bluuebunny/crossref_metadata_2025 huggingface dataset:
The next common and widespread bunting to go? Global population decline in the Rustic BuntingEmberiza rustica
Authors: EDENIUS LARS , CHOI CHANG-YONG , HEIM WIELAND , JAAKKONEN TUOMO , DE JONG ADRIAAN , OZAKI KIYOAKI , ROBERGE JEAN-MICHEL
Published: April 2016

Populations of several long-distance migratory songbirds in Eurasia are in peril, drastically illustrated by the recent range-wide population collapse in the Yellow-breasted BuntingEmberiza aureola. There are signals of a strong decline also in the Rustic BuntingE. rustica, but no range-wide assessment of population trends in this superabundant and widespread bunting species has yet been undertaken. The conservation status of Rustic Bunting is ‘Least Concern’ on the global IUCN Red List, but it has recently been upgraded to ‘Vulnerable’ on the European Red List. To assess the Rustic Bunting’s global conservation status we compiled, for the first time, population data across its breeding and wintering ranges. The analysis reveals a 75–87% decline in overall population size over the last 30 years and a 32–91% decline over the last 10 years. The trend estimates indicate that the long-term (30-year) range-wide population decline in the Rustic Bunting is of similar magnitude to two well-known examples of declining species within the same genus, the Yellow-breasted Bunting and the Ortolan BuntingE. hortulana. The magnitude of the range-wide population decline over the last 10 years suggests that the Rustic Bunting could be upgraded from ‘Least Concern’ to ‘Vulnerable’ or ‘Endangered’ on the IUCN global Red List. Agricultural intensification in the wintering range and intensified levels of disturbance, including logging and fire, in the breeding range could be important drivers of the range-wide population decline, and persecution could also contribute. Untangling threat factors and their interactions on Rustic Bunting is necessary for conservation, but hampered by our currently limited understanding of the relationships between population dynamics and different threats.
Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure
Authors: Axelgaard Sofie , Holmboe Sarah , Ringgaard Steffen , Hillgaard Thomas K. , Andersen Stine , Hansen Mona S. , Andersen Asger , Nielsen-Kudsk Jens E.
Published: April 2016

Background

Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure.

Methods

Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10). The banded rats were randomised to 6 weeks of treatment with a moderate dose of treprostinil (300 ng/kg/minute), a high dose of treprostinil (900 ng/kg/minute), or vehicle.

Results

Pulmonary trunk banding effectively induced hypertrophy, dilatation, and decreased right ventricular function. The severely banded animals presented with decompensated heart failure with extracardial manifestations. Treatment with treprostinil neither reduced right ventricular hypertrophy nor improved right ventricular function.

Conclusions

In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.
The comparative relationships between locations of the papillary muscles and electrophysiologic QRS axis in patients with atrioventricular septal defect and common as opposed to separate orifices in the valve guarding the common atrioventricular junction
Authors: Low Liying , Idriss Salim F. , Anderson Robert H. , Maynard Charles , Wagner Galen , Hakacova Nina
Published: April 2016

Background

Knowledge regarding factors that influence deviation of the QRS axis is important when seeking to differentiate between physiological and pathological changes. We hypothesised that, in contrast to those patients with an atrioventricular septal defect and common atrioventricular junction permitting only atrial shunting, those associated with ventricular shunting would show no relationship between the positions of the papillary muscles and the degree of the leftward deviation of the QRS axis.

Methods

We compared the positions of endocardial origin of the papillary muscles, and the frontal plane QRS axis, in patients with atrioventricular septal defects and common atrioventricular junction permitting exclusively atrial as opposed to atrial and ventricular shunting.

Results

We analysed 18 patients with atrial and ventricular shunting and 23 patients with exclusively atrial shunting. The correlation coefficient between the ratio of distances of the papillary muscles from the mid-septum and the amount of leftward deviation in the frontal plane QRS axis was 0.1 (p=0.4) in those with ventricular shunting and 0.26 (p=0.01) in those with exclusively atrial shunting.

Conclusions

In contrast to patients with the so-called primum form of atrioventricular septal defect, in whom the locations of the papillary muscles correlate with the degree of QRS axis, such relationships are lacking in patients with defects permitting both atrial and ventricular shunting. It may be, therefore, that the presence of ventricular shunting and/or their younger age causes pressure overload, which negates the leftward QRS forces caused by the abnormally positioned papillary muscles.
Paediatric cardiac surgery in a peripheral European region: is a joint programme a safe alternative to regionalisation?
Authors: Iacona Gabriele M. , Giamberti Alessandro , Abella Raul F. , Pomè Giuseppe , Agredo Julio , Mendieta Saúl G. , Forcano Antonio , Sobrado Concepción , Suaréz Josepha , Peñate Sonia , Melián Asunción , Volo Montserrat , González Rafael , Antúnez Marisa L. , Falcón Hipólito L. , Cabrera Francisco J. , Rubio Carlos , Fernández Javier , Suárez Pedro , Perera Cesar , Frigiola Alessandro
Published: April 2016

Background

In 2007, a partnership was initiated between a small-volume paediatric cardiac surgery unit located in Las Palmas de Gran Canaria, Spain, and a large-volume cardiac surgery unit located in Milan, Italy. The main goal of this partnership was to provide surgical treatment to children with CHD in the Canary Islands.

Methods

An operative algorithm for performing surgery in elective, urgent, and emergency cases was adopted by the this joint programme. Demographic and in-hospital variables were collected from the medical records of all the patients who had undergone surgical intervention for CHD from January, 2009 to March, 2013. Data were introduced into the congenital database of the European Congenital Heart Surgeons Association Congenital Database and the database was interrogated.

Results

In total, 65 surgical mission trips were performed during the period of this study. The European Congenital Heart Surgeons Association Congenital Database documented 214 total patients with a mean age at operation of 36.45 months, 316 procedures in total with 198 cardiopulmonary bypass cases, 46 non-cardiopulmonary bypass cases, 26 cardiovascular cases without cardiopulmonary bypass, 22 miscellaneous other types of cases, 16 interventional cardiology cases, six thoracic cases, one non-cardiac, non-thoracic procedure on a cardiac patient with cardiac anaesthesia, and one extracorporeal membrane oxygenation case. The 30-day mortality was 6.07% (13 patients).

Conclusions

A joint programme between a small-volume centre and a large-volume centre may represent a valid and reproducible model for safe paediatric cardiac surgery in the context of a peripheral region.
Worlding the Social Sciences and Humanities
Authors: D’haen Theo
Published: April 2016

Under the impact of globalization, the study and teaching of the social sciences and humanities is rapidly changing. In many ways, what we see is a growing transfer of research, knowledge, and method from the West to other parts of the world, and in the first instance China. This development is steered by far-reaching changes in the organization of higher education in both the West and in this case China, changes that in themselves have to do with changing economic conditions, and the political decisions following from them, as the result of globalization. In the final part of this article I focus upon how this works out in one particular field or discipline in the humanities: world literature.1
An East Asian Paradigm of Interculturalism
Authors: He Chengzhou
Published: April 2016

Based on a close study of the Sino-Japanese collaboration in Kunqu OperaThe Peony Pavilion(2008), this article proposes a different conception of interculturalism onstage in East Asia in comparison with the prevailing East–West paradigm of intercultural performance and theatre. Some of the interesting questions that are raised and discussed in this paper are: How does the Japanese actor Bando Tamasaburo impersonate a young lady Du Liniang in the Chinese classical play without speaking the Chinese language? In what ways does the Sino-Japanese co-production connect and interweave Kunqu Opera and Kabuki? How has the intercultural performance been mediatized, received as well as perceived in China, Japan and elsewhere? The Sino-Japanese co-production features such important notions of interculturalism as connecting instead of othering, sharing instead of influencing, and complementing instead of exploiting.
Reassessing the semantic history of OEbrēad/ MEbrēd
Authors: PONS-SANZ SARA M.
Published: April 2016

Our etymological understanding of PDEbreadhas been influenced, to a considerable extent, by Otto Jespersen's comment that ‘An Englishman cannotthriveor beillordiewithout Scandinavian words; they are to the language whatbreadandeggsare to the daily fare.’ This article analyses the evidence behind the possibility that PDEbreadmight represent a Norse-derived semantic loan, i.e. that OEbrēadacquired the meaning ‘bread’, which was more frequently expressed by OEhlāf, because of the influence of its Viking Age Norse cognate (cp. OIcbrauð‘bread’). On the basis of an in-depth study of the attestations of OEbrēadandhlāfand their early Middle English reflexes, as well as the use of their cognates in various Germanic languages, the article challenges the traditional view that OEbrēadoriginally meant ‘piece, morsel of bread’ and concludes that Norse influence is not needed in order to account for the semantic history of PDEbread.
The role of mother’s education in the nutritional status of children in Serbia
Authors: Stamenkovic Zeljka , Djikanovic Bosiljka , Laaser Ulrich , Bjegovic-Mikanovic Vesna
Published: April 2016

Objective

The present study aimed to identify the role of mother’s education in the nutritional status of children aged 2–5 years in Serbia.

Design

Nationally representative population-based study. Age- and gender-specific BMI percentiles of children were analysed. In accordance with the WHO growth reference, children with BMI less than the 5th percentile were considered undernourished. Logistic regression was used to calculate the association between mother’s education and other socio-economic determinants as possible confounders.

Setting

UNICEF’s fourth Multiple Indicator Cluster Survey, conducted in both Roma and non-Roma settlements in Serbia.

Subjects

Children (n 2603) aged 2–5 years (mean age 3·05 years).

Results

Less than 5 % of children aged 2–5 years were undernourished. There were significantly more undernourished children among the Roma population, in the capital of Serbia and among those whose mothers were less educated. There were statistically significant differences according to mother’s education in all socio-economic characteristics (ethnicity, area, region of living and wealth index). Mother’s level of education proved to be the most important factor for child’s nutritional status; place of living (region) was also associated.

Conclusions

Mother’s education is the most significant predictor of children’s undernutrition. It confirms that investment in females’ education will bring benefits and progress not only for women and their children, but also for society as a whole.
Vitamin D deficiency and depression among women from an urban community in a tropical country
Authors: Moy Foong Ming , Hoe Victor CW , Hairi Noran Naqiah , Vethakkan Shireene Ratna , Bulgiba Awang
Published: April 2016

Objective

To determine the association of vitamin D status with depression and health-related quality of life among women.

Design

This was a cross-sectional study conducted among women in Kuala Lumpur, Malaysia. Sociodemographic characteristics, physical activity status, perceived depression and health-related quality of life were assessed via a self-administered questionnaire. Fasting blood samples were taken for the analysis of 25-hydroxyvitamin D, parathyroid hormone, fasting blood glucose and full lipid profile. Complex samples multiple logistic regression analysis was performed.

Setting

Public secondary schools in Kuala Lumpur, Malaysia.

Subjects

Seven hundred and seventy female teachers were included.

Results

The mean age of participants was 41·15 (95 % CI 40·51, 41·78) years and the majority were ethnic Malays. Over 70 % of them had vitamin D deficiency (<20 ng/ml or <50 nmol/l) and two-thirds were at risk for depression. In the multivariate analysis, ethnic Malays (adjusted OR (aOR)=14·72; 95 % CI 2·12, 102·21) and Indians (aOR=14·02; 95 % CI 2·27, 86·59), those at risk for depression (aOR=1·88, 95 % CI 1·27, 2·79) and those with higher parathyroid hormone level (aOR=1·13; 95 % CI 1·01, 1·26) were associated with vitamin D deficiency, while vitamin D deficiency was negatively associated with mental health-related quality of life (Mental Component Summary) scores (aOR=0·98; 95 % CI 0·97, 0·99).

Conclusions

Vitamin D deficiency is significantly associated with depression and mental health-related quality of life among women in Kuala Lumpur, Malaysia.
Changes in caesarean section rates and milk feeding patterns of infants between 1986 and 2013 in the Dominican Republic
Authors: McLennan John D
Published: April 2016

Objective

The relationship between caesarean sections (C-sections) and infant feeding varies between different samples and indicators of feeding. The current study aimed to determine the relationship between C-sections and five indicators of infant milk feeding (breast-feeding within 1 h after delivery, at the time of the survey (current) and ever; milk-based prelacteal feeds; and current non-breast milk use) over time in a country with a rapidly rising C-section rate.

Design

Secondary data analysis on cross-sectional data from Demographic and Health Surveys from six different time points between 1986 and 2013.

Setting

Dominican Republic.

Subjects

Infants under 6 months of age.

Results

Over 90 % of infants were ever breast-fed in each survey sample. However, non-breast milk use has expanded over time with a concomitant drop in predominant breast-feeding. C-section prevalence has increased over time reaching 63 % of sampled infants in the most recent survey. C-sections remained significantly related to three infant feeding practices – the child not put to the breast within 1 h after delivery, milk-based prelacteal feeds and current non-breast milk use – in multivariate models that included sociodemographic control variables. However, current non-breast milk use was no longer related to C-sections when milk-based prelacteal feeds were factored into the model.

Conclusions

Reducing or avoiding milk-based prelacteal feeds, particularly among those having C-sections, may improve subsequent breast-feeding patterns. Simultaneously, efforts are needed to understand and help reduce the exceptionally high C-section rate in the Dominican Republic.
Human pregnane X receptor compromises the function of p53 and promotes malignant transformation
Authors: Robbins D , Cherian M , Wu J , Chen T
Published: April 2016

The pregnane X receptor (PXR) is well established as a nuclear receptor that has a central role in xenobiotic metabolism and disposition. However, emerging evidence suggests that PXR is also a regulator of apoptosis, promoting a malignant phenotype both in vitro and in vivo. The tumor suppressor p53 can be activated in the presence of DNA damage and induce cell cycle arrest to allow for DNA repair or, ultimately, apoptosis to suppress tumor formation. We previously identified p53 as a novel PXR-associated protein by using a mass spectrometric approach. In the current study, we identified a novel inhibitory effect of PXR on p53, revealing an anti-apoptotic function of PXR in colon carcinogenesis. PXR expression reduced p53 transactivation and the expression of its downstream target genes involved in cell cycle arrest and apoptosis by decreasing p53 recruitment to the promoter regions of these genes. Consistent with the inhibitory effect of PXR on p53, elevated PXR levels decreased doxorubicin- or nutlin-3a-mediated toxicity and promoted malignant transformation in colon cancer cells. Our findings show for the first time that PXR expression modulates p53 target gene promoter binding and contributes to the downregulation of p53 function in human colon cancer cells. These results define the functional significance of PXR expression in modulating p53-mediated mechanisms of tumor suppression.
A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals
Authors: Chen Jieming , Rozowsky Joel , Galeev Timur R. , Harmanci Arif , Kitchen Robert , Bedford Jason , Abyzov Alexej , Kong Yong , Regan Lynne , Gerstein Mark
Published: April 2016

Large-scale sequencing in the 1000 Genomes Project has revealed multitudes of single nucleotide variants (SNVs). Here, we provide insights into the functional effect of these variants using allele-specific behaviour. This can be assessed for an individual by mapping ChIP-seq and RNA-seq reads to a personal genome, and then measuring ‘allelic imbalances’ between the numbers of reads mapped to the paternal and maternal chromosomes. We annotate variants associated with allele-specific binding and expression in 382 individuals by uniformly processing 1,263 functional genomics data sets, developing approaches to reduce the heterogeneity between data sets due to overdispersion and mapping bias. Since many allelic variants are rare, aggregation across multiple individuals is necessary to identify broadly applicable ‘allelic elements’. We also found SNVs for which we can anticipate allelic imbalance from the disruption of a binding motif. Our results serve as an allele-specific annotation for the 1000 Genomes variant catalogue and are distributed as an online resource (alleledb.gersteinlab.org).
Explanation of efficient quenching of molecular ion vibrational motion by ultracold atoms
Authors: Stoecklin Thierry , Halvick Philippe , Gannouni Mohamed Achref , Hochlaf Majdi , Kotochigova Svetlana , Hudson Eric R.
Published: April 2016

Buffer gas cooling of molecules to cold and ultracold temperatures is a promising technique for realizing a host of scientific and technological opportunities. Unfortunately, experiments using cryogenic buffer gases have found that although the molecular motion and rotation are quickly cooled, the molecular vibration relaxes at impractically long timescales. Here, we theoretically explain the recently observed exception to this rule: efficient vibrational cooling of BaCl+ by a laser-cooled Ca buffer gas. We perform intense close-coupling calculations that agree with the experimental result, and use both quantum defect theory and a statistical capture model to provide an intuitive understanding of the system. This result establishes that, in contrast to the commonly held opinion, there exists a large class of systems that exhibit efficient vibrational cooling and therefore supports a new route to realize the long-sought opportunities offered by molecular structure.
Repulsive cues combined with physical barriers and cell–cell adhesion determine progenitor cell positioning during organogenesis
Authors: Paksa Azadeh , Bandemer Jan , Hoeckendorf Burkhard , Razin Nitzan , Tarbashevich Katsiaryna , Minina Sofia , Meyen Dana , Biundo Antonio , Leidel Sebastian A. , Peyrieras Nadine , Gov Nir S. , Keller Philipp J. , Raz Erez
Published: April 2016

The precise positioning of organ progenitor cells constitutes an essential, yet poorly understood step during organogenesis. Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops. Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions. This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell–cell interaction time. Using particle-based simulations, we demonstrate the role of reflecting barriers, from which cells turn away on contact, and the importance of proper cell–cell adhesion level for maintaining the tight cell clusters and their correct positioning at the target region. The combination of these developmental and cellular mechanisms prevents organ fusion, controls organ positioning and is thus critical for its proper function.
Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis
Authors: Yin Shu-Yi , Jian Feng-Yin , Chen Yung-Hsiang , Chien Shih-Chang , Hsieh Mao-Chih , Hsiao Pei-Wen , Lee Wen-Hwa , Kuo Yueh-Hsiung , Yang Ning-Sun
Published: April 2016

Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.
The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy
Authors: Lukey Michael J. , Greene Kai Su , Erickson Jon W. , Wilson Kristin F. , Cerione Richard A.
Published: April 2016

Many transformed cells exhibit altered glucose metabolism and increased utilization of glutamine for anabolic and bioenergetic processes. These metabolic adaptations, which accompany tumorigenesis, are driven by oncogenic signals. Here we report that the transcription factor c-Jun, product of the proto-oncogene JUN, is a key regulator of mitochondrial glutaminase (GLS) levels. Activation of c-Jun downstream of oncogenic Rho GTPase signalling leads to elevated GLS gene expression and glutaminase activity. In human breast cancer cells, GLS protein levels and sensitivity to GLS inhibition correlate strongly with c-Jun levels. We show that c-Jun directly binds to the GLS promoter region, and is sufficient to increase gene expression. Furthermore, ectopic overexpression of c-Jun renders breast cancer cells dependent on GLS activity. These findings reveal a role for c-Jun as a driver of cancer cell metabolic reprogramming, and suggest that cancers overexpressing JUN may be especially sensitive to GLS-targeted therapies.
Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity
Authors: Alguel Yilmaz , Amillis Sotiris , Leung James , Lambrinidis George , Capaldi Stefano , Scull Nicola J. , Craven Gregory , Iwata So , Armstrong Alan , Mikros Emmanuel , Diallinas George , Cameron Alexander D. , Byrne Bernadette
Published: April 2016

The uric acid/xanthine H+ symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1–11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin.
Structural basis for Mep2 ammonium transceptor activation by phosphorylation
Authors: van den Berg Bert , Chembath Anupama , Jefferies Damien , Basle Arnaud , Khalid Syma , Rutherford Julian C.
Published: April 2016

Mep2 proteins are fungal transceptors that play an important role as ammonium sensors in fungal development. Mep2 activity is tightly regulated by phosphorylation, but how this is achieved at the molecular level is not clear. Here we report X-ray crystal structures of the Mep2 orthologues from Saccharomyces cerevisiae and Candida albicans and show that under nitrogen-sufficient conditions the transporters are not phosphorylated and present in closed, inactive conformations. Relative to the open bacterial ammonium transporters, non-phosphorylated Mep2 exhibits shifts in cytoplasmic loops and the C-terminal region (CTR) to occlude the cytoplasmic exit of the channel and to interact with His2 of the twin-His motif. The phosphorylation site in the CTR is solvent accessible and located in a negatively charged pocket ∼30 Å away from the channel exit. The crystal structure of phosphorylation-mimicking Mep2 variants from C. albicans show large conformational changes in a conserved and functionally important region of the CTR. The results allow us to propose a model for regulation of eukaryotic ammonium transport by phosphorylation.
The complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1
Authors: Sethi Ashish , Bruell Shoni , Patil Nitin , Hossain Mohammed Akhter , Scott Daniel J. , Petrie Emma J. , Bathgate Ross A. D. , Gooley Paul R.
Published: April 2016

H2 relaxin activates the relaxin family peptide receptor-1 (RXFP1), a class A G-protein coupled receptor, by a poorly understood mechanism. The ectodomain of RXFP1 comprises an N-terminal LDLa module, essential for activation, tethered to a leucine-rich repeat (LRR) domain by a 32-residue linker. H2 relaxin is hypothesized to bind with high affinity to the LRR domain enabling the LDLa module to bind and activate the transmembrane domain of RXFP1. Here we define a relaxin-binding site on the LDLa-LRR linker, essential for the high affinity of H2 relaxin for the ectodomain of RXFP1, and show that residues within the LDLa-LRR linker are critical for receptor activation. We propose H2 relaxin binds and stabilizes a helical conformation of the LDLa-LRR linker that positions residues of both the linker and the LDLa module to bind the transmembrane domain and activate RXFP1.
Temporal decorrelation by SK channels enables efficient neural coding and perception of natural stimuli
Authors: Huang Chengjie G. , Zhang Zhubo D. , Chacron Maurice J.
Published: April 2016

It is commonly assumed that neural systems efficiently process natural sensory input. However, the mechanisms by which such efficient processing is achieved, and the consequences for perception and behaviour remain poorly understood. Here we show that small conductance calcium-activated potassium (SK) channels enable efficient neural processing and perception of natural stimuli. Specifically, these channels allow for the high-pass filtering of sensory input, thereby removing temporal correlations or, equivalently, whitening frequency response power. Varying the degree of adaptation through pharmacological manipulation of SK channels reduced efficiency of coding of natural stimuli, which in turn gave rise to predictable changes in behavioural responses that were no longer matched to natural stimulus statistics. Our results thus demonstrate a novel mechanism by which the nervous system can implement efficient processing and perception of natural sensory input that is likely to be shared across systems and species.
MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways
Authors: Moore C. E. J. , Pickford J. , Cagampang F. R. , Stead R. L. , Tian S. , Zhao X. , Tang X. , Byrne C. D. , Proud C. G.
Published: April 2016

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.
Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling
Authors: Lai Cheng-Wei , Chen Hsiao-Ling , Tsai Tung-Chou , Chu Te-Wei , Yang Shang-Hsun , Chong Kowit-Yu , Chen Chuan-Mu
Published: April 2016

Sexually dimorphic gene expression is commonly found in the liver and many of these genes are linked to different incidences of liver diseases between sexes. However, the mechanism of sexually dimorphic expression is still not fully understood. In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver and the expression was activated by testosterone during puberty. The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation. Through this de novo sexually dimorphic expression of the transgene, the Akr1A1eGFP mouse provides a useful model to study the mechanisms and the dynamic changes of sexually dimorphic gene expression during either development or pathogenesis of the liver.
Improved emotional conflict control triggered by the processing priority of negative emotion
Authors: Yang Qian , Wang Xiangpeng , Yin Shouhang , Zhao Xiaoyue , Tan Jinfeng , Chen Antao
Published: April 2016

The prefrontal cortex is responsible for emotional conflict resolution and this control mechanism is affected by the emotional valence of distracting stimuli. In the present study, we investigated effects of negative and positive stimuli on emotional conflict control using a face-word Stroop task in combination with functional brain imaging. Emotional conflict was absent in the negative face context, in accordance with the null activation observed in areas regarding emotional face processing (fusiform face area, middle temporal/occipital gyrus). Importantly, these visual areas negatively coupled with the dorsolateral prefrontal cortex (DLPFC). However, the significant emotional conflict was observed in the positive face context, this effect was accompanied by activation in areas associated with emotional face processing and the default mode network (DMN), here, DLPFC mainly negatively coupled with DMN, rather than visual areas. These results suggested that the conflict control mechanism exerted differently between negative faces and positive faces, it implemented more efficiently in the negative face condition, whereas it is more devoted to inhibiting internal interference in the positive face condition. This study thus provides a plausible mechanism of emotional conflict resolution that the rapid pathway for negative emotion processing efficiently triggers control mechanisms to preventively resolve emotional conflict.
Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin
Authors: Richter Corinna , Mukherjee Oindrilla , Ermert David , Singh Birendra , Su Yu-Ching , Agarwal Vaibhav , Blom Anna M. , Riesbeck Kristian
Published: April 2016

Helicobacter pylori is an important human pathogen and a common cause of peptic ulcers and gastric cancer. Despite H. pylori provoking strong innate and adaptive immune responses, the bacterium is able to successfully establish long-term infections. Vitronectin (Vn), a component of both the extracellular matrix and plasma, is involved in many physiological processes, including regulation of the complement system. The aim of this study was to define a receptor in H. pylori that binds Vn and determine the significance of the interaction for virulence. Surprisingly, by using proteomics, we found that the hydrogen peroxide-neutralizing enzyme catalase KatA is a major Vn-binding protein. Deletion of the katA gene in three different strains resulted in impaired binding of Vn. Recombinant KatA was generated and shown to bind with high affinity to a region between heparin-binding domain 2 and 3 of Vn that differs from previously characterised bacterial binding sites on the molecule. In terms of function, KatA protected H. pylori from complement-mediated killing in a Vn-dependent manner. Taken together, the virulence factor KatA is a Vn-binding protein that moonlights on the surface of H. pylori to promote bacterial evasion of host innate immunity.
In situ synchrotron study of electromigration induced grain rotations in Sn solder joints
Authors: Shen Hao , Zhu Wenxin , Li Yao , Tamura Nobumichi , Chen Kai
Published: April 2016

Here we report an in situ study of the early stage of microstructure evolution induced by electromigration in a Pb-free β-Sn based solder joint by synchrotron polychromatic X-ray microdiffraction. With this technique, crystal orientation evolution is monitored at intragranular levels with high spatial and angular resolution. During the entire experiment, no crystal growth is detected and rigid grain rotation is observed only in the two grains within the current crowding region, where high density and divergence of electric current occur. Theoretical calculation indicates that the trend of electrical resistance drop still holds under the present conditions in the grain with high electrical resistivity, while the other grain with low resistivity reorients to align its a-axis more parallel with the ones of its neighboring grains. A detailed study of dislocation densities and subgrain boundaries suggests that grain rotation in β-Sn, unlike grain rotation in high melting temperature metals which undergo displacive deformation, is accomplished via diffusional process mainly, due to the high homologous temperature.
Optical vortex knots – one photon at a time
Authors: Tempone-Wiltshire Sebastien J. , Johnstone Shaun P. , Helmerson Kristian
Published: April 2016

Feynman described the double slit experiment as “a phenomenon which is impossible, absolutely impossible, to explain in any classical way and which has in it the heart of quantum mechanics”. The double-slit experiment, performed one photon at a time, dramatically demonstrates the particle-wave duality of quantum objects by generating a fringe pattern corresponding to the interference of light (a wave phenomenon) from two slits, even when there is only one photon (a particle) at a time passing through the apparatus. The particle-wave duality of light should also apply to complex three dimensional optical fields formed by multi-path interference, however, this has not been demonstrated. Here we observe particle-wave duality of a three dimensional field by generating a trefoil optical vortex knot – one photon at a time. This result demonstrates a fundamental physical principle, that particle-wave duality implies interference in both space (between spatially distinct modes) and time (through the complex evolution of the superposition of modes) and has implications for topologically entangled single photon states, orbital angular momentum multiplexing and topological quantum computing.
Regulatory mechanisms link phenotypic plasticity to evolvability
Authors: van Gestel Jordi , Weissing Franz J.
Published: April 2016

Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question – the optimal timing of bacterial sporulation – we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.
EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice
Authors: Li Weixin , Fang Qilu , Zhong Peng , Chen Lingfeng , Wang Lintao , Zhang Yali , Wang Jun , Li Xiaokun , Wang Yi , Wang Jingying , Liang Guang
Published: April 2016

Obesity is often associated with increased risk of cardiovascular diseases. Previous studies suggest that epidermal growth factor receptor (EGFR) antagonism may be effective for the treatment of angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. This study was performed to demonstrate if EGFR plays a role in the pathogenesis of hyperlipidemia/obesity-related cardiac injuries. The in vivo studies using both wild type (WT) and apolipoprotein E (ApoE) knockout mice fed with high fat diet (HFD) showed the beneficial effects of small-molecule EGFR inhibitors, AG1478 and 542, against obesity-induced myocardial injury. Administration of AG1478 and 542 significantly reduced myocardial inflammation, fibrosis, apoptosis and dysfunction in both two obese mouse models. In vitro, EGFR signaling was blocked by either siRNA silencing or small-molecule EGFR inhibitors in palmitic acid (PA)-stimulated cardiomyocytes. EGFR inhibition attenuated PA-induced inflammatory response and apoptosis in H9C2 cells. Furthermore, we found that PA-induced EGFR activation was mediated by the upstream TLR4 and c-Src. This study has confirmed the detrimental effect of EGFR activation in the pathogenesis of obesity-induced cardiac inflammatory injuries in experimental mice and has demonstrated the TLR4/c-Src-mediated mechanisms for PA-induced EGFR activation. Our data suggest that EGFR may be a therapeutic target for obesity-related cardiovascular diseases.
Halogenated hydrocarbon solvent-related cholangiocarcinoma risk: biliary excretion of glutathione conjugates of 1,2-dichloropropane evidenced by untargeted metabolomics analysis
Authors: Toyoda Yu , Takada Tappei , Suzuki Hiroshi
Published: April 2016

Recently, the International Agency for Research on Cancer issued a warning about the carcinogenicity of 1,2-dichloropropane (1,2-DCP) to humans based on an epidemiological study suggesting a relationship between the incidence of cholangiocarcinoma and occupational exposure to halogenated hydrocarbon solvent comprised mostly of 1,2-DCP. Although this dihaloalkane has been used in various industrial fields, there has been no biological evidence explaining the cholangiocarcinoma latency, as well as little understanding of general cholangiocarcinoma risk. In the present study, we explored the biliary excretion of 1,2-DCP metabolites by an untargeted metabolomics approach and the related molecular mechanism with in vitro and in vivo experiments. We hypothesized that the biliary excretion of carcinogens derived from 1,2-DCP contribute to the increased cholangiocarcinoma risk. We found that 1,2-DCP was conjugated with glutathione in the liver, and that the glutathione-conjugated forms of 1,2-DCP, including a potential carcinogen that contains a chloride atom, were excreted into bile by the bile canalicular membrane transporter, ABCC2. These results may reflect a risk in the backfiring of biliary excretion as a connatural detoxification systems for xenobiotics. Our findings would contribute to uncover the latent mechanism by which the chronic exposure to 1,2-DCP increases cholangiocarcinoma risk and future understanding of cholangiocarcinoma biology.
Crypt cells are involved in kin recognition in larval zebrafish
Authors: Biechl Daniela , Tietje Kristin , Gerlach Gabriele , Wullimann Mario F.
Published: April 2016

Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal.
The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats
Authors: Gris Georgia , Portillo-Salido Enrique , Aubel Bertrand , Darbaky Yassine , Deseure Kristof , Vela José Miguel , Merlos Manuel , Zamanillo Daniel
Published: April 2016

E-52862 is a selective σ1R antagonist currently undergoing phase II clinical trials for neuropathic pain and represents a potential first-in-class analgesic. Here, we investigated the effect of single and repeated administration of E-52862 on different pain-related behaviours in several neuropathic pain models in rats: mechanical allodynia in cephalic (trigeminal) neuropathic pain following chronic constriction injury of the infraorbital nerve (IoN), mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic polyneuropathy and cold allodynia in oxaliplatin (OX)-induced polyneuropathy. Mechanical hypersensitivity induced after IoN surgery or STZ administration was reduced by acute treatment with E-52862 and morphine, but not by pregabalin. In the OX model, single administration of E-52862 reversed the hypersensitivity to cold stimuli similarly to 100 mg/kg of gabapentin. Interestingly, repeated E-52862 administration twice daily over 7 days did not induce pharmacodynamic tolerance but an increased antinociceptive effect in all three models. Additionally, as shown in the STZ and OX models, repeated daily treatment with E-52862 attenuated baseline pain behaviours, which supports a sustained modifying effect on underlying pain-generating mechanisms. These preclinical findings support a role for σ1R in neuropathic pain and extend the potential for the use of selective σ1R antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain.
Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement
Authors: Xu Rui , Xia Hesheng , He Weifeng , Li Zhichao , Zhao Jian , Liu Bo , Wang Yuzhen , Lei Qiang , Kong Yi , Bai Yang , Yao Zhihui , Yan Rongshuai , Li Haisheng , Zhan Rixing , Yang Sisi , Luo Gaoxing , Wu Jun
Published: April 2016

A desirable microenvironment is essential for wound healing, in which an ideal moisture content is one of the most important factors. The fundamental function and requirement for wound dressings is to keep the wound at an optimal moisture. Here, we prepared serial polyurethane (PU) membrane dressings with graded water vapor transmission rates (WVTRs), and the optimal WVTR of the dressing for wound healing was identified by both in vitro and in vivo studies. It was found that the dressing with a WVTR of 2028.3 ± 237.8 g/m2·24 h was able to maintain an optimal moisture content for the proliferation and regular function of epidermal cells and fibroblasts in a three-dimensional culture model. Moreover, the dressing with this optimal WTVR was found to be able to promote wound healing in a mouse skin wound model. Our finds may be helpful in the design of wound dressing for wound regeneration in the future.
Novel asymmetric representation method for solving the higher-order Ginzburg-Landau equation
Authors: Wong Pring , Pang Lihui , Wu Ye , Lei Ming , Liu Wenjun
Published: April 2016

In ultrafast optics, optical pulses are generated to be of shorter pulse duration, which has enormous significance to industrial applications and scientific research. The ultrashort pulse evolution in fiber lasers can be described by the higher-order Ginzburg-Landau (GL) equation. However, analytic soliton solutions for this equation have not been obtained by use of existing methods. In this paper, a novel method is proposed to deal with this equation. The analytic soliton solution is obtained for the first time and is proved to be stable against amplitude perturbations. Through the split-step Fourier method, the bright soliton solution is studied numerically. The analytic results here may extend the integrable methods and could be used to study soliton dynamics for some equations in other disciplines. It may also provide the other way to obtain two-soliton solutions for higher-order GL equations.