bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of chicken ovalbumin upstream promoter transcription factor II in the regulation of hepatic fatty acid oxidation and gluconeogenesis in newborn mice
Authors: Planchais Julien , Boutant Marie , Fauveau Véronique , Qing Lou Dan , Sabra-Makke Lina , Bossard Pascale , Vasseur-Cognet Mireille , Pégorier Jean-Paul
Published: March 2015

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor involved in the control of numerous functions in various organs (organogenesis, differentiation, metabolic homeostasis, etc.). The aim of the present work was to characterize the regulation and contribution of COUP-TFII in the control of hepatic fatty acid and glucose metabolisms in newborn mice. Our data show that postnatal increase in COUP-TFII mRNA levels is enhanced by glucagon (via cAMP) and PPARα. To characterize COUP-TFII function in the liver of suckling mice, we used a functional (dominant negative form; COUP-TFII-DN) and a genetic (shRNA) approach. Adenoviral COUP-TFII-DN injection induces a profound hypoglycemia due to the inhibition of gluconeogenesis and fatty acid oxidation secondarily to reduced PEPCK, Gl-6-Pase, CPT I, and mHMG-CoA synthase gene expression. Using the crossover plot technique, we show that gluconeogenesis is inhibited at two different levels: 1) pyruvate carboxylation and 2) trioses phosphate synthesis. This could result from a decreased availability in fatty acid oxidation arising cofactors such as acetyl-CoA and reduced equivalents. Similar results are observed using the shRNA approach. Indeed, when fatty acid oxidation is rescued in response to Wy-14643-induced PPARα target genes (CPT I and mHMG-CoA synthase), blood glucose is normalized in COUP-TFII-DN mice. In conclusion, this work demonstrates that postnatal increase in hepatic COUP-TFII gene expression is involved in the regulation of liver fatty acid oxidation, which in turn sustains an active hepatic gluconeogenesis that is essential to maintain an appropriate blood glucose level required for newborn mice survival.
Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence
Authors: Coallier Émilie , Michelet Thomas , Kalaska John F.
Published: March 2015

We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1.
Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment
Authors: Ding Shengyuan , Li Li , Zhou Fu-Ming
Published: March 2015

The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1BRs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT1BRs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT1BRs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRI-based antidepressant treatment sensitizes this presynaptic 5-HT1BR-mediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment.
Adaptive shaping of cortical response selectivity in the vibrissa pathway
Authors: Zheng He J. V. , Wang Qi , Stanley Garrett B.
Published: March 2015

One embodiment of context-dependent sensory processing is bottom-up adaptation, where persistent stimuli decrease neuronal firing rate over hundreds of milliseconds. Adaptation is not, however, simply the fatigue of the sensory pathway, but shapes the information flow and selectivity to stimulus features. Adaptation enhances spatial discriminability (distinguishing stimulus location) while degrading detectability (reporting presence of the stimulus), for both the ideal observer of the cortex and awake, behaving animals. However, how the dynamics of the adaptation shape the cortical response and this detection and discrimination tradeoff is unknown, as is to what degree this phenomenon occurs on a continuum as opposed to a switching of processing modes. Using voltage-sensitive dye imaging in anesthetized rats to capture the temporal and spatial characteristics of the cortical response to tactile inputs, we showed that the suppression of the cortical response, in both magnitude and spatial spread, is continuously modulated by the increasing amount of energy in the adapting stimulus, which is nonuniquely determined by its frequency and velocity. Single-trial ideal observer analysis demonstrated a tradeoff between detectability and spatial discriminability up to a moderate amount of adaptation, which corresponds to the frequency range in natural whisking. This was accompanied by a decrease in both detectability and discriminability with high-energy adaptation, which indicates a more complex coupling between detection and discrimination than a simple switching of modes. Taken together, the results suggest that adaptation operates on a continuum and modulates the tradeoff between detectability and discriminability that has implications for information processing in ethological contexts.
A Unique Presentation of Occult Primary Breast Cancer with a Review of the Literature
Authors: Ahmed Inaya , Dharmarajan Kavita , Tiersten Amy , Bleiweiss Ira , Schmidt Hank , Green Sheryl , Bakst Richard L.
Published: March 2015

We are reporting a case of a 34-year-old woman with occult primary breast cancer discovered after initially presenting with neurological symptoms. She was successfully treated with neoadjuvant chemotherapy followed by definitive axillary lymph node dissection and ipsilateral whole breast radiotherapy. The case presented is unique due to the rarity of occult primary breast cancer, especially in light of her initial confounding neurological signs and symptoms, which highlights the importance of careful staging.
Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway
Authors: Huang Xiaoying , Tang Jiangfeng , Cai Hui , Pan Yi , He Yicheng , Dai Caijun , Chen Ali , Yu Xiaoming , Chen Mayun , Zou Lizhen , Wang Liangxing
Published: March 2015

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.
Reconciling Homeostatic and Use-Dependent Plasticity in the Context of Somatosensory Deprivation
Authors: Orczyk John J. , Garraghty Preston E.
Published: March 2015

The concept of homeostatic plasticity postulates that neurons maintain relatively stable rates of firing despite changing inputs. Homeostatic and use-dependent plasticity mechanisms operate concurrently, although they have different requirements for induction. Depriving central somatosensory neurons of their primary activating inputs reduces activity and results in compensatory changes that favor excitation. Both a reduction of GABAergic inhibition and increase in glutamatergic excitatory transmission are observed in input-deprived cortex. Topographic reorganization of the adult somatosensory cortex is likely driven by both homeostatic and use-dependent mechanisms. Plasticity is induced by changes in the strengths of synaptic inputs, as well as changes in temporal correlation of neuronal activity. However, there is less certainty regarding thein vivocontribution of homeostatic mechanisms asin vitroexperiments rely on manipulations that create states that do not normally occur in the living nervous system. Homeostatic plasticity seems to occur, but morein vivoresearch is needed to determine mechanisms.In vitroresearch is also needed but should better conform to conditions that might occur naturallyin vivo.
Barriers to Implementation of Evidence Based Practice in Zahedan Teaching Hospitals, Iran, 2014
Authors: Khammarnia Mohammad , Haj Mohammadi Mahsa , Amani Zahra , Rezaeian Shahab , Setoodehzadeh Fatemeh
Published: March 2015

This study aimed to determine the barriers to implementation of EBP among nurses. This cross-sectional study was conducted in Zahedan City, South East of Iran, in 2014. The questionnaire of barriers to implementation of EBP consists of 27 statements which was distributed among 280 nurses. More than half of the participants agreed that 56% and 57% of barriers to implementation of evidence based practice are related to organizational and individual aspects, respectively. Participants identified barriers at organizational level included the lack of human resources (78.3%), lack of internet access at work (72.2%), and heavy workload (70.0%). Barrier at individual level included lack of time to read literature (83.7%), lack of ability to work with computer (68.8%), and insufficient proficiency in English language (62.0%). Age, educational level, job experience, and employment status were associated with organizational barriers to implementation of EBP. At the individual level only education was associated with barriers to implementation of EBP. Barriers to implementation of EBP occur at both individual and organizational levels. The indicator of quality in nursing practice is EBP. Hence, familiarity with EBP is recommended for Iranian nurses. In addition, knowledge of barriers will help health care system and policy makers to provide a culture of EBP.
A Case of Coronary Vasospasm after Repeat Rituximab Infusion
Authors: Ke Calvin , Khosla Amit , Davis Margot K. , Hague Cameron , Toma Mustafa
Published: March 2015

Coronary artery vasospasm (CAV) can be triggered by medication reactions. CAV occurring after multiple exposures to rituximab has not been previously described. A 61-year-old woman with no cardiac risk factors was treated with the sixth cycle of gemcitabine, cisplatin, dexamethasone, and rituximab therapy. Fifteen minutes after rituximab infusion commenced, she developed typical cardiac chest pain with ST segment elevations on electrocardiogram. Angiogram revealed evidence of coronary vasospasm. The patient was successfully treated with amlodipine. This case underlines the importance of monitoring cardiac side effects of rituximab therapy, even after multiple cycles.
Potential Influence of Climate Change on the Acid-Sensitivity of High-Elevation Lakes in the Georgia Basin, British Columbia
Authors: Strang Donna , Aherne Julian
Published: March 2015

Global climate models predict increased temperature and precipitation in the Georgia Basin, British Colmbia; however, little is known about the impacts on high-elevation regions. In the current study, fifty-four high-elevation lakes (754–2005 m a.s.l.) were studied to investigate the potential influence of climate change on surface water acid-sensitivity. Redundancy analysis indicated that the concentration of nitrate, dissolved organic carbon, and associated metals was significantly influenced by climate parameters. Furthermore, these components differed significantly between biogeoclimatic zones. Modelled soil base cation weathering for a subset of the study lakes(n=11)was predicted to increase by 9% per 1°C increase in temperature. Changes in temperature and precipitation may potentially decrease the pH of surface waters owing to changes in anthropogenic deposition and organic acid production. In contrast, increased soil base cation weathering may increase the critical load (of acidity) of high-elevation lakes. Ultimately, the determining factor will be whether enhanced base cation weathering is sufficient to buffer changes in natural and anthropogenic acidity. Mountain and high-elevation regions are considered early warning systems to climate change; as such, future monitoring is imperative to assess the potential ramifications of climate change on the hydrochemistry and acid-sensitivity of these surface waters.
Patterns, Consequences, and Possible Causes of Dropout in Upper Secondary Education in Mexico
Authors: Bentaouet Kattan Raja , Székely Miguel
Published: March 2015

The present study provides a detailed analysis of upper secondary education dropout patterns in Mexico, exploring its consequences and possible causes. To perform the analysis we combine different databases and statistical methods ranging from the use of surveys with information on specific individuals to data aggregated at the municipal and state level. The main value added is the simultaneous analysis of the influence of individual-family, community, and macroaggregate factors, on school dropout in the country.
Rapid Characterization of Tanshinone Extract Powder by Near Infrared Spectroscopy
Authors: Luo Gan , Xu Bing , Shi Xinyuan , Li Jianyu , Dai Shengyun , Qiao Yanjiang
Published: March 2015

Chemical and physical quality attributes of herbal extract powders play an important role in the research and development of Chinese medicine preparations. The active pharmaceutical ingredients have a direct impact on the herbal extract’s efficacy, while the physical properties of raw material affect the pharmaceutical manufacturing process and the final products’ quality. In this study, tanshinone extract powders from Salvia miltiorrhiza which are widely used for the treatment of cardiovascular diseases in the clinic are taken as the research object. Both the chemical information and physical information of tanshinone extract powders are analyzed by near infrared (NIR) spectroscopy. The partial least squares (PLS) and least square support vector machine (LS-SVM) models are investigated to build the relationship between NIR spectra and reference values. PLS models performed well for the content of crytotanshinone, tanshinone IIA, the moisture, and average median particle size, while, for specific surface area and tapped density, the LS-SVM models performed better than the PLS models. Results demonstrated NIR to be a valid and fast process analytical technology tool to simultaneously determine multiple quality attributes of herbal extract powders and indicated that there existed some nonlinear relationship between NIR spectra and physical quality attributes.
Modelling and Optimizing an Open-Pit Truck Scheduling Problem
Authors: Chang Yonggang , Ren Huizhi , Wang Shijie
Published: March 2015

This paper addresses a special truck scheduling problem in the open-pit mine with different transport revenue consideration. A mixed integer programming model is formulated to define the problem clearly and a few valid inequalities are deduced to strengthen the model. Some properties and two upper bounds of the problem are proposed. Based on these inequalities, properties, and upper bounds, a heuristic solution approach with two improvement strategies is proposed to resolve the problem and the numerical experiment demonstrates that the proposed solution approach is effective and efficient.
Caspase Activation and Aberrant Cell Growth in a p53+/+ Cell Line from a Li-Fraumeni Syndrome Family
Authors: Sherif Zaki A.
Published: March 2015

Wild-type p53 is well known to induce cell cycle arrest and apoptosis to block aberrant cell growth. However, p53’s unique role in apoptosis and cell proliferation in Li-Fraumeni Syndrome (LFS) has not been well elucidated. The aim of this study is to characterize the activity of wild-type p53 protein in LFS family dominated by a germline negative mutant p53. As expected, etoposide-treated wild-type p53-containing cell lines, LFS 2852 and control Jurkat, showed a greater rate of caspase- and annexin V-induced apoptotic cell death compared to the p53-mutant LFS 2673 cell line although mitochondrial and nuclear assays could not detect apoptosis in these organelles. The most intriguing part of the observation was the abnormal proliferation rate of the wild-type p53-containing cell line, which grew twice as fast as 2673 and Jurkat cells. This is important because apoptosis inducers acting through the mitochondrial death pathway are emerging as promising drugs against tumors where the role of p53 is not only to target gene regulation but also to block cell proliferation. This study casts a long shadow on the possible dysregulation of p53 mediators that enable cell proliferation. The deregulation of proliferation pathways represents an important anticancer therapeutic strategy for patients with the LFS phenotype.
Bidens pilosaFormulation Improves Blood Homeostasis andβ-Cell Function in Men: A Pilot Study
Authors: Lai Bun-Yueh , Chen Tzung-Yan , Huang Shou-Hsien , Kuo Tien-Fen , Chang Ting-Hsiang , Chiang Chih-Kang , Yang Meng-Ting , Chang Cicero Lee-Tian
Published: March 2015

B. pilosahas long been purported to have antidiabetes activity, but despite the advancement in phytochemistry and animal models of diabetes, no human clinical trials have been conducted to date. Here, we evaluated the effect of aB. pilosaformulation on fasting blood glucose (FBG), fasting serum insulin, and glycosylated hemoglobin A1c(HbA1c)in diabetic subjects. TheB. pilosaformulation reduced the level of FBG andHbA1cin diabetics but increased fasting serum insulin in healthy subjects. Moreover, combination ofB. pilosaformulation with antidiabetic drugs had better glycemic control in diabetics. The homeostatic model assessment (HOMA) data suggested that the antidiabetic activity of this formulation was via improvement ofβ-cell function. We also tested the safety of theB. pilosaformulation in healthy subjects and observed no obvious side effects. We conclude thatB. pilosahas potential as an antidiabetes treatment.
Antitumor Activities of Ethyl Acetate Extracts fromSelaginella doederleiniiHieronIn VitroandIn Vivoand Its Possible Mechanism
Authors: Wang Jia-zhi , Li Juan , Zhao Ping , Ma Wen-tao , Feng Xie-he , Chen Ke-li
Published: March 2015

The antitumor activities of ethyl acetate extracts fromSelaginella doederleiniiHieron (SD extracts)in vitroandin vivoand its possible mechanism were investigated. HPLC method was developed for chemical analysis. SD extracts were submitted to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on different cells, flow cytometry, and RT-PCR analysis using HepG2 cell and antitumor activityin vivousing H-22 xenograft tumor mice. Six biflavonoids from SD extracts were submitted to molecular docking assay. The results showed that SD extracts had considerable antitumor activityin vitroandin vivowithout obvious toxicity on normal cells and could induce cell apoptosis. The mechanisms of tumorigenesis and cell apoptosis induced by SD extracts may be associated with decreasing the ratio of bcl-2 and bax mRNA level, activating caspase-3, suppressing survivin, and decreasing the gene expression of COX-2, 5-LOX, FLAP, and 12-LOX mRNA. The main active component in SD extracts is biflavonoids and some exhibited strong interactions with COX-2, 5-LOX, 12-LOX, and 15-LOX. These results offering evidence of possible mechanisms of SD extracts suppress cell proliferation and promote apoptosis and provide the molecular theoretical basis of clinical application ofS. doederleiniifor cancer therapy.
Yokukansan Improves Mechanical Allodynia through the Regulation of Interleukin-6 Expression in the Spinal Cord in Mice with Neuropathic Pain
Authors: Ebisawa Shigeru , Andoh Tsugunobu , Shimada Yutaka , Kuraishi Yasushi
Published: March 2015

Neuropathic pain is caused by nerve injury. Yokukansan (Yi-Gan San), a traditional Japanese (Kampo) medicine, has been widely used for neuropathic pain control. However, the analgesic mechanisms remain unknown. In this study, we investigated the analgesic mechanisms of yokukansan in a mouse model of neuropathic pain. Partial sciatic nerve ligation (PSL) induced mechanical allodynia in mice. Repetitive oral administration of the extracts of yokukansan and the constituent herbal medicine Atractylodis Lanceae Rhizoma, but not Glycyrrhizae Radix, relieved mechanical allodynia in the PSL mice and inhibited the PSL-induced expression of interleukin- (IL-) 6 mRNA in the spinal cord. Yokukansan did not attenuate intrathecal IL-6-induced mechanical allodynia. IL-6 immunoreactivity was detected in microglia and astrocytes in the spinal dorsal horn. These results suggest that yokukansan relieves mechanical allodynia in PSL mice by regulating the expression of IL-6 in astrocytes and/or microglia in the spinal cord. In addition, the components of Atractylodis Lanceae Rhizoma, one of the constituent herbal medicines in yokukansan, may play an important role in the regulation of IL-6 expression and neuropathic pain control.
Preparation and Antibacterial Properties of Substituted 1,2,4-Triazoles
Authors: Ledeţi Ionuţ , Bercean Vasile , Alexa Anda , Şoica Codruţa , Şuta Lenuţa-Maria , Dehelean Cristina , Trandafirescu Cristina , Muntean Delia , Licker Monica , Fuliaş Adriana
Published: March 2015

Background. Both 1,2,3- and 1,2,4-triazoles are nowadays incorporated in numerous antibacterial pharmaceutical formulations.Aim. Our study aimed to prepare three substituted 1,2,4-triazoles and to evaluate their antibacterial properties.Materials and Methods. One disubstituted and two trisubstituted 1,2,4-triazoles were prepared and characterised by physical and spectroscopic properties (melting point, FTIR, NMR, and GC-MS). The antibacterial properties were studied against three bacterial strains:Staphylococcus aureus(ATCC 25923),Escherichia coli(ATCC 25922), andPseudomonas aeruginosa(ATCC 27853), by the agar disk diffusion method and the dilution method with MIC (minimal inhibitory concentration) determination.Results. The spectroscopic characterization of compounds and the working protocol for the synthesis of the triazolic derivatives are described. The compounds were obtained with 15–43% yields and with high purities, confirmed by the NMR analysis. The evaluation of biological activities showed that the compounds act as antibacterial agents againstStaphylococcus aureus(ATCC 25923), while being inactive againstEscherichia coli(ATCC 25922) andPseudomonas aeruginosa(ATCC 27853).Conclusions. Our results indicate that compounds containing 1,2,4-triazolic moiety have great potential in developing a wide variety of new antibacterial formulations.
Elaboration of Nanoparticles Containing Indomethacin: Argan Oil for Transdermal Local and Cosmetic Application
Authors: Badri Waisudin , Miladi Karim , Eddabra Rkia , Fessi Hatem , Elaissari Abdelhamid
Published: March 2015

The objective of this work is the preparation of nanocapsules which are intended for the treatment of rheumatoid arthritis (RA). We use Argan oil as vehicle of hydrophobic drugs such as indomethacin. Nanoprecipitation technique was used like a method for preparation of nanocapsules, where polycaprolactone, acetone, and Argan oil are used as polymer, solvent, and carrier, respectively. Primarily, investigation of Argan oil amount addition was performed; then systematic study to optimize the formulation was done. Nanocapsules containing indomethacin (loaded nanocapsules) and others without indomethacin (blank nanocapsules) were characterized by studying particles size, zeta potential, and encapsulation efficiency. It is shown that particle size ranged between 290 nm and 350 nm. The zeta potential values were negative (from −40 up to −50 mV) while encapsulation efficiency ranged between 65 and 75%.
CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration
Authors: Wei Yuhong , Vellanki Ravi N. , Coyaud Étienne , Ignatchenko Vladimir , Li Lei , Krieger Jonathan R. , Taylor Paul , Tong Jiefei , Pham Nhu-An , Liu Geoffrey , Raught Brian , Wouters Bradly G. , Kislinger Thomas , Tsao Ming Sound , Moran Michael F.
Published: March 2015

Coiled-coil-helix-coiled-coil-helix domain-containing 2, a mitochondrial protein, encoded by CHCHD2 is located at chromosome 7p11.2 and proximal to the EGFR gene. Here, bioinformatic analyses revealed that CHCHD2 is consistently coamplified with EGFR in non–small cell lung carcinoma (NSCLC). In addition, CHCHD2 and EGFR protein expression levels were positively correlated and upregulated relative to normal lung in NSCLC tumor-derived xenografts. Knockdown of CHCHD2 expression in NSCLC cells attenuated cell proliferation, migration, and mitochondrial respiration. CHCHD2 protein–protein interactions were assessed by the complementary approaches of affinity purification mass spectrometry and in vivo proximity ligation. The CHCHD2 interactome includes the apparent hub proteins C1QBP (a mitochondrial protein) and YBX1 (an oncogenic transcription factor), and an overlapping set of hub-associated proteins implicated in cell regulation.

Implications: CHCHD2 influences mitochondrial and nuclear functions and contributes to the cancer phenotype associated with 7p11.2 amplification in NSCLC. Mol Cancer Res; 13(7); 1119–29. ©2015 AACR.
Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis
Authors: Baldassarre Tomas , Watt Kathleen , Truesdell Peter , Meens Jalna , Schneider Mark M. , Sengupta Sandip K. , Craig Andrew W.
Published: March 2015

Triple-negative breast cancers (TNBCs) are highly aggressive cancers that lack targeted therapies. However, EGFR is frequently activated in a subset of TNBCs and represents a viable clinical target. Because the endocytic adaptor protein Endophilin A2 (SH3GL1/Endo II) has been implicated in EGFR internalization, we investigated Endo II expression and function in human TNBCs. Endo II expression was high in several TNBC cells compared with normal breast epithelial cells. Stable knockdown (KD) of Endo II was achieved in two TNBC cell lines, and although cell viability was unaffected, defects in receptor-mediated endocytosis were observed. EGFR signaling to Erk and Akt kinases was impaired in Endo II KD cells, and this correlated with reduced rates of EGFR internalization and cell motility. Endo II KD cells also displayed defects in three dimensional (3D) cell invasion, and this correlated with impaired extracellular matrix degradation and internalization of MT1-MMP. Endo II silencing also caused a significant reduction in TNBC tumor growth and lung metastasis in mammary orthotopic tumor xenograft assays. In human breast tumor specimens, Endo II expression was highest in TNBC tumors compared with other subtypes, and at the level of gene expression, high Endo II was associated with reduced relapse-free survival in patients with basal-like breast cancers. Together, these results identify a positive role for Endo II in TNBC tumor metastasis and a potential link with poor prognosis.

Implications: Endophilin A2 and related adaptor proteins represent important signaling hubs to target in metastatic cancers. Mol Cancer Res; 13(6); 1044–55. ©2015 AACR.
UCP2 Knockout Suppresses Mouse Skin Carcinogenesis
Authors: Li Wenjuan , Zhang Chunjing , Jackson Kasey , Shen Xingui , Jin Rong , Li Guohong , Kevil Christopher G. , Gu Xin , Shi Runhua , Zhao Yunfeng
Published: March 2015

Mitochondrial uncoupling (uncouples electron transport from ATP production) has recently been proposed as a novel survival mechanism for cancer cells, and reduction in free radical generation is the accepted mechanism of action. However, there is no direct evidence supporting that uncoupling proteins promote carcinogenesis. Herein, we examined whether mitochondrial uncoupling affects mouse skin carcinogenesis using uncoupling protein 2 (UCP2) homozygous knockout and wild-type mice. The results indicate that knockout of Ucp2 significantly reduced the formation of both benign (papilloma) and malignant (squamous cell carcinoma) tumors. UCP2 knockout did not cause increases in apoptosis during skin carcinogenesis. The rates of oxygen consumption were decreased only in the carcinogen-treated UCP2 knockout mice, whereas glycolysis was increased only in the carcinogen-treated wild-type mice. Finally, the levels of metabolites pyruvate, malate, and succinate showed different trends after carcinogen treatments between the wild-type and UCP2 knockout mice. Our study is the first to demonstrate that Ucp2 knockout suppresses carcinogenesis in vivo. Together with early studies showing that UCP2 is overexpressed in a number of human cancers, UCP2 could be a potential target for cancer prevention and/or therapy. Cancer Prev Res; 8(6); 487–91. ©2015 AACR.
3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21
Authors: Peng Xiaoli , Chang Hui , Gu Yeyun , Chen Junli , Yi Long , Xie Qi , Zhu Jundong , Zhang Qianyong , Mi Mantian
Published: March 2015

Our previous study selected a promising chemopreventive agent 3,6-dihydroxyflavone (3,6-DHF) and found that 3,6-DHF significantly upregulates miR-34a and downregulates miR-21 in breast carcinogenesis, yet the upstream and downstream events of the anticancer mechanism remain unclear. The present study showed that 3,6-DHF cotreatment effectively inhibits carcinogens-induced breast carcinogenic transformation in human breast epithelial MCF10A cells. The data revealed the significant downregulation of miR-34a and upregulation of miR-21 in breast carcinogenesis, which could be mitigated by 3,6-DHF treatment. Methylation-specific PCR detections showed that 3,6-DHF inhibits the hypermethylation of the miR-34a promoter. Further studies indicated that 3,6-DHF is an effective methyltransferase (DNMT)1 inhibitor, docking to the putative cytosine pocket of the protein, and thus decreases the DNMT activity in a dose-dependent manner. Moreover, the ChIP-qPCR analysis for histone modifications showed that 3,6-DHF treatment significantly lowers the H3K9-14ac on the miR-21 promoter. In addition, our study revealed that 3,6-DHF represses the PI3K/Akt/mTOR signaling pathway in breast carcinogenesis in vitro and in vivo. Inhibition of miR-34a or overexpression of miR-21 significantly reduced the effects of 3,6-DHF on Notch-1 and PTEN, and consequently weakened the suppression of 3,6-DHF on PI3K/Akt/mTOR. We concluded that 3,6-DHF upregulates miR-34a via inhibiting DNMT1 and hypermethylation, whereas downregulates miR-21 by modulating histone modification, and consequently suppresses the PI3K/Akt/mTOR signaling pathway in breast carcinogenesis. Cancer Prev Res; 8(6); 509–17. ©2015 AACR.
Receptor for Advanced Glycation End-Product Antagonist Reduces Blood–Brain Barrier Damage After Intracerebral Hemorrhage
Authors: Yang Fan , Wang Zhe , Zhang John H. , Tang Jiping , Liu Xin , Tan Liang , Huang Qing-Yuan , Feng Hua
Published: March 2015

Background and Purpose—

To determine whether the receptor for advanced glycation end-products (RAGE) plays a role in early brain injury from intracerebral hemorrhage (ICH), RAGE expression and activation after injury were examined in a rat model of ICH with or without administration of a RAGE-specific antagonist (FPS-ZM1).

Methods—

Autologous arterial blood was injected into the basal ganglia of rats to induce ICH. The motor function of the rats was examined, and water content was detected after euthanization. Blood–brain barrier permeability was determined by Evans blue staining and colloidal gold nanoparticle tracers. Nerve fiber injury in white matter was determined by diffusion tensor imaging analysis, and the expression of target genes was analyzed by Western blotting and quantitative reverse transcription polymerase chain reaction. FPS-ZM1 was administered by intraperitoneal injection.

Results—

Expression of RAGE and its ligand high-mobility group protein B1 were increased at 12 hours after ICH, along with blood–brain barrier permeability and perihematomal nerve fiber injury. RAGE and nuclear factor-κB p65 upregulation were also observed when FeCl
2
was infused into the basal ganglia at 24 hours. FPS-ZM1 administration resulted in significant improvements of blood–brain barrier damage, brain edema, motor dysfunction, and nerve fiber injury, and the expression of RAGE, nuclear factor-κB p65, proinflammatory mediators interleukin 1β, interleukin-6, interleukin-8R, cyclooxygenase-2, inducible nitric oxide synthase, and matrix metallopeptidase-9 was attenuated. Moreover, decreases in claudin-5 and occludin expression were partially recovered. FPS-ZM1 also reversed FeCl
2
-induced RAGE and nuclear factor-κB p65 upregulation.

Conclusions—

RAGE signaling is involved in blood–brain barrier and white matter fiber damage after ICH, the initiation of which is associated with iron. RAGE antagonists represent a novel therapeutic intervention to prevent early brain injury after ICH.
Brüstle v. Greenpeace: Implications for Commercialisation of Translational Stem Cell Research
Authors: Mansnérus Juli
Published: March 2015

The lack of consensus on a common definition of the term ‘embryo’ has resulted in legal uncertainty affecting the permissibility of human embryonic stem cell (hESC) research and the commercialisation prospects and patenting of inventions of hESC origin in the eu. The Brüstle v. Greenpeace case, which by providing a very broad definition of a human embryo restricts the patentability of hESC-based inventions, aims at harmonising the patenting practices regarding interpretation of Article 6.2.c of Directive 98/44/ec. It fills the gaps in national laws by providing binding interpretation guidelines for national courts. As currently no marketing authorisations have been granted to hESC-based products, implications of this judgment for translational hESC research together with other barriers to commercialisation of such research need to be analysed. In addition, whether the main obstacles relate to patenting restrictions or whether something else in the innovation system is impeding the market entry of these innovative products is discussed.
A method for establishing taxonomic research priorities in a megadiverse country
Authors: Victor Janine , Smith Gideon F. , VAN WYK ABRAHAM E.
Published: March 2015

A coordinated strategy for biosystematics research that addresses the needs of end-users can improve the relevance and impact of research products. The basic types of information that taxonomists provide, common to all organisms, are the names, descriptions, and a mechanism for identifying components of biodiversity, and associated data such as distribution information. This information is provided through taxonomic research.      A biosystematics research strategy has been developed in South Africa to focus on the main gaps in taxonomic knowledge. A prioritisation process has been developed and applied to plants, but can potentially be used for all organisms. The methodology for development of the taxonomic priorities to formulate a research strategy is described. Determining priorities for taxonomic research and development of the strategy will facilitate bridging the gaps among compilers, users and implementers of taxonomic information, and streamline the taxonomy-conservation impediment.
A systematic study on Endotribelos Grodhaus (Diptera: Chironomidae) from Brazil including DNA barcoding to link males and females
Authors: TRIVINHO-STRIXINO SUSANA , PEPINELLI MATEUS
Published: March 2015

Six new species of Endotribelos from Brazil are described and illustrated as male, female, pupa and larva: E. bicolor sp. n., E. fulvidus sp. n., E. jaragua sp. n., E. jiboia sp. n., E. semibruneus sp. n. and E. sublettei sp. n. The female of E. calophylli Roque & Trivinho-Strixino and the larvae of four unknown morphotypes are also described. Keys including males and larvae of all known species of Endotribelos are provided. Adults’ males and females from five species were linked using DNA Barcoding mtCOI sequences.
A new species of Compsoneuriella Ulmer, 1939 (Ephemeroptera: Heptageniidae) from Thailand
Authors: BOONSOONG BOONSATIEN , SARTORI MICHEL
Published: March 2015

A new species of Compsoneuriella Ulmer, 1939 is described based on male and female imagos, nymphs and eggs from Ratchaburi province, western Thailand. Compsoneuriella braaschi sp. nov. is closely related to C. thienemanni Ulmer, 1939, from Java and Sumatra, but differs in the larval stage by the maxilla bearing only 8–9 comb-shaped setae on the crown, two strong medial setae on the glossa, gills V–VII apically acutely pointed and the posterior margin of the abdominal terga without distinct rows of submarginal microdenticles. In the male imaginal stage, the new species differs from C. thienemanni by having more reduced spines on the penis lobes and the titillators being directed outwards and strongly pointed at their apices.
Signatures of Hydrometeor Species from Airborne Passive Microwave Data for Frequencies 10–183 GHz
Authors: Leppert Kenneth D. , Cecil Daniel J.
Published: March 2015

Passive microwave brightness temperatures (BTs) collected above severe thunderstorms using the Advanced Microwave Precipitation Radiometer and Conical Scanning Millimeter-Wave Imaging Radiometer during the Midlatitude Continental Convective Clouds Experiment are compared with a hydrometeor identification applied to dual-polarimetric Weather Surveillance Radar-1988 Doppler radar data collected at Vance Air Force Base, Oklahoma (KVNX). The goal of this work is to determine the signatures of various hydrometeor species in terms of BTs measured at frequencies used by the Global Precipitation Measurement mission Microwave Imager. Results indicate that hail is associated with an ice-scattering signature at all frequencies examined, including 10.7 GHz. However, it appears that frequencies ≤ 37.1 GHz are most useful for identifying hail. Low-level (below 2.5 km) hail becomes probable for a BT below 240 K at 19.4 GHz, 170 K at 37.1 GHz, 90 K at 85.5 GHz, 80 K at 89.0 GHz, 100 K at 165.5 GHz, and 100 K at 183.3 ± 7 GHz. Graupel may be distinguished from hail and profiles without any hydrometeor species by its strong scattering signature at higher frequencies (e.g., 165.5 GHz) and its relative lack of scattering at frequencies ≤ 19.4 GHz. There is a clearer distinction between profiles that contain liquid precipitation and profiles without any hydrometeors when the liquid is associated above with hail and/or graupel (i.e., a hydrometeor category with a strong scattering signature) than when the liquid is associated with smaller ice. Near-surface precipitation is much more likely for a 19.4-GHz BT < 250 K, 37.1-GHz BT < 240 K, 89.0-GHz BT < 220 K, and 165.5-GHz BT < 140 K.
Estimating the Response of Extreme Precipitation over Midlatitude Mountains to Global Warming
Authors: Shi Xiaoming , Durran Dale R.
Published: March 2015

Global warming–induced changes in extreme orographic precipitation are investigated using a hierarchy of models: a global climate model, a limited-area weather forecast model, and a linear mountain wave model. The authors consider precipitation changes over an idealized north–south midlatitude mountain barrier at the western margin of an otherwise flat continent. The intensities of the extreme events on the western slopes increase by approximately 4% K−1 of surface warming, close to the “thermodynamic” sensitivity of vertically integrated condensation in those events due to temperature variations when vertical motions stay constant. In contrast, the intensities of extreme events on the eastern mountain slopes increase at about 6% K−1. This higher sensitivity is due to enhanced ascent during the eastern-slope events, which can be explained in terms of linear mountain wave theory as arising from global warming–induced changes in the upper-tropospheric static stability and the tropopause level. Similar changes to these two parameters also occur for the western-slope events, but the cross-mountain flow is much stronger in those events; as a consequence, linear theory predicts no increase in the western-slope vertical velocities. Extreme western-slope events tend to occur in winter, whereas those on the eastern side are most common in summer. Doubling CO2 not only increases the precipitation, but during extreme western slope events it shifts much of the precipitation from snow to rain, potentially increasing the risk of heavy runoff and flooding.
Global Ensemble Forecast Tracks for Tropical Storm Debby
Authors: Colby Frank P.
Published: March 2015

Operational-model track forecasts for Tropical Storm Debby (June 2012) diverged as much as 180°, making the National Hurricane Center forecast particularly challenging. Forecast tracks from the members of the National Centers for Environmental Prediction Global Ensemble Forecast System (GEFS) were similarly divergent; some forecast Debby to turn westward, some forecast Debby to go northward, and others forecast Debby to go eastward. Part of the divergence in the operational models can be from differences in model code, but the divergence in the GEFS is due only to differences in initial conditions. To understand the meteorological reasons for this model divergence, GEFS forecasts for Debby were examined in detail. Debby formed in the south-central Gulf of Mexico and then became a tropical storm by 1200 UTC 23 June 2012. Careful examination of the GEFS tracks showed that those storms turning east were stronger and deeper than those turning west. The storm strength was measured by the mean sea level pressure at the center of the storms and the maximum 10-m wind speed. The correlation coefficients between these two quantities and the longitude 12 and 24 h later were between 0.60 and 0.90, for all GEFS model runs initialized between 0000 UTC 24 June and 1200 UTC 26 June 2012. Further investigation showed that the initial midlevel moisture (specific humidity at 850 and 700 hPa) determined the subsequent strength and depth of the member storms. This variation in depth changed the effective layer for steering currents, which determined the direction to which the storms moved.
Usefulness of Serum Albumin Concentration to Predict High Coronary SYNTAX Score and In-Hospital Mortality in Patients With Acute Coronary Syndrome
Authors: Kurtul Alparslan , Murat Sani Namik , Yarlioglues Mikail , Duran Mustafa , Ocek Adil Hakan , Koseoglu Cemal , Celık Ibrahim Etem , Kilic Alparslan , Aksoy Ozlem
Published: March 2015

High SYNTAX score is a predictor of adverse cardiovascular events, including mortality, in acute coronary syndromes (ACSs). Decreased serum albumin (SA) concentration is associated with an increased risk of cardiovascular events. We aimed to investigate whether SA levels at admission are associated with high SYNTAX score and in-hospital mortality in patients with ACS. The study included 1303 patients with ACS who underwent coronary angiography (CA). The patients were divided into 2 groups as high SYNTAX score (≥33) and lower SYNTAX score (≤32). Baseline SA levels were significantly lower in patients with high SYNTAX score than with lower SYNTAX score (3.46 ± 0.42 mg/dL vs 3.97±0.37 mg/dL, respectively; P < .001). On multivariate logistic regression, SA (<3.65 mg/dL) was an independent predictor of high SYNTAX score (odds ratio 4.329, 95% confidence interval 2.028-8.264; P < .001) together with admission glucose, estimated glomerular filtration rate, and left ventricular ejection fraction. In Cox regression analyses, systolic blood pressure, high SYNTAX score, and SA (<3.65 mg/dL) were found as independent predictors of in-hospital all-cause mortality. In conclusion, SA concentration on admission is inversely associated with high SYNTAX score and in-hospital mortality in ACS.
Reflections of a group of South African teenage mothers: Sexual health implications
Authors: Singh Shakila , Hamid Alvi
Published: March 2015

Objectives:

In the context of women’s vulnerability to sexual violence, HIV infection and unintended pregnancy in South Africa, this paper explores the ways in which teenage mothers who are in school reflect on their experiences of pregnancy and motherhood. We attempt to understand how teenage mothers reflect on their experiences within the cultural and institutionalised discourses in which they are embedded, and how their reflections lead to critical assessment and questioning of the dominant discourses of femininity that compromise women’s sexual health.

Methods:

This paper draws on findings from a study with a selected group of teenage mothers in a Durban school. Main data collection strategies comprised individual and group interviews. Participants’ reflections on their experiences of teenage motherhood are discussed in relation to three themes: ‘regret and pride’, ‘contesting female victimhood’ and ‘lessons learned’.

Results:

Many teenage mothers indicate that being pregnant and having a child while still at school provides an impetus to take control of their lives. The data suggest that study participants use their reflections to construct a version of femininity that enables them to express themselves in ways that demonstrate greater agency.

Conclusion:

The greater agency expressed by teenage mothers has implications for their future sexual health and prevention of subsequent unintended pregnancies. In particular, it opens up possibilities for engaging them as peers in health education focusing on prevention of unintended pregnancy, by drawing on useful insights from lessons learned.