bluuebunny/crossref_metadata_2025_split huggingface dataset:
B1.12: a novel peptide interacting with the extracellular loop of the EBV oncoprotein LMP1
Authors: Ammous-Boukhris Nihel , Mosbah Amor , Ayadi Wajdi , Sahli Emna , Chevance Soizic , Bondon Arnaud , Gargouri Ali , Baudy-Floc’h Michele , Mokdad-Gargouri Raja 
Published: March 2019

AbstractLatent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) plays an important role in EBV-induced cell transformation. Down-regulation of the LMP1 expression had shown promising results on cancer cell therapy. In this study, we identified by Phage display a novel peptide called B1.12 (ACPLDLRSPCG) which selectively binds to the extracellular loop (B1) of the LMP1 oncoprotein as demonstrated by molecular docking, NMR and ITC. Using an LMP1 expressing cell line, we showed that B1.12 decreased cell viability, and induced G0/G1 cell cycle arrest. In addition, the expression of A20, pAkt, and pNFkb (pRelA536) in C666-1 cells treated with B1.12 decreased compared to the untreated cells. In conclusion, we selected a novel peptide able to bind specifically to the extracellular loop of LMP1 and thus modulate its oncogenic properties.
Heterochromatin protein 1 (HP1) is intrinsically required for post-transcriptional regulation of Drosophila Germline Stem Cell (GSC) maintenance
Authors: Casale Assunta Maria , Cappucci Ugo , Fanti Laura , Piacentini Lucia 
Published: March 2019

AbstractA very important open question in stem cells regulation is how the fine balance between GSCs self-renewal and differentiation is orchestrated at the molecular level. In the past several years much progress has been made in understanding the molecular mechanisms underlying intrinsic and extrinsic controls of GSC regulation but the complex gene regulatory networks that regulate stem cell behavior are only partially understood. HP1 is a dynamic epigenetic determinant mainly involved in heterochromatin formation, epigenetic gene silencing and telomere maintenance. Furthermore, recent studies have revealed the importance of HP1 in DNA repair, sister chromatid cohesion and, surprisingly, in positive regulation of gene expression. Here, we show that HP1 plays a crucial role in the control of GSC homeostasis in Drosophila. Our findings demonstrate that HP1 is required intrinsically to promote GSC self-renewal and progeny differentiation by directly stabilizing the transcripts of key genes involved in GSCs maintenance.
The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism
Authors: Misselbeck Karla , Marchetti Luca , Priami Corrado , Stover Patrick J. , Field Martha S. 
Published: March 2019

AbstractIn folate-mediated one-carbon metabolism (FOCM), 5-formyltetrahydrofolate (5fTHF), a one-carbon substituted tetrahydrofolate (THF) vitamer, acts as an intracellular storage form of folate and as an inhibitor of the folate-dependent enzymes phosphoribosylaminoimidazolecarboxamide formyltransferase (AICARFT) and serine hydroxymethyltransferase (SHMT). Cellular levels of 5fTHF are regulated by a futile cycle comprising the enzymes SHMT and 5,10-methenyltetrahydrofolate synthetase (MTHFS). MTHFS is an essential gene in mice; however, the roles of both 5fTHF and MTHFS in mammalian FOCM remain to be fully elucidated. We present an extension of our previously published hybrid-stochastic model of FOCM by including the 5fTHF futile-cycle to explore its effect on the FOCM network. Model simulations indicate that MTHFS plays an essential role in preventing 5fTHF accumulation, which consequently averts inhibition of all other reactions in the metabolic network. Moreover, in silico experiments show that 10-formylTHF inhibition of MTHFS is critical for regulating purine synthesis. Model simulations also provide evidence that 5-methylTHF (and not 5fTHF) is the predominant physiological binder/inhibitor of SHMT. Finally, the model simulations indicate that the 5fTHF futile cycle dampens the stochastic noise in FOCM that results from both folate deficiency and a common variant in the methylenetetrahydrofolate reductase (MTHFR) gene.
Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load
Authors: Alkan E. , Taporoski T. P. , Sterr A. , von Schantz M. , Vallada H. , Krieger J. E. , Pereira A. C. , Alvim R. , Horimoto A. R. V. R. , Pompéia S. , Negrão A. B. , Evans S. L. H. 
Published: March 2019

AbstractCardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50–85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.
A Nationwide, Population-based Cohort Study on Potential Autoimmune Association of Ménière Disease to Atopy and Vitiligo
Authors: Hahn Hyung Jin , Kwak Sang Gyu , Kim Dong-Kyu , Kim Jong-Yeup 
Published: March 2019

AbstractMénière disease (MD), an idiopathic disorder of sensorineural hearing loss and vertigo, shares many similarities with two common skin conditions, atopic dermatitis (AD) and vitiligo. Recent studies have suggested that MD may be related to or triggered by autoimmune conditions, notably Hashimoto thyroiditis and alopecia areata. These evidences led to the authors contemplating the possibility of immunological bridge between MD and the two skin conditions. The authors have tested this hypothesis with population-based cohort from the National Health Insurance Service Database of Korea. A cohort of 1.1 million patients was extracted from the database. Using χ2 tests, prevalence of the two skin disorders in relation to MD status was analysed. In MD patients, the odds ratios for having concurrent AD and vitiligo were 0.717 (95% CI, 0.535–0.962, p = 0.026) and 2.149 (95% CI, 1.396–3.308, p = 0.001), respectively. Females and older patients were more than twice likely to be affected by the two skin conditions. The relationship between vitiligo and MD was significant in younger subgroup only. Socio-economic subgroup analysis revealed the observed patterns are primarily a middle-upper class phenomenon. Uncertainty regarding temporal sequence of onset, and lack of detail on disease severity and subtype kept the study from more refined conclusion. In concluding, AD and vitiligo might be linked to MD through Treg-driven action of cellular immunity, but further big data-based investigations must follow.
Infants’ brain responses to pupillary changes in others are affected by race
Authors: Kelsey Caroline M. , Krol Kathleen M. , Kret Mariska E. , Grossmann Tobias 
Published: March 2019

AbstractSensitive responding to eye cues plays a key role during human social interactions. Observed changes in pupillary size provide a range of socially-relevant information including cues regarding a person’s emotional and arousal states. Recently, infants have been found to mimic observed pupillary changes in others, instantiating a foundational mechanism for eye-based social communication. Among adults, perception of pupillary changes is affected by race. Here, we examined whether and how race impacts the neural processing of others’ pupillary changes in early ontogeny. We measured 9-month-old infants’ brain responses to dilating and constricting pupils in the context of viewing own-race and other-race eyes using functional near-infrared spectroscopy (fNIRS). Our results show that only when responding to own-race eyes, infants’ brains distinguished between changes in pupillary size. Specifically, infants showed enhanced responses in the right superior temporal cortex when observing own-race pupil dilation. Moreover, when processing other-race pupillary changes, infants recruited the dorsolateral prefrontal cortex, a brain region linked to cognitive control functions. These findings suggest that, early in development, the fundamental process of responding to pupillary changes is impacted by race and interracial interactions may afford greater cognitive control or effort. This critically informs our understanding of the early origins of responding to pupillary signals in others and further highlights the impact of race on the processing of social signals.
The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood
Authors: Lähdepuro Anna , Savolainen Katri , Lahti-Pulkkinen Marius , Eriksson Johan G. , Lahti Jari , Tuovinen Soile , Kajantie Eero , Pesonen Anu-Katriina , Heinonen Kati , Räikkönen Katri 
Published: March 2019

AbstractEarly life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934–1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65–77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31–0.58); B = 0.33 (95% CI = 0.20–0.46); B = 0.10 (95% CI = 0.01–0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.
Conditional knockout of UBC13 produces disturbances in gait and spontaneous locomotion and exploration in mice
Authors: Wozniak David F. , Valnegri Pamela , Dearborn Joshua T. , Fowler Stephen C. , Bonni Azad 
Published: March 2019

AbstractHere we have characterized the functional impairments resulting from conditional knockout of the ubiquitin-conjugating E2 enzyme (UBC13) in rodent cerebellar granule neurons, which greatly increases the parallel fiber presynaptic boutons and functional parallel fiber/Purkinje cell synapses. We report that conditional UBC13 knockout mice exhibit reliable deficits on several gait-related variables when their velocity of ambulation is tightly controlled by a moving treadmill and by restricting space for movement. Selected gait parameters and movement patterns related to spontaneous exploration in an open field may also be affected in conditional UBC13 knockout mice. Analysis of open-field data as a function of test session half using force-plate actometer instrumentation suggest that conditional UBC13 knockout mice have alterations in emotionality, possibly affecting gait and movement variables. These findings suggest that conditional UBC13 knockout mice represent a valuable platform for assessing the effects of disturbances in cerebellar granule cell circuitry on gait and other aspects of locomotion. Also, the possibility that psychological factors such as altered emotionality may impact gait and movement patterns in these mice suggest that these mice may provide a useful model for evaluating analogous behavioral impairments in autism spectrum disorders and other neurodevelopmental syndromes associated with deregulation of ubiquitin signaling.
Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus
Authors: Seok Hannah , Lee Minyoung , Shin Eugene , Yun Mi Ra , Lee Yong-ho , Moon Jae Hoon , Kim Eosu , Lee Phil Hyu , Lee Byung-Wan , Kang Eun Seok , Lee Hyun Chul , Cha Bong Soo 
Published: March 2019

AbstractAmyloid-β (Aβ) accumulation in the brain is a pathological feature of Alzheimer’s disease (AD) and enhancing Aβ clearance is a potential therapeutic strategy. Pioglitazone is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist and is widely used to treat type 2 diabetes. We previously reported that low-dose pioglitazone increased the expression of low-density lipoprotein receptor-related protein 1 (LRP1), which upregulates the clearance of Aβ, using human brain microvascular endothelial cells. We investigated whether low-dose pioglitazone can rescue the pathological phenotype and memory impairment in senescence-accelerated mouse prone-8 (SAMP8) mice by increasing LRP1 levels. SAMP8 mice were treated with vehicle or pioglitazone in dosages of 2 or 5 mg/kg/day for 7 weeks. In the water maze test, 2 mg/kg/day of pioglitazone significantly attenuated the increased escape latency in SAMP8 mice (p = 0.026), while 5 mg/kg/day of treatment did not. Compared with vehicle treatment, the hippocampi of SAMP8 mice with 2 mg/kg/day of pioglitazone exhibited fewer Aβ deposits and reduced Aβ1–40 levels, along with elevated LRP1 expression (p = 0.005). Collectively, our results proposed that a new therapeutic application of the PPAR-γ agonist for AD treatment should be considered at a lower dose than the conventional dose used to treat diabetes.
Arrow of time and its reversal on the IBM quantum computer
Authors: Lesovik G. B. , Sadovskyy I. A. , Suslov M. V. , Lebedev A. V. , Vinokur V. M. 
Published: March 2019

AbstractUncovering the origin of the “arrow of time” remains a fundamental scientific challenge. Within the framework of statistical physics, this problem was inextricably associated with the Second Law of Thermodynamics, which declares that entropy growth proceeds from the system’s entanglement with the environment. This poses a question of whether it is possible to develop protocols for circumventing the irreversibility of time and if so to practically implement these protocols. Here we show that, while in nature the complex conjugation needed for time reversal may appear exponentially improbable, one can design a quantum algorithm that includes complex conjugation and thus reverses a given quantum state. Using this algorithm on an IBM quantum computer enables us to experimentally demonstrate a backward time dynamics for an electron scattered on a two-level impurity.
Changes in temperature, pH, and salinity affect the sheltering responses of Caribbean spiny lobsters to chemosensory cues
Authors: Ross Erica , Behringer Donald 
Published: March 2019

AbstractFlorida Bay is home to a network of shallow mud-banks which act as barriers to circulation creating small basins that are often subject to extremes in temperature and salinity. Florida bay is also important juvenile habitat for the Caribbean spiny lobster Panulirus argus. While our understanding of the effect of environmental changes on the survival, growth, and movement of spiny lobsters is growing, the effect on their chemosensory abilities has not yet been investigated. Lobsters rely heavily on chemical cues for many biological and ecological activities, and here we report on the effect of extreme environmental events in temperature (32 °C), salinity (45ppt), and pH (7.65 pH) on social behavior and sheltering preference in P. argus. Under normal conditions, chemical cues from conspecifics are used by spiny lobsters to identify suitable shelter and cues from stone crabs and diseased individuals are used to determine shelters to be avoided. In all altered conditions, lobsters lost the ability to aggregate with conspecifics and avoid stone crabs and diseased conspecifics. Thus, seasonal extreme events, and potentially future climate change conditions, alter the chemosensory-driven behavior of P. argus and may result in decreased survivorship due to impaired shelter selection or other behaviors.
Loss of the Polycomb group protein Rnf2 results in derepression of tbx-transcription factors and defects in embryonic and cardiac development
Authors: Chrispijn Naomi D. , Elurbe Dei M. , Mickoleit Michaela , Aben Marco , de Bakker Dennis E.M. , Andralojc Karolina M. , Huisken Jan , Bakkers Jeroen , Kamminga Leonie M. 
Published: March 2019

AbstractThe Polycomb group (PcG) protein family is a well-known group of epigenetic modifiers. We used zebrafish to investigate the role of Rnf2, the enzymatic subunit of PRC1. We found a positive correlation between loss of Rnf2 and upregulation of genes, especially of those whose promoter is normally bound by Rnf2. The heart of rnf2 mutants shows a tubular shaped morphology and to further understand the underlying mechanism, we studied gene expression of single wildtype and rnf2 mutant hearts. We detected the most pronounced differences at 3 dpf, including upregulation of heart transcription factors, such as tbx2a, tbx2b, and tbx3a. These tbx genes were decorated by broad PcG domains in wildtype whole embryo lysates. Chamber specific genes such as vmhc, myh6, and nppa showed downregulation in rnf2 mutant hearts. The marker of the working myocard, nppa, is negatively regulated by Tbx2 and Tbx3. Based on our findings and literature we postulate that loss of Rnf2-mediated repression results in upregulation and ectopic expression of tbx2/3, whose expression is normally restricted to the cardiac conductive system. This could lead to repression of chamber specific gene expression, a misbalance in cardiac cell types, and thereby to cardiac defects observed in rnf2 mutants.
Steered molecular dynamic simulations of conformational lock of Cu, Zn-superoxide dismutase
Authors: Xiao Bao-Lin , Ning Yan-Na , Niu Nan-Nan , Li Di , Moosavi-Movahedi Ali Akbar , Sheibani Nader , Hong Jun 
Published: March 2019

AbstractThe conformational lock was a bio-thermodynamic theory to explain the characteristics of interfaces in oligomeric enzymes and their effects on catalytic activity. The previous studies on superoxide dismutases (Cu, Zn-SODs) showed that the dimeric structure contributed to the high catalytic efficiency and the stability. In this study, steered molecular dynamics simulations were used firstly to study the main interactions between two subunits of Cu, Zn-SODs. The decomposition process study showed that there were not only four pairs of hydrogen bonds but also twenty-five residue pairs participating hydrophobic interactions between A and B chains of SOD, and van der Waals interactions occupied a dominant position among these residue pairs. Moreover, the residue pairs of hydrogen bonds played a major role in maintaining the protein conformation. The analysis of the energy and conformational changes in the SMD simulation showed that there were two groups (two conformational locks) between A and B chains of SOD. The first group consisted of one hydrogen-bond residues pair and seven hydrophobic interactions residues pairs with a total average energy of −30.10 KJ/mol, and the second group of three hydrogen-bond residues pair and eighteen hydrophobic interactions residues pairs formed with a total average energy of −115.23 KJ/mol.
Mesolimbic white matter connectivity mediates the preference for sweet food
Authors: Francke Paul , Tiedemann Lena J. , Menz Mareike M. , Beck Judith , Büchel Christian , Brassen Stefanie 
Published: March 2019

AbstractDopaminergic brain structures like the nucleus accumbens (NAc) are thought to encode the incentive salience of palatable foods motivating appetitive behaviour. Animal studies have identified neural networks mediating the regulation of hedonic feeding that comprise connections of the NAc with the ventral tegmental area (VTA) and the lateral hypothalamus (LH). Here, we investigated how structural connectivity of these pathways relates to individual variability in decisions on sweet food consumption in humans. We therefore combined probabilistic tractography on diffusion imaging data from 45 overnight fasted lean to overweight participants with real decisions about high and low sugar food consumption. Across all individuals, sugar preference and connectivity strength were not directly related, however, multiple regression analysis revealed interaction of mesolimbic structure and sugar preference to depend on individuals’ BMI score. In overweight individuals (BMI: ≥25 kg/m², N = 22) higher sugar preference was thereby specifically related to stronger connectivity within the VTA-NAc pathway while the opposite pattern emerged in participants with normal BMI (BMI: <25 kg/m², N = 23). Our structural results complement previous functional findings on the critical role of the human mesolimbic system for regulating hedonic eating in overweight individuals.
Structural transition in social networks: The role of homophily
Authors: Murase Yohsuke , Jo Hang-Hyun , Török János , Kertész János , Kaski Kimmo 
Published: March 2019

AbstractWe introduce a model for the formation of social networks, which takes into account the homophily or the tendency of individuals to associate and bond with similar others, and the mechanisms of global and local attachment as well as tie reinforcement due to social interactions between people. We generalize the weighted social network model such that the nodes or individuals haveFfeatures and each feature can haveqdifferent values. Here the tendency for the tie formation between two individuals due to the overlap in their features represents homophily. We find a phase transition as a function ofForq, resulting in a phase diagram. For fixedqand as a function ofFthe system shows two phases separated atFc. ForF < Fclarge, homogeneous, and well separated communities can be identified within which the features match almost perfectly (segregated phase). WhenFbecomes larger thanFc, the nodes start to belong to several communities and within a community the features match only partially (overlapping phase). Several quantities reflect this transition, including the average degree, clustering coefficient, feature overlap, and the number of communities per node. We also make an attempt to interpret these results in terms of observations on social behavior of humans.