Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription promotes the restoration of chromatin following DNA replication

DNA replication results in the transient eviction of nucleosomes, RNAPII and transcription regulators. How chromatin organization is duplicated on the two daughter strands is a central question in epigenetics. In mammals, transcription restarts on newly replicated DNA within a couple of hours, promoting chromatin accessibility. However, the role of transcription in the restoration of other chromatin determinants following DNA replication remains unclear. Here we have monitored protein re-association to newly replicated DNA upon inhibition of transcription using iPOND coupled to quantitative mass spectrometry. We show that nucleosome assembly and the re-establishment of most histone modifications are uncoupled from transcription restart. However, upon transcription inhibition, the re-association of many proteins was altered, including ATP-dependent remodellers, transcription regulators, the histone variant H2A.Z, histone modifiers as well as the restoration of H3.3K36me2. Finally, transcription also provoked the recruitment of several DNA repair proteins, revealing that transcription promotes chromatin reestablishment post-replication but is also a potential source of genotoxic stress.
Dysregulation of GABAergic System in the Hippocampus and Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy

Epilepsy is tightly associated with dysfunction of inhibitory γ-aminobutyric acid (GABA) neurotransmission. In this study, Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5-2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) and the hippocampus of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl− cotransporter 1 (NKCC1) expression was increased, while in adults K+/Cl− cotransporter 2 (KCC2) was downregulated indicating impairment of postsynaptic GABA action both at early and later stages of postnatal development. In the hippocampus of young KM rats, we observed a decrease in activity of GABAergic neurons and downregulation of KCC2 and NKCC1. Adult rats, in opposite, demonstrated elevated activity of the hippocampal GABAergic cells and unchanged expression of chlorine transporters indicating upregulation of GABA transmission. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats, while in the hippocampus, upregulation of GABAergic system can restrict the spreading of epileptiform activity from the brainstem.
Validation of polymorphic Gompertzian model of cancer through in vitro and in vivo data

Mathematical modeling plays an important role in our understanding and targeting therapy resistance mechanisms in cancer. The polymorphic Gompertzian model, analyzed theoretically by Viossat and Noble, describes a heterogeneous cancer population consisting of therapy sensitive and resistant cells. This theoretically promising model has not previously been validated with real-world data. In this study, we provide this validation. We demonstrate that the polymorphic Gompertzian model successfully captures trends in both in vitro and in vivo data on non-small cell lung cancer (NSCLC) dynamics under treatment. Additionally, for the in vivo data of tumor dynamics in patients undergoing treatment, we compare the polymorphic Gompertzian model to the classical oncologic models, which were previously identified as the models that fit this data best. We show that the polymorphic Gompertzian model can successfully capture the U-shape trend in tumor size during cancer relapse, which can not be fitted with the classical oncologic models. In general, the polymorphic Gompertzian model corresponds well to both in vitro and in vivo real-world data, suggesting it as a candidate for improving the efficacy of cancer therapy, for example through evolutionary/adaptive therapies.
DECODING COMPLEXITY IN BIOMOLECULAR RECOGNITION OF DNA I-MOTIFS

DNA i-motifs (iMs) are non-canonical C-rich secondary structures implicated in numerous cellular processes. Though iMs exist throughout the genome, our understanding of iM recognition by proteins or small molecules is limited to a few examples. We designed a DNA microarray containing 10,976 genomic iM sequences to examine the binding profiles of four iM-binding proteins, mitoxantrone, and the iMab antibody. iMab microarray screens demonstrated that pH 6.5, 5% BSA buffer was optimal, and fluorescence was correlated with iM C-tract length. hnRNP K broadly recognizes diverse iM sequences, favoring 3-5 cytosine repeats flanked by thymine-rich loops of 1-3 nucleotides. Array binding mirrored public ChIP-Seq datasets, in which 35% of well-bound array iMs are enriched in hnRNP K peaks. In contrast, other reported iM-binding proteins had weaker binding or preferred G-quadruplex (G4) sequences instead. Mitoxantrone broadly binds both shorter iMs and G4s, consistent with an intercalation mechanism. These results suggest that hnRNP K may play a role in iM-mediated regulation of gene expression in vivo, whereas hnRNP A1 and ASF/SF2 are possibly more selective in their binding preferences. This powerful approach represents the most comprehensive investigation of how biomolecules selectively recognize genomic iMs to date.
AI becomes a masterbrain scientist

Recent rapid and unexpected advancements in Artificial Intelligence (AI) have dramatically shocked the world. Large language models, such as ChatGPT and GPT-4, have demonstrated remarkable potential in aggregating and organizing knowledge while providing insights and solutions to specific questions. In this study, we further explore the possibility of GPT-4 taking on a central role in a complete closed-loop biological research, functioning as a masterbrain scientist responsible for generating hypotheses, designing experiments, analyzing results, and drawing conclusions. Our findings suggest that AI has the potential to evolve into a genuine scientist, and could lead an unprecedented revolution in the area of science.
Nucleus accumbens neurons dynamically encode positive and aversive associative learning

To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in Pavlovian associations, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks. Sucrose was used as a positive unconditioned stimulus (US) and foot shock was used as a negative US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general decrease in activity in response to CS and to US across learning, with dynamic, and partially overlapping, activity responses to CS and US. During the aversive Pavlovian conditioning, D1- and D2-neurons showed an increase in the activity in response to the CS and to the US (shock). Our data supports a synchronous role for D1- and D2-neurons in appetitive and aversion processing.
The Promise and Pitfalls of Prophages

Phages dominate every ecosystem on the planet. While virulent phages sculpt the microbiome by killing their bacterial hosts, temperate phages provide unique growth advantages to their hosts through lysogenic conversion. Many prophages benefit their host, and prophages are responsible for genotypic and phenotypic differences that separate individual microbial strains. However, the microbes also endure a cost to maintain those phages: additional DNA to replicate and proteins to transcribe and translate. We have never quantified those benefits and costs. Here, we analysed over two and a half million prophages from over half a million bacterial genome assemblies. Analysis of the whole dataset and a representative subset of taxonomically diverse bacterial genomes demonstrated that the normalised prophage density was uniform across all bacterial genomes above 2 Mbp. We identified a constant carrying capacity of phage DNA per bacterial DNA. We estimated that each prophage provides cellular services equivalent to approximately 2.4 % of the cell’s energy or 0.9 ATP per bp per hour. We demonstrate analytical, taxonomic, geographic, and temporal disparities in identifying prophages in bacterial genomes that provide novel targets for identifying new phages. We anticipate that the benefits bacteria accrue from the presence of prophages balance the energetics involved in supporting prophages. Furthermore, our data will provide a new framework for identifying phages in environmental datasets, diverse bacterial phyla, and from different locations.
Analysis of the correlation between BMI and respiratory tract microbiota in acute exacerbation of COPD

Objective To investigate the distribution differences in the respiratory tract microbiota of AECOPD patients in different BMI groups and explore its guiding value for treatment. Methods Sputum samples of thirty-eight AECOPD patients were collected. The patients were divided into low, normal and high BMI group. The sputum microbiota was sequenced by 16S rRNA detection technology, and the distribution of sputum microbiota was compared. Rarefaction curve, α-diversity, principal coordinate analysis (PCoA) and measurement of sputum microbiota abundance in each group were performed and analyzed by bioinformatics methods. Results 1. The rarefaction curve in each BMI group reached a plateau. No significant differences were observed in the OTU total number or α-diversity index of microbiota in each group. PCoA showed significant differences in the distance matrix of sputum microbiota between the three groups, which was calculated by the Binary Jaccard and the Bray Curtis algorithm. 2. At the phylum level, most of the microbiota were Proteobacteria, Bacteroidetes Firmicutes, Actinobacteria, and Fusobacteria. At the genus level, most were Streptococcus, Prevotella, Haemophilus, Neisseria and Bacteroides. 3. At the phylum level, the abundance of Proteobacteria in the low group was significantly higher than that in normal and high BMI groups, the abundances of Firmicutes in the low and normal groups were significantly lower than that in high BMI groups. At the genus level, the abundance of Haemophilus in the low group was significantly higher than that in high BMI group, and the abundances of Streptococcus in the low and normal BMI groups were significantly lower than that in the high BMI group. Conclusions 1. The sputum microbiota of AECOPD patients in different BMI groups covered almost all microbiota, and BMI had no significant association with total number of respiratory tract microbiota or α-diversity in AECOPD patients. However, there was a significant difference in the PCoA between different BMI groups. 2. The microbiota structure of AECOPD patients differed in different BMI groups. Gram-negative bacteria (G-) in the respiratory tract of patients predominated in the low BMI group, while gram-positive bacteria (G+) predominated in the high BMI group.
Magnetic-field dependence of Brownian and Néel relaxation times

The investigation of the rotational dynamics of magnetic nanoparticles in magnetic fields is of academic interest but also important for applications such as magnetic particle imaging where the particles are exposed to magnetic fields with amplitudes of up to 25 mT. We have experimentally studied the dependence of Brownian and Neel relaxation times on ac and dc magnetic field amplitude using ac susceptibility measurements in the frequency range between 2 Hz and 9 kHz for field amplitudes up to 9 mT. As samples, single-core iron oxide nanoparticles with core diameters between 20 nm and 30 nm were used either suspended in water-glycerol mixtures or immobilized by freeze-drying. The experimentally determined relaxation times are compared with theoretical models. It was found that the Neel relaxation time decays much faster with increasing field amplitude than the Brownian one. Whereas the dependence of the Brownian relaxation time on the ac and dc field amplitude can be well explained with existing theoretic.
A versatile workflow for linear modelling in R

Linear models are applied widely to analyse empirical data. Modern software allows implementation of linear models with a few clicks or lines of code. While convenient, this increases the risk of ignoring essential assessment steps. Indeed, inappropriate application of linear models is an important source of inaccurate statistical inference. Despite extensive guidance and detailed demonstration of exemplary analyses, many users struggle to implement and assess their own models. To fill this gap, we present a versatile R-workflow template that facilitates (Generalized) Linear (Mixed) Model analyses. The script guides users from data exploration through model formulation, assessment and refinement to the graphical and numerical presentation of results. The workflow accommodates a variety of data types, distribution families, and dependency structures that arise from hierarchical sampling. To apply the routine, minimal coding skills are required for data preparation, naming of variables of interest, linear model formulation, and settings for summary graphs. Beyond that, default functions are provided for visual data exploration and model assessment. Focused on graphs, model assessment offers qualitative feedback and guidance on model refinement, pointing to more detailed or advanced literature where appropriate. With this workflow, we hope to contribute to research transparency, comparability, and reproducibility.
Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive–compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial

Background Psilocybin may help treat obsessive–compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin’s effects on OCD have also not been studied. Objectives This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin’s effects on OCD. Design We use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms. Methods and analysis We are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive–Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg. Ethics statement All participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483). Discussion This study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.
Features of gut microbiota and short-chain fatty acids in patients with first-episode depression and their relationship with the clinical symptoms

Objective To compare the differences in gut microbiota and short-chain fatty acids (SCFAs; metabolites of gut microbiota) in the serum of patients with first-episode depression and the healthy population and to analyze the relationship between gut microbiota and metabolite SCFAs and the clinical symptoms of major depressive disorder (MDD). Methods A total of 45 patients with first-episode depression and 22 healthy volunteers were chosen to complete relevant scale evaluations, and feces samples and venous blood samples were collected. The 16S RNA method was used to analyze the intestinal microflora and the characteristics of serum SCFAs detection by ELISA kit, as well as the intestinal flora, SCFAs content and their correlation with MDD clinical indicators. Results The abundance of Akkermansia, Megamonas, Prevotellaceae NK3B31 group, and butyrate-producing bacteria, Lachnospira, Subdoligranulum, Blautia, and Dialister, and acetate-producing bacteria, Streptococcus, in the gut microbiota of the MDD group was lower than that in the control (C) group. The abundance of Parasutterella in the MDD group was higher than that in the C group. Dialister negatively correlated with all measured clinical symptoms (r < 0, P < 0.05). The serum SCFA content in the MDD group was higher than that in the C group, and the content positively correlated with the Hamilton anxiety scale scores (r = 0.584, P < 0.05). Conclusion The results demonstrated that the MDD group differed from the C group in terms of gut microbiota and SCFAs in the serum and that the change in certain intestinal bacteria might participate in the pathogenic mechanism of MDD.
Supplementation with inulin-type fructans affects gut microbiota and attenuates some of the cardiometabolic benefits of a plant-based diet in individuals with overweight or obesity

Background The gut microbiota has emerged as a potential therapeutic target to improve the management of obesity and its comorbidities. Objective We investigated the impact of a high fiber (∼38 g/d) plant-based diet, consumed ad libitum, with or without added inulin-type fructans (ITF), on the gut microbiota composition and cardiometabolic outcomes in subjects with obesity. We also tested if baseline Prevotella/Bacteroides (P/B) ratio predicts weight loss outcomes. Methods This is a secondary exploratory analysis from the PREVENTOMICS study, in which 100 subjects (82 completers) aged 18–65 years with body mass index 27–40 kg/m2 were randomized to 10 weeks of double-blinded treatment with a personalized or a generic plant-based diet. Changes from baseline to end-of-trial in gut microbiota composition (16S rRNA gene amplicon sequencing), body composition, cardiometabolic health and inflammatory markers were evaluated in the whole cohort (n = 82), and also compared in the subgroup of subjects who were supplemented with an additional 20 g/d ITF-prebiotics (n = 21) or their controls (n = 22). Results In response to the plant-based diet, all subjects lost weight (−3.2 [95% CI –3.9, −2.5] kg) and experienced significant improvements in body composition and cardiometabolic health indices. Addition of ITF to the plant-based diet reduced microbial diversity (Shannon index) and selectively increased Bifidobacterium and Faecalibacterium (q < 0.05). The change in the latter was significantly associated with higher values of insulin and HOMA-IR and lower HDL cholesterol. In addition, the LDL:HDL ratio and the concentrations of IL-10, MCP-1 and TNFα were significantly elevated in the ITF-subgroup. There was no relationship between baseline P/B ratio and changes in body weight (r = −0.07, p = 0.53). Conclusion A plant-based diet consumed ad libitum modestly decreases body weight and has multiple health benefits in individuals with obesity. Addition of ITF-prebiotics on top this naturally fiber-rich background selectively changes gut microbiota composition and attenuates some of the realized cardiometabolic benefits. Clinical trial registration [https://clinicaltrials.gov/ct2/show/NCT04590989], identifier [NCT04590989].
A community outbreak of Legionnaires’ disease caused by outdoor hot tubs for private use in a hotel

During the period October–November 2017, an outbreak of Legionnaires’ disease involving 27 cases occurred in the tourist area of Palmanova (Mallorca, Spain). The majority of cases were reported by the European Centre of Disease Prevention and Control (ECDC) as travel associated cases of Legionnaires’ disease (TALD). Most cases belonged to different hotel cluster alerts. No cases were reported among the local population residing in the area. All tourist establishments associated with one or more TALD cases were inspected and sampled by public health inspectors. All relevant sources of aerosol emission detected were investigated and sampled. The absence of active cooling towers in the affected area was verified, by documents and on-site. Samples from hot tubs for private use located on the terraces of the penthouse rooms of a hotel in the area were included in the study. Extremely high concentrations (> 106 CFU/l) of Legionella pneumophila, including the outbreak strain, were found in the hot tubs of vacant rooms of this hotel thus identifying the probable source of infection. Meteorological situation may have contributed to the geographical distribution pattern of this outbreak. In conclusion, hot tubs for private use located outdoors should be considered when investigating community outbreaks of Legionnaires’ disease of unclear origin.
Editorial: Challenges to EEG/MEG graph analysis and how to face them

COPYRIGHT © 2023 Blinowska, Baccala, Kaminski and Sameshima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Challenges to EEG/MEG graph analysis and how to face them