Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbial biomass, composition, and functions are responsible for the differential removal of trace organic chemicals in biofiltration systems

Biofiltration processes help to remove trace organic chemicals (TOrCs) both in wastewater and drinking water treatment systems. However, the detailed TOrCs biotransformation mechanisms as well as the underlying drivers behind the variability of site specific transformation processes remain elusive. In this study, we used laboratory batch incubations to investigate the biotransformation of 51 TOrCs in eight bioactive filter materials of different origins treating a range of waters, from wastewater effluents to drinking water. Microscopy, 16S rRNA amplicon and whole metagenome sequencing for assessing associations between the biotransformation rate constants, microbial composition and genetic potential complemented chemical analysis. We observed strong differences in the mean global removal of TOrCs between the individual sand filters (−1.4% to 58%), which were mirrored in overall biomass, microbial community composition, and enzyme encoding genes. From the six investigated biomass markers, ATP turned out to be a major predictor of the mean global biotransformation rate, while compound specific biotransformations were correlated with the microbial community composition. High biomass ecosystems were indicated in our systems by a dominance of Nitrospirae, but individual TOrC biotransformation was statistically connected to rare taxa (< 2%) such as Hydrogenophaga, or indiviudal enzymes such as the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase gene. In general, this study provides new insights into so far rarely addressed variability of TOrCs biotransformation. We propose novel biological indicators for the removal performance of TOrCs in biofiltration systems, highlighting the role of ATP in predicting and normalizing the global transformation, and the role of the microbial community for the individual transformation of TOrCs in engineered and natural systems. One sentence summary The variability of global micropollutant transformation performance of biofiltration media taken from different sites is foremost explained by microbial biomass as ATP, however, residual variation of single comound removal rates is correlated with the biofilter’s microbiome.
Evaluation of the Biodistribution of Mesenchymal Stem Cells in a Pre-clinical Renal Tuberculosis Model by Non-linear Magnetic Response Measurements

Bone-marrow derived mesenchymal stem cells (MSCs) exert anti-tuberculosis effects due to their potential to repair damaged tissues and modulate inflammatory immune responses. MSCs were reported to be recruited to the Mycobacterium tuberculosis (Mtb) affected sites in the organism. However, due to limitations of presently applied in vivo imaging techniques the trafficking and biodistribution of MSCs in Mtb-infected organisms is not possible. In the current study MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) as a negative MR contrast agent for imaging the biodistribution of MSCs in vivo. Trafficking of SPIONs-labeled MSCs was analyzed in a preclinical model of renal tuberculosis in male Chinchilla rabbits (n = 18) following intravenous administration on the days 0, 2, 3, and 7 employing a highly sensitive method of non-linear longitudinal magnetic response (NLR-M2) measurements. Within 48 h after injection, nanoparticle-labeled MSCs accumulated predominantly in lung, spleen, liver tissues, and paratracheal lymph nodes with subsequent decrease over the observation period of 7 days. The recruitment of MSCs to Mtb-affected organs was further proven by immunohistological analysis. NLR-M2 allowed the detection of SPIONs-labeled cells at low concentrations in different organs and tissues giving insights of in vivo mesenchymal stem cells trafficking in organism after TB infection.
Unperturbed dormancy recording reveals stochastic awakening strategies in endocrine treated breast cancer cells

Hormone dependent breast cancer (HDBC) is the most commonly diagnosed tumor type in women. Adjuvant endocrine therapies (ET) have been the cornerstone in the clinical management of HDBC patients for over forty years. A vast proportion of HDBC patients incur long periods of clinical dormancy following ET, with tumour awakening appearing at a steady pace for up to 25 years (Pan et al., 2017). Extensive genomic studies have demonstrated that 15-30% of clinical relapses develop recurrent genomic changes which contribute to drug resistance (i.e. ESR1 activating mutations) (Bertucci et al., 2019; Magnani et al., 2017; Razavi et al., 2018). However, even in these cases, there is no conclusive evidence around the pre-existence vs. de novo nature of these events. We previously showed that ETs can trigger and select for dormancy in subpopulations of breast cancer(Hong et al., 2019). In this work we took two novel approaches to investigate the dormancy and awakening roadmap of HDBC cells in unprecedented detail. Firstly, we leveraged a rare cohort of n=5 patients which were treated with primary adjuvant ETs in the absence of surgery (TRACING-HT) to dissect the contribution of genomic aberrations to tumor awakening. Next, we developed a first of its kind evolutionary study in vitro to systematically annotate cancer cells adaptive strategies at single cell level in unperturbed systems during a period of several months (TRADITIOM). Collectively our data suggest that ETs steer HDBC cells into an inherently unstable dormant state. Over time, routes to awakening emerge sporadically and spontaneously in single lineages. Each dormant cell retains an intrinsic awakening probability which we propose is a function of epigenetic decay. Awakening occurs without an external trigger and involves multiple apparent endpoint phenotypes that cannot be fully explained by conventional Darwinian genetic selection processes. Finally, our data show that common genetic hits associated with resistance happen downstream of awakening. Overall, our data have uncovered previously unsuspected roles for stochastic nongenetic events during dormancy with profound clinical implications.
Mouse Retinal Organoid Growth and Maintenance in Longer-Term Culture

Using retinal organoid systems, organ-like 3D tissues, relies implicitly on their robustness. However, essential key parameters, particularly retinal growth and longer-term culture, are still insufficiently defined. Here, we hypothesize that a previously optimized protocol for high yield of evenly-sized mouse retinal organoids with low variability facilitates assessment of such parameters. We demonstrate that these organoids reliably complete retinogenesis, and can be maintained at least up to 60 days in culture. During this time, the organoids continue to mature on a molecular and (ultra)structural level: They develop photoreceptor outer segments and synapses, transiently maintain its cell composition for about 5–10 days after completing retinogenesis, and subsequently develop pathologic changes – mainly of the inner but also outer retina and reactive gliosis. To test whether this organoid system provides experimental access to the retina during and upon completion of development, we defined and stimulated organoid growth by activating sonic hedgehog signaling, which in patients and mice in vivo with a congenital defect leads to enlarged eyes. Here, a sonic hedgehog signaling activator increased retinal epithelia length in the organoid system when applied during but not after completion of development. This experimentally supports organoid maturation, stability, and experimental reproducibility in this organoid system, and provides a potential enlarged retina pathology model, as well as a protocol for producing larger organoids. Together, our study advances the understanding of retinal growth, maturation, and maintenance, and further optimizes the organoid system for future utilization.
Correlations Between Cognitive Functions and Clinical Symptoms in Adolescents With Complex Post-traumatic Stress Disorder

Introduction: Complex post-traumatic stress disorder (C-PTSD) is characterized by the typical symptoms of PTSD, in addition to affective dysregulation, negative self-concept, and disturbances in interpersonal relationships. Children and adolescents with C-PTSD have been reported to have deficits in emotional and cognitive functions. We hypothesized that the following are associated with the severity of C-PTSD symptoms: (1) adolescents with C-PTSD who show deficits in emotional perception and cognitive functions, including executive function and attention; and (2) deficits in neurocognitive functions. Methods: Information on 69 adolescents with PTSD, aged 10–19 years, was gathered from seven shelters. All participants were assessed using complete clinical scales, including the C-PTSD Interview and Depression, Anxiety, and Stress Scales, and neurocognitive function tests, including the emotional perception, mental rotation, and modified Tower of London tests. Results: Adolescents with C-PTSD were more likely to have a history of sexual assault, dissociation, and self-harm than those with PTSD. The total and subscale scores of the C-PTSD Interview Scale in adolescents with C-PTSD were higher than that in adolescents with PTSD. In addition, neurocognitive functions, including emotional perception, attention, and working memory, were correlated with the severity of C-PTSD symptoms. Discussion: Adolescents with C-PTSD experienced more serious clinical symptoms and showed more deficits in neurocognitive functions than adolescents with PTSD. Clinicians should pay careful attention toward the emotional and neurocognitive functions when assessing and treating patients with C-PTSD.
Brain‐wide inferiority and equivalence tests in fMRI group analyses: Selected applications

Null hypothesis significance testing is the major statistical procedure in the field of fMRI, but provides only a rather limited picture of the effects in a data set. When sample size and power is low relying only on strict significance testing may lead to a host of false negative findings. In contrast, with very large data sets virtually every voxel might become significant. It is thus desirable to complement significance testing with procedures like inferiority and equivalence tests that allow to formally compare effect sizes within and between data sets and offer novel approaches to obtain insight into fMRI data. The major component of these tests are estimates of standardized effect sizes and their confidence intervals. Here we show how Hedge’s g, the bias corrected version of Cohen’s d, and its confidence interval can be obtained from SPM t maps. We then demonstrate how these values can be used to evaluate whether non-significant effects are really statistically smaller than significant effects to obtain “regions of undecidability” within a data set, and to test for the replicability and lateralization of effects. This method allows the analysis of fMRI data beyond point estimates enabling researchers to take measurement uncertainty into account when interpreting their findings.
TRPM4 Expression During Postnatal Developmental of Mouse CA1 Pyramidal Neurons

TRPM4 is a non-selective cation channel activated by intracellular calcium and permeable to monovalent cations. This channel participates in the control of neuronal firing, neuronal plasticity, and neuronal death. TRPM4 depolarizes dendritic spines and is critical for the induction of NMDA receptor-dependent long-term potentiation in CA1 pyramidal neurons. Despite its functional importance, no subcellular localization or expression during postnatal development has been described in this area. To examine the localization and expression of TRPM4, we performed duplex immunofluorescence and patch-clamp in brain slices at different postnatal ages in C57BL/6J mice. At P0 we found TRPM4 is expressed with a somatic pattern. At P7, P14, and P35, TRPM4 expression extended from the soma to the apical dendrites but was excluded from the axon initial segment. Patch-clamp recordings showed a TRPM4-like current active at the resting membrane potential from P0, which increased throughout the postnatal development. This current was dependent on intracellular Ca2+ (ICAN) and sensitive to 9-phenanthrol (9-Ph). Inhibiting TRPM4 with 9-Ph hyperpolarized the membrane potential at P14 and P35, with no effect in earlier stages. Together, these results show that TRPM4 is expressed in CA1 pyramidal neurons in the soma and apical dendrites and associated with a TRPM4-like current, which depolarizes the neurons. The expression, localization, and function of TRPM4 throughout postnatal development in the CA1 hippocampal may underlie an important mechanism of control of membrane potential and action potential firing during critical periods of neuronal development, particularly during the establishment of circuits.
Multiple morphogens and rapid elongation promote segmental patterning during development

The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately-sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development. Author Summary In segmental pattern formation, chemical gradients control gene expression in a concentration-dependent manner to specify distinct gene expression domains. Despite the stochasticity inherent to such biological processes, precise and accurate borders form between segmental gene expression domains. Previous work has revealed synergy between gene regulation and cell sorting in sharpening borders that are initially rough. However, it is still poorly understood how size and boundary sharpness of multiple segments are regulated in a tissue that changes dramatically in its morphology as the embryo develops. Here we develop a stochastic multiscale cell-base model to investigate these questions. Two novel strategies synergize to promote accurate segment formation, a combination of long- and short-range morphogens plus rapid tissue convergence, with one responsible for pattern initiation and the other enabling pattern refinement.
Mechanisms Underlying Pneumococcal Transmission and Factors Influencing Host-Pneumococcus Interaction: A Review

Streptococcus pneumoniae (also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and meningitis. The mechanism of pneumococcal infection has been extensively studied, but the process of transmission has not been fully elucidated because of the lack of tractable animal models. Novel animal models of transmission have enabled further progress in investigating pneumococcal transmission mechanisms including the processes such as pneumococcal shedding, survival in the external environment, and adherence to the nasopharynx of a new host. Herein, we present a review on these animal models, recent research findings about pneumococcal transmission, and factors influencing the host-pneumococcus interaction.
Segment number threshold determines juvenile onset of germline cluster proliferation in Platynereis dumerilii

Many animals rely on sexual reproduction to propagate by using gametes (oocytes and sperm). Development of sexual characters and generation of gametes are tightly coupled with the growth of an organism. Platynereis dumerilii is a marine segmented worm which has been used to study germline development and gametogenesis. Platynereis has 4 Primordial Germ Cells (PGCs) that arise early in development and these cells are thought to give rise to germ cell clusters found across the body in the juvenile worms. The germ cell clusters eventually form the gametes. The stages of germline development and how the 4 PGCs become the numerous germ cell clusters are not well-documented in the juvenile stages. Platynereis, like other segmented worms, grows by adding new segments at its posterior end. The number of segments generally reflect the growth state of the worms and therefore is a useful and easily measurable growth state metric. To understand how growth correlates with development and gametogenesis, we investigated germline development across several developmental stages using germline/multipotency markers. We found that segment number predicted the state of germline development and the abundance of germline clusters. Additionally, we found that keeping worms short in segment number via changing external conditions or via amputations supported segment number threshold requirement for germline development. Finally, we asked if these clusters in Platynereis play a role in regeneration (as similar free-roaming cells are observed in Hydra and planarian regeneration) and found that the clusters were not required for regeneration in Platynereis, suggesting a strictly germline nature. Overall, these molecular analyses suggest a previously unidentified developmental transition dependent on the growth state in juvenile Platynereis when germline proliferation is substantially increased.
Eukaryotic ribosome recognizes 3′ context and stimulates stop codon readthrough

It is known that the nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. In eukaryotes, various 3′ contexts have been described that are unfavourable for translation termination; however, the exact molecular mechanism that mediates their effect remains unknown. In this study, we used a reconstituted mammalian translation system to examine the efficiency of stop codons in different contexts, including several previously described weak 3′ stop codon contexts. Our results revealed that ribosomes can independently recognize certain contexts and ignore stop codons that are followed by these sequences. Moreover, the efficiency of translation termination at the weak 3′ contexts was almost equal to the one at the standard context. We propose that weak 3′ contexts interact with the 18S rRNA provoking a conformational change in the U-turn-like structure of the stop codon in the A site of ribosome. This change makes incorporation of the near-cognate tRNA more preferable than recognition of the stop codon by the release factors and increases readthrough.
The Protective Role of Maternal Immunization in Early Life

With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called “immunology blunting,” i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.
Mesoporous silica particles functionalized with newly extracted fish oil (Omeg@Silica) inhibit lung cancer cell growth

Omeg@Silica microparticles consisting of whole fish oil rich in omega-3 lipids, vitamin D3 and zeaxanthin extracted with biobased limonene from anchovy fillet leftovers (AnchoisOil) encapsulated within mesoporous silica particles are highly effective in modulating oxidative stress, mitochondrial damage or in promoting antitumor effects in lung cancer cells. A panel of three different human non-small cell lung cancer (NSCLC) cell lines (A549, Colo 699 and SKMES) was used. Cancer cells were treated with AnchoisOil dispersed in ethanol (10 and 15 μg/ml) or encapsulated in silica, and cell cycle, reactive oxigen species (ROS) and mitochondrial stress (MitoSOX) assessed by flow cytometry. The effects on long-term proliferation (clonogenic assay) were also evaluated. The sub-micron Omeg@Silica microparticles were more effective than fish oil alone in increasing ROS and mitocondrial damage, in altering cell cycle as well as in reducing colony formation ability in the tested lung cancer cell lines. These results suggest that Omeg@Silica mesoporous silica functionalized with whole fish oil has antitumor effects in NSCLC cell lines and support its investigation in lung cancer therapy.
The genetic basis of structural colour variation in mimetic Heliconius butterflies

Structural colours, produced by the reflection of light from ultrastructures, have evolved multiple times in butterflies. Unlike pigmentary colours and patterns, little is known about the genetic basis of these colours. Reflective structures on wing-scale ridges are responsible for iridescent structural colour in many butterflies, including the Müllerian mimics Heliconius erato and Heliconius melpomene. Here we quantify aspects of scale ultrastructure variation and colour in crosses between iridescent and non-iridescent subspecies of both of these species and perform quantitative trait locus (QTL) mapping. We show that iridescent structural colour has a complex genetic basis in both species, with offspring from crosses having wide variation in blue colour (both hue and brightness) and scale structure measurements. We detect two different genomic regions in each species that explain modest amounts of this variation, with a sex-linked QTL in H. erato but not H. melpomene. We also find differences between species in the relationships between structure and colour, overall suggesting that these species have followed different evolutionary trajectories in their evolution of structural colour. We then identify genes within the QTL intervals that are differentially expressed between subspecies and/or wing regions, revealing likely candidates for genes controlling structural colour formation.