Miracle-dz/UniFAR-FTUs huggingface dataset:
SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks progress slowly in cells depleted for SAF-A, also contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed that the boundaries between early- and late-replicating domains are blurred in cells depleted for SAF-A. Associated with these defects, SAF-A-depleted cells show elevated γH2A phosphorylation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.
High diversity and heterogeneity define microbial communities across an active municipal landfill

Global waste production is increasing rapidly, with the majority of waste destined for landfills. Microbial communities in landfills transform waste and generate methane in an environment unique from other built and natural environments. Previous work has largely considered landfill microbial diversity only at the phylum level, identifying complex and variable communities. The extent of shared organismal diversity across landfills or over time and at more precise levels of classification remains unknown. We used 16S rRNA gene amplicon and metagenomic sequencing to examine the taxonomic and functional diversity of the microbial communities inhabiting a Southern Ontario landfill. The diversity of microbial populations in leachate and groundwater samples was correlated with geochemical conditions to determine drivers of microbial heterogeneity. Across the landfill, 25 bacterial and archaeal phyla were present at >1% relative abundance within at least one landfill sample. The Patescibacteria, Bacteroidota, Firmicutes, and Proteobacteria had the highest relative abundances, with most other phyla present at low (<5%) abundance. Below the phylum level, very few populations were identified at multiple sites, with only 121 of 8,030 populations present at five or more sites. This indicates that, although phylum-level signatures are conserved, individual landfill microbial populations vary widely. Significant differences in geochemistry occurred across the leachate and groundwater wells sampled, with calcium, iron, magnesium, boron, meta and para xylenes, ortho xylenes, and ethylbenzene concentrations contributing most strongly to observed site differences. This study illustrates that leachate microbial communities are much more complex and diverse within landfills than previously reported, with implications for waste management best practices.
Concentrations of essential and nonessential elements in shoots and storage roots of carrot grown in NaCl and Na2SO4 salinity

This study was undertaken to examine the effects of NaCl and Na2SO4 salinity on the growth of carrot (Daucus carota L.) and the concentrations of essential and nonessential elements in the shoots and storage roots determined by polarized energy dispersive x-ray fluorescence (PEDXRF). Both types of salinity reduced plant growth, but growth reduction in NaCl salinity was more pronounced. Na concentrations in shoots and roots were increased by salinity treatment. The concentration of Cl was also increased by NaCl salinity. Salinity treatments decreased K concentrations in the shoots and storage roots, and Ca concentrations in the shoots. Concentration of P in shoots and roots, and S, Mg, and Si in roots were not significantly affected by salinity treatments, while the NaCl salinity reduced S and Si and increased Mg concentrations in the shoots. Fe, Zn, Mn and Mo concentrations in the shoots were not significantly affected by salinity treatments. In the storage roots, the concentration of Fe was significantly increased by NaCl salinity, while Na2SO4 salinity significantly increased Zn and Mn concentrations in storage roots. Concentration of Al in the storage roots was significantly higher with NaCl treatment than with Na2SO4 treatment. Ni concentrations in the shoots were strongly increased by NaCl salinity, while concentrations of Br in the shoots and storage roots were significantly reduced by NaCl salinity. Rb concentrations in shoots and storage roots were significantly reduced by Na2SO4 salinity, but not by NaCl salinity. Concentration of Cs in the shoots was increased by both types of salinity, but Cs concentration of the roots was increased by Na2SO4. Concentration of Ba in the shoots was lowered by Na2SO4 treatment, while it was increased in the roots by Na2SO4 salinity. Salinity did not affect the Ce concentration in the shoots but increased it in the storage root, and NaCl salinity increased U concentration in the roots of the carrot plants. Copyright © 2008 John Wiley & Sons, Ltd.
Sample Preparation and Prediction of Soil Organic Matter Properties by Near Infra-red Reflectance Spectroscopy

Near infra-red reflectance spectroscopy (NIRS) offers the potential for rapid and cost-effective soil analysis. Unfortunately, soil NIRS calibrations have not performed well across soil types, and this is believed to be due to the differences in soil particle size and, or, soil mineralogy. In this study we evaluated the influence of grinding, removal of organic matter, removal of mineral component, and scanning soils through plastic bags, on the prediction of three soil organic matter properties across 25 soils. The three properties were mineralizable nitrogen, total soil carbon, and total soil nitrogen. Seven soil preparations were made from coarse whole soil (CWS) samples, and their spectra acquired. The preparations were as follows: CWS, finely ground whole soil (FWS), CWS scanned through plastic (PWS), and two methods for the approximation of mineral and soil organic matter (SOM) within the CWS. Mineral soil spectra were derived from combustion or chemical treatment. SOM spectra were approximated by the subtraction of mineral spectra from CWS spectra. The preparations influenced soil NIRS calibrations in different ways for each property, and their performance was compared with the predictive ability derived from calibrations with CWS. FWS, PWS, and mineral preparations did little to enhance the predictions, and were more likely to reduce predictive ability. SOM spectra gave the best predictions of total soil nitrogen and mineralizable nitrogen (20–30% lower in error), while total soil carbon was best predicted from the CWS spectra. The best calibrations for all three properties suggest they can be predicted within at least 8 classes. It was concluded that approximated SOM spectra could improve predictions of some soil properties by reducing soil mineralogical noise in NIRS calibration development.
Polycomb repressive complex 2 coordinates with Sin3 histone deacetylase complex to epigenetically reprogram genome-wide expression of effectors and regulate pathogenicity in Magnaporthe oryzae

The strict suppression and reprogramming of gene expression are necessary at different development stages and/or in response to environment stimuli in eukaryotes. In Rice Magnaporthe oryzae pathosystem, effectors from pathogen are kept transcriptionally silenced in the vegetative growth stage and are highly expressed during invasive growth stage to adapt to the host environment. However, the mechanism of how such effectors are stably repressed in the vegetative stage and its roles during rice blast infection remain unclear so far. Here, we showed that all subunits of Polycomb Repressive Complex 2 are required for such repression by direct H3K27me3 occupancy and pathogenic process in M. oryzae. Suppression of polycomb-mediated H3K27me3 causes an improper induction of effectors during vegetative growth thus simulating a host environment. Notably, the addition subunit P55 not only acts as the bridge to connect with core subunits to form a complex in M. oryzae, but also recruits Sin3 histone deacetylase complex to prompt H3K27me3 occupancy for stable maintenance of transcriptional silencing of the target genes in the absence of PRC1. In contrast, during invasive growth stage, the repressed state of effectors chromatin can be partially erased during pathogenic development resulting in transcriptional activation of effectors therein. Overall, Polycomb repressive complex 2 coordinates with Sin3 histone deacetylase complex to epigenetically reprogram genome-wide expression of effectors, which act as molecular switch to memorize the host environment from vegetative to invasive growth, thus contributing to the infection of rice blast.
Grp78 alleviates sodium iodate-induced retinal cell injury in vivo and in vitro

Objective Glucose-regulated protein 78 (Grp78) has been regarded as a main member of the endoplasmic reticulum proteins, Grp78 could protect cells from apoptosis under stress conditions. However, whether Grp78 could protect retinal pigment epithelium (RPE) cells from oxidative injury and then protect retinas from morphological changes and functional abnormalities remain undetermined. Here, we try to explore the effect of Grp78 on retinal cell injury induced by sodium iodate in vivo and in vitro. Methods To investigate whether Grp78 has a protective effect on RPE injury in vitro, human retinal pigment epithelium (ARPE-19) cells were treated with sodium iodate. The cell proliferation, morphology, apoptosis and ROS production assays were detected. In vivo, We established sodium iodate-induced retinal injury model in mice by intravenous injection of sodium iodate into tail vein. After that, we examined the morphology and function of retina in mice by fundus photography, OCT and ERG. Finally, we removed the retina of mice for histological examination. Results Grp78 significantly inhibited sodium iodate-induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. Furthermore, Grp78 significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of morphological changes of retina, and improving the function of retina. The underlying mechanisms included inhibited caspase3 and Nos, and increased expression of Bcl2, thereby protecting RPE from SI-induced ROS and apoptosis. Conclusion Grp78 could reduce the injury of retinal cells induced by sodium iodate in vitro and in vivo. These findings suggested Grp78 may become a new therapeutic target for retinal injury in clinical practice.
Recurrent chromosomal translocations in sarcomas create a megacomplex that mislocalizes NuA4/TIP60 to Polycomb target loci

Chromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins. Recent studies have identified highly recurrent chromosomal translocations in patients with Endometrial Stromal Sarcomas (ESS) and Ossifying FibroMyxoid Tumors (OFMT) leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex. While NuA4/TIP60 is a co-activator that acetylates chromatin and loads the H2A.Z histone variant, PHF1 is part of the Polycomb repressive complex 2 (PRC2) linked to transcriptional repression of key developmental genes through methylation of histone H3 on lysine 27. In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation. The chimeric protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 activities and leads to mislocalization of chromatin marks in the genome, in particular over an entire topologically- associating domain including part of the HOXD cluster. This is linked to aberrant gene expression, most notably increased expression of PRC2 target genes. Furthermore, we show that JAZF1, implicated with a PRC2 component in the most frequent translocation in ESS, JAZF1-SUZ12, is a potent transcription activator that physically associates with NuA4/TIP60, its fusion creating similar outcomes as EPC1-PHF1. Importantly, the specific increased expression of PRC2 targets/HOX genes was also confirmed with ESS patient samples. Altogether, these results indicate that most chromosomal translocations linked to these sarcomas employ the same molecular oncogenic mechanism through a physical merge of NuA4/TIP60 and PRC2 complexes leading to mislocalization of histone marks and aberrant polycomb target gene expression.
Sensitivity and resolution improvement for in-vivo magnetic resonance current density imaging (MRCDI) of the human brain

Purpose Magnetic resonance current density imaging (MRCDI) combines MR brain imaging with the injection of time-varying weak currents (1-2 mA) to assess the current flow pattern in the brain. However, the utility of MRCDI is still hampered by low measurement sensitivity and poor image quality. Methods We recently introduced a multi-gradient-echo-based MRCDI approach that has the hitherto best documented efficiency. We now advanced our MRCDI approach in three directions and performed phantom and in-vivo human brain experiments for validation: First, we verified the importance of enhanced spoiling and optimize it for imaging of the human brain. Second, we improved the sensitivity and spatial resolution by using acquisition weighting. Third, we added navigators as a quality control measure for tracking physiological noise. Combining these advancements, we tested our optimized MRCDI method by using 1 mA transcranial electrical stimulation (TES) currents injected via two different electrode montages in five subjects. Results For a session duration of 4:20 min, the new MRCDI method was able to detect magnetic field changes caused by the TES current flow at a sensitivity level of 84 pT, representing in a twofold increase relative to our original method. Comparing both methods to current flow simulations based on personalized head models demonstrated a consistent increase in the coefficient of determination of ΔR2=0.12 for the current-induced magnetic fields and ΔR2=0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite of the strongly improved measurement quality. This suggests that MRCDI can reveal useful information for the improvement of head models used for current flow simulations. Conclusion The advanced method strongly improves the sensitivity and robustness of MRCDI and is an important step from proof-of-concept studies towards a broader application of MRCDI in clinical and basic neuroscience research.
A short ERK5 isoform modulates nucleocytoplasmic shuttling of active ERK5 and associates with poor survival in breast cancer

Background The nucleocytoplasmic shuttling of ERK5 has gained recent attention as a regulator of its diverse roles in cancer progression but the exact mechanisms for this shuttling are still under investigation. Methods Using in vitro, in vivo and in silico studies, we investigated the roles of shorter ERK5 isoforms in regulating the nucleocytoplasmic shuttling of active phosphorylated-ERK5 (pERK5). Retrospective cohorts of primary and metastatic breast cancer cases were used to evaluate the association of the subcellular localization of pERK5 with clinicopathological features. Results Extranuclear localization of pERK5 was observed during cell migration in vitro and at the invasive fronts of metastatic tumors in vivo. The nuclear and extranuclear cell fractions contained different isoforms of pERK5, which are encoded by splice variants expressed in breast and other cancers in the TCGA data. One isoform, isoform-3, lacks the C-terminal transcriptional domain and the nuclear localization signal. The co-expression of isoform-3 and full-length ERK5 associated with high epithelial-to-mesenchymal transition (EMT) and poor patient survival. Experimentally, expressing isoform-3 with full-length ERK5 in breast cancer cells increased cell migration, drove EMT and led to tamoxifen resistance. In breast cancer patient samples, pERK5 showed variable subcellular localizations where its extranuclear localization associated with aggressive clinicopathological features, metastasis, and poor survival. Conclusion Our studies support a model of ERK5 nucleocytoplasmic shuttling driven by splice variants in an interplay between mesenchymal and epithelial states during metastasis. Using ERK5 as a biomarker and a therapeutic target should account for its splicing and context-dependent biological functions. Graphical Abstract ERK5 isoform-3 expression deploys active ERK5 (pERK5) outside the nucleus to facilitate EMT and cell migration. In cells dominantly expressing isoform-1, pERK5 shuttles to the nucleus to drive cell expansion.
Drift as a Driver of Language Change: An Artificial Language Experiment

Over half a century ago, George Zipf observed that more frequent words tend to be older. Corpus studies since then have confirmed this pattern, with more frequent words being replaced and regularized less often than less frequent words. Two main hypotheses have been proposed to explain this: that frequent words change less because selection against innovation is stronger at higher frequencies, or that they change less because stochastic drift is stronger at lower frequencies. Here, we report the first experimental test of these hypotheses. Participants were tasked with learning a miniature language consisting of two nouns and two plural markers. Nouns occurred at different frequencies and were subjected to treatments that varied drift and selection. Using a model that accounts for participant heterogeneity, we measured the rate of noun regularization, the strength of selection, and the strength of drift in participant responses. Results suggest that drift alone is sufficient to generate the elevated rate of regularization we observed in low-frequency nouns, adding to a growing body of evidence that drift may be a major driver of language change.
Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration

Significance We investigate microbe–host interaction in the context of neurodegeneration by screening for Escherichia coli genes whose deletion alleviates Parkinson’s disease symptoms in the nematode Caenorhabditis elegans overexpressing human α-synuclein (α-syn, A53T). The screen yields 38 E. coli genes that promote neurodegeneration. Two of these genes, csgA and csgB, code for proteins that form curli, one type of bacterial amyloid fibers. Curli cross-seeds and colocalizes with α-syn both in C. elegans neurons and human neuroblastoma cells. Curli-induced α-syn aggregations down-regulate mitochondrial genes, causing energy failure in neurons. Moreover, we found that curli may have general effects in promoting neuropathologies induced by different aggregation-prone proteins, such as A-β in Alzheimer’s disease, Huntingtin in Huntington’s disease, and SOD1 in amyotrophic lateral sclerosis. Growing evidence indicates that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases such as Parkinson’s disease. The molecular mechanism underlying such microbe–host interaction is unclear. In this study, by feeding Caenorhabditis elegans expressing human α-syn with Escherichia coli knockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways including curli formation, lipopolysaccharide assembly, and adenosylcobalamin synthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA in E. coli reduced α-syn–induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with α-syn inside neurons and promoted α-syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration in C. elegans models of Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease and in human neuroblastoma cells.
Anterior claustrum cells are responsive during behavior but not passive sensory stimulation

The claustrum is uniquely positioned to communicate with almost all higher-order cortical areas through widespread and reciprocal anatomical projections, yet the in vivo functional properties of claustrum neurons are not well understood. Here we use microendoscope imaging in mice to measure activity in populations of genetically-labelled Gnb4+ claustrum neurons. We find that only a small fraction of cells in the anterior claustrum are responsive to visual or auditory stimuli when delivered under passive yet wakeful conditions. In contrast, during a visual behavioral task, the majority of cells in the anterior claustrum are strongly modulated, with separate and spatially intermingled cell populations showing either increases or decreases in activity relative to spontaneous levels. Our results suggest that the Gnb4+ cells in the anterior claustrum do not represent passively presented sensory stimuli; rather, these cells are strongly engaged during behavior associated with sensory-motor transformations.
Dilatancy in liquid foams

It is shown that dilatancy (a change in liquid fraction due to shear) can be a large effect in foams. Theory and simulations for the standard idealized model of a two-dimensional liquid foam are found to be in good agreement. The estimate of the maximum effect of static shear at constant osmotic pressure gives an absolute increase in liquid fraction of roughly 1.5%, halfway between the wet and the dry limits. The same theory, which uses the established dependence of shear rnodulus on liquid fraction, predicts a qualitatively and quantitatively similar behaviour in three dimensions.
PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIAR

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a c-Myc motif in their promoter. C-MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.