bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning foreign-language sounds in adulthood: Listening, speaking, and individual differences
Authors: McQueen James M. , Krutwig Jana , Jager Lisette , Desain Peter , Witteman Jurriaan , Schiller Niels O.
Published: November 2018

Adult native Dutch speakers tend to have difficulty learning the English /æ/-/ɛ/ contrast because both English vowels can be assimilated to Dutch /ε/. Two experiments examined how this contrast is acquired by Dutch adults and the relationship between perception and production in this process. In Experiment 1, a four-day perceptual training protocol on the /æ/-/ε/ contrast was combined with related or unrelated production practice (participants said the target word or a phonologically unrelated word after each perceptual decision). There was improvement over the four days in perception and production, but no effect of type of production practice. Perceptual training can thus boost production learning even when participants have to produce the new vowels. Some individuals, however, are more successful in acquiring foreign sounds. In Experiment 2, Dutch students were followed longitudinally over their first year studying English at university. Preliminary results indicate that, in a passive oddball paradigm testing for a MisMatch Negativity (MMN) effect, students could discriminate English /æ/ from English /ε/ already at initial test, but Dutch /ɛ/ from English /ɛ/ only at final test. We will ask whether students who show a larger increase in MMN over time improve more in pronunciation of /æ/ and /ε/.
Considering a Holistic Focus of Attention as an Alternative to an External Focus
Authors: Becker Kevin A. , Georges Ayana F. , Aiken Christopher A.
Published: November 2018

Empirical findings consistently suggest that an external focus of attention leads to superior performance when compared to an internal focus by encouraging more automatic processing. However, for certain skills (e.g., gymnastics routines) it can be challenging to identify a meaningful external focus cue. A related line of research suggests that focusing on the general feeling of a movement (i.e., holistic focus) may also be useful in avoiding conscious control of movements. The purpose of this study was to determine how an internal focus (INT), external focus (EXT), and holistic focus (HOL) impact the performance of a standing long jump. Participants (N = 27) completed two baseline jumps followed by two jumps in each focus condition. Jump distance was analyzed in a 6 (Order) × 4 (Focus) mixed ANOVA. Results indicated a significant main effect of focus (p < .001), with EXT and HOL resulting in farther jumps than INT and baseline conditions (p-values < .05). EXT and HOL did not differ significantly from each other, and INT did not differ significantly from baseline. The findings suggest that a holistic focus can be another effective means of avoiding conscious control of movement when an external focus is not practical or desired.
Response to Comment on “Contrasting carbon cycle responses of the tropical continents to the 2015–2016 El Niño”
Authors: Liu Junjie , Bowman Kevin W. , Schimel David , Parazoo Nicolas C. , Jiang Zhe , Lee Meemong , Bloom A. Anthony , Wunch Debra , Frankenberg Christian , Sun Ying , O’Dell Christopher W. , Gurney Kevin R. , Menemenlis Dimitris , Gierach Michelle , Crisp David , Eldering Annmarie
Published: November 2018

Chevallier showed a column CO
2
(

X

CO

2

) anomaly of ±0.5 parts per million forced by a uniform net biosphere exchange (NBE) anomaly of 2.5 gigatonnes of carbon over the tropical continents within a year, so he claimed that the inferred NBE uncertainties should be larger than presented in Liu
et al
. We show that a much concentrated NBE anomaly led to much larger

X

CO

2

perturbations.
A gamma-ray determination of the Universe’s star formation history
Authors:   The Fermi-LAT Collaboration, Abdollahi S. , Ackermann M. , Ajello M. , Atwood W. , Baldini L. , Ballet J. , Barbiellini G. , Bastieri D. , González J. Becerra , Bellazzini R. , Bissaldi E. , Blandford R. , Bloom E. , Bonino R. , Bottacini E. , Buson S. , Bregeon J. , Bruel P. , Buehler R. , Cameron R. , Caputo R. , Caraveo P. A. , Cavazzuti E. , Charles E. , Chen S. , Cheung T. , Chiaro G. , Ciprini S. , Cohen-Tanugi J. , Cominsky L. , Conrad J. , Costantin D. , Cutini S. , D’Ammando F. , de Palma F. , Desai A. , Digel S. , Di Lalla N. , Di Mauro M. , Di Venere L. , Domínguez A. , Favuzzi C. , Fegan S. , Finke J. , Franckowiak A. , Fukazawa Y. , Funk S. , Fusco P. , Romero G. Gallardo , Gargano F. , Gasparrini D. , Giglietto N. , Giordano F. , Giroletti M. , Green D. , Grenier I. , Guillemot L. , Guiriec S. , Hartmann D. H. , Hays E. , Helgason K. , Horan D. , Jóhannesson G. , Kocevski D. , Kuss M. , Larsson S. , Latronico L. , Li J. , Longo F. , Loparco F. , Lott B. , Lovellette M. , Lubrano P. , Madejski G. , Magill J. , Maldera S. , Manfreda A. , Marcotulli L. , Mazziotta M. , McEnery J. , Meyer M. , Michelson P. , Mizuno T. , Monzani M. E. , Morselli A. , Moskalenko I. , Negro M. , Nuss E. , Ojha R. , Omodei N. , Orienti M. , Orlando E. , Ormes J. , Palatiello M. , Paliya V. , Paneque D. , Perkins J. , Persic M. , Pesce-Rollins M. , Petrosian V. , Piron F. , Porter T. , Primack J. R. , Principe G. , Rainò S. , Rando R. , Razzano M. , Razzaque S. , Reimer A. , Reimer O. , Parkinson P. Saz , Sgrò C. , Siskind E. J. , Spandre G. , Spinelli P. , Suson D. J. , Tajima H. , Takahashi M. , Thayer J. , Tibaldo L. , Torres D. F. , Torresi E. , Tosti G. , Tramacere A. , Troja E. , Valverde J. V. , Vianello G. , Vogel M. , Wood K. , Zaharijas G.
Published: November 2018

Gamma rays reveal the Universe's history

How many stars have formed in the Universe, and when did they do so? These fundamental questions are difficult to answer because there are systematic uncertainties in converting the light we observe into the total mass of stars in galaxies. The Fermi-LAT Collaboration addressed these questions by exploiting the way that gamma rays from distant blazars propagate through intergalactic space, which depends on the total amount of light emitted by all galaxies. The collaboration found that star formation peaked about 3 billion years after the Big Bang (see the Perspective by Prandini). Although this is similar to previous estimates from optical and infrared observations, the results provide valuable confirmation because they should be affected by different systematic effects.

Science
, this issue p.
1031
; see also p.
995
1.9-million- and 2.4-million-year-old artifacts and stone tool–cutmarked bones from Ain Boucherit, Algeria
Authors: Sahnouni Mohamed , Parés Josep M. , Duval Mathieu , Cáceres Isabel , Harichane Zoheir , van der Made Jan , Pérez-González Alfredo , Abdessadok Salah , Kandi Nadia , Derradji Abdelkader , Medig Mohamed , Boulaghraif Kamel , Semaw Sileshi
Published: November 2018

Early humans in northern Africa

Evidence for the earliest stone tools produced by human ancestors (from ∼2.6 million years ago) has hitherto come from East Africa. Sahnouni
et al.
report the discovery of Oldowan stone artifacts and associated cutmarks on fossil bones excavated in Algeria, with the earliest dated to 2.4 million years ago. Thus, hominins inhabited the Mediterranean fringe in North Africa earlier than commonly believed. Furthermore, either stone tool manufacture and use dispersed early from East Africa or stone tool manufacture and use originated in both North and East Africa.

Science
, this issue p.
1297
Culture and conformity shape fruitfly mating
Authors: Whiten Andrew
Published: November 2018

Potent social learning sustains the inheritance of mating preferences over generations
The last of Asia conquered by
Homo sapiens
Authors: Zhang Jia-Fu , Dennell Robin
Published: November 2018

Excavation reveals the earliest human colonization of the Tibetan Plateau
Repeated anaerobic tests predict performance among a group of advanced CrossFit-trained athletes
Authors: Feito Yuri , Giardina Michael J. , Butcher Scotty , Mangine Gerald T.
Published: November 2018

High-intensity functional training (HIFT) (i.e., CrossFit (CF) training) uses a combination of movements and self-selected time periods of work and rest. However, little is known about the physiological responses to an acute bout of HIFT exercise or about the physical parameters that distinguish performance. The purpose of this study was to examine the physiological responses in advanced CF athletes to consecutive Wingate trials with short, active recovery periods. Twenty-nine advanced-level CF-trained athletes volunteered for this study. The participants were required to complete 4 consecutive Wingate anaerobic tests (WAnTs) and a 15-min CF-style workout. Across the 4 WAnT trials, significant (p < 0.001) changes were observed in oxygen consumption, respiratory exchange ratio, and heart rate. Significant (p ≤ 0.001) differences among WAnT trials were observed in all anaerobic performance measures. Compared with all other trials, greater peak power (p < 0.04), relative peak power (p < 0.02), average power (p < 0.001), relative average power (p < 0.001), and total work (p < 0.001), together with a lower fatigue index (p < 0.01), were observed during WAnT 1. Overall, the 4 consecutive WAnT trials resulted in a significant (F = 177.0, p < 0.001) increase in blood lactate response. Stepwise regression revealed that the ability to predict total repetitions completed during the 15-min trial to complete as many repetitions as possible improved as the participants progressed from the first to the third WAnT trial. Our data suggest that, combined with the ability to better maintain performance across high-intensity exercise bouts, the ability to quickly recover between bouts is the most important factor in CF performance.
Response of alfalfa and sugar beet to field dodder (Cuscuta campestris Yunck.) parasitism: a physiological and anatomical approach
Authors: Saric-Krsmanovic Marija , Bozic Dragana , Radivojevic Ljiljana , Gajic Umiljendic Jelena , Vrbnicanin Sava
Published: November 2018

The physiological and anatomical impact of field dodder (Cuscuta campestris Yunck.) on alfalfa and sugar beet was examined under controlled conditions. The following parameters were checked: physiological — content of pigments (chlorophyll a, chlorophyll b, and carotenoids) and mineral nutrients: nitrogen, phosphorus, potassium, and percent of organic and mineral nutrients; and anatomical — thickness of the epidermis and cortex, diameter of the stem and central cylinder of alfalfa plants, diameter of tracheids and phloem cells, area of xylem and phloem, and hydraulic conductance of petiole bundles in petiole vascular bundles of sugar beet plants. Leaf parameters were also measured on both host plants: thickness of upper and underside leaf epidermis, thickness of palisade, spongy and mesophyll tissue, and diameter of vascular bundle cells. Pigments content and anatomical parameters were measured 7, 14, 21, 28, 35, and 42 d after infestation (DAI), while mineral nutrient contents were determined 20 and 40 DAI. Field dodder caused a significant reduction in pigments content in infested alfalfa (15%–68%) and sugar beet plants (1%–54%). The results obtained in this study confirmed that this parasitic flowering plant has a strong effect on most anatomical parameters of the stem and leaf of alfalfa and leaf and petiole of sugar beet. Also, it was revealed that field dodder increased the contents of N, P2O5, K2O, and organic nutrients in infested alfalfa plants, while infested sugar beet plants had higher contents of N and organic nutrients compared with non-infested plants.
Impact of traffic lights on car accidents at intersections
Authors: Marzoug R. , Lakouari N. , Oubram O. , Ez-Zahraouy H. , Khallouk A. , Limón-Mendoza M. , Vera-Dimas J. G.
Published: November 2018

Using the cellular automata Nagel–Schreckenberg (NaSch) model, we numerically study the impact of traffic lights on the probability of car accidents ([Formula: see text]) at the intersection of two roads. It is found that, the probability [Formula: see text] is more stable with variation of the green light ([Formula: see text]) when the symmetric lights are adopted. Moreover, simulation results show the existence of a critical time [Formula: see text], below which ([Formula: see text]) [Formula: see text] increases as the injection rate ([Formula: see text]) increases, however, above which ([Formula: see text]) the growing of [Formula: see text] has for effect the decrease of [Formula: see text]. Furthermore, the decrease of [Formula: see text] is almost always accompanied by a loss of the flux, especially with asymmetrical lights. To overcome this problem, we proposed a strategy that can greatly increase the flux and keep the probability [Formula: see text] as small as possible, especially for the low and high injection rates.
Bioinformatic identification of differentially expressed genes associated with prognosis of locally advanced lymph node-positive prostate cancer
Authors: Kudryavtseva Anna V. , Lukyanova Elena N. , Kharitonov Sergey L. , Nyushko Kirill M. , Krasheninnikov Alexey A. , Pudova Elena A. , Guvatova Zulfiya G. , Alekseev Boris Y. , Kiseleva Marina V. , Kaprin Andrey D. , Dmitriev Alexey A. , Snezhkina Anastasiya V. , Krasnov George S.
Published: November 2018

Prostate cancer (PCa) is one of the primary causes of cancer-related mortality in men worldwide. Patients with locally advanced PCa with metastases in regional lymph nodes are usually marked as a high-risk group. One of the chief concerns for this group is to make an informed decision about the necessity of conducting adjuvant androgen deprivation therapy after radical surgical treatment. During the oncogenic transformation and progression of the disease, the expression of many genes is altered. Some of these genes can serve as markers for diagnosis, predicting the prognosis or effectiveness of drug therapy, as well as possible therapeutic targets. We undertook bioinformatic analysis of the RNA-seq data deposited in The Cancer Genome Atlas consortium database to identify possible prognostic markers. We compared the groups with favorable and unfavorable prognosis for the cohort of patients with PCa showing lymph node metastasis (pT2N1M0, pT3N1M0, and pT4N1M0) and for the most common molecular type carrying the fusion transcript TMPRSS2-ERG. For the entire cohort, we revealed at least six potential markers (IDO1, UGT2B15, IFNG, MUC6, CXCL11, and GBP1). Most of these genes are involved in the positive regulation of immune response. For the TMPRSS2-ERG subtype, we also identified six genes, the expression of which may be associated with prognosis: TOB1, GALNT7, INAFM1, APELA, RAC3, and NNMT. The identified genes, after additional studies and validation in the extended cohort, could serve as a prognostic marker of locally advanced lymph node-positive PCa.
Estrogen but not testosterone preserves myofilament function from doxorubicin-induced cardiotoxicity by reducing oxidative modifications
Authors: Rattanasopa Chutima , Kirk Jonathan A. , Bupha-Intr Tepmanas , Papadaki Maria , de Tombe Pieter P. , Wattanapermpool Jonggonnee
Published: November 2018

Here, we aimed to explore sex differences and the impact of sex hormones on cardiac contractile properties in doxorubicin (DOX)-induced cardiotoxicity. Male and female Sprague-Dawley rats were subjected to sham surgery or gonadectomy and then treated or untreated with DOX (2 mg/kg) every other week for 10 wk. Estrogen preserved maximum active tension (Tmax) with DOX exposure, whereas progesterone and testosterone did not. The effects of sex hormones and DOX correlated with both altered myosin heavy chain isoform expression and myofilament protein oxidation, suggesting both as possible mechanisms. However, acute treatment with oxidative stress (H2O2) or a reducing agent (DTT) indicated that the effects on Tmaxwere mediated by reversible myofilament oxidative modifications and not only changes in myosin heavy chain isoforms. There were also sex differences in the DOX impact on myofilament Ca2+sensitivity. DOX increased Ca2+sensitivity in male rats only in the absence of testosterone and in female rats only in the presence of estrogen. Conversely, DOX decreased Ca2+sensitivity in female rats in the absence of estrogen. In most instances, this mechanism was through altered phosphorylation of troponin I at Ser23/Ser24. However, there was an additional DOX-induced, estrogen-dependent, irreversible (by DTT) mechanism that altered Ca2+sensitivity. Our data demonstrate sex differences in cardiac contractile responses to chronic DOX treatment. We conclude that estrogen protects against chronic DOX treatment in the heart, preserving myofilament function.

NEW & NOTEWORTHY We identified sex differences in cardiotoxic effects of chronic doxorubicin (DOX) exposure on myofilament function. Estrogen, but not testosterone, decreases DOX-induced oxidative modifications on myofilaments to preserve maximum active tension. In rats, DOX exposure increased Ca2+sensitivity in the presence of estrogen but decreased Ca2+sensitivity in the absence of estrogen. In male rats, the DOX-induced shift in Ca2+sensitivity involved troponin I phosphorylation; in female rats, this was through an estrogen-dependent mechanism.
P209L mutation in Bag3 does not cause cardiomyopathy in mice
Authors: Fang Xi , Bogomolovas Julius , Zhou Paul Shichao , Mu Yongxin , Ma Xiaolong , Chen Zee , Zhang Lunfeng , Zhu Mason , Veevers Jennifer , Ouyang Kunfu , Chen Ju
Published: November 2018

Bcl-2-associated athanogene 3 (BAG3) is a cochaperone protein and a central player of the cellular protein quality control system. BAG3 is prominently expressed in the heart and plays an essential role in cardiac protein homeostasis by interacting with chaperone heat shock proteins (HSPs) in large, functionally distinct multichaperone complexes. The BAG3 mutation of proline 209 to leucine (P209L), which resides in a critical region that mediates the direct interaction between BAG3 and small HSPs (sHSPs), is associated with cardiomyopathy in humans. However, the mechanism by which the BAG3 P209L missense mutation leads to cardiomyopathy remains unknown. To determine the molecular basis underlying the cardiomyopathy caused by the BAG3 P209L mutation, we generated a knockin (KI) mouse model in which the endogenous Bag3 gene was replaced with mutant Bag3 containing the P215L mutation, which is equivalent to the human P209L mutation. We performed physiological, histological, and biochemical analyses of Bag3 P209L KI mice to determine the functional, morphological, and molecular consequences of the P209L mutation. We found that Bag3 P209L KI mice exhibited normal cardiac function and morphology up to 16 mo of age. Western blot analysis further revealed that levels of sHSPs, stress-inducible HSPs, ubiquitinated proteins, and autophagy were unaffected in P209L mutant mouse hearts. In conclusion, the P209L mutation in Bag3 does not cause cardiomyopathy in mice up to 16 mo of age under baseline conditions.

NEW & NOTEWORTHY Bcl-2-associated athanogene 3 (BAG3) P209L mutation is associated with human cardiomyopathy. A recent study reported that transgenic mice overexpressing human BAG3 P209L in cardiomyocytes have cardiac dysfunction. In contrast, our P209L mice that express mutant BAG3 at the same level as that of wild-type mice displayed no overt phenotype. Our results suggest that human cardiomyopathy may result from species-specific requirements for the conserved motif that is disrupted by P209L mutation or from genetic background-dependent effects.
Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells
Authors: Cheng Yan , Tang Xin-Ying , Li Yi-Xuan , Zhao Dan-Dan , Cao Qiu-Hua , Wu Hong-Xi , Yang Hong-Bao , Hao Kun , Yang Yong
Published: November 2018

Purpose:

Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer.

Experimental Design:

We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression.

Results:

Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68+ TAM infiltration and stronger NPY and IL6 expression.

Conclusions:

Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression.

See related commentary by Mohammadpour et al., p. 2363
Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial
Authors: Bernard-Tessier Alice , Jeannot Emmanuelle , Guenat David , Debernardi Alice , Michel Marc , Proudhon Charlotte , Vincent-Salomon Anne , Bièche Ivan , Pierga Jean-Yves , Buecher Bruno , Meurisse Aurélia , François Éric , Cohen Romain , Jary Marine , Vendrely Véronique , Samalin Emmanuelle , El Hajbi Farid , Baba-Hamed Nabil , Borg Christophe , Bidard François-Clément , Kim Stefano
Published: November 2018

Purpose:

Human papillomavirus (HPV) is found in 90% of squamous cell carcinomas of the anal canal (SCCA). We investigated the clinical validity of HPV circulating tumor DNA (ctDNA) detection in patients enrolled in the Epitopes-HPV02 trial that demonstrated the efficacy of docetaxel, cisplatin, and 5-FU as first-line chemotherapy in advanced SCCA.

Experimental Design:

According to the protocol, serum samples were collected before chemotherapy and on completion of chemotherapy. HPV16 ctDNA was quantified by droplet digital PCR (ddPCR) and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of chemotherapy completion for postchemotherapy progression-free survival (PFS) analyses.

Results:

Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% confidence interval, 81.1–96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cutoff obtained by AUC (area under the curve) was associated with a longer PFS (HR = 2.1; P = 0.04). Among the 36 patients who completed 5 months of chemotherapy, residual HPV ctDNA was detected after chemotherapy in 38.9% of patients. Residual HPV ctDNA detected at chemotherapy completion was associated with shorter postchemotherapy PFS (median PFS 3.4 months vs. not reached; HR = 5.5; P < 0.001) and a reduction of 1-year overall survival rate (OR = 7.0; P = 0.02).

Conclusions:

This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line chemotherapy and HPV ctDNA negativity after chemotherapy completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.

See related commentary by Morris, p. 2030
Massive Arteriovenous Malformation with Stroke-Like Presentation
Authors: Bürki Mathias , Kappeler Liliane , Bühler Robert , Springe Dirk , Ebnöther Lukas , Delgado Marcos
Published: November 2018

We report of a 75-year-old patient with stroke-like presentation, where cerebral imaging led to the diagnosis of a massive arteriovenous malformation (AVM) of the whole left hemisphere. We suggest considering AVM as a differential diagnosis in patients with symptoms of acute stroke despite age and, in the absence of contraindications, in this setting to obtain MRI or CT angiography of the brain.
Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis
Authors: Dou Huihong , Qin Yuanhan , Chen Guoli , Zhao Yanjun
Published: November 2018

Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (>30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.
Increased Expression of Circular RNA circ_0005230 Indicates Dismal Prognosis in Breast Cancer and Regulates Cell Proliferation and Invasion via miR-618/ CBX8 Signal Pathway
Authors: Xu Yi , Yao Yue , Leng Kaiming , Ji Daolin , Qu Lijun , Liu Yueping , Cui Yunfu
Published: November 2018

Background/Aims: Circular RNAs (circRNAs) are a class of non-coding RNAs. They have been proved to be critically involved in tumorigenesis and progression of malignancies through competing endogenous RNA (ceRNA) mechanism. Nevertheless, the exploration between circRNAs and pathogenesis of breast cancer (BC) is limited. Previously, circ_0005230 was identified upregulated in BC tissues screened by circRNA microarray. In the present study, we aimed to investigate the expression pattern, functional role, and mechanism of circ_0005230 in BC. Methods: qRT-PCR was conducted to elucidate the expression levels of circ_0005230 in BC tissues and cells. Additionally, the clinical severity and prognostic value were investigated. CCK-8, colony-forming, flow cytometric assays were performed. Animal study was conducted to validate the in vitro data. What’s more, Transwell assays were induced to detect the cell metastatic properties of circ_0005230 exerts in BC cells. Luciferase reporter assay was used to measure the mechanism of circ_0005230. Results: circ_0005230 was overexpressed in BC tissue specimens and cell lines. The overexpression of circ_0005230 was related to adverse phenotypes in the patients with BC. In addition, circ_0005230 could be regarded as a prognostic predictor in BC patients. In vitro and in vivo data demonstrated the cell growth promoting role of circ_0005230. Moreover, circ_0005230 could also promote cell migratory and invasive capacities. For the mechanism investigation, circ_0005230 was proved to be a sponge of miR-618, and expression of miR-618 could regulate CBX8 expression via targeting the 3’UTR of CBX8. Rescue assays also illustrated an oncogenic function of circ_0005230 in BC via acting as a miR-618 sponge to promote CBX8 expression. Conclusion: circ_0005230/miR-618/CBX8 axis might play a key role in BC tumorigenesis and development.
TRPC1 Deficiency Exacerbates Cerebral Ischemia/Reperfusion-Induced Neurological Injury by Potentiating Nox4-Derived Reactive Oxygen Species Generation
Authors: Xu Ning , Meng Hao , Liu Tianyi , Feng Yingli , Qi Yuan , Wang Honglei
Published: November 2018

Background/Aims: Transient receptor potential cation channel 1 (TRPC1)-mediated the calcium (Ca2+) influx plays an important role in several brain disorders. However, the function of TRPC1 in ischemia/reperfusion (I/R)-induced neurological injury is unclear. Methods: Wild-type or TRPC1 knockout mice underwent middle cerebral artery occlusion for 90 min followed by 24 h of reperfusion. In an in vitro study, neuronal cells were treated with oxygen–glucose deprivation and reoxygenation (OGD/R) to mimic I/R. The intracellular Ca2+ concentration [Ca2+]i was measured by Fura 2-AM under a microscope. Cerebral infarct volume was measured by triphenyltetrazolium chloride staining. Neurological function was examined by neurological severity score, Morris water maze test, rotarod test and string test. Oxidative parameters were detected by malondialdehyde, glutathione peroxidase, and superoxide dismutase commercially available kits. The protein expression levels of TRPC1, Nox4, p22phox, p47phox, and p67phox were analyzed by western blotting. Results: Brain tissues from cerebral I/R mice showed decreased TRPC1 expression. Similarly, TRPC1 expression was reduced in HT22 cells upon exposure to OGD/R treatment, followed by decreased Ca2+ influx. However, TRPC1 overexpression reversed the OGD/R-induced decrease in [Ca2+]i. TRPC1 knockout significantly exacerbated I/R-induced brain infarction, edema, neurological severity score, memory impairment, neurological deficits, and oxidative stress. In contrast, TRPC1 upregulation inhibited the increase in reactive oxygen species (ROS) generation induced by OGD/R. Analysis of key subunits of the Nox family and mitochondrial ROS revealed that the effects of TRPC1 downregulation on oxidative stress were associated with activation of Nox4-containing NADPH oxidase. TRPC1 interacted with Nox4 and facilitated Nox4 protein degradation under OGD/R conditions. In addition, TRPC1 inhibition potentiated the OGD/R-induced translocation of p47phox and p67phox as well as the interaction between Nox4 and p47phox or p67phox, whereas TRPC1 overexpression had the opposite effects. Conclusion: TRPC1 deficiency potentiates ROS generation via Nox4-containing NADPH oxidase, which exacerbates cerebral I/R injury. TRPC1 may be a promising molecular target for the treatment of stroke.
Hyperglycaemia Stress-Induced Renal Injury is Caused by Extensive Mitochondrial Fragmentation, Attenuated MKP1 Signalling, and Activated JNK-CaMKII-Fis1 Biological Axis
Authors: Zhang Yunfang , Feng Junxia , Wang Qi , Zhao Shili , Yang Shen , Tian Lu , Meng Ping , Li Jingchun , Li Hongyan
Published: November 2018

Background/Aims: Hyperglycaemia stress-induced renal injury is closely associated with mitochondrial dysfunction through poorly understood mechanisms. The aim of our study is to explore the upstream trigger and the downstream effector driving diabetic nephropathy via modulating mitochondrial homeostasis. Methods: A diabetic nephropathy model was generated in wild-type (WT) mice and MAP Kinase phosphatase 1 transgenic (MKP1-TG) mice using STZ injection. Cell experiments were conducted via high-glucose treatment in the human renal mesangial cell line (HRMC). MKP1 overexpression assay was carried out via adenovirus transfection. Renal function was evaluated via ELISA, western blotting, histopathological staining, and immunofluorescence. Mitochondrial function was determined via mitochondrial potential analysis, ROS detection, ATP measurement, mitochondrial permeability transition pore (mPTP) opening evaluation, and immunofluorescence for mitochondrial pro-apoptotic factors. Loss- and gain-of-function assays for mitochondrial fragmentation were performed using a pharmacological agonist and blocker. Western blotting and the pathway blocker were used to establish the signalling pathway in response to MKP1 overexpression in the presence of hyperglycaemia stress. Results: MKP1 was downregulated in the presence of chronic high-glucose stress in vivo and in vitro. However, MKP1 overexpression improved the metabolic parameters, enhanced glucose control, sustained renal function, attenuated kidney oxidative stress, inhibited the renal inflammation response, alleviated HRMC apoptosis, and repressed tubulointerstitial fibrosis. Molecular investigation found that MKP1 overexpression enhanced the resistance of HRMC to the hyperglycaemic injury by abolishing mitochondrial fragmentation. Hyperglycaemia-triggered mitochondrial fragmentation promoted mitochondrial dysfunction, as evidenced by decreased mitochondrial potential, elevated mitochondrial ROS production, increased pro-apoptotic factor leakage, augmented mPTP opening and activated caspase-9 apoptotic pathway. Interestingly, MKP1 overexpression strongly abrogated mitochondrial fragmentation and sustained mitochondrial homeostasis via inhibiting the JNK-CaMKII-Fis1 pathway. After re-activation of the JNK-CaMKII-Fis1 pathway, the beneficial effects of MKP1 overexpression on mitochondrial protection disappeared. Conclusion: Taken together, our data identified the protective role played by MKP1 in regulating diabetic renal injury via repressing mitochondrial fragmentation and inactivating the JNK-CaMKII-Fis1 pathway, which may pave the road to new therapeutic modalities for the treatment of diabetic nephropathy.
Targeting CD44 by CRISPR-Cas9 in Multi-Drug Resistant Osteosarcoma Cells
Authors: Xiao Zheng , Wan Jia , Nur Ayub Abdulle , Dou Pencheng , Mankin Henry , Liu Tang , Ouyang Zhengxiao
Published: November 2018

Background/Aims: Drug resistance is the main difficulty for the current treatment for osteosarcoma. Cluster of differentiation 44 (CD44) is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression, metastasis and drug resistance. In this study, we aimed to determine the effects of CD44 on migration, invasion, proliferation, and the drug-sensitivity of osteosarcoma. Methods: 96 human osteosarcoma tissues from 56 patients were collected to evaluate the expression of CD44 in osteosarcoma tissue by immunohistochemistry. CRISPR-Cas9 system was used to specifically silence CD44 in drug-resistant cell lines (KHOSR2 and U-2OSR2). The migration and invasion activities of cells was demonstrated by wound healing and transwell invasion assay. The proliferation speed of the cells was detected under 3D cell culture condition. Drug resistance of cells was detected by MTT and drug uptake assay. Results: The immunohistochemistry results demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis, recurrence and drug resistance in patients with osteosarcoma. After knocking-out of CD44 by the CRISPR-Cas9 system, not only the migration and invasion activities of osteosarcoma cells were significantly inhibited, but the drug sensitivity was also enhanced. Conclusion: CD44 silencing could inhibit the development of osteosarcoma migration, invasion, proliferation and ameliorate drug resistance to current treatment in osteosarcoma. This study applies new strategy to target CD44, which may improve the prognosis of osteosarcoma.
Taxonomic revision of species of Haematoloechus Looss, 1899 (Digenea: Plagiorchioidea), with molecular phylogenetic analysis and the description of three new species from Mexico
Authors: LEÓN-RÈGAGNON VIRGINIA , TOPAN JANET
Published: November 2018

Lung flukes of the genus Haematoloechus Looss, 1899 are common parasites of anurans worldwide, but the taxonomy of the group has been confusing. In this taxonomic revision, 89 species of Haematoloechus (= Pneumonoeces Looss, 1902, Ostioloides Odening, 1960, Ostiolum Pratt, 1903, Skrjabinoeces Sudarikov, 1950, Neohaematoloechus Odening, 1960, Metahaematoloechus Yamaguti, 1971) are listed. Of these, 70 are considered valid, three are species inquirendae (H. legrandi Mañé–Garzón & Gil, 1959, H. latoricensis Kozák, 1968 & H. vitelloconfluentum (Rai, 1962) Saeed, Al–Barwari & Al-Harmni, 2007), one is a nomen nudum H. sudarikovi Belouss, 1962, 14 are junior synonyms and one belongs to Ostioloides. This publication also describes three new species, H. occidentalis n. sp., H. veracruzanus n. sp. and H. mexicanus n. sp., parasitizing species of Rana Linnaeus in Mexico and redescribes Haematoloechus caballeroi (Skrjabin & Antipin, 1962) Yamaguti, 1971. The phylogenetic hypotheses based on sequences of mitochondrial and ribosomal DNA of Haematoloechus spp. show that genera proposed on the basis of morphological characters are not supported. The host records for species of Haematoloechus, together with the phylogenetic hypothesis of the genus, suggest that this host-parasite association predates the ranid diversification in the Cretaceous.
Recovering the local: From glocalization to localization
Authors: Roudometof Victor
Published: November 2018

Addressing a major theoretical lacuna in the literature concerning ‘the local’ and localization, different interpretations of the local are presented and critiqued and a different account of the local and localization as a focal point for social research is offered. In the article, it is argued that social theory needs to give the local its due and avoid surrendering the local to localism. The local is thematized in terms of the space/place nexus; although it is impossible to bind the local in terms of space, it is possible to do so in terms of place. Hence, the suggestion is to think of the local as a place. Through these lenses, localization is conceived as a process of place-making, which in turn successfully differentiates the local from the related concepts of globalization and glocalization. The increasing pace of globalization emerges as a factor counteracting localization, thereby giving birth to various localisms. Possible avenues for developing alternatives to current versions of exclusivist localism are explored.
Smart controller for grid stabilization in the optoelectric system
Authors: Ramya K , Ramesh Kumar KA
Published: November 2018

The power generated from the optoelectric source in the conversion system and the connected system should satisfy several factors such as high efficiency, less total harmonic distortion, reduced cost, less complexity, better boosting capability, etc. The boosting capability can be achieved by means of single juncture or two juncture architecture in DC–DC boost converter. Among different architecture, the Z-source riven bias inverter controls the parameter on the AC and DC sections. The steady state quantity and the time-varying parameter are regulated by controlling the intonation index. The modulation indexes are framed by digital to look at its supervision theme in grid coupled structure that has certainly not been studied so far. Hence, in this paper, the Z-source riven bias electrical converter modeling has been studied in conjunction with the decoupled space vector modulation as a control technique. The deliberate theme is studied and simulated by using a MATLAB/Simulink model to approve the analysis and simulations.
A hands-on approach to teaching system identification using first-order plus dead time modelling of step response data
Authors: Burn Kevin , Cox Chris
Published: November 2018

This paper describes three step response-based system identification methods of increasing complexity, together with a range of exercises that will enhance student understanding of this area in an engaging and practical way. For illustration purposes and practicality, it is assumed that the model to be identified is of the first-order plus dead time type. The first method uses a popular graphical technique, which is easy to understand and apply, but inaccurate when the response data are not ideal. The second uses the Nelder–Mead simplex method, which is a more powerful technique and has the added benefit of introducing undergraduate students to the concepts of numerical optimisation. The third uses an integral equation algorithm. The latter two methods, which can be readily extended to other model structures and input types, are also demonstrated using experimental data obtained from a tank level control system.
Farewell Letters I: The Dying Process of a Healthy Man
Authors: Wittkowski Joachim
Published: November 2018

This qualitative case study describes the dying process from a purely psychological perspective. The letters of Count Moltke, who was sentenced to death and executed during the Nazi regime, to his wife were analyzed content analytically. A work program of four self-imposed tasks emerged, namely first to avert the death sentence, second to prepare for the ideological and intellectual battle with the chairman of the court, third to support his wife in her anticipatory mourning, and fourth to achieve willingness for his dying by strangulation and for losing his life. Contrasting these findings with two cases of incurably ill men confirmed work and structure as the overarching way of coping. Religious coping is also of central importance. There was neither a linear trajectory nor a sequence of phases; rather, Moltke’s dying process corresponds to a circular model. A consequence of the findings is outlined.
Electrospun poly(vinyl alcohol) nanofibrous membranes containing Coptidis Rhizoma extracts for potential biomedical applications
Authors: Jeong Jin , Lee Seungsin
Published: November 2018

Coptidis Rhizoma is a medicinal plant that is well known for its high antibacterial activity against various pathogens and its anti-inflammatory, antioxidant, and hemostatic effects. Here, nanofibrous membranes containing 10, 20, and 30 wt% of Coptidis Rhizoma extracts were fabricated by electrospinning using poly(vinyl alcohol) as the drug carrier and thermally treated to increase their aqueous stability. The antibacterial properties and release characteristics of Coptidis Rhizoma nanofibrous membranes were investigated. Coptidis Rhizoma-loaded nanocomposite fibers exhibited a high drug-loading efficiency ranging from 92% to 97%. The release profile from the nanofibrous membranes of Coptidis Rhizoma showed an initial fast release followed by a gradual release for 48 h. High antibacterial activity of the Coptidis Rhizoma-loaded nanofibrous membranes was exhibited against both Staphylococcus aureus and Staphylococcus epidermidis. These results demonstrate that poly(vinyl alcohol) nanofibrous membranes containing Coptidis Rhizoma extracts have considerable potential to be effective antimicrobial wound dressings based on natural substances.
The Mysticism of Resistance: The Global Suffering of Women as an Ethical Imperative for the Church
Authors: McManus Kathleen
Published: November 2018

The Catholic Church’s evangelizing and healing presence throughout the world also entails the unintended reinforcement of cultural forces of misogyny that contribute to the suffering of women. This presents an urgent ethical imperative for the church to examine and reform its patriarchal structures of decision-making, ministry, and worship. Ecofeminist epistemologies and Schillebeeckx’s theory of the proportional norm are employed in a movement through the steps of a theological reflection process that the author learned in collaboration with women theologians from Latin America. The symbolic paradigm guiding the movement is the Lukan Gospel’s bent-over woman, standing up straight and glorifying God.
Be(com)ing Critical Scholars: The Emergence of Urban Youth Scholar Identities Through Research and Critical Civic Praxis
Authors: Allen-Handy Ayana , Thomas-EL Shawnna L.
Published: November 2018

This phenomenological case study examined the emergence of critical scholar identities among five urban youth who participated in a 2-year critical research fellows program. The program was grounded on the theoretical framework of Social Justice Youth Development, which included the development of self, social/community, and global awareness leading to critical consciousness and social action. Findings depict the personal and programmatic components of nurturing urban youth’s critical scholar identities and contribute to the growing body of literature in critical youth studies and scholar identity development with marginalized urban youth.
China in Latin America: South-South Cooperation with Chinese Characteristics
Authors: Vadell Javier A.
Published: November 2018

The central questions for a critical analysis of the economic relations between China and Latin America and the Caribbean countries since the beginning of the twenty-first century are how to interpret the changes in them since the end of the commodities boom and whether they have resulted in the emulation in these countries of the Chinese model of development. Analysis suggests that, although the Chinese presence was welcome during the turbulence of the 2001 economic crisis, relations with China are becoming increasingly complex and reflect the political and economic principles of South-South cooperation.

Las preguntas centrales para un análisis crítico de las relaciones económicas entre China y los países de América Latina y el Caribe desde principios del siglo XXI son cómo interpretar los cambios en ellos desde el final del auge de los productos básicos y si han resultado en la emulación en estos países del modelo de desarrollo chino. El análisis sugiere que, aunque la presencia china fue bienvenida durante la turbulencia de la crisis económica de 2001, las relaciones con China son cada vez más complejas y reflejan los principios políticos y económicos de la cooperación Sur-Sur.
The smartphone as a lifeline: an exploration of refugees’ use of mobile communication technologies during their flight
Authors: Alencar Amanda , Kondova Katerina , Ribbens Wannes
Published: November 2018

Building on the results of a qualitative study with 16 male refugees (mostly from Syria) settled in the Netherlands, this article reports on an investigation that applied insights from the Uses and Gratifications (U&G) framework and refugee studies to examine the media use of refugees and to link these to the material, social and psychological needs emerging from the journey. With a focus on the smartphone, our study distinguished four significant clusters of media U&G among the sampling population: smartphone as companion, an organisational hub, a lifeline and diversion. First, the use of smartphones was linked to refugees’ need to contact family, friends and connect with migrant communities. The importance of establishing contact with other refugees and smugglers through smartphones reinforces the agency of these migration networks within mobility processes. The findings also point to refugees’ smartphone usage for getting a sense of security. Finally, this study demonstrated the use of smartphones for preserving memories of the journey through the storage of pictures taken of important moments experienced during the flight. Additional studies should include other methodologies and samples to further validate our theoretical framework and findings.
Othello’s ‘travels’ history’ illuminated anew: Beyond black and white in Iqbal Khan’s RSC revival (2015)
Authors: Fischer Susan L
Published: November 2018

Two consummate black actors took on the lead roles in Iqbal Khan’s 2015 revival of Othello with the Royal Shakespeare Company (RSC): the British-Ghanaian actor Hugh Quarshie played Othello and the British-Tanzanian/Zimbabwean actor Lucian Msamati made theatre history as the RSC’s first black Iago. The play did not come across as either Othello- or Iago-centred but as a choreographed dance between Quarshie and Msamati, which involved trustable coordination with the cast. Their performances in a multicultural and racially diverse world increased the available data to arrest our spectating gaze and so expanded received notions of what the play is ‘about’.