-γ-like response and likely contributes to clinically overt inflammation in these individuals.

BACKGROUND: Phytochromes are the best characterized photoreceptors that perceive Red (R)/Far-Red (FR) signals and mediate key developmental responses in plants. It is well established that photoperiodic control of flowering is regulated by PHY A (phytochrome A) gene. So far, the members of PHY A gene family remains unexplored in Lablab purpureus, and therefore, their functions are still not deciphered. PHYA3 is the homologue of phytochrome A and known to be involved in dominant suppression of flowering under long day conditions by downregulating florigens in Glycine max. The present study is the first effort to identify and characterize any photoreceptor gene (PHYA3, in this study) in Lablab purpureus and decipher its phylogeny with related legumes.
RESULTS: PHYA3 was amplified in Lablab purpureus cv GNIB-21 (photo-insensitive and determinate) by utilizing primers designed from GmPHYA3 locus of Glycine max. This study was successful in partially characterizing PHYA3 in Lablab purpureus (LprPHYA3) which is 2 kb longer and belongs to exon 1 region of PHYA3 gene. Phylogenetic analysis of the nucleotide and protein sequences of PHYA genes through MEGA X delineated the conservation and evolution of Lablab purpureus PHYA3 (LprPHYA3) probably from PHYA genes of Vigna unguiculata, Glycine max and Vigna angularis. A conserved basic helix-loop-helix motif bHLH69 was predicted having DNA binding property. Domain analysis of GmPHYA protein and predicted partial protein sequence corresponding to exon-1 of LprPHYA3 revealed the presence of conserved domains (GAF and PAS domains) in Lablab purpureus similar to Glycine max.
CONCLUSIONS: Partial characterization of LprPHYA3 would facilitate the identification of complete gene in Lablab purpureus utilizing sequence information from phylogenetically related species of Fabaceae. This would allow screening of allelic variants for LprPHYA3 locus and their role in photoperiod responsive flowering. The present study could aid in modulating photoperiod responsive flowering in Lablab purpureus and other related legumes in near future through genome editing.