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1.
Cell Death Dis ; 12(1): 117, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483469

RESUMO

The WW-and-C2-domain-containing (WWC) protein family is involved in the regulation of cell differentiation, cell proliferation, and organ growth control. As upstream components of the Hippo signaling pathway, WWC proteins activate the Large tumor suppressor (LATS) kinase that in turn phosphorylates Yes-associated protein (YAP) and its paralog Transcriptional coactivator-with-PDZ-binding motif (TAZ) preventing their nuclear import and transcriptional activity. Inhibition of WWC expression leads to downregulation of the Hippo pathway, increased expression of YAP/TAZ target genes and enhanced organ growth. In mice, a ubiquitous Wwc1 knockout (KO) induces a mild neurological phenotype with no impact on embryogenesis or organ growth. In contrast, we could show here that ubiquitous deletion of Wwc2 in mice leads to early embryonic lethality. Wwc2 KO embryos display growth retardation, a disturbed placenta development, impaired vascularization, and finally embryonic death. A whole-transcriptome analysis of embryos lacking Wwc2 revealed a massive deregulation of gene expression with impact on cell fate determination, cell metabolism, and angiogenesis. Consequently, a perinatal, endothelial-specific Wwc2 KO in mice led to disturbed vessel formation and vascular hypersprouting in the retina. In summary, our data elucidate a novel role for Wwc2 as a key regulator in early embryonic development and sprouting angiogenesis in mice.

2.
Nat Commun ; 11(1): 5499, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127892

RESUMO

The epiblast, which provides the foundation of the future body, is actively reshaped during early embryogenesis, but the reshaping mechanisms are poorly understood. Here, using a 3D in vitro model of early epiblast development, we identify the canonical Wnt/ß-catenin pathway and its central downstream factor Esrrb as the key signalling cascade regulating the tissue-scale organization of the murine pluripotent lineage. Although in vivo the Wnt/ß-catenin/Esrrb circuit is dispensable for embryonic development before implantation, autocrine Wnt activity controls the morphogenesis and long-term maintenance of the epiblast when development is put on hold during diapause. During this phase, the progressive changes in the epiblast architecture and Wnt signalling response show that diapause is not a stasis but instead is a dynamic process with underlying mechanisms that can appear redundant during transient embryogenesis.


Assuntos
Diapausa/fisiologia , Células-Tronco Embrionárias/metabolismo , Receptores Estrogênicos/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Desenvolvimento Embrionário , Feminino , Camadas Germinativas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfogênese , Proteínas Serina-Treonina Quinases/metabolismo , Receptores Estrogênicos/genética , beta Catenina/genética
3.
Environ Pollut ; 268(Pt A): 115906, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33120333

RESUMO

Fluorescence spectroscopy is a commonly used technique to analyze dissolved organic matter in aquatic environments. Given the high sensitivity and non-destructive analysis, fluorescence has recently been used to study water-soluble organic carbon (WSOC) in atmospheric aerosols, which have substantial abundance, various sources and play an important role in climate change. Yet, current research on WSOC characterization is rather sparse and limited to a few isolated sites, making it challenging to draw fundamental and mechanistic conclusions. Here we presented a review of the fluorescence properties of atmospheric WSOC reported in various field and laboratory studies, to discuss the current advances and limitations of fluorescence applications. We highlighted that photochemical reactions and relevant aging processes have profound impacts on fluorescence properties of atmospheric WSOC, which were previously unnoticed for organic matter in aquatic environments. Furthermore, we discussed the differences in sources and chemical compositions of fluorescent components between the atmosphere and hydrosphere. We concluded that the commonly used fluorescence characteristics derived from aquatic environments may not be applicable as references for atmospheric WSOC. We emphasized that there is a need for more systematic studies on the fluorescence properties of atmospheric WSOC and to establish a more robust reference and dataset for fluorescence studies in atmosphere based on extensive source-specific experiments.

4.
Sci Adv ; 6(36)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917606

RESUMO

OCT4 (also known as POU5F1) plays an essential role in reprogramming. It is the only member of the POU (Pit-Oct-Unc) family of transcription factors that can induce pluripotency despite sharing high structural similarities to all other members. Here, we discover that OCT6 (also known as POU3F1) can elicit reprogramming specifically in human cells. OCT6-based reprogramming does not alter the mesenchymal-epithelial transition but is attenuated through the delayed activation of the pluripotency network in comparison with OCT4-based reprogramming. Creating a series of reciprocal domain-swapped chimeras and mutants across all OCT factors, we clearly delineate essential elements of OCT4/OCT6-dependent reprogramming and, conversely, identify the features that prevent induction of pluripotency by other OCT factors. With this strategy, we further discover various chimeric proteins that are superior to OCT4 in reprogramming. Our findings clarify how reprogramming competences of OCT factors are conferred through their structural components.

5.
Sci Adv ; 6(29): eaba1593, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32832621

RESUMO

Mouse embryonic stem cells cultured with MEK (mitogen-activated protein kinase kinase) and GSK3 (glycogen synthase kinase 3) inhibitors (2i) more closely resemble the inner cell mass of preimplantation blastocysts than those cultured with SL [serum/leukemia inhibitory factor (LIF)]. The transcriptional mechanisms governing this pluripotent ground state are unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. We show that ß-catenin, stabilized by GSK3 inhibition in medium with 2i, supplies transcriptional coregulators at pluripotency loci. This selectively strengthens pluripotency loci and renders them addicted to transcription initiation for productive gene body elongation in detriment to Pol2 pause release. By contrast, cell cycle genes are not bound by ß-catenin, and proliferation/self-renewal remains tightly controlled by Pol2 pause release under 2i conditions. Our findings explain how pluripotency is reinforced in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other contexts.

6.
Nat Chem Biol ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807969

RESUMO

Identifying molecular and cellular processes that regulate reprogramming competence of transcription factors broadens our understanding of reprogramming mechanisms. In the present study, by a chemical screen targeting major epigenetic pathways in human reprogramming, we discovered that inhibiting specific epigenetic roadblocks including disruptor of telomeric silencing 1-like (DOT1L)-mediated H3K79/K27 methylation, but also other epigenetic pathways, catalyzed by lysine-specific histone demethylase 1A, DNA methyltransferases and histone deacetylases, allows induced pluripotent stem cell generation with almost all OCT factors. We found that simultaneous inhibition of these pathways not only dramatically enhances reprogramming competence of most OCT factors, but in fact enables dismantling of species-dependent reprogramming competence of OCT6, NR5A1, NR5A2, TET1 and GATA3. Harnessing these induced permissive epigenetic states, we performed an additional screen with 98 candidate genes. Thereby, we identified 25 transcriptional regulators (OTX2, SIX3, and so on) that can functionally replace OCT4 in inducing pluripotency. Our findings provide a conceptual framework for understanding how transcription factors elicit reprogramming in dependency of the donor cell epigenome that differs across species.

7.
ACS Appl Mater Interfaces ; 12(26): 29566-29574, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510190

RESUMO

For applications in energy storage and conversion, many metal oxide (MO)/C composite fibers have been synthesized using cellulose as the template. However, MO particles in carbon fibers usually experience anomalous growth to a size of >200 nm, which is detrimental to the overall performance of the composite. In this paper, we report the successful development of a generic approach to synthesize a fiber composite with highly dispersed MO nanoparticles (10-80 nm) via simple swelling, nitrogen doping, and carbonization of the cellulose microfibril. The growth of the MO nanoparticles is confined by the structure of the microfibrils. Density functional theory calculation further reveals that the doped N atoms supply ample nucleation sites for size confinement of the nanoparticles. The encapsulation structure of small MO nanoparticles in the conductive carbon matrix improves their electrochemical performance. For example, the formed SnOx/carbon nanocomposite exhibits high specific capacities of 1011.0 mA h g-1 at 0.5 A g-1 and 581.8 mA h g-1 at 5 A g-1. Moreover, the fiber-like nanocomposite can be combined with carbon nanotubes to form a flexible binder-free electrode with a capacity of ∼10 mA h cm-2, far beyond the commercial level. The process developed in this study offers an alternative approach to sophisticated electrospinning for the synthesis of other fiber-like MO/carbon nanocomposites for versatile applications.

8.
Stem Cells ; 38(8): 960-972, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32346926

RESUMO

Aberrant epigenetic reprogramming is one of the major barriers for somatic cell reprogramming. Although our previous study has indicated that H3K27me3 demethylase KDM6A can improve the nuclear reprogramming efficiency, the mechanism remains unclear. In this study, we demonstrate that the overexpression of Kdm6a may improve induced pluripotent stem cell (iPSC) reprogramming efficiency in a demethylase enzymatic activity-dependent manner. KDM6A erased H3K27me3 on pluripotency- and metabolism-related genes, and consequently facilitated changing the gene expression profile and metabolic pattern to an intermediate state. Furthermore, KDM6A may promote IL-6 expression, and the secreted IL-6 may further improve iPSC reprogramming efficiency. In addition, KDM6A may promote PTEN expression to decrease p-AKT and p-mTOR levels, which in turn facilitates reprogramming. Overall, our results reveal that KDM6A may promote iPSC reprogramming efficiency by accelerating changes in the gene expression profile and the metabolic pattern in a demethylation-activity-dependent manner. These results may provide an insight into the relationship between epigenomics, transcriptomics, metabolomics, and reprogramming.

9.
FEBS J ; 287(1): 122-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31569299

RESUMO

The functional consequences of cancer-associated missense mutations are unclear for the majority of proteins. We have previously demonstrated that the activity of SOX and Pit-Oct-Unc (POU) family factors during pluripotency reprogramming can be switched and enhanced with rationally placed point mutations. Here, we interrogated cancer mutation databases and identified recurrently mutated positions at critical structural interfaces of the DNA-binding domains of paralogous SOX and POU family transcription factors. Using the conversion of mouse embryonic fibroblasts to induced pluripotent stem cells as functional readout, we identified several gain-of-function mutations that enhance pluripotency reprogramming by SOX2 and OCT4. Wild-type SOX17 cannot support reprogramming but the recurrent missense mutation SOX17-V118M is capable of inducing pluripotency. Furthermore, SOX17-V118M promotes oncogenic transformation, enhances thermostability and elevates cellular protein levels of SOX17. We conclude that the mutational profile of SOX and POU family factors in cancer can guide the design of high-performance reprogramming factors. Furthermore, we propose cellular reprogramming as a suitable assay to study the functional impact of cancer-associated mutations.


Assuntos
Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Mutação de Sentido Incorreto , Neoplasias/patologia , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXF/genética , Animais , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Células-Tronco Embrionárias/metabolismo , Perfilação da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Neoplasias/genética , Neoplasias/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Fatores de Transcrição SOXF/metabolismo
10.
Environ Pollut ; 257: 113616, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761583

RESUMO

Brown carbon (BrC) has been proposed as an important driving factor in climate change due to its light absorption properties. However, our understanding of BrC's chemical and optical properties are inadequate, particularly at remote regions. This study conducts a comprehensive investigation of BrC aerosols in summer (Aug. 2013) and winter (Jan. 2014) at Southeast Tibetan Plateau, which is ecologically fragile and sensitive to global warming. The concentrations of methanol-soluble BrC (MeS-BrC) are approximately twice of water-soluble BrC (WS-BrC), demonstrating the environmental importance of water-insoluble BrC are previously underestimated with only WS-BrC considered. The mass absorption efficiency of WS-BrC (0.27-0.86 m2 g-1) is lower than those in heavily polluted South Asia, indicating a distinct contrast between the two sides of Himalayas. Fluorescence reveals that the absorption of BrC is mainly attributed to humic-like and protein-like substances, which broaden the current knowledge of BrC's chromophores. Combining organic tracer, satellite MODIS data and air-mass backward trajectory analysis, this study finds BrC is mainly derived from bioaerosols and secondary formation in summer, while long-range transport of biomass burning emissions in winter. Our study provides new insights into the optical and chemical properties of BrC, which may have implications for environmental effect and sources of organic aerosols.


Assuntos
Aerossóis/química , Poluentes Atmosféricos/análise , Carbono , Monitoramento Ambiental , Aerossóis/análise , Poluentes Atmosféricos/química , Ásia , Fluorescência , Tibet
11.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683567

RESUMO

The trans-resveratrol (RSV)-loaded silica aerogel (RLSA) was prepared by the sol-gel method, adding the drug during the aging process, solvent replacement and freeze drying. A series of characterizations showed that RSV stays in the silica aerogel in two ways. First, RSV precipitates due to minimal solubility in water during the solvent replacement process. After freeze drying, the solvent evaporates and the RSV recrystallizes. It can be seen from scanning electron microscope (SEM) and transmission electron microscope (TEM) images that the recrystallized RSV with micron-sized long rod-shaped is integrated with the dense silica network skeleton. Second, from small-angle X-ray scattering (SAXS) results, a portion of the RSV molecules is not crystallized and the size is extremely small. This can be attached to the primary and secondary particles of silica to enhance its network structure and inhibit shrinkage, which is why the volume and pore size of RLSA is larger. In addition, the diffusion of RSV in silica alcogel was studied by a one-dimensional model. The apparent diffusion coefficients of inward diffusion, outward diffusion and internal diffusion were calculated by fitting the time- and position-dependent concentration data. It was found that the outward diffusion coefficient (5.25 × 10-10 m2/s) is larger than the inward (2.93 × 10-10 m2/s), which is probably due to the interface effect. The diffusion coefficients obtained for different concentrations in the same process (inward diffusion) are found to be different. This suggests that the apparent diffusion coefficient obtained is affected by molecular adsorption.


Assuntos
Géis/química , Resveratrol/química , Dióxido de Silício/química , Adsorção , Difusão , Liofilização , Nitrogênio/química , Porosidade , Espalhamento a Baixo Ângulo , Temperatura , Termogravimetria , Difração de Raios X
12.
Cell Stem Cell ; 25(6): 737-753.e4, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31708402

RESUMO

Oct4 is widely considered the most important among the four Yamanaka reprogramming factors. Here, we show that the combination of Sox2, Klf4, and cMyc (SKM) suffices for reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs). Simultaneous induction of Sox2 and cMyc in fibroblasts triggers immediate retroviral silencing, which explains the discrepancy with previous studies that attempted but failed to generate iPSCs without Oct4 using retroviral vectors. SKM induction could partially activate the pluripotency network, even in Oct4-knockout fibroblasts. Importantly, reprogramming in the absence of exogenous Oct4 results in greatly improved developmental potential of iPSCs, determined by their ability to give rise to all-iPSC mice in the tetraploid complementation assay. Our data suggest that overexpression of Oct4 during reprogramming leads to off-target gene activation during reprogramming and epigenetic aberrations in resulting iPSCs and thereby bear major implications for further development and application of iPSC technology.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Animais , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Células HEK293 , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Camundongos Knockout , Fator 3 de Transcrição de Octâmero/genética , Reação em Cadeia da Polimerase , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Análise de Sequência de RNA , Tetraploidia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Environ Sci Technol ; 53(21): 12247-12256, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31558018

RESUMO

Nitrogenous aerosols are ubiquitous in the environment and thus play a vital role in the nutrient balance as well as the Earth's climate system. However, their abundance, sources, and deposition are poorly understood, particularly in the fragile and ecosensitive Himalayan and Tibetan Plateau (HTP) region. Here, we report concentrations of nitrogen species and isotopic composition (δ15N) in aerosol samples collected from a forest site in the HTP (i.e., Southeast Tibet). Our results revealed that both organic and inorganic nitrogen contribute almost equally with high abundance of ammonium nitrogen (NH4+-N) and water-insoluble organic nitrogen (WION), contributing ∼40% each to aerosol total nitrogen (TN). The concentrations and δ15N exhibit a significant seasonality with ∼2 times higher in winter than in summer with no significant diurnal variations for any species. Moreover, winter aerosols mainly originated from biomass burning emissions from North India and East Pakistan and reached the HTP through a long-range atmospheric transport. The TN dry deposition and total deposition fluxes were 2.04 kg ha-1 yr-1 and 6.12 kg ha-1 yr-1 respectively. Our results demonstrate that the air contamination from South Asia reach the HTP and is most likely impacting the high altitude ecosystems in an accepted scenario of increasing emissions over South Asia.


Assuntos
Poluentes Atmosféricos , Nitrogênio , Aerossóis , Ecossistema , Monitoramento Ambiental , Florestas , Índia , Paquistão , Estações do Ano , Tibet
14.
Small ; 15(31): e1901747, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215181

RESUMO

A local electric field is induced to engineer the interface of vanadium pentoxide nanofibers (V2 O5 -NF) to manipulate the charge transport behavior and obtain high-energy and durable supercapacitors. The interface of V2 O5 -NF is modified with oxygen vacancies (Vö) in a one-step polymerization process of polyaniline (PANI). In the charge storage process, the local electric field deriving from the lopsided charge distribution around Vö will provide Coulombic forces to promote the charge transport in the resultant Vö-V2 O5 /PANI nanocable electrode. Furthermore, an ≈7 nm porous PANI coating serves as the external percolated charge transport pathway. As the charge transfer kinetics are synergistically enhanced by the dual modifications, Vö-V2 O5 /PANI-based supercapacitors exhibit an excellent specific capacitance (523 F g-1 ) as well as a long cycling lifespan (110% of capacitance remained after 20 000 cycles). This work paves an effective way to promote the charge transfer kinetics of electrode materials for next-generation energy storage systems.

15.
Sci Rep ; 9(1): 7486, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097772

RESUMO

Certain point-mutations in the human SERPINA1-gene can cause severe α1-antitrypsin-deficiency (A1AT-D). Affected individuals can suffer from loss-of-function lung-disease and from gain-of-function liver-disease phenotypes. However, age of onset and severity of clinical appearance is heterogeneous amongst carriers, suggesting involvement of additional genetic and environmental factors. The generation of authentic A1AT-D mouse-models has been hampered by the complexity of the mouse Serpina1-gene locus and a model with concurrent lung and liver-disease is still missing. Here, we investigate point-mutations in the mouse Serpina1a antitrypsin-orthologue, which are homolog-equivalent to ones known to cause severe A1AT-D in human. We combine in silico and in vitro methods and we find that analyzed mutations do introduce potential disease-causing properties into Serpina1a. Finally, we show that introduction of the King's-mutation causes inactivation of neutrophil elastase inhibitory-function in both, mouse and human antitrypsin, while the mouse Z-mutant retains activity. This work paves the path to generation of better A1AT-D mouse-models.


Assuntos
Mutação com Perda de Função , Simulação de Dinâmica Molecular , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/química , Animais , Células COS , Chlorocebus aethiops , Células HEK293 , Células Hep G2 , Humanos , Camundongos , Domínios Proteicos , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo
16.
Cell Rep ; 27(1): 30-39.e4, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30943410

RESUMO

Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency before establishing the neural fate. We employed genetic lineage tracing and found that induction of iNSCs with individual vectors leads to direct lineage conversion. In contrast, polycistronic expression produces a Brn4-Klf4 fusion protein that enables induction of pluripotency. Our study demonstrates that a combination of pluripotency and tissue-specific factors allows direct somatic cell transdifferentiation, bypassing the acquisition of a pluripotent state. This result has major implications for lineage conversion technologies, which hold potential for providing a safer alternative to iPSCs for clinical application both in vitro and in vivo.


Assuntos
Diferenciação Celular/genética , Linhagem da Célula/genética , Transdiferenciação Celular/genética , Reprogramação Celular/genética , Células Híbridas/fisiologia , Fatores de Transcrição/genética , Animais , Fusão Celular , Células Cultivadas , Diploide , Embrião de Mamíferos , Feminino , Células-Tronco Pluripotentes Induzidas/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Células-Tronco Embrionárias Murinas/fisiologia , Células-Tronco Neurais/fisiologia , Fatores de Transcrição/metabolismo
17.
ACS Appl Mater Interfaces ; 11(18): 16647-16655, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30977632

RESUMO

Oxygen vacancies (Vö) play a crucial role in energy storage materials. Oxygen-vacancy-enriched vanadium pentoxide/poly(3,4-ethylenedioxythiophene) (Vö-V2O5/PEDOT) nanocables were prepared through the one-pot oxidative polymerization of PEDOT. PEDOT is used to create tunable concentrations of Vö in the surface layer of V2O5, which has been confirmed by X-ray absorption near edge structure (XANES) analysis and X-ray photoelectron spectroscopy (XPS) measurements. Applied as electrode materials for supercapacitors, the electrochemical performance of Vö-V2O5/PEDOT is improved by the synergistic effects of Vö in V2O5 cores and PEDOT shells with rapid charge transfer and fast Na+ ion diffusion; however, it is compromised subsequently by excessive Vö in consuming more V5+ cations for Faradic reactions. Consequently, the specific capacitance and the energy density of Vö-V2O5/PEDOT nanocables are significantly enhanced when the overall concentration of Vö is 1.3%. The migration of Vö renders an increased capacitance (105% retention) after 10 000 cycles, which is verified and corroborated with density functional theory simulations and XANES analysis. This work provides an illumination for the fabrication of high-performance electrode materials in the energy storage field through Vö.

18.
Stem Cells ; 37(8): 1018-1029, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31021473

RESUMO

The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cellular pluripotency. In this article, we show that ubiquitous and multifunctional poly(C) DNA/RNA-binding protein hnRNP-K occupies Oct4 (Pou5f1) enhancers in embryonic stem cells (ESCs) but is dispensable for the initiation, maintenance, and downregulation of Oct4 gene expression. Nevertheless, hnRNP-K has an essential cell-autonomous function in ESCs to maintain their proliferation and viability. To better understand mechanisms of hnRNP-K action in ESCs, we have performed ChIP-seq analysis of genome-wide binding of hnRNP-K and identified several thousands of hnRNP-K target sites that are frequently co-occupied by pluripotency-related and common factors (Oct4, TATA-box binding protein, Sox2, Nanog, Otx2, etc.), as well as active histone marks. Furthermore, hnRNP-K localizes exclusively within open chromatin, implying its role in the onset and/or maintenance of this chromatin state. Stem Cells 2019;37:1018-1029.


Assuntos
Proliferação de Células , Cromatina/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular , Cromatina/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Camundongos , Fatores de Transcrição/genética
19.
Environ Sci Technol ; 53(7): 3471-3479, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30848122

RESUMO

Brown carbon (BrC) has recently emerged as an important light-absorbing aerosol. This study provides interannual and seasonal variations in light absorption properties, chemical composition, and sources of water-soluble BrC (WS-BrC) based on PM10 samples collected in Godavari, Nepal, from April 2012 to May 2014. The mass absorption efficiency of WS-BrC at 365 nm (MAE365) shows a clear seasonal variability, with the highest MAE365 of 1.05 ± 0.21 m2 g-1 in premonsoon season and the lowest in monsoon season (0.59 ± 0.16 m2 g-1). The higher MAE365 values in nonmonsoon seasons are associated with fresh biomass burning emissions. This is further substantiated by a strong correlation ( r = 0.79, P < 0.01) between Abs365 (light absorption coefficient at 365 nm) and levoglucosan. We found, using fluorescence techniques, that humic-like and protein-like substances are the main chromophores in WS-BrC and responsible for 80.2 ± 4.1% and 19.8 ± 4.1% of the total fluorescence intensity, respectively. BrC contributes to 8.78 ± 3.74% of total light absorption over the 300-700 nm wavelength range. Considering the dominant contribution of biomass burning to BrC over Godavari, this study suggests that reduction in biomass burning emission may be a practical method for climate change mitigation in South Asia.


Assuntos
Carbono , Água , Aerossóis , Ásia , Monitoramento Ambiental , Nepal
20.
Sensors (Basel) ; 19(5)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862018

RESUMO

Pedestrian trajectory prediction under crowded circumstances is a challenging problem owing to human interaction and the complexity of the trajectory pattern. Various methods have been proposed for solving this problem, ranging from traditional Bayesian analysis to Social Force model and deep learning methods. However, most existing models heavily depend on specific scenarios because the trajectory model is constructed in absolute coordinates even though the motion trajectory as well as human interaction are in relative motion. In this study, a novel trajectory prediction model is proposed to capture the relative motion of pedestrians in extremely crowded scenarios. Trajectory sequences and human interaction are first represented with relative motion and then integrated to our model to predict pedestrians' trajectories. The proposed model is based on Long Short Term Memory (LSTM) structure and consists of an encoder and a decoder which are trained by truncated back propagation. In addition, an anisotropic neighborhood setting is proposed instead of traditional neighborhood analysis. The proposed approach is validated using trajectory data acquired at an extremely crowded train station in Tokyo, Japan. The trajectory prediction experiments demonstrated that the proposed method outperforms existing methods and is stable for predictions of varying length even when the model is trained with a controlled short trajectory sequence.


Assuntos
Modelos Teóricos , Pedestres , Teorema de Bayes , Aprendizado Profundo , Humanos , Japão
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