Shades of Gray: Internal Control Reporting by Chinese U.S.-listed Firms

Chinese firms listing in the U.S. via reverse mergers (CRMs) have dominated prior media, regulator and research attention. Yet CRMs have effectively ceased, leaving Chinese firms listing via initial public offerings (CIPOs) as the relevant remaining class of Chinese firms listing on U.S. exchanges. This study documents salient differences between CIPOs, CRMs and U.S.-domiciled U.S.-listed firms by examining Sarbanes-Oxley Act Section 302 and 404 ineffective internal control (IIC) and related disclosures that underlie financial reporting quality, with three main findings. First, both CIPOs and CRMs report significantly more IICs than U.S.-domiciled counterparts. Second, both CIPOs and CRMs under-report IICs to a greater degree than U.S.-domiciled counterparts (CIPO for only 302 disclosures). Third, CIPOs report and under-report IICs significantly less than CRMs. Collectively, our results clarify and recast prior characterizations of internal controls underlying the reporting quality of Chinese firms listed in the U.S. and elsewhere.preprin

Defining the role of oxygen tension in human neural progenitor fate.

Hypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and hypoxia-inducible factor (HIF) activity instead promote appropriate hESC differentiation. Through gain- and loss-of-function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate toward neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types

The effect of psychological stress on iron absorption in rats

© 2009 Chen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Reproducibility of an HPLC-ESI-MS/MS Method for the Measurement of Stable-Isotope Enrichment of in Vivo-Labeled Muscle ATP Synthase Beta Subunit

We sought to evaluate the reproducibility of a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approach to measure the stable-isotope enrichment of in vivo-labeled muscle ATP synthase β subunit (β-F1-ATPase), a protein most directly involved in ATP production, and whose abundance is reduced under a variety of circumstances. Muscle was obtained from a rat infused with stable-isotope-labeled leucine. The muscle was homogenized, β-F1-ATPase immunoprecipitated, and the protein was resolved using 1D-SDS PAGE. Following trypsin digestion of the isolated protein, the resultant peptide mixtures were subjected to analysis by HPLC-ESI-MS/MS, which resulted in the detection of multiple β-F1-ATPase peptides. There were three β-F1-ATPase unique peptides with a leucine residue in the amino acid sequence, and which were detected with high intensity relative to other peptides and assigned with >95% probability to β-F1-ATPase. These peptides were specifically targeted for fragmentation to access their stable-isotope enrichment based on MS/MS peak areas calculated from extracted ion chromatographs for selected labeled and unlabeled fragment ions. Results showed best linearity (R2 = 0.99) in the detection of MS/MS peak areas for both labeled and unlabeled fragment ions, over a wide range of amounts of injected protein, specifically for the β-F1-ATPase134-143 peptide. Measured stable-isotope enrichment was highly reproducible for the β-F1-ATPase134-143 peptide (CV = 2.9%). Further, using mixtures of synthetic labeled and unlabeled peptides we determined that there is an excellent linear relationship (R2 = 0.99) between measured and predicted enrichment for percent enrichments ranging between 0.009% and 8.185% for the β-F1-ATPase134-143 peptide. The described approach provides a reliable approach to measure the stable-isotope enrichment of in-vivo-labeled muscle β-F1-ATPase based on the determination of the enrichment of the β-F1-ATPase134-143 peptide

In Silico Simulation of Corticosteroids Effect on an NFkB- Dependent Physicochemical Model of Systemic Inflammation

During the onset of an inflammatory response signaling pathways are activated for "translating" extracellular signals into intracellular responses converging to the activation of nuclear factor (NF)-kB, a central transcription factor in driving the inflammatory response. An inadequate control of its transcriptional activity is associated with the culmination of a hyper-inflammatory response making it a desired therapeutic target. Predicated upon the nature of the response, a systems level analysis might provide rational leads for the development of strategies that promote the resolution of the response.A physicochemical host response model is proposed to integrate biological information in the form of kinetic rules and signaling cascades with pharmacokinetic models of drug action for the modulation of the response. The unifying hypothesis is that the response is triggered by the activation of the NFkB signaling module and corticosteroids serve as a template for assessing anti-inflammatory strategies. The proposed in silico model is evaluated through its ability to predict and modulate uncontrolled responses. The pre-exposure of the system to hypercortisolemia, i.e. 6 hr before or simultaneously with the infectious challenge "reprograms" the dynamics of the host towards a balanced inflammatory response. However, if such an intervention occurs long before the inflammatory insult a symptomatic effect is observed instead of a protective relief while a steroid infusion after inducing inflammation requires much higher drug doses.We propose a reversed engineered inflammation model that seeks to describe how the system responds to a multitude of external signals. Timing of intervention and dosage regimes appears to be key determinants for the protective or symptomatic effect of exogenous corticosteroids. Such results lie in qualitative agreement with in vivo human studies exposed both to LPS and corticosteroids under various time intervals thus improving our understanding of how interacting modules generate a behavior

Examining the effects of sodium ions on the binding of antagonists to dopamine D2 and D3 receptors

Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo

Co-variations and Clustering of Chronic Disease Behavioral Risk Factors in China: China Chronic Disease and Risk Factor Surveillance, 2007

BACKGROUND: Chronic diseases have become the leading causes of mortality in China and related behavioral risk factors (BRFs) changed dramatically in past decades. We aimed to examine the prevalence, co-variations, clustering and the independent correlates of five BRFs at the national level. METHODOLOGY/PRINCIPAL FINDINGS: We used data from the 2007 China Chronic Disease and Risk Factor Surveillance, in which multistage clustering sampling was adopted to collect a nationally representative sample of 49,247 Chinese aged 15 to 69 years. We estimated the prevalence and clustering (mean number of BRFs) of five BRFs: tobacco use, excessive alcohol drinking, insufficient intake of vegetable and fruit, physical inactivity, and overweight or obesity. We conducted binary logistic regression models to examine the co-variations among five BRFs with adjustment of demographic and socioeconomic factors, chronic conditions and other BRFs. Ordinal logistic regression was constructed to investigate the independent associations between each covariate and the clustering of BRFs within individuals. Overall, 57.0% of Chinese population had at least two BRFs and the mean number of BRFs is 1.80 (95% confidence interval: 1.78-1.83). Eight of the ten pairs of bivariate associations between the five BRFs were found statistically significant. Chinese with older age, being a male, living in rural areas, having lower education level and lower yearly household income experienced increased likelihood of having more BRFs. CONCLUSIONS/SIGNIFICANCE: Current BRFs place the majority of Chinese aged 15 to 69 years at risk for the future development of chronic disease, which calls for urgent public health programs to reduce these risk factors. Prominent correlations between BRFs imply that a combined package of interventions targeting multiple BRFs might be appropriate. These interventions should target elder population, men, and rural residents, especially those with lower SES

Visual Information Alone Changes Behavior and Physiology during Social Interactions in a Cichlid Fish (Astatotilapia burtoni)

Social behavior can influence physiological systems dramatically yet the sensory cues responsible are not well understood. Behavior of male African cichlid fish, Astatotilapia burtoni, in their natural habitat suggests that visual cues from conspecifics contribute significantly to regulation of social behavior. Using a novel paradigm, we asked whether visual cues alone from a larger conspecific male could influence behavior, reproductive physiology and the physiological stress response of a smaller male. Here we show that just seeing a larger, threatening male through a clear barrier can suppress dominant behavior of a smaller male for up to 7 days. Smaller dominant males being “attacked” visually by larger dominant males through a clear barrier also showed physiological changes for up to 3 days, including up-regulation of reproductive- and stress-related gene expression levels and lowered plasma 11-ketotestesterone concentrations as compared to control animals. The smaller males modified their appearance to match that of non-dominant males when exposed to a larger male but they maintained a physiological phenotype similar to that of a dominant male. After 7 days, reproductive- and stress- related gene expression, circulating hormone levels, and gonad size in the smaller males showed no difference from the control group suggesting that the smaller male habituated to the visual intruder. However, the smaller male continued to display subordinate behaviors and assumed the appearance of a subordinate male for a full week despite his dominant male physiology. These data suggest that seeing a larger male alone can regulate the behavior of a smaller male but that ongoing reproductive inhibition depends on additional sensory cues. Perhaps, while experiencing visual social stressors, the smaller male uses an opportunistic strategy, acting like a subordinate male while maintaining the physiology of a dominant male

Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Cellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases, and hence natural antioxidants have significant importance in human health. The present study was carried out to evaluate the <it>in vitro </it>antioxidant and reactive oxygen species scavenging activities of <it>Terminalia chebula</it>, <it>Terminalia belerica </it>and <it>Emblica officinalis </it>fruit extracts.</p> <p>Methods</p> <p>The 70% methanol extracts were studied for <it>in vitro </it>total antioxidant activity along with phenolic and flavonoid contents and reducing power. Scavenging ability of the extracts for radicals like DPPH, hydroxyl, superoxide, nitric oxide, hydrogen peroxide, peroxynitrite, singlet oxygen, hypochlorous acid were also performed to determine the potential of the extracts.</p> <p>Results</p> <p>The ability of the extracts of the fruits in exhibiting their antioxative properties follow the order <it>T. chebula </it>><it>E. officinalis </it>><it>T. belerica</it>. The same order is followed in their flavonoid content, whereas in case of phenolic content it becomes <it>E. officinalis </it>><it>T. belerica </it>><it>T. chebula</it>. In the studies of free radicals' scavenging, where the activities of the plant extracts were inversely proportional to their IC₅₀values, <it>T. chebula </it>and <it>E. officinalis </it>were found to be taking leading role with the orders of <it>T. chebula </it>><it>E. officinalis </it>><it>T. belerica </it>for superoxide and nitric oxide, and <it>E. officinalis </it>><it>T. belerica </it>><it>T. chebula </it>for DPPH and peroxynitrite radicals. Miscellaneous results were observed in the scavenging of other radicals by the plant extracts, viz., <it>T. chebula </it>><it>T. belerica </it>><it>E. officinalis </it>for hydroxyl, <it>T. belerica </it>><it>T. chebula </it>><it>E. officinalis </it>for singlet oxygen and <it>T. belerica </it>><it>E. officinalis </it>><it>T. chebula </it>for hypochlorous acid. In a whole, the studied fruit extracts showed quite good efficacy in their antioxidant and radical scavenging abilities, compared to the standards.</p> <p>Conclusions</p> <p>The evidences as can be concluded from the study of the 70% methanol extract of the fruits of <it>Terminalia chebula</it>, <it>Terminalia belerica </it>and <it>Emblica officinalis</it>, imposes the fact that they might be useful as potent sources of natural antioxidant.</p