bluuebunny/crossref_metadata_2025 huggingface dataset:
New molecular genetic findings in the genetics of affective disorders
Authors: Souery D. , Mendlewicz J.
Published: July 2016

Molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome. Specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. These include genes on chromosomes 18, 21, 4, 5, 11 and X. Other studies have reported the presence of anticipation in BPAD and in unipolar affective disorder (UPAD). This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (trinucleotide repeat sequences). Associations with these mutations have been reported in different populations of BPAD-patients and may represent a genetic factor involved in the transmission of the disorder.

These findings are all preliminary and require to be confirmed. Large multi-centres and multi-disciplinary projects are currently underway in Europe and in the US and hopefully will improve our understanding of the genetic factors involved in affective disorders. In addition, genetic approaches used in psychiatry are being combined with an assessment of non-genetic susceptibility factors. The investigation of interactions between gene and environment is one of the most promising areas dealing with complex multi-factorial diseases such as the affective disorders.
On the unique profile of action of clozapine as assessed with fos-protein induction in rat brain regions
Authors: Korf J. , Andries D. , Sebens J.B.
Published: July 2016

Clozapine (Leponex®) has been shown to be therapeutically effective in patients resistant to long-term medication with classical antipsychotics. The mode of action of clozapine is not clear, but several cerebral receptors have been implicated, including the dopamine D2, D3 and D4 types, α-adrenergic, serotonin (type 2A) and glutamate (NMDA-type) receptors. Moreover, clozapine has anti-cholinergic and antihistaminergic potencies. Thusfar, receptor profiles are based virtually exclusively on in vitro binding assays. It appeared, that pharmacological and physiological stimuli activate particular gene expression, in vivo, so at cellular level the action of e.g. antipsychotics can now be traced. In this communication we present data on the in vivo profile of clozapine as revealed with Fos-protein expression. The immediate early gene c-fos is, as other members of the class of such genes, rapidly and transiently induced in the brain. The prototypic members of this class all encode nuclear proteins that regulate gene transcription. Recent studies have shown that the antipsychotics haloperidol (Haldol®) and clozapine, when given acutely, induce different patterns of Fos-like immunoreactivity in the forebrain of the rat. The most marked effects of haloperidol were found in the striatum, the nucleus accumbens and the lateral septum.
New dopaminergic and non-dopaminergic theories in schizophrenia and their therapeutic impact
Authors: Kahn R.S.
Published: July 2016

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).

Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.
Will light brighten the future of the depressed patient?
Authors: Van Den Hoofdakker R.H. , Gordijn M.C.M.
Published: July 2016

The present explosive growth of interest in the therapeutic possibilities of exposure to light was triggered by a patient, Herbert Kern. He suffered from episodic depressive and manic complaints and discovered, by registering these over the years, a seasonal pattern in their occurrence. Discussions with scientists of the NIMH resulted in his participation in a bright light-treatment experiment when he was depressed in the winter of 1980-1981. He recovered.

Next, the same group of investigators defined the criteria for a new syndrome, Seasonal Affective Disorder (SAD): a history of major affective disorder (according to the Research Diagnostic Criteria), at least two consecutive years in which the depressions have occurred during fall or winter and remitted in the following spring or summer, and the absence of any clear-cut seasonally changing psychosocial variable, such as work, stress and so on.
Biological and psychopharmacological aspects of impulse-control disorders
Authors: Verhoeven W.M.A. , Tuinier S.
Published: July 2016

Over the past decades extensive research has been performed on the presumed relationship between neurotransmitter functionality in the central nervous system and psychopathological states. Originally, in the mid-sixties it was hypothesized that depressive states may be associated with disorders in brain noradrenalin and/or serotonin (5-hydroxytryptamine; 5-HT) metabolism or function resulting in the socalled monoamine hypothesis of depression. Subsequent investigations revealed that altered 5-HT metabolism is not related to mood disorder per se, but to components of the depressive syndrome and more specifically to increased anxiety and/or signs of dysregulated aggression, including violent suicidal attempts.

Concerning aggression and other types of disruptive or impulsive behavior, research on their neurobiological determinants has been focussed mainly on indicators of central 5-HT function.
Is CO2 inhalation a specific marker for panic disorder? An experimental panic model
Authors: Griez E.
Published: July 2016

Patients with panic disorder (PD) report a transient feeling of anxiety upon inhalation of CO2 enriched air. They rate this experience as similar to symptoms of a panic attack. This hypersensitivity has been proposed as an experimental disease model. This paper examines the validity of single breath inhalation of 35% CO2 as a model for PD.
Pharmacological treatment strategies in mood, panic and obsessive compulsive disorders
Authors: Verhoeven W.M.A. , Tuinier S. , Noten J.B.G.M.
Published: July 2016

Since the introduction of the monoamine oxydase inhibitors and the first tricyclic antidepressant (TCA) imipramine in the late fifties, the treatment of depressive disorders has been changed dramatically. Althought a great variety of antidepressants such as TCA's, selective serotoninte-re-uptake inhibitors (SSRI's) mianserin, trazodone, mirtazapine, moclobemide and venlafaxine has become available, the exact mode of action is not revealed as yet, and classification should be done according to the interference of antidepressants with central monoaminergic processes.

As to the potential of causing interactions, special attention has to be given to the SSRI's because of their interference with the CYP450 isozyme system. Therapeutic monotoring is recommended for the TCA's. The choiseforan antidepressant should be based on various factors like symptomatology and severity of the depression, potential interactions and somatic and/or psychiatric comorbidity.

Extensive clinical research has demonstrated that TCA's are the most effective for major depression with melancholia (vital depression) and depressive disorders in the elderly.
Autism and autistic-like disorders: the hypothalamic-pituita-ry-adrenal system as a model for research
Authors: Jansen L.M.C. , Wied C.C. Gispen-De , Engeland H. Van
Published: July 2016

In this article an overview is given of the differential diagnosis of autism and autistic-like disorders. The diagnosis of the so-called ‘Multiple Complex Developmental Disorders’ (MCDD) as a distinct entity is discussed in relation to autism and schizophrenia.

Biological research and the relevance of results until recently are discussed. Finally, the importance of the hypothalamic-pituitary-adrenal system (HPA system) as a model for research is proposed. Research on the flexibility of this system may contribute in understanding the ways of stress processing in disorders like autism, MCDD and schizophrenia.
Social stress in rats: An animal model of depression?
Authors: Koolhaas J.M. , Meerlo P. , de Boer S.F. , Strubbe J.H. , Bohus B.
Published: July 2016

Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches should operate in close interaction, each providing additional information to the other approach. However, in practice the animal model approach seems to be rather independent from the human studies. In a critical evaluation of the available animal models of depression, Willner concluded that none of the models fulfilled the criteria of a sufficient face, construct and predictive validity. Although this evaluation was made ten years ago, we feel that the situation has improved very little since that time. Most animal models fail to sufficiently mimic both the etiology and the symptomatology of human depressive disorders. With respect to the etiology, stress and major life events are generally considered to be an important factor in the development of depression. Most of the animal models however use stressors which bear little or no relationship to the biology of the species, i.e. to the situations an animal may meet in its everyday life in a natural habitat. Moreover, these models do not pay attention to the temporal dynamics of the disease. In humans, the disease is characterized by its gradual onset, which is often preceded by symptoms of anxiety. Moreover, a relatively large number of patients suffers from recurrent episodes of depression, which tend to occur with decreasing intervals and increasing duration and severity. If we want to improve our knowledge of the causal mechanisms of depression, animal models which allow an experimental analysis of the temporal dynamics of the disease are essential.
Biological theories of depressions: premisses - and progress?
Authors: van den Burg W.
Published: July 2016

Although less undisputed in biological psychiatry than formerly, there are basically still two premisses which underly most hypotheses in biological depression research. These are deeply rooted in the medical way of thinking and have guided the construction of DSM-III. The first is that depressive symptoms and complaints cluster in one or more discrete syndromes, and the second is that these correspond to separate nosological entities, characterized by specific biological derangements and pathogenetic processes. Below a number of issues are raised which cast doubts on the validity of these premisses and on the progress made in pinpointing the derangements looked for.
The timing of light therapy and response assessment in winter depression
Authors: Meesters Y.
Published: July 2016

Since Rosenthal et al published their first study about the effects of light treatment on mood in patients suffering from winter depression, many research centres have become interested in the study and treatment of seasonal affective disorders (SAD), one of them being the department of Biological Psychiatry in Groningen. In 1987, we started the first experiments under the inspiring direction of Prof. Rudi van den Hoofdakker and hundreds of patients have participated in various investigations ever since.
Lithium treatment in affective disorders: The significance of strongly elevated erythrocyte choline levels
Authors: Flentge F. , Slooff C.J.
Published: July 2016

In manic-depressive patients treated with lithium salts the transport of choline over the erythrocyte membrane is strongly inhibited, resulting in dramatically increased erythrocyte choline levels (for review see ref. 1). Whether or not there is a relationship between this effect and treatment response is not clear. Data on this issue are scarce possibly because the measurement of treatment response in lithium prophylaxis is very difficult and time consuming. Also the effect on erythrocyte choline is specific for lithium and not for manic-depressive illness. We will address here the question of a possible relation between erythrocyte choline and clinical effects of lithium.
Treating Depression and Anxiety with Digital Cognitive Behavioural Therapy for Insomnia: A Real World NHS Evaluation Using Standardized Outcome Measures
Authors: Luik Annemarie I. , Bostock Sophie , Chisnall Leanne , Kyle Simon D. , Lidbetter Nicky , Baldwin Nick , Espie Colin A.
Published: July 2016

Background: Evidence suggests that insomnia may be an important therapeutic target to improve mental health. Aims: Evaluating changes in symptoms of depression and anxiety after supported digital cognitive behavioural therapy (dCBT) for insomnia delivered via a community-based provider (Self Help Manchester) of the Improving Access to Psychological Therapies (IAPT) service. Method: Supported dCBT for insomnia was delivered to 98 clients (mean age 44.9 years, SD 15.2, 66% female) of Self Help Manchester. All clients received six support calls from an eTherapy coordinator to support the self-help dCBT. During these calls levels of depression (Patient Health Questionnaire, PHQ-9) and anxiety (Generalized Anxiety Disorder, GAD-7) were determined. Results: Depression (Mdifference-5.7, t(70) = 12.5, p < .001) and anxiety [Generalized Anxiety Disorder-7 (GAD-7), Mdifference-4.1, t(70) = 8.0, p < .001] were reduced following supported dCBT for insomnia. This translated into an IAPT recovery rate of 68% for depression and anxiety. Conclusions: These results suggest that dCBT for insomnia alleviates depression and anxiety in clients presenting with mental health complaints in routine healthcare.
Ultraviolet irradiation of glycine in presence of pyrite as a model of chemical evolution: an experimental and molecular modelling approach
Authors: de la Cruz-López Azarhel , del Ángel-Meraz Ebelia , Colín-García María , Ramos-Bernal Sergio , Negrón-Mendoza Alicia , Heredia Alejandro
Published: July 2016

In this work, the molecular interaction of the amino acid glycine and the mineral pyrite was performed to gain insight into the potential role of the mineral as a precursor of chemical complexity in the presence of ultraviolet (UV) radiation. Glycine samples were self-assembled on pyrite with and without exposure to UV radiation and subsequently characterized by scanning electron microscopy, infrared spectroscopy (with the second-derivative method), and AM1 and PM3 semi-empirical molecular computational simulations. In this work, our molecular modelling results suggest that pyriteactsas a template for self-assembly of glycine, and it is a potential catalyst for the glycine dimerization of relevance in interstellar space and ancient Earth conditions. A change in the structural complexity of glycine from the α to its γ polymorph when irradiated with UV radiation can be a condition for chemical evolution towards living forms.
The Twin Study of Negative Valence Emotional Constructs
Authors: Carney Dever M. , Moroney Elizabeth , Machlin Laura , Hahn Shannon , Savage Jeanne E. , Lee Minyoung , Towbin Kenneth A. , Brotman Melissa A. , Pine Daniel S. , Leibenluft Ellen , Roberson-Nay Roxann , Hettema John M.
Published: July 2016

The Twin Study of Negative Valence Emotional Constructs is a multi-site study designed to examine the relationship between a broad selection of potential measures designed to assess putative endophenotypes for negative valence systems (NVS) and early symptoms of internalizing disorders (IDs). In this article, we describe the sample characteristics, data collection protocols, and measures used. Pre-adolescent Caucasian twin pairs were recruited through the Mid-Atlantic Twin Registry; data collection began in February of 2013. Enrolled twins completed various dimensional self-report measures along with cognitive, emotional, and psychophysiological tasks designed to assess NVS function. Parents also completed surveys about their twins and themselves. In addition, a subset of the twins also participated in a neuroimaging protocols. Data collection is in the final stages, and preliminary analyses are underway. The findings will potentially expand our understanding of the mechanisms by which genetic and environmental factors contribute to individual differences in NVS phenotypes and provide new insights into underlying risk factors for IDs.
New Geophysical Research Letters Editorial, Revisions Policies
Authors: Diffenbaugh Noah , Beal Lisa , Cardenas M. , Cobb Kim , Cronin Meghan , Dombard Andrew , Ilyina Tatiana , Lavraud Benoit , Newman Andrew , Peterson W. , Ritsema Jeroen , Stroeve Julienne , Thornton Joel , Williams Paul
Published: July 2016

Changes in submittal, editorial, and review policies support high standards and timely publication in the face of the increasing number of papers submitted.
Dehydrogenation of anhydrous methanol at room temperature by o-aminophenol-based photocatalysts
Authors: Wakizaka Masanori , Matsumoto Takeshi , Tanaka Ryota , Chang Ho-Chol
Published: July 2016

Dehydrogenation of anhydrous methanol is of great importance, given its ubiquity as an intermediate for the production of a large number of industrial chemicals. Since dehydrogenation of methanol is an endothermic reaction, heterogeneous or homogeneous precious-metal-based catalysts and high temperatures are usually required for this reaction to proceed. Here we report the photochemical dehydrogenation of anhydrous methanol at room temperature catalysed by o-aminophenol (apH2), o-aminophenolate (apH−) and the non-precious metal complex trans-[FeII(apH)2(MeOH)2]. Under excitation at 289±10 nm and in the absence of additional photosensitizers, these photocatalysts generate hydrogen and formaldehyde from anhydrous methanol with external quantum yields of 2.9±0.15%, 3.7±0.19% and 4.8±0.24%, respectively, which are the highest values reported so far to the best of our knowledge. Mechanistic investigations reveal that the photo-induced formation of hydrogen radicals triggers the reaction.
Magnetic structures and dynamics of multiferroic systems obtained with neutron scattering
Authors: Ratcliff William , Lynn Jeffrey W , Kiryukhin Valery , Jain Prashant , Fitzsimmons Michael R
Published: July 2016

Multiferroics are materials that evince both ferroelectric and magnetic order parameters. These order parameters when coupled can lead to both exciting new physics as well as new device applications. Potential device applications include memory, magnetic field sensors, small antennas and so on. Since Kimura’s discovery of multiferroicity in TbMnO3, there has been a renaissance in the study of these materials. Great progress has been made in both materials discovery and in the theoretical understanding of these materials. In type-II systems the magnetic order breaks the inversion symmetry of the material, driving a secondary ferroelectric phase transition in which the ferroelectric polarisation is exquisitely coupled to the magnetic structure and thus to magnetic field. In type-I systems, the magnetic and ferroelectric orders are established on different sublattices of the material and typically are weakly coupled, but electric field can still drive changes in the magnetisation. Besides single-phase multiferroics, there has been exciting progress in composite heterostructures of multiferroics. Here, we review neutron measurements of prototypical examples of these different approaches to achieving multiferrocity.
Genetic architecture dissection by genome-wide association analysis reveals avian eggshell ultrastructure traits
Authors: Duan Zhongyi , Sun Congjiao , Shen ManMan , Wang Kehua , Yang Ning , Zheng Jiangxia , Xu Guiyun
Published: July 2016

The ultrastructure of an eggshell is considered the major determinant of eggshell quality, which has biological and economic significance for the avian and poultry industries. However, the interrelationships and genome-wide architecture of eggshell ultrastructure remain to be elucidated. Herein, we measured eggshell thickness (EST), effective layer thickness (ET), mammillary layer thickness (MT) and mammillary density (MD) and conducted genome-wide association studies in 927 F2hens. The SNP-based heritabilities of eggshell ultrastructure traits were estimated to be 0.39, 0.36, 0.17 and 0.19 for EST, ET, MT and MD, respectively and a total of 719, 784, 1 and 10 genome-wide significant SNPs were associated with EST, ET, MT and MD, respectively. ABCC9, ITPR2, KCNJ8 and WNK1, which are involved in ion transport, were suggested to be the key genes regulating EST and ET. ITM2C and KNDC1 likely affect MT and MD, respectively. Additionally, there were linear relationships between the chromosome lengths and the variance explained per chromosome for EST (R2 = 0.57) and ET (R2 = 0.67). In conclusion, the interrelationships and genetic architecture of eggshell ultrastructure traits revealed in this study are valuable for our understanding of the avian eggshell and contribute to research on a variety of other calcified shells.
Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system
Authors: VanWormer Elizabeth , Carpenter Tim E , Singh Purnendu , Shapiro Karen , Wallender Wesley W. , Conrad Patricia A. , Largier John L. , Maneta Marco P. , Mazet Jonna A. K.
Published: July 2016

Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals and wildlife.
The p-wave superconductivity in the presence of Rashba interaction in 2DEG
Authors: Weng Ke-Chuan , Hu C. D.
Published: July 2016

We investigate the effect of the Rashba interaction on two dimensional superconductivity. The presence of the Rashba interaction lifts the spin degeneracy and gives rise to the spectrum of two bands. There are intraband and interband pairs scattering which result in the coupled gap equations. We find that there are isotropic and anisotropic components in the gap function. The latter has the form of cos φk where "Equation missing". The former is suppressed because the intraband and the interband scatterings nearly cancel each other. Hence, −the system should exhibit the p-wave superconductivity. We perform a detailed study of electron-phonon interaction for 2DEG and find that, if only normal processes are considered, the effective coupling strength constant of this new superconductivity is about one-half of the s-wave case in the ordinary 2DEG because of the angular average of the additional "Equation missing" in the anisotropic gap function. By taking into account of Umklapp processes, we find they are the major contribution in the electron-phonon coupling in superconductivity and enhance the transition temperature Tc.
DisSim: an online system for exploring significant similar diseases and exhibiting potential therapeutic drugs
Authors: Cheng Liang , Jiang Yue , Wang Zhenzhen , Shi Hongbo , Sun Jie , Yang Haixiu , Zhang Shuo , Hu Yang , Zhou Meng
Published: July 2016

The similarity of pair-wise diseases reveals the molecular relationships between them. For example, similar diseases have the potential to be treated by common therapeutic chemicals (TCs). In this paper, we introduced DisSim, an online system for exploring similar diseases, and comparing corresponding TCs. Currently, DisSim implemented five state-of-the-art methods to measure the similarity between Disease Ontology (DO) terms and provide the significance of the similarity score. Furthermore, DisSim integrated TCs of diseases from the Comparative Toxicogenomics Database (CTD), which can help to identify potential relationships between TCs and similar diseases. The system can be accessed from http://123.59.132.21:8080/DisSim.
Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma
Authors: Koirala Pratistha , Roth Michael E. , Gill Jonathan , Piperdi Sajida , Chinai Jordan M. , Geller David S. , Hoang Bang H. , Park Amy , Fremed Michael A. , Zang Xingxing , Gorlick Richard
Published: July 2016

Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.
Multi-Scale Correlative Tomography of a Li-Ion Battery Composite Cathode
Authors: Moroni Riko , Börner Markus , Zielke Lukas , Schroeder Melanie , Nowak Sascha , Winter Martin , Manke Ingo , Zengerle Roland , Thiele Simon
Published: July 2016

Focused ion beam/scanning electron microscopy tomography (FIB/SEMt) and synchrotron X-ray tomography (Xt) are used to investigate the same lithium manganese oxide composite cathode at the same specific spot. This correlative approach allows the investigation of three central issues in the tomographic analysis of composite battery electrodes: (i) Validation of state-of-the-art binary active material (AM) segmentation: Although threshold segmentation by standard algorithms leads to very good segmentation results, limited Xt resolution results in an AM underestimation of 6 vol% and severe overestimation of AM connectivity. (ii) Carbon binder domain (CBD) segmentation in Xt data: While threshold segmentation cannot be applied for this purpose, a suitable classification method is introduced. Based on correlative tomography, it allows for reliable ternary segmentation of Xt data into the pore space, CBD and AM. (iii) Pore space analysis in the micrometer regime: This segmentation technique is applied to an Xt reconstruction with several hundred microns edge length, thus validating the segmentation of pores within the micrometer regime for the first time. The analyzed cathode volume exhibits a bimodal pore size distribution in the ranges between 0–1 μm and 1–12 μm. These ranges can be attributed to different pore formation mechanisms.
Manipulating Ce Valence in RE2Fe14B Tetragonal Compounds by La-Ce Co-doping: Resultant Crystallographic and Magnetic Anomaly
Authors: Jin Jiaying , Zhang Yujing , Bai Guohua , Qian Zeyu , Wu Chen , Ma Tianyu , Shen Baogen , Yan Mi
Published: July 2016

Abundant and low-cost Ce has attracted considerable interest as a prospective alternative for those critically relied Nd/Pr/Dy/Tb in the 2:14:1-type permanent magnets. The (Nd, Ce)2Fe14B compound with inferior intrinsic magnetic properties to Nd2Fe14B, however, cannot provide an equivalent magnetic performance. Since Ce valence is sensitive to local steric environment, manipulating it towards the favorable trivalent state provides a way to enhance the magnetic properties. Here we report that such a desirable Ce valence can be induced by La-Ce co-doping into [(Pr, Nd)1−x(La, Ce)x]2.14Fe14B (0 ≤ x ≤ 0.5) compounds via strip casting. As verified by X-ray photoelectron spectroscopy results, Ce valence shifts towards the magnetically favorable Ce3+ state in the composition range of x > 0.3, owing to the co-doping of large radius La3+ into 2:14:1 phase lattice. As a result, both crystallographic and magnetic anomalies are observed in the same vicinity of x = 0.3, above which lattice parameters a and c and saturation magnetization Ms increase simultaneously. Over the whole doping range, 2:14:1 tetragonal structure forms and keeps stable even at 1250 K. This finding may shed light on obtaining a favorable Ce valence via La-Ce co-doping, thus maintaining the intrinsic magnetic properties of 2:14:1-type permanent magnets.
Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
Authors: Xu Zheng , Wang Shudong , Ji Honglei , Zhang Zhiguo , Chen Jing , Tan Yi , Wintergerst Kupper , Zheng Yang , Sun Jian , Cai Lu
Published: July 2016

To develop a clinic-relevant protocol for systemic up-regulation of NFE2-related factor 2 (Nrf2) to prevent diabetic cardiomyopathy (DCM), male db/db and age-matched wild-type (WT) mice were given sulforaphane (SFN, an Nrf2 activator) and its natural source, broccoli sprout extract (BSE) by gavage every other day for 3 months, with four groups: vehicle (0.1 ml/10 g), BSE-low dose (estimated SFN availability at 0.5 mg/kg), BSE-high dose (estimated SFN availability at 1.0 mg/kg) and SFN (0.5 mg/kg). Cardiac function and pathological changes (hypertrophy, fibrosis, inflammation and oxidative damage) were assessed by echocardiography and histopathological examination along with Western blot and real-time PCR, respectively. Both BSE and SFN significantly prevented diabetes-induced cardiac dysfunction, hypertrophy and fibrosis. Mechanistically, BSE, like SFN, significantly up-regulated Nrf2 transcriptional activity, evidenced by the increased Nrf2 nuclear accumulation and its downstream gene expression. This resulted in a significant prevention of cardiac oxidative damage and inflammation. For all these preventive effects, BSE at high dose provided a similar effect as did SFN. These results indicated that BSE at high dose prevents DCM in a manner congruent with SFN treatment. Therefore, it suggests that BSE could potentially be used as a natural and safe treatment against DCM via Nrf2 activation.
Recruitment of Arabidopsis RNA Helicase AtRH9 to the Viral Replication Complex by Viral Replicase to Promote Turnip Mosaic Virus Replication
Authors: Li Yinzi , Xiong Ruyi , Bernards Mark , Wang Aiming
Published: July 2016

Positive-sense RNA viruses have a small genome with very limited coding capacity and are highly dependent on host components to fulfill their life cycle. Recent studies have suggested that DEAD-box RNA helicases play vital roles in many aspects of RNA metabolism. To explore the possible role of the RNA helicases in viral infection, we used the Turnip mosaic virus (TuMV)-Arabidopsis pathosystem. The Arabidopsis genome encodes more than 100 putative RNA helicases (AtRH). Over 41 Arabidopsis T-DNA insertion mutants carrying genetic lesions in the corresponding 26 AtRH genes were screened for their requirement in TuMV infection. TuMV infection assays revealed that virus accumulation significantly decreased in the Arabidopsis mutants of three genes, AtRH9, AtRH26 and PRH75. In the present work, AtRH9 was further characterized. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays showed that AtRH9 interacted with the TuMV NIb protein, the viral RNA-dependent RNA polymerase. Moreover, the subcellular distribution of AtRH9 was altered in the virus-infected cells and AtRH9 was recruited to the viral replication complex. These results suggest that Arabidopsis AtRH9 is an important component of the TuMV replication complex, possibly recruited via its interaction with NIb.
Direct observation of the Dirac nodes lifting in semimetallic perovskite SrIrO3 thin films
Authors: Liu Z. T. , Li M. Y. , Li Q. F. , Liu J. S. , Li W. , Yang H. F. , Yao Q. , Fan C. C. , Wan X. G. , Wang Z. , Shen D. W.
Published: July 2016

Perovskite SrIrO3 has long been proposed as an exotic semimetal induced by the interplay between the spin-orbit coupling and electron correlations. However, its low-lying electronic structure is still lacking. We synthesize high-quality perovskite SrIrO3 (100) films by means of oxide molecular beam epitaxy, and then systemically investigate their low energy electronic structure using in-situ angle-resolved photoemission spectroscopy. We find that the hole-like bands around R and the electron-like bands around U(T) intersect the Fermi level simultaneously, providing the direct evidence of the semimetallic ground state in this compound. Comparing with the density functional theory, we discover that the bandwidth of states near Fermi level is extremely small, and there exists a pronounced mixing between the Jeff = 1/2 and Jeff = 3/2 states. Moreover, our data reveal that the predicted Dirac degeneracy protected by the mirror-symmetry, which was theoretically suggested to be the key to realize the non-trivial topological properties, is actually lifted in perovskite SrIrO3 thin films. Our findings pose strong constraints on the current theoretical models for the 5d iridates.
Mouse aldehyde-oxidase-4 controls diurnal rhythms, fat deposition and locomotor activity
Authors: Terao Mineko , Barzago Maria Monica , Kurosaki Mami , Fratelli Maddalena , Bolis Marco , Borsotti Andrea , Bigini Paolo , Micotti Edoardo , Carli Mirjana , Invernizzi Roberto William , Bagnati Renzo , Passoni Alice , Pastorelli Roberta , Brunelli Laura , Toschi Ivan , Cesari Valentina , Sanoh Seigo , Garattini Enrico
Published: July 2016

Aldehyde-oxidase-4 (AOX4) is one of the mouse aldehyde oxidase isoenzymes and its physiological function is unknown. The major source of AOX4 is the Harderian-gland, where the enzyme is characterized by daily rhythmic fluctuations. Deletion of the Aox4 gene causes perturbations in the expression of the circadian-rhythms gene pathway, as indicated by transcriptomic analysis. AOX4 inactivation alters the diurnal oscillations in the expression of master clock-genes. Similar effects are observed in other organs devoid of AOX4, such as white adipose tissue, liver and hypothalamus indicating a systemic action. While perturbations of clock-genes is sex-independent in the Harderian-gland and hypothalamus, sex influences this trait in liver and white-adipose-tissue which are characterized by the presence of AOX isoforms other than AOX4. In knock-out animals, perturbations in clock-gene expression are accompanied by reduced locomotor activity, resistance to diet induced obesity and to hepatic steatosis. All these effects are observed in female and male animals. Resistance to obesity is due to diminished fat accumulation resulting from increased energy dissipation, as white-adipocytes undergo trans-differentiation towards brown-adipocytes. Metabolomics and enzymatic data indicate that 5-hydroxyindolacetic acid and tryptophan are novel endogenous AOX4 substrates, potentially involved in AOX4 systemic actions.
Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine
Authors: Wei Yandi , Qi Lu , Gao Huijie , Sun Honglei , Pu Juan , Sun Yipeng , Liu Jinhua
Published: July 2016

To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus–specific CD4+ and CD8+ T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens.
High-yield cell-free synthesis of human EGFR by IRES-mediated protein translation in a continuous exchange cell-free reaction format
Authors: Quast Robert B. , Sonnabend Andrei , Stech Marlitt , Wüstenhagen Doreen A. , Kubick Stefan
Published: July 2016

Cell-free protein synthesis systems derived from eukaryotic sources often provide comparatively low amounts of several μg per ml of de novo synthesized membrane protein. In order to overcome this, we herein demonstrate the high-yield cell-free synthesis of the human EGFR in a microsome-containing system derived from cultured Sf21 cells. Yields were increased more than 100-fold to more than 285 μg/ml by combination of IRES-mediated protein translation with a continuous exchange cell-free reaction format that allowed for prolonged reaction lifetimes exceeding 24 hours. In addition, an orthogonal cell-free translation system is presented that enabled the site-directed incorporation of p-Azido-L-phenylalanine by amber suppression. Functionality of cell-free synthesized receptor molecules is demonstrated by investigation of autophosphorylation activity in the absence of ligand and interaction with the cell-free synthesized adapter molecule Grb2.
Wide-Band Spatially Tunable Photonic Bandgap in Visible Spectral Range and Laser based on a Polymer Stabilized Blue Phase
Authors: Lin Jia-De , Wang Tsai-Yen , Mo Ting-Shan , Huang Shuan-Yu , Lee Chia-Rong
Published: July 2016

This work successfully develops a largely-gradient-pitched polymer-stabilized blue phase (PSBP) photonic bandgap (PBG) device with a wide-band spatial tunability in nearly entire visible region within a wide blue phase (BP) temperature range including room temperature. The device is fabricated based on the reverse diffusion of two injected BP-monomer mixtures with a low and a high chiral concentrations and afterwards through UV-curing. This gradient-pitched PSBP can show a rainbow-like reflection appearance in which the peak wavelength of the PBG can be spatially tuned from the blue to the red regions at room temperature. The total tuning spectral range for the cell is as broad as 165 nm and covers almost the entire visible region. Based on the gradient-pitched PSBP, a spatially tunable laser is also demonstrated in this work. The temperature sensitivity of the lasing wavelength for the laser is negatively linear and approximately −0.26 nm/°C. The two devices have a great potential for use in applications of photonic devices and displays because of their multiple advantages, such as wide-band tunability, wide operated temperature range, high stability and reliability, no issue of hysteresis, no need of external controlling sources and not slow tuning speed (mechanically).
A novel peptide ADAM8 inhibitor attenuates bronchial hyperresponsiveness and Th2 cytokine mediated inflammation of murine asthmatic models
Authors: Chen Jun , Deng Linhong , Dreymüller Daniela , Jiang Xuemei , Long Jiaoyue , Duan Yiyuan , Wang Yue , Luo Mingzhi , Lin Feng , Mao Lizhen , Müller Bernd , Koller Garrit , Bartsch Jörg W.
Published: July 2016

A disintegrin and metalloproteinase 8 (ADAM8) has been identified as a signature gene associated with moderate and severe asthma. Studies in mice have demonstrated that the severity of asthma can be reduced by either transgenic knock-out or by antibodies blocking ADAM8 function, highlighting ADAM8 as potential drug target for asthma therapy. Here, we examined the therapeutic effect of an ADAM8 inhibitor peptide (BK-1361) that specifically blocks cellular ADAM8 activity in ovalbumin-sensitized and challenged Balb/c mice. We found that BK-1361 (25 μg/g body weight) attenuated airway responsiveness to methacholine stimulation by up to 42%, concomitantly reduced tissue remodeling by 50% and decreased inflammatory cells (e.g. eosinophils down by 54%)/inflammatory factors (e.g. sCD23 down by 50%)/TH2 cytokines (e.g. IL-5 down by 70%)/ADAM8-positive eosinophils (down by 60%) in the lung. We further verified that BK-1361 specifically targets ADAM8 in vivo as the peptide caused significantly reduced levels of soluble CD23 in wild-type but not in ADAM8-deficient mice. These findings suggest that BK-1361 blocks ADAM8-dependent asthma effects in vivo by inhibiting infiltration of eosinophils and TH2 lymphocytes, thus leading to reduction of TH2-mediated inflammation, tissue remodeling and bronchial hyperresponsiveness. Taken together, pharmacological ADAM8 inhibition appears as promising novel therapeutic strategy for the treatment of asthma.
A novel approach to estimate the eruptive potential and probability in open conduit volcanoes
Authors: De Gregorio Sofia , Camarda Marco
Published: July 2016

In open conduit volcanoes, volatile-rich magma continuously enters into the feeding system nevertheless the eruptive activity occurs intermittently. From a practical perspective, the continuous steady input of magma in the feeding system is not able to produce eruptive events alone, but rather surplus of magma inputs are required to trigger the eruptive activity. The greater the amount of surplus of magma within the feeding system, the higher is the eruptive probability.Despite this observation, eruptive potential evaluations are commonly based on the regular magma supply and in eruptive probability evaluations, generally any magma input has the same weight. Conversely, herein we present a novel approach based on the quantification of surplus of magma progressively intruded in the feeding system. To quantify the surplus of magma, we suggest to process temporal series of measurable parameters linked to the magma supply. We successfully performed a practical application on Mt Etna using the soil CO2 flux recorded over ten years.
Entanglement as a resource to distinguish orthogonal product states
Authors: Zhang Zhi-Chao , Gao Fei , Cao Tian-Qing , Qin Su-Juan , Wen Qiao-Yan
Published: July 2016

It is known that there are many sets of orthogonal product states which cannot be distinguished perfectly by local operations and classical communication (LOCC). However, these discussions have left the following open question: What entanglement resources are necessary and/or sufficient for this task to be possible with LOCC? In m ⊗ n, certain classes of unextendible product bases (UPB) which can be distinguished perfectly using entanglement as a resource, had been presented in 2008. In this paper, we present protocols which use entanglement more efficiently than teleportation to distinguish some classes of orthogonal product states in m ⊗ n, which are not UPB. For the open question, our results offer rather general insight into why entanglement is useful for such tasks and present a better understanding of the relationship between entanglement and nonlocality.
Relation between admission plasma fibrinogen levels and mortality in Chinese patients with coronary artery disease
Authors: Peng Yong , Wang Hua , Li Yi-ming , Huang Bao-tao , Huang Fang-yang , Xia Tian-li , Chai Hua , Wang Peng-ju , Liu Wei , Zhang Chen , Chen Mao , Huang De-jia
Published: July 2016

Fibrinogen (Fib) was considered to be a potential risk factor for the prognosis of patients with coronary artery disease (CAD), but there was lack of the evidence from Chinese contemporary population. 3020 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 2 categories by the optimal Fib cut-off value (3.17 g/L) for all-cause mortality prediction. The end points were all-cause mortality and cardiac mortality. Cumulative survival curves showed that the risk of all-cause mortality was significantly higher in patients with Fib ≥3.17 g/L compared to those with Fib <3.17 g/L (mortality rate, 11.5% vs. 5.7%, p < 0.001); and cardiovascular mortality obtained results similar to those mentioned above (cardiac mortality rate, 5.9% vs. 3.6%, p = 0.002). Subgroup analysis showed that elevated Fib levels were predictive for the risk of all-cause mortality in the subgroups according to age, medical history and diagnosis. COX multivariate regression analysis showed that plasma Fib levels remained independently associated with all-cause mortality after adjustment for multiple cardiovascular risk factors (all-cause mortality, HR 2.01, CI 1.51–2.68, p < 0.001). This study has found that Fib levels were independently associated with the mortality risk in Chinese CAD patients.