bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG spectral power, but not theta/beta ratio, is a neuromarker for adult ADHD
Authors: Kiiski Hanni , Bennett Marc , Rueda-Delgado Laura M. , Farina Francesca , Knight Rachel , Boyle Rory , Roddy Darren , Grogan Katie , Bramham Jessica , Kelly Clare , Whelan Robert 
Published: July 2019

AbstractBackgroundAdults with attention-deficit/hyperactivity disorder (ADHD) have been described as having altered resting-state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behavior (mediational endophenotypes).MethodsResting-state eyes-open and eyes-closed EEG were measured from 38 adults with ADHD, 45 first-degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1-45 Hz) and TBR could classify participants into ADHD, first-degree relatives and/or control groups. Random-label permutation was used to quantify any bias in the analysis.ResultsEyes-open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = .71-.77). The best predictors of ADHD status were increased power in delta, theta and low-alpha over centro-parietal regions, and in frontal low-beta and parietal mid-beta. TBR did not classify ADHD status. Elevated eyes-open power in delta, theta, low-alpha and low-beta distinguished first-degree relatives from controls (area under receiver operating characteristic = .68-.72), suggesting that these features may be a mediational endophenotype for adult ADHD.ConclusionsResting-state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.
Temporal cascade of frontal, motor and muscle processes underlying human action-stopping
Authors: Jana Sumitash , Hannah Ricci , Muralidharan Vignesh , Aron Adam R. 
Published: July 2019

AbstractAction-stopping is a canonical executive function thought to involve top-down control over the motor system. Here we aimed to validate this stopping system using high temporal resolution methods in humans. We show that, following the requirement to stop, there was an increase of right frontal beta (∼13 to 30 Hz) at ∼120 ms, likely a proxy of right inferior frontal gyrus; then, at 140 ms, there was a broad skeletomotor suppression, likely reflecting the impact of the subthalamic nucleus on basal ganglia output; then, at ∼160 ms, suppression was detected in the muscle, and, finally, the behavioral time of stopping was ∼220 ms. This temporal cascade confirms a detailed model of action-stopping, and partitions it into subprocesses that are isolable to different nodes and are more precise than the behavioral speed of stopping. Variation in these subprocesses, including at the single-trial level, could better explain individual differences in impulse control.
Viral rebound kinetics following single and combination immunotherapy for HIV/SIV
Authors: Prague Mélanie , Gerold Jeffrey M , Balelli Irene , Pasin Chloé , Li Jonathan Z , Barouch Dan H , Whitney James B , Hill Alison L 
Published: July 2019

AbstractHIV infection can be treated but not cured with antiretroviral therapy, motivating the development of new therapies that instead target host immune responses. Three such immunotherapies were recently tested in non-human primates – a TLR7-agonist, therapeutic vaccine, and broadly-neutralizing antibody – and cured a subset of animals by preventing or controlling viral rebound after antiretrovirals were stopped. However, their mechanism of action remains unknown; for example, whether they reduced the pool of latently-infected cells versus boosted antiviral immunity, and whether they acted independently or synergistically. Here we conduct a detailed analysis of the kinetics of viral rebound after immunotherapy, and use mathematical models combined with rigorous statistical fitting to quantify the impact of these interventions on viral dynamics. We find that the vaccine reduced reactivation of latent virus by 4-fold, and boosted the avidity of antiviral immune responses by 17-fold when alone and 210-fold when combined with the TLR7-agonist. In the context of later initiation of antiretroviral therapy only, the TLR7-agonist reduced latent reservoir reactivation by 8-fold, but also slightly increased target cell availability (1.5-fold). The antibody boosted immune response avidity (8-fold) and displayed no detectable synergy with the TLR7-agonist. To predict the impact of these immunotherapies in clinical trials, we calibrated a model of HIV rebound to human treatment interruption trials and simulated the effect of adding each therapy. Overall, our results provide a framework for understanding the relative contributions of different mechanisms of preventing viral rebound and highlight the multifaceted roles of TLR7-agonists for HIV/SIV cure.
Host defense responses of CO441 and CL30 maize lines toFusarium graminearumanalyzed by comparative label-free quantitative proteomics
Authors: Reid Lana M. , Altosaar Illimar 
Published: July 2019

AbstractGibberella ear rot is a disease of maize associated with low yields and the production of harmful mycotoxins therein. The disease is caused by the infection of hostZea mayswith fungal pathogenFusarium graminearum. Resistant (CO441) and susceptible (CL30) inbred maize line kernels were inoculated with conidial suspensions ofF. graminearumor water (controls). Ears of maize (cobs) from each line were harvested upon maturation and proteins were extracted from the embryo tissue of the kernels to study tissue-specific response of the host. Embryo proteins from both CO441 and CL30 lines were sequenced using mass spectrometry (LC-MS/MS) and quantified using Label Free Quantification (LFQ). Following filtering, 509 proteins were identified. These proteins were grouped into nine functional categories:Fusarium-derived, late embryogenesis abundant, oil-body, metabolism, stress, cellular, protein storage, metabolism, and defense. Defense proteins were up-regulated in response to infection in both CO441 and CL30 lines. Furthermore,F. graminearumderived proteins were only found in CL30 infected kernels suggesting that resistance may be attributed in part to the inability ofFusariumto establish itself in the embryo. To our knowledge this is the first successful application of LFQ mass spectrometry to the study of host-pathogen response toF. graminearum.Biological significanceFungal pathogenFusarium graminearumis responsible for billion dollar losses in crops and contamination of global grains with harmful mycotoxins. By studying host-pathogen interactions ofFusariumand maize on a proteomic level with resistant and susceptible genotypes, the biological interactions occurring during infection of the maturing seed were characterized. Mature kernels of theF. graminearumsusceptible maize line CL30 and resistant CO441 line were dissected to permit a proteomic survey of the new sporophytic generation, the embryo. Detailed knowledge of this Host-pathogen interactome will assist development of new cereal lines resistant to the rot diseases caused byFusarium graminearum.HighlightsSusceptible (CL30) and Resistant (CO441) lines were injected with water mock or F. graminearum LC-MS/MS of maize embryo protein extracts followed by Label Free Quantification (LFQ) permitted identification, quantification and comparison of proteomes between maize genotypes and treatments Fusarium-derived proteins were abundant only in the susceptible infected embryo Defense proteomes were up-regulated in both lines following infection nsLTP and Protease Inhibitor were significantly over-expressed in the Susceptible line after infection; chitinase and WIP1 were significantly over-expressed in the Resistant line after infection
Sugar-phosphate metabolism regulates stationary phase entry and stalk elongation inCaulobacter crescentus
Authors: de Young Kevin D. , Stankeviciute Gabriele , Klein Eric A. 
Published: July 2019

AbstractBacteria have a variety of mechanisms for adapting to environmental perturbations. Changes in oxygen availability result in a switch between aerobic and anaerobic respiration, whereas iron limitation may lead to siderophore secretion. In addition to metabolic adaptations, many organisms respond by altering their cell shape.Caulobacter crescentus, when grown under phosphate limiting conditions, dramatically elongates its polar stalk appendage. The stalk is hypothesized to facilitate phosphate uptake; however, the mechanistic details of stalk synthesis are not well characterized. We used a chemical mutagenesis approach to isolate and characterize stalk-deficient mutants, one of which had two mutations in the phosphomannose isomerase gene (manA) that were necessary and sufficient to inhibit stalk elongation. Transcription of thephoregulon was unaffected in themanAmutant; therefore, ManA plays a unique regulatory role in stalk synthesis. The mutant ManA had reduced enzymatic activity resulting in a 5-fold increase in the intracellular fructose 6-phosphate: mannose 6-phosphate ratio. This metabolic imbalance impaired the synthesis of cellular envelope components derived from mannose 6-phosphate, namely lipopolysaccharide O-antigen and exopolysaccharide. Furthermore, themanAmutations preventedC. crescentuscells from efficiently entering stationary phase. Deletion of the stationary-phase response regulatorspdRinhibited stalk elongation in wild-type cells while overproduction of the alarmone ppGpp, which triggers growth arrest and stationary phase entry, increased stalk length in themanAmutant strain. These results demonstrate that sugar-phosphate metabolism regulates stalk elongation independently of phosphate starvation.ImportanceBacteria have various mechanisms for adapting to environmental perturbations including morphological alterations. During phosphate limitation,Caulobacter crescentusdramatically elongates its polar stalk appendage. The stalk is hypothesized to facilitate phosphate uptake; however, the mechanism of stalk synthesis is not well characterized. We isolated stalk-deficient mutants, one of which had mutations in the phosphomannose isomerase gene (manA) that blocked stalk elongation, despite normal activation of the phosphate-starvation response. The mutant ManA produced an imbalance in sugar-phosphate concentrations that impaired the synthesis of cellular envelope components and prevented entry into stationary phase. Overproduction of the alarmone ppGpp, which promotes stationary phase entry, increased stalk length in themanAmutant demonstrating that sugar-phosphate metabolism regulates stalk elongation independently of phosphate starvation.
Direct Metatranscriptome RNA-seq and Multiplex RT-PCR Amplicon Sequencing on Nanopore MinION – Promising Strategies for Multiplex Identification of Viable Pathogens in Food
Authors: Yang Manyun , Cousineau Alyssa , Liu Xiaobo , Sun Daniel , Li Shaohua , Gu Tingting , Sun Luo , Luo Yaguang , Xu Mingqun , Zhang Boce 
Published: July 2019

AbstractViable pathogenic bacteria are major biohazards that pose a significant threat to food safety. Despite the recent developments in detection platforms, multiplex identification of viable pathogens in food remains a major challenge. A novel strategy is developed through direct metatranscriptome RNA-seq and multiplex RT-PCR amplicon sequencing on Nanopore MinION to achieve real-time multiplex identification of viable pathogen in food. Specifically, this study reports an optimized universal Nanopore sample extraction and library preparation protocol applicable to both Gram-positive and Gram-negative pathogenic bacteria, demonstrated using a cocktail culture ofE. coliO157:H7,Salmonella enteritidis, andListeria monocytogenes, which were selected based on their impact on economic loss or prevalence in recent outbreaks. Further evaluation and validation confirmed the accuracy of direct metatranscriptome RNA-seq and multiplex RT-PCR amplicon sequencing using Sanger sequencing and selective media. The study also included a comparison of different bioinformatic pipelines for metatranscriptomic and amplicon genomic analysis. MEGAN without rRNA mapping showed the highest accuracy of multiplex identification using the metatranscriptomic data. EPI2ME also demonstrated high accuracy using multiplex RT-PCR amplicon sequencing. In addition, a systemic comparison was drawn between Nanopore sequencing of the direct metatranscriptome RNA-seq and RT-PCR amplicons. Both methods are comparable in accuracy and time. Nanopore sequencing of RT-PCR amplicon has higher sensitivity, but Nanopore metatranscriptome sequencing excels in read length and dealing with complex microbiome and non-bacterial transcriptome backgrounds. To the best of our knowledge, this is the first report of metatranscriptome sequencing of cocktail microbial RNAs on the emerging Nanopore platform. Direct RNA-seq and RT-PCR amplicons sequencing of metatranscriptome enable the direct identification of nucleotide analogs in RNAs, which is highly informative for determining microbial identities while detecting ecologically relevant processes. The information pertained in this study could be important for future revelatory research, including predicting antibiotic resistance, elucidating host-pathogen interaction, prognosing disease progression, and investigating microbial ecology, etc.
Extent and context dependence of pleiotropy revealed by high-throughput single-cell phenotyping
Authors: Geiler-Samerotte Kerry A , Li Shuang , Lazaris Charalampos , Taylor Austin , Ziv Naomi , Ramjeawan Chelsea , Paaby Annalise B , Siegal Mark L 
Published: July 2019

AbstractPleiotropy – when a single mutation affects multiple traits – is a controversial topic with far-reaching implications. Pleiotropy plays a central role in debates about how complex traits evolve and whether biological systems are modular or are organized such that every gene has the potential to affect many traits. Pleiotropy is also critical to initiatives in evolutionary medicine that seek to trap infectious microbes or tumors by selecting for mutations that encourage growth in some conditions at the expense of others. Research in these fields, and others, would benefit from understanding the extent to which pleiotropy reflects inherent relationships among phenotypes that correlate no matter the perturbation (vertical pleiotropy). Alternatively, pleiotropy may result from genetic changes that impose correlations between otherwise independent traits (horizontal pleiotropy). We distinguish these possibilities by using clonal populations of yeast cells to quantify the inherent relationships between single-cell morphological features. Then, we demonstrate how often these relationships underlie vertical pleiotropy and how often these relationships are modified by genetic variants (QTL) acting via horizontal pleiotropy. Our comprehensive screen measures thousands of pairwise trait correlations across hundreds of thousands of yeast cells and reveals ample evidence of both vertical and horizontal pleiotropy. Additionally, we observe that the correlations between traits can change with the environment, genetic background and cell-cycle position. These changing dependencies suggest a nuanced view of pleiotropy: biological systems demonstrate limited pleiotropy in any given context, but across contexts (e.g., across diverse environments and genetic backgrounds) each genetic change has the potential to influence a larger number of traits. Our method suggests that exploiting pleiotropy for applications in evolutionary medicine would benefit from focusing on traits with correlations that are less dependent on context.
Biocontrol of PGPR strain Bacillus amyloliquefaciens Ba168 against Phytophthora nicotianae on tobacco
Authors: Guo Dongsheng , Yuan Chenhong , Luo Yunyan , Chen YaHan , Lu Meihuan , Chen Guochan , Ren Guangwei , Cui Chuanbin , Zhang Jiatao , An Derong 
Published: July 2019

AbstractTobacco black shank (TBS) caused by Phytophthora nicotianae is destructive to almost all kinds of tobacco cultivars and is widespread in many tobacco-planted countries. Here, an isolated plant growth-promoting rhizobacteria (PGPR) strain Ba168 is promise in biocontrol of TBS. In vitro assays disclosed a strong P. nicotianae suppression activity and the field utilization potential (FUP) by characterized the crude extract of culture filtrates of Ba168. P. nicotianae’s growth was inhibited by the crude extract at minimum inhibitory concentration (MIC) of 5μl/mL. Extracellular conductivity, pH and the wet, dry weight of P. nicotianae’s mycelia, were significantly different after treated with different concentrations of the crude extract and the deformity and perforation of treated P. nicotianae’s hyphae can be observed in scanning electron microscope (SEM) analysis. Proteome characterizations of the crude extract were used as supplementary proofs that further evaluated FUP of Ba168. We then identified strain Ba168 as B. amyloliquefaciens by its genetic and phenotypic characteristics. Field assays comparatively evaluated TBS control efficacy of these PGPRs and agrochemicals. Pooling analysis of the results showed that the biocontrol efficacy of Ba168 preparation is only lower than Mixture of Propamocarb hydrochloride and Azoxystrobin (MPA) but better than other tested subjects. Although the existence of differences in biocontrol efficacy, PGPR preparations effectively reduced the disease index of tobacco.ImportanceThis work demonstrates the promising biocontrol potential of B. amyloliquefaciens Ba168 and highlights the positive roles of PGPR in suppression of this soil-borne disease.
Malassezia interaction with a reconstructed human epidermis: imaging studies
Authors: Pedrosa Ana Filipa , Lisboa Carmen , Branco Joana , Almeida Ana Coelho , Mendes Claudia , Pellevoisin Christian , Leite-Moreira Adelino , Miranda Isabel Marcos , Rodrigues Acácio Gonçalves 
Published: July 2019

ABSTRACTBackgroundBiofilm formation represents a major microbial virulence attribute especially at epithelial surfaces such as the skin. Malassezia biofilm formation at the skin surface has not yet been addressed.ObjectiveThe present study aimed to evaluate Malassezia interaction with a reconstructed human epidermis (RhE) model.MethodsMalassezia clinical isolates were previously isolated from volunteers with pityriasis versicolor and seborrheic dermatitis. Yeasts of two strains of M. furfur and M. sympodialis were inoculated onto the SkinEthic™ RHE. The tissues were processed for light microscopy, wide-field fluorescence microscopy and scanning-electron microscopy.ResultsColonization of the RhE surface with aggregates of Malassezia yeasts entrapped in a multilayer sheet with variable amount of extracellular matrix was unveiled by imaging techniques following 24, 48, 72 and 96 hours of incubation. Whenever yeasts were suspended in RPMI medium supplemented with lipids, the biofilm substantially increased with a dense extracellular matrix in which the yeast cells were embedded (not seen in control samples). Slight differences were found in the biofilm architectural structure between the two tested species.ConclusionSkin isolates of M. furfur and M. sympodialis were capable of forming biofilm in vitro at the epidermal surface simulating in vivo conditions. Following 24 hours of incubation, without added lipids, rudimental matrix was barely visible, conversely to the reported at plastic surfaces. The amount of biofilm apparently increased progressively from 48 to 96 hours. A structural heterogeneity of biofilm between species was found with higher entrapment by a denser and more gelatinous extracellular matrix in M. furfur biofilm.
Optimized visual stimuli for BCI with hessenberg decomposition based extreme learning machine
Authors: Yayık Apdullah , Kutlu Yakup , Altan Gökhan 
Published: July 2019

AbstractBackground and ObjectivesBrain-computer interfaces (BCIs) aim to provide neuroscientific communication platform for human-beings, in particular locked-in patients. In most cases event-related potentials (ERPs), averaged voltage responses to a specific target stimuli over time, have key roles in designing BCIs. With this reason, for the last several decades BCI researchers heavily have focused on signal processing methods to improve quality of ERPs. However, designing visual stimulus with considering their physical properties with regard to rapid and also reliable machine learning algorithms for BCIs remain relatively unexplored. Addressing the issues explained above, in summary the main contributions of this study are as follows: (1) optimizing visual stimulus in terms of size, color and background and, (2) to enhance learning capacity of conventional extreme learning machine (ELM) using advanced linear algebra techniques.MethodsTwo different sized (small and big), three different colored (blue, red and colorful) images with four different backgrounds (white, black and concentric) for each of them were designed and utilized as single object paradigm. Hessenberg decomposition method was proposed for learning process and compared with conventional ELM and multi-layer perceptron in terms of training duration and performance measures.ResultsPerformance measures of small colorful images with orange-concentric background were statistically higher than those of others. Visual stimulus with white background led to relatively higher performance measures than those with black background. Blue colored images had much more impact on improvement of P300 waves than red colored ones had. Hessenberg decomposition method provided 1.5 times shortened training duration than conventional ELM, in addition with comparable performance measures.ConclusionsHerein, a visual stimuli model based on improving quality of ERP responses and machine learning algorithm relies on hessenberg decomposition method are introduced with demonstration of their advantages in the context of BCI. Methods and findings described in this study may pave the way for widespread applications, particularly in clinical health-informatics.
Mechanistic Elucidation of the Antitumor Properties of a Novel Death Receptor 5 Activator
Authors: Wang Mengxiong , Law Mary E. , Davis Bradley J. , Yaaghubi Elham , Ghilardi Amanda F. , Ferreira Renan B. , Chiang Chi-Wu , Guryanova Olga A. , Kopinke Daniel , Heldermon Coy D. , Castellano Ronald K. , Law Brian K. 
Published: July 2019

AbstractDisulfide bond Disrupting Agents (DDAs) are a new chemical class of agents recently shown to have activity against breast tumors in animal models. However, it is unknown how DDAs trigger cancer cell death without affecting nontransformed cells. As demonstrated here, DDAs are the first compounds identified that upregulate the TRAIL receptor DR5 through both transcriptional and posttranscriptional mechanisms. At the protein level, DDAs alter DR5 disulfide bonding to increase steady-state DR5 levels and oligomerization, leading to downstream Caspase 8 and 3 activation. DDAs and TRAIL synergize to kill cancer cells and are cytotoxic to HER2+ cancer cells with acquired resistance to the EGFR/HER2 tyrosine kinase inhibitor. Investigation of the mechanisms responsible for DDA selectivity for cancer cells reveals that DDA-induced upregulation of DR5 is enhanced in the context of EGFR overexpression, and DDA-induced cytotoxicity is strongly amplified by MYC overexpression. Together, the results demonstrate selective DDA lethality against oncogene-transformed cells, DDA-mediated DR5 upregulation and protein stabilization, and DDAs against drug-resistant and metastatic cancer cells. DDAs thus represent a new therapeutic approach to cancer therapy.