bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal-pair word learning by bilingual toddlers: the Catalan /e/-/ɛ/ contrast revisited
Authors: RAMON-CASAS MARTA , FENNELL CHRISTOPHER T. , BOSCH LAURA
Published: November 2016

Twelve-month-old bilingual and monolingual infants show comparable phonetic discrimination skills for vowels belonging to their native language/s. However, Catalan–Spanish bilingual toddlers, but not Catalan monolinguals, appear insensitive to a vowel mispronunciation in familiar words involving the Catalan–Specific /e/-/ɛ/ contrast. Here bilingual and monolingual toddlers were tested in a challenging minimal-pair word learning task involving that contrast (i.e., [bepi]-[bɛpi]). Both groups succeeded, suggesting that bilinguals can successfully use their phonetic categories to phonologically encode novel words. It is argued that bilinguals’ impoverished vowel representations in familiar words might be the result of experiential input factors (e.g., cognate words and mispronunciations due to accented speech).
Disruptive Affektregulations- störung: eine umstrittene neue Diagnose im DSM-5
Authors: Birkle Sarah Maria , Legenbauer Tanja , Grasmann Dörte , Holtmann Martin
Published: November 2016

Zusammenfassung. Die Disruptive Affektregulationsstörung wurde in die 5. Auflage des DSM erstmals als Störungsbild aufgenommen. Den Anlass, eine eigenständige diagnostische Kategorie im Kapitel „Depressive Störungen“ für einen Verhaltensphänotyp aus chronischer, nichtepisodischer Reizbarkeit und häufigen plötzlichen Wutanfällen zu entwickeln, gab die transatlantische Kontroverse um das klinische Bild und die Prävalenz früh beginnender bipolarer Störungen. Die vorliegende Arbeit stellt erste vorliegende Arbeiten dar, die auf die neuen Kriterien zurückgreifen. Während die Abgrenzbarkeit der Disruptiven Affektregulationsstörung in Symptomatik und Verlauf von bipolaren Störungen gut gelingt, finden sich Hinweise auf starke Überlappungen mit oppositionell-gereizten Symptombildern. Für die anstehende Revision der ICD sollte daher diskutiert werden, keine neue Diagnose, sondern eher eine Zusatzcodierung einzuführen, die kennzeichnet, ob eine oppositionelle Störung auch reizbar-wütendes Verhalten umfasst. Unabhängig von der nosologischen Einordnung besteht die Herausforderung, den Verhaltensphänotyp hinsichtlich Ätiologie, Entwicklungspsychopathologie und Prognose besser zu verstehen und hilfreiche Behandlungsmöglichkeiten zu entwickeln.
Das subjektive Erleben des Übergangs in die weiterführende Schule
Authors: Knoppick Henrike , Becker Michael , Neumann Marko , Maaz Kai , Baumert Jürgen
Published: November 2016

Zusammenfassung. Hinsichtlich der Bewältigung des Übergangs in die weiterführende Schule werden in der Literatur differenzielle Entwicklungsverläufe berichtet. Diesbezüglich wird diskutiert, welche Bedeutung die subjektive Antizipation dieses kritischen Lebensereignisses besitzt. Bezug nehmend auf die kognitiv-transaktionale Theorie von Lazarus und Folkman (1987) untersucht die vorliegende Studie die Zusammenhänge zwischen den Einschätzungen gegenüber dem potentiell stresshaften Ereignis (primary und secondary appraisals) und dem Wohlbefinden nach dem Übergang sowie der retrospektiven Bewertung der Übergangserfahrung. Untersucht wird eine Stichprobe von Berliner Schülerinnen und Schülern beim Übergang von der 6. zur 7. Klasse. Mithilfe latenter Regressionsanalysen kann ein Einfluss der Antizipationen unter Berücksichtigung von Kontrollvariablen bestätigt werden. Insbesondere Antizipationen bezüglich der veränderten Leistungsanforderungen an der weiterführenden Schule erweisen sich als prädiktiv für die Bewältigung des Übergangs. Dabei gehen positive Einschätzungen mit einem positiveren Wohlbefinden und einer positiveren Bewertung des Übergangs einher. Grundlagentheoretische und praktische Implikationen der Resultate werden diskutiert.
The genomic basis of circadian and circalunar timing adaptations in a midge
Authors: Kaiser Tobias S. , Poehn Birgit , Szkiba David , Preussner Marco , Sedlazeck Fritz J. , Zrim Alexander , Neumann Tobias , Nguyen Lam-Tung , Betancourt Andrea J. , Hummel Thomas , Vogel Heiko , Dorner Silke , Heyd Florian , von Haeseler Arndt , Tessmar-Raible Kristin
Published: November 2016

Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes. The region most strongly associated with circadian chronotypes generates strain-specific differences in the abundance of calcium/calmodulin-dependent kinase II.1 (CaMKII.1) splice variants. As equivalent variants were shown to alter CaMKII activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma-CYCLE, we suggest that modulation of alternative splicing is a mechanism for natural adaptation in circadian timing.
3D visualization of additive occlusion and tunable full-spectrum fluorescence in calcite
Authors: Green David C. , Ihli Johannes , Thornton Paul D. , Holden Mark A. , Marzec Bartosz , Kim Yi-Yeoun , Kulak Alex N. , Levenstein Mark A. , Tang Chiu , Lynch Christophe , Webb Stephen E. D. , Tynan Christopher J. , Meldrum Fiona C.
Published: November 2016

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallization processes. There is growing evidence that these additives are often occluded within the crystal lattice. This promises an elegant means of creating nanocomposites and tuning physical properties. Here we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy is then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required.
USP21 prevents the generation of T-helper-1-like Treg cells
Authors: Li Yangyang , Lu Yue , Wang Shuaiwei , Han Zhijun , Zhu Fuxiang , Ni Yingmeng , Liang Rui , Zhang Yan , Leng Qibin , Wei Gang , Shi Guochao , Zhu Ruihong , Li Dan , Wang Haikun , Zheng Song Guo , Xu Hongxi , Tsun Andy , Li Bin
Published: November 2016

FOXP3+Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption ofFoxp3expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted ofUsp21specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stabilityin vivo.
Assessment of Circulating LncRNAs Under Physiologic and Pathologic Conditions in Humans Reveals Potential Limitations as Biomarkers
Authors: Schlosser Kenny , Hanson Jennifer , Villeneuve Patrick J. , Dimitroulakos Jim , McIntyre Lauralyn , Pilote Louise , Stewart Duncan J.
Published: November 2016

Long non-coding RNAs (lncRNA) are a new class of regulatory molecules with diverse cellular functions. Recent reports have suggested that extracellular lncRNAs are detectable in human plasma and may serve as biomarkers. Here, we sought to investigate circulating lncRNAs as potential biomarkers for pulmonary arterial hypertension (PAH). Eighty-four lncRNAs, representing some of the most abundant and functionally relevant candidates identified in cellular studies, were assessed via RT-qPCR in plasma from PAH and healthy subjects. However, despite preamplification, the majority of lncRNAs were surprisingly undetectable or sporadically detectable, and showed no differential changes. Systematic characterization of plasma/RNA quality and technical performance via internal and external controls revealed no evidence of RNA degradation or RT-qPCR inhibition, and most lncRNAs were robustly detectable in pulmonary tissue. In plasma, lncRNA levels were the lowest among several different RNA species examined, and this was generalizable to other chronic and acute vascular conditions including coronary artery disease, acute coronary syndrome, and septic shock. In addition, two of three previously reported circulating lncRNA biomarker candidates were not detectable in any of the plasma samples. This study reveals new insight on the relative levels of lncRNAs in circulation, which has important implications for their potential development as biomarkers.
Different brain responses to electro-acupuncture and moxibustion treatment in patients with Crohn’s disease
Authors: Bao Chunhui , Liu Peng , Liu Huirong , Jin Xiaoming , Calhoun Vince D. , Wu Luyi , Shi Yin , Zhang Jianye , Zeng Xiaoqing , Ma Lili , Qin Wei , Zhang Jingzhi , Liu Xiaoming , Tian Jie , Wu Huangan
Published: November 2016

This study aimed to investigate changes in resting state brain activity in remissive Crohn’s Disease (CD) patients after electro-acupuncture or moxibustion treatment. Fifty-two CD patients and 36 healthy subjects were enrolled, and 36 patients were equally and randomly assigned to receive either electro-acupuncture or moxibustion treatment for twelve weeks. We used resting state functional magnetic resonance imaging to assess Regional Homogeneity (ReHo) levels, and Crohn’s Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ) scores to evaluate disease severity and quality of life. The results show that (i) The ReHo levels in CD patients were significantly increased in cortical but decreased in subcortical areas, and the coupling between them was declined. (ii) Both treatments decreased CDAI, increased IBDQ scores, and normalized the ReHo values of the cortical and subcortical regions. (iii) ReHo changes in multiple cortical regions were significantly correlated with CDAI score decreases. ReHo changes in several subcortical regions in the electro-acupuncture group, and those of several cortical regions in the moxibustion group, were correlated with reduced CDAI. These findings suggest that both treatments improved cortex-subcortical coupling in remissive CD patients, but electro-acupuncture regulated homeostatic afferent processing network, while moxibustion mainly regulated the default mode network of the brain.
Inhibiting MDSC differentiation from bone marrow with phytochemical polyacetylenes drastically impairs tumor metastasis
Authors: Wei Wen-Chi , Lin Sheng-Yen , Lan Chun-Wen , Huang Yu-Chen , Lin Chih-Yu , Hsiao Pei-Wen , Chen Yet-Ran , Yang Wen-Chin , Yang Ning-Sun
Published: November 2016

Myeloid-derived suppressor cells (MDSCs) are implicated in the promotion of tumor metastasis by protecting metastatic cancerous cells from immune surveillance and have thus been suggested as novel targets for cancer therapy. We demonstrate here that oral feeding with polyacetylenic glycosides (BP-E-F1) from the medicinal plant Bidens pilosa effectively suppresses tumor metastasis and inhibits tumor-induced accumulation of granulocytic (g) MDSCs, but does not result in body weight loss in a mouse mammary tumor-resection model. BP-E-F1 is further demonstrated to exert its anti-metastasis activity through inhibiting the differentiation and function of gMDSCs. Pharmacokinetic and mechanistic studies reveal that BP-E-F1 suppresses the differentiation of gMDSCs via the inhibition of a tumor-derived, G-CSF-induced signaling pathway in bone marrow cells of test mice. Taken together, our findings suggest that specific plant polyacetylenic glycosides that target gMDSC differentiation by communicating with bone marrow cells may hence be seriously considered for potential application as botanical drugs against metastatic cancers.
STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit
Authors: Tian Meng , Xu Jian , Lei Gang , Lombroso Paul J. , Jackson Michael F. , MacDonald John F.
Published: November 2016

N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP3Rs and can depress NMDA-evoked currents with modest intracellular Ca2+buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca2+buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca2+dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation.
Action observation: the less-explored part of higher-order vision
Authors: Platonov Artem , Orban Guy A.
Published: November 2016

Little is presently known about action observation, an important perceptual component of high-level vision. To investigate this aspect of perception, we introduce a two-alternative forced-choice task for observed manipulative actions while varying duration or signal strength by noise injection. We show that accuracy and reaction time in this task can be modeled by a diffusion process for different pairs of action exemplars. Furthermore, discrimination of observed actions is largely viewpoint-independent, cannot be reduced to judgments about the basic components of action: shape and local motion, and requires a minimum duration of about 150–200 ms. These results confirm that action observation is a distinct high-level aspect of visual perception based on temporal integration of visual input generated by moving body parts. This temporal integration distinguishes it from object or scene perception, which require only very brief presentations and are viewpoint-dependent. The applicability of a diffusion model suggests that these aspects of high-level vision differ mainly at the level of the sensory neurons feeding the decision processes.
Molecular Mechanism of Action of Antimalarial Benzoisothiazolones: Species-Selective Inhibitors of the Plasmodium spp. MEP Pathway enzyme, IspD
Authors: Price Kathryn E. , Armstrong Christopher M. , Imlay Leah S. , Hodge Dana M. , Pidathala C. , Roberts Natalie J. , Park Jooyoung , Mikati Marwa , Sharma Raman , Lawrenson Alexandre S. , Tolia Niraj H. , Berry Neil G. , O’Neill Paul M. , John Audrey R. Odom
Published: November 2016

The methylerythritol phosphate (MEP) pathway is an essential metabolic pathway found in malaria parasites, but absent in mammals, making it a highly attractive target for the discovery of novel and selective antimalarial therapies. Using high-throughput screening, we have identified 2-phenyl benzo[d]isothiazol-3(2H)-ones as species-selective inhibitors of Plasmodium spp. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD), the third catalytic enzyme of the MEP pathway. 2-Phenyl benzo[d]isothiazol-3(2H)-ones display nanomolar inhibitory activity against P. falciparum and P. vivax IspD and prevent the growth of P. falciparum in culture, with EC50 values below 400 nM. In silico modeling, along with enzymatic, genetic and crystallographic studies, have established a mechanism-of-action involving initial non-covalent recognition of inhibitors at the IspD binding site, followed by disulfide bond formation through attack of an active site cysteine residue on the benzo[d]isothiazol-3(2H)-one core. The species-selective inhibitory activity of these small molecules against Plasmodium spp. IspD and cultured parasites suggests they have potential as lead compounds in the pursuit of novel drugs to treat malaria.
Empirically testing vaterite structural models using neutron diffraction and thermal analysis
Authors: Chakoumakos Bryan C. , Pracheil Brenda M. , Koenigs Ryan P. , Bruch Ronald M. , Feygenson Mikhail
Published: November 2016

Otoliths, calcium carbonate (CaCO3) ear bones, are among the most commonly used age and growth structures of fishes. Most fish otoliths are comprised of the most dense CaCO3 polymorph, aragonite. Sturgeon otoliths, in contrast, have been characterized as the rare and structurally enigmatic polymorph, vaterite—a metastable polymorph of CaCO3. Vaterite is an important material ranging from biomedical to personal care applications although its crystal structure is highly debated. We characterized the structure of Lake Sturgeon otoliths using thermal analysis and neutron powder diffraction, which is used non-destructively. We confirmed that while Lake Sturgeon otoliths are primarily composed of vaterite, they also contain the denser CaCO3 polymorph, calcite. For the vaterite fraction, neutron diffraction data provide enhanced discrimination of the carbonate group compared to x-ray diffraction data, owing to the different relative neutron scattering lengths, and thus offer the opportunity to uniquely test the more than one dozen crystal structural models that have been proposed for vaterite. Of those, space group P6522 model, a = 7.1443(4)Å, c = 25.350(4)Å, V = 1121.5(2)Å3 provides the best fit to the neutron powder diffraction data, and allows for a structure refinement using rigid carbonate groups.
To What Extent Local Forest Soil Pollen Can Assist Restoration in Subtropical China?
Authors: Sun Zhongyu , Wang Jun , Ren Hai , Guo Qinfeng , Shu Junwu , Liu Nan
Published: November 2016

Long-term ecological data play a vital role in ecological conservation and restoration, however, using information from local forest soil pollen data to assist restoration remains a challenge. This study analyzed two data sets, including 1) surface soil pollen (0–5 cm) and current vegetation data from four near-natural communities and four plantations, and 2) fossil pollen from soil profiles (0–80 cm) from a regional climax community and a degraded land. The pollen representativeness and similarity indexes were calculated. The results showed a low similarity between soil pollen and current vegetation (about 20%) thus forest soil pollen data should be used with caution when defining reference ecosystems. Pollen from Gironniera and Rutaceae which were abundant in broadleaved forest, were also detected in the 40–80 cm layer of a soil profile from the degraded land, which indicates its restoration possibility. Our study considered that the early restoration stage of the study area may benefit from using plant taxa of Pinus, Poaceae, Lonicera, Casuarina, Trema and Quercus. As Pinus, Castanopsis, Gironniera, Rutaceae, Helicia, Randia, Poaceae, Dicranopteris and Pteris always existed during succession, for regional forest restoration under global climate change, the roles of such “stable species” should be considered.
Postnatal auditory preferences in piglets differ according to maternal emotional experience with the same sounds during gestation
Authors: Tallet Céline , Rakotomahandry Marine , Guérin Carole , Lemasson Alban , Hausberger Martine
Published: November 2016

Prenatal sensory experience, notably auditory experience, is a source of fetal memories in many species. The contiguity between sensory stimuli and maternal emotional reactions provides opportunity for associative learning in utero but no clear evidence for this associative learning has been presented to date. Understanding this phenomenon would advance our knowledge of fetal sensory learning capacities. In the present study we tested the hypothesis that sounds (human voice) broadcast to pregnant sows while they experienced positive or negative emotional situations influences postnatal reactions of their offspring to these same sounds. The results show that: 1) from the first testing at the age of 2 days, the experimental piglets were less distressed by a social separation than controls if they heard the “familiar” voice, 2) piglets generalized to any human voice although the influence of novel voices was less pronounced, 3) in a challenging situation, piglets were more distressed if they heard the voice that was associated with maternal negative emotional state in utero. These findings open a whole line of new research on the long term effect of in utero associative learning that goes well beyond pigs, providing a framework for reconsidering the importance of sensory and emotional experiences during gestation.
Aspirin upregulates αB-Crystallin to protect the myocardium against heat stress in broiler chickens
Authors: Tang Shu , Yin Bin , Song Erbao , Chen Hongbo , Cheng Yanfen , Zhang Xiaohui , Bao Endong , Hartung Joerg
Published: November 2016

We established in vivo and in vitro models to investigate the role of αB-Crystallin (CryAB) and assess the ability of aspirin (ASA) to protect the myocardium during prolonged heat stress. Thirty-day-old chickens were divided into three groups (n = 90): heat stress (HS, 40±1 °C); ASA(−)HS(+), 1 mg/kg ASA orally 2 h before heat stress; and ASA(+)HS(−), pretreated with aspirin, no heat stress (25 °C). Hearts were excised after 0, 1, 2, 3, 5, 7, 10, 15 and 24 h. Heat stress increased body temperature, though the ASA(−)HS(+) group had significantly higher temperatures than the ASA(+)HS(+) group at all time points. Compared to ASA(+)HS(+), the ASA(−)HS(+) group displayed increased sensitivity to heat stress. Pathological analysis revealed the ASA (+)HS(+) myocardium showed less severe changes (narrowed, chaotic fibers; fewer necrotic cells) than the ASA(−)HS(+) group (bleeding and extensive cell death). In vitro, ASA-pretreatment significantly increased primary chicken myocardial cell survival during heat stress. ELISAs indicated ASA induced CryAB in vivo to protect against heat stress-induced myocardial damage, but ASA did not induce CryAB in primary chicken myocardial cells. The mechanisms by which ASA induces the expression of CryAB in vivo and protects the myocardium during heat stress merit further research.
A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients
Authors: Zhou Xueyan , Zhu Jing , Bao Zejun , Shang Zhenhai , Wang Tao , Song Jinfang , Sun Juan , Li Wei , Adelusi Temitope Isaac , Wang Yan , Lv Dongmei , Lu Qian , Yin Xiaoxing
Published: November 2016

Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).
Strong interactions between learned helplessness and risky decision-making in a rat gambling model
Authors: Nobrega José N. , Hedayatmofidi Parisa S. , Lobo Daniela S.
Published: November 2016

Risky decision-making is characteristic of depression and of addictive disorders, including pathological gambling. However it is not clear whether a propensity to risky choices predisposes to depressive symptoms or whether the converse is the case. Here we tested the hypothesis that rats showing risky decision-making in a rat gambling task (rGT) would be more prone to depressive-like behaviour in the learned helplessness (LH) model. Results showed that baseline rGT choice behaviour did not predict escape deficits in the LH protocol. In contrast, exposure to the LH protocol resulted in a significant increase in risky rGT choices on retest. Unexpectedly, control rats subjected only to escapable stress in the LH protocol showed a subsequent decrease in riskier rGT choices. Further analyses indicated that the LH protocol affected primarily rats with high baseline levels of risky choices and that among these it had opposite effects in rats exposed to LH-inducing stress compared to rats exposed only to the escape trials. Together these findings suggest that while baseline risky decision making may not predict LH behaviour it interacts strongly with LH conditions in modulating subsequent decision-making behaviour. The suggested possibility that stress controllability may be a key factor should be further investigated.
YY1 binding association with sex-biased transcription revealed through X-linked transcript levels and allelic binding analyses
Authors: Chen Chih-yu , Shi Wenqiang , Balaton Bradley P. , Matthews Allison M. , Li Yifeng , Arenillas David J. , Mathelier Anthony , Itoh Masayoshi , Kawaji Hideya , Lassmann Timo , Hayashizaki Yoshihide , Carninci Piero , Forrest Alistair R. R. , Brown Carolyn J. , Wasserman Wyeth W.
Published: November 2016

Sex differences in susceptibility and progression have been reported in numerous diseases. Female cells have two copies of the X chromosome with X-chromosome inactivation imparting mono-allelic gene silencing for dosage compensation. However, a subset of genes, named escapees, escape silencing and are transcribed bi-allelically resulting in sexual dimorphism. Here we conducted in silico analyses of the sexes using human datasets to gain perspectives into such regulation. We identified transcription start sites of escapees (escTSSs) based on higher transcription levels in female cells using FANTOM5 CAGE data. Significant over-representations of YY1 transcription factor binding motif and ChIP-seq peaks around escTSSs highlighted its positive association with escapees. Furthermore, YY1 occupancy is significantly biased towards the inactive X (Xi) at long non-coding RNA loci that are frequent contacts of Xi-specific superloops. Our study suggests a role for YY1 in transcriptional activity on Xi in general through sequence-specific binding, and its involvement at superloop anchors.
Bright blue-shifted fluorescent proteins with Cys in the GAF domain engineered from bacterial phytochromes: fluorescence mechanisms and excited-state dynamics
Authors: Hontani Yusaku , Shcherbakova Daria M. , Baloban Mikhail , Zhu Jingyi , Verkhusha Vladislav V. , Kennis John T. M.
Published: November 2016

Near-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes (BphPs) are of great interest for in vivo imaging. They utilize biliverdin (BV) as a chromophore, which is a heme degradation product, and therefore they are straightforward to use in mammalian tissues. Here, we report on fluorescence properties of NIR FPs with key alterations in their BV binding sites. BphP1-FP, iRFP670 and iRFP682 have Cys residues in both PAS and GAF domains, rather than in the PAS domain alone as in wild-type BphPs. We found that NIR FP variants with Cys in the GAF or with Cys in both PAS and GAF show blue-shifted emission with long fluorescence lifetimes. In contrast, mutants with Cys in the PAS only or no Cys residues at all exhibit red-shifted emission with shorter lifetimes. Combining these results with previous biochemical and BphP1-FP structural data, we conclude that BV adducts bound to Cys in the GAF are the origin of bright blue-shifted fluorescence. We propose that the long fluorescence lifetime follows from (i) a sterically more constrained thioether linkage, leaving less mobility for ring A than in canonical BphPs, and (ii) that π-electron conjugation does not extend on ring A, making excited-state deactivation less sensitive to ring A mobility.
Origin of unusual HREE-Mo-rich carbonatites in the Qinling orogen, China
Authors: Song Wenlei , Xu Cheng , Smith Martin P. , Kynicky Jindrich , Huang Kangjun , Wei Chunwan , Zhou Li , Shu Qihai
Published: November 2016

Carbonatites, usually occurring within intra-continental rift-related settings, have strong light rare earth element (LREE) enrichment; they rarely contain economic heavy REE (HREE). Here, we report the identification of Late Triassic HREE-Mo-rich carbonatites in the northernmost Qinling orogen. The rocks contain abundant primary HREE minerals and molybdenite. Calcite-hosted fluid inclusions, inferred to represent a magmatic-derived aqueous fluid phase, contain significant concentrations of Mo (~17 ppm), reinforcing the inference that these carbonatitic magmas had high Mo concentrations. By contrast, Late Triassic carbonatites in southernmost Qinling have economic LREE concentrations, but are depleted in HREE and Mo. Both of these carbonatite types have low δ26Mg values (−1.89 to −1.07‰), similar to sedimentary carbonates, suggesting a recycled sediment contribution for REE enrichment in their mantle sources. We propose that the carbonatites in the Qinling orogen were formed, at least in part, by the melting of a subducted carbonate-bearing slab, and that 10 Ma younger carbonatite magmas in the northernmost Qinling metasomatized the thickened eclogitic lower crust to produce high levels of HREE and Mo.
Mobile phone signal exposure triggers a hormesis-like effect in Atm+/+ and Atm−/− mouse embryonic fibroblasts
Authors: Sun Chuan , Wei Xiaoxia , Fei Yue , Su Liling , Zhao Xinyuan , Chen Guangdi , Xu Zhengping
Published: November 2016

Radiofrequency electromagnetic fields (RF-EMFs) have been classified by the International Agency for Research on Cancer as possible carcinogens to humans; however, this conclusion is based on limited epidemiological findings and lacks solid support from experimental studies. In particular, there are no consistent data regarding the genotoxicity of RF-EMFs. Ataxia telangiectasia mutated (ATM) is recognised as a chief guardian of genomic stability. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of 1,800 MHz RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm+/+) or deficient (Atm−/−) ATM. In Atm+/+ MEFs, RF-EMF exposure for 1 h at an average special absorption rate of 4.0 W/kg induced significant DNA single-strand breaks (SSBs) and activated the SSB repair mechanism. This effect reduced the DNA damage to less than that of the background level after 36 hours of exposure. In the Atm−/− MEFs, the same RF-EMF exposure for 12 h induced both SSBs and double-strand breaks and activated the two repair processes, which also reduced the DNA damage to less than the control level after prolonged exposure. The observed phenomenon is similar to the hormesis of a toxic substance at a low dose. To the best of our knowledge, this study is the first to report a hormesis-like effect of an RF-EMF.
NapB in excess inhibits growth of Shewanella oneidensis by dissipating electrons of the quinol pool
Authors: Jin Miao , Zhang Qianyun , Sun Yijuan , Gao Haichun
Published: November 2016

Shewanella, a group of ubiquitous bacteria renowned for respiratory versatility, thrive in environments where various electron acceptors (EAs) of different chemical and physiological characteristics coexist. Despite being extensively studied, we still know surprisingly little about strategies by which multiple EAs and their interaction define ecophysiology of these bacteria. Previously, we showed that nitrite inhibits growth of the genus representativeShewanella oneidensison fumarate and presumably some other CymA (quinol dehydrogenase)-dependent EAs by reducing cAMP production, which in turn leads to lowered expression of nitrite and fumarate reductases. In this study, we demonstrated that inhibition of fumarate growth by nitrite is also attributable to overproduction of NapB, the cytochromecsubunit of nitrate reductase. Further investigations revealed that excessive NapBper seinhibits growth on all EAs tested, including oxygen. When overproduced, NapB acts as an electron shuttle to dissipate electrons of the quinol pool, likely to extracellullar EAs, because the Mtr system, the major electron transport pathway for extracellular electron transport, is implicated. The study not only sheds light on mechanisms by which certain EAs, especially toxic ones, impact the bacterial ecophysiology, but also provides new insights into how electron shuttlec-type cytochromes regulate multi-branched respiratory networks.
A self-regenerable soot sensor with a proton-conductive thin electrolyte and a nanostructured platinum sensing electrode
Authors: Lv Peiling , Ito Takenori , Oogushi Akihide , Nakashima Kensaku , Nagao Masahiro , Hibino Takashi
Published: November 2016

In recent years, exhaust sensors have become increasingly attractive for use in energy and environmental technologies. Important issues regarding practical applications of these sensors, especially for soot measurements, include the further development of ion-conductive electrolytes and active electrode catalysts for meeting performance and durability requirements. Herein, we design a proton conductor with a high breakdown voltage and a sensing electrode with high sensitivity to electrochemical carbon oxidation, enabling continuous soot monitoring with self-regeneration of the sensor. A Si0.97Al0.03HxP2O7-δ layer with an excellent balance between proton conductivity and voltage endurance was grown on the surface of a Si0.97Al0.03O2-δ substrate by reacting it with liquid H3PO4 at 600 °C. Specific reactivity of the electrochemically formed active oxygen toward soot was accomplished by adding a Pt-impregnated Sn0.9In0.1HxP2O7-δ catalyst into a Pt sensing electrode. To make the best use of these optimized materials, a unipolar electrochemical device was fabricated by configuring the sensing and counter electrodes on the same surface of the electrolyte layer. The resulting amperometric mode sensor successfully produced a current signal that corresponded to the quantity of soot.
Erratum: REAC technology modifies pathological neuroinflammation and motor behaviour in an Alzheimer’s disease mouse model
Authors: Lorenzini Luca , Giuliani Alessandro , Sivilia Sandra , Baldassarro Vito Antonio , Fernandez Mercedes , Margotti Matteo Lotti , Giardino Luciana , Fontani Vania , Rinaldi Salvatore , Calzà Laura
Published: November 2016

Scientific Reports 6: Article number: 35719; published online: 24 October 2016; updated: 18 November 2016.
Neural correlates underlying impaired memory facilitation and suppression of negative material in depression
Authors: Zhang Dandan , Xie Hui , Liu Yunzhe , Luo Yuejia
Published: November 2016

Previous behavioral studies demonstrated that depressed individuals have difficulties in forgetting unwanted, especially negative, event. However, inconsistent results still exit and the neural mechanism of this phenomenon has not been investigated. This study examined the intentional memory facilitation/suppression of negative and neutral materials in depression using Think/No-Think paradigm. We found that compared with nondepressed group, depressed group recalled more negative items, irrespective of either "Think" or "No-Think" instructions. Accordingly, the frontal N2 (reflecting voluntary memory inhibition) and parietal late positive component (LPC) (reflecting conscious recollection) showed deflection for negative items in depressed compared with nondepressed participants. On the one hand, the reduced N2 for negative "No-Think" items indicated that depressed individuals have low motivation to suppress negative items so intentional forgetting is less successful for mood-congruent events. On the other hand, the enhanced LPC for negative "Think" items suggested that negative memories are excessively revisited by depressed participants (compared with nondepressed ones) due to their mood-congruent and intrusive nature. Thus we demonstrated that depressed individuals show behavioral and ERP deviations from healthy controls for both voluntary suppression and conscious retrieval of negative memory; the two abnormalities of memory control together contribute to the difficulties in forgetting negative material in depression.
Cloning and characterization of TaVIP2 gene from Triticum aestivum and functional analysis in Nicotiana tabacum
Authors: Zhao Pei , Wang Ke , Lin Zhishan , Zhang Wei , Du Lipu , Zhang Yunlong , Ye Xingguo
Published: November 2016

Wheat is recalcitrant to genetic transformation. A potential solution is to manipulate the expression of some host proteins involved in T-DNA integration process. VirE2 interacting protein 2 (VIP2) plays an important role in T-DNA transport and integration. In this study, a TaVIP2 gene was cloned from common wheat. Southern blot and allele-specific polymerase chain reaction (AS-PCR) combined with an online chromosomal location software tool revealed that three TaVIP2 genes were located on wheat chromosomes 1AL, 1BL, and 1DL. These three homoeoallelic TaVIP2 genes all contained 13 exons and 12 introns, and their coding sequences were the same; there were a few single nucleotide polymorphisms (SNPs) among the three genes. The heterologous expression of the TaVIP2 gene in tobacco led to enhancement of the Agrobacterium-mediated transformation efficiency up to 2.5-fold. Transgenic tobacco plants expressing TaVIP2 showed enhanced resistance to powdery mildew. Further quantitative real-time PCR (qRT-PCR) revealed that overexpression of TaVIP2 in transgenic tobacco up-regulated the expression of an endogenous gene, NtPR-1, which likely contributed to powdery mildew resistance in transgenic tobacco. Our study indicates that the TaVIP2 gene may be highly useful in efforts to improve Agrobacterium-mediated transformation efficiency and to enhance powdery mildew resistance in wheat.
mGlu2 Receptor Positive Allosteric Modulators
Authors: Trabanco A. A. , Cid J. M. , Tresadern G.
Published: November 2016

Positive allosteric modulation of the metabotropic glutamate type 2 (mGlu2) receptor has emerged as a promising mechanism for the treatment of central nervous system diseases, with the potential to provide a new and more effective avenue for the treatment of schizophrenia. Since the first discovery of mGlu2 receptor positive allosteric modulators (PAMs) multiple families of mGlu2 modulators have been reported. This chapter summarises the state of the art of the mGlu2 PAM arena by reviewing the different chemotypes reported to date, their proposed binding modes and the development status of those that have advanced into clinical evaluation.
Development of AMPA Receptor Modulators as Cognition Enhancers
Authors: Jamieson Craig , Duffy Emma L.
Published: November 2016

The positive mnemonic effects of positive modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor have been well documented in the preclinical setting. This encouraging level of target validation has galvanised efforts by a number of research organisations towards identifying developable and efficacious AMPA receptor modulators for the treatment of cognitive deficits associated with both schizophrenia and Alzheimer’s Disease. This contribution will give an overview of significant developments in the area, including chemical classes studied and associated pharmacology, as well as discussing the impact of Structure Based Drug Design (SBDD) in efforts to identify new chemotypes for this important molecular target.
Allosteric Modulation of Neuronal Nicotinic Acetylcholine Receptors
Authors: Levandoski Mark M. , Koganti Sivaramakrishna
Published: November 2016

Nicotinic acetylcholine receptors (nAChRs) are a diverse family of integral membrane proteins involved in neurotransmission. These pentameric complexes, of numerous subtypes, are expressed in nervous tissue, striated muscle and some non-neuronal tissues. The nAChRs are quintessential allosteric proteins in that they function to change conformation, from closed to open, upon activation with the endogenous ligand acetylcholine. This opening allows ions to pass across the cell membrane, thus transforming a chemical signal into an electrical one. Neuronal nAChRs mediate many neurophysiological and cognitive processes; as such, they are implicated in important disease states such as schizophrenia, Alzheimer's and Parkinson's diseases, as well as being the molecular point of origin for addiction to nicotine. Although allosteric modulation of nicotinic receptors is recognized as important, our currently limited understanding of molecular mechanisms of this modulation undermines development of clinical applications. In this chapter, we sketch a conceptual framework for allosteric modulation of nAChRs that embraces the inherent symmetry of the system and that treats agonist activation and positive and negative modulation as a functional spectrum.
Allosteric Binding in the Serotonin Transporter – Pharmacology, Structure, Function and Potential Use as a Novel Drug Target
Authors: Loland Claus J. , Sanchez Connie , Plenge Per , Bøgesø Klaus P. , Bang-Andersen Benny
Published: November 2016

The serotonin transporter (SERT) is an important drug target and the majority of currently used antidepressants are potent inhibitors of SERT, binding primarily to the substrate binding site. However, even though the existence of an allosteric modulator site was realized more than 30 years ago, the research into this mechanism is still in its early days. The current knowledge about the allosteric site with respect to pharmacology, structure and function, and pharmacological tool compounds, is reviewed and a perspective is given on its potential as a drug target.
Allosteric Inhibition of Abl Kinase
Authors: Fallacara Anna Lucia , Schenone Silvia , Botta Maurizio
Published: November 2016

Since the mechanism of allosteric regulation was postulated for the first time in 1965 by Monod, Wyman and Changeux, 50 years have passed. From that moment our vision and understanding of the ligand–protein interaction process have been completely changed. Proteins started to be considered to be not fixed biological entities but flexible structures endowed with an activity which could be finely tuned by interaction with other proteins or new small molecules able to bind pockets different from the catalytic sites. In this chapter an in-depth description of one of the most studied allosteric modulation mechanisms will be provided. Abelson murine-leukemia viral-oncogene homolog-1 (c-Abl) protein kinase represents a noteworthy example of how a small post-translational modification (myristoylation of the N-terminal region of the protein sequence) can drive a mechanism of complex domain rearrangements, determining the activation state of the enzyme. Many efforts have been devoted, by scientists all around the world, to studying the molecular basis for the autoinhibition mechanism of c-Abl, and its derived oncogenic fusion protein breakpoint cluster region–Abl (Bcr–Abl), leading to the identification of the first allosteric inhibitor GNF-5, currently undergoing a Phase I clinical trial for the treatment of chronic myelogenous leukemia (CML).
Formation of large nanodomains in liquid solutions near the phase boundary
Authors: Kang Xinchen , Ma Xiaoxue , Zhang Jianling , Xing Xueqing , Mo Guang , Wu Zhonghua , Li Zhihong , Han Buxing
Published: November 2016

Large nanodomains were formed in liquid solutions near the phase separation point where the size of nanodomains increased dramatically.
Selective Tsuji–Trost type C-allylation of hydrazones: a straightforward entry into 4,5-dihydropyrazoles
Authors: El Mamouni El Hachemia , Cattoen Martin , Cordier Marie , Cossy Janine , Arseniyadis Stellios , Ilitki Hocine , El Kaïm Laurent
Published: November 2016

Tsuji–Trost typeC-allylation access to 4,5-dihydropyrazoles.
Radical-promoted site-specific cross dehydrogenative coupling of heterocycles with nitriles
Authors: Liu Zhong-Quan , Li Zejiang
Published: November 2016

A first free-radical triggered site-specific cross dehydrogenative coupling reaction of heterocycles with simple nitriles is developed. It allows efficient and facile access to various C-2 cyanoalkylated furans, thiophenes, indoles, and pyrroles. The extremely high selectivities in this case indicate that functionalization of an inert C–H bond could be well-controlled by radical initiation.
CO2 reduction with Re(i)–NHC compounds: driving selective catalysis with a silicon nanowire photoelectrode
Authors: Jin Tong , He Da , Li Wei , Stanton Charles J. , Pantovich Sebastian A. , Majetich George F. , Schaefer Henry F. , Agarwal Jay , Wang Dunwei , Li Gonghu
Published: November 2016

Excellent selectivity was observed in CO2 reduction using Re(i)–NHC catalysts on a silicon nanowire photoelectrode.
Multiplex miRNA assay using lanthanide-tagged probes and the duplex-specific nuclease amplification strategy
Authors: Zhang Shixi , Liu Rui , Xing Zhi , Zhang Sichun , Zhang Xinrong
Published: November 2016

A multiplex ICP-MS-based miRNA assay was achieved with duplex-specific nuclease amplification using bifunctional oligonucleotide probes with lanthanide tags.
The magnetization orientation of Fe ultrathin layers in contact with graphene
Authors: Cattelan Mattia , Píš Igor , Nappini Silvia , Magnano Elena , Bondino Federica , Agnoli Stefano
Published: November 2016

In this paper, we study the magnetic and chemical properties of Fe/graphene vertically stacked ultrathin films by means of X-ray magnetic circular dichroism and X-ray photoelectron spectroscopy.
Self-assembled monolayer structures of hexadecylamine on Cu surfaces: density-functional theory
Authors: Liu Shih-Hsien , Balankura Tonnam , Fichthorn Kristen A.
Published: November 2016

We used dispersion-corrected density-functional theory to probe possible structures for adsorbed layers of hexadecylamine (HDA) on Cu(111) (left) and Cu(100) (right).
Impact of position and number of boron atom substitution on hydrogen uptake capacity of Li-decorated pentalene
Authors: Tavhare Priyanka , Deshmukh Amol , Chaudhari Ajay
Published: November 2016

We have performed an ab initio and density functional theory study of the hydrogen adsorption on a lithium (Li)-decorated pentalene (C8H6Li2) complex.
Synthesis and reductive elimination of arylPd(ii) trifluoromethyl complexes: a remarkable concentration effect on chemoselectivity
Authors: Zhang Song-Lin , Deng Zhu-Qin
Published: November 2016

A remarkable and unprecedented concentration effect on chemoselectivity is observed for the thermal decomposition of Pd(ii) aryl trifluoromethyl complexes. As the concentration increases, the Ar–CF3 cross-coupling is suppressed gradually whilst the Ar–Ar homocoupling increases steadily.