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Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate SOX9 expression at genomic distances over 1.25 Mb. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. We observed pronounced changes in locus topology between cell types. Subsequent analysis of single-chromatin fiber traces revealed that these ensemble-average differences arise through changes in the frequency of commonly sampled topologies. We further identified two CTCF-bound elements, internal to the SOX9 topologically associating domain, which promote stripe formation, are positioned near the domain's 3D geometric center, and bridge enhancer-promoter contacts in a series of chromatin loops. Ablation of these elements results in diminished SOX9 expression and altered domain-wide contacts. Polymer models with uniform loading across the domain and frequent cohesin collisions recapitulate this multi-loop, centrally clustered geometry. Together, we provide mechanistic insights into architectural stripe formation and gene regulation over ultra-long genomic ranges.

SummaryEnhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulateSOX9expression at genomic distances over 1.25 megabases. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. While we observed pronounced changes in locus topology between cell-types, analysis of single chromatin fiber traces revealed that these ensemble-average differences arise not from the presence of cell-type unique conformations, but through changes in frequency of commonly sampled topologies. We further identified two CTCF-bound elements, internal to theSOX9topologically associating domain, which are positioned near its 3D geometric center and bridge enhancer-promoter contacts in a series of chromatin loops. Ablation of these elements results in diminishedSOX9expression and altered domain-wide contacts. Polymer models with uniform loading across the domain and frequent cohesin collisions recapitulate this multiloop, centrally clustered geometry, suggesting a mechanism for gene regulation over ultralong ranges.Four short bullet points that convey the key message of the paperSOX9domain topology dynamically changes during a developmental transitionStructural elements promote TAD-wide interactions, stripe formation and transcriptionStructural elements are CTCF-dependent and situated centrally in the 3D TAD structurePolymer simulations of multi-loop model best recapitulate topological features

N-Methyl-d-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (GluN2) subunit composition of NMDARs determines whether they activate the transcription factor cAMP-responsive element-binding protein 1 (CREB). However, whether the developmentally regulated GluN3A subunit also modulates NMDAR-induced transcription is unknown. Here, using an array of techniques, including quantitative real-time PCR, immunostaining, reporter gene assays, RNA-Seq, and two-photon glutamate uncaging with calcium imaging, we show that knocking down GluN3A in rat hippocampal neurons promotes the inducible transcription of a subset of NMDAR-sensitive genes. We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity-induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Our evidence that GluN3A regulates MEF2C-dependent transcription reveals a novel mechanism by which NMDAR subunit composition confers specificity to the program of synaptic activity-regulated gene transcription in developing neurons.

BackgroundChlamydia trachomatis infection is the most common sexually transmitted infectious disease and carries a risk of complications. However, the optimal treatment for rectal chlamydial infection remains unclear.ObjectivesTo compare the efficacy of doxycycline and azithromycin for the treatment of rectal chlamydia by undertaking a systematic review and meta-analysis of published data.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science and clinicaltrials.gov databases from inception to 7 July 2021 for randomized controlled trials (RCTs) and observational studies that compared the efficacy of doxycycline and single-dose azithromycin on rectal chlamydia cure rates. Data were synthesized using a random-effects model, and subgroup analysis was conducted.ResultsAll included studies were conducted in developed countries. Two RCTs and nine observational studies, with a total of 2457 patients, were analysed. Doxycycline had a higher microbiological cure rate than azithromycin (risk ratio = 1.21; 95% CI = 1.15–1.28; P ConclusionsOn the basis of our findings, we recommend doxycycline rather than azithromycin as a first-line treatment for rectal chlamydia in developed countries. More RCTs from developing countries are warranted.

Background: Although tranexamic acid (TXA), a readily accessible antifibrinolytic agent, is widely adopted in hemorrhage scenarios, its role on mortality in patients with hemoptysis remains uncertain. New evidence is yet to be generated to evaluate the risk of mortality after using TXA in patients with hemoptysis. Methods: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were searched from inception to May 2020. Randomized controlled trials and observational studies that evaluated the effect of TXA on patients with hemoptysis were included. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. Main results: Five studies with a total of 20,047 patients were analyzed. When compared with the control, administration of TXA was associated with a reduction in short-term mortality (risk ratio = 0.78, 95% confidence interval [CI] 0.72–0.85; I2 = 0), shorter bleeding time (mean difference = − 24.61 hours, 95% CI − 35.96 to −13.26, I2 = 0), shorter length of hospital stay (mean difference = −1.94 days, 95% CI −2.48 to −1.40, I2 = 0), and lower need for intervention (risk ratio = 0.38, 95% CI 0.16–0.87, I2 = 0) in patients with hemoptysis. Compared with control, administration of TXA did not cause increased major or minor adverse effects. Conclusions: TXA provided benefits in terms of a lower short-term mortality rate, less bleeding time, shorter length of hospital stays, and less need for intervention in patients with hemoptysis. Use of TXA was not associated with increased adverse effects.

Supplemental Digital Content is available in the text, Background: Magnesium sulfate (MgSO4) is widely used in analgesia for different conditions. Recent randomized controlled trials (RCTs) have evaluated the effects of MgSO4 on renal colic; however, this new evidence has not been synthesized. Thus, we conducted a systematic review and meta-analysis to assess the efficacy and safety of MgSO4 in comparison with control for renal colic. Methods: PubMed, EMBASE, and Scopus databases were searched from inception to February 2020. We included RCTs that evaluated MgSO4 vs control for patients with renal colic. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. Results: Four studies with a total of 373 patients were analyzed. Intravenous MgSO4 15 to 50 mg/kg did not significantly reduce renal colic pain severity at 15 minutes (mean difference [MD] = 0.35, 95% confidence interval [CI] −0.51 to 1.21; 2 RCTs), 30 minutes (MD = 0.19, 95% CI −0.74 to 1.13; 4 RCTs), and 60 minutes (MD = −0.28, 95% CI −0.72 to 0.16; 3 RCTs) in comparison with controls. In patients who failed to respond to initial analgesics, intravenous MgSO4 15 mg/kg or 2 ml of 50% solution provided similar pain relief to ketorolac or morphine at 30 minutes (P = .90) and 60 minutes (P = .57). No significant hemodynamic changes were observed with short-term use of MgSO4 in these studies. Conclusion: MgSO4 provides no superior therapeutic benefits in comparison with control treatments. MgSO4 may be used as a rescue medication in patients not responding to initial analgesics. The short-term use of MgSO4 did not affect hemodynamic values.

Frequent occurring of haze pollution events and high fine particulate matter (PM(2.5)) concentration in China have attracted more and more attention in the world. Satellite remote sensing can be used to characterize the air pollution. However, haze is usually misidentified as fog, thin cloud or bright surface in NASA’s Moderate Resolution Imaging Spectrometer (MODIS) cloud and clear days’ aerosol products, and the retrieval of its optical properties is not included in MODIS cloud detection and dark target algorithm. This approach first studies the spectral characters of cloud, fog, haze, and land cover pixels. Second, following the previous cloud detection and aerosol retrieval literatures, a threshold algorithm is developed to distinguish haze from other pixels based on MODIS multi-band apparent reflectance and brightness temperature. This algorithm is used to detect the haze distribution over North China Plain in 2008 spring and summer. Our result shows a good agreement with the true-color satellite images, which enhances MODIS’s ability to monitor the severe air pollution episodes. In addition, the high AOD data from Beijing and Xiang Aerosol Robotic NETwork (AERONET) sites indicate nearly 80% haze days are detected by our approach. Finally, we analyze the errors and uncertainties in haze detection algorithm, and put forward the potential improvements.

SUMMARY Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to show that Fos and Npas4 are transcribed in stochastic bursts in mouse neurons and that membrane depolarization increases mRNA expression by increasing burst frequency. We then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. Inhibiting histone acetylation reduced Fos transcription by reducing burst frequency and impaired experience-dependent Fos protein induction in the hippocampus in vivo. Thus, activity-inducible histone acetylation tunes the transcriptional dynamics of experience-regulated genes to affect selective changes in neuronal gene expression and cellular function., In Brief Using CRISPR-mediated epigenome editing, Chen et al. show that enhancer histone acetylation fine-tunes the activity-dependent transcription of Fos in neurons., Graphical Abstract

Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cells. We developed a computational pipeline (BayFish) to infer the kinetic parameters of gene expression from smFISH data at multiple time points after gene induction. Given an underlying model of gene expression, BayFish uses a Monte Carlo method to estimate the Bayesian posterior probability of the model parameters and quantify the parameter uncertainty given the observed smFISH data. We tested BayFish on synthetic data and smFISH measurements of the neuronal activity-inducible gene Npas4 in primary neurons. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1297-9) contains supplementary material, which is available to authorized users.

Zebra finches (Taeniopygia guttata) learn to produce songs in a manner reminiscent of spoken language development in humans. One candidate gene implicated in influencing learning is the N-methyl-D-aspartate (NMDA) subtype 2B glutamate receptor (NR2B). Consistent with this idea, NR2B levels are high in the song learning nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) during juvenile vocal learning, and decreases to low levels in adults after learning is complete and the song becomes more stereotyped. To test for the role of NR2B in generating song plasticity, we manipulated NR2B expression in LMAN of adult male zebra finches by increasing its protein levels to those found in juvenile birds, using a lentivirus containing the full-length coding sequence of the human NR2B subunit. We found that increased NR2B expression in adult LMAN induced increases in song sequence diversity and slower song tempo more similar to juvenile songs, but also increased syllable repetitions similar to stuttering. We did not observe these effects in control birds with overexpression of NR2B outside of LMAN or with the green fluorescent protein (GFP) in LMAN. Our results suggest that low NR2B subunit expression in adult LMAN is important in conserving features of stereotyped adult courtship song.

Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution on the abundance and localization of nascent and mature transcripts in single cells. Gene expression dynamics are typically inferred by measuring mRNA abundance in small numbers of fixed cells sampled from a population at multiple time-points after induction. The sparse data that arise from the small number of cells obtained using smFISH present a challenge for inferring transcription dynamics. Here, we developed a computational pipeline (BayFish) to infer kinetic parameters of gene expression from smFISH data at multiple time points after induction. Given an underlying model of gene expression, BayFish uses a Monte Carlo method to estimate the Bayesian posterior probability of the model parameters and quantify the parameter uncertainty given the observed smFISH data. We tested BayFish on smFISH measurements of the neuronal activity inducible gene Npas4 in primary neurons. We showed that a 2-state promoter model can recapitulate Npas4 dynamics after induction and we inferred that the transition rate from the promoter OFF state to the ON state is increased by the stimulus.Author SummaryGene expression can exhibit cell-to-cell variability due to the stochastic nature of biochemical reactions. Single cell assays (e.g. smFISH) directly quantify stochastic gene expression by measuring the number of active promoters and transcripts per cell in a population of cells. The data are distributions and their shape and time-evolution contain critical information on the underlying process of gene expression. Recent work has combined models of stochastic gene expression with maximum likelihood methods to infer kinetic parameters from smFISH distributions. However, these approaches do not provide a probability distribution or likelihood of model parameters inferred from the smFISH data. This information is useful because it indicates which parameters are loosely constrained by the data and suggests follow up experiments. We developed a suite of MATLAB programs (BayFish) that estimate the Bayesian posterior probability of model parameters from smFISH data. The user specifies an underlying model of stochastic gene expression with unknown parameters (θ) and provides smFISH data (Y). BayFish uses a Monte Carlo algorithm to estimate the Bayesian posterior probability P(θ|Y) of model parameters. BayFish is easily modified and can be applied to other models of stochastic gene expression and smFISH data sets.

The wiring of synaptic connections in the developing mammalian brain is shaped by both intrinsic and extrinsic signals. One point where these regulatory pathways converge is via the sensory experience-dependent regulation of new gene transcription. Recent studies have elucidated a number of molecular mechanisms that allow nuclear transcription factors and chromatin regulatory proteins to encode aspects of specificity in experience-dependent synapse development. Here we review the evidence for the transcriptional mechanisms that sculpt activity-dependent aspects of synaptic connectivity during postnatal development and discuss how disruption of these processes is associated with aberrant brain development in autism and intellectual disability.

A key feature of the CNS is structural plasticity, the ability of neurons to alter their morphology and connectivity in response to sensory experience and other changes in the environment. How this structural plasticity is achieved at the molecular level is not well understood. We provide evidence that changes in sensory experience simultaneously trigger multiple signaling pathways that either promote or restrict growth of the dendritic arbor; structural plasticity is achieved through a balance of these opposing signals. Specifically, we have uncovered a novel, activity-dependent signaling pathway that restricts dendritic arborization. We demonstrate that the GTPase Rem2 is regulated at the transcriptional level by calcium influx through L-VGCCs and inhibits dendritic arborization in cultured rat cortical neurons and in theXenopus laevistadpole visual system. Thus, our results demonstrate that changes in neuronal activity initiate competing signaling pathways that positively and negatively regulate the growth of the dendritic arbor. It is the balance of these opposing signals that leads to proper dendritic morphology.

Ozone is a particularly critical trace gas in the Earth's atmosphere, since this molecule plays a key role in the photochemical reactions and climate change. The TIR measurements can capture the variability of ozone and are weakly sensitive to the lowermost tropospheric ozone content but can provide accurate measurements of tropospheric ozone and higher vertical resolution ozone profiles, with the additional advantage that measurements are also possible during the night. Because of the influence of atmospheric temperature, the ozone profile retrieval accuracy is severely limited. This paper analyze and discuss the ozone absorption spectra and weighting function sensitivity of temperature and its influence on ozone profile retrieval in detail. First, we simulate the change of atmospheric transmittance and radiance by importing 1 K temperature uncertainty, using line-by-line radiative transfer mode under 6 different atmosphere modes. The results show that the transmittance change ratio for 1 K temperature variation was consistent with the transmittance change ratio for 5%-6% change of ozone density variation in all layers of the profile. Then, we calculate the change of weighting function by a temperature error of 1 K, using the Community Radiative Transfer Model (CRTM) for the Cross-track Infrared Sounder (CrIS) on the Suomi National Polar-orbiting Partnership (Suomi NPP) satellite and calculate the corresponding change of retrieval result. The results demonstrate that CrIS is sensitive to Ozone in the middle to upper stratosphere, with the peak vertical sensitivity between 10-100 hPa and the change of weighting function for 1 K temperature variation was consistent with 6% change in the ozone profile. Finally, the paper retrieves ozone profiles from the CrIS radiances with a nonlinear Newton iteration method and use the eigenvector regression algorithm to construct the a priori state. In order to resolve the problem of temperature uncertainty and get high accuracy ozone profile, atmospheric temperature profile and ozone profile are simultaneously retrieved. Comparison of the CrIS retrieved ozone profile with high-vertical-resolution ozonesonde profiles provided by the World Ozone and Ultraviolet Radiation Data Centre (WOUDC) and ERA-Interim ozone profiles indicated that the retrieved ozone profiles are in good agreement with the ozonesonde profiles, and a notable improvement in this algorithm than the retrieval without atmospheric temperature profile, are also better than the ECMWF model profiles. The relative differences are less than 20% for the stratosphere and 50% for the lower troposphere.

Nitrous Oxide is a very important greenhouse gases and ozone-depleting substances. Due to the limited observations, there are still many uncertainties to quantitatively describe the role of nitrous oxide played in both cases. We can retrieve the methane and carbon dioxide gas using thermal infrared satellite data AIRS, but it is rarely for the nitrous oxide retrieval. Therefore, this paper retrieves nitrous oxide profiles from the AIRS data with an Optimal Estimate Method for the first time in China. The issue of the a priori and channels election is discussed. Comparison of the retrieved AIRS profiles with HIPPO profiles show the retrieved profiles are in good agreement with the smoothed HIPPO profiles, and a notable improvement in this algorithm than the eigen vector regression algorithm. For pressures between 300 and 900 hPa, we got the most accurate profiles and the relative error is only 0.1%, which is consistent with the jacobian peaks of the selected channels.

Syncytin 2 is a newly identified placental membrane protein with fusogenic and immunosuppressive activities. Major facilitator superfamily domain containing 2A (MFSD2A) is the cognate receptor for syncytin 2-mediated cell-cell fusion. Both syncytin 2 and MFSD2A are highly expressed in placenta. In this study to understand the regulation of syncytin 2 and MFSD2A expression in placenta, we found that syncytin 2 gene is epigenetically silenced in nonplacental cells by cytosine-phosphate-guanine (CpG) dinucleotide methylation and that expression of syncytin 2 and MFSD2A genes are regulated by the placental transcription factor GCM1 in placental cells. Functional GCM1-binding sites were identified in syncytin 2 and MFSD2A promoters based on electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Because GCM1 activity is decreased in hypoxic placental cells, we further confirmed that expression of MFSD2A is downregulated in hypoxic BeWo choriocarcinoma cells. Interestingly, ectopic expression of GCM1 activated syncytin 2 and MFSD2A expression in MCF-7 breast cancer cells and facilitated MCF-7 cell fusion. The expression of syncytin 2 in MCF-7 cells was partly attributed to CpG demethylation in the syncytin 2 promoter in the presence of GCM1. Our results suggest that GCM1 is a critical factor in controlling placental cell fusion through transcriptional regulation of syncytin 2 and MFSD2A gene expression in placenta. In addition, GCM1 may also play an important role in the epigenetic regulation of syncytin 2 gene expression.

Glial cell missing homolog 1 (GCM1) is an important transcription factor regulating placental cell fusion. Recently, we have demonstrated that GCM1 is a labile protein and that the F-box protein FBXW2 (F-box and WD repeat domain containing 2) mediates GCM1 ubiquitination for proteasomal degradation. Multiple factors are involved in the ubiquitin-proteasome degradation system. Therefore, in order to better understand the mechanism regulating GCM1 stability, we further isolated and characterized the E2 ubiquitin-conjugating enzyme responsible for FBXW2-mediated ubiquitination of GCM1 in this study. We prepared and screened a variety of E2 proteins in an in vitro ubiquitination assay system for GCM1 and found that UBE2D2 is required for the SCFFBXW2 E3 ligase in regulation of GCM1 ubiquitination. We also demonstrated that the enzyme activity of UBE2D2 is required for GCMa ubiquitination and for association with the SCF FBXW2 complex. Moreover, knocking down UBE2D2 expression by RNA interference not only suppressed FBXW2-mediated GCM1 ubiquitination, but also prolonged the half-life of GCM1 in vivo. Our results suggest that UBE2D2 is a functional E2 protein which, together with FBXW2, regulates GCM1 stability in the placenta.

Syncytin is an envelope protein of the human endogenous retrovirus family W (HERV-W). Syncytin is specifically expressed in the human placenta and mediates trophoblast cell fusion into the multinucleated syncytiotrophoblast layer. It is a polypeptide of 538 amino acids and is predicted to be posttranslationally cleaved into a surface (SU) subunit and a transmembrane (TM) subunit. Functional characterization of syncytin protein can aid understanding of the molecular mechanism underlying syncytin-mediated cell fusion. In this report, we studied the structure-function relationship of syncytin in 293T and HeLa cells transiently expressing wild-type syncytin or syncytin mutants generated by linker scanning and deletion mutagenesis. Of the 22 linker-inserted mutants, mutants InS51, InV139, InE156, InS493, InA506, and InL529 were fusogenic, suggesting that regions around amino acids S51, V139, and E156 in the SU subunit and S493, A506, and L529 in the cytoplasmic domain (CTM) of syncytin are flexible in conformation. Of the 17 deletion mutants, nine mutants with deletions in the region from amino acids 479 to 538 were fusogenic. The deletion mutant DelI480, containing only the first four amino acid residues in the cytoplasmic domain, had enhanced fusogenic activity in comparison with the wild-type. In addition, two heptad repeat regions (HRA and B) were defined in the TM subunit of syncytin. A peptide inhibitor derived from the C-terminal heptad repeat region (HRB) was shown to potently inhibit syncytin-mediated cell fusion. Our results suggest that the cytoplasmic domain of syncytin is not essential for syncytin-mediated fusion but may play a regulatory role, and an intramolecular interaction between HRA and B is involved in the fusion process.

Neuronal activity sculpts brain development by inducing the transcription of genes such as brain-derived neurotrophic factor (Bdnf) that modulate the function of synapses. Sensory experience is transduced into changes in gene transcription via the activation of calcium signaling pathways downstream of both L-type voltage-gated calcium channels (L-VGCCs) and NMDA-type glutamate receptors (NMDARs). These signaling pathways converge on the regulation of transcription factors including calcium-response factor (CaRF). Although CaRF is dispensable for the transcriptional induction of Bdnf following the activation of L-VGCCs, here we show that the loss of CaRF leads to enhanced NMDAR-dependent transcription of Bdnf as well as Arc. We identify the NMDAR subunit-encoding gene Grin3a as a regulatory target of CaRF, and we show that expression of both Carf and Grin3a is depressed by the elevation of intracellular calcium, linking the function of this transcriptional regulatory pathway to neuronal activity. We find that light-dependent activation of Bdnf and Arc transcription is enhanced in the visual cortex of young CaRF knockout mice, suggesting a role for CaRF-dependent dampening of NMDAR-dependent transcription in the developing brain. Finally, we demonstrate that enhanced Bdnf expression in CaRF-lacking neurons increases inhibitory synapse formation. Taken together, these data reveal a novel role for CaRF as an upstream regulator of NMDAR-dependent gene transcription and synapse formation in the developing brain. NMDARs promote brain development by inducing the transcription of genes, including brain-derived neurotrophic factor (BDNF). We show that the transcription factor calcium-response factor (CaRF) limits NMDAR-dependent BDNF induction by regulating expression of the NMDAR subunit GluN3A. Loss of CaRF leads to enhanced BDNF-dependent GABAergic synapse formation indicating the importance of this process for brain development. Our observation that both CaRF and GluN3A are down-regulated by intracellular calcium suggests that this may be a mechanism for experience-dependent modulation of synapse formation.

Biomass burning makes up an important part of both trace gases and particulate matter emissions, which can efficiently degrade air quality and reduce visibility, destabilize the global climate system at regional to global scales. Burned area is one of the primary parameters necessary to estimate emissions, and considered to be the largest source of error in the emission inventory. Satellite-based fire observations can offer a reliable source of fire occurrence data on regional and global scales, a variety of sensors have been used to detect and map fires in two general approaches: burn scar mapping and active fire detection. However, both of the two approaches have limitations. In this article, we explore the relationship between hotspot data and burned area for the Southeastern United States, where a significant amount of biomass burnings from both prescribed and wild fire took place. MODIS (Moderate resolution imaging spectrometer) data, which has high temporal-resolution, can be used to monitor ground biomass. burning in time and provided hot spot data in this study. However, pixel size of MODIS hot spot can't stand for the real ground burned area. Through analysis of the variation of vegetation band reflectance between pre- and post-burn, we extracted the burned area from Landsat-5 TM (Thematic Mapper) images by using the differential normalized burn ratio (dNBR) which is based on TM band4 (0.84 μm) and TM band 7(2.22 μm) data. We combined MODIS fire hot spot data and Landsat-5 TM burned scars data to build the burned area estimation model, results showed that the linear correlation coefficient is 0.63 and the relationships vary as a function of vegetation cover. Based on the National Land Cover Database (NLCD), we built burned area estimation model over different vegetation cover, and got effective burned area per fire pixel, values for forest, grassland, shrub, cropland and wetland are 0.69, 1.27, 0.86, 0.72 and 0.94 km2 respectively. We validated the burned area estimates by using the ground survey data from National interagency Fire Center (NIFC), our results are more close to the ground survey data than burned area from Global Fire Emissions Database (GFED) and MODIS burned area product (MCD45), which omitted many small prescribed fires. We concluded that our model can provide more accurate burned area parameters for developing fire emission inventory, and be better for estimating emissions from biomass burning.

Mutations in PARKIN (PARK2), an ubiquitin ligase, cause early onset Parkinson disease. Parkin was shown to bind, ubiquitinate, and target depolarized mitochondria for destruction by autophagy. This process, mitophagy, is considered crucial for maintaining mitochondrial integrity and suppressing Parkinsonism. Here, we report that under moderate mitochondrial stress, parkin does not translocate to mitochondria to induce mitophagy; rather, it stimulates mitochondrial connectivity. Mitochondrial stress-induced fusion requires PINK1 (PARK6), mitofusins, and parkin ubiquitin ligase activity. Upon exposure to mitochondrial toxins, parkin binds α-synuclein (PARK1), and in conjunction with the ubiquitin-conjugating enzyme Ubc13, stimulates K63-linked ubiquitination. Importantly, α-synuclein inactivation phenocopies parkin overexpression and suppresses stress-induced mitochondria fission, whereas Ubc13 inactivation abrogates parkin-dependent mitochondrial fusion. The convergence of parkin, PINK1, and α-synuclein on mitochondrial dynamics uncovers a common function of these PARK genes in the mitochondrial stress response and provides a potential physiological basis for the prevalence of α-synuclein pathology in Parkinson disease. Background: Parkin is proposed to maintain mitochondrial QC through promoting mitophagy. Results: Under moderate mitochondrial stress conditions, parkin stimulates mitochondrial fusion instead of mitophagy by catalyzing K63-linked ubiquitination and inactivating α-synuclein. Conclusion: Parkin, PINK1, and α-synuclein form a regulatory circuit to regulate mitochondrial stress response. Significance: This study provides a physiological context to functionally connect key PARK genes in the pathogenesis of Parkinson disease.

A series of W-, Ru-, and Mo-promoted Ni−B amorphous nanocatalysts were prepared by chemical reduction of the precursors of promoters, respectively, and nickel acetate with sodium borohydride in methanol/water (1:1) solution. The catalysts were characterized by X-ray diffraction, nitrogen sorption, X-ray photoelectron spectroscopy, differential scanning calorimetry, and transmission electron microscopy. With a specific concentration of promoter, the particles of the Ni−B catalysts became smaller. The catalysts also demonstrated higher thermal resistance, protecting the amorphous structure from high-temperature treatment. The correlation of the catalytic performance to both the structural and the electronic characteristics was discussed. W6+ and Mo6+ cations were not reduced by NaBH4. They formed oxides or hydroxides since the preparation solutions were basic. They acted as spacers and prevented Ni−B from sintering and agglomeration. Ru3+ could be reduced by NaBH4 to Ru metal. Ru is also a catalyst for this...

In order to get higher vertical resolution atmosphere profile information, the present paper retrieves atmospheric temperature and moisture profiles from the Cross-track Infrared Sounder (CrIS) on the newly-launched Suomi National Polar-orbiting Partnership (Suomi NPP) and future Joint Polar Satellite System (JPSS) with a nonlinear Newton iteration method by using the profiles retrieved via statical regression method as the first guess, and the issue of channel selection is discussed. The retrieved profiles are compared with radiosonde observations, and National Centers for Environmental Prediction (NCEP) Global Data Assimilation System (GDAS) analyses show that the physical retrievals of temperature and moisture are in good agreement with the distributions from GDAS analysis fields and radiosonde observations, and have a notable improvements of the atmospheric profile retrieval accuracy as compared with the eigenvector regression algorithm. For pressures between 200 and 700 hPa the accuracy is of the order of 1 K for the temperature profile, and 20% for the relative humidity profile is consistent with the jacobian peaks of the selected channels.

In the present, for the characteristic of HJ-1 CCD camera, after receiving aerosol optical depth (AOD) from deep blue algorithm which was developed by Hsu et al. assisted by MODerate-resolution imaging spectroradiometer (MODIS) surface reflectance database, bidirectional reflectance distribution function (BRDF) correction with Kernel-Driven Model, and the calculation of viewing geometry with auxiliary data, a new atmospheric correction method of HJ-1 CCD was developed which can be used over vegetation, soil and so on. And, when the CCD data is processed to correct atmospheric influence, with look up table (LUT) and bilinear interpolation, atmospheric correction of HJ-1 CCD is completed quickly by grid calculation of atmospheric parameters and matrix operations of interface define language (IDL). The experiment over China North Plain on July 3rd, 2012 shows that by our method, the atmospheric influence was corrected well and quickly (one CCD image of 1 GB can be corrected in eight minutes), and the reflectance after correction over vegetation and soil was close to the spectrum of vegetation and soil. The comparison with MODIS reflectance product shows that for the advantage of high resolution, the corrected reflectance image of HJ-1 is finer than that of MODIS, and the correlation coefficient of the reflectance over typical surface is greater than 0.9. Error analysis shows that the recognition error of aerosol type leads to 0. 05 absolute error of surface reflectance in near infrared band, which is larger than that in visual bands, and the 0. 02 error of reflectance database leads to 0.01 absolute error of surface reflectance of atmospheric correction in green and red bands.

Enzymes that regulate histone lysine methylation play important roles in neuronal differentiation, but little is known about their contributions to activity-regulated gene transcription in differentiated neurons. We characterized activity-regulated expression of lysine demethylases and lysine methyltransferases in the hippocampus of adult male mice following pilocarpine-induced seizure. Pilocarpine drove a 20-fold increase in mRNA encoding the histone H3 lysine 27-specific demethylase Kdm6b selectively in granule neurons of the dentate gyrus, and this induction was recapitulated in cultured hippocampal neurons by bicuculline and 4-aminopyridine (Bic + 4AP) stimulation of synaptic activity. Because activity-regulated gene expression is highly correlated with neuronal survival, we tested the requirement for Kdm6b expression in Bic + 4AP induced preconditioning of neuronal survival. Prior exposure to Bic + 4AP promoted neuronal survival in control neurons upon growth factor withdrawal; however, this effect was ablated when we knocked down Kdm6b expression. Loss of Kdm6b did not disrupt activity-induced expression of most genes, including that of a gene set previously established to promote neuronal survival in this assay. However, using bioinformatic analysis of RNA sequencing data, we discovered that Kdm6b knockdown neurons showed impaired inducibility of a discrete set of genes annotated for their function in inflammation. These data reveal a novel function for Kdm6b in activity-regulated neuronal survival, and they suggest that activity- and Kdm6b-dependent regulation of inflammatory gene pathways may serve as an adaptive pro-survival response to increased neuronal activity.

The electrical properties of positive temperature coefficient of resistance (PTCR) ceramics of composition (Ba,Pb,La)TiO/sub 3/ prepared from commercial BaTiO/sub 3/ powders doped with different additives were studied. It was proposed here that different additives might have generated the corresponding number of possible surface states, such as, the segregation behavior of Mn ions (3d transition metal ions), oxygen adsorption reaction resulting from BN addition, the action of Ca replacing the Ti sites (Ca/sub Ti/") and the natural intrinsic defects (V/sub Ba/", V/sub Pb/"). In general, some experimental derivations were also offered that majority of the surface states, which possessed their individual surface energy level, possibly coexisted onto the grain surface. Utilizing the concept of the coexistence of different types of surface states in the energy band, a satisfactory point-to-point agreement was obtained between the measured result and calculated values for the resistivity curve. Our experimental results were analyzed based on the terms of the Heywang-Jonker model and have shown that the assumption of a Hewang barrier was a reasonable approach for our set of samples; however, the distribution and types of grain-boundary acceptor states classification were required.

With the urbanizing in China, haze days occur frequently, which have largely impacted air quality. In the present paper, based on haze physical properties, haze optical properties were calculated by Mie theory and apparent reflectance of haze in Environment Satellite 1 (HJ-1) channels was simulated by Radiative Transfer (RT) 3. Simulated results show that it is reasonable to extract the haze from apparent reflectance in the first and second channels. By Deep Blue algorithm, Haze Optical Depth (HOD) was retrieved from HJ-1 data supported by reflectance database from MODIS product. From HJ-1 data in 2009 over Beijing area, the haze days were monitored and validated by AERONET/PHOTONS Beijing site. The validation shows that the correlation coefficient of HOD is greater than 0.9, but HOD from HJ-1 is greater than that from ground-based measurements. The discussions show that the error from reflectance database is less than 0.1 and radiance resolution of HJ-1 needs to advance for haze monitoring.

Generally, aerosols over land are composed of fine and coarse aerosols, which have different optical properties. How to derive the fine mode and coarse mode aerosols from satellite observations is an important issue in the aerosol retrieving. In the present paper, information of aerosol models (including refractive index and size distribution function) was retrieved from the ground-based measurement of the AERONET/PHOTONS site in Beijing. The retrievals indicate that, aerosols over Beijing have a bi-model distribution, and the optical properties of fine and coarse aerosols are distinct. Based on the dark dense vegetation (DDV) method, optical depth of the fine, coarse and total aerosols were derived from MODIS data over Beijing area in 2007. The validation of these satellite retrievals shows that from MODIS data, the optical depth of fine and total aerosols can be retrieved well (with correlation coefficients greater than 0.8), and so can the Angstrom exponent (having a correlation coefficient of 0.517). However, relatively poor results were obtained when retrieving the optical depth of coarse aerosols.

The potentiality of the retrieval of surface reflectance using CCD camera aboard HJ-1A/B satellite was studied. It is very difficult to use dark targets in atmospheric correction due to the lack of near infrared band. The alternative normalized difference vegetation index (NDVI) and the red/blue reflectance ratio are detected from the spectral experiment in Beijing and the Pearl River Delta. Ground-based spectral data including grass, dense vegetation, water body, soil, residential roof and bright building etc. were used to validate the surface reflectance in Beijing, and the relative error in red, blue band is under 38.7% and 37.2% respectively. Uncertainties of the surface reflectance retrievals were analyzed. The comparison of MODIS surface reflectance product showed that there is a good agreement in the dense targets, and the correlation coefficient (R2) in red, blue band is as high as 0.809 4 and 0.723 9 respectively. HJ-1-CCD data can effectively reduce pixel-mixed impact on the cement roof and bright buildings, and the inversion accuracy is higher than MODIS products.

The Ring effect is a significant limitation to the accuracy of the retrieval of trace gas constituents in atmosphere, while using satellite data with differential optical absorption spectroscopy technique. The Ring effect refers to the filling in of Fraunhofer lines, known as solar absorption lines, caused almost entirely by rotational Raman scattering. The inelastic component of the molecular scattering results in a net increase in radiance in the line because more radiation is shifted to the wavelength of an absorption line than shifted from this wavelength to other wavelengths. The rotational Raman scattering by N2 and Oz in the atmosphere is the main factor that leads to Ring effect. Basically, the Ring effect is considered as a pseudo-absorption process in retrieval of trace gas constituents in atmosphere. The solar spectrum measured by OMI/AURA is convolved with rotational Raman cross sections of N2 and O2, divided by the original solar spectrum, with a cubic polynomial subtracted off, to create differential Ring spectrum. This method has been suggested in order to obtain an effective differential Ring cross-section for the DOAS fitting process. The differential Ring spectrum could be used to improve the accuracy of the retrieval of the trace gases concentration. The results in this paper have been in basic agreement with the corresponding results calculated with RTM, and the R2 Statistic is 0. 966 3.

Syncytin 2 is a newly identified placental membrane protein with fusogenic and immunosuppressive activities. Major facilitator superfamily domain containing 2A (MFSD2A) is the cognate receptor for syncytin 2-mediated cell-cell fusion. Both syncytin 2 and MFSD2A are highly expressed in placenta. In this study to understand the regulation of syncytin 2 and MFSD2A expression in placenta, we found that syncytin 2 gene is epigenetically silenced in nonplacental cells by cytosine-phosphate-guanine (CpG) dinucleotide methylation and that expression of syncytin 2 and MFSD2A genes are regulated by the placental transcription factor GCM1 in placental cells. Functional GCM1-binding sites were identified in syncytin 2 and MFSD2A promoters based on electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Because GCM1 activity is decreased in hypoxic placental cells, we further confirmed that expression of MFSD2A is downregulated in hypoxic BeWo choriocarcinoma cells. Interestingly, ectopic expression of GCM1 activated syncytin 2 and MFSD2A expression in MCF-7 breast cancer cells and facilitated MCF-7 cell fusion. The expression of syncytin 2 in MCF-7 cells was partly attributed to CpG demethylation in the syncytin 2 promoter in the presence of GCM1. Our results suggest that GCM1 is a critical factor in controlling placental cell fusion through transcriptional regulation of syncytin 2 and MFSD2A gene expression in placenta. In addition, GCM1 may also play an important role in the epigenetic regulation of syncytin 2 gene expression.

Glial cell missing homolog 1 (GCM1) is an important transcription factor regulating placental cell fusion. Recently, we have demonstrated that GCM1 is a labile protein and that the F-box protein FBXW2 (F-box and WD repeat domain containing 2) mediates GCM1 ubiquitination for proteasomal degradation. Multiple factors are involved in the ubiquitin-proteasome degradation system. Therefore, in order to better understand the mechanism regulating GCM1 stability, we further isolated and characterized the E2 ubiquitin-conjugating enzyme responsible for FBXW2-mediated ubiquitination of GCM1 in this study. We prepared and screened a variety of E2 proteins in an in vitro ubiquitination assay system for GCM1 and found that UBE2D2 is required for the SCF(FBXW2) E3 ligase in regulation of GCM1 ubiquitination. We also demonstrated that the enzyme activity of UBE2D2 is required for GCMa ubiquitination and for association with the SCF(FBXW2) complex. Moreover, knocking down UBE2D2 expression by RNA interference not only suppressed FBXW2-mediated GCM1 ubiquitination, but also prolonged the half-life of GCM1 in vivo. Our results suggest that UBE2D2 is a functional E2 protein which, together with FBXW2, regulates GCM1 stability in the placenta.

Fusion of cytotrophoblasts into the multinucleated syncytiotrophoblast layer is essential for the development of a functional placenta. The envelope protein of a human endogenous retrovirus W (HERV-W) family member, syncytin 1, has been shown to mediate placental cell fusion. Recently, the envelope protein of another HERV family member (HERV-FRD), syncytin 2, has been identified and shown to be highly expressed in the placenta. To better understand the biology of syncytin 2, in this study we first investigated syncytin 2 gene expression in normal and preeclamptic placentas and then characterized the functions of syncytin 2. The expression of syncytin 2 gene was decreased in preeclamptic placentas and could be stimulated by the cAMP stimulant forskolin. The endoprotease furin was found to be involved in the posttranslational cleavage of syncytin 1 and 2 polypeptides into surface and transmembrane subunits. In addition, proper association of the subunits of syncytins 1 and 2 is probably required for the functional integrity of each protein, because subunit swapping of syncytins 1 and 2 failed to generate fusogenic chimeras. Finally, we demonstrated that the disulfide bridge-forming CX(2)C and CX(7)C motifs found in syncytins 1 and 2 are essential for their fusogenic activities, because mutations in the CX(2)C motif not only abolished fusogenesis but also functioned as dominant-negative mutants. Our results suggest that syncytin 2 may function as a second fusogenic protein for placental cell fusion.

Glial cell missing Drosophila homolog a (GCMa) is an essential transcription factor for placental development, which controls the differentiation of the syncytiotrophoblast layer. Although the activity of GCMa can be post-translationally regulated by protein phosphorylation, ubiquitination, and acetylation, it is unknown whether GCMa activity can be regulated by sumoylation. In this report, we investigated the role of sumoylation in the regulation of GCMa activity. We demonstrated that Ubc9, the E2 component of the sumoylation machinery, specifically interacts with the N-terminal domain of GCMa and promotes GCMa sumoylation on lysine 156. Moreover, GCMa-mediated transcriptional activation was repressed by sumoylation but was enhanced in the presence of the SUMO-specific protease, SENP1. The repressive effect of sumoylation on GCMa transcriptional activity was attributed to decreased DNA binding activity of GCMa. Furthermore, structural analysis revealed a steric clash between the SUMO1 moiety of sumoylated GCMa and the DNA-binding surfaces of GCMa, which may destabilize the interaction between GCMa and its cognate DNA sequence. Our study demonstrates that GCMa is a new sumoylation substrate and its activity is down-regulated by sumoylation.