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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]

This study aims to investigate how alternations of the land surface temperature (LST) affects the normalized difference vegetation index (NDVI) in Paphos forest, Cyprus, using Landsat-5 and Landsat-8 imagery for the time periods 1993–2000 and 2013–2018, respectively. A total of 262 Landsat images were processed to compute the mean monthly NDVI and LST values and create a time series. Using the Cook's distance, the effect of missing values in the analysis of the time series were examined. Results from the cross-correlation and cross-variograms, decomposition model, and the BFAST algorithm were compared to produce reliable conclusions on forest changes and satellite, meteorological, and environmental data were combined to interpret the changes that occurred inside the forest. The decomposition analysis showed a decrease of 2.7% in the LST for the period 1993–2000 and an increase of 4.6% in the LST during the period 2013–2018. The NDVI trend is negatively correlated to the LST trend for both time periods. An increase in the LST trend was identified in November 1998 as well as in the NDVI trend in October 1994 and May 2014 that was caused by favorable climatic conditions. An increase in the NDVI trend from May 2014 to December 2015 may be related to reduced pityocampa attacks. An abrupt decrease was detected in December 2015 that was probably caused by the locust invasion that occurred in the island earlier that year. A positive correlation appears for LST and NDVI variables for time lags 4, 5, 6, 7, and 8 months. Overall, it was shown that LST and NDVI analysis is very promising for identifying potential forest decline. [ABSTRACT FROM AUTHOR]

Maturing male germ cells undergo a unique developmental process in spermiogenesis that replaces nucleosomal histones with protamines, the process of which is critical for testicular development and male fertility. The progress of this exchange is regulated by complex mechanisms that are not well understood. Now, with mouse genetic models, we show that barrier-to-autointegration factor-like protein (BAF-L) plays an important role in spermiogenesis and spermatozoal function. BAF-L is a male germ cell marker, whose expression is highly associated with the maturation of male germ cells. The genetic deletion of BAF-L in mice impairs the progress of spermiogenesis and thus male fertility. This effect on male fertility is a consequence of the disturbed homeostasis of histones and protamines in maturing male germ cells, in which the interactions between BAF-L and histones/protamines are implicated. Finally, we show that reduced testicular expression of BAF-L represents a risk factor of human male infertility. [ABSTRACT FROM AUTHOR]

This research investigated the combined use of sewage sludge (SS) and plant growth-promoting rhizobia (PGPR) for Ridge gourd (Luffa acutangula (L.) Roxb.) cultivated under field conditions. The different treatments of SS and PGPR such as 0% (soil as control), 5% SS, 5% SS + PGPR, 10% SS, and 10% SS + PGPR were applied to assess their impacts on seedling growth, biochemical response, and yield performance of Ridge gourd. The results showed that the highest seedling emergence (92.3 ± 2.1%), fresh biomass (9.6 ± 0.3 g), growth rate (1.4 ± 0.1 g/day), seedling length (15.5 ± 0.3 cm), root length (10.4 ± 0.3 cm), total chlorophyll (3.2 ± 0.1 mg/g), crop yield (13.8 ± 0.1 kg/plant), and average crop yield per harvest (2.8 ± 0.1 kg/plant) were observed in 10% SS + PGPR treatment. The enzyme activities of superoxide dismutase (SOD; µg/g) and catalase (CAT: µg/g) were significantly lowered after PGPR inoculation in higher SS treatments. The results of principal component (PC) and Euclidian clustered distance analyses showed a positive influence of SS dose on soil nutrient availability and Ridge gourd's growth, biochemical responses, and yield performance. Moreover, the elemental analysis showed that the bioaccumulation factor (BAF < 0.90) and health risk index (HRI < 0.40) of selected metal elements (Cd, Cr, Cu, Fe, Mn, and Zn) were within the permissible limits, indicating consumption of Ridge gourd fruits was safe. The outcomes of this study suggest the potential use of SS and PGPR for improved Ridge gourd production and contribution towards sustainable development goal (SDG) 12 on responsible consumption and production of vegetable crops. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of multicolor light-emitting nanomaterials based on rare earths (RE3+) are of great importance due to their possible use in optoelectronic devices, such as LEDs or displays. In the present work, oxyfluoride glass-ceramics containing BaF2 nanocrystals co-doped with Tb3+, Eu3+ ions were fabricated from amorphous xerogels at 350 °C. The analysis of the thermal behavior of fabricated xerogels was performed using TG/DSC measurements (thermogravimetry (TG), differential scanning calorimetry (DSC)). The crystallization of BaF2 phase at the nanoscale was confirmed by X-ray diffraction (XRD) measurements and transmission electron microscopy (TEM), and the changes in silicate sol–gel host were determined by attenuated total reflectance infrared (ATR-IR) spectroscopy. The luminescent characterization of prepared sol–gel materials was carried out by excitation and emission spectra along with decay analysis from the 5D4 level of Tb3+. As a result, the visible light according to the electronic transitions of Tb3+ (5D4 → 7FJ (J = 6–3)) and Eu3+ (5D0 → 7FJ (J = 0–4)) was recorded. It was also observed that co-doping with Eu3+ caused the shortening in decay times of the 5D4 state from 1.11 ms to 0.88 ms (for xerogels) and from 6.56 ms to 4.06 ms (for glass-ceramics). Thus, based on lifetime values, the Tb3+/Eu3+ energy transfer (ET) efficiencies were estimated to be almost 21% for xerogels and 38% for nano-glass-ceramics. Therefore, such materials could be successfully predisposed for laser technologies, spectral converters, and three-dimensional displays. [ABSTRACT FROM AUTHOR]

Search for doped superconducting topological insulators is of prime importance for new quantum technologies. We report on fabrication of Sr-doped Bi 2 Te 3 single crystals. We found that Bridgman grown samples have p-type conductivity in the low 10 19 cm − 3 , high mobility of 4000 cm 2 V − 1 s − 1 , crystal structure independent on nominal dopant content, and no signs of superconductivity. We also studied molecular beam epitaxy grown Sr x Bi 2 − x Te 3 films on lattice matched (1 1 1) BaF 2 polar surface. Contrary to the bulk crystals thin films have n-type conductivity. Carrier concentration, mobility and c-lattice constant demonstrate pronounced dependence on Sr concentration x. Variation of the parameters did not lead to superconductivity. We revealed, that transport and structural parameters are governed by Sr dopants incorporation in randomly inserted Bi bilayers into the parent matrix. Thus, our data shed light on the structural position of dopant in Bi 2 Te 3 and should be helpful for further design of topological insulator-based superconductors. [ABSTRACT FROM AUTHOR]

The possibility of using complex structure modification for aluminium casting alloys' mechanical properties improvement was studied. The fluxes widely used in the industry are mainly intended for the modification of a single structural component of Al–Si alloys, which does not allow unifying of the modification process in a production environment. Thus, a new modifying flux that has a complex effect on the structure of Al–Si alloys has been developed. It consists of the following components: TiO2, containing a primary α-Al grain size modifier; BaF2 containing a eutectic silicon modifier; KF used to transform titanium and barium into the melt. The effect of the complex titanium dioxide-based modifier on the macro-, microstructure and the mechanical properties of industrial aluminium–silicon casting alloys containing 5%, 6%, 9%, 11% and 17% Si by weight was studied. It was found that the tensile strength (σB) of Al–Si alloys exceeds the similar characteristics for the alloys modified using the standard sodium-containing flux to 32%, and the relative elongation (δ) increases to 54%. The alloys' mechanical properties improvement was shown to be the result of the flux component's complex effect on the macro- and microstructure. The effect includes the simultaneous reduction in secondary dendritic arm spacing due to titanium, the refinement and decreasing size of silicon particles in the eutectic with barium and potassium, and the modifying of the primary silicon. The reliability of the studies was confirmed using up-to-date test systems, a significant amount of experimental data and the repeatability of the results for a large number of samples in the identical initial state. [ABSTRACT FROM AUTHOR]

(1) Indocyanine green angiography (ICG-A) shows the presence of mid-phase hyperfluorescent area in central serous chorioretinopathy (CSCR). However, their exact meaning remains uncertain. (2) The clinical and multimodal imaging findings of 100 patients (133 eyes) with CSCR, including the enhanced-depth-imaging OCT (EDI-OCT), blue-light fundus autofluorescence (BAF), fluorescein and indocyanine green angiography (FA and ICG-A) findings were reviewed. Mid-phase hyperfluorescent plaques (MPHP) were defined as fairly well circumscribed hyperfluorescent regions during the midphase of the ICG-A. The association between MPHP and other clinical/imaging parameters was assessed using a multiple logistic regression analysis. (3) MPHP were detected in 59.4% of eyes with CSCR. The chronic form of the disease, the presence of irregular pigment epithelium detachments (PED) and the retinal pigment epithelium (RPE) changes seen on FA were associated with the presence of MPHP in the multivariate analysis (p = 0.015; p = 0.018 and p = 0.002; respectively). OCT showed RPE bulges or PED in 98.7% of areas with MPHP and BAF showed changes in 57.3% of areas with MPHP. (4) MPHP were associated with a chronic form of CSCR and colocated with PED or RPE bulges. MPHP should be recognized as a sign of early RPE dysfunction before it is detected with BAF. [ABSTRACT FROM AUTHOR]