bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Brain Vasculature Reconstruction at the Single Capillary Level
Authors: Di Giovanna Antonino Paolo , Tibo Alessandro , Silvestri Ludovico , Müllenbroich Marie Caroline , Costantini Irene , Allegra Mascaro Anna Letizia , Sacconi Leonardo , Frasconi Paolo , Pavone Francesco Saverio 
Published: August 2018

AbstractThe distinct organization of the brain’s vascular network ensures that it is adequately supplied with oxygen and nutrients. However, despite this fundamental role, a detailed reconstruction of the brain-wide vasculature at the capillary level remains elusive, due to insufficient image quality using the best available techniques. Here, we demonstrate a novel approach that improves vascular demarcation by combining CLARITY with a vascular staining approach that can fill the entire blood vessel lumen and imaging with light-sheet fluorescence microscopy. This method significantly improves image contrast, particularly in depth, thereby allowing reliable application of automatic segmentation algorithms, which play an increasingly important role in high-throughput imaging of the terabyte-sized datasets now routinely produced. Furthermore, our novel method is compatible with endogenous fluorescence, thus allowing simultaneous investigations of vasculature and genetically targeted neurons. We believe our new method will be valuable for future brain-wide investigations of the capillary network.
Sex-specific associations of infants’ gut microbiome with arsenic exposure in a US population
Authors: Hoen Anne G. , Madan Juliette C. , Li Zhigang , Coker Modupe , Lundgren Sara N. , Morrison Hilary G. , Palys Thomas , Jackson Brian P. , Sogin Mitchell L. , Cottingham Kathryn L. , Karagas Margaret R. 
Published: August 2018

AbstractArsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.
Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia
Authors: Bunditvorapoom Duangkamon , Kochakarn Theerarat , Kotanan Namfon , Modchang Charin , Kümpornsin Krittikorn , Loesbanluechai Duangkamon , Krasae Thanyaluk , Cui Liwang , Chotivanich Kesinee , White Nicholas J. , Wilairat Prapon , Miotto Olivo , Chookajorn Thanat 
Published: August 2018

AbstractArtemisinin is the most rapidly effective drug for Plasmodium falciparum malaria treatment currently in clinical use. Emerging artemisinin-resistant parasites pose a great global health risk. At present, the level of artemisinin resistance is still relatively low with evidence pointing towards a trade-off between artemisinin resistance and fitness loss. Here we show that artemisinin-resistant P. falciparum isolates from Cambodia manifested fitness loss, showing fewer progenies during the intra-erythrocytic developmental cycle. The loss in fitness was exacerbated under the condition of low exogenous amino acid supply. The resistant parasites failed to undergo maturation, whereas their drug-sensitive counterparts were able to complete the erythrocytic cycle under conditions of amino acid deprivation. The artemisinin-resistant phenotype was not stable, and loss of the phenotype was associated with changes in the expression of a putative target, Exp1, a membrane glutathione transferase. Analysis of SNPs in haemoglobin processing genes revealed associations with parasite clearance times, suggesting changes in haemoglobin catabolism may contribute to artemisinin resistance. These findings on fitness and protein homeostasis could provide clues on how to contain emerging artemisinin-resistant parasites.
Functional diversity of TMPRSS6 isoforms and variants expressed in hepatocellular carcinoma cell lines
Authors: Dion Sébastien P. , Béliveau François , Morency Louis-Philippe , Désilets Antoine , Najmanovich Rafaël , Leduc Richard 
Published: August 2018

AbstractTMPRSS6, also known as matriptase-2, is a type II transmembrane serine protease that plays a major role in iron homeostasis by acting as a negative regulator of hepcidin production through cleavage of the BMP co-receptor haemojuvelin. Iron-refractory iron deficiency anaemia (IRIDA), an iron metabolism disorder, is associated with mutations in the TMPRSS6 gene. By analysing RNA-seq data encoding TMPRSS6 isoforms and other proteins involved in hepcidin production, we uncovered significant differences in expression levels between hepatocellular carcinoma (HCC) cell lines and normal human liver samples. Most notably, TMPRSS6 and HAMP expression was found to be much lower in HepG2 and Huh7 cells when compared to human liver samples. Furthermore, we characterized the common TMPRSS6 polymorphism V736A identified in Hep3B cells, the V795I mutation found in HepG2 cells, also associated with IRIDA, and the G603R substitution recently detected in two IRIDA patients. While variant V736A is as active as wild-type TMPRSS6, mutants V795I and G603R displayed significantly reduced proteolytic activity. Our results provide important information about commonly used liver cell models and shed light on the impact of two TMPRSS6 mutations associated with IRIDA.
Deep Learning and Radiomics predict complete response after neo-adjuvant chemoradiation for locally advanced rectal cancer
Authors: Bibault Jean-Emmanuel , Giraud Philippe , Housset Martin , Durdux Catherine , Taieb Julien , Berger Anne , Coriat Romain , Chaussade Stanislas , Dousset Bertrand , Nordlinger Bernard , Burgun Anita 
Published: August 2018

AbstractTreatment of locally advanced rectal cancer involves chemoradiation, followed by total mesorectum excision. Complete response after chemoradiation is an accurate surrogate for long-term local control. Predicting complete response from pre-treatment features could represent a major step towards conservative treatment. Patients with a T2-4 N0-1 rectal adenocarcinoma treated between June 2010 and October 2016 with neo-adjuvant chemoradiation from three academic institutions were included. All clinical and treatment data was integrated in our clinical data warehouse, from which we extracted the features. Radiomics features were extracted from the tumor volume from the treatment planning CT Scan. A Deep Neural Network (DNN) was created to predict complete response, as a methodological proof-of-principle. The results were compared to a baseline Linear Regression model using only the TNM stage as a predictor and a second model created with Support Vector Machine on the same features used in the DNN. Ninety-five patients were included in the final analysis. There were 49 males (52%) and 46 females (48%). Median tumour size was 48 mm (15–130). Twenty-two patients (23%) had pathologic complete response after chemoradiation. One thousand six hundred eighty-three radiomics features were extracted. The DNN predicted complete response with an 80% accuracy, which was better than the Linear Regression model (69.5%) and the SVM model (71.58%). Our model correctly predicted complete response after neo-adjuvant rectal chemoradiotherapy in 80% of the patients of this multicenter cohort. Our results may help to identify patients who would benefit from a conservative treatment, rather than a radical resection.
A nonlinear updating algorithm captures suboptimal inference in the presence of signal-dependent noise
Authors: Egger Seth W. , Jazayeri Mehrdad 
Published: August 2018

AbstractBayesian models have advanced the idea that humans combine prior beliefs and sensory observations to optimize behavior. How the brain implements Bayes-optimal inference, however, remains poorly understood. Simple behavioral tasks suggest that the brain can flexibly represent probability distributions. An alternative view is that the brain relies on simple algorithms that can implement Bayes-optimal behavior only when the computational demands are low. To distinguish between these alternatives, we devised a task in which Bayes-optimal performance could not be matched by simple algorithms. We asked subjects to estimate and reproduce a time interval by combining prior information with one or two sequential measurements. In the domain of time, measurement noise increases with duration. This property takes the integration of multiple measurements beyond the reach of simple algorithms. We found that subjects were able to update their estimates using the second measurement but their performance was suboptimal, suggesting that they were unable to update full probability distributions. Instead, subjects’ behavior was consistent with an algorithm that predicts upcoming sensory signals, and applies a nonlinear function to errors in prediction to update estimates. These results indicate that the inference strategies employed by humans may deviate from Bayes-optimal integration when the computational demands are high.
Attentional Selection of Social Features Persists Despite Restricted Bottom-Up Information and Affects Temporal Viewing Dynamics
Authors: Flechsenhar Aleya , Rösler Lara , Gamer Matthias 
Published: August 2018

AbstractPrevious studies have shown an attentional bias towards social features during free-viewing of naturalistic scenes. This social attention seems to be reflexive and able to defy top-down demands in form of explicit search tasks. However, the question remains whether social features continue to be prioritized when peripheral information is limited, thereby reducing the influence of bottom-up image information on gaze orienting. Therefore, we established a gaze-contingent viewing paradigm, in which the visual field was constrained and updated in response to the viewer’s eye movements. Participants viewed social and non-social images that were randomly allocated to a free and a gaze-contingent viewing condition while their eye movements were tracked. Our results revealed a strong attentional bias towards social features in both conditions. However, gaze-contingent viewing altered temporal and spatial dynamics of viewing behavior. Additionally, recurrent fixations were more frequent and closer together in time for social compared to non-social stimuli in both viewing conditions. Taken together, this study implies a predominant selection of social features when bottom-up influences are diminished and a general influence of social content on visual exploratory behavior, thus highlighting mechanisms of social attention.
Glycosylation Significantly Inhibits the Aggregation of Human Prion Protein and Decreases Its Cytotoxicity
Authors: Yi Chuan-Wei , Wang Li-Qiang , Huang Jun-Jie , Pan Kai , Chen Jie , Liang Yi 
Published: August 2018

AbstractPrion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species. The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date. In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP. As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane. In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm. In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane. As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane. Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126. Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
Depression is associated with enhanced aversive Pavlovian control over instrumental behaviour
Authors: Nord C. L. , Lawson R. P. , Huys Q. J. M. , Pilling S. , Roiser J. P. 
Published: August 2018

AbstractThe dynamic modulation of instrumental behaviour by conditioned Pavlovian cues is an important process in decision-making. Patients with major depressive disorder (MDD) are known to exhibit mood-congruent biases in information processing, which may occur due to Pavlovian influences, but this hypothesis has never been tested directly in an unmedicated sample. To address this we tested unmedicated MDD patients and healthy volunteers on a computerized Pavlovian-Instrumental Transfer (PIT) task designed to separately examine instrumental approach and withdrawal actions in the context of Pavlovian appetitive and aversive cues. This design allowed us to directly measure the degree to which Pavlovian cues influence instrumental responding. Depressed patients were profoundly influenced by aversive Pavlovian stimuli, to a significantly greater degree than healthy volunteers. This was the case for instrumental behaviour both in the approach condition (in which aversive Pavlovian cues inhibited ‘go’ responses), and in the withdrawal condition (in which aversive Pavlovian cues facilitated ‘go’ responses). Exaggerated aversive PIT provides a potential cognitive mechanism for biased emotion processing in major depression. This finding also has wider significance for the understanding of disrupted motivational processing in neuropsychiatric disorders.
Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice
Authors: de Genaro Isabella Santos , de Almeida Francine Maria , Hizume-Kunzler Deborah Camargo , Moriya Henrique Takachi , Silva Ronaldo Aparecido , Cruz João Carlos Gonçalves , Lopes Renan Boeira , Righetti Renato Fraga , de Paula Vieira Rodolfo , Saiki Mitiko , Martins Milton Arruda , Tibério Iolanda de Fátima Lopes Calvo , Arantes-Costa Fernanda Magalhães , Saraiva-Romanholo Beatriz Mangueira 
Published: August 2018

AbstractWork-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl2 exposure is 3 mg/ m3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.
Plasma proteomics reveals gestational age-specific responses to mechanical ventilation and identifies the mechanistic pathways that initiate preterm lung injury
Authors: Pereira-Fantini Prue M. , Byars Sean G. , McCall Karen E. , Perkins Elizabeth J. , Oakley Regina B. , Dellacà R. L. , Dargaville Peter A. , Davis Peter G. , Ignjatovic Vera , Tingay David G. 
Published: August 2018

AbstractThe preterm lung is particularly vulnerable to ventilator-induced lung injury (VILI) as a result of mechanical ventilation. However the developmental and pathological cellular mechanisms influencing the changing patterns of VILI have not been comprehensively delineated, preventing the advancement of targeted lung protective therapies. This study aimed to use SWATH-MS to comprehensively map the plasma proteome alterations associated with the initiation of VILI following 60 minutes of standardized mechanical ventilation from birth in three distinctly different developmental lung states; the extremely preterm, preterm and term lung using the ventilated lamb model. Across these gestations, 34 proteins were differentially altered in matched plasma samples taken at birth and 60 minutes. Multivariate analysis of the plasma proteomes confirmed a gestation-specific response to mechanical ventilation with 79% of differentially-expressed proteins altered in a single gestation group only. Six cellular and molecular functions and two physiological functions were uniquely enriched in either the extremely preterm or preterm group. Correlation analysis supported gestation-specific protein-function associations within each group. In identifying the gestation-specific proteome and functional responses to ventilation we provide the founding evidence required for the potential development of individualized respiratory support approaches tailored to both the developmental and pathological state of the lung.
Physiological characterization of the emergence from diapause: A transcriptomics approach
Authors: Roncalli Vittoria , Sommer Stephanie A. , Cieslak Matthew C. , Clarke Cheryl , Hopcroft Russell R. , Lenz Petra H. 
Published: August 2018

AbstractOrganisms inhabiting high-latitude environments have evolved adaptations, such as diapause to time reproduction and growth to optimize their survival. However, the physiological regulation of the timing of complex life histories is poorly understood, particularly for marine copepods, that diapause at depth. A member of the pelagic community of the sub-Arctic Pacific Ocean,Neocalanus flemingerienters diapause in June. Egg production occurs in winter/spring. In order to characterize the transition from diapause to egg release, females were collected in late September from 400–700 m depth, incubated in the dark at 4–5 °C and sampled for RNASeq at weekly intervals. The diapause phenotype showed down-regulation of protein turnover and up-regulation of stress genes. Activation of the reproductive program was marked by the up-regulation of genes involved in germline development. Thereafter, progress through phases of oocyte development could be linked to changes in gene expression. At 5 weeks, females showed up-regulation of spermatogenesis, indicating that stored sperm had been in a quiescent stage and completed their maturation inside the female. Gene expression profiles provide a framework to stage field-collected females. The 7-week progression from diapause to late oogenesis suggests that females typically spawning in January initiated the reproductive program in November.
Influence of the external field on the excitation properties of plasmon in linear atomic chain
Authors: Wu Reng-lai , Quan Jun , Sun Mengtao 
Published: August 2018

AbstractBased on the self-consistent linear response theory, the plasmon-energy absorption in linear atomic chain are studied by using the tight-binding approximation. Results indicate that the eigen-frequency of the plasmon is uninfluenced by the external electric potential, but the plasmon modes excited by various electric potentials are obviously different. Each mode of plasmon corresponds to one kind of eigen-charge distribution. When the plasmon mode is excited, the resonant charge will show a distribution characteristic the same as the one of eigen charge. And the plasmon mode can be precisely controlled by external electric potential if the eigen-charge distribution at such plasmon is known. The relationship between plasmon-energy absorption and atom number are also affected by the external electric potential. However, most of the other studies only show the normal case that the plasmon-energy absorption increases with the atom number increasing. Here, we demonstrate that the normal case commonly occurs under monotone increasing potential. And abnormal case may occur under monotone decreasing potential, ie, the plasmon-energy absorption will decrease with the atom number increasing. But, in the presence of arbitrary potential applied to the same atomic chain, the plasmon-energy absorption will always increase with the electron number increasing.
Evolution of morphological crypsis in the Tetramorium caespitum ant species complex (Hymenoptera: Formicidae)
Authors: Wagner Herbert C. , Gamisch Alexander , Arthofer Wolfgang , Moder Karl , Steiner Florian M. , Schlick-Steiner Birgit C. 
Published: August 2018

AbstractCryptic species are morphologically very similar to each other. To what extent stasis or convergence causes crypsis and whether ecology influences the evolution of crypsis has remained unclear. The Tetramorium caespitum complex is one of the most intricate examples of cryptic species in ants. Here, we test three hypotheses concerning the evolution of its crypsis: H1: The complex is monophyletic. H2: Morphology resulted from evolutionary stasis. H3: Ecology and morphology evolved concertedly. We confirmed (H1) monophyly of the complex; (H2) a positive relation between morphological and phylogenetic distances, which indicates a very slow loss of similarity over time and thus stasis; and (H3) a positive relation between only one morphological character and a proxy of the ecological niche, which indicates concerted evolution of these two characters, as well as a negative relation between p-values of correct species identification and altitude, which suggests that species occurring in higher altitudes are more cryptic. Our data suggest that species-specific morphological adaptations to the ecological niche are exceptions in the complex, and we consider the worker morphology in this complex as an adaptive solution for various environments.