Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons

ChIP-Array 2: integrating multiple omics data to construct gene regulatory networks

published_or_final_versio

The [O II] lambda 3727 Luminosity Function at z ~ 1

We measure the evolution of the [OII]lambda 3727 luminosity function at 0.75<z<1.45 using high-resolution spectroscopy of ~14,000 galaxies observed by the DEEP2 galaxy redshift survey. We find that brighter than L_{OII}=10^{42} erg s^(-1) the luminosity function is well-represented by a power law dN/dL ~ L^{\alpha} with slope \alpha ~ -3. The number density of [OII] emitting galaxies above this luminosity declines by a factor of >~2.5 between z ~ 1.35 and z ~ 0.84. In the limit of no number-density evolution, the characteristic [OII] luminosity, L^*_[OII], defined as the luminosity where the space density equals 10^{-3.5} dex^{-1} Mpc^{-3}, declines by a factor of ~1.8 over the same redshift interval. Assuming that L_[OII] is proportional to the star-formation rate (SFR), and negligible change in the typical dust attenuation in galaxies at fixed [OII] luminosity, the measured decline in L^*_[OII] implies a ~25% per Gyr decrease in the amount of star formation in galaxies during this epoch. Adopting a faint-end power-law slope of -1.3\pm0.2, we derive the comoving SFR density in four redshift bins centered around z~1 by integrating the observed [OII] luminosity function using a local, empirical calibration between L_[OII] and SFR, which statistically accounts for variations in dust attenuation and metallicity among galaxies. We find that our estimate of the SFR density at z~1 is consistent with previous measurements based on a variety of independent SFR indicators.Comment: 10 pages, 6 figures, 2 tables, resubmitted to ApJ, in emulateapj style. Comparison with narrow-band observations added. Wavelength coverage included into complete function, little effects. The data is available on http://bias.cosmo.fas.nyu.edu/galevolution

DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that both proteins are required for normal levels of cytosine methylation and hydroxymethylation in murine embryonic stem cells. Furthermore, Mbd2 and Mbd3 regulate overlapping sets of genes that are also regulated by DNA methylation/hydroxymethylation factors. These findings reveal an interdependent regulatory mechanism mediated by the DNA methylation machinery and its readers

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4–5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4–5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment

The chromatin assembly factor complex 1 (CAF1) and 5-Azacytidine (5-AzaC) affect cell motility in Src-transformed human epithelial cells

Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes

A study on city motor vehicle emission factors by tunnel test

2001-2002 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

A review of physical supply and EROI of fossil fuels in China

This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found

Probing star formation across cosmic time with absorption line systems

We present an empirical connection between cold gas in galactic halos and star formation. Using a sample of more than 8,500 MgII absorbers from SDSS quasar spectra, we report the detection of a 15 sigma correlation between the rest equivalent width W0 of MgII absorbers and the associated OII luminosity, an estimator of star formation rate. This correlation has interesting implications: using only observable quantities we show that MgII absorbers trace a substantial fraction of the global OII luminosity density and recover the overall star formation history of the Universe derived from classical emission estimators up to z~2. We then show that the distribution function of MgII rest equivalent widths, dN/dW0 inherits both its shape and amplitude from the OII luminosity function Phi(L). These distributions can be naturally connected, without any free parameter. Our results imply a high covering factor of cold gas around star forming galaxies: C>0.5, favoring outflows as the mechanism responsible for MgII absorption. We then argue that intervening MgII absorbers and blue-shifted MgII absorption seen in the spectra of star forming galaxies are essentially the same systems. These results not only shed light on the nature of MgII absorbers but also provide us with a new probe of star formation, in absorption, i.e. in a way which does not suffer from dust extinction and with a redshift-independent sensitivity. As shown in this analysis, such a tool can be applied in a noise-dominated regime, i.e. using a dataset for which emission lines are not detected in individual objects. This is of particular interest for high redshift studies.Comment: 13 pages, 7 figures, submitted to MNRA

The local star-formation rate density: assessing calibrations using [OII], Ha and UV luminosities

We explore the use of simple star-formation rate (SFR) indicators (such as may be used in high-redshift galaxy surveys) in the local Universe using [OII], Ha, and u-band luminosities from the deeper 275 deg^2 Stripe 82 subsample of the Sloan Digital Sky Survey (SDSS) coupled with UV data from the Galaxy Evolution EXplorer satellite (GALEX). We examine the consistency of such methods using the star-formation rate density (SFRD) as a function of stellar mass in this local volume, and quantify the accuracy of corrections for dust and metallicity on the various indicators. Rest-frame u-band promises to be a particularly good SFR estimator for high redshift studies since it does not require a particularly large or sensitive extinction correction, yet yields results broadly consistent with more observationally expensive methods. We suggest that the [OII]-derived SFR, commonly used at higher redshifts (z~1), can be used to reliably estimate SFRs for ensembles of galaxies, but for high mass galaxies (log(M*/Msun)>10), a larger correction than is typically used is required to compensate for the effects of metallicity dependence and dust extinction. We provide a new empirical mass-dependent correction for the [OII]-SFR.Comment: 22 pages, 16 figures. This version corrects typos in equations 2, 7, and 9 of the published version, as described in the MNRAS Erratum. Published results are unaffected. A simple piece of IDL Code for applying the mass-dependent correction to [OII] SFR available from http://astro.uwaterloo.ca/~dgilbank/data/corroii.pr