bluuebunny/crossref_metadata_2025 huggingface dataset:
George Eliot's Estuarial Form
Authors: McAuley Kyle
Published: February 2020

This essay recasts the central locale ofThe Mill on the Flossin order to show how the geography and society of George Eliot's novel function together as a conjoined ecological system. I show that the port at St. Ogg's is set on an estuary, and from this observation, I claim that the entanglement of multiple estuarial waters provides a formal model for the overall ecology of the novel. Referring to this system as “ecological form,” the essay shows how the characters’ misunderstanding of the estuarial nature of the St. Ogg's hydrography is the primary source of the communal divisions with which the novel is so famously riven. In so doing, this essay makes two methodological interventions, one local, and one slightly more global. In the first, I show how unsticking the progression of our criticism from that of a novel's plot—especially one with such a catastrophically strong telos asMill’s—can allow us to view form and, particularly, geography as newly vital to literary history. This leads to the second intervention, in which I suggest that reading practices in an age of environmental collapse should look beyond disaster itself and toward affected communities’ systemic ties to those extraneous systems—economic, legal, imperial—that aid and abet disasters elsewhere and even ignore the potential for catastrophic reoccurrence in the near future. In other words, reading for water readily yields a wide-ranging map of global capitalism perhaps unexpectedly centered on a small town in Lincolnshire.
Pulpy Fiction
Authors: Mershon Ella
Published: February 2020

Taking a long view of mycological history, this essay considers how studies of fungal life have modeled fugitive, cryptic, and queer forms of belonging that open the body and the body politic to modes of collectivity that trouble the equation of ecology with holistic closure. Turning to Arthur Machen'sThe Hill of Dreams, this essay shows how the geographies of desire and belonging created through fungal intimacies make it impossible to speak of either the self-contained individual or ecology in the singular. Open and plural, selves and worlds proliferate, contaminate, and interpenetrate through the infectious touch of fungal relations.
A Discussion of Avidit Acharya, Matthew Blackwell, and Maya Sen’sDeep Roots: How Slavery Still Shapes Southern Politics
Authors: McKee Seth C.
Published: February 2020

If the election of Donald Trump has proven anything indisputably, it is that the notion of America as a “postracial” society in the aftermath of the Obama presidency is a canard. Yet how should we understand the specific pattern of race’s persistent salience in US politics? InDeep Roots, Avidit Acharya, Matthew Blackwell, and Maya Sen argue that it is the long legacy of chattel slavery that continues to shape politics in the US South in distinctive fashion. Comparing regions that were once marked by slavery with those that were not, the authors develop the concept of “behavioral path dependence” to describe the production and reproduction of a political culture marked by intergenerational racial prejudice. They argue that this legacy continues to shape US politics today in a fashion that is both understandable and predictable with the tools of empirical political science. We asked several scholars with expertise on politics and race, US political development, and political behavior to address this controversial argument.
Embryonic exposures to mono-2-ethylhexyl phthalate induce larval steatosis in zebrafish independent of Nrf2a signaling
Authors: Sant Karilyn E. , Moreau Hadley M. , Williams Larissa M. , Jacobs Haydee M. , Bowsher Anna M. , Boisvert Jason D. , Smolowitz Roxanna M. , Pantazis Jacob , Annunziato Kate , Nguyen Malina , Timme-Laragy Alicia
Published: February 2020

Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type andnrf2amutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha targetfabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.
Measuring Simultaneous Emotions: Existing Problems and a New Way Forward
Authors: Rhodes-Purdy Matthew , Navarre Rachel , Utych Stephen M.
Published: February 2020

Studies on discrete emotions typically work to evoke one emotion at a time. Yet many political phenomena cause multiple emotions. Threats, for example, cause, anger, and fear, have diametrically opposing behavioral consequences. As a result, the effect of experimental treatments can be masked by the countervailing influence of emotions with similar affect. This issue is exacerbated by existing measures of negative emotions, such as the Positive and Negative Affect Schedule (PANAS). We show that the PANAS is contaminated by systematic measurement error, as negative affect produced by one emotion influences responses on the other. To overcome this, we develop an alternative version of the PANAS that allows respondents to select which emotions they are feeling, then rate the severity. This technique accurately captures respondent’s emotional reactions, reducing measurement error and thus decreasing the correlation between fear and anger. The tactics we developed have broad relevance for experimental researchers analyzing emotional responses to politics.
The Tensor‐based Feature Analysis of Spatiotemporal Field Data With Heterogeneity
Authors: Li Dongshuang , Yu Zhaoyuan , Wu Fan , Luo Wen , Hu Yong , Yuan Linwang
Published: February 2020

Heterogeneity is an essential characteristic of the geographic phenomenon. However, most existing researches concerning heterogeneity are based on the matrix. The bidimensional nature of the matrix cannot well support the multidimensional analysis of spatiotemporal field data. Here, we introduce an improved tensor‐based feature analysis method for spatiotemporal field data with heterogeneous variation, by utilizing the similarity measurement in multidimensional space and feature capture of tensor decomposition. In this method, the heterogeneous spatiotemporal field data are reorganized first according to the similarity and difference within the data. The feature analysis by integrating the spatiotemporal coupling is then obtained by tensor decomposition. Since the reorganized data have a more consistent internal structure than original data, the feature analysis bias caused by heterogeneous variation in tensor decomposition can be effectively avoided. We demonstrate our method based on the climatic reanalysis field data released by the National Oceanic and Atmospheric Administration. The comparison with conventional tensor decomposition showed that the proposed method can approximate the original data more accurately both in global and local regions. Especially in the area influenced by the complex modal aliasing and in the period time of the climatic anomaly events, the approximation accuracy can be significantly improved. The proposed method can also reveal the zonal variation of temperature gradient and abnormal variations of air temperature ignored in the conventional tensor method.
Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case–control plasma proteomics study
Authors: Manousopoulou Antigoni , Abad Fatma S. , Garay-Baquero Diana J. , Birch Brian R. , van Rijn Bas B. , Lwaleed Bashir A. , Garbis Spiros D.
Published: February 2020

Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case–control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann–Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE.
Stress adaptation is associated with insulin resistance in women with gestational diabetes mellitus
Authors: Feng Yan , Feng Qi , Qu Hongmei , Song Xinna , Hu Jianwei , Xu Xiaomeng , Zhang Li , Yin Shaohua
Published: February 2020

Aim

Oxidative stress is known to increase the risk of insulin resistance (IR). The aim of this study was to investigate the association between stress hormones and IR in women with gestational diabetes mellitus (GDM), in an attempt to gain insights into the pathogenesis of GDM.

Methods

Recruited in this study were 70 GDM women and 70 healthy pregnant women as control. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), plasma epinephrine (E), noradrenaline (NE), glucagon, and cortisol levels were detected. IR was assessed by homeostasis model assessment of IR (HOMA-IR) in both groups. Correlations among stress hormones, oxidative stress, and IR were analyzed by Pearson’s correlation after log transformation.

Results

Compared with the Control group, MDA was increased and anti-oxidative enzymes SOD and GSH were decreased significantly in the GDM group. Glucagon, E, and NE in the GDM group were increased by 22.42%, 36.82%, and 35.09%, respectively, as compared with those in the Control group. MDA showed a significant positive correlation, and SOD showed a negative correlation with HOMA-IR in the GDM group. In addition, HOMA-IR was positively related to glucagon, E, NE, and cortisol.

Conclusions

Elevation of stress hormones and stress adaptation disturbance may be associated with the pathogenesis of GDM in pregnant women.
EGFRvIII upregulates DNA mismatch repair resulting in increased temozolomide sensitivity of MGMT promoter methylated glioblastoma
Authors: Struve Nina , Binder Zev A. , Stead Lucy F. , Brend Tim , Bagley Stephen J. , Faulkner Claire , Ott Leonie , Müller-Goebel Justus , Weik Anna-Sophie , Hoffer Konstantin , Krug Leonie , Rieckmann Thorsten , Bußmann Lara , Henze Marvin , Morrissette Jennifer J. D. , Kurian Kathreena M. , Schüller Ulrich , Petersen Cordula , Rothkamm Kai , O´ Rourke Donald M. , Short Susan C. , Kriegs Malte
Published: February 2020

The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR.
Correction: Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development
Authors: Breen Michael S. , Bierer Linda M. , Daskalakis Nikolaos P. , Bader Heather N. , Makotkine Iouri , Chattopadhyay Mitali , Xu Changxin , Grice Ariela Buxbaum , Tocheva Anna S. , Flory Janine D. , Buxbaum Joseph D. , Meaney Michael J. , Brennand Kristen , Yehuda Rachel
Published: February 2020

This Article was originally published without the correct Supplemental Table file (Table S1 was missing). In total, there are seven Supplemental Tables, and six were in the original submission. Furthermore, Fig. 1 was misplaced in the main text; it was embedded in the manuscript file even before the results section. Both issues have now been fixed in the HTML and PDF versions of this Article.
Genomic prediction of alcohol-related morbidity and mortality
Authors: Kiiskinen Tuomo , Mars Nina J. , Palviainen Teemu , Koskela Jukka , Rämö Joel T. , Ripatti Pietari , Ruotsalainen Sanni ,   FinnGen, GSCAN Consortium, Palotie Aarno , Madden Pamela A. F. , Rose Richard J. , Kaprio Jaakko , Salomaa Veikko , Mäkelä Pia , Havulinna Aki S. , Ripatti Samuli
Published: February 2020

While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85–12.58 g, p = 2.3 × 10–58). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66–2.01, p = 1.6 × 10–36). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive baseline data from prospective cohorts, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI = 1.26–1.99, p = 8.2 × 10–5). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI = 1.20–1.47, p = 4.5 × 10–8) in the adjusted model. In conclusion, the PRS for alcohol consumption independently associates for both alcohol-related morbidity and all-cause mortality. Together, these findings underline the importance of heritable factors in alcohol-related health burden while highlighting how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.
Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders
Authors: Erli Filippo , Palmos Alish B. , Raval Pooja , Mukherjee Jayanta , Sellers Katherine J. , Gatford Nicholas J. F. , Moss Stephen J. , Brandon Nicholas J. , Penzes Peter , Srivastava Deepak P.
Published: February 2020

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17β-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia 1 (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number.
Delayed sleep timing and circadian rhythms in pregnancy and transdiagnostic symptoms associated with postpartum depression
Authors: Obeysekare Jessica L. , Cohen Zachary L. , Coles Meredith E. , Pearlstein Teri B. , Monzon Carmen , Flynn E. Ellen , Sharkey Katherine M.
Published: February 2020

Later sleep timing, circadian preference, and circadian rhythm timing predict worse outcomes across multiple domains, including mood disorders, substance use, impulse control, and cognitive function. Disturbed sleep is common among pregnant and postpartum women. We examined whether sleep timing during third trimester of pregnancy predicted postpartum symptoms of mania, depression, and obsessive-compulsive disorder (OCD). Fifty-one women with a previous, but not active, episode of unipolar or bipolar depression had symptoms evaluated and sleep recorded with wrist actigraphy at 33 weeks of gestation and 2, 6, and 16 weeks postpartum. Circadian phase was measured in a subset of women using salivary dim light melatonin onset (DLMO). We divided the sample into “early sleep” and “late sleep” groups using average sleep onset time at 33 weeks of gestation, defined by the median-split time of 11:27 p.m. The “late sleep” group reported significantly more manic and depressive symptoms at postpartum week 2. Longer phase angle between DLMO and sleep onset at 33 weeks was associated with more manic symptoms at postpartum week 2 and more obsessive-compulsive symptoms at week 6. Delayed sleep timing in this sample of at-risk women was associated with more symptoms of mania, depression, and OCD in the postpartum period. Sleep timing may be a modifiable risk factor for postpartum depression.
Genome-wide association study of dietary intake in the UK biobank study and its associations with schizophrenia and other traits
Authors: Niarchou Maria , Byrne Enda M. , Trzaskowski Maciej , Sidorenko Julia , Kemper Kathryn E. , McGrath John J. , O’ Donovan Michael C. , Owen Michael J. , Wray Naomi R.
Published: February 2020

Motivated by observational studies that report associations between schizophrenia and traits, such as poor diet, increased body mass index and metabolic disease, we investigated the genetic contribution to dietary intake in a sample of 335,576 individuals from the UK Biobank study. A principal component analysis applied to diet question item responses generated two components: Diet Component 1 (DC1) represented a meat-related diet and Diet Component 2 (DC2) a fish and plant-related diet. Genome-wide association analysis identified 29 independent single-nucleotide polymorphisms (SNPs) associated with DC1 and 63 SNPs with DC2. Estimated from over 35,000 3rd-degree relative pairs that are unlikely to share close family environments, heritabilities for both DC1 and DC2 were 0.16 (standard error (s.e.) = 0.05). SNP-based heritability was 0.06 (s.e. = 0.003) for DC1 and 0.08 (s.e = 0.004) for DC2. We estimated significant genetic correlations between both DCs and schizophrenia, and several other traits. Mendelian randomisation analyses indicated a negative uni-directional relationship between liability to schizophrenia and tendency towards selecting a meat-based diet (which could be direct or via unidentified correlated variables), but a bi-directional relationship between liability to schizophrenia and tendency towards selecting a fish and plant-based diet consistent with genetic pleiotropy.
Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression
Authors: Zoubovsky Sandra P. , Hoseus Sarah , Tumukuntala Shivani , Schulkin Jay O. , Williams Michael T. , Vorhees Charles V. , Muglia Louis J.
Published: February 2020

Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavior, neuroendocrine function, and gene expression changes in molecular regulators of the HPA axis in the early postpartum period. Postpartum female mice exposed to CGS display abnormalities in maternal behavior, including fragmented and erratic maternal care patterns, and the emergence of depression and anxiety-like phenotypes. Dysregulation in postpartum HPA axis function, evidenced by blunted circadian peak and elevation of stress-induced corticosterone levels, was accompanied by increased CRH mRNA expression and a reduction in CRH receptor 1 in the paraventricular nucleus of the hypothalamus (PVN). We further observed decreased PVN expression of nuclear steroid hormone receptors associated with CRH transcription, suggesting these molecular changes could underlie abnormalities in postpartum HPA axis and behavior observed. Overall, our study demonstrates that psychosocial stress during pregnancy induces changes in neuroendocrine function and maternal behavior in the early postpartum period and introduces our CGS paradigm as a viable model that can be used to further dissect the molecular defects that lead to PPD.
ADHD and ASD: distinct brain patterns of inhibition-related activation?
Authors: Albajara Sáenz Ariadna , Septier Mathilde , Van Schuerbeek Peter , Baijot Simon , Deconinck Nicolas , Defresne Pierre , Delvenne Véronique , Passeri Gianfranco , Raeymaekers Hubert , Salvesen Leila , Victoor Laurent , Villemonteix Thomas , Willaye Eric , Peigneux Philippe , Massat Isabelle
Published: February 2020

Attention-deficit/hyperactivity (ADHD) and autism spectrum (ASD) disorders often co-occur. In both cases, response inhibition deficits and inhibition-related atypical brain activation have been reported, although less consistently in ASD. Research exploring the overlap/distinctiveness between ADHD and ASD has significantly increased in recent years, but direct comparison of the inhibition-related neuronal correlates between these disorders are scarce in the literature. This study aimed at disentangling the shared and specific inhibitory brain dysfunctions in ASD and ADHD. Using functional magnetic resonance imaging (fMRI), brain activity was compared between children with ADHD, ASD and typically developing (TD) children aged 8–12 years during an inhibition stop-signal task, using stringent inclusion criteria. At the behavioural level, only children with ADHD exhibited inhibition deficits when compared with the TD group. Distinct patterns of brain activity were observed during successful inhibition. In children with ADHD, motor inhibition was associated with right inferior parietal activation, whereas right frontal regions were activated in children with ASD. Between-group comparisons disclosed higher middle frontal activation in the ASD group compared with the ADHD and the TD groups. Our results evidence different patterns of activation during inhibition in these two disorders, recruiting different regions of the fronto-parietal network associated to inhibition. Besides brain activity differences, behavioural inhibition deficits found only in children with ADHD further suggest that reactive inhibition is one of the core deficits in ADHD, but not in ASD. Our findings provide further evidence contributing to disentangle the shared and specific inhibitory dysfunctions in ASD and ADHD.
Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease
Authors: Ray Balmiki , Maloney Bryan , Sambamurti Kumar , Karnati Hanuma K. , Nelson Peter T. , Greig Nigel H. , Lahiri Debomoy K.
Published: February 2020

Rivastigmine (or Exelon) is a cholinesterase inhibitor, currently used as a symptomatic treatment for mild-to-moderate Alzheimer’s disease (AD). Amyloid-β peptide (Aβ) generated from its precursor protein (APP) by β-secretase (or BACE1) and γ-secretase endoproteolysis. Alternative APP cleavage by α-secretase (a family of membrane-bound metalloproteases– Adamalysins) precludes the generation of toxic Aβ and yields a neuroprotective and neurotrophic secreted sAPPα fragment. Several signal transduction pathways, including protein kinase C and MAP kinase, stimulate α-secretase. We present data to suggest that rivastigmine, in addition to anticholinesterase activity, directs APP processing away from BACE1 and towards α-secretases. We treated rat neuronal PC12 cells and primary human brain (PHB) cultures with rivastigmine and the α-secretase inhibitor TAPI and assayed for levels of APP processing products and α-secretases. We subsequently treated 3×Tg (transgenic) mice with rivastigmine and harvested hippocampi to assay for levels of APP processing products. We also assayed postmortem human control, AD, and AD brains from subjects treated with rivastigmine for levels of APP metabolites. Rivastigmine dose-dependently promoted α-secretase activity by upregulating levels of ADAM-9, -10, and -17 α-secretases in PHB cultures. Co-treatment with TAPI eliminated rivastigmine-induced sAPPα elevation. Rivastigmine treatment elevated levels of sAPPα in 3×Tg mice. Consistent with these results, we also found elevated sAPPα in postmortem brain samples from AD patients treated with rivastigmine. Rivastigmine can modify the levels of several shedding proteins and directs APP processing toward the non-amyloidogenic pathway. This novel property of rivastigmine can be therapeutically exploited for disease-modifying intervention that goes beyond symptomatic treatment for AD.
Genetic factors underlie the association between anxiety, attitudes and performance in mathematics
Authors: Malanchini Margherita , Rimfeld Kaili , Wang Zhe , Petrill Stephen A. , Tucker-Drob Elliot M. , Plomin Robert , Kovas Yulia
Published: February 2020

Students struggling with mathematics anxiety (MA) tend to show lower levels of mathematics self-efficacy and interest as well as lower performance. The current study addresses: (1) how MA relates to different aspects of mathematics attitudes (self-efficacy and interest), ability (understanding numbers, problem-solving ability, and approximate number sense) and achievement (exam scores); (2) to what extent these observed relations are explained by overlapping genetic and environmental factors; and (3) the role of general anxiety in accounting for these associations. The sample comprised 3410 twin pairs aged 16–21 years, from the Twins Early Development Study. Negative associations of comparable strength emerged between MA and the two measures of mathematics attitudes, phenotypically (~ −0.45) and genetically (~ −0.70). Moderate negative phenotypic (~ −0.35) and strong genetic (~ −0.70) associations were observed between MA and measures of mathematics performance. The only exception was approximate number sense whose phenotypic (−0.10) and genetic (−0.31) relation with MA was weaker. Multivariate quantitative genetic analyses indicated that all mathematics-related measures combined accounted for ~75% of the genetic variance in MA and ~20% of its environmental variance. Genetic effects were largely shared across all measures of mathematics anxiety, attitudes, abilities and achievement, with the exception of approximate number sense. This genetic overlap was not accounted for by general anxiety. These results have important implications for future genetic research concerned with identifying the genetic underpinnings of individual variation in mathematics-related traits, as well as for developmental research into how children select and modify their mathematics-related experiences partly based on their genetic predispositions.
Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome
Authors: Berg E. L. , Pride M. C. , Petkova S. P. , Lee R. D. , Copping N. A. , Shen Y. , Adhikari A. , Fenton T. A. , Pedersen L. R. , Noakes L. S. , Nieman B. J. , Lerch J. P. , Harris S. , Born H. A. , Peters M. M. , Deng P. , Cameron D. L. , Fink K. D. , Beitnere U. , O’Geen H. , Anderson A. E. , Dindot S. V. , Nash K. R. , Weeber E. J. , Wöhr M. , Ellegood J. , Segal D. J. , Silverman J. L.
Published: February 2020

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am−/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p− paternal transmission cohort. We also discovered Ube3am−/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am−/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p− did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS.
Treatment-resistant psychotic symptoms and the 15q11.2 BP1–BP2 (Burnside-Butler) deletion syndrome: case report and review of the literature
Authors: Farrell Martilias , Lichtenstein Maya , Harner Matthew K. , Crowley James J. , Filmyer Dawn M. , Lázaro-Muñoz Gabriel , Dietterich Tyler E. , Bruno Lisa M. , Shaughnessy Rita A. , Biondi Tamara F. , Burkholder Stephan , Donmoyer Jane , Berg Jonathan S. , Szatkiewicz Jin , Sullivan Patrick F. , Josiassen Richard C.
Published: February 2020

The 15q11.2 BP1-BP2 (Burnside-Butler) deletion is a rare copy number variant impacting four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5), and carries increased risks for developmental delay, intellectual disability, and neuropsychiatric disorders (attention-deficit/hyperactivity disorder, autism, and psychosis). In this case report (supported by extensive developmental information and medication history), we present the complex clinical portrait of a 44-year-old woman with 15q11.2 BP1-BP2 deletion syndrome and chronic, treatment-resistant psychotic symptoms who has resided nearly her entire adult life in a long-term state psychiatric institution. Diagnostic and treatment implications are discussed.
Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1
Authors: Zhang Kai , Yang Chun , Chang Lijia , Sakamoto Akemi , Suzuki Toru , Fujita Yuko , Qu Youge , Wang Siming , Pu Yaoyu , Tan Yunfei , Wang Xingming , Ishima Tamaki , Shirayama Yukihiko , Hatano Masahiko , Tanaka Kenji F. , Hashimoto Kenji
Published: February 2020

In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either (R)-ketamine (10 mg/kg) or (S)-ketamine (10 mg/kg) was administered to susceptible mice after chronic social defeat stress (CSDS). RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent GSEA (gene set enrichment analysis) revealed that transforming growth factor (TGF)-β signaling might contribute to the different antidepressant effects of the two enantiomers. (R)-ketamine, but not (S)-ketamine, ameliorated the reduced expressions of Tgfb1 and its receptors (Tgfbr1 and Tgfbr2) in the PFC and hippocampus of CSDS susceptible mice. Either pharmacological inhibitors (i.e., RepSox and SB431542) or neutralizing antibody of TGF-β1 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Moreover, depletion of microglia by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Similar to (R)-ketamine, the recombinant TGF-β1 elicited rapid and long-lasting antidepressant effects in animal models of depression. Our data implicate a novel microglial TGF-β1-dependent mechanism underlying the antidepressant effects of (R)-ketamine in rodents with depression-like phenotype. Moreover, TGF-β1 and its receptor agonists would likely constitute a novel rapid-acting and sustained antidepressant in humans.
Intermittent cafeteria diet identifies fecal microbiome changes as a predictor of spatial recognition memory impairment in female rats
Authors: Leigh Sarah-Jane , Kaakoush Nadeem O. , Bertoldo Michael J. , Westbrook R. Frederick , Morris Margaret J.
Published: February 2020

Excessive consumption of diets high in saturated fat and sugar impairs short-term spatial recognition memory in both humans and rodents. Several studies have identified associations between the observed behavioral phenotype and diet-induced changes in adiposity, hippocampal gene expression of inflammatory and blood–brain barrier-related markers, and gut microbiome composition. However, the causal role of such variables in producing cognitive impairments remains unclear. As intermittent cafeteria diet access produces an intermediate phenotype, we contrasted continuous and intermittent diet access to identify specific changes in hippocampal gene expression and microbial species that underlie the cognitive impairment observed in rats fed continuous cafeteria diet. Female adult rats were fed either regular chow, continuous cafeteria diet, or intermittent cafeteria diet cycles (4 days regular chow and 3 days cafeteria) for 7 weeks (12 rats per group). Any cafeteria diet exposure affected metabolic health, hippocampal gene expression, and gut microbiota, but only continuous access impaired short-term spatial recognition memory. Multiple regression identified an operational taxonomic unit, from species Muribaculum intestinale, as a significant predictor of performance in the novel place recognition task. Thus, contrasting intermittent and continuous cafeteria diet exposure allowed us to identify specific changes in microbial species abundance and growth as potential underlying mechanisms relevant to diet-induced cognitive impairment.
Correction: Performance in delayed non-matching to sample task predicts the diagnosis of obsessive–compulsive disorder
Authors: Maatoug Redwan , Le Goff Benoît , Rotge Jean-Yves , Jaafari Nemat , Guillin Olivier , Millet Bruno
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Theory of Noise-Scaled Stability Bounds and Entanglement Rate Maximization in the Quantum Internet
Authors: Gyongyosi Laszlo , Imre Sandor
Published: February 2020

Crucial problems of the quantum Internet are the derivation of stability properties of quantum repeaters and theory of entanglement rate maximization in an entangled network structure. The stability property of a quantum repeater entails that all incoming density matrices can be swapped with a target density matrix. The strong stability of a quantum repeater implies stable entanglement swapping with the boundness of stored density matrices in the quantum memory and the boundness of delays. Here, a theoretical framework of noise-scaled stability analysis and entanglement rate maximization is conceived for the quantum Internet. We define the term of entanglement swapping set that models the status of quantum memory of a quantum repeater with the stored density matrices. We determine the optimal entanglement swapping method that maximizes the entanglement rate of the quantum repeaters at the different entanglement swapping sets as function of the noise of the local memory and local operations. We prove the stability properties for non-complete entanglement swapping sets, complete entanglement swapping sets and perfect entanglement swapping sets. We prove the entanglement rates for the different entanglement swapping sets and noise levels. The results can be applied to the experimental quantum Internet.
DNA repair gene expression is associated with differential prognosis between HPV16 and HPV18 positive cervical cancer patients following radiation therapy
Authors: Sample Klarke M.
Published: February 2020

Cervical cancers are almost always induced by HPV infections, of which HPV16 and HPV18 are predominant. Cancers associated with these strains are induced through DNA repair factors and have a differential response to radiation therapy. Hence this study focuses on finding DNA repair gene expression differences in HPV16 and HPV18 positive cervical cancers after radiation therapy. A higher number of somatic mutations were observed in HPV16 positive cervical tumours for patients that were disease free when compared to those who recurred/progressed. Moreover, hierarchal clustering of RNAseq data from The Cancer Genome Atlas was conducted to identify groups of DNA repair genes associated with a differential prognosis for cervical cancer following postoperative radiation therapy. TP53BP1, MCM9 (at higher than mean levels), POLR2F and SIRT6 (at lower than mean levels), were associated with an increase in patients experiencing cervical cancer recurrence/progression following postoperative radiation therapy when HPV18 positive, but not HPV16 positive. The expression patterns of these genes provide an explanation for the higher rate of postoperative radiation therapy resistance associated with HPV18 positive cervical cancer patients. Therefore, HPV18 positive cervical tumours may be more likely retain a greater non-homologous end joining and homologous recombination pathway activity, which could dampen the effect of postoperative radiation therapy. Moreover, greater susceptibility to postoperative radiation therapy could be caused by the reliance of cervical cancer cells upon the single-strand annealing and nucleotide excision pathways for repair of DNA damage.
In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
Authors: Ashokkumar Manickam , Sonawane Aanand , Sperk Maike , Tripathy Srikanth P. , Neogi Ujjwal , Hanna Luke Elizabeth
Published: February 2020

Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempted to determine IFN-α susceptibility and productivity of infectious transmitted/founder (TF) (n = 8) and non-transmitted (NT) viruses (n = 8) derived from HIV-1 infected infants. Independent experiments were carried out to determine IFN-α resistance, replication fitness, and viral productivity in CD4+T cells over a short period.In vitrostudies showed that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much difference in replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was significant in the case of NT viruses obtained from the same individual. Despite increased susceptibility to IFN-α, NT viruses produced more viral particles than TF viruses. Similar results were also obtained in cultures treated with maraviroc (MVC). The study identified unique characteristics of TF viruses thus prompting further investigation into virus-host interaction occurring during the early stages of HIV infection.
Physical Layer Security in Multimode Fiber Optical Networks
Authors: Rothe Stefan , Koukourakis Nektarios , Radner Hannes , Lonnstrom Andrew , Jorswieck Eduard , Czarske Jürgen W.
Published: February 2020

The light propagation through a multimode fiber is used to increase information security during data transmission without the need for cryptographic approaches. The use of an inverse precoding method in a multimode fiber-optic communication network is based on mode-dependent losses on the physical layer. This leads to an asymmetry between legitimate (Bob) and illegitimate (Eve) recipients of messages, resulting in significant SNR advantage for Bob. In combination with dynamic mode channel changes, there are defined hurdles for Eve to reconstruct a sent message even in a worst-case scenario in which she knows the channel completely. This is the first time that physical layer security has been investigated in a fiber optical network based on measured transmission matrices. The results show that messages can be sent securely using traditional communication techniques. The technology introduced is a step towards the development of cyber physical systems with increased security.
A facile chemical synthesis of CuxNi(1−x)Fe2O4 nanoparticles as a nonprecious ferrite material for electrocatalytic oxidation of acetaldehyde
Authors: Khalaf Mai M. , Abd El-Lateef Hany M. , Alnajjar Ahmed O. , Mohamed Ibrahim M. A.
Published: February 2020

In the present work, Cu-doped nickel ferrite (CuxNi(1−x)Fe2O4) nanoparticles (CuNFNPs) were chemically fabricated by adding citric acid as a capping agent followed by combustion and calcination for acetaldehyde oxidation reaction (AOR) in KOH electrolytes. The as-prepared CuNFNPs were studied in terms of Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), Field emission scanning electron microscope (FE-SEM), Energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET) specific surface area analyses. The morphology of CuNFNPs has sponges-structure containing irregular pores. Additionally, XRD analysis indicated that the prepared CuNFNPs have a cubic-crystals ferrite without the existence of impurities and the crystal size around 20.2 nm. The electrooxidation of acetaldehyde by the presented CuNFNPs was investigated using cyclic voltammetry (CV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) in −OH media. Furthermore, the effects of −OH and acetaldehyde on the electrocatalytic performance were studied with and without Cu-doping in addition to EIS and CA studies which confirm the high-performance of CuNFNPs as an electrocatalyst for AOR.
Giant thermal expansion of a two-dimensional supramolecular network triggered by alkyl chain motion
Authors: Scherb Sebastian , Hinaut Antoine , Pawlak Rémy , Vilhena J. G. , Liu Yi , Freund Sara , Liu Zhao , Feng Xinliang , Müllen Klaus , Glatzel Thilo , Narita Akimitsu , Meyer Ernst
Published: February 2020

Thermal expansion, the response in shape, area or volume of a solid with heat, is usually large in molecular materials compared to their inorganic counterparts. Resulting from the intrinsic molecule flexibility, conformational changes or variable intermolecular interactions, the exact interplay between these mechanisms is however poorly understood down to the molecular level. Here, we investigate the structural variations of a two-dimensional supramolecular network on Au(111) consisting of shape persistent polyphenylene molecules equipped with peripheral dodecyl chains. By comparing high-resolution scanning probe microscopy and molecular dynamics simulations obtained at 5 and 300 K, we determine the thermal expansion coefficient of the assembly of 980 ± 110 × 10−6 K−1, twice larger than other molecular systems hitherto reported in the literature, and two orders of magnitude larger than conventional materials. This giant positive expansion originates from the increased mobility of the dodecyl chains with temperature that determine the intermolecular interactions and the network spacing.
Emerging Role of CXCR4 in Fibrosis
Authors: Wang Xilun Anthony , Griffiths Katherine , Foley Michael
Published: February 2020

Recent evidence has shown that the chemokine receptor CXCR4 and its natural chemokine ligand CXCL12 promote pro-inflammatory responses in a variety of situations and this axis has emerged as a central player in tissue fibrosis. Although its role as a co-receptor for human immunodeficiency virus (HIV) and a key player in various cancers has been well established, the role of CXCR4 in various types of fibrosis has emerged only recently. This review will explore the involvement of CXCR4 in the development of fibrosis, focusing mainly on lung, kidney and eye fibrosis.
Revealing the unexpected promotion effect of diverse potassium precursors on α-MnO2 for the catalytic destruction of toluene
Authors: Zhu Qing , Jiang Zeyu , Ma Mudi , He Chi , Yu Yanke , Liu Xiaohe , Albilali Reem
Published: February 2020

The alkali metal potassium has the functions of structure promotion and electronic modulation in metal oxides.