bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Resting State Connectivity Patterns and Impaired Semantically Cued List Learning Test Performance in Early Course Remitted Major Depressive Disorder
Authors: Rao Julia A. , Jenkins Lisanne M. , Hymen Erica , Feigon Maia , Weisenbach Sara L. , Zubieta Jon-Kar , Langenecker Scott A.
Published: February 2016

Objectives: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting-state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. Methods: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. Results: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity. (JINS, 2016, 22, 225–239)
Is the secular trend in height delaying overweight rise among adolescents? The Brazilian case
Authors: Conde Wolney Lisboa , Rinaldi Ana Elisa Madalena , Enes Carla Cristina
Published: February 2016

Objective

To explore if the secular trend in height is contributing to delay overweight rise among Brazilian adolescents.

Design

Changes in BMI mean over time were fitted using linear regression including as independent variables survey year, height, survey-specific income quintiles, age and an interaction term of height × survey year. Overweight was defined as BMI≥25·0 kg/m2. Changes in overweight prevalence over time were fitted using Poisson regression.

Setting

Four national household surveys: 1974/5, 1989, 2002/3 and 2008/9.

Subjects

Brazilian adolescents.

Results

Mean values of height and BMI increased over the period, for both sexes and in all age ranges, except for girls aged 14–19 years from 1989 to 2002/3. The highest average increment and mean rate of height were between 1989 and 2002/3 and in 10–15-year-olds. The annual increment of height decreased from 2002/3 to 2008/9 in parallel with the increment in BMI rate. After fitting the regression model, the height × survey year interaction and per capita income were strong vectors to increase BMI mean. Changes in increment rate of height played a protective role against overweight in the last two periods for both sexes, mainly for girls. The period from 1989 to 2002/3 was the strongest vector associated with overweight in boys and the association decreased to the next period, from 2002/3 to 2008/9.

Conclusions

BMI and height of adolescents have increased in a wavering and alternate way throughout four decades in Brazil. The rate of height increment has played a protective role against overweight in adolescents.
Associative and Implicit Memory Performance as a Function of Cognitive Reserve in Elderly Adults with and without Mild Cognitive Impairment
Authors: Algarabel Salvador , Sales Alicia , Pitarque Alfonso , Meléndez Juan C. , Escudero Joaquín , Mayordomo Teresa
Published: February 2016

This study aims to analyze implicit and explicit memory performance as a function of cognitive reserve (CR) in a healthy control group (N = 39) and a mild cognitive impairment (MCI) group (N = 37). Both groups were subdivided into high and low cognitive reserve, and were asked to complete an explicit and implicit associative recognition tasks. The results showed that the control group was able to learn both tasks (η2 = .19, p < .0001), and the high CR group fared better (η2 = .06, p < .05). The MCI sample, conversely, was unable to learn the implicit relationship, and showed very little learning on the explicit association task. Participants diagnosed with MCI showed little plasticity in learning associations regardless of CR (η2 = .12, p < .01).
Prefactual Thoughts: Mental Simulations about What Might Happen
Authors: Epstude Kai , Scholl Annika , Roese Neal J.
Published: February 2016

Thought about the future can take many forms, from goal planning to intentions and from fantasies to magical thinking. The term prefactual has guided some past research, yet its potential impact has been hampered by inconsistency in its definition. Here we define prefactual thought as a conditional (if-then) proposition about an action-outcome linkage that may (or may not) take place in the future, such as “If I take action X, it will lead to outcome Y.” A prefactual embraces a causal belief that an action (if taken) will result in the outcome with a high degree of certainty. A form of mental simulation, prefactuals often derive from counterfactuals (which focus on the past) and feed into intentions (which center on the future). This article provides an overview of extant findings, draws connections to goal pursuit and affect regulation, and clarifies the value of the prefactual construct for conceptualizations of prospection.
Relationship Expectations and Relationship Quality
Authors: Lemay Edward P. , Venaglia Rachel B.
Published: February 2016

This article reviews research that examines the effects of relationship expectations on interpersonal relationships. Most of the published research suggests that positive relationship expectations are associated with better interpersonal functioning, as indicated by greater relationship persistence, more positive relationship evaluations and motivations, more prorelationship behavior, more forgiveness, and reduced contempt. Research on related constructs, such as relationship efficacy, implicit theories, trust, and insecurity dispositions, suggests a similar conclusion. However, there is some evidence that positive relationship expectations may sometimes have negative effects on healthy relationship functioning. A model of the multiple pathways through which relationship expectations may promote and threaten relationship quality is described, and several directions for future research are suggested.
Angiopoietin 2 induces astrocyte apoptosis via αvβ5-integrin signaling in diabetic retinopathy
Authors: Yun J-H , Park S W , Kim J H , Park Y-J , Cho C-H , Kim J H
Published: February 2016

The vascular leakage in diabetic retinopathy leads to macular edema and vision loss. Although astrocyte play an important role in regulating blood-brain barrier integrity in the brain, the precise role of astrocyte in blood-retinal barrier was yet to be elucidated. This study aimed to investigate the role of angiopoietin 2 (Ang2) in astrocyte loss and vascular leakage in the early streptozotocin-induced diabetic retinopathy. We demonstrated that vascular leakage occurred with astrocyte loss in early diabetic mice retina as Ang2 increased. The astrocyte loss and vascular leakage were inhibited by intravitreal injection of Ang2-neutralizing antibody. In vitro, Ang2 aggravated high glucose-induced astrocyte apoptosis via GSK-3β activation. Ang2 directly bound to αvβ5 integrin, which was abundant in astrocyte, and the blockade of αvβ5 integrin, in vitro, effectively attenuated Ang2-induced astrocyte apoptosis. In vivo, intravitreal injection of anti-αvβ5-integrin antibody inhibited astrocyte loss in early diabetic retinopathy. Taken together, Ang2 induced astrocyte apoptosis under high glucose via αvβ5-integrin/GSK-3β/β-catenin pathway. Therefore, we suggest that Ang2/integrin signaling could be a potential therapeutic target to prevent the vascular leakage by astrocyte loss in early diabetic retinopathy.
The transcriptional coactivator PGC1α protects against hyperthermic stress via cooperation with the heat shock factor HSF1
Authors: Xu L , Ma X , Bagattin A , Mueller E
Published: February 2016

Heat shock proteins (HSPs) are required for the clearance of damaged and aggregated proteins and have important roles in protein homeostasis. It has been shown that the heat shock transcription factor, HSF1, orchestrates the transcriptional induction of these stress-regulated chaperones; however, the coregulatory factors responsible for the enhancement of HSF1 function on these target genes have not been fully elucidated. Here, we demonstrate that the cold-inducible coactivator, PGC1α, also known for its role as a regulator of mitochondrial and peroxisomal biogenesis, thermogenesis and cytoprotection from oxidative stress, regulates the expression of HSPs in vitro and in vivo and modulates heat tolerance. Mechanistically, we show that PGC1α physically interacts with HSF1 on HSP promoters and that cells and mice lacking PGC1α have decreased HSPs levels and are more sensitive to thermal challenges. Taken together, our findings suggest that PGC1α protects against hyperthermia by cooperating with HSF1 in the induction of a transcriptional program devoted to the cellular protection from thermal insults.
Not just a colourful metaphor: modelling the landscape of cellular development using Hopfield networks
Authors: Fard Atefeh Taherian , Srihari Sriganesh , Mar Jessica C , Ragan Mark A
Published: February 2016

The epigenetic landscape was introduced by Conrad Waddington as a metaphor of cellular development. Like a ball rolling down a hillside is channelled through a succession of valleys until it reaches the bottom, cells follow specific trajectories from a pluripotent state to a committed state. Transcription factors (TFs) interacting as a network (the gene regulatory network (GRN)) orchestrate this developmental process within each cell. Here, we quantitatively model the epigenetic landscape using a kind of artificial neural network called the Hopfield network (HN). An HN is composed of nodes (genes/TFs) and weighted undirected edges, resulting in a weight matrix (W) that stores interactions among the nodes over the entire network. We used gene co-expression to compute the edge weights. Through W, we then associate an energy score (E) to each input pattern (pattern of co-expression for a specific developmental stage) such that each pattern has a specific E. We propose that, based on the co-expression values stored in W, HN associates lower E values to stable phenotypic states and higher E to transient states. We validate our model using time course gene-expression data sets representing stages of development across 12 biological processes including differentiation of human embryonic stem cells into specialized cells, differentiation of THP1 monocytes to macrophages during immune response and trans-differentiation of epithelial to mesenchymal cells in cancer. We observe that transient states have higher energy than the stable phenotypic states, yielding an arc-shaped trajectory. This relationship was confirmed by perturbation analysis. HNs offer an attractive framework for quantitative modelling of cell differentiation (as a landscape) from empirical data. Using HNs, we identify genes and TFs that drive cell-fate transitions, and gain insight into the global dynamics of GRNs.
GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification
Authors: Chung Vin Yee , Tan Tuan Zea , Tan Ming , Wong Meng Kang , Kuay Kuee Theng , Yang Zhe , Ye Jieru , Muller Julius , Koh Cheryl M. , Guccione Ernesto , Thiery Jean Paul , Huang Ruby Yun-Ju
Published: February 2016

Epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, has been implicated to contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). Here we report that a transcription factor—Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. EOC tumours with lower GRHL2 levels are associated with the Mes/Mesenchymal molecular subtype and a poorer overall survival. shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype results in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, microRNA-200b/a is identified as the direct transcriptional target of GRHL2 and regulates the epithelial status of EOC through ZEB1 and E-cadherin. Our study demonstrates that loss of GRHL2 increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding sites at miR-200b/a and E-cadherin genes. These findings support GRHL2 as a pivotal gatekeeper of EMT in EOC via miR-200-ZEB1.
SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation
Authors: Doiguchi Masamichi , Nakagawa Takeya , Imamura Yuko , Yoneda Mitsuhiro , Higashi Miki , Kubota Kazuishi , Yamashita Satoshi , Asahara Hiroshi , Iida Midori , Fujii Satoshi , Ikura Tsuyoshi , Liu Ziying , Nandu Tulip , Kraus W. Lee , Ueda Hitoshi , Ito Takashi
Published: February 2016

Histone acetylation plays a pivotal role in transcriptional regulation and ATP-dependent nucleosome remodeling activity is required for optimal transcription from chromatin. While these two activities have been well characterized, how they are coordinated remains to be determined. We discovered ATP-dependent histone H2A acetylation activity in Drosophila nuclear extracts. This activity was column purified and demonstrated to be composed of the enzymatic activities of CREB-binding protein (CBP) and SMARCAD1, which belongs to the Etl1 subfamily of the Snf2 family of helicase-related proteins. SMARCAD1 enhanced acetylation by CBP of H2A K5 and K8 in nucleosomes in an ATP-dependent fashion. Expression array analysis of S2 cells having ectopically expressed SMARCAD1 revealed up-regulated genes. Using native genome templates of these up-regulated genes, we found that SMARCAD1 activates their transcription in vitro. Knockdown analysis of SMARCAD1 and CBP indicated overlapping gene control and ChIP-seq analysis of these commonly controlled genes showed that CBP is recruited to the promoter prior to SMARCAD1. Moreover, Drosophila genetic experiments demonstrated interaction between SMARCAD1/Etl1 and CBP/nej during development. The interplay between the remodeling activity of SMARCAD1 and histone acetylation by CBP sheds light on the function of chromatin and the genome-integrity network.
Musical Creativity “Revealed” in Brain Structure: Interplay between Motor, Default Mode and Limbic Networks
Authors: Bashwiner David M. , Wertz Christopher J. , Flores Ranee A. , Jung Rex E.
Published: February 2016

Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus and temporal pole) and c) emotion-related regions (orbitofrontal cortex, temporal pole and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music.
“APEC Blue”: Secondary Aerosol Reductions from Emission Controls in Beijing
Authors: Sun Yele , Wang Zifa , Wild Oliver , Xu Weiqi , Chen Chen , Fu Pingqing , Du Wei , Zhou Libo , Zhang Qi , Han Tingting , Wang Qingqing , Pan Xiaole , Zheng Haitao , Li Jie , Guo Xiaofeng , Liu Jianguo , Worsnop Douglas R.
Published: February 2016

China implemented strict emission control measures in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit. We conducted synchronous aerosol particle measurements with two aerosol mass spectrometers at different heights on a meteorological tower in urban Beijing to investigate the variations in particulate composition, sources and size distributions in response to emission controls. Our results show consistently large reductions in secondary inorganic aerosol (SIA) of 61–67% and 51–57% and in secondary organic aerosol (SOA) of 55% and 37%, at 260 m and ground level, respectively, during the APEC summit. These changes were mainly caused by large reductions in accumulation mode particles and by suppression of the growth of SIA and SOA by a factor of 2–3, which led to blue sky days during APEC commonly referred to as “APEC Blue”. We propose a conceptual framework for the evolution of primary and secondary species and highlight the importance of regional atmospheric transport in the formation of severe pollution episodes in Beijing. Our results indicate that reducing the precursors of secondary aerosol over regional scales is crucial and effective in suppressing the formation of secondary particulates and mitigating PM pollution.
Abnormal tau induces cognitive impairment through two different mechanisms: synaptic dysfunction and neuronal loss
Authors: Di J. , Cohen L. S. , Corbo C. P. , Phillips G. R. , El Idrissi A. , Alonso A. D.
Published: February 2016

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimer-like dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization to the nucleus. Induction of PH-Tau triggered neuronal death (60% in CA3), astrocytosis, and loss of the processes in CA1. These findings suggest, that phosphorylated tau is sufficient to induce neurodegeneration and that two different mechanisms can induce cognitive impairment depending on the levels of PH-Tau expression.
Persistent activation of microglia and NADPH oxidase drive hippocampal dysfunction in experimental multiple sclerosis
Authors: Di Filippo Massimiliano , de Iure Antonio , Giampà Carmela , Chiasserini Davide , Tozzi Alessandro , Orvietani Pier Luigi , Ghiglieri Veronica , Tantucci Michela , Durante Valentina , Quiroga-Varela Ana , Mancini Andrea , Costa Cinzia , Sarchielli Paola , Fusco Francesca Romana , Calabresi Paolo
Published: February 2016

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression.
Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death
Authors: Fang Yuan , Su Tu , Qiu Xiaorong , Mao Pingan , Xu Yidan , Hu Zizhong , Zhang Yi , Zheng Xinhua , Xie Ping , Liu Qinghuai
Published: February 2016

It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 μM H2O2-induced apoptosis of RPE cells. 200 μM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-δ and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD.
Calstabin 2: An important regulator for learning and memory in mice
Authors: Yuan Qi , Deng Ke-Yu , Sun Le , Chi Shaopeng , Yang Zhiguang , Wang Jun , Xin Hong-Bo , Wang Xiaoqun , Ji Guangju
Published: February 2016

Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca2+ dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca2+ leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.
GeneiASE: Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information
Authors: Edsgärd Daniel , Iglesias Maria Jesus , Reilly Sarah-Jayne , Hamsten Anders , Tornvall Per , Odeberg Jacob , Emanuelsson Olof
Published: February 2016

Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.
Digit-only sauropod pes trackways from China – evidence of swimming or a preservational phenomenon?
Authors: Xing Lida , Li Daqing , Falkingham Peter L. , Lockley Martin G. , Benton Michael J. , Klein Hendrik , Zhang Jianping , Ran Hao , Persons W. Scott , Dai Hui
Published: February 2016

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all.
Diabetes Caused by Elastase-Cre-Mediated Pdx1 Inactivation in Mice
Authors: Kodama Sota , Nakano Yasuhiro , Hirata Koji , Furuyama Kenichiro , Horiguchi Masashi , Kuhara Takeshi , Masui Toshihiko , Kawaguchi Michiya , Gannon Maureen , Wright Christopher V. E. , Uemoto Shinji , Kawaguchi Yoshiya
Published: February 2016

Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors and ultimately fewer β cells. Notably, postnatal expansion of the endocrine cell content was extremely poor and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages.
Correction: Corrigendum: Contractile dynamics change before morphological cues during fluorescence illumination
Authors: Knoll S. G. , Ahmed W. W. , Saif T. A.
Published: February 2016

Scientific Reports 5: Article number: 18513; published online: 22 December 2015; updated: 18 February 2016. The original version of this Article contained an error in the title of the paper, where the word “fluorescence” was incorrectly given as “florescence”. This has now been corrected in the PDF and HTML versions of the Article.
An Atomistic-Scale Study for Thermal Conductivity and Thermochemical Compatibility in (DyY)Zr2O7 Combining an Experimental Approach with Theoretical Calculation
Authors: Qu Liu , Choy Kwang-Leong , Wheatley Richard
Published: February 2016

Ceramic oxides that have high-temperature capabilities can be deposited on the superalloy components in aero engines and diesel engines to advance engine efficiency and reduce fuel consumption. This paper aims to study doping effects of Dy3+ and Y3+on the thermodynamic properties of ZrO2 synthesized via a sol-gel route for a better control of the stoichiometry, combined with molecular dynamics (MD) simulation for the calculation of theoretical properties. The thermal conductivity is investigated by the MD simulation and Clarke’s model. This can improve the understanding of the microstructure and thermodynamic properties of (DyY)Zr2O7 (DYZ) at the atomistic level. The phonon-defect scattering and phonon-phonon scattering processes are investigated via the theoretical calculation, which provides an effective way to study thermal transport properties of ionic oxides. The measured and predicted thermal conductivity of DYZ is lower than that of 4 mol % Y2O3 stabilized ZrO2 (4YSZ). It is discovered that DYZ is thermochemically compatible with Al2O3 at 1300 °C, whereas at 1350 °C DYZ reacts with Al2O3 forming a small amount of new phases.
Dnd knockout ablates germ cells and demonstrates germ cell independent sex differentiation in Atlantic salmon
Authors: Wargelius Anna , Leininger Sven , Skaftnesmo Kai Ove , Kleppe Lene , Andersson Eva , Taranger Geir Lasse , Schulz Rüdiger W , Edvardsen Rolf B
Published: February 2016

Introgression of farmed salmon escapees into wild stocks is a major threat to the genetic integrity of wild populations. Using germ cell-free fish in aquaculture may mitigate this problem. Our study investigated whether it is possible to produce germ cell-free salmon in F0 by using CRISPR-Cas9 to knock out dnd, a factor required for germ cell survival in vertebrates. To avoid studying mosaic animals, sgRNA targeting alb was simultaneously used as a visual tracer since the phenotype of alb KO is complete loss of pigmentation. Induced mutations for the tracer (alb) and the target (dnd) genes were highly correlated and produced germ cell-less fish lacking pigmentation, underlining the suitability of alb KO to serve as tracer for targeted double allelic mutations in F0 animals in species with prohibitively long generation times. This is also the first report describing dnd knockout in any fish species. Analyzing gene expression and histology of dnd KO fish revealed that sex differentiation of the somatic compartment does not depend on the presence of germ cells. However, the organization of the ovarian somatic compartment seems compromised in mutant fish.
Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release
Authors: Snäll Johanna , Linnér Anna , Uhlmann Julia , Siemens Nikolai , Ibold Heike , Janos Marton , Linder Adam , Kreikemeyer Bernd , Herwald Heiko , Johansson Linda , Norrby-Teglund Anna
Published: February 2016

Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus.
Assortativity and leadership emerge from anti-preferential attachment in heterogeneous networks
Authors: Sendiña-Nadal I. , Danziger M. M. , Wang Z. , Havlin S. , Boccaletti S.
Published: February 2016

Real-world networks have distinct topologies, with marked deviations from purely random networks. Many of them exhibit degree-assortativity, with nodes of similar degree more likely to link to one another. Though microscopic mechanisms have been suggested for the emergence of other topological features, assortativity has proven elusive. Assortativity can be artificially implanted in a network via degree-preserving link permutations, however this destroys the graph’s hierarchical clustering and does not correspond to any microscopic mechanism. Here, we propose the first generative model which creates heterogeneous networks with scale-free-like properties in degree and clustering distributions and tunable realistic assortativity. Two distinct populations of nodes are incrementally added to an initial network by selecting a subgraph to connect to at random. One population (the followers) follows preferential attachment, while the other population (the potential leaders) connects via anti-preferential attachment: they link to lower degree nodes when added to the network. By selecting the lower degree nodes, the potential leader nodes maintain high visibility during the growth process, eventually growing into hubs. The evolution of links in Facebook empirically validates the connection between the initial anti-preferential attachment and long term high degree. In this way, our work sheds new light on the structure and evolution of social networks.
Multi-functional reactively-sputtered copper oxide electrodes for supercapacitor and electro-catalyst in direct methanol fuel cell applications
Authors: Pawar Sambhaji M. , Kim Jongmin , Inamdar Akbar I. , Woo Hyeonseok , Jo Yongcheol , Pawar Bharati S. , Cho Sangeun , Kim Hyungsang , Im Hyunsik
Published: February 2016

This work reports on the concurrent electrochemical energy storage and conversion characteristics of granular copper oxide electrode films prepared using reactive radio-frequency magnetron sputtering at room temperature under different oxygen environments. The obtained films are characterized in terms of their structural, morphological, and compositional properties. X-ray diffraction, X-ray photoelectron spectroscopy and scanning electron microscope studies reveal that granular, single-phase Cu2O and CuO can be obtained by controlling the oxygen flow rate. The electrochemical energy storage properties of the films are investigated by carrying out cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy tests. The electrochemical analysis reveals that the Cu2O and CuO electrodes have high specific capacitances of 215 and 272 F/g in 6 M KOH solution with a capacity retention of about 80% and 85% after 3000 cycles, respectively. Cyclic voltammetry and chronoamperometry are used to study the electrochemical energy conversion properties of the films via methanol electro-oxidation. The results show that the Cu2O and CuO electrodes are electro-catalytically active and highly stable.
Strong hole-doping and robust resistance-decrease in proton-irradiated graphene
Authors: Lee Chul , Kim Jiho , Kim SangJin , Chang Young Jun , Kim Keun Soo , Hong ByungHee , Choi E. J.
Published: February 2016

Great effort has been devoted in recent years to improve the electrical conductivity of graphene for use in practical applications. Here, we demonstrate the hole carrier density of CVD graphene on a SiO2/Si substrate increases by more than one order of magnitude to n = 3 × 1013 cm−2 after irradiation with a high energy 5 MeV proton beam. As a result, the dc-resistance (R) of graphene is reduced significantly by 60%. Only a negligible amount of defect is created by the irradiation. Also the hole-doped low resistance state of graphene remains robust against external perturbations. This carrier doping is achieved without requiring the bias-gate voltage as is the case for other field effect devices. We make two important observations, (i) occurrence of the doping after the irradiation is turned off (ii) indispensability of the SiO2-layer in the substrate, which leads to a purely electronic mechanism for the doping where electron-hole pair creation and interlayer Coulomb attraction play a major role. A flux-dependent study predicts that an ultrahigh doping may be obtained by longer irradiation. We expect the irradiation doping method could be applied to other atomically thin solids, facilitating the fundamental study and application of the 2d materials.
Reduced brain activation in violent adolescents during response inhibition
Authors: Qiao Yi , Mei Yi , Du XiaoXia , Xie Bin , Shao Yang
Published: February 2016

Deficits in inhibitory control have been linked to aggression and violent behaviour. This study aimed to observe whether violent adolescents show different brain activation patterns during response inhibition and to ascertain the roles these brain regions play. A self-report method and modified overt aggression scale (MOAS) were used to evaluate violent behaviour. Functional magnetic resonance imaging was performed in 22 violent adolescents and 17 matched healthy subjects aged 12 to 18 years. While scanning, a go/no-go task was performed. Between-group comparisons revealed that activation in the bilateral middle and superior temporal gyrus, hippocampus, and right orbitofrontal area (BA11) regions were significantly reduced in the violent group compared with the control group. Meanwhile, the violent group had more widespread activation in the prefrontal cortex than that observed in the control group. Activation of the prefrontal cortex in the violent group was widespread but lacking in focus, failing to produce intensive activation in some functionally related regions during response inhibition.
Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma
Authors: Liu Hao , Shen Zhenbin , Wang Zhenglin , Wang Xuefei , Zhang Heng , Qin Jing , Qin Xinyu , Xu Jiejie , Sun Yihong
Published: February 2016

Clinical significance of 2,3-dioxygenase (IDO) has been studied in types of tumors, but the role that IDO played in gastric adenocarcinoma (GAC) is still unclear. Here, we aim to investigate the prognostic value of IDO expression in patients with GAC. We examined intratumoral IDO expression in retrospectively enrolled 357 patients with GAC undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of IDO expression and its association with clinical pathological factors. We generated a predictive nomogram by integrating IDO expression with the TNM staging system for overall survival of GAC patients. High expression of intratumoral IDO predicted a dismal outcome. Intratumoral IDO expression gave a further discrimination for the prognosis of GAC patients. By Cox multivariate analysis, IDO expression was defined as an independent prognosticator. The generated nomogram performed well in predicting the 3- and 5-year overall survival of GAC patients. Conclusively, IDO is a potential prognostic biomarker for overall survival of patients with GAC after gastrectomy.
Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner
Authors: Saland Samantha K. , Schoepfer Kristofer J. , Kabbaj Mohamed
Published: February 2016

We recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response.
Temporal dynamics of Puumala hantavirus infection in cyclic populations of bank voles
Authors: Voutilainen Liina , Kallio Eva R. , Niemimaa Jukka , Vapalahti Olli , Henttonen Heikki
Published: February 2016

Understanding the dynamics of zoonotic pathogens in their reservoir host populations is a prerequisite for predicting and preventing human disease epidemics. The human infection risk of Puumala hantavirus (PUUV) is highest in northern Europe, where populations of the rodent host (bank vole, Myodes glareolus) undergo cyclic fluctuations. We conducted a 7-year capture-mark-recapture study to monitor seasonal and multiannual patterns of the PUUV infection rate in bank vole populations exhibiting a 3-year density cycle. Infected bank voles were most abundant in mid-winter months during years of increasing or peak host density. Prevalence of PUUV infection in bank voles exhibited a regular, seasonal pattern reflecting the annual population turnover and accumulation of infections within each year cohort. In autumn, the PUUV transmission rate tracked increasing host abundance, suggesting a density-dependent transmission. However, prevalence of PUUV infection was similar during the increase and peak years of the density cycle despite a twofold difference in host density. This may result from the high proportion of individuals carrying maternal antibodies constraining transmission during the cycle peak years. Our exceptionally intensive and long-term dataset provides a solid basis on which to develop models to predict the dynamic public health threat posed by PUUV in northern Europe.
Topologically nontrivial bismuth(111) thin films
Authors: Yao Meng-Yu , Zhu Fengfeng , Han C. Q. , Guan D. D. , Liu Canhua , Qian Dong , Jia Jin-feng
Published: February 2016

Using high-resolution angle-resolved photoemission spectroscopy (ARPES), the topological property of the three-dimensional Bi(111) films grown on the Bi2Te3(111) substrate were studied. Very different from the bulk Bi, we found another surface band near the "Equation missing" point besides the two well-known surface bands on the 30 nm films. With this new surface band, the bulk valence band and the bulk conduction band can be connected by the surface states in the Bi(111)/Bi2Te3 films. Our band mapping revealed odd number of Fermi crossings of the surface bands, which provided new experimental evidences that Bi(111)/Bi2Te3 films of a certain thickness can be topologically nontrivial in three dimension.
Biodegradation of DDT by Stenotrophomonas sp. DDT-1: Characterization and genome functional analysis
Authors: Pan Xiong , Lin Dunli , Zheng Yuan , Zhang Qian , Yin Yuanming , Cai Lin , Fang Hua , Yu Yunlong
Published: February 2016

A novel bacterium capable of utilizing 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) as the sole carbon and energy source was isolated from a contaminated soil which was identified as Stenotrophomonas sp. DDT-1 based on morphological characteristics, BIOLOG GN2 microplate profile and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate DDT-1 showed a 4,514,569 bp genome size, 66.92% GC content, 4,033 protein-coding genes and 76 RNA genes including 8 rRNA genes. Totally, 2,807 protein-coding genes were assigned to Clusters of Orthologous Groups (COGs) and 1,601 protein-coding genes were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The degradation half-lives of DDT increased with substrate concentration from 0.1 to 10.0 mg/l, whereas decreased with temperature from 15 °C to 35 °C. Neutral condition was the most favorable for DDT biodegradation. Based on genome annotation of DDT degradation genes and the metabolites detected by GC-MS, a mineralization pathway was proposed for DDT biodegradation in which it was orderly converted into DDE/DDD, DDMU, DDOH and DDA via dechlorination, hydroxylation and carboxylation and ultimately mineralized to carbon dioxide. The results indicate that the isolate DDT-1 is a promising bacterial resource for the removal or detoxification of DDT residues in the environment.
RETRACTED ARTICLE: Increased biomass productivity in green algae by tuning non-photochemical quenching
Authors: Berteotti Silvia , Ballottari Matteo , Bassi Roberto
Published: February 2016

Photosynthetic microalgae have a high potential for the production of biofuels and highly valued metabolites. However, their current industrial exploitation is limited by a productivity in photobioreactors that is low compared to potential productivity. The high cell density and pigment content of the surface layers of photosynthetic microalgae result in absorption of excess photons and energy dissipation through non-photochemical quenching (NPQ). NPQ prevents photoinhibition, but its activation reduces the efficiency of photosynthetic energy conversion. In Chlamydomonas reinhardtii, NPQ is catalyzed by protein subunits encoded by three lhcsr (light harvesting complex stress related) genes. Here, we show that heat dissipation and biomass productivity depends on LHCSR protein accumulation. Indeed, algal strains lacking two lhcsr genes can grow in a wide range of light growth conditions without suffering from photoinhibition and are more productive than wild-type. Thus, the down-regulation of NPQ appears to be a suitable strategy for improving light use efficiency for biomass and biofuel production in microalgae.