bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pupil size reflects successful encoding and recall of memory in humans
Authors: Kucewicz Michal T. , Dolezal Jaromir , Kremen Vaclav , Berry Brent M. , Miller Laura R. , Magee Abigail L. , Fabian Vratislav , Worrell Gregory A. 
Published: March 2018

AbstractPupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten – the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.
Plastic antibodies tailored on quantum dots for an optical detection of myoglobin down to the femtomolar range
Authors: Piloto Ana Margarida , Ribeiro David S. M. , Rodrigues S. Sofia M. , Santos Catarina , Santos João L. M. , Sales M. Goreti F. 
Published: March 2018

AbstractA highly sensitive fluorescence detection probe was developed by tailoring plastic antibodies on the external surface of aqueous soluble quantum dots (QDs). The target was Myoglobin (Myo), a cardiac biomarker that quenched the intrinsic fluorescent emission of cadmium telluride (CdTe) QDs capped with mercaptopropionic acid (CdTe-MPA-QDs). The QDs were incubated with the target protein and further modified with a molecularly-imprinted polymer (MIP) produced by radical polymerization of acrylamide and bisacrylamide. The main physical features of the materials were assessed by electron microscopy, dynamic light scattering (DLS), UV/Vis spectrophotometry and spectrofluorimetry. The plastic antibodies enabled Myo rebinding into the QDs with subsequent fluorescence quenching. This QD-probe could detect Myo concentrations from 0.304 to 571 pg/ml (50.6 fM to 95 pM), with a limit of detection of 0.045 pg/ml (7.6 fM). The proposed method was applied to the determination of Myo concentrations in synthetic human serum. The results obtained demonstrated the ability of the modified-QDs to determine Myo below the cut-off values of myocardial infarction. Overall, the nanostructured MIP-QDs reported herein displayed quick responses, good stability and sensitivity, and high selectivity for Myo, offering the potential to be explored as new emerging sensors for protein detection in human samples.
Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease
Authors: Crowe J. Scott , Roberts Kevin J. , Carlton Timothy M. , Maggiore Luana , Cubitt Marion F. , Clare Simon , Harcourt Katherine , Reckless Jill , MacDonald Thomas T. , Ray Keith P. , Vossenkämper Anna , West Michael R. 
Published: March 2018

AbstractTNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.
The generation mechanism of spike-and-slow wave discharges appearing on thalamic relay nuclei
Authors: Hu Bing , Guo Yu , Shi Feng , Zou Xiaoqiang , Dong Jing , Pan Long , Yu Min , Zhou Chaowei , Cheng Zhang , Tang Wanyue , Sun Haochen , Chen Luonan 
Published: March 2018

AbstractIn this paper, we use a model modified from classic corticothalamic network(CT) to explore the mechanism of absence seizures appearing on specific relay nuclei (SRN) of the thalamus. It is found that typical seizure states appear on SRN through tuning several critical connection strengths in the model. In view of previous experimental and theoretical works which were mainly on epilepsy seizure phenomena appearing on excitatory pyramidal neurons (EPN) of the cortex, this is a novel model to consider the seizure observed on thalamus. In particular, the onset mechanism is different from previous theoretical studies. Inspired by some previous clinical and experimental studies, we employ the external stimuli voltage on EPN and SRN in the network, and observe that the seizure can be well inhibited by tuning the stimulus intensity appropriately. We further explore the effect of the signal transmission delays on seizures, and found that the polyspike phenomenon appears only when the delay is sufficiently large. The experimental data also confirmed our model. Since there is a complex network in the brain and all organizations are interacting closely with each other, the results obtained in this paper provide not only biological insights into the regulatory mechanisms but also a reference for the prevention and treatment of epilepsy in future.
Novel crab predator causes marine ecosystem regime shift
Authors: Kotta J. , Wernberg T. , Jänes H. , Kotta I. , Nurkse K. , Pärnoja M. , Orav-Kotta H. 
Published: March 2018

AbstractThe escalating spread of invasive species increases the risk of disrupting the pathways of energy flow through native ecosystems, modify the relative importance of resource (‘bottom-up’) and consumer (‘top-down’) control in food webs and thereby govern biomass production at different trophic levels. The current lack of understanding of interaction cascades triggered by non-indigenous species underscores the need for more basic exploratory research to assess the degree to which novel species regulate bottom-up and/or top down control. Novel predators are expected to produce the strongest effects by decimating consumers, and leading to the blooms of primary producers. Here we show how the arrival of the invasive crab Rhithropanopeus harrisii into the Baltic Sea – a bottom-up controlled ecosystem where no equivalent predators ever existed – appeared to trigger not only strong top-down control resulting in a decline in richness and biomass of benthic invertebrates, but also an increase in pelagic nutrients and phytoplankton biomass. Thus, the addition of a novel interaction – crab predation – to an ecosystem has a potential to reduce the relative importance of bottom-up regulation, relax benthic-pelagic coupling and reallocate large amounts of nutrients from benthic to pelagic processes, resulting in a regime shift to a degraded ecosystem state.
The transcriptional profiles and functional implications of long non-coding RNAs in the unfolded protein response
Authors: Quan Hongyang , Fan Qianqian , Li Chuang , Wang Yan-ying , Wang Lin 
Published: March 2018

AbstractThe unfolded protein response (UPR) is activated, when the folding capacity is compromised in the endoplasmic reticulum (ER). To date, most studies focused on the coding genes and microRNAs in UPR. Other non-coding RNAs affected by UPR and their roles in UPR have not been systematically studied. Long noncoding RNAs (lncRNAs) are increasingly recognized as powerful epigenetic regulators. In this study, we transcriptomically profiled the lncRNAs and mRNAs from mouse embryonic fibroblasts under ER stress, and identified many differentially expressed lncRNAs and mRNAs. Genomic location and mRNA-lncRNA co-expression analyses predicted a number of lncRNAs, which potentially regulate the expression of UPR genes. In particular, FR229754, an exonic sense lncRNA, is significantly up-regulated in UPR. FR229754 overlaps with Sel1l, and their expressions correlated with each other. Sel1l is involved in the ER-associated protein degradation. Silencing of FR229754 did not much affect the expression of Sel1l, but markedly reduced the levels of BiP/GRP78/Hspa5, a major ER chaperon up-regulated in UPR. Probing with pathway-specific inhibitors showed that up-regulation of FR229754 and Sel1 depended on the activation of PERK. Together, our study identified a number of candidate lncRNAs and paved the way for future characterization of their functions in UPR.
Using high-amplitude and focused transcranial alternating current stimulation to entrain physiological tremor
Authors: Khatoun Ahmad , Breukers Jolien , Op de Beeck Sara , Nica Ioana Gabriela , Aerts Jean-Marie , Seynaeve Laura , Haeck Tom , Asamoah Boateng , Mc Laughlin Myles 
Published: March 2018

AbstractTranscranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that can entrain physiological tremor in healthy volunteers. We conducted two experiments to investigate the effectiveness of high-amplitude and focused tACS montages at entraining physiological tremor. Experiment 1 used saline-soaked sponge electrodes with an extra-cephalic return electrode and compared the effects of a motor (MC) and prefrontal cortex (PFC) electrode location. Average peak-amplitude was 1.925 mA. Experiment 2 used gel-filled cup-electrodes in a 4 × 1 focused montage and compared the effects of MC and occipital cortex (OC) tACS. Average peak-amplitude was 4.45 mA. Experiment 1 showed that unfocused MC and PFC tACS both produced phosphenes and significant phase entrainment. Experiment 2 showed that focused MC and OC tACS produced no phosphenes but only focused MC tACS caused significant phase entrainment. At the group level, tACS did not have a significant effect on tremor amplitude. However, with focused tACS there was a significant correlation between phase entrainment and tremor amplitude modulation: subjects with higher phase entrainment showed more tremor amplitude modulation. We conclude that: (1) focused montages allow for high-amplitude tACS without phosphenes and (2) high amplitude focused tACS can entrain physiological tremor.
Haplotype Heritability Mapping Method Uncovers Missing Heritability of Complex Traits
Authors: Shirali Masoud , Knott Sara A. , Pong-Wong Ricardo , Navarro Pau , Haley Chris S. 
Published: March 2018

AbstractWe propose a novel approach to analyze genomic data that incorporates haplotype information for detecting rare variants within a regional heritability mapping framework. The performance of our approach was tested in a simulation study based on human genotypes. The phenotypes were simulated by generating regional variance using either SNP(s) or haplotype(s). Regional genomic relationship matrices, constructed with either a SNP-based or a haplotype-based estimator, were employed to estimate the regional variance. The results from the study show that haplotype heritability mapping captures the regional effect, with its relative performance decreasing with increasing analysis window size. The SNP-based regional mapping approach often misses the effect of causal haplotype(s); however, it has a greater power to detect simulated SNP-based-variants. Heritability estimates suggest that the haplotype heritability mapping estimates the simulated regional heritability accurately for all phenotypes and analysis windows. However, the SNP-based analysis overestimates the regional heritability and performs less well than our haplotype-based approach for the simulated rare haplotype-based-variant. We conclude that haplotype heritability mapping is a useful tool to capture the effect of rare variants, and explain a proportion of the missing heritability.
Detection of aryl hydrocarbon receptor agonists in human samples
Authors: Rothhammer Veit , Borucki Davis M. , Kenison Jessica E. , Hewson Patrick , Wang Zhongyan , Bakshi Rohit , Sherr David H. , Quintana Francisco J. 
Published: March 2018

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with important functions in the immune response and cancer. AHR agonists are provided by the environment, the commensal flora and the metabolism. Considering AHR physiological functions, AHR agonists may have important effects on health and disease. Thus, the quantification of AHR agonists in biological samples is of scientific and clinical relevance. We compared different reporter systems for the detection of AHR agonists in serum samples of Multiple Sclerosis (MS) patients, and assessed the influence of transfection methods and cell lines in a reporter-based in vitro assay. While the use of stable or transient reporters did not influence the measurement of AHR agonistic activity, the species of the cell lines used in these reporter assays had important effects on the reporter readings. These observations suggest that cell-specific factors influence AHR activation and signaling. Thus, based on the reported species selectivity of AHR ligands and the cell species-of-origin effects that we describe in this manuscript, the use of human cell lines is encouraged for the analysis of AHR agonistic activity in human samples. These findings may be relevant for the analysis of AHR agonists in human samples in the context of inflammatory and neoplastic disorders.
Investigating the state dependence of drug binding in hERG channels using a trapped-open channel phenotype
Authors: Thouta Samrat , Lo Garman , Grajauskas Lukas , Claydon Tom 
Published: March 2018

AbstractThe hERG channel is a key player in repolarization of the cardiac action potential. Pharmacological blockade of hERG channels depletes the cardiac repolarization reserve, increasing the risk of cardiac arrhythmias. The promiscuous nature of drug interactions with hERG presents a therapeutic challenge for drug design and development. Despite considerable effort, the mechanisms of drug binding remain incompletely understood. One proposed mechanism is that high-affinity drug binding preferentially occurs when channels are in the inactivated state. However, this has been difficult to test, since inactivation is rapid in hERG and access to the drug binding site is limited by slower opening of the activation gate. Here, we have directly assessed the role of inactivation in cisparide and terfenadine drug binding in mutant (I663P) hERG channels where the activation gate is trapped-open. We firstly demonstrate the utility of this approach by showing that inactivation, ion selectivity and high affinity drug binding are preserved in I663P mutant channels. We then assess the role of inactivation by applying cisapride and terfenadine at different membrane voltages, which induce varying degrees of inactivation. We show that the extent of block does not correlate with the extent of inactivation. These data suggest that inactivation is not a major determinant of cisapride or terfenadine binding in hERG channels.
Modelling the sensory space of varietal wines: Mining of large, unstructured text data and visualisation of style patterns
Authors: Valente Carlo C. , Bauer Florian F. , Venter Fritz , Watson Bruce , Nieuwoudt Hélène H. 
Published: March 2018

AbstractThe increasingly large volumes of publicly available sensory descriptions of wine raises the question whether this source of data can be mined to extract meaningful domain-specific information about the sensory properties of wine. We introduce a novel application of formal concept lattices, in combination with traditional statistical tests, to visualise the sensory attributes of a big data set of some 7,000 Chenin blanc and Sauvignon blanc wines.Complexitywas identified as an important driver of style in hereto uncharacterised Chenin blanc, and the sensory cues for specific styles were identified. This is the first study to apply these methods for the purpose of identifying styles within varietal wines. More generally, our interactive data visualisation and mining driven approach opens up new investigations towards better understanding of the complex field of sensory science.
The effects of promoter variations of the N-Methylcanadine 1-Hydroxylase (CYP82Y1) gene on the noscapine production in opium poppy
Authors: Abedini Davar , Monfared Sajad Rashidi , Abbasi Alireza 
Published: March 2018

AbstractNoscapine is an antitumor alkaloid produced in opium poppy (Papaver somniferum) and some members of the Papaveraceae family. It has been primarily used for its antitussive effects; more recently, its anticancer properties were shown. Herein, we detected an SSR embedded in the promoter region of the CYP82Y1 gene, which was found to be the first committed-step enzyme in the noscapine biosynthesis pathway, using the MISA program. Some collected ecotypes of P. somniferum were investigated for understanding of SSRs role in the regulation of gene expression and metabolite content. Quantitative PCR showed that a variation in the motif repeat number (either a decrease or increase) down-regulated the expression of the CYP82Y1 gene. Furthermore, the analysis of noscapine content suggested that a variation in the promoter region influence noscapine amount. Moreover, P. bracteatum was analyzed in both transcript and metabolite levels, and illustrated much less expression and metabolite level in comparison to P. somniferum. By exploiting the transcriptome data from the eight genera of the Papaveraceae family, we found that noscapine biosynthesis genes are present in P. bracteatum and are not shared in other genera of the Papaveraceae family. This results may explain production of a confined metabolite within a genus.
Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling
Authors: Willems Brecht A. , Furmanik Malgorzata , Caron Marjolein M. J. , Chatrou Martijn L. L. , Kusters Dennis H. M. , Welting Tim J. M. , Stock Michael , Rafael Marta S. , Viegas Carla S. B. , Simes Dina C. , Vermeer Cees , Reutelingsperger Chris P. M. , Schurgers Leon J. 
Published: March 2018

AbstractVascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP−/− mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, β-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.
Do Participants Report Any Undesired Effects in Ultrasound Speech Therapy?
Authors: Preston Jonathan L. , Holliman-Lopez Gabriela , Leece Megan C. 
Published: March 2018

Purpose
Ultrasound visual feedback of the tongue is increasingly used as a component of speech therapy in clinical research and practice. The purpose is to offer a preliminary summary of the nature of participant-reported undesired effects related to ultrasound visual feedback.

Method
Sixty-two participants across 3 sites (mean age = 11.9 years) and 38 parents responded to a 2-item verbal questionnaire following 14–16 hr of treatment regarding any aspects of the treatment they did not like. Responses were thematically categorized.

Results
The 62 participants provided 65 distinct responses, which were categorized as follows: 31% no concerns, 40% gel-related (e.g., cold, sticky), 21% positioning of the probe (e.g., uncomfortable, annoying), 3% chin hurting (qualified as being minor in nature), and 5% other (i.e., unrelated to the use of the ultrasound). Responses from all parents suggested no concerns about the use of ultrasound; however, 8% expressed concerns unrelated to ultrasound use (e.g., fatigue).

Conclusion
These data inform clinicians and researchers about participant's experience and highlight the type of comments most likely to be encountered with ultrasound in speech therapy. Although the reported adverse effects can be considered minor, they should be weighed against the potential benefits of visual feedback in treatment.
Effective Use of Auditory Bombardment as a Therapy Adjunct for Children With Developmental Language Disorders
Authors: Plante Elena , Tucci Alexander , Nicholas Katrina , Arizmendi Genesis D. , Vance Rebecca 
Published: March 2018

Purpose
Modeling of grammatical forms has been used in conjunction with conversational recast treatment in various forms. This study tests the relative effect of providing bombardment prior to or after recast treatment.

Method
Twenty-eight children with developmental language disorder participated in daily conversational recast treatment for morpheme errors. This treatment was either preceded or followed by a brief period of intensive auditory bombardment. Generalization to untreated lexical contexts was measured throughout the treatment period to assess the degree of learning and how quickly the onset of measurable learning occurred.

Results
There were no significant differences in elicited use of morphemes for the groups of children who received auditory bombardment before or after enhanced conversational recast treatment. However, there was a difference in the number of children who could be considered treatment responders versus nonresponders, favoring those who received auditory bombardment after recast treatment.

Conclusion
A brief period of auditory bombardment is a relatively low cost addition to recast treatment methods, given how little time it takes. There is a small but measurable advantage to following recast treatment with a period of auditory bombardment.

Supplemental Material

https://doi.org/10.23641/asha.5960005