bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a deep, distributed and dynamic semantic code in human ventral anterior temporal cortex
Authors: Rogers Timothy T. , Cox Christopher , Lu Qihong , Shimotake Akihiro , Kikuch Takayuki , Kunieda Takeharu , Miyamoto Susumu , Takahashi Ryosuke , Ikeda Akio , Matsumoto Riki , Ralph Matthew A. Lambon 
Published: July 2019

AbstractHow does the human brain encode semantic information about objects? This paper reconciles two seemingly contradictory views. The first proposes that local neural populations independently encode semantic features; the second, that semantic representations arise as a dynamic distributed code that changes radically with stimulus processing. Combining simulations with a well-known neural network model of semantic memory, multivariate pattern classification, and human electrocorticography, we find that both views are partially correct: semantic information is distributed across ventral temporal cortex in a dynamic code that possesses stable feature-like elements in posterior regions but with elements that change rapidly and nonlinearly in anterior regions. This pattern is consistent with the view that anterior temporal lobes serve as a deep cross-modal “hub” in an interactive semantic network, and more generally suggests that tertiary association cortices may adopt dynamic distributed codes difficult to detect with common brain imaging methods.
Historical contingency in the evolution of antibiotic resistance after decades of relaxed selection
Authors: Card Kyle J. , LaBar Thomas , Gomez Jasper B. , Lenski Richard E. 
Published: July 2019

AbstractPopulations often encounter changed environments that remove selection for the maintenance of particular phenotypic traits. The resulting genetic decay of those traits under relaxed selection reduces an organism’s fitness in its prior environment. However, whether and how such decay alters the subsequent evolvability of a population upon restoration of selection for a previously diminished trait is not well understood. We addressed this question usingEscherichia colistrains from the long-term evolution experiment (LTEE) that independently evolved for multiple decades in the absence of antibiotics. We first confirmed that these derived strains are typically more sensitive to various antibiotics than their common ancestor. We then subjected the ancestral and derived strains to various concentrations of these drugs to examine their potential to evolve increased resistance. We found that evolvability was idiosyncratic with respect to initial genotype; that is, the derived strains did not generally compensate for their greater susceptibility by “catching up” to the resistance level of the ancestor. Instead, the capacity to evolve increased resistance was constrained in some backgrounds, implying that evolvability depended upon prior mutations in a historically contingent fashion. We further subjected a time-series of clones from one LTEE population to tetracycline and determined that an evolutionary constraint arose early in that population, corroborating the role of contingency. In summary, relaxed selection not only can drive populations to increased antibiotic susceptibility, but it can also affect the subsequent evolvability of antibiotic resistance in an unpredictable manner. This conclusion has potential implications for public health, and it underscores the need to consider the genetic context of pathogens when designing drug-treatment strategies.
Long solids retention times and attached growth phase favor prevalence of comammox bacteria in nitrogen removal systems
Authors: Cotto Irmarie , Dai Zihan , Huo Linxuan , Anderson Christopher L. , Vilardi Katherine J. , Ijaz Umer , Khunjar Wendell , Wilson Christopher , De Clippeleir Haydee , Gilmore Kevin , Bailey Erika , Pinto Ameet J. 
Published: July 2019

ABSTRACTThe discovery of the complete ammonia oxidizing (comammox) bacteria overturns the traditional two-organism nitrification paradigm which largely underpins the design and operation of nitrogen removal during wastewater treatment. Quantifying the abundance, diversity, and activity of comammox bacteria in wastewater treatment systems is important for ensuring a clear understanding of the nitrogen biotransformations responsible for ammonia removal. To this end, we conducted a yearlong survey of 14 full-scale nitrogen removal systems including mainstream conventional and simultaneous nitrification-denitrification and side-stream partial nitrification-anammox systems with varying process configurations. Metagenomics and genome-resolved metagenomics identified comammox bacteria in mainstream conventional and simultaneous nitrification-denitrification systems, with no evidence for their presence in side-stream partial nitrification-anammox systems. Further, comammox bacterial diversity was restricted to clade A and these clade A comammox bacteria were detected in systems with long solids retention times (>10 days) and/or in the attached growth phase. Using a newly designed qPCR assay targeting theamoBgene of clade A comammox bacteria in combination with quantitation of other canonical nitrifiers, we show that long solids retention time is the key process parameter associated with the prevalence and abundance of comammox bacteria. The increase in comammox bacterial abundance was not associated with concomitant decrease in the abundance of canonical nitrifiers; however, systems with comammox bacteria showed significantly better and temporally stable ammonia removal compared to systems where they were not detected. Finally, in contrast to recent studies, we do not find any significant association of comammox bacterial prevalence and abundance with dissolved oxygen concentrations in this study.HighlightsClade A comammox bacteria were detected in wastewater nitrogen removal systems.New qPCR assay targeting theamoBgene of clade A comammox bacteria was developed.Comammox bacteria are prevalent in mainstream conventional and simultaneous nitrification-denitrification systems with long solids retention times (>10 days).Comammox bacteria were not detected in sidestream partial nitrification-anammox systems included in this study.GRAPHICAL ABSTRACT
Codon-optimized TDP-43-mediated neurodegeneration in a Drosophila model for ALS/FTLD
Authors: Yusuff Tanzeen , Chatterjee Shreyasi , Chang Ya-Chu , Sang Tzu-Kang , Jackson George R. 
Published: July 2019

ABSTRACTTransactive response DNA binding protein-43 (TDP-43) is known to mediate neurodegeneration associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The exact mechanism by which TDP-43 exerts toxicity in the brains of affected patients remains unclear. In a novelDrosophila melanogastermodel, we report gain-of-function phenotypes due to misexpression of insect codon-optimized version of human wild-type TDP-43 (CO-TDP-43) using both the binary GAL4/UAS system and direct promoter fusion constructs. The CO-TDP-43 model showed robust tissue specific phenotypes in the adult eye, wing, and bristles in the notum. Compared to non-codon optimized transgenic flies, the CO-TDP-43 flies produced increased amount of high molecular weight protein, exhibited pathogenic phenotypes, and showed cytoplasmic aggregation with both nuclear and cytoplasmic expression of TDP-43. Further characterization of the adult retina showed a disruption in the morphology and function of the photoreceptor neurons with the presence of acidic vacuoles that are characteristic of autophagy. Based on our observations, we propose that TDP-43 has the propensity to form toxic protein aggregates via a gain-of-function mechanism, and such toxic overload leads to activation of protein degradation pathways such as autophagy. The novel codon optimized TDP-43 model is an excellent resource that could be used in genetic screens to identify and better understand the exact disease mechanism of TDP-43 proteinopathies and find potential therapeutic targets.
INeo-Epp: A novel T-cell HLA class-I immunogenicity or neoantigenic epitope prediction method based on sequence related amino acid features
Authors: Wang Guangzhi , Wan Huihui , Jian Xingxing , Li Yuyu , Ouyang Jian , Tan Xiaoxiu , Zhao Yong , Lin Yong , Xie Lu 
Published: July 2019

AbstractIn silico T-cell epitope prediction plays an important role in immunization experimental design and vaccine preparation. Currently, most epitope prediction research focuses on peptide processing and presentation, e.g. proteasomal cleavage, transporter associated with antigen processing (TAP) and major histocompatibility complex (MHC) combination. To date, however, the mechanism for immunogenicity of epitopes remains unclear. It is generally agreed upon that T-cell immunogenicity may be influenced by the foreignness, accessibility, molecular weight, molecular structure, molecular conformation, chemical properties and physical properties of target peptides to different degrees. In this work, we tried to combine these factors. Firstly, we collected significant experimental HLA-I T-cell immunogenic peptide data, as well as the potential immunogenic amino acid properties. Several characteristics were extracted, including amino acid physicochemical property of epitope sequence, peptide entropy, eluted ligand likelihood percentile rank (EL rank(%)) score and frequency score for immunogenic peptide. Subsequently, a random forest classifier for T cell immunogenic HLA-I presenting antigen epitopes and neoantigens was constructed. The classification results for the antigen epitopes outperformed the previous research (the optimal AUC=0.81, external validation data set AUC=0.77). As mutational epitopes generated by the coding region contain only the alterations of one or two amino acids, we assume that these characteristics might also be applied to the classification of the endogenic mutational neoepitopes also called ‘neoantigens’. Based on mutation information and sequence related amino acid characteristics, a prediction model of neoantigen was established as well (the optimal AUC=0.78). Further, an easy-to-use web-based tool ‘INeo-Epp’ was developed (available at http://www.biostatistics.online/INeo-Epp/neoantigen.php)for the prediction of human immunogenic antigen epitopes and neoantigen epitopes.
Urocortin-3 Neurons in the Mouse Perifornical Area Promote Infant-directed Neglect and Aggression
Authors: Autry Anita E , Wu Zheng , Kapoor Vikrant , Kohl Johannes , Bambah-Mukku Dhananjay , Rubinstein Nimrod D , Marin-Rodriguez Brenda , Carta Ilaria , Sedwick Victoria , Tang Ming , Dulac Catherine 
Published: July 2019

ABSTRACTWhile recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.
Metacontrast masking as a measure of change detection: Children with poor reading fluency show impaired change detection for both letters and shapes
Authors: Crewther David , Rutkowski Jacqueline , Crewther Sheila 
Published: July 2019

AbstractDevelopmental dyslexia, a specific learning difficulty in reading, manifests as effortful decoding of words and as such is commonly associated with reduced phonemic awareness. However, its underlying cause remains elusive, with magnocellular visual processing, temporal auditory processing, visual attentional deficits and cerebellar dysfunction all gaining some traction. More recent theories have concerned visual attention span, measuring the parallel attentive capacity of the sensory visual system. However the VA span task as implemented requires reports, both conscious recall and recognition of letters, that activate many cortical areas beyond sensory visual cortex. Change detection, in contrast, does not require the conscious recognition of items, but simply awareness that the stimulus has changed, or not, again testing visual attention in a parallel fashion, but avoiding the complications of higher order cognitive processes. Thus, we investigated change detection in 33 good and poor readers with ages of around 10 yr, using a gap paradigm. Groups of 4 letters or 4 shapes were presented for a fixed time (0.7 s), followed after a 0.25 s gap, by a second similar group, each item surrounded by an annular frame filled with dynamic random noise of variable contrast. Detection performance was manipulated by varying the contrast of these meta-contrast mask frames, yielding a threshold contrast of the frames at which participants could just detect change. In two separate experiments, letters and rectangular shapes were used as target items, in order to test whether previous findings of superior change detection in good compared with poor readers was a result of greater automaticity in letter recognition of the good readers. The results indicate that the good readers were able to detect change at higher levels of masking distraction for both the letter and shape targets, indicating that this difference is not specifically related to to the training of graphemic or lexical information but more likely reflects a difference in alerting or pre-recognition stages of visual processing. Together, the results provide further support of the notion that there is a low level attentional performance difference between dyslexic and normal reading children. Thus, the results further bring transient spatial attention directly into the spotlight as an ability critical for learning to read.
Eye morphogenesis in the blind Mexican cavefish
Authors: Devos Lucie , Agnès François , Edouard Joanne , Simon Victor , Legendre Laurent , Khallouki Naima El , Barbachou Sosthène , Sohm Frédéric , Rétaux Sylvie 
Published: July 2019

AbstractThe morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Disturbances in these events can lead to developmental defects and blindness. Here, we have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the speciesAstyanax mexicanus. Using comparative live imaging on targeted enhancer-trapZic1:hsp70:GFPreporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified defects in migratory cell behaviors during evagination which participate in the reduced optic vesicle size in cavefish, without proliferation defect. Further, impaired optic cup invagination shifts the relative position of the lens and contributes to coloboma in cavefish. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.
Hotspot coevolution at protein-protein interfaces is a key identifier of native protein complexes
Authors: Mishra Sambit K. , Cooper Sarah J. , Parks Jerry M. , Mitchell Julie C. 
Published: July 2019

AbstractProtein-protein interactions play a key role in mediating numerous biological functions, with more than half the proteins in living organisms existing as either homo- or hetero-oligomeric assemblies. Protein subunits that form oligomers minimize the free energy of the complex, but exhaustive computational search-based docking methods have not comprehensively addressed the protein docking challenge of distinguishing a natively bound complex from non-native forms. In this study, we propose a scoring function, KFC-E, that accounts for both conservation and coevolution of putative binding hotspot residues at protein-protein interfaces. For a benchmark set of 53 bound complexes, KFC-E identifies a near-native binding mode as the top-scoring pose in 38% and in the top 5 in 55% of the complexes. For a set of 17 unbound complexes, KFC-E identifies a near-native pose in the top 10 ranked poses in more than 50% of the cases. By contrast, a scoring function that incorporates information on coevolution at predicted non-hotspots performs poorly by comparison. Our study highlights the importance of coevolution at hotspot residues in forming natively bound complexes and suggests a novel approach for coevolutionary scoring in protein docking.Author SummaryA fundamental problem in biology is to distinguish between the native and non-native bound forms of protein-protein complexes. Experimental methods are often used to detect the native bound forms of proteins but, are demanding in terms of time and resources. Computational approaches have proven to be a useful alternative; they sample the different binding configurations for a pair of interacting proteins and then use an heuristic or physical model to score them. In this study we propose a new scoring approach, KFC-E, which focuses on the evolutionary contributions from a subset of key interface residues (hotspots) to identify native bound complexes. KFC-E capitalizes on the wealth of information in protein sequence databases by incorporating residue-level conservation and coevolution of putative binding hotspots. As hotspot residues mediate the binding energetics of protein-protein interactions, we hypothesize that the knowledge of putative hotspots coupled with their evolutionary information should be helpful in the identification of native bound protein-protein complexes.
Determinants of Nutritional Status among Children Under five age in Ethiopia: A Further Analysis of the Ethiopian Demographic and Health Survey (EDHS) 2016 Data
Authors: Amare Zerihun Yohannes , Ahmed Mossa Endris , Mehari AdeyBelete 
Published: July 2019

ABSTRACTChild malnutrition is an underlying cause for almost half (45%) of child deaths, particularly in low socioeconomic communities of developing countries like Ethiopia. Globally, in 2018, 149 million children under five were stunted and over 49 million children were wasted. In Ethiopia, from the year 2005 to 2016, there is a decrease in stunting from 47% to 39%, but the prevalence of wasting changed little over the same time period (11% to 10%). Despite efforts made by the Ethiopian government and improvements in reducing malnutrition, the current rate of progress is not fast enough to have reached the global target by 2025.The aim of this study was to examine the determinants of nutritional status among children under five in Ethiopia. This study used data from 2016 Ethiopia Demographic and Heath Survey (EDHS) to examine determinants of nutritional status among children under five (0-59 months). This study used stunting and wasting as dependent variables for the analysis. Children’s, mothers, households, and environmental characteristics were used as determinant variables. Children not alive, and other missing values were considered as missing and was not included in the analyses. Sample weights were applied in all analysis due to the two stage cluster sampling design in the EDHS datasets. Multicollinearity among independent variables were checked. Logistic regression was used to analyse the determinants of nutritional status among under five age children. Bivariate analysis was also used to analyse the association between the dependent and independent variables. The chi-square test used to see the significance of association. The level of significance for the analysis was p<0.05. Age, and sex of child, educational status and body mass index, and short stature of mothers, residence, region, wealth quintile, toilet facilities and fuel types of households’ have significant association with stunting and wasting. However, mother’s short stature has significant association with only stunting. The study found child, maternal, household and environmental characteristics were significantly associated with stunting and wasting among of children under five. This implies a multi-sectorial and multidimensional approach is important to address malnutrition in Ethiopia.
Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer
Authors: de Andrade Diocésio Alves Pinto , da Silva Vinicius Duval , de Macedo Matsushita Graziela , Alves de Lima Marcos , de Andrade Vieira Marcelo , Cunha Andrade Carlos Eduardo Mattos , Luís Schmidt Ronaldo , Reis Rui Manuel , Reis Ricardo dos 
Published: July 2019

ABSTRACTBackgroundEndometrial cancer presents well-defined risk factors (myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI)). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. The aim of this study was to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer.MethodsA case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution between 2009 and 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (histological characteristics (endometrioid vs endometrioid with squamous differentiation), tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging.ResultsTwenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p=0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p=0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p=0.103) were associated with disease recurrence on univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p=0.031).ConclusionOur data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence.