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The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients. V-ATPase, an ATP-driven proton pump positioned at lysosomal surfaces, is responsible for maintaining the stability of lysosome. Herein, we reported that the potassium voltage-gated channel subfamily J member 15 (KCNJ15) protein, which may bind to V-ATPase, can regulate the function of lysosome. The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy. The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase, contributing to the amelioration of drug resistance. Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading, advanced stages, more metastases of lymph nodes, and shorter disease free survival of patients with breast cancer. KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy. Moreover, we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes. In conclusion, KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer, which might guide the choice of therapeutic strategies. [ABSTRACT FROM AUTHOR]

This work aimed to detect changes in trace element chemical speciation in sewage sludge (SS) after the ozonation process. The modified Community Bureau of Reference (BCR) sequential extraction procedure was performed to determine the chemical speciation of trace elements in SS after the ozonation process. To assess potential soil contamination with trace elements from sewage sludge after the ozonation process, the risk assessment code (RAC) coefficient was used. The bioaccumulation factor (BAF) and translocation factor (TF) values were also calculated to characterize the efficiency of trace element accumulation in the studied plant species from soil fertilized with sludges after the ozonation process. Generally, the mean concentration of total trace elements in the SS after the ozonation process was higher, but the differences were statistically significant only in the case of Mn, Cu, Pb, and Cd. The dominant fraction of Fe, Cr, Pb, and Cd was the residual fraction F4, while the extractable/exchangeable fraction F1 was present in the smallest amount. Therefore, in the case of Mn, Zn, and Ni, the ozonation process had a significant impact on the increase in the content of these elements in the F1 fraction. The application of the SS stabilized by ozonation process for maize and wheat fertilization did not significantly affect the bioaccumulation of most of the analyzed metals in aboveground biomass. Higher values of BAF coefficients after the application of ozonated SS were found only in the case of Cu and Ni. In turn, the determined TF coefficients were lower than 1 in most cases. The obtained results showed that the slight change in the concentration of Zn, Mn, and Ni in fraction F1 causes a specific risk of their mobility in the soil environment. It should be noted that due to the variable composition of sewage sludge, an analysis of the content of individual trace elements in chemical fractions should be carried out to assess its actual impact on the environment. This can help to indicate further actions that should be undertaken to limit their negative impact on the environment. [ABSTRACT FROM AUTHOR]

Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies. Barrier-to-autointegration factor 1 (BAF) is a DNA binding protein involved in numerous pathways including transcriptional regulation, DNA damage response and nuclear assembly. Here, Broussard and colleagues characterise its role in gammaherpesvirus reactivation. [ABSTRACT FROM AUTHOR]

Although China has been the main manufacturer and consumer of phthalate esters (PAEs), human health ambient water quality criteria (AWQCs) have not been proposed for these chemicals. In this study, the distribution and bioaccumulation of six PAEs (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP)) were investigated in 11 edible fish species collected from Poyang Lake, China. The results showed that the total concentrations of the six PAEs in the fish ranged between 118.63 and 819.84 μg/kg wet weight (mean of 327.50 ± 190.44 μg/kg). DMP, DEP, DBP, and DEHP were detected in all samples, of which DEHP and DBP were two of the most predominant phthalates, accounting for more than 90% of the total PAEs. The DEHP concentrations in fish with different habitat preferences were different, demersal species were significantly higher than pelagic species (p < 0.05). The mean natural logarithmic bioaccumulation factors (log BAFs) of PAEs increased with increasing lipophilicity of the substances, which yielded the following regression equation: log BAF (L/kg) = 0.103 log Kow + 2.158 (r2 = 0.940, p < 0.05, n = 4). Using this quantitative structure–activity relationship to calculate BAFs for the remaining undetected substances (BBP and DnOP) to derive AWQCs. According to the natural parameters, the human health AWQCs relating to PAE concentrations for water and fish consumption were derived as 9.4 × 103 (DMP), 5.0 × 102 (DEP), 4.2 × 101 (DBP), 1.1 (BBP), 8.6 × 10− 2 (DEHP), and 2.0 (DnOP) μg/L. Human health risk assessment indicated that the dietary intake of DEHP may exert a carcinogenic effect on residents of the Poyang Lake region. The results provide important input to assess the health risk posed by PAEs contaminated surface water. [ABSTRACT FROM AUTHOR]

Mutations in DNAJC5/CSPα are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent storage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS. Functional proteomics identifies a previously unknown DNAJC5 interactor SLC3A2/CD98hc that is essential for the perinuclear DNAJC5 localization and MAPS but dispensable for microautophagy. Importantly, uncoupling these two processes, as seen in cells lacking SLC3A2 or expressing ANCL-associated DNAJC5 mutants, generates DNAJC5-containing AFSMs resembling NCL patient-derived lipofuscin and induces neurodegeneration in a Drosophila ANCL model. These findings suggest that MAPS safeguards microautophagy to avoid DNAJC5-associated lipofuscinosis and neurodegeneration. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AFSM: autofluorescent storage materials; ANCL: adult neuronal ceroid lipofuscinosis; Baf. A1: bafilomycin A1; CLN: ceroid lipofuscinosis neuronal; CLU: clusterin; CS: cysteine string domain of DNAJC5/CSPα; CUPS: compartment for unconventional protein secretion; DN: dominant negative; DNAJC5/CSPα: DnaJ heat shock protein family (Hsp40) member C5; eMI: endosomal microautophagy; ESCRT: endosomal sorting complex required for transport; GFP: green fluorescent protein; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INCL: infant neuronal ceroid lipofuscinosis; JNCL: juvenile neuronal ceroid lipofuscinosis; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAPTM4B: lysosomal protein transmembrane 4 beta; LN: linker domain of DNAJC5/CSPα; MAPS: misfolding-associated protein secretion; mCh/Ch: mCherry; mCi/Ci: mCitrine; MTOR: mechanistic target of rapamycin kinase; NCL: neuronal ceroid lipofuscinosis; PPT1: palmitoyl-protein thioesterase 1; PQC: protein quality control; SBP: streptavidin binding protein; SGT: small glutamine-rich tetratricopeptide repeat; shRNA: short hairpin RNA; SLC3A2/CD98hc: solute carrier family 3 member 2; SNCA/α-synuclein: synuclein alpha; TMED10: transmembrane p24 trafficking protein 10; UV: ultraviolet; VPS4: vacuolar protein sorting 4 homolog; WT: wild type. [ABSTRACT FROM AUTHOR]

The two-meter-long DNA is compressed into chromatin in the nucleus of every cell, which serves as a significant barrier to transcription. Therefore, for processes such as replication and transcription to occur, the highly compacted chromatin must be relaxed, and the processes required for chromatin reorganization for the aim of replication or transcription are controlled by ATP-dependent nucleosome remodelers. One of the most highly studied remodelers of this kind is the BRG1- or BRM-associated factor complex (BAF complex, also known as SWItch/sucrose non-fermentable (SWI/SNF) complex), which is crucial for the regulation of gene expression and differentiation in eukaryotes. Chromatin remodeling complex BAF is characterized by a highly polymorphic structure, containing from four to 17 subunits encoded by 29 genes. The aim of this paper is to provide an overview of the role of BAF complex in chromatin remodeling and also to use literature mining and a set of computational and bioinformatics tools to analyze structural properties, intrinsic disorder predisposition, and functionalities of its subunits, along with the description of the relations of different BAF complex subunits to the pathogenesis of various human diseases. [ABSTRACT FROM AUTHOR]

BAF and PBAF are mammalian SWI/SNF family chromatin remodeling complexes that possess multiple histone/DNA-binding subunits and create nucleosome-depleted/free regions for transcription activation. Despite previous structural studies and recent advance of SWI/SNF family complexes, it remains incompletely understood how PBAF-nucleosome complex is organized. Here we determined structure of 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state. Four PBAF-specific subunits work together with nine BAF/PBAF-shared subunits to generate PBAF-specific modular organization, distinct from that of BAF at various regions. PBAF-nucleosome structure reveals six histone-binding domains and four DNA-binding domains/modules, the majority of which directly bind histone/DNA. This multivalent nucleosome-binding pattern, not observed in previous studies, suggests that PBAF may integrate comprehensive chromatin information to target genomic loci for function. Our study reveals molecular organization of subunits and histone/DNA-binding domains/modules in PBAF-nucleosome complex and provides structural insights into PBAF-mediated nucleosome association complimentary to the recently reported PBAF-nucleosome structure. BAF and PBAF are SWI/SNF family chromatin remodeling complexes that create nucleosome-depleted regions for transcription activation. Here the authors report the structure of a 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state that provides structural insights into PBAF-mediated nucleosome association. [ABSTRACT FROM AUTHOR]

Double-PHD fingers 3 (DPF3) is a BAF-associated human epigenetic regulator, which is increasingly recognised as a major contributor to various pathological contexts, such as cardiac defects, cancer, and neurodegenerative diseases. Recently, we unveiled that its two isoforms (DPF3b and DPF3a) are amyloidogenic intrinsically disordered proteins. DPF3 isoforms differ from their C-terminal region (C-TERb and C-TERa), containing zinc fingers and disordered domains. Herein, we investigated the disorder aggregation properties of C-TER isoforms. In agreement with the predictions, spectroscopy highlighted a lack of a highly ordered structure, especially for C-TERa. Over a few days, both C-TERs were shown to spontaneously assemble into similar antiparallel and parallel β-sheet-rich fibrils. Altered metal homeostasis being a neurodegeneration hallmark, we also assessed the influence of divalent metal cations, namely Cu2+, Mg2+, Ni2+, and Zn2+, on the C-TER aggregation pathway. Circular dichroism revealed that metal binding does not impair the formation of β-sheets, though metal-specific tertiary structure modifications were observed. Through intrinsic and extrinsic fluorescence, we found that metal cations differently affect C-TERb and C-TERa. Cu2+ and Ni2+ have a strong inhibitory effect on the aggregation of both isoforms, whereas Mg2+ impedes C-TERb fibrillation and, on the contrary, enhances that of C-TERa. Upon Zn2+ binding, C-TERb aggregation is also hindered, and the amyloid autofluorescence of C-TERa is remarkably red-shifted. Using electron microscopy, we confirmed that the metal-induced spectral changes are related to the morphological diversity of the aggregates. While metal-treated C-TERb formed breakable and fragmented filaments, C-TERa fibrils retained their flexibility and packing properties in the presence of Mg2+ and Zn2+ cations. [ABSTRACT FROM AUTHOR]

Haemoglobinopathies, including thalassaemias and sickle-cell syndromes, are demanding, lifelong conditions that pose a significant burden to patients, families, and healthcare systems. Despite the therapeutic advances and the resulting improvements in prognosis accomplished in past decades, these patients still face important challenges, including suboptimal access to quality care in areas with developing economies, changing epidemiology due to massive migration flows, an evolving clinical spectrum due to ageing in well-treated patients, and limited access to novel high-cost therapies. We herein describe the organization of healthcare services for haemoglobinopathies in Cyprus--with particular focus on beta-thalassaemia, the most prevalent condition in this region--along with selected patient outcomes. This report aims at underscoring the fact that nationally funded and well-coordinated prevention and care programmes for chronic and complex conditions, such as haemoglobinopathies, with active involvement from patient organizations lead to effective disease control and excellent outcomes in survival, quality of life, social adaptation, and public health savings, and allow timely and effective responses to emerging crises, such as the COVID-19 pandemic. The Cyprus paradigm could therefore serve as a blueprint for the organization or adaptation of haemoglobinopathy programs in other countries since these disorders are still widely occurring. [ABSTRACT FROM AUTHOR]

Four-wave mixing processes are ubiquitous in ultrafast optics and the determination of the coefficients of the χ(3) tensor is thus essential. We introduce a novel time-resolved ultrafast spectroscopic method to characterize the third-order nonlinearity on the femtosecond time-scale. This approach, coined as "nonlinear chirped interferometry," makes use of the variation of the optical group delay of a transmitted probe under the effect of an intense pump pulse in the nonlinear medium of interest. The observable is the spectral interference between the probe and a reference pulse sampled upstream and the metric is the transient swing of the probe group delay. We show that the detected signal is enhanced when the pulses are weakly chirped, and that, although interferometric, the method is intrinsically less sensitive to environmental phase fluctuations and drifts. By chirping adequately the reference pulse, the transient frequency shift of the probe pulses is also detected in the time domain and the detected nonlinear signal is enhanced. Nonlinear phase shifts as low as 10 mrad, corresponding to a frequency shift of 30 GHz, i.e., 0.01% of the carrier frequency, are detected without heterodyne detection or active phase-stabilization. The diagonal and/or non-diagonal terms of reference glasses (SiO2) and crystals (Al2O3, BaF2, CaF2) are characterized. The method is finally applied to measure the soft vibration mode of KTiOAsO4 (KTA). [ABSTRACT FROM AUTHOR]

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most common chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA21 that directly contribute to cognitive deficits remain incompletely understood. Here, we found that the HSA21-encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued deficits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes. The molecular mechanisms underlying deficits in Down syndrome remain unclear. Here, the authors show that copy number restoration of a chromatin remodeler in trisomic mice is sufficient to rescue epigenomic, physiological and cognitive deficits. [ABSTRACT FROM AUTHOR]

The current study examines the bioaccumulation potential of Taif rose shrubs by analyzing the shrubs' wastes. f. At Al-Shafa Highland, four farms with plants of different ages were chosen to collect soil samples and vegetative waste (leaves and stems) for morphological and chemical analysis. The tallest stem and largest crown diameter (184.2 and 243.5 cm, respectively) were found in the oldest (20-year-old) shrubs, which also produced the highest biomass of pruning wastes of stems and leaves (3.9 and 1.3 t/ha, respectively). The 10-year-old shrubs gathered the highest concentration of Co and Pb (1.74 and 7.34 mg kg−1) in the stem and the highest Fe, Mn, and Ni (18.55, 18.60, and 9.05 mg kg−1) in the leaves, while the youngest plants (4 years) accumulated the highest Cr and Zn (0.83 and 13.44 mg kg−1) in their leaves. The highest contents of Cd, Cr, Cu, Fe, Mn, Pb, and Zn were found in the oldest Taif rose stem (34.94, 1.16, 36.29, 49.32, 51.22, 24.76, and 32.51 g ha−1), while the highest contents of Co and Ni were found in the stems of plants that were 10 and 12 years old (3.21 and 9.54 g ha−1, respectively). The Taif rose's stem and leaves can absorb the majority of heavy metals that have been studied with BAF values greater than one. Significant relationships between various heavy metals in the soil and the same in the stems (Al, Co, and Pb) and leaves (Co, Fe, Mn, Ni, and Pb) of Taif roses have been observed. According to the current findings, the Taif rose is a promising viable and safe crop for heavy metals phytoremediation if it is grown in polluted soil because there is little to no risk of contamination in the use of its end products, high biomass of pruning wastes, and high efficiency of heavy metal removal. [ABSTRACT FROM AUTHOR]

Observing phenological changes are important for evaluating the natural regeneration process of forests, especially in Mediterranean areas where the regeneration of coniferous forests depends on seeds and the changes in blossoming time are influenced by climate change. The high temporal resolution of Sentinel-1 data allows the time series analysis of synthetic aperture radar (SAR) data, but it is still unknown how these data could be utilised for better understanding forest phenology and climate-related alternations. This study investigates the phenological cycle of Paphos forest, Cyprus using SAR data from 1992 to 2021, acquired by ERS-1/2, Envisat and Sentinel-1. An average phenological diagram was created for each space mission and a more detailed analysis was performed from October 2014 to November 2021, using the higher temporal resolution of Sentinel-1 data. Meteorological data were used to better understand the drivers of blooming alternations. Using the interquartile range (IQR), outliers were detected and replaced using the Kalman filter imputation. Forecasting trend lines were used to estimate the amplitude of the summer peaks and the annual mean. The observation of the average phenology from each satellite mission showed that there were two main blooming peaks each year: the winter and the summer peak. We argue that the winter peak relates to increased foliage, water content and/or increased soil moisture. The winter peak was followed by a fall in February reaching the lower point around March, due to the act of pine processionary (Thaumetopoea pityocampa). The summer peak should relate to the annual regeneration of needles and the drop of the old ones. A delay in the summer peak—in August 2018—was associated with increased high temperatures in May 2018. Simultaneously, the appearance of one peak instead of two in the σ V H time series during the period November 2014–October 2015 may be linked to a reduced act of the pine processionary associated with low November temperatures. Furthermore, there was an outlier in February 2016 with very low backscattering coefficients and it was associated with a drought year. Finally, predicting the amplitude of July 2020 returned high relevant Root Mean Square Error (rRMSE). Seven years of time series data are limiting for predicting using trend lines and many parameters need to be taken into consideration, including the increased rainfall between November 2018 and March 2020. [ABSTRACT FROM AUTHOR]

The effect of BaF2, MgF2, and AlF3 on the structural and luminescent properties of gallo-germanate glass (BGG) doped with erbium ions was investigated. A detailed analysis of infrared and Raman spectra shows that the local environment of erbium ions in the glass was influenced mainly by [GeO]4 and [GeO]6 units. Moreover, the highest number of non-bridging oxygens was found in the network of the BGG glass modified by MgF2. The 27Al MAS NMR spectrum of BGG glass with AlF3 suggests the presence of aluminum in tetra-, penta-, and octahedral coordination geometry. Therefore, the probability of the 4I13/2→4I15/2 transition of Er3+ ions increases in the BGG + MgF2 glass system. On the other hand, the luminescence spectra showed that the fluoride modifiers lead to an enhancement in the emission of each analyzed transition when different excitation sources are employed (808 nm and 980 nm). The analysis of energy transfer mechanisms shows that the fluoride compounds promote the emission intensity in different channels. These results represent a strong base for designing glasses with unique luminescent properties. [ABSTRACT FROM AUTHOR]

Background: Nowadays, wound healing is one of the main problems of patients. Therefore, extensive research is underway to discover mechanisms associated with non-scarring of wounds. Using amniotic fluid and laser may potentially play a key role in wound healing and scar reduction due to its presence in tissue growth and repair agents. Aim: The present study evaluated the effect of bovine amniotic fluid (BAF)-derived cream and low-power laser (LPL) on accelerating skin wound healing and reducing scarring in an animal model. Materials and Methods: Therefore, 72 male Wistar rats were randomly divided into three groups (each group: 24). A wound 6 mm in diameter was then inflicted on the rats' backs. In the first group that was the control group, the wound was only used. Moreover, BAF was implemented for the second group, and in the third group, LPL radiation was utilized. On the 1st, 3rd, 5th, 14th, and 21st days, the healing condition of the wound and scar created were examined. Results: Hence, evaluation of wound healing status on days 5 and 14 showed that the wound healing scale in the BAF group and LPL group was significantly better than that of the control group. On the 21st day, the average Scar Scoring Scale in the BAF and LPL groups was significantly lower than that of the control group. Histological images showed a significant repair in the LPL and BAF groups. Conclusion: To conclude, considering the positive effect of LPL and BAF on wound healing and less scarring, it seems that LPL and BAF can heal wounds faster. Moreover, they can be used to prevent scarring after wound healing. [ABSTRACT FROM AUTHOR]

YBa2Cu3O7−δ (YBCO) thin films with the addition of Cl were prepared on Hastelloy tape by the extremely low fluorine metal-organic deposition (MOD) technique. The composition and microstructure of the present samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was revealed that the Cl-added YBCO thin films achieved better texture and density compared with the pure YBCO films. The superconducting properties at magnetic fields were measured using the magnetic property measurement system (MPMS). The results showed that the sample onset transition temperature (Tc, on) did not change significantly after the addition of Cl. The critical current density (Jc) in the presence of YBCO with the addition of Cl increased significantly. Meanwhile, both the Jc and gravitational force (Fp) of the (Cl, Hf) co-added YBCO films were further enhanced at different magnetic fields. The thermodynamic analysis of the BaCO3 removal reaction revealed that the addition of Cl to YBCO formed chlorine compounds, which were effective in avoiding the formation of BaCO3. Further, the calculation results of the Gibbs free energy at different pressure quotients showed that the stability of the relevant chlorine compounds occurred in the order of BaCl2 > CuCl2 > YCl3 and the oxidation of BaCl2 to BaO required a higher temperature compared to BaF2, implying the potential advantages of inhibiting the a-axis growth. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription. Here the authors show mutation of the BAF chromatin remodeler subunit ARID1A results in an ARID1B-dependent upregulation of HERVH, an ERV required for the pluripotency regulatory network. These HERVH RNAs can partition into BRD4 foci, affecting BRD4-dependent transcription. Suppression of HERVH in colorectal cancer cells and patient-derived organoids impairs tumor growth. [ABSTRACT FROM AUTHOR]

Background: The exit from pluripotency or pluripotent-somatic transition (PST) landmarks an event of early mammalian embryonic development, representing a model for cell fate transition. Results: In this study, using a robust JUN-induced PST within 8 h as a model, we investigate the chromatin accessibility dynamics (CAD) as well as the behaviors of corresponding chromatin remodeling complex SS18/BAFs, to probe the key events at the early stage of PST. Here, we report that, JUN triggers the open of 34661 chromatin sites within 4 h, accomplished with the activation of somatic genes, such as Anxa1, Fosl1. ChIP-seq data reveal a rapid relocation of SS18/BAFs from pluripotent loci to AP-1 associated ones. Consistently, the knockdown of Brg1, core component of BAF complexes, leads to failure in chromatin opening but not closing, resulting in delay for JUN induced PST. Notably, the direct interaction between SS18/BAFs and JUN-centric protein complexes is undetectable by IP-MS. Instead, we show that H3K27ac deposited by cJUN dependent process regulates SS18/BAFs complex to AP1-containing loci and facilitate chromatin opening and gene activation. Conclusions: These results reveal a rapid transfer of chromatin remodeling complexes BAF from pluripotent to somatic loci during PST, revealing a simple mechanistic aspect of cell fate control. [ABSTRACT FROM AUTHOR]

Over millions of years, eukaryotes evolved from unicellular to multicellular organisms with increasingly complex genomes and sophisticated gene expression networks. Consequently, chromatin regulators evolved to support this increased complexity. The ATP-dependent chromatin remodelers of the SWI/SNF family are multiprotein complexes that modulate nucleosome positioning and appear under different configurations, which perform distinct functions. While the composition, architecture, and activity of these subclasses are well understood in a limited number of fungal and animal model organisms, the lack of comprehensive information in other eukaryotic organisms precludes the identification of a reliable evolutionary model of SWI/SNF complexes. Here, we performed a systematic analysis using 36 species from animal, fungal, and plant lineages to assess the conservation of known SWI/SNF subunits across eukaryotes. We identified evolutionary relationships that allowed us to propose the composition of a hypothetical ancestral SWI/SNF complex in the last eukaryotic common ancestor. This last common ancestor appears to have undergone several rounds of lineage-specific subunit gains and losses, shaping the current conformation of the known subclasses in animals and fungi. In addition, our results unravel a plant SWI/SNF complex, reminiscent of the animal BAF subclass, which incorporates a set of plant-specific subunits of still unknown function. The ancestral history of SWI/SNF subunits, responsible for nucleosome positioning, are explored in this work, revealing a plant SWI/SNF complex similar to the animal BAF subclass. [ABSTRACT FROM AUTHOR]

A cross polarized wave (XPW) generation experiment with double BaF2 crystals in air was demonstrated with 120 µJ input pulse. A circular aperture was used to truncate the near field profile of the input beam and remove the outer part of the beam, and circularly symmetric beam profiles were generated at the BaF2 crystal positions. The measured focal spot size was close to the diffraction limit, and the energy stability of XPW was improved from ∼1.89% (without the aperture) to ∼0.67% (with the aperture). [ABSTRACT FROM AUTHOR]

In the present research work, we have theoretically analyzed the photonic band-gap properties of one-dimensional photonic structures composed of polycarbonate and non-glass materials. These photonic structures, PC1, PC2, PC3 and PC4, are composed of alternating layers of polycarbonate/Al2O3, polycarbonate/MgF2, polycarbonate/BaF2 and polycarbonate/TiO2 materials, respectively. The period of each photonic structure is made up of a thin non-glass material layer sandwiched between two identical polycarbonate layers. The transfer matrix method has been used to investigate the transmission properties of PC1 to PC4. The comparison between the transmission spectra of PC1 to PC4 shows that the polycarbonate and TiO2-based photonic structure (PC4) possess three PBGs of zero transmission located at far-ultraviolet, visible and near-infrared regions of the electromagnetic spectrum at normal and oblique incidence (θ0 = 55°), both corresponding to TE wave only. The index of refraction of all five materials used in this study was obtained by applying the Sellmeier-type dispersion relationship to ensure accuracy in the results. The purpose of selecting polycarbonate along with Al2O3, TiO2, MgF2 or BaF2 as constituent materials of these photonic structures is due to the heat resistance properties of polycarbonate and the unique optical properties of oxide and fluoride materials with wide transparency from the ultraviolet to the near-infrared regions of the electromagnetic spectrum. The proposed work can be used to design some influential wavelength-selective reflectors composed of 1D PCs behind the active region of the solar cells for improving the photovoltaic performance of solar panels. This study can further be utilized for the fabrication of advanced solar cell designs consisting of 1D photonic mirror-based luminescence and reflection concentrators. The low temperature problem which arises in satellites may also be overcome with the help of smart windows based on the proposed multilayer structures. [ABSTRACT FROM AUTHOR]

Single crystals of Ca1– хBaхF2 (x = 0.001–0.05 and 0.85–0.99) solid solutions have been grown by the Bridgman method, and their thermal conductivity has been measured in the range 50–300 K by an absolute steady-state axial heat flow technique. The thermal conductivity of all samples has been shown to decrease with increasing temperature. At 300 K, the lowest thermal conductivity of the samples with x ≤ 0.05 exceeds 6 W/(m K), and that of the samples with x ≥ 0.85 is a factor of 2 lower. [ABSTRACT FROM AUTHOR]

Aquatic contamination can settle into sediments, where it complexes with organic matter and becomes bioavailable. The resulting bioaccumulation of these contaminants by benthic fauna poses a serious threat due to the potential for trophic transfer. This paper offers an insight into the heterogenous accumulation behavior of different elements, and the consequences for ecological risk. In this study, we present field quantification of sediment-associated bioaccumulation factors (BAF S) in freshwater benthic macroinvertebrates. 17 elements were quantified using ICP-MS in sediment and Asellus aquaticus and Gammarus sp. samples. Previously published reports of contaminant concentrations in freshwater and marine sediments and benthic fauna were likewise analyzed to provide a complementary picture of bioaccumulation across contaminants and taxa. We demonstrate that the BAF S correlates strongly with the thiophilicity of the elemental contaminants, as defined by (Kepp, 2016), for all strata examined. These findings support the hypothesis that thiol-mediated processes, such as that of metallothionein, play a larger role in bioaccumulation than typically afforded. In conclusion, we demonstrate the potential for the thiophilic scale to act as a predictor of accumulation potential. [Display omitted] • Accumulation correlates strongly with thiophilicity across orders and environments. • Results support a thiol-based bioaccumulation process. • Bioavailability of contaminants can be predicted using the thiophilic scale. [ABSTRACT FROM AUTHOR]

The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly. Female embryonic stem cells (ESCs) are the ideal model to study X chromosome inactivation (XCI) establishment; however, these cells are challenging to keep in culture. Here the authors create fluorescent 'Xmas' reporter mice as a renewable source of ESCs and show nucleosome remodelers Smarcc1 and Smarca4 create a nucleosome-free promoter region prior to the establishment of silencing. [ABSTRACT FROM AUTHOR]

Marine fishery products have been contaminated with microplastic (MPs), including molluscs, crustacean, and fish. The study aimed to analyze the number and types of MPs in the digestive tract and sediment, correlation between number of MPs with total body length, and estimated uptake of MPs in the fish from sediment using Bioaccumulation Factor (BAF). The method of determining sampling point involved purposive sampling and direct observation at Pramuka Island, Seribu Islands, Indonesia. Groupers fish were found in 20 individuals with 4 species of Epinephelus areolatus, E. ongus, E. sexfasciatus, and E. fuscoguttatus. The number of MPs found in the gastrointestinal tract of Epinephelus is 1648 particles with 3 types: fiber, fragment, and pellet. The highest number of MPs in the sediment was at dock and the lowest was at Gosong Pramuka Island. The numbers of MPs in the digestion tract does not affect the body length of individual species. The BAF value indicates result that the MPs uptake in sediments to gastrointestinal tract of Epinephelus grouper is low. All samples of the Epinephelus grouper were contaminated with MPs. [ABSTRACT FROM AUTHOR]

The overexpansion of adipose tissues leads to obesity and eventually results in metabolic disorders. Garcinia cambogia (G. cambogia) has been used as an antiobesity supplement. However, the molecular mechanisms underlying the effects of G. cambogia on cellular processes have yet to be fully understood. Here, we discovered that G. cambogia attenuated the expression of CEBPB (CCAAT/enhancer binding protein (C/EBP), beta), an important adipogenic factor, suppressing its transcription in differentiated cells. In addition, G. cambogia inhibited macroautophagic/autophagic flux by decreasing autophagy-related gene expression and autophagosome formation. Notably, G. cambogia markedly elevated the expression of KLF3 (Kruppel-like factor 3 (basic)), a negative regulator of adipogenesis, by reducing SQSTM1/p62-mediated selective autophagic degradation. Furthermore, increased KLF3 induced by G. cambogia interacted with CTBP2 (C-terminal binding protein 2) to form a transcriptional repressor complex and inhibited Cebpa and Pparg transcription. Importantly, we found that RPS6KA1 and STAT3 were involved in the G. cambogia-mediated regulation of CEBPB and autophagic flux. In an obese animal model, G. cambogia reduced high-fat diet (HFD)-induced obesity by suppressing epididymal and inguinal subcutaneous white adipose tissue mass and adipocyte size, which were attributed to the regulation of targets that had been consistently identified in vitro. These findings provide new insight into the mechanism of G. cambogia-mediated regulation of adipogenesis and suggest molecular links to therapeutic targets for the treatment of obesity. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; ATG: autophagy-related; Baf: bafilomycin A1; BECN1: beclin 1; CEBP: CCAAT/enhancer binding protein (C/EBP); CHX: cycloheximide; CREB: cAMP response element binding protein; CTBP: C-terminal binding protein; EGCG: (-)-epigallocatechin gallate; eWAT: epididymal white; G. cambogia: Garcinia cambogia; GFP: green fluorescent protein; H&E: hematoxylin and eosin; HFD: high-fat diet; iWAT: inguinal subcutaneous white; KLF: Kruppel-like factor; LAP: liver-enriched transcriptional activating proteins; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; ND: normal diet; PPARG: peroxisome proliferator activated receptor gamma; qPCR: quantitative real-time PCR; RFP: red fluorescent protein; RPS6KA1: ribosomal protein S6 kinase A1; siRNA: small-interfering RNA; SQSTM1/p62: sequestosome 1; STAT: signal transducer and activator of transcription; TEM: transmission electron microscopy [ABSTRACT FROM AUTHOR]

The Mediterranean Sea is subjected to a high anthropic pressure, which determines direct or indirect discharges of persistent organic pollutants deriving from intensive industrial activities. These compounds could easily enter and contaminate the whole marine compartment, with possible transfers (and contamination) among water, sediment and biota. Based on the above-mentioned assumptions, in this work we studied the presence of 16 polycyclic aromatic hydrocarbons (PAHs) and 14 dioxin and non-dioxin-like polychlorinated biphenyls (PCBs) in the neritic protected marine area of the Southern Ligurian Sea, affected by the impact of human activities. The study was focused on the possible partition of micropollutants within seawater, sediment and zooplankton. Results showed that both seasonal and anthropic causes strongly affect contaminant transfer behaviors, with summertime periods more impacted by PAH and PCB contamination. Regarding the PAH contamination, low molecular weight congeners were mainly detected in the target matrices, revealing concentrations up to 1 µg/L in seawater (anthracene), 250 µg/Kg in sediments (benzo[b]fluoranthene) and 2.3 mg/Kg in carnivorous copepods. Concerning PCBs, only few congeners were detected in the matrices studied. To better understand the occurrence of preferential bioaccumulation pathways in zooplankton, partition studies were also performed in several taxa (hyperbenthic Isopoda, holoplanktonic crustacean copepods and ichthyoplankton) through the calculation of BAF values, observing that both living and feeding habits could influence the bioaccumulation process. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is emerging as a major pathway that regulates both aging and stem cell function. Previous studies have demonstrated a positive correlation of autophagy with longevity; however, these studies did not directly address the consequence of altered autophagy in stem cells during aging. In this study, we used Becn1F121A/F121A knockin mice (designated as Becn1 KI mice) with the F121A allele in the autophagy gene Becn1 to investigate the consequences of enhanced autophagy in postnatal neural stem cells (NSCs) during aging. We found that increased autophagy protected NSCs from exhaustion and promoted neurogenesis in old (≥18-months-old) mice compared with age-matched wild-type (WT) mice, although it did not affect NSCs in young (3-months-old) mice. After pharmacologically-induced elimination of proliferative cells in the subventricular zone (SVZ), there was enhanced re-activation of quiescent NSCs in old Becn1 KI mice as compared to those in WT mice, with more efficient exit from quiescent status to generate proliferative cells and neuroblasts. Moreover, there was also improved maintenance and increased neuronal differentiation of NSCs isolated from the SVZ of old Becn1 KI mice in in vitro assays. Lastly, the increased neurogenesis in Becn1 KI mice was associated with better olfactory function in aged animals. Together, our results suggest a protective role of increased autophagy in aging NSCs, which may help the development of novel strategies to treat age-related neurodegeneration. Abbreviations: ATG: autophagy related; Baf A1: bafilomycin A1; Becn1: beclin 1; BrdU: bromodeoxyuridine/5-bromo-2ʹ-deoxyuridine; DCX: doublecortin; GFAP: glial fibrillary acidic protein; GFP: green fluorescent protein; H&E: hematoxylin and eosin; HSCs: hematopoietic stem cells; KI: knockin; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; mo: month; NSCs: neural stem cells; OB: olfactory bulb; RB1CC1: RB1-inducible coiled-coil 1; ROS: reactive oxygen species; SOX2: SRY (sex determining region Y)-box 2; SGZ: subgranular zone; SVZ: subventricular zone; TMZ: temozolomide; WT: wild type. [ABSTRACT FROM AUTHOR]

Featured Application: laser surface-processing. Monocrystalline barium fluoride (BaF2) slab targets were irradiated by focused 46.9-nm laser radiation at various fluence levels above the ablation threshold. Well-developed ablation patterns with sharp edges were studied by AFM (atomic force microscopy). Their inner surfaces were uniformly covered by periodic structures. The spatial period of the ripples depends on the laser fluence. When the sample is rotated by 45°, the orientation of the grating-like structure changes accordingly. Thus, the grating vector of the periodic structure seems to be coupled to the crystallographic planes of the single crystal. This means that the XUV-laser induced ripples reported here differ from LIPSS (laser-induced periodic surface structures) associated with interference phenomena occurring on illuminated surfaces. Therefore, other mechanisms are discussed to explain the formation of the periodic nanostructures reported in this article. [ABSTRACT FROM AUTHOR]

Background: Basilar artery fenestration has been proposed as a contributor to ischemic stroke, as unique flow patterns induced by fenestration may be related to thrombus formation or insufficiency. This study aimed to evaluate the hemodynamics of basilar artery fenestration (BAF) using computational fluid dynamics (CFD). Methods: Patients with BAF and normal vertebrobasilar system were recruited and separately evaluated using CFD. Specific geometric vascular models were reconstructed based on 3D-rotational angiography (3D-RA). Patients were divided into the BAF group and control group (i.e., patients with the normal vertebrobasilar system). Hemodynamic and geometric variables were calculated and compared between groups using Student's t -test or Wilcoxon rank-sum test. Results: Overall, 24 patients were included, with 12 patients each in the BAF group and the control group. The BAF group had a significantly smaller basilar artery diameter than the control group (3.1 ± 0.51 vs. 3.76 ± 0.4, p = 0.002). Compared to the control group, the BAF group had higher values of maxOSI (median, 0.3 vs. 0.09, p = 0.028), TAWSSG (median, 983.42 vs. 565.39, p = 0.038) in the flow confluence, higher SAR-TAWSSG in bifurcation (median, 70.22 vs. 27.65, p = 0.002) and higher SAR-TAWSSG in basilar artery (median, 48.75 vs. 16.17, p < 0.001) of the vertebrobasilar artery. Conclusions: This pilot study suggested that hemodynamic differences between BAF and normal vertebrobasilar artery across multiple shear flow parameters. The disturbed flow in the BAF may increase the risk of thrombus formation, plaque instability, and subsequent ischemic cerebrovascular events. These should be confirmed by future studies. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is elevated to ensure the high demand for nutrients for the growth of cancer cells. Here we demonstrated that MCOLN1/TRPML1 is a pharmaceutical target of oncogenic autophagy in cancers such as pancreatic cancer, breast cancer, gastric cancer, malignant melanoma, and glioma. First, we showed that activating MCOLN1, by increasing expression of the channel or using the MCOLN1 agonists, ML-SA5 or MK6-83, arrests autophagic flux by perturbing fusion between autophagosomes and lysosomes. Second, we demonstrated that MCOLN1 regulates autophagy by mediating the release of zinc from the lysosome to the cytosol. Third, we uncovered that zinc influx through MCOLN1 blocks the interaction between STX17 (syntaxin 17) in the autophagosome and VAMP8 in the lysosome and thereby disrupting the fusion process that is determined by the two SNARE proteins. Furthermore, we demonstrated that zinc influx originating from the extracellular fluid arrests autophagy by the same mechanism as lysosomal zinc, confirming the fundamental function of zinc as a participant in membrane trafficking. Last, we revealed that activating MCOLN1 with the agonists, ML-SA5 or MK6-83, triggers cell death of a number of cancer cells by evoking autophagic arrest and subsequent apoptotic response and cell cycle arrest, with little or no effect observed on normal cells. Consistent with the in vitro results, administration of ML-SA5 in Patu 8988 t xenograft mice profoundly suppresses tumor growth and improves survival. These results establish that a lysosomal cation channel, MCOLN1, finely controls oncogenic autophagy in cancer by mediating zinc influx into the cytosol. Abbreviation: Abbreviations: 3-MA: 3-methyladenine; AA: amino acid; ATG12: autophagy related 12; Baf-A1: bafilomycin A1; BAPTA-am: 1,2-bis(2-aminophenoxy)ethane-N, N,N',N'-tetraacetic acid tetrakis-acetoxymethyl ester; co-IP: coimmunoprecipitaion; CQ: chloroquine; DMEM: Dulbecco's Modified Eagle Medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde- 3-phosphate dehydrogenase; HCQ: hydroxychloroquine; HEK: human embryonic kidney; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MTORC1: mechanistic target of rapamycin kinase complex 1; NC: negative control; NRK: normal rat kidney epithelial cells; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; RPS6KB/S6K: ribosomal protein S6 kinase B; shRNA: short hairpin RNA; siRNA: short interfering RNA; SNARE: soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TPEN: N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; TTM: tetrathiomolybdate; ULK1: unc-51 like autophagy activating kinase 1; VAMP8: vesicle associated membrane protein 8; Zn2+: zinc. [ABSTRACT FROM AUTHOR]

Basal macroautophagy/autophagy has recently been found in anucleate platelets. Platelet autophagy is involved in platelet activation and thrombus formation. However, the mechanism underlying autophagy in anucleate platelets require further clarification. Our data revealed that LC3-II formation and SQSTM1/p62 degradation were noted in H2O2-activated human platelets, which could be blocked by 3-methyladenine and bafilomycin A1, indicating that platelet activation may cause platelet autophagy. AMPK phosphorylation and MTOR dephosphorylation were also detected, and block of AMPK activity by the AMPK inhibitor dorsomorphin reversed SQSTM1 degradation and LC3-II formation. Moreover, autophagosome formation was observed through transmission electron microscopy and deconvolution microscopy. These findings suggest that platelet autophagy was induced partly through the AMPK-MTOR pathway. In addition, increased LC3-II expression occurred only in H2O2-treated Atg5f/f platelets, but not in H2O2-treated atg5−/− platelets, suggesting that platelet autophagy occurs during platelet activation. atg5−/− platelets also exhibited a lower aggregation in response to agonists, and platelet-specific atg5−/− mice exhibited delayed thrombus formation in mesenteric microvessles and decreased mortality rate due to pulmonary thrombosis. Notably, metabolic analysis revealed that sphingolipid metabolism is involved in platelet activation, as evidenced by observed several altered metabolites, which could be reversed by dorsomorphin. Therefore, platelet autophagy and platelet activation are positively correlated, partly through the interconnected network of sphingolipid metabolism. In conclusion, this study for the first time demonstrated that AMPK-MTOR signaling could regulate platelet autophagy. A novel linkage between AMPK-MTOR and sphingolipid metabolism in anucleate platelet autophagy was also identified: platelet autophagy and platelet activation are positively correlated. Abbreviations: 3-MA: 3-methyladenine; A.C.D.: citric acid/sod. citrate/glucose; ADP: adenosine diphosphate; AKT: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy-related; B4GALT/LacCS: beta-1,4-galactosyltransferase; Baf-A1: bafilomycin A1; BECN1: beclin 1; BHT: butylate hydrooxytoluene; BSA: bovine serum albumin; DAG: diacylglycerol; ECL: enhanced chemiluminescence; EDTA: ethylenediamine tetraacetic acid; ELISA: enzyme-linked immunosorbent assay; GALC/GCDase: galactosylceramidase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/GluSDase: glucosylceramidase beta; GPI: glycosylphosphatidylinositol; H2O2: hydrogen peroxide; HMDB: human metabolome database; HRP: horseradish peroxidase; IF: immunofluorescence; IgG: immunoglobulin G; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP1: lysosomal associated membrane protein 1; LC-MS/MS: liquid chromatography-tandem mass spectrometry; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MPV: mean platelet volume; MTOR: mechanistic target of rapamycin kinase; ox-LDL: oxidized low-density lipoprotein; pAb: polyclonal antibody; PC: phosphatidylcholine; PCR: polymerase chain reaction; PI3K: phosphoinositide 3-kinase; PLS-DA: partial least-squares discriminant analysis; PRP: platelet-rich plasma; Q-TOF: quadrupole-time of flight; RBC: red blood cell; ROS: reactive oxygen species; RPS6KB/p70S6K: ribosomal protein S6 kinase B; SDS: sodium dodecyl sulfate; S.E.M.: standard error of the mean; SEM: scanning electron microscopy; SGMS: sphingomyelin synthase; SM: sphingomyelin; SMPD/SMase: sphingomyelin phosphodiesterase; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; UGT8/CGT: UDP glycosyltransferase 8; UGCG/GCS: UDP-glucose ceramide glucosyltransferase; ULK1: unc-51 like autophagy activating kinase 1; UPLC: ultra-performance liquid chromatography; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns3P: phosphatidylinositol-3-phosphate; WBC: white blood cell; WT: wild type [ABSTRACT FROM AUTHOR]

Spiral ganglion neurons (SGNs) are auditory neurons that relay sound signals from the inner ear to the brainstem. The ototoxic drug cisplatin can damage SGNs and thus lead to sensorineural hearing loss (SNHL), and there are currently no methods for preventing or treating this. Macroautophagy/autophagy plays a critical role in SGN development, but the effect of autophagy on cisplatin-induced SGN injury is unclear. Here, we first found that autophagic flux was activated in SGNs after cisplatin damage. The SGN apoptosis and related hearing loss induced by cisplatin were alleviated after co-treatment with the autophagy activator rapamycin, whereas these were exacerbated by the autophagy inhibitor 3-methyladenine, indicating that instead of inducing SGN death, autophagy played a neuroprotective role in SGNs treated with cisplatin both in vitro and in vivo. We further demonstrated that autophagy attenuated reactive oxygen species (ROS) accumulation and alleviated cisplatin-induced oxidative stress in SGNs to mediate its protective effects. Notably, the role of the antioxidant enzyme PRDX1 (peroxiredoxin 1) in modulating autophagy in SGNs was first identified. Deficiency in PRDX1 suppressed autophagy and increased SGN loss after cisplatin exposure, while upregulating PRDX1 pharmacologically or by adeno-associated virus activated autophagy and thus inhibited ROS accumulation and apoptosis and attenuated SGN loss induced by cisplatin. Finally, we showed that the underlying mechanism through which PRDX1 triggers autophagy in SGNs was, at least partially, through activation of the PTEN-AKT signaling pathway. These findings suggest potential therapeutic targets for the amelioration of drug-induced SNHL through autophagy activation. Abbreviations: 3-MA: 3-methyladenine; AAV : adeno-associated virus; ABR: auditory brainstem responses; AKT/protein kinase B: thymoma viral proto-oncogene; Baf: bafilomycin A1; CAP: compound action potential; COX4I1: cytochrome c oxidase subunit 4I1; Cys: cysteine; ER: endoplasmic reticulum; H2O2: hydrogen peroxide; HC: hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NAC: N-acetylcysteine; PRDX1: peroxiredoxin 1; PTEN: phosphatase and tensin homolog; RAP: rapamycin; ROS: reactive oxygen species; SGNs: spiral ganglion neurons; SNHL: sensorineural hearing loss; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling; WT: wild type. [ABSTRACT FROM AUTHOR]

Hepatic macroautophagy/autophagy and fatty acid metabolism are transcriptionally regulated by nuclear receptors (NRs); however, it is not known whether their transcriptional co-activators are involved in autophagy. We thus examined MED1 (mediator complex subunit 1), a key component of the Mediator Complex that directly interacts with NRs, on these processes. We found that MED1 knockdown (KD) in cultured hepatic cells decreased autophagy and mitochondrial activity that was accompanied by decreased transcription of genes involved in these processes. Lipophagy and fatty acid β-oxidation also were impaired. These effects also occurred after thyroid hormone stimulation, nutrient-replete or -deplete conditions, and in liver-specific Med1 KD (Med1 LKD) mice under fed and fasting conditions. Together, these findings showed that Med1 played a key role in hepatic autophagy, mitochondria function, and lipid metabolism under these conditions. Additionally, we identified downregulated hepatic genes in Med1 LKD mice, and subjected them to ChIP Enrichment Analysis. Our findings showed that the transcriptional activity of several NRs and transcription factors (TFs), including PPARA and FOXO1, likely were affected by Med1 LKD. Finally, Med1 expression and autophagy also were decreased in two mouse models of nonalcoholic fatty liver disease (NAFLD) suggesting that decreased Med1 may contribute to hepatosteatosis. In summary, MED1 plays an essential role in regulating hepatic autophagy and lipid oxidation during different hormonal and nutrient conditions. Thus, MED1 may serve as an integrator of multiple transcriptional pathways involved in these metabolic processes. Abbreviations: BAF: bafilomycin A1; db/db mice; Leprdb/db mice; ECAR: extracellular acidification rate; KD: knockdown; MED1: mediator complex subunit 1; NAFLD: nonalcoholic fatty liver disease; OCR: oxygen consumption rate; PPARA/PPARα: peroxisomal proliferator activated receptor alpha; TF: transcription factor; TFEB: transcription factor EB; tf-LC3: tandem fluorescence RFP-GFP-LC3; TG: triglyceride; TH: Thyroid hormone; TR: thyroid hormone receptors; V-ATPase: vacuolar-type H+-ATPase; WDF: Western diet with 15% fructose in drinking water [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters the myogenic program and maintains the proliferative state while blocking terminal differentiation. Here, we investigated the contributions of chromatin regulatory complexes to FP-RMS tumor maintenance. We define the mSWI/SNF functional repertoire in FP-RMS. We find that SMARCA4 (encoding BRG1) is overexpressed in this malignancy compared to skeletal muscle and is essential for cell proliferation. Proteomic studies suggest proximity between PAX3-FOXO1 and BAF complexes, which is further supported by genome-wide binding profiles revealing enhancer colocalization of BAF with core regulatory transcription factors. Further, mSWI/SNF complexes localize to sites of de novo histone acetylation. Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes, which is recapitulated by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor. Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage with an aggressive subtype caused by translocations involving PAX3- /PAX7-FOXO1 chimeric transcription factors. Here the authors show that the BRG1-containing BAF complex is overexpressed and acts largely independently of the PAX3-FOXO1 chimera on chromatin to result in a myogenic differentiation blockade in this malignancy. [ABSTRACT FROM AUTHOR]

Although large exons cannot be readily recognized by the spliceosome, many are evolutionarily conserved and constitutively spliced for inclusion in the processed transcript. Furthermore, whether large exons may be enriched in a certain subset of proteins, or mediate specific functions, has remained unclear. Here, we identify a set of nearly 3,000 SRSF3‐dependent large constitutive exons (S3‐LCEs) in human and mouse cells. These exons are enriched for cytidine‐rich sequence motifs, which bind and recruit the splicing factors hnRNP K and SRSF3. We find that hnRNP K suppresses S3‐LCE splicing, an effect that is mitigated by SRSF3 to thus achieve constitutive splicing of S3‐LCEs. S3‐LCEs are enriched in genes for components of transcription machineries, including mediator and BAF complexes, and frequently contain intrinsically disordered regions (IDRs). In a subset of analyzed S3‐LCE‐containing transcription factors, SRSF3 depletion leads to deletion of the IDRs due to S3‐LCE exon skipping, thereby disrupting phase‐separated assemblies of these factors. Cytidine enrichment in large exons introduces proline/serine codon bias in intrinsically disordered regions and appears to have been evolutionarily acquired in vertebrates. We propose that layered splicing regulation by hnRNP K and SRSF3 ensures proper phase‐separation of these S3‐LCE‐containing transcription factors in vertebrates. Synopsis: Although their recognition poses a challenge to spliceosomes, large exons are often conserved and spliced. Here, this is linked to their nucleotide composition, which drives splicing factor recruitment and endows encoded proteins with specific properties. Analysis of ˜ 3,000 SRSF3‐dependent large exons reveals enrichment for cytidine nucleotidesCytidine enrichment favors recruitment of splicing factors SRSF3 and hnRNP KInclusion of cytidine‐rich large exons encoding serine/proline‐rich intrinsically disordered regions (IDRs) is found in vertebrate transcription factorsLoss of IDR inclusion upon SRSF3 depletion‐induced exon‐skipping disrupts transcription factor phase separation. [ABSTRACT FROM AUTHOR]

Subunit switches in the BAF chromatin remodeler are essential during development. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause neurodevelopmental disorders, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we leveraged ARID1B+/− Coffin-Siris patient-derived iPSCs and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF). ARID1B-BAF regulates exit from pluripotency and lineage commitment by attenuating thousands of enhancers and genes of the NANOG and SOX2 networks. In iPSCs, these enhancers are maintained active by ARID1A-containing BAF. At the onset of differentiation, cells transition from ARID1A- to ARID1B-BAF, eliciting attenuation of the NANOG/SOX2 networks and triggering pluripotency exit. Coffin-Siris patient cells fail to perform the ARID1A/ARID1B switch, and maintain ARID1A-BAF at the pluripotency enhancers throughout all stages of CNCC formation. This leads to persistent NANOG/SOX2 activity which impairs CNCC formation. Despite showing the typical neural crest signature (TFAP2A/SOX9-positive), ARID1B-haploinsufficient CNCCs are also aberrantly NANOG-positive. These findings suggest a connection between ARID1B mutations, neuroectoderm specification and a pathogenic mechanism for Coffin-Siris syndrome. Mutations in the ARID1B subunit of the BAF chromatin remodeling complex are associated with the neurodevelopmental Coffin-Siris syndrome. Here the authors reveal that there is a transition from ARID1A-containing complexes to ARID1B during cranial neural crest cell differentiation that is impaired in Coffin-Siris patient-derived cells, which is important for exit from pluripotency. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against glioma; however, the molecular target and mechanism of action of CBD in glioma are poorly understood. Here we investigated the molecular mechanisms underlying the antitumor effect of CBD in preclinical models of human glioma. Our results showed that CBD induced autophagic rather than apoptotic cell death in glioma cells. We also showed that CBD induced mitochondrial dysfunction and lethal mitophagy arrest, leading to autophagic cell death. Mechanistically, calcium flux induced by CBD through TRPV4 (transient receptor potential cation channel subfamily V member 4) activation played a key role in mitophagy initiation. We further confirmed TRPV4 levels correlated with both tumor grade and poor survival in glioma patients. Transcriptome analysis and other results demonstrated that ER stress and the ATF4-DDIT3-TRIB3-AKT-MTOR axis downstream of TRPV4 were involved in CBD-induced mitophagy in glioma cells. Lastly, CBD and temozolomide combination therapy in patient-derived neurosphere cultures and mouse orthotopic models showed significant synergistic effect in both controlling tumor size and improving survival. Altogether, these findings showed for the first time that the antitumor effect of CBD in glioma is caused by lethal mitophagy and identified TRPV4 as a molecular target and potential biomarker of CBD in glioma. Given the low toxicity and high tolerability of CBD, we therefore propose CBD should be tested clinically for glioma, both alone and in combination with temozolomide. Abbreviations: 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; ATF4: activating transcription factor 4; Baf-A1: bafilomycin A1; CANX: calnexin; CASP3: caspase 3; CAT: catalase; CBD: cannabidiol; CQ: chloroquine; DDIT3: DNA damage inducible transcript 3; ER: endoplasmic reticulum; GBM: glioblastoma multiforme; GFP: green fluorescent protein; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PARP1: poly(ADP-ribose) polymerase; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; SLC8A1: solute carrier family 8 member A1; SQSTM1: sequestosome 1; TCGA: The cancer genome atlas; TEM: transmission electron microscopy; TMZ: temozolomide; TRIB3: tribbles pseudokinase 3; TRPC: transient receptor potential cation channel subfamily C; TRPV4: transient receptor potential cation channel subfamily V member 4 [ABSTRACT FROM AUTHOR]

Although macroautophagy/autophagy has been proposed as a critical defense mechanism against HIV-1 by targeting viral components for degradation, its contribution as a catabolic process in providing optimal anti-HIV-1 immunity has never been addressed. The failure to restore proper antiviral CD8A/CD8 T-cell immunity, especially against HIV-1, is still the major limitation of current antiretroviral therapies. Consequently, it is of clinical imperative to provide new strategies to enhance the function of HIV-1-specific CD8A T-cells in patients under antiretroviral treatments (ART). Here, we investigated whether targeting autophagy activity could be an optional solution to make this possible. Our data show that, after both polyclonal and HIV-1-specific activation, CD8A T-cells from ART displayed reduced autophagy-dependent degradation of lysosomal contents when compared to naturally HIV-1 protected elite controllers (EC). We further confirmed in EC, by using specific BECN1 gene silencing and lysosomal inhibitors, the critical role of active autophagy in superior CD8A T-cell protection against HIV-1. More importantly, we found that an IL21 treatment was effective in rescuing the antiviral CD8A T-cell immunity from ART in an autophagy-dependent manner. Finally, we established that IL21-dependent rescue occurred due to the enhanced degradation of endogenous lipids via autophagy, referred to as lipophagy, which fueled the cellular rates of mitochondrial beta-oxidation. In summary, our data show that autophagy/lipophagy can be considered as a therapeutic tool to elicit functional antiviral CD8 T-cell responses. Our results also provide additional insights toward the development of improved T-cell-based prevention and cure strategies against HIV-1. Abbreviations: ART: patients under antiretroviral therapy; BaF: bafilomycin A1; BECN1: beclin 1; CEF: cytomegalo-, Epstein-Barr- and flu-virus peptide pool; Chloro.: chloroquine; EC: elite controllers; FAO: fatty acid beta-oxidation; HIVneg: HIV-1-uninfected control donors; IFNG/IFN-γ: interferon gamma; IL21: interleukin 21; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PBMC: peripheral blood mononuclear cells; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1. [ABSTRACT FROM AUTHOR]

Efficient subsampling designs reduce forest inventory costs by focusing sampling efforts on more variable forest attributes. Sector subsampling is an efficient and accurate alternative to big basal area factor (big BAF) sampling to estimate the mean basal area to biomass ratio. In this study, we apply sector subsampling of spherical images to estimate aboveground biomass and compare our image-based estimates with field data collected from three early spacing trials on western Newfoundland Island in eastern Canada. The results show that sector subsampling of spherical images produced increased sampling errors of 0.3–3.4 per cent with only about 60 trees measured across 30 spherical images compared with about 4000 trees measured in the field. Photo-derived basal area was underestimated because of occluded trees; however, we implemented an additional level of subsampling, collecting field-based basal area counts, to correct for bias due to occluded trees. We applied Bruce's formula for standard error estimation to our three-level hierarchical subsampling scheme and showed that Bruce's formula is generalizable to any dimension of hierarchical subsampling. Spherical images are easily and quickly captured in the field using a consumer-grade 360° camera and sector subsampling, including all individual tree measurements, were obtained using a custom-developed python software package. The system is an efficient and accurate photo-based alternative to field-based big BAF subsampling. [ABSTRACT FROM AUTHOR]

Autophagic flux is a critical cellular process that is vastly under-appreciated in terms of its importance to human health. Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling. To date, translation of this knowledge has been hampered because there has been no way to directly measure autophagic flux in humans. In this study we detail a method whereby human macroautophagic/autophagic flux can be directly measured from human blood samples. We show that whole blood samples can be treated with the lysosomal inhibitor chloroquine, and peripheral blood mononuclear cells isolated from these samples could be used to measure autophagic machinery protein LC3B-II. Blocking of autophagic flux in cells while still in whole blood represents an important advance because it preserves genetic, nutritional, and signaling parameters inherent to the individual. We show this method was reproducible and defined LC3B-II as the best protein to measure autophagic flux in these cells. Finally, we show that this method is relevant to assess intra-individual variation induced by an intervention by manipulating nutrition signaling with an ex vivo treatment of whole blood that comprised leucine and insulin. Significantly, this method will enable the identification of factors that alter autophagic flux in humans, and better aid their translation in the clinic. With further research, it could also be used as a novel biomarker for risk of age-related chronic disease. Abbreviations: AMPK: AMP-activated protein kinase; ACTB: actin beta; ATG5: autophagy related 5; BAF: bafilomycin A1; CQ: chloroquine; DMSO: dimethyl sulfoxide; DPBS: Dulbecco's phosphate-buffered saline; EDTA: ethylenediaminetetraacetic acid; KO: knockout; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; PBMCs: peripheral blood mononuclear cells; PMNs: polymorphonuclear cells; RPMI: Roswell Park Memorial Institute; SQSTM1: sequestosome 1; TBST: Tris-buffered saline containing 0.1% (v:v) Tween 20; TEM: transmission electron microscopy. [ABSTRACT FROM AUTHOR]

The structure of our Galaxy has been studied from ultraviolet (UV) star counts obtained with the Ultra-Violet Imaging Telescope (UVIT) on board the AstroSat satellite, in Far-UV (FUV) and Near-UV (NUV) bands. The F154W (BaF2) and N263M (NUVB4) filters were used in the FUV and NUV bands, respectively. The point sources are separated from the extra-galactic sources of UVIT observations using infrared (IR) color cut method. The observed UVIT star counts match well with the simulations obtained from the Besançon model of stellar population synthesis towards several Galactic directions. We also estimated the scale length and scale height of the thick disc and the scale height of the thin disc using the space density function and the exponential density law for the stars of intermediate galactic latitudes. The scale length of the thick disc ranges from 3.11 to 5.40 kpc whereas the scale height ranges from 530 ± 32 pc to 630 ± 29 pc. The scale height of the thin disc comes out to be in the range of 230 ± 20 pc to 330 ± 11 pc. [ABSTRACT FROM AUTHOR]

We present far ultraviolet (FUV) observations of globular cluster NGC 4147 using three FUV filters, BaF 2 (F154W), sapphire (F169M), and silica (F172M) of Ultra-Violet Imaging Telescope (UVIT) on-board the AstroSat satellite. We confirmed the cluster membership of the UVIT observed sources using proper motions from Gaia data release 2 (GAIA DR2). We identified 37 blue horizontal branch stars (BHBs), one blue straggler star (BSS) and 15 variable stars using UV-optical color magnitude diagrams (CMDs). We find that all the FUV bright BHBs are second generation population stars. Using UV-optical CMDs, we identify two sub-populations, BHB1 and BHB2, among the UV-bright BHBs in the cluster with stars count ratio of 24:13 for BHB1 and BHB2. The effective temperatures ( T eff ) of BHB1 and BHB2 were derived using color-temperature relation of BaSTI-IAC zero-age horizontal branch (ZAHB). We found that BHB1 stars are more centrally concentrated than BHB2 stars. We also derive physical parameters of the detected FUV bright BSS by fitting younger age BaSTI-IAC isochrones on optical and UV-optical CMDs. [ABSTRACT FROM AUTHOR]

Multiple placental pathologies are associated with failures in trophoblast differentiation, yet the underlying transcriptional regulation is poorly understood. Here, we discovered msh homeobox 2 (MSX2) as a key transcriptional regulator of trophoblast identity using the human trophoblast stem cell model. Depletion of MSX2 resulted in activation of the syncytiotrophoblast transcriptional program, while forced expression of MSX2 blocked it. We demonstrated that a large proportion of the affected genes were directly bound and regulated by MSX2 and identified components of the SWItch/Sucrose nonfermentable (SWI/SNF) complex as strong MSX2 interactors and target gene cobinders. MSX2 cooperated specifically with the SWI/SNF canonical BAF (cBAF) subcomplex and cooccupied, together with H3K27ac, a number of differentiation genes. Increased H3K27ac and cBAF occupancy upon MSX2 depletion imply that MSX2 prevents premature syncytiotrophoblast differentiation. Our findings established MSX2 as a repressor of the syncytiotrophoblast lineage and demonstrated its pivotal role in cell fate decisions that govern human placental development and disease. [ABSTRACT FROM AUTHOR]

Interstitial deletions on the long arm of chromosome 12 (12q deletions) are rare, and are associated with intellectual disability, developmental delay, failure to thrive and congenital anomalies. The precise genotype-phenotype correlations of different deletions has not been completely resolved. Ascertaining individuals with overlapping deletions and complex phenotypes may help to identify causative genes and improve understanding of 12q deletion syndromes. We here describe two individuals with non-overlapping 12q14 deletions encountered at our clinical genetics outpatient clinic and perform a review of all previously published interstitial 12q deletions to further delineate genotype-phenotype correlations. Both individuals presented with a neurodevelopmental disorder with various degrees of intellectual disability, failure to thrive and dysmorphic features. Previously, larger deletions overlapping large parts of the deletions encountered in both individuals have been described. Whereas, individual 1 seems to fit into the previously described phenotypic spectrum of the 12q14 microdeletion syndrome, individual 2 displays more severe neurological symptoms, which are likely caused by haploinsufficiency of the BAF complex member SMARCC2 , which is included in the deletion. We furthermore perform a review of all previously published interstitial 12q deletions which we found to cluster amongst 5 regions on chromosome 12, to further delineate genotype-phenotype correlations, and we discuss likely disease relevant genes for each of these deletion clusters. Together, this expands knowledge on deletions on chromosome 12q which might facilitate patient counseling. Also, it illustrates that re-analysis of previously described microdeletions syndromes in the next generation sequencing era can be useful to delineate genotype-phenotype correlations and identify disease relevant genes in individuals with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

β-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation. β-actin loss can affect gene expression and heterochromatin organization. Here the authors conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) to investigate the impact of changes in β-actin levels on 3d genome architecture and chromatin remodeling activities of BAF and polycomb proteins. [ABSTRACT FROM AUTHOR]

Barium fluoride (BaF2) crystals are attracting much attention as efficient inorganic scintillator promising for high‐energy physics, industrial inspection, and other fields because of the fast component of the decay time (0.6 ns) and high radiation resistance. However, two major drawbacks limit its practical application: (i) a slow decay time of ~600 ns is derived from self‐trapping excitons; (ii) the absolute light yield from the fast luminescence component is not competitive. The introducing of rare earth ions and preparation of BaF2 polycrystalline ceramics is considered to be effective measures to solve these bottlenecks. Pr3+ is extremely suitable as the activated ion of scintillation materials, which possess emission peaks located in visible band and the faster 5d–4f transition. In this work, highly sinterable Pr3+:BaF2 precursor powder was synthesized via the coprecipitation method by adjusting the reactant concentration and temperature. The morphology and microstructure of as‐synthesized powders were characterized using scanning electron microscopy (SEM) and transmittance electron microscopy analysis. The 5 at.% Pr3+:BaF2 transparent ceramic with a transmittance of 50.7% at the wavelength of 500 nm was fabricated by hot pressing the as‐prepared powders at 900°C for 4 h under the axial pressure of 50 MPa. The SEM images of ceramic cross‐section show that the residual pore is the main light scattering source. The absorption and emission spectrum of ceramic samples were discussed. [ABSTRACT FROM AUTHOR]

The system xBa(PO3)2·(99 – x)(AlF3–BaF2–CaF2–MgF2–SrF2)–1NdF3, where x = 2, 5, 10, 15, 20, 30, and 40 mol %, is considered. The dependences of the thermal coefficient of linear expansion, Tg, Tx. Tx–Tg, HV, and K1C on the concentration of Ba(PO3)2 are determined. It is found that an increase in the concentration of Ba(PO3)2 with the uniform replacement of the fluoride component leads to a decrease in the thermal coefficient of linear expansion, an increase in the glass transition temperature and crystallization, and a broadening of the interval Tx–Tg. It is shown that an increase in Ba(PO3)2 in the glass leads to an increase in microhardness HV and fracture toughness K1C of the glasses. The main thermomechanical characteristics of the studied glasses are compared with those of their commercial analogs. [ABSTRACT FROM AUTHOR]

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