bluuebunny/crossref_metadata_2025 huggingface dataset:
Contiguous Metastasis of Pulmonary Adenocarcinoma to Meningioma
Authors: Nakaya Masato , Kurebayashi Yutaka , Mochizuki Youichi , Fukaya Raita , Fukuchi Masahito , Fujii Koji , Ichimura Shinya
Published: October 2018

Background Metastasis from one tumor into another is known as tumor-to-tumor metastasis. We report a case of a contiguous occurrence of meningioma and brain cancer metastasis.

Patient A 91-year-old woman presented with a sudden onset of weakness in her right limbs and gait disturbance. Fourteen years previously, she had a tumor that was suspected to be a meningioma in the left frontal convexity with no change for several years. One year earlier to presentation she was diagnosed with lung carcinoma in the left lower lobe.

Results Magnetic resonance images revealed enlargement of the tumor with perifocal edema. Histologic examination showed a meningioma with contiguous metastatic poorly differentiated adenocarcinoma, as well as a clearly defined border between the two components. The clinical origin of the metastasis was presumed to be from the left lower lobe of the lung.

Conclusion Although our case does not strictly fulfill the definition of tumor-to-tumor metastasis, we suggest a contiguous occurrence develops by the same mechanism and may be a subtype of this process. Although previous reports suggested the loss of epithelial cadherin (E-cadherin) expression in the recipient tumor as the cause of contiguous metastasis, E-cadherin expression was positive in our case and did not seem to be involved in the localization of the metastasis.
Using macrofaunal communities to inform estuarine classification
Authors: Beard Jason M. , Moltschaniwskyj Natalie A. , Crawford Christine M. , Gibson John A. E. , Ross D. Jeff
Published: October 2018

Worldwide, geomorphological classifications of estuaries are often used to guide the design of monitoring programs and management strategies. However, if classifications do not reflect biotic patterns, the effectiveness of monitoring and management is potentially reduced. In this study, we consider the effectiveness of one classification scheme in describing biotic patterns by examining and comparing spatial variation of macrofaunal assemblages and their relationship with the environment in 12 estuaries of 2 geomorphological types (mesotidal river dominated and permanently open barrier estuaries). Estuaries were sampled at three locations (upper, mid and lower) for macroinvertebrates and environmental characteristics. Differences in macrofaunal assemblages occurred between the estuary types at the lower and mid locations, but not the upper. Similarities in the upper locations were related to sediment, whereas at the mid and lower locations differences were linked to salinity, dissolved oxygen concentrations and seagrass area. Within estuaries, location effects were definitive and unique within each estuary type, correlating to changes in sediment particle size, nitrogen concentration, microphytobenthos and percentage organic carbon. These results suggest that estuarine classification based on physical attributes alone does have the potential to capture important biological attributes if the biological scales of variability within these systems are well understood.
Project ECHO: telementoring to educate and support prescribing of HIV pre-exposure prophylaxis by community medical providers
Authors: Wood Brian R. , Mann Maren S. , Martinez-Paz Natalia , Unruh Kenton T. , Annese Mary , Spach David H. , Scott John D. , Stekler Joanne D.
Published: October 2018

Background Pre-exposure prophylaxis (PrEP) is an effective tool to prevent HIV infection for at-risk individuals, but access requires medical providers to be aware of and comfortable with prescribing PrEP. Project ECHO (Extension for Community Healthcare Outcomes) was started to support hepatitis C virus treatment in rural New Mexico, but has since expanded to train health practitioners to treat other medical conditions in other locations. Methods: In 2012, a Project ECHO telehealth program was launched to mentor community HIV practitioners in our region. In July 2015, quarterly PrEP didactics and monthly PrEP case discussions were incorporated into this program. The result was a pilot PrEP telementoring intervention. An initial nine-question survey assessed baseline community practitioner knowledge and attitudes towards PrEP, and a follow-up 16-item survey 2 years later assessed the effect of Project ECHO on PrEP knowledge, concerns and prescribing practices. Results: Twenty-four and 45 medical providers completed the baseline and follow-up surveys respectively. In follow-up, providers reported that Project ECHO participation helped them stay current on PrEP guidelines, improved knowledge, increased likelihood to prescribe PrEP and addressed most concerns about prescribing PrEP. One exception was continued concerns about cost and insurance access, which were addressed by adjusting the didactic curriculum. Many participants reported that the Project ECHO pilot PrEP telementoring intervention assisted them in disseminating PrEP knowledge to other medical providers in their region. Conclusions: It is feasible to incorporate PrEP training into Project ECHO distance telementoring programs as a tool to educate community practitioners and support PrEP prescribing.
Trap Crops and Insectary Plants in the Order Brassicales
Authors: Badenes-Pérez Francisco Rubén
Published: October 2018

This paper reviews the most important cases of trap crops and insectary plants in the order Brassicales. Most trap crops in the order Brassicales target insects that are specialist in plants belonging to this order, such as the diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), the pollen beetle, Meligethes aeneus Fabricius (Coleoptera: Nitidulidae), and flea beetles in the genera Phyllotreta and Psylliodes (Coleoptera: Chrysomelidae). In most cases, the mode of action of these trap crops is the preferential attraction of the insect pest for the trap crop located next to the main crop. With one exception, these trap crops in the order Brassicales have been used with brassicaceous crops. Insectary plants in the order Brassicales attract a wide variety of natural enemies, but most studies focus on their effect on aphidofagous hoverflies and parasitoids. The parasitoids benefiting from insectary plants in the order Brassicales target insects pests ranging from specialists, such as P. xylostella, to highly polyfagous, such as the stink bugs Euschistus conspersus Uhler and Thyanta pallidovirens Stål (Hemiptera: Pentatomidae). In the order Brassicales, the three most common trap crops are Indian mustard, Brassica juncea (L.) Czern, Chinese cabbage, Brassica rapa L., and yellow rocket, Barbarea vulgaris R. Br., while the three most common insectary plants are sweet alyssum, Lobularia maritima (L.) Desv., white mustard, Sinapis alba L, and B. vulgaris. Except for Tropaeolum majus L. (Tropaeolaceae) and Capparis decidua (Forssk.) Edgew. (Capparaceae), the tested trap crops and insectary plants in the order Brassicales belong to the family Brassicaceae.
Reading and Deafness: Eye Tracking in Deaf Readers with Different Linguistic Background
Authors: Tomasuolo Elena , Roccaforte Maria , Di Fabio Andrea
Published: October 2018

The aim of this study was to investigate, using an eye-tracking tool, the processes behind the exploration of written texts performed by deaf people with different language skills and different educational backgrounds. Our sample comprised 36 deaf participants (12 of whom use Italian sign language most of the time, 12 who use Italian only, and 12 who can use both languages) and 12 hearing participants who could not understand any sign language. This research shows how in respect of oculomotor movements the discriminant variable is linked to the different educational backgrounds and the reading habits of participants.
Video Messaging as an Innovative Practice for CNO Communication
Authors: Stone Sherry , LaMotte Welch Edgar , Hofler Linda
Published: October 2018

In an effort to meet the challenge of facilitating communication between the chief nursing officer (CNO) and the nursing staff in a large academic medical center, an innovative approach was developed. Brainstorming with the Media Services Team, a plan was devised that created an avenue for sustained connection between the CNO and the nursing staff and a vehicle for staff to connect with one another: video segments known as Nurses Notebook.
Artificial intelligence policy in India: a framework for engaging the limits of data-driven decision-making
Authors: Marda Vidushi
Published: October 2018

Artificial intelligence (AI) is an emerging focus area of policy development in India. The country's regional influence, burgeoning AI industry and ambitious governmental initiatives around AI make it an important jurisdiction to consider, regardless of where the reader of this article lives. Even as existing policy processes intend to encourage the rapid development of AI for economic growth and social good, an overarching trend persists in India, and several other jurisdictions: the limitations and risks of data-driven decisions still feature as retrospective considerations for development and deployment of AI applications. This article argues that the technical limitations of AI systems should be reckoned with at the time of developing policy, and the societal and ethical concerns that arise due to such limitations should be used to
inform
what policy processes aspire to achieve. It proposes a framework for such deliberation to occur, by analysing the three main stages of bringing machine learning (the most popular subset of AI techniques) to deployment—the data, model and application stage. It is written against the backdrop of India's current AI policy landscape, and applies the proposed framework to ongoing sectoral challenges in India. With a view to influence existing policy deliberation in the country, it focuses on potential risks that arise from data-driven decisions in general, and in the Indian context in particular.

This article is part of the theme issue ‘Governing artificial intelligence: ethical, legal, and technical opportunities and challenges'.
Deep Recurrent Attention Models for Histopathological Image Analysis
Authors: Momeni Alexandre , Thibault Marc , Gevaert Olivier
Published: October 2018

Histopathology defines the gold standard in oncology. Automatic analysis of pathology images could thus have a significant impact on diagnoses, prognoses and treatment decisions for cancer patients. Recently, convolutional neural networks (CNNs) have shown strong performance in computational histopathology tasks. However, given it remains intractable to process pathology slides in their entirety, CNNs have traditionally performed inference on small individual patches extracted from the image. This often requires a significant amount of computation and can result in ignoring potentially relevant spatial and contextual information. Being able to process larger input patches and locating discriminatory regions more efficiently could help improve both computational and task specific performance. Inspired by the recent success of Deep Recurrent Attention Models (DRAMs) in image recognition tasks, we propose a novel attention-based architecture for classification in histopathology. Similar to CNNs, DRAMs have a degree of translation invariance built-in, but the amount of computation performed can be controlled independently from the input image size. The model is a deep recurrent neural network trained with reinforcement learning to attend to the most relevant areas of large input patches. We evaluate our model on histological and molecular subtype classification tasks for the glioma cohorts of The Cancer Genome Atlas (TCGA). Our results suggest that the DRAM has comparable performance to state-of-the-art CNNs despite only processing a select number of patches.
Robust Estimation of the Phylogenetic Origin of Plastids Using a tRNA-Based Phyloclassifier
Authors: Lawrence Travis J. , Amrine Katherine C. H. , Swingley Wesley D. , Ardell David H.
Published: October 2018

The trait of oxygenic photosynthesis was acquired by the last common ancestor of Archaeplastida through endosymbiosis of the cyanobacterial progenitor of modern-day plastids. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies report contradictory evidence that plastids branch either early or late within the cyanobacterial Tree of Life. Here we describe CYANO-MLP, a general-purpose phyloclassifier of cyanobacterial genomes implemented using a Multi-Layer Perceptron. CYANO-MLP exploits consistent phylogenetic signals in bioinformatically estimated structure-function maps of tRNAs. CYANO-MLP accurately classifies cyanobacterial genomes into one of eight well-supported cyanobacterial clades in a manner that is robust to missing data, unbalanced data and variation in model specification. CYANO-MLP supports a late-branching origin of plastids: we classify 99.32% of 440 plastid genomes into one of two late-branching cyanobacterial clades with strong statistical support, and confidently assign 98.41% of plastid genomes to one late-branching clade containing unicellular starch-producing marine/freshwater diazotrophic Cyanobacteria. CYANO-MLP correctly classifies the chromatophore of Paulinella chromatophora and rejects a sister relationship between plastids and the early-branching cyanobacterium Gloeomargarita lithophora. We show that recently applied phylogenetic models and character recoding strategies fit cyanobacterial/plastid phylogenomic datasets poorly, because of heterogeneity both in substitution processes over sites and compositions over lineages.
Metatranscriptome profiling of the dynamic transcription of mRNA and sRNA of a probioticLactobacillusstrain in human gut
Authors: Wang Jicheng , Sun Zhihong , Qiao Jianmin , Chen Dong , Cheng Chao , Luo Xiaotian , Ding Jia , Zhang Jiachao , Hou Qiangchuan , Zhang Yi , Zhang Heping
Published: October 2018

Metatranscriptomic sequencing has recently been applied to study how pathogens and probiotics affect human gastrointestinal (GI) tract microbiota, which provides new insights into their mechanisms of action. In this study, metatranscriptomic sequencing was applied to deduce thein vivoexpression patterns of an ingestedLactobacillus caseistrain, which was compared with itsin vitrogrowth transcriptomes. Extraction of the strain-specific reads revealed that transcripts from the ingestedL. caseiwere increased, while those from the residentL. paracaseistrains remained unchanged. Mapping of all metatranscriptomic reads and transcriptomic reads toL. caseigenome showed that gene expressionin vitroandin vivodiffered dramatically. About 39% (1163) mRNAs and 45% (93) sRNAs ofL. caseiwell-expressed were repressed after ingested into human gut. Expression of ABC transporter genes and amino acid metabolism genes was induced at day-14 of ingestion; and genes for sugar and SCFA metabolisms were activated at day-28 of ingestion. Moreover, expression of sRNAs specific to thein vitrolog phase was more likely to be activated in human gut. Expression of rli28c sRNA with peaked expression during thein vitrostationary phase was also activated in human gut; this sRNA repressedL. caseigrowth and lactic acid productionin vitro. These findings implicate that the ingestedL. caseimight have to successfully change its transcription patterns to survive in human gut, and the time-dependent activation patterns indicate a highly dynamic cross-talk between the probiotic and human gut including its microbe community.

Importance

Probiotic bacteria are important in food industry and as model microorganisms in understanding bacterial gene regulation. Although probiotic functions and mechanisms in human gastrointestinal tract are linked to the unique probiotic gene expression, it remains elusive how transcription of probiotic bacteria is dynamically regulated after being ingested. Previous study of probiotic gene expression in human fecal samples has been restricted due to its low abundance and the presence of of closely related species. In this study, we took the advantage of the good depth of metatranscriptomic sequencing reads and developed a strain-specific read analysis method to discriminate the transcription of the probioticLactobacillus caseiand those of its resident relatives. This approach and additional bioinformatics analysis allowed the first study of the dynamic transcriptome profiles of probioticL casei in vivo. The novel findings indicate a highly regulated repression and dynamic activation of probiotic genome in human GI tract.
Tissue-specific genes as an underutilized resource in drug discovery
Authors: Ryaboshapkina Maria , Hammar Mårten
Published: October 2018

Tissue-specific genes are believed to be good drug targets due to improved safety. Here we show that this intuitive notion is not reflected in phase 1 and 2 clinical trials, despite the historic success of tissue-specific targets and their 2.3-fold overrepresentation among targets of marketed non-oncology drugs. We compare properties of tissue-specific genes and drug targets. We show that tissue-specificity of the target may also be related to efficacy of the drug. The relationship may be indirect (enrichment in Mendelian disease genes) or direct (elevated ability to spread perturbations in human protein-protein interactome for tissue-specifically produced enzymes and secreted proteins). Reduced evolutionary conservation of tissue-specific genes may represent a bottleneck for drug projects, prompting development of novel models with smaller evolutionary gap to humans. We highlight numerous open opportunities to use tissue-specific genes in drug research and hope that the current study will facilitate discovery efforts.
I knew that! Response-based Outcome Predictions and Confidence Regulate Feedback Processing and Learning
Authors: Frömer R. , Nassar M.R. , Bruckner R. , Stürmer B. , Sommer W. , Yeung N.
Published: October 2018

Influential theories emphasize the importance of predictions in learning: we learn from feedback to the extent that it is surprising, and thus conveys new information. Here we explore the hypothesis that surprise depends not only on comparing current events to past experience, but also on online evaluation of performance via internal monitoring. Specifically, we propose that people leverage insights from response-based performance monitoring – outcome predictions and confidence – to control learning from feedback. In line with predictions from a Bayesian inference model, we find that people who are better at calibrating their confidence to the precision of their outcome predictions learn more quickly. Further in line with our proposal, EEG signatures of feedback processing are sensitive to the accuracy of, and confidence in, post-response outcome predictions. Taken together, our results suggest that online predictions and confidence serve to calibrate neural error signals to improve the efficiency of learning.
Differential generation of saccade, fixation and image onset event-related potentials in the human mesial temporal lobe
Authors: Katz Chaim N. , Patel Kramay , Talakoub Omid , Groppe David , Hoffman Kari , Valiante Taufik A.
Published: October 2018

The electrophysiological signatures of encoding and retrieval recorded from mesial temporal lobe (MTL) structures are observed as event related potentials (ERPs) during visual memory tasks. The waveforms of the ERPs associated with the onset of visual stimuli (image-onset) and eye movements (saccades and fixations) provide insights into the mechanisms of their generation. We hypothesized that since eye movements and image-onset (common methods of stimulus presentation when testing memory) provide MTL structures with salient visual information, that perhaps they both engage similar neural mechanisms. To explore this question, we used intracranial electroencephalographic (iEEG) data from the MTLs of 11 patients with medically refractory epilepsy who participated in a visual search task. We sought to characterize electrophysiological responses of MTL structures to saccades, fixations and image onset. We demonstrate that the image-onset response is an evoked/additive response with a low-frequency power increase and post-stimulus phase clustering. In contrast, ERPs following eye movements appeared to arise from phase resetting of higher frequencies than the image onset ERP. Intriguingly, this reset was associated with saccade onset and not saccade termination (fixation), suggesting it is likely the MTL response to a corollary discharge, rather than a response to visual stimulation - in stark contrast to the image onset response. The distinct mechanistic underpinnings of these two ERP may help guide future development of visual memory tasks.
Affectively biased competition: sustained attention is tuned to rewarding expressions and is not modulated by norepinephrine receptor gene variant
Authors: Roberts Kevin H. , Manaligod Maria G. M. , Ross Colin J. D. , Müller Daniel J. , Wieser Matthias J. , Todd Rebecca M.
Published: October 2018

It is well established that emotionally salient stimuli evoke greater visual cortex activation than neutral ones, and can distract attention from competing tasks. Yet less is known about underlying neurobiological processes. As a proxy of population level biased competition, EEG steady-state visual evoked potentials are sensitive to competition effects from salient stimuli. Here we wished to examine whether individual differences in norepinephrine activity play a role in emotionally-biased competition.

Our previous research has found robust effects of a common variation in the ADRA2B gene, coding for alpha2B norepinephrine (NE) receptors, on emotional modulation of attention and memory. In the present study, EEG was collected while 87 carriers of the ADRA2B deletion variant and 95 non-carriers (final sample) performed a change detection task in which target gratings (gabor patches) were superimposed directly over angry, happy, and neutral faces. Participants indicated the number of phase changes (0-3) in the target. Overlapping targets and distractors were flickered at a distinct driving frequencies. Relative EEG power for faces vs. targets at the driving frequency served as an index of cortical resources allocated to each of the competing stimuli. Deletion carriers and non-carriers were randomly assigned to Discovery and Replication samples and reliability of results across samples was assessed before the groups were combined for greater power.

Overall happy faces evoked higher competition than angry or neutral faces; however, we observed no hypothesized effects of ADRA2B. Increased competition from happy faces was not due to the effect of low-level visual features or individuals low in social anxiety. Our results indicate that emotionally biased competition during sustained attention, while reliably observed in young adults, is not influenced by commonly observed individual differences linked to NE receptor function. They further indicate an overall pattern of affectively-biased competition for happy faces, which we interpret in relation to previously observed boundary conditions.
ADAR2-mediated Q/R editing of GluK2 regulates kainate receptor upscaling in response to suppression of synaptic activity
Authors: Gurung Sonam , Evans Ashley J. , Wilkinson Kevin A. , Henley Jeremy M.
Published: October 2018

Kainate receptors (KARs) regulate neuronal excitability and network function. Most KARs contain the subunit GluK2 and the properties of these receptors are determined in part by ADAR2-mediated mRNA editing of GluK2 that changes a genomically encoded glutamine (Q) to arginine (R). Suppression of synaptic activity reduces ADAR2-dependent Q/R editing of GluK2 with a consequential increase in GluK2-containing KAR surface expression. However, the mechanism underlying this reduction in GluK2 editing has not been addressed. Here we show that induction of KAR upscaling results in proteasomal degradation of ADAR2, which reduces GluK2 Q/R editing. Because KARs incorporating unedited GluK2(Q) assemble and exit the ER more efficiently this leads to an upscaling of KAR surface expression. Consistent with this, we demonstrate that partial ADAR2 knockdown phenocopies and occludes KAR upscaling. Moreover, we show that although the AMPAR subunit GluA2 also undergoes ADAR2-dependent Q/R editing, this process does not mediate AMPAR upscaling. These data demonstrate that activity-dependent regulation of ADAR2 proteostasis and GluK2 Q/R editing are key determinants of KAR, but not AMPAR, trafficking and upscaling.

Summary statement

Synaptic suppression promotes proteasomal degradation of the mRNA-editing enzyme ADAR2. Decreased ADAR2 levels reduce Q/R editing of the kainate receptor subunit GluK2 leading to enhanced surface expression and homeostatic upscaling.
Mutually exclusive locales for N-linked glycans and disorder in glycoproteins
Authors: Singh Alvina , Kumari Indu , Pally Dharma , Goutham Shyamili , Ghosh Sujasha , Akhter Yusuf , Bhat Ramray
Published: October 2018

Several post-translational modifications of proteins lie within regions of disorder, stretches of amino acid residues that exhibit a dynamic tertiary structure and resist crystallization. Such localization has been proposed to expand the binding versatility of the disordered regions, and hence, the repertoire of interacting partners for the proteins. However, investigating a dataset of 500 human N-linked glycoproteins, we observed that the sites of N-linked glycosylations, or N-glycosites, lay predominantly within the regions of predicted order rather than their unstructured counterparts. This mutual exclusivity between disordered stretches and N-glycosites could not be reconciled merely through asymmetry in distribution of asparagines, serines or threonines residues, which comprise the minimum-required signature for conjugation by N-linked glycans, but rather by a contextual enrichment of these residues next to each other within the ordered portions. In fact, N-glycosite neighborhoods and disordered stretches showed distinct sets of enriched residues suggesting their individualized roles in protein phenotype. N-glycosite neighborhood residues also showed higher phylogenetic conservation than disordered stretches within amniote orthologs of glycoproteins. However, a universal search for residue-combinations that are putatively domain-constitutive ranked the disordered regions higher than the N-glycosite neighborhoods. We propose that amino acid residue-combinations bias the permissivity for N-glycoconjugation within ordered regions, so as to balance the tradeoff between the evolution of protein stability, and function, contributed by the N-linked glycans and disordered regions respectively.
Mis-perception of motion in depth originates from an incomplete transformation of retinal signals
Authors: Scott Murdison T. , Leclercq Guillaume , Lefèvre Philippe , Blohm Gunnar
Published: October 2018

Depth perception requires the use of an internal model of the eye-head geometry to infer distance from binocular retinal images and extraretinal 3D eye-head information, particularly ocular vergence. Similarly for motion in depth perception, gaze angle is required to correctly interpret the spatial direction of motion from retinal images; however, it is unknown whether the brain can make adequate use of extraretinal version and vergence information to correctly interpret binocular retinal motion for spatial motion in depth perception. Here, we tested this by asking participants to reproduce the perceived spatial trajectory of an isolated point stimulus moving on different horizontal-depth paths either peri-foveally or peripherally while participants’ gaze was oriented at different vergence and version angles. We found large systematic errors in the perceived motion trajectory that reflected an intermediate reference frame between a purely retinal interpretation of binocular retinal motion (ignoring vergence and version) and the spatially correct motion. A simple geometric model could capture the behavior well, revealing that participants tended to underestimate their version by as much as 17%, overestimate their vergence by as much as 22%, and underestimate the overall change in retinal disparity by as much as 64%. Since such large perceptual errors are not observed in everyday viewing, we suggest that other monocular and/or contextual cues are required for accurate real-world motion in depth perception.
Microplate Assay for Denatured Collagen using Collagen Hybridizing Peptides
Authors: Lin Allen H. , Zitnay Jared L. , Li Yang , Yu S. Michael , Weiss Jeffrey A.
Published: October 2018

The purpose of this study was to develop a microplate assay for quantifying denatured collagen by measuring the fluorescence of carboxyfluorescein bound collagen hybridizing peptides (F-CHP). We have shown that F-CHP binds selectively with denatured collagen, and that mechanical overload of tendon fascicles causes collagen denaturation. Proteinase K was used to homogenize tissue samples after F-CHP staining, allowing fluorescence measurement using a microplate reader. We compared our new assay to our previous image analysis method and the trypsin-hydroxyproline assay, which is the only other available method to directly quantify denatured collagen. Relative quantification of denatured collagen was performed in rat tail tendon fascicles subjected to incremental tensile overload, and normal and ostoeoarthritic guinea pig cartilage. In addition, the absolute amount of denatured collagen was determined in rat tail tendon by correlating F-CHP fluorescence with percent denatured collagen as determined by the trypsin-hydroxyproline assay. Rat tail tendon fascicles stretched to low strains (<7.5%) exhibited minimal denature collagen, but values rapidly increased at medium strains (7.5-10.5%) and plateaued at high strains (≥12%). Osteoarthritic cartilage had higher F-CHP fluorescence than healthy cartilage. Both of these outcomes are consistent with previous studies. With the calibration curve, the microplate assay was able to absolutely quantify denatured collagen in mechanically damaged rat tail tendon fascicles as reliably as the trypsin-hydroxyproline assay. Further, we achieved these results more efficiently than current methods in a rapid, high-throughput manner, with multiple types of collagenous tissue while maintaining accuracy.
The effects of training population design on genomic prediction accuracy in wheat
Authors: Edwards Stefan McKinnon , Buntjer Jaap B. , Jackson Robert , Bentley Alison R. , Lage Jacob , Byrne Ed , Burt Chris , Jack Peter , Berry Simon , Flatman Edward , Poupard Bruno , Smith Stephen , Hayes Charlotte , Gaynor R. Chris , Gorjanc Gregor , Howell Phil , Ober Eric , Mackay Ian J. , Hickey John M.
Published: October 2018

Genomic selection offers several routes for increasing genetic gain or efficiency of plant breeding programs. In various species of livestock there is empirical evidence of increased rates of genetic gain from the use of genomic selection to target different aspects of the breeder’s equation. Accurate predictions of genomic breeding value are central to this and the design of training sets is in turn central to achieving sufficient levels of accuracy. In summary, small numbers of close relatives and very large numbers of distant relatives are expected to enable accurate predictions.

To quantify the effect of some of the properties of training sets on the accuracy of genomic selection in crops we performed an extensive field-based winter wheat trial. In summary, this trial involved the construction of 44 F2:4 bi- and triparental populations, from which 2992 lines were grown on four field locations and yield was measured. For each line, genotype data were generated for 25,000 segregating single nucleotide polymorphism markers. The overall heritability of yield was estimated to 0.65, and estimates within individual families ranged between 0.10 and 0.85. Within cross genomic prediction accuracies of yield BLUEs were 0.125 – 0.127 using two different cross-validation approaches, and generally increased with training set size. Using related crosses in training and validation sets generally resulted in higher prediction accuracies than using unrelated crosses. The results of this study emphasize the importance of the training set design in relation to the genetic material to which the resulting prediction model is to be applied.
Programmed Delayed Splicing: A Mechanism for Timed Inflammatory Gene Expression
Authors: Majumdar Devdoot S. , Frankiw Luke , Burns Christian H. , Garcia-Flores Yvette , Baltimore David
Published: October 2018

Inflammation involves timed gene expression, suggesting that the fine-tuned onset, amplitude, and termination of expression of hundreds of genes is of critical importance to organismal homeostasis. Recent study of post-transcriptional regulation of inflammatory gene expression led to the suggestion of a regulatory role for pre-mRNA splicing. Here, using a hybrid capture approach to purify incompletely spliced, chromatin-associated pre-mRNAs, we use deep sequencing to study pre-mRNA splicing of the NF-kB transcriptome. By freezing transcription and examining subsequent splicing of complete transcripts, we find many introns splice tens to hundreds of times slower than average. In many cases, this is attributable to poor splice donor sequences that are evolutionarily conserved. When these introns were altered by ~2 base pairs to yield stronger splice donors, gene expression levels increased markedly for several genes in the context of a reporter system. We propose that such splice sites represent a regulatory mechanism that determines the timing of production of the mRNAs from certain inflammatory genes and may also limit mRNA expression from these genes. Further work will be needed to understand the roles of this regulation in the inflammatory response. The suggestion of extensive temporal regulation of pre-mRNA splicing as a regulatory process in inflammation raises the question of where else in biology there may be timed processes with a similar underlying cause.
A bibliometric analysis of event detection in social media
Authors: Chen Xieling , Wang Shan , Tang Yong , Hao Tianyong
Published: October 2018

Purpose

The purpose of this paper is to explore the research status and development trend of the field of event detection in social media (ED in SM) through a bibliometric analysis of academic publications.

Design/methodology/approach

First, publication distributions are analyzed including the trends of publications and citations, subject distribution, predominant journals, affiliations, authors, etc. Second, an indicator of collaboration degree is used to measure scientific connective relations from different perspectives. A network analysis method is then applied to reveal scientific collaboration relations. Furthermore, based on keyword co-occurrence analysis, major research themes and their evolutions throughout time span are discovered. Finally, a network analysis method is applied to visualize the analysis results.

Findings

The area of ED in SM has received increasing attention and interest in academia with Computer Science and Engineering as two major research subjects. The USA and China contribute the most to the area development. Affiliations and authors tend to collaborate more with those within the same country. Among the 14 identified research themes, newly emerged themes such as Pharmacovigilance event detection are discovered.

Originality/value

This study is the first to comprehensively illustrate the research status of ED in SM by conducting a bibliometric analysis. Up-to-date findings are reported, which can help relevant researchers understand the research trend, seek scientific collaborators and optimize research topic choices.
Two‐ and three‐dimensional ultrasonographic features related to histopathology of the uterine endometrial‐myometrial junctional zone
Authors: Rasmussen Christina Kjaergaard , Hansen Estrid Staehr , Dueholm Margit
Published: October 2018

Introduction

Our aim was to correlate junctional zone thickening and irregularity (junctional zone disease) and other ultrasonographic features of adenomyosis with the histopathology of the endometrial‐myometrial junctional zone.

Material and methods

Consecutively enrolled premenopausal women (n = 110) scheduled for hysterectomy or transcervical endometrial resection due to abnormal uterine bleeding and/or menstrual pain, underwent two‐ and three‐dimensional transvaginal ultrasonography on the day of surgery with the observer blinded to previous diagnosis. Junctional zone maximum thickness (JZmax), junctional zone maximum irregularity (JZdif) and ultrasonographic characteristics of adenomyosis were compared with histopathology of the junctional zone defined as (1) adenomyosis of the inner myometrium, ≥2 mm myometrial invasion without contact to the basal endometrium, (2) serrated junctional zone, >3 mm myometrial invasion with contact to the basal endometrium or (3) linear junctional zone, no or marginal myometrial invasion ≤3 mm with contact to the basal endometrium.

Results

Adenomyosis of the inner myometrium, serrated junctional zone and linear junctional zone was present in 29%, 35% and 35% of the women, respectively. Median JZmax and median JZdif expanded from linear junctional zone (8.5 and 3.3 mm) to serrated junctional zone (10.1 and 4.1 mm) to adenomyosis of the inner myometrium (14.6 and 9.2 mm) (P < 0.05). In addition, the median number of characteristic adenomyosis‐like ultrasonographic features increased from the linear junctional zone to the serrated junctional zone to adenomyosis of the inner myometrium (P < 0.05).

Conclusions

A slightly thickened and/or irregular junctional zone corresponds to a histopathologically defined serrated junctional zone. This study emphasizes three distinct appearances of the junctional zone: adenomyosis of the inner myometrium, junctional zone disease (serrated junctional zone) and linear junctional zone. This classification may be useful in future clinical studies.
Socioeconomic Inequality and the Developing Brain: Spotlight on Language and Executive Function
Authors: Merz Emily C. , Wiltshire Cynthia A. , Noble Kimberly G.
Published: October 2018

Robust evidence of the deleterious effects of poverty on children's academic achievement has generated considerable interest in the neural mechanisms underlying these associations. In studies of specific neurocognitive skills, researchers have found pronounced socioeconomic disparities in children's language and executive function (EF) skills. In this article, we review research linking socioeconomic factors (e.g., family income, parental education) with children's brain structure and function, focusing on the neural systems involved in language and EF. Then, we cover the potential mediators of these associations, developmental timing, and strategies for prevention and intervention. To complement research at the behavioral level, we conclude with recommendations for integrating measures of the developing brain into this ongoing work.
Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation
Authors: Xing S , Zhang X , Liu J H , Huang X , Zhou P
Published: October 2018

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c+ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.
Challenges of next‐generation sequencing in conservation management: Insights from long‐term monitoring of corridor effects on the genetic diversity of mouse lemurs in a fragmented landscape
Authors: Montero B. Karina , Refaly Ernest , Ramanamanjato Jean‐Baptiste , Randriatafika Faly , Rakotondranary S. Jacques , Wilhelm Kerstin , Ganzhorn Jörg U. , Sommer Simone
Published: October 2018

Long‐term genetic monitoring of populations is essential for efforts aimed at preserving genetic diversity of endangered species. Here, we employ a framework of long‐term genetic monitoring to evaluate the effects of fragmentation and the effectiveness of the establishment of corridors in restoring population connectivity and genetic diversity of mouse lemurs Microcebus ganzhorni. To this end, we supplement estimates of neutral genetic diversity with the assessment of adaptive genetic variability of the major histocompatibility complex (MHC). In addition, we address the challenges of long‐term genetic monitoring of functional diversity by comparing the genotyping performance and estimates of MHC variability generated by single‐stranded conformation polymorphism (SSCP)/Sanger sequencing with those obtained by high‐throughput sequencing (next‐generation sequencing [NGS], Illumina), an issue that is particularly relevant when previous work serves as a baseline for planning management strategies that aim to ensure the viability of a population. We report that SSCP greatly underestimates individual diversity and that discrepancies in estimates of MHC diversity attributable to the comparisons of traditional and NGS genotyping techniques can influence the conclusions drawn from conservation management scenarios. Evidence of migration among fragments in Mandena suggests that mouse lemurs are robust to the process of fragmentation and that the effect of corridors is masked by ongoing gene flow. Nonetheless, results based on a larger number of shared private alleles at neutral loci between fragment pairs found after the establishment of corridors in Mandena suggest that gene flow is augmented as a result of enhanced connectivity. Our data point out that despite low effective population size, M. ganzhorni maintains high individual heterozygosity at neutral loci and at MHC II DRB gene and that selection plays a predominant role in maintaining MHC diversity. These findings highlight the importance of long‐term genetic monitoring in order to disentangle between the processes of drift and selection maintaining adaptive genetic diversity in small populations.
Drebrin 1 in dendritic cells regulates phagocytosis and cell surface receptor expression through recycling for efficient antigen presentation
Authors: Elizondo Diana M. , Andargie Temesgen E. , Haddock Naomi L. , Boddie Thomas A. , Lipscomb Michael W.
Published: October 2018

Phagocytosis, macropinocytosis and antigen presentation by dendritic cells (DC) requires reorganization of the actin cytoskeleton. Drebrin (Dbn1) is an actin binding and stabilizing protein with roles in endocytosis, formation of dendrite spines in neurons and coordinating cell–cell synapses in immune cells. However, its role in DC phagocytosis and antigen presentation is unknown. These studies now report that silencing of Dbn1 in DC resulted in restrained cell surface display of receptors, most notably MHC class I and II and co‐stimulatory molecules. This, as expected, resulted in impaired antigen‐specific T‐cell activation and proliferation. Studies additionally revealed that knockdown of Dbn1 in DC impaired macropinocytosis and phagocytosis. However, there was a concomitant increase in fluid‐phase uptake, suggesting that Dbn1 is responsible for the differential control of macropinocytosis versus micropinocytosis activities. Taken together, these findings now reveal that Dbn1 plays a major role in coordinating the actin cytoskeletal activities responsible for antigen presentation in DC.
PML‐RARα interferes with erythropoiesis by repressing LMO2 in acute promyelocytic leukaemia
Authors: Yang Xianwen , Tan Yun , Wang Ping , Zhang Hui , Zhao Ming , Zhao Xujie , Wang Kankan
Published: October 2018

The PML‐RARα fusion gene, generated by the t(15;17) chromosome translocation, is regarded as the initiating factor of acute promyelocytic leukaemia (APL). In addition to the well‐known effects on blocking myeloid differentiation at the promyelocytic stage, promyelocytic leukaemia‐retinoic acid receptor α (PML‐RARα) has also been reported to interfere with multiple differentiation processes, including erythroid differentiation. However, the detailed molecular mechanism by which PML‐RARα impairs erythropoiesis has not yet been fully addressed. By chromatin immunoprecipitation‐PCR assay, we found that PML‐RARα bound to the distal promoter region of LMO2 (LIM‐only protein 2), a critical erythroid‐specific transcription factor. Luciferase reporter assays and qRT‐PCR results demonstrated that PML‐RARα down‐regulated the expression of the LMO2 distal transcript through transrepressing its promoter activity. Analysis of gene expression profiling data from large cohorts of acute myeloid leukaemia (AML) patients confirmed that LMO2 expressed at a markedly lower level in APL patients in comparison to non‐APL AML patients. Further flow cytometry analysis demonstrated that PML‐RARα inhibited erythropoietin‐induced erythroid differentiation by down‐regulating LMO2 expression. Our findings reveal a previously unidentified mechanism, by which PML‐RARα interferes with erythropoiesis through directly targeting and transrepressing LMO2 expression in the development of APL.
Cardioprotective effects of the novel curcumin analogue C66 in diabetic mice is dependent on JNK2 inactivation
Authors: Li Cheng , Miao Xiao , Lou Yan , Lu Zhengyang , Adhikari Binay Kumar , Wang Yangwei , Liu Quan , Sun Jian , Wang Yonggang
Published: October 2018

Aim

Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes‐induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66‐mediated cardioprotection.

Methods

An experimental diabetic model was established using JNK2−/− and wild‐type (WT) mice. C66 (5 mg/kg) was administered orally every other day for 3 months. Body weight, plasma glucose levels, cardiac function, and structure were measured. Masson trichrome and TUNEL staining were used to assess myocardial fibrosis and apoptosis, respectively. mRNA and protein levels of inflammation, fibrosis, oxidative stress, and apoptosis molecules were measured by quantitative PCR and Western blot, respectively.

Results

Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2−/− diabetic mice compared to JNK2−/− control mice, and C66 treatment did not further affect these parameters in JNK2−/− diabetic mice.

Conclusions

Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.