bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Changes of Genome-Wide DNA Methylation during Soybean Seed Development
Authors: An Yong-qiang Charles , Goettel Wolfgang , Han Qiang , Bartels Arthur , Liu Zongrang , Xiao Wenyan 
Published: September 2017

AbstractSeed development is programmed by expression of many genes in plants. Seed maturation is an important developmental process to soybean seed quality and yield. DNA methylation is a major epigenetic modification regulating gene expression. However, little is known about the dynamic nature of DNA methylation and its effects on gene expression during plant development. Through whole-genome bisulfite sequencing, we showed that DNA methylation went through dynamic changes during seed maturation. An average of 66% CG, 45% CHG and 9% CHH contexts was methylated in cotyledons. CHH methylation levels in cotyledons changed greatly from 6% at the early stage to 11% at the late stage. Transcribed genes were approximately two-fold more likely to be differentially methylated than non-transcribed genes. We identified 40, 66 and 2136 genes containing differentially methylated regions (DMRs) with negative correlation between their expression and methylation in the CG, CHG and CHH contexts, respectively. The majority of the DMR genes in the CHH context were transcriptionally down-regulated as seeds mature: 99% of them during early maturation were down-regulated, and preferentially associated with DNA replication and cell division. The results provide novel insights into the dynamic nature of DNA methylation and its relationship with gene regulation in seed development.
Determinants of the assembly and function of antibody variable domains
Authors: Herold Eva Maria , John Christine , Weber Benedikt , Kremser Stephan , Eras Jonathan , Berner Carolin , Deubler Sabrina , Zacharias Martin , Buchner Johannes 
Published: September 2017

AbstractThe antibody Fv module which binds antigen consists of the variable domains VLand VH. These exhibit a conserved ß-sheet structure and comprise highly variable loops (CDRs). Little is known about the contributions of the framework residues and CDRs to their association. We exchanged conserved interface residues as well as CDR loops and tested the effects on two Fvs interacting with moderate affinities (KDs of ~2.5 µM and ~6 µM). While for the rather instable domains, almost all mutations had a negative effect, the more stable domains tolerated a number of mutations of conserved interface residues. Of particular importance for Fv association are VLP44 and VHL45. In general, the exchange of conserved residues in the VL/VHinterface did not have uniform effects on domain stability. Furthermore, the effects on association and antigen binding do not strictly correlate. In addition to the interface, the CDRs modulate the variable domain framework to a significant extent as shown by swap experiments. Our study reveals a complex interplay of domain stability, association and antigen binding including an unexpected strong mutual influence of the domain framework and the CDRs on stability/association on the one side and antigen binding on the other side.
An invertebrate infection model for evaluating anti-fungal agents against dermatophytosis
Authors: Ishii Masaki , Matsumoto Yasuhiko , Yamada Tsuyoshi , Abe Shigeru , Sekimizu Kazuhisa 
Published: September 2017

AbstractAnimal models of pathogenic infection are needed to evaluate candidate compounds for the development of anti-infectious drugs. Dermatophytes are pathogenic fungi that cause several infectious diseases. We established a silkworm dermatophyte infection model to evaluate anti-fungal drugs. Injection of conidia of the dermatophyte Arthroderma vanbreuseghemii into silkworms was lethal. A. vanbreuseghemii conidia germinated in liquid culture were more potent against silkworms than non-germinated conidia. Germinated conidia of other dermatophytes, Arthroderma benhamiae, Trichophyton rubrum, and Microsporum canis, also killed silkworms. Injection of heat-treated germinated A. vanbreuseghemii conidia did not kill silkworms, suggesting that only viable fungi are virulent. Injecting terbinafine or itraconazole, oral drugs used clinically to treat dermatophytosis, into the silkworm midgut had therapeutic effects against infection with germinated A. vanbreuseghemii conidia. When silkworms were injected with A. vanbreuseghemii expressing enhanced green fluorescent protein (eGFP), mycelial growth of the fungus was observed in the fat body and midgut. Injection of terbinafine into the silkworm midgut, which corresponds to oral administration in humans, inhibited the growth of A. vanbreuseghemii expressing eGFP in the fat body. These findings suggest that the silkworm infection model with eGFP-expressing dermatophytes is useful for evaluating the therapeutic activity of orally administered anti-fungal agents against dermatophytes.
Kinetic constraints on self-assembly into closed supramolecular structures
Authors: Michaels Thomas C. T. , Bellaiche Mathias M. J. , Hagan Michael F. , Knowles Tuomas P. J. 
Published: September 2017

AbstractMany biological and synthetic systems exploit self-assembly to generate highly intricate closed supramolecular architectures, ranging from self-assembling cages to viral capsids. The fundamental design principles that control the structural determinants of the resulting assemblies are increasingly well-understood, but much less is known about the kinetics of such assembly phenomena and it remains a key challenge to elucidate how these systems can be engineered to assemble in an efficient manner and avoid kinetic trapping. We show here that simple scaling laws emerge from a set of kinetic equations describing the self-assembly of identical building blocks into closed supramolecular structures and that this scaling behavior provides general rules that determine efficient assembly in these systems. Using this framework, we uncover the existence of a narrow range of parameter space that supports efficient self-assembly and reveal that nature capitalizes on this behavior to direct the reliable assembly of viral capsids on biologically relevant timescales.
Premature contractions of the bladder are suppressed by interactions between TRPV4 and SK3 channels in murine detrusor PDGFRα+ cells
Authors: Lee Haeyeong , Koh Byoung H. , Peri Lauren E. , Corrigan Robert D. , Lee Hyun-Tai , George Nikita E. , Bhetwal Bhupal P. , Xie Yeming , Perrino Brian A. , Chai Toby C. , Sanders Kenton M. , Koh Sang Don 
Published: September 2017

AbstractDuring filling, urinary bladder volume increases dramatically with little change in pressure. This is accomplished by suppressing contractions of the detrusor muscle that lines the bladder wall. Mechanisms responsible for regulating detrusor contraction during filling are poorly understood. Here we describe a novel pathway to stabilize detrusor excitability involving platelet-derived growth factor receptor-α positive (PDGFRα+) interstitial cells. PDGFRα+ cells express small conductance Ca2+-activated K+ (SK) and TRPV4 channels. We found that Ca2+ entry through mechanosensitive TRPV4 channels during bladder filling stabilizes detrusor excitability. GSK1016790A (GSK), a TRPV4 channel agonist, activated a non-selective cation conductance that coupled to activation of SK channels. GSK induced hyperpolarization of PDGFRα+ cells and decreased detrusor contractions. Contractions were also inhibited by activation of SK channels. Blockers of TRPV4 or SK channels inhibited currents activated by GSK and increased detrusor contractions. TRPV4 and SK channel blockers also increased contractions of intact bladders during filling. Similar enhancement of contractions occurred in bladders of Trpv4−/− mice during filling. An SK channel activator (SKA-31) decreased contractions during filling, and rescued the overactivity of Trpv4−/− bladders. Our findings demonstrate how Ca2+ influx through TRPV4 channels can activate SK channels in PDGFRα+ cells and prevent bladder overactivity during filling.
Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes
Authors: Alosco M L , Kasimis A B , Stamm J M , Chua A S , Baugh C M , Daneshvar D H , Robbins C A , Mariani M , Hayden J , Conneely S , Au R , Torres A , McClean M D , McKee A C , Cantu R C , Mez J , Nowinski C J , Martin B M , Chaisson C E , Tripodis Y , Stern R A 
Published: September 2017

AbstractPrevious research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19–3.91; MI, 2.10,1.17–3.76; CES-D, 3.08,1.65–5.76; AES, 2.39,1.32–4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76–0.97) and CES-D (OR, 95% CI: 0.85, 0.74–0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.
Ketamine: differential neurophysiological dynamics in functional networks in the rat brain
Authors: Ahnaou A , Huysmans H , Biermans R , Manyakov N V , Drinkenburg W H I M 
Published: September 2017

AbstractRecently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep–wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2.5, 5 and 10 mg kg−1) on sleep–wake cycle, multichannels network interactions assessed by coherence and phase–amplitude cross-frequency coupling, locomotor activity (LMA), cognitive information processing as reflected by the mismatch negativity-like (MMN) component of event-related brain potentials (ERPs). Acute ketamine elicited a short, lasting inhibition of rapid eye movement (REM) sleep, increased coherence in higher gamma frequency oscillations independent of LMA, altered theta-gamma phase–amplitude coupling, increased MMN peak-amplitude response and evoked higher gamma oscillations. In contrast, chronic ketamine reduced large-scale communication among cortical regions by decreasing oscillations and coherent activity in the gamma frequency range, shifted networks activity towards slow alpha rhythm, decreased MMN peak response and enhanced aberrant higher gamma neuronal network oscillations. Altogether, our data show that acute and chronic ketamine elicited differential changes in network connectivity, ERPs and event-related oscillations (EROs), supporting possible underlying alterations in NMDAR–GABAergic signaling. The findings underscore the relevance of intermittent dosing of ketamine to accurately maintain the functional integrity of neuronal networks for long-term plastic changes and therapeutic effect.
Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets
Authors: Umpleby A. Margot , Shojaee-Moradie Fariba , Fielding Barbara , Li Xuefei , Marino Andrea , Alsini Najlaa , Isherwood Cheryl , Jackson Nicola , Ahmad Aryati , Stolinski Michael , Lovegrove Julie A. , Johnsen Sigurd , Jeewaka R. Mendis A.S. , Wright John , Wilinska Malgorzata E. , Hovorka Roman , Bell Jimmy D. , Thomas E. Louise , Frost Gary S. , Griffin Bruce A. 
Published: September 2017

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat ‘controls’ (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.
There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P&lt;0.02) and low sugar (P&lt;0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P&lt;0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P&lt;0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P&lt;0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P&lt;0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.
Conformal MIMO loop antenna for ingestible capsule applications
Authors: Xu Li‐Jie , Li Bo , Zhang Ming , Bo Yaming 
Published: September 2017

An MIMO antenna consisting two loop elements is presented at 2.45 GHz industrial, scientific and medical band. The two elements are attached on the inner surface of the capsule, so that inner capsule space is saved to its maximum extent. Additionally, by orthogonally placing the two elements at bottom and side of the capsule, different polarisation directions are achieved; therefore, resulting in good isolation without introducing additional decoupling structures. Furthermore, communication link of the MIMO antenna with outside dipole is evaluated, revealing reliable communication performance. Finally, simulation results are validated by experimental results with good agreement.
Low‐complexity and efficient image coder/decoder with quad‐tree search model for embedded computing platforms
Authors: Ma Tao 
Published: September 2017

Among the existing image coding methods, set partition in hierarchy tree (SPIHT) becomes a favourable choice for the energy‐constrained embedded computing system because of its simplicity and high coding efficiency. In this study, the authors presented a quad‐tree search model which is able to provide the higher coding efficiency than the model used in SPIHT. By applying this model, the authors proposed a new image codec, which is able to surpass SPIHT by 0.2–0.5 dB in peak signal‐to‐noise ratio over various code rates, and its performance is even comparable to SPIHT with adaptive arithmetic code and JPEG2000. Also an experiment is conducted to show the complexity of the proposed codec is the same as SPIHT without the complicated arithmetic codes. This property is critically favoured in embedded processing communication systems where energy consumption and speed are priority concerns.
Polycystic Ovary Syndrome (PCOS) in Juvenile and Adult Type 1 Diabetes in a German/Austrian Cohort
Authors: Reinauer Christina , Bollow Esther , Fröhlich-Reiterer Elke , Laubner Katharina , Bergis Dominik , Schöfl Christof , Kempe Hans-Peter , Hummel Michael , Hennes Pia , Gollisch Katja , Haberland Holger , Datz Nicolin , Meissner Thomas , Holl Reinhard 
Published: September 2017

Abstract
Context While an association between PCOS and type 2 diabetes is well established, to date there have been few data on clinical care of type 1 diabetes (T1D) patients with PCOS.
Objective The aim of our study was to characterize T1D patients with the comorbidity of PCOS within the DPV cohort with regard to diabetes phenotype, therapy and metabolic control.
Design and Setting Clinical data from the prospective German/Austrian DPV cohort on patients with T1D and documented PCOS (n=76) were compared to female T1D controls (n=32,566) in reproductive age.
Results The age at T1D manifestation in PCOS patients was later than in the control group (14.9±8.2 vs. 11.8±7.0 years, p<0.001). PCOS patients had higher BMI-SDS (0.92±0.11 vs. 0.38±0.01, p<0.001), metformin and oral contraceptives were used more frequently (p<0.001). A1c levels were significantly lower (7.92 +/− 0.23% vs. 8.43±0.01%, p<0.05) despite of lower insulin requirements (0.76±0.04 IU/kg/d vs. 0.84±0.00 IU/kg/d, p<0.05). In the PCOS group, higher rates of dyslipidemia (63.4 vs. 48.7%, p =0.032) and thyroid disorders (42.2% vs. 21.2%, p<0.001) were present.
Discussion While patients with T1D and comorbid PCOS showed features of a “type 1.5 diabetes” phenotype, insulin requirements per kg body weight were not higher and metabolic control was better, which could be explained only partially by additional metformin therapy. A more precise genetic and metabolic characterisation of these patients is needed to answer open questions on the underlying autoimmune process and residual ß-cell function.
Purification and Characterization of the Soluble form of the Receptor for Advanced Glycation End-Products (sRAGE): A Novel Fast, Economical and Convenient Method
Authors: Kumar Varun , Sulaj Alba , Fleming Thomas , Nawroth Peter 
Published: September 2017

AbstractThe receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor which belongs to the pattern recognition receptor family and can bind to various ligands such as advanced glycation end-products (AGEs), members of the S100 protein family, glycosaminoglycans, amyloid β peptides, high-mobility group box-1 (HMGB1) and nucleic acids through its extracellular domain. The RAGE-ligand interaction leads to the activation of MAP kinase and NF-kB signaling pathways. Further ligand-induced up-regulation of RAGE is involved in various patho-physiological situations including late diabetic complications, Alzheimer disease and several other neurodegenerative diseases. A secreted soluble isoform of RAGE (sRAGE), corresponding to the extracellular domain only, has the ability to block RAGE-associated cellular activation and signaling. Further application of recombinant sRAGE has been shown to block RAGE-mediated pathophysiological conditions in various models of cancer or multiple sclerosis. These finding demonstrates sRAGE as a therapeutic tool to block RAGE-associated inflammatory signaling. In this manuscript, we describe a two-step simple, novel and convenient method for expressing and purifying scalable quantities of biologically active murine form of sRAGE by using E.coli as an expression host. The method we propose has several advantages over the current available methods particularly in terms of yield and quality of preparation. The sRAGE produced by this expression system retains all the secondary structural properties as analyzed by the ligand binding affinities. The produced protein also retains all the DNA-RAGE binding functional properties and thus can be a valuable tool for studying dynamics of this novel RAGE ligand. Moreover this method can be utilized by researchers to generate biologically active endotoxin-free sRAGE for in vivo applications to study and treat RAGE-associated pathologies.
Psychometrische Eigenschaften der deutschen Version des Sibling Perception Questionnaire (SPQ)
Authors: Baumann Ines , Niemitz Mandy , Goldbeck Lutz 
Published: September 2017

ZusammenfassungDer Sibling Perception Questionnaire (SPQ) erfasst die Auswirkungen einer Krebserkrankung eines Kindes auf gesunde Geschwister hinsichtlich intrafamiliärer Beziehungen und Kommunikation sowie individuelle krankheitsbezogene Wahrnehmungen und Ängste. Ziel dieser Studie ist die Untersuchung der psychometrischen Eigenschaften der ins Deutsche übersetzten Version des SPQ. Dazu wurden die Daten zu 216 gesunden Geschwistern mit 164 Fragebögen im Selbstbericht und 212 Elternberichten gesammelt. Anhand dessen wurden die 4 Subskalen „Interpersonale Schwierigkeiten“, „Intrapersonale Schwierigkeiten“, „offene Kommunikation“ und „Angst vor der Erkrankung“ mit insgesamt 23 Items untersucht. Es zeigten sich akzeptable bis gute Skalenkonsistenzen im Elternbericht (Cronbach’s α=0,73–0,87) und im Selbstbericht (α=0,59–0,80), mit Ausnahme der Skala Angst vor der Erkrankung (α=0,35 und 0,16). Im Hinblick auf die konvergente Validität zeigten sich ein deutlicher korrelativer Zusammenhang zwischen Skalen des SPQ und Skalen des Strengths and Difficulties Questionnaire (SDQ) und des Lebensqualitätsinventars für Kinder (LQ-KID) (r=− 0,37; r=0,63; p≤0,001). Die deutsche Version des SPQ stellt sowohl als Selbst- und Elternbericht ein reliables und valides Instrument zur Erfassung der emotionalen Reaktion eines gesunden Kindes auf die Krebserkrankung eines Geschwisterkindes dar. Weitere Untersuchungen an unterschiedlichen Stichproben werden empfohlen.
Asymmetric mechanosensitivity in a eukaryotic ion channel
Authors: Clausen Michael V. , Jarerattanachat Viwan , Carpenter Elisabeth P. , Sansom Mark S. P. , Tucker Stephen J. 
Published: September 2017

Significance
One important way in which living organisms are able to detect and respond to their environment is via the conversion of mechanical forces into electrical signals. However, the molecular mechanisms that enable mammalian “mechanosensitive” ion channels to detect a wide profile of forces within the membrane remain unclear. By studying the functional activity of individual TREK-2 K2P channels inserted in different directions into a lipid bilayer, we are now able to describe how the asymmetric structure of this channel enables it to sense such a broad profile of forces. These results help us understand how eukaryotic ion channels respond to a rich variety of sensory stimuli.
Continuous track paths reveal additive evidence integration in multistep decision making
Authors: Buc Calderon Cristian , Dewulf Myrtille , Gevers Wim , Verguts Tom 
Published: September 2017

Significance
Many daily-life decisions consist of multiple steps (e.g., go outside, go left, arrive at Italian restaurant). We distinguish four prominent models of such multistep decision making. We further propose a paradigm in two experiments to disentangle these models. Only the models implementing additive integration from second- to first-step choices were able to account for track path movements. Specifically, we find that first-step decisions are initially based on the sum/mean of second-step future rewards. As information regarding the optimal second-step choice increases, the decision gradually becomes based on the maximal future reward. Hence, we suggest that multistep decision making involves progressive unraveling of future outcomes during decision making.