bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obsessive compulsive disorder: Opportunities within and beyond the serotonergic domain
Authors: Zohar J. , Sasson Y. 
Published: July 2016

Abnormality of the serotonin (5-hydroxytryptamine – 5-HT) system and particularly hypersensitivity of postsynaptic 5-HT receptors remained the leading hypothesis for the underlying pathophysiology of obsessive compulsive disorder (OCD) during the 1980s. A number of lines of evidence supported this serotonergic hypothesis, not least the treatment studies which demonstrated clearly and consistently that anti-obsessional efficacy was a function of serotonin re-uptake inhibition. Studies of markers and biological probes provided further evidence: platelet studies, for example, linked reductions in 5-HT activity with clinical response, and treatment response was correlated with decreased 5-hydroxyindolacetic acid (5-HIAA) levels within the cerebrospinal fluid of OCD patients.Added to this was the evidence from the behavioral or physiological responses observed following serotonergic challenge with the serotonin agonists meta-chlorophenylpiperazine, a compound with high affinity for 5-HT1A-, 5-HT1D- and 5-HT2C-receptors.
The role of the ‘central’ cholecystokinin-B receptor in panic disorder
Authors: Megen H.J.G.M. Van , Westenberg H.G.M. , Boer J.A. Den 
Published: July 2016

SummaryResearch investigating the neurobiological underpinnings of anxiety disorder have mainly been focused on dysfunction of the GABA, noradrenergic and serotonergic (5-HT) neuronal systems. Just recently, in both animal and human studies, evidence has been found for a possible role of the cholecystokinin (CCK) neuronal system in the pathogenesis of anxiety disorder.Behaviorally, animal studies revealed anxiogenic-like properties for the ‘central’ CCKB receptor agonists, while CCKB receptor antagonists displayed intrinsic anxiolytic properties. Similarly, in man, CCKB receptor agonists, like pentagastrin and CCK4, were found to be able to elicited panic attacks in both panic disorder (PD) patients and healthy volunteers. These effects appear due to stimulation of the CCKB receptor. In addition, clinically effective panicolytic agents reduce the sensitivity to CCK4 in PD patients. Taken together, these findings may suggest a role for CCK in the neurobiology of PD. On the other hand, there is circumstantial evidence for involvement of several other neuronal systems, such as the serotonergic, noradrenergic and GABA-ergic system, in the regulation of anxiety. Interestingly, evidence has been found for an interaction between CCK and 5-HT and that this interaction plays a role in the mediation of anxiety.This presentation will critically discuss the evidence for the role of the CCKB receptor in anxiety and in addition, will focus on the putative evidence that the role of CCK in anxiety is mediated by its interaction with the serotonergic neuronal system.
Benzodiazepinen in perspectief (I): De GABAA-benzodiazepine-receptor
Authors: Vermeulen P.J.L. , Zitman F.G. 
Published: July 2016

SummaryIn this first part of a review on recent insights into the structure and function of the γ-aminobuty rie acid type A - benzodiazepine receptor system, the γ-aminobutyric acid type A (GABAA) receptor and the different types of benzodiazepine (BDZ) receptors known at this moment are dicussed. GABAA- and BDZ receptors are coupled in a supramolecular GABAA-BDZ-ionophore receptor complex, each consisting of five acidic glycoprotein molecules called subunits. These subunits can be classified into five groups: α, β, γ, σ and ρ. Present evidence indicates the existence of multiple subtypes of these subunits. Multiple GABAA-BDZ receptors exist in the brain that show differential distribution and developmental patterns. These receptors differ from their subunit composition. The final functional properties of the receptor are determined by the different subunits constituting this receptor. Heterogeneity among α- subunits may determine the diversity of BDZ pharmacology in different regions of the nervous system.
The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses
Authors: Werf Y.D. Van Der , Jongste M.J.L. De , Horst G.J. Ter 
Published: July 2016

SummaryIn this investigation the effects of immune activation on the brain are characterized. In order to study this, we used a model for chronic immune activation, the myocardial infarction, and intravenous injections with the pro-inflammatory cytokine Tumour Necrosis Factor alpha (TNF-α). The incentive for this study is the observation that myocardial infarction is accompanied by behavioural and neuronal abnormalities. The effects of myocardial infarction on the brain and its functioning are widespread. In order to examine the mechanism through which this interaction occurs, a group of rats underwent an experimentally induced myocardial infarction whereafter immunohistochemistry was performed on slices of the brain. This experiment revealed regional serum protein extravasation, pointing to leakage of the blood-brain barrier. This process occurred in certain cortical, subcortical and hindbrain areas in discrete patches. The leakage was co-localized with the expression of the immune activation marker ICAM-1. A second group of rats was therefore injected with TNF-α, a major pro-inflammatory cytokine, to assess the involvement of the immune system in the effects shown. This procedure rendered the same results. It is concluded that myocardial infarction may interfere with the integrity of the blood-brain barrier and possibly with brain functioning through activation of the immune system. The relevance for pathophysiological processes is discussed.
Melatonine en stemmingsstoornissen
Authors: Beullens J. 
Published: July 2016

SummaryMelatonin is a hormone secreted by the pineal gland mainly during the night. The discovery that this melatonin secretion decreases under the influence of bright light, gave rise to the use of light therapy in some affective disorders. The literature on the relationship between melatonin secretion and mood is reviewed concerning seasonal affective disorder, non-seasonal affective disorder and premenstrual syndrome. Light therapy could reduce an abnormal high melatonin secretion back to normal proportions. None of the affective disorders, however, is accompanied by an unusual high melatonin level. Nevertheless, light therapy as well as other therapies that suppress melatonin have a therapeutic effect. This is not the case with the administration of melatonin. Mood is not affected by extra melatonin in seasonal affective disorder but it is in both other affective disorders. Melatonin plays a part in the pathogenesis of the affective disorders but it is not yet clear which one.
An interpersonal view on depression
Authors: Bouhuys A.L. , Geerts E. , Mersch P.P.A. , Jenner J.A. 
Published: July 2016

Cognitive and behavioural processes may constitute a risk for onset and persistence of depression. People who become depressed frequently show enduring negative cognitions which predispose them to depression. In addition, interpersonal processes are supposed to contribute to the etiology and maintenance of depression. Depression-prone persons are presumed to display deficient or problematic social behaviours that elicit negative reactions in others, finally resulting in withdrawal by family and friends.About 60% of human communication is non-verbal. An ethological approach may therefore contribute to reveal behavioural and cognitive vulnerability factors for depression onset or persistence. Various studies support this presumption: High levels of patients' observed behaviour indicating involvement in the interaction between depressives and clinicians at admission are related with persistence of depression.
Suppressing Electron Exposure Artifacts: An Electron Scanning Paradigm with Bayesian Machine Learning
Authors: Hujsak Karl , Myers Benjamin D. , Roth Eric , Li Yue , Dravid Vinayak P. 
Published: July 2016

AbstractElectron microscopy of biological, polymeric, and other beam-sensitive structures is often hampered by deleterious electron beam interactions. In fact, imaging of such beam-sensitive materials is limited by the allowable radiation dosage rather that capabilities of the microscope itself, which has been compounded by the availability of high brightness electron sources. Reducing dwell times to overcome dose-related artifacts, such as radiolysis and electrostatic charging, is challenging due to the inherently low contrast in imaging of many such materials. These challenges are particularly exacerbated during dynamic time-resolved, fluidic cell imaging, or three-dimensional tomographic reconstruction—all of which undergo additional dosage. Thus, there is a pressing need for the development of techniques to produce high-quality images at ever lower electron doses. In this contribution, we demonstrate direct dose reduction and suppression of beam-induced artifacts through under-sampling pixels, by as much as 80% reduction in dosage, using a commercial scanning electron microscope with an electrostatic beam blanker and a dictionary learning in-painting algorithm. This allows for multiple sparse recoverable images to be acquired at the cost of one fully sampled image. We believe this approach may open new ways to conduct imaging, which otherwise require compromising beam current and/or exposure conditions.
The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux
Authors: Yoshino Seiko , Hara Toshiro , Nakaoka Hiroki J , Kanamori Akane , Murakami Yoshinori , Seiki Motoharu , Sakamoto Takeharu 
Published: July 2016

AbstractLoss of anchorage to the extracellular matrix leads to apoptosis (anoikis) in normal cells, but cancerous cells are usually resistant to such stress. Here we report the pivotal role of an E3 ubiquitin ligase, ring-finger protein 126 (RNF126), in the resistance of cancer cells to the stress associated with non-adherent conditions. Non-adherent cancer cells exhibited increased flux through the tricarboxylic acid cycle via increased conversion of pyruvate to acetyl-CoA. RNF126 was found to act as a ubiquitin ligase for pyruvate dehydrogenase kinases (PDKs), resulting in their proteasomal degradation. This decrease in PDK levels allowed pyruvate dehydrogenases to catalyze the conversion of pyruvate to acetyl-CoA. Moreover, depletion of RNF126 or increased expression of PDK1 in cancer cells suppressed colony formation in soft agar as well as tumorigenicity in mice. RNF126 expression in cancer cells was found to be under the control of the extracellular signal-regulated kinase signaling pathway, which is essential for anoikis resistance. Thus, RNF126 is an attractive molecule for treating cancer by selectively targeting anchorage-independent growth.
Healthy ageing of cloned sheep
Authors: Sinclair K. D. , Corr S. A. , Gutierrez C. G. , Fisher P. A. , Lee J.-H. , Rathbone A. J. , Choi I. , Campbell K. H. S. , Gardner D. S. 
Published: July 2016

AbstractThe health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental long-term health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7–9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5-and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals.
Dengue virus infection induces interferon-lambda1 to facilitate cell migration
Authors: Hsu Yu-Lin , Wang Mei-Yi , Ho Ling-Jun , Lai Jenn-Haung 
Published: July 2016

AbstractA marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-λ1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-λ1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-κB). Blocking interaction between IFN-λ1 and its receptor IFN-λR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-λ1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-λ1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection.
ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
Authors: Wee Boyoung , Pietras Alexander , Ozawa Tatsuya , Bazzoli Elena , Podlaha Ondrej , Antczak Christophe , Westermark Bengt , Nelander Sven , Uhrbom Lene , Forsberg-Nilsson Karin , Djaballah Hakim , Michor Franziska , Holland Eric C. 
Published: July 2016

AbstractGlioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.
The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy
Authors: Zhao Tingting , Xu Zhi , Gu Dongying , Wu Peng , Huo Xinying , Wei Xiaowei , Tang Yongfei , Gong Weida , He Ming-Liang , Chen Jinfei 
Published: July 2016

Abstract5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU treatment and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted. In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased death risk, however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes. TS 5′-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU. And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3′-UTR DD + DI and TS 5′-UTR 2R3R + 3R3R genotypes. Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5′-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU.
Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1
Authors: Kawaguchi Kosuke , Okamoto Takumi , Morita Masashi , Imanaka Tsuneo 
Published: July 2016

AbstractWe previously demonstrated that ABCD4 does not localize to peroxisomes but rather, the endoplasmic reticulum (ER), because it lacks the NH2-terminal hydrophilic region required for peroxisomal targeting. It was recently reported that mutations in ABCD4 result in a failure to release vitamin B12 from lysosomes. A similar phenotype is caused by mutations in LMBRD1, which encodes the lysosomal membrane protein LMBD1. These findings suggested to us that ABCD4 translocated from the ER to lysosomes in association with LMBD1. In this report, it is demonstrated that ABCD4 interacts with LMBD1 and then localizes to lysosomes and this translocation depends on the lysosomal targeting ability of LMBD1. Furthermore, endogenous ABCD4 was localized to both lysosomes and the ER and its lysosomal localization was disturbed by knockout of LMBRD1. To the best of our knowledge, this is the first report demonstrating that the subcellular localization of the ABC transporter is determined by its association with an adaptor protein.
Reversible “triple-Q” elastic field structures in a chiral magnet
Authors: Hu Yangfan , Wang Biao 
Published: July 2016

AbstractThe analytical solution of the periodic elastic fields in chiral magnets caused by presence of periodically distributed eigenstrains is obtained. For the skyrmion phase, both the periodic displacement field and the stress field are composed of three “triple-Q” structures with different wave numbers. The periodic displacement field, obtained by combining the three “triple-Q” displacement structures, is found to have the same lattice vectors with the magnetic skyrmion lattice. We find that for increasing external magnetic field, one type of “triple-Q” displacement structure and stress structure undergo a “configurational reversal”, where the initial and the final field configuration share similar pattern but with opposite direction of all the field vectors. The solution obtained is of fundamental significance for understanding the emergent mechanical properties of skyrmions in chiral magnets.
Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation
Authors: Yang Zijiang , Concannon John , Ng Kelvin S. , Seyb Kathleen , Mortensen Luke J. , Ranganath Sudhir , Gu Fangqi , Levy Oren , Tong Zhixiang , Martyn Keir , Zhao Weian , Lin Charles P. , Glicksman Marcie A. , Karp Jeffrey M. 
Published: July 2016

AbstractPre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.
Hospitalizations from Hypertensive Diseases, Diabetes, and Arrhythmia in Relation to Low and High Temperatures: Population-Based Study
Authors: Bai Li , Li Qiongsi , Wang Jun , Lavigne Eric , Gasparrini Antonio , Copes Ray , Yagouti Abderrahmane , Burnett Richard T. , Goldberg Mark S. , Villeneuve Paul J. , Cakmak Sabit , Chen Hong 
Published: July 2016

AbstractLittle is known about the extent to which ambient temperatures contribute to the burden of hospitalizations from hypertensive diseases, diabetes, and arrhythmia. To fill this knowledge gap, we conducted a time-series study comprising entire population of Ontario, Canada during 1996–2013. A distributed lag non-linear model was developed to estimate the cumulative effect of temperatures over a 21-day lag period. We computed the burden of hospitalizations attributable to cold and heat. Furthermore, we separated the burden into components related to mild and extreme temperatures. Compared to the temperature with minimum risk of morbidity, cold temperatures (1st percentile) were associated with a 37% (95% confidence interval: 5%, 78%) increase in hypertension-related hospitalizations whereas no significant association with hot temperatures (99th percentile) was observed. Cold and hot temperatures were also associated with a 12% (1%, 24%) and a 30% (6%, 58%) increase in diabetes-related hospitalizations, respectively. Arrhythmia was not linked to temperatures. These estimates translate into ~10% of hypertension-related hospitalizations attributable to total cold, and ~9% from mild cold. Similarly, ~11% of diabetes-related hospitalizations were due to total heat, virtually all of which were from mild heat. In conclusion, ambient temperatures, especially in moderate ranges, contribute to excess hospitalizations from hypertension and diabetes.
Giant quantum Hall plateaus generated by charge transfer in epitaxial graphene
Authors: Alexander-Webber J. A. , Huang J. , Maude D. K. , Janssen T. J. B. M. , Tzalenchuk A. , Antonov V. , Yager T. , Lara-Avila S. , Kubatkin S. , Yakimova R. , Nicholas R. J. 
Published: July 2016

AbstractEpitaxial graphene has proven itself to be the best candidate for quantum electrical resistance standards due to its wide quantum Hall plateaus with exceptionally high breakdown currents. However one key underlying mechanism, a magnetic field dependent charge transfer process, is yet to be fully understood. Here we report measurements of the quantum Hall effect in epitaxial graphene showing the widest quantum Hall plateau observed to date extending over 50 T, attributed to an almost linear increase in carrier density with magnetic field. This behaviour is strong evidence for field dependent charge transfer from charge reservoirs with exceptionally high densities of states in close proximity to the graphene. Using a realistic framework of broadened Landau levels we model the densities of donor states and predict the field dependence of charge transfer in excellent agreement with experimental results, thus providing a guide towards engineering epitaxial graphene for applications such as quantum metrology.