bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy is required for proper meiosis of porcine oocytes maturing in vitro
Authors: Shen Xing-Hui , Jin Yong-Xun , Liang Shuang , Kwon Jeong-Woo , Zhu Ji-Wei , Lei Lei , Kim Nam-Hyung
Published: August 2018

Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components; however, the contribution of autophagy during meiosis has not been studied in porcine oocytes maturing in vitro. In this study, we observed that the autophagy-related gene, LC3, was expressed in porcine oocytes during maturation for 44 h in vitro. Knockdown of the autophagy-related gene, BECN1, reduced both BECN1 and LC3 protein expression levels. Moreover, BECN1 knockdown and treatment with the autophagy inhibitor, LY294002, during maturation of porcine oocytes in vitro impaired polar body extrusion, disturbed mitochondrial function, triggered the DNA damage response, and induced early apoptosis in porcine oocytes. Autophagy inhibition during oocyte maturation also impaired the further developmental potential of porcine oocytes. These results indicate that autophagy is required for the in vitro maturation of porcine oocytes.
UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation
Authors: Notara M. , Behboudifard S. , Kluth M. A. , Maßlo C. , Ganss C. , Frank M. H. , Schumacher B. , Cursiefen C.
Published: August 2018

UVB irradiation has been linked to pathogenesis of pterygium, a conjunctival tumor growing onto transparent cornea, the windscreen of the eye. Due to corneal anatomy, ambient UVB irradiation is amplified at the stem cell-containing nasal limbus. The aim of this study was to analyse the effect of a UV-blocking contact lens (UVBCL, senofilcon A, Class 1 UV blocker) on limbal epithelial cells and fibroblasts under UVB irradiation compared to a non-UVB-blocking contact lens. UVBCL prevented UVB-induced DNA damage (as assessed by cyclobutane pyrimidine dimer immunostaining) as well as a decrease in proliferation and scratch wound closure rate of both limbal epithelial and fibroblast cells. Similarly, UVBCL protected limbal epithelial cells from UVB-induced loss of their phenotype in terms of colony forming efficiency and stem cell marker expression (ABCB5, P63α, integrin β1) compared to controls. Moreover, with UVBCL pro-inflammatory cytokines such as TNFα and MCP1 remained unchanged. These data demonstrate the significance of UV-protection in preserving the limbal niche in response to at least short-term UVB. Our data support the use of UVBCL in protecting limbal niche cells, especially after limbal stem cell transplantation and in patients after pterygium surgery, to help prevent recurrences.
The transcriptome of human mammary epithelial cells infected with the HCMV-DB strain displays oncogenic traits
Authors: Moussawi Fatima Al , Kumar Amit , Pasquereau Sébastien , Tripathy Manoj K. , Karam Walid , Diab-Assaf Mona , Herbein Georges
Published: August 2018

Increasing evidence indicates that human cytomegalovirus (HCMV) populations under the influence of host environment, can either be stable or rapidly differentiating, leading to tissue compartment colonization. We isolated previously from a 30-years old pregnant woman, a clinical isolate of HCMV, that we refered to as the HCMV-DB strain (accession number KT959235). The HCMV-DB clinical isolate demonstrated its ability to infect primary macrophages and to upregulate the proto-oncogene Bcl-3. We observed in this study that the genome of HCMV-DB strain is close to the genomes of other primary clinical isolates including the Toledo and the JP strains with the later having been isolated from a glandular tissue, the prostate. Using a phylogenetic analysis to compare the genes involved in virus entry, we observed that the HCMV-DB strain is close to the HCMV strain Merlin, the prototype HCMV strain. HCMV-DB infects human mammary epithelial cells (HMECs) which in turn display a ER−/PR−/HER2− phenotype, commonly refered to as triple negative. The transcriptome of HCMV-DB-infected HMECs presents the characteristics of a pro-oncogenic cellular environment with upregulated expression of numerous oncogenes, enhanced activation of pro-survival genes, and upregulated markers of cell proliferation, stemcellness and epithelial mesenchymal transition (EMT) that was confirmed by enhanced cellular proliferation and tumorsphere formation in vitro. Taken together our data indicate that some clinical isolates could be well adapted to the mammary tissue environment, as it is the case for the HCMV-DB strain. This could influence the viral fitness, ultimately leading to breast cancer development.
Publisher Correction: Across-subject offline decoding of motor imagery from MEG and EEG
Authors: Halme Hanna-Leena , Parkkonen Lauri
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Reproducibility of antimicrobial test methods
Authors: Parker Albert E. , Hamilton Martin A. , Goeres Darla M.
Published: August 2018

We review reproducibility results for methods that test antimicrobial efficacy against biofilms, spores and bacteria dried onto a surface. Our review, that included test results for Pseudomonas aeruginosa, Salmonella choleraesuis and Bacillus subtilis, suggests that the level of reproducibility depends on the efficacy of the antimicrobial agent being tested for each microbe and microbial environment. To determine the reproducibility of a method, several laboratories must independently test the same antimicrobial agent using the method. Little variability among the efficacy results suggests good reproducibility. Such reproducibility assessments currently are hampered by the absence of an objective process for deciding whether the variability is sufficiently small. We present a quantitative decision process that objectively determines whether any method that assesses antimicrobial efficacy is reproducible. Because the perception of acceptable reproducibility may differ among stakeholders, the decision process is governed by a stakeholder’s specifications that necessarily includes the efficacy of the agents to be tested.
Phyllostachys edulis forest reduces atmospheric PM2.5 and PAHs on hazy days at suburban area
Authors: Bi Yu Fang , Guo Fei Yan , Yang Liu , Zhong Hao , Wang An Ke , Wang Yu Kui , Wu Zhi Zhuang , Du Xu Hua
Published: August 2018

This study is aim to illustrate Phyllostachys edulis’ role in affecting air quality under hazy day and solar day. P. edulis is a crucial plants growing well at suburban area at China Southern. In this manuscript, on 2 weather conditions (hazy day; solar day), changes in atmospheric particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), associated volatile organic compounds (VOCs), and PAHs in leaves and soils were measured, with PM-detection equipment and the GC-MC method, in a typical bamboo forest at suburban areas. The results showed that: (1) Bamboo forest decreased atmospheric PM2.5 and PM10 concentrations significantly by 20% and 15%, respectively, on the hazy day nightfall time, when they were times higher than that on any other time. Also, similar effects on atmospheric PAHs and VOCs were found. (2) Significant increases in PAHs of leaves and soil were found inside the forest on the hazy day. (3) Bamboo forest also reduced the atmospheric VOC concentrations, and changed the compounds of 10 VOCs present in the highest concentration list. Thus, bamboo forests strongly regulate atmospheric PM2.5 through capture or retention, for the changes in atmospheric VOCs and increase in PAHs of leaves and soil.
Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus
Authors: Noh Ji Yeong , Jeong Dae Gwin , Yoon Sun-Woo , Kim Ji Hyung , Choi Yong Gun , Kang Shien-Young , Kim Hye Kwon
Published: August 2018

The bat paramyxovirus B16-40 was first isolated in Korea in this study. Using the isolated virus, we could obtain not only genomic information, but also several biological characteristics of the virus. In the phylogenetic analysis, the virus was found to belong to the recently proposed genus Shaanvirus. Through sequence analyses and in vitro testing, the isolated virus was also found to have haemagglutinin-neuraminidase (HN) protein as one of the structural proteins. When mouse antiserum was generated against the isolated virus and tested, it was cross-reactive to human parainfluenza virus 1 in an indirect immunofluorescence assay but could not cross-neutralize human parainfluenza virus 1. In addition, the bat paramyxovirus B16-40 was not infectious in the mouse model. Collectively, this study provided basic information on further classification of the bat paramyxovirus B16-40 and related viruses in the proposed genus Shaanvirus.
Nanospikes-mediated Anomalous Dispersities of Hydropobic Micro-objects and their Application for Oil Emulsion Cleaning
Authors: Chen Hui-Jiuan , Yang Chengduan , Hang Tian , Liu Guishi , Wu Jiangming , Lin Di-an , Zhang Aihua , Li Yan , Yang Bo-ru , Xie Xi
Published: August 2018

Many fields of applications require dispersion of hydrophobic particles in water, which is traditionally achieved by using surfactants or amphiphilic molecules to modify particle surfaces. However, surfactants or amphiphilic molecules may disturb the native solution or particles’ surface hydrophobicity, limiting extended applications such as oil emulsion cleaning. Recently one example of 2 μm-size polystyrene microparticles covered with ZnO nanospikes has been shown to exhibit excellent dispersity in water in spite of surface hydrophobicity. Whether this anomalous dispersion phenomenon was applicable to other hydrophobic microparticle systems was still unclear and its application scope was limited. Here the anomalous dispersities of different hydrophobic spiky micro-objects were systematically explored. The results show that the anomalous dispersion phenomenon was universally observed on different hydrophobic spiky micro-objects including different hydrophobic coating, particle sizes, material compositions and core particle morphologies. In addition, the spiky micro-objects displayed anomalous dispersity in water without compromising surface hydrophobicity, and their applications for oil spills absorption and oil emulsion cleaning were demonstrated. This work offers unique insight on the nanospikes-mediated anomalous dispersion phenomenon of hydrophobic micro-object and potentially extends its applicability and application scopes.
Enrichment of genetic markers of recent human evolution in educational and cognitive traits
Authors: Srinivasan Saurabh , Bettella Francesco , Frei Oleksandr , Hill W. David , Wang Yunpeng , Witoelar Aree , Schork Andrew J. , Thompson Wesley K. , Davies Gail , Desikan Rahul S. , Deary Ian J. , Melle Ingrid , Ueland Torill , Dale Anders M. , Djurovic Srdjan , Smeland Olav B. , Andreassen Ole A.
Published: August 2018

Higher cognitive functions are regarded as one of the main distinctive traits of humans. Evidence for the cognitive evolution of human beings is mainly based on fossil records of an expanding cranium and an increasing complexity of material culture artefacts. However, the molecular genetic factors involved in the evolution are still relatively unexplored. Here, we investigated whether genomic regions that underwent positive selection in humans after divergence from Neanderthals are enriched for genetic association with phenotypes related to cognitive functions. We used genome wide association data from a study of college completion (N = 111,114), one of educational attainment (N = 293,623) and two different studies of general cognitive ability (N = 269,867 and 53,949). We found nominally significant polygenic enrichment of associations with college completion (p = 0.025), educational attainment (p = 0.043) and general cognitive ability (p = 0.015 and 0.025, respectively), suggesting that variants influencing these phenotypes are more prevalent in evolutionarily salient regions. The enrichment remained significant after controlling for other known genetic enrichment factors, and for affiliation to genes highly expressed in the brain. These findings support the notion that phenotypes related to higher order cognitive skills typical of humans have a recent genetic component that originated after the separation of the human and Neanderthal lineages.
Raman micro-spectroscopy for accurate identification of primary human bronchial epithelial cells
Authors: Surmacki Jakub M. , Woodhams Benjamin J. , Haslehurst Alexandria , Ponder Bruce A. J. , Bohndiek Sarah E.
Published: August 2018

Live cell Raman micro-spectroscopy is emerging as a promising bioanalytical technique for label-free discrimination of a range of different cell types (e.g. cancer cells and fibroblasts) and behaviors (e.g. apoptosis). The aim of this study was to determine whether confocal Raman micro-spectroscopy shows sufficient sensitivity and specificity for identification of primary human bronchial epithelial cells (HBECs) to be used for live cell biological studies in vitro. We first compared cell preparation substrates and media, considering their influence on lung cell proliferation and Raman spectra, as well as methods for data acquisition, using different wavelengths (488 nm, 785 nm) and scan protocols (line, area). Evaluating these parameters using human lung cancer (A549) and fibroblast (MRC5) cell lines confirmed that line-scan data acquisition at 785 nm using complete cell media on a quartz substrate gave optimal performance. We then applied our protocol to acquisition of data from primary human bronchial epithelial cells (HBEC) derived from three independent sources, revealing an average sensitivity for different cell types of 96.3% and specificity of 95.2%. These results suggest that Raman micro-spectroscopy is suitable for delineating primary HBEC cell cultures, which in future could be used for identifying different lung cell types within co-cultures and studying the process of early carcinogenesis in lung cell culture.
Biogenic amines analysis and microbial contribution in traditional fermented food of Douchi
Authors: Li Lu , Ruan Liying , Ji Anying , Wen Zhiyou , Chen Shouwen , Wang Ling , Wei Xuetuan
Published: August 2018

Biogenic amines (BAs) have been reported to threaten the Douchi safety, while the BAs formation mechanism and corresponding control method have not been clarified for Douchi. The present study aims to investigate the microbial contribution to BAs in Douchi, and to find the beneficial strain for BAs control. Firstly, the BAs profiles of 15 Douchi samples were analyzed, and common 6 kinds of BAs were detected from different samples. All the samples showed the total BAs contents within the safe dosage range, while the histamine concentrations in 2 samples and β-phenethylamine in 6 samples were above the toxic level. Then, the bacterial and fungal communities were investigated by high-throughput sequencing analysis, and Bacillus and Candida were identified as the dominant bacteria and fungi genus, respectively. Furthermore, nineteen strains were selected from the dominant species of Douchi samples, including 14 Bacillus strains, 2 Staphylococcus strains, 1 Enterococcus strain and 2 Candida strains, and their BAs formation and degradation abilities were evaluated. B. subtilis HB-1 and S. pasteuri JX-2 showed no BAs producing ability, and B. subtilis GD-4 and Candida sp. JX-3 exhibited high BAs degradation ability. Finally, fermented soybean model analysis further verified that B. subtilis HB-1 and S. pasteuri JX-2 could significantly reduce BAs. This study not only contributed to understanding the BAs formation mechanism in Douchi, but also provided potential candidates to control the BAs in fermented soybean products.
Immune Persistence After Infant Hepatitis-B Vaccination: A Systematic Review and Meta-Analysis
Authors: Mahmood Sajid , Shah Kifayat Ullah , Khan Tahir Mehmood
Published: August 2018

A systematic review was performed to estimate the duration of protection of Hepatitis-B vaccine after primary vaccination during infancy. The number of seropositive participants with anti-HBs antibody titer ≥ 10 mIU/ml and seronegative participants who had anti-HBs antibody titer ≤ 10 mIU/ml after booster dose was the main outcome criteria to find out the protection time of Hepatitis-B vaccine. Twelve studies were selected for systematic review. Overall, results from the meta-analysis have revealed that the risk of Anti-HBs Titer ≤ 10 mIU/ml reduced by 50%. Upon performing the sub-group analysis it was revealed that the overall risk of having Anti-HBs Titre ≤ 10 mIU/ml was reduced up to 62% among the subjects age 21–30 years (0.38 [0.34, 0.44]; I2 = 0.0%, p = 0.938). Furthermore, it was observed that the risk of having titre level less than 10 mIU/ml for plasma derived vaccines were to be 56% [0.44, CI 0.33–0.57, I2 90.9%, p = <0.001]. Vaccination in early infancy does not ensure protection against Hepatitis-B infection. There is a strong correlation between the duration of protection and time elapsed after primary immunization during infancy.
China’s most typical nonferrous organic-metal facilities own specific microbial communities
Authors: Liu Jian-li , Yao Jun , Wang Fei , Ni Wen , Liu Xing-yu , Sunahara Geoffrey , Duran Robert , Jordan Gyozo , Hudson-Edwards Karen A. , Alakangas Lena , Solevic-Knudsen Tatjana , Zhu Xiao-zhe , Zhang Yi-yue , Li Zi-fu
Published: August 2018

The diversity and function of microorganisms have yet to be explored at non-ferrous metal mining facilities (NMMFs), which are the world’s largest and potentially most toxic sources of co-existing metal(loid)s and flotation reagents (FRs). The diversity and inferred functions of different bacterial communities inhabiting two types of sites (active and abandoned) in Guangxi province (China) were investigated for the first time. Here we show that the structure and diversity of bacteria correlated with the types of mine sites, metal(loid)s, and FRs concentrations; and best correlated with the combination of pH, Cu, Pb, and Mn. Combined microbial coenobium may play a pivotal role in NMMFs microbial life. Arenimonas, specific in active mine sites and an acidophilic bacterium, carries functions able to cope with the extreme conditions, whereas Latescibacteria specific in abandoned sites can degrade organics. Such a bacterial consortium provides new insights to develop cost-effective remediation strategies of co-contaminated sites that currently remain intractable for bioremediation.
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

The 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.
Author Correction: A comparative genomics and reductive dehalogenase gene transcription study of two chloroethene-respiring bacteria, Dehalococcoides mccartyi strains MB and 11a
Authors: Low Adrian , Shen Zhiyong , Cheng Dan , Rogers Matthew J. , Lee Patrick K. H. , He Jianzhong
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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

Arsenic 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

Artemisinin 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

TMPRSS6, 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

Treatment 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.
Publisher Correction: The ciliopathy protein TALPID3/KIAA0586 acts upstream of Rab8 activation in zebrafish photoreceptor outer segment formation and maintenance
Authors: Ojeda Naharros Irene , Cristian Flavia B. , Zang Jingjing , Gesemann Matthias , Ingham Philip W. , Neuhauss Stephan C. F. , Bachmann-Gagescu Ruxandra
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A nonlinear updating algorithm captures suboptimal inference in the presence of signal-dependent noise
Authors: Egger Seth W. , Jazayeri Mehrdad
Published: August 2018

Bayesian 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

Previous 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.
Author Correction: Prediction of Treatment Response for Combined Chemo- and Radiation Therapy for Non-Small Cell Lung Cancer Patients Using a Bio-Mathematical Model
Authors: Geng Changran , Paganetti Harald , Grassberger Clemens
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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

Prion 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

The 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

Work-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

The 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

Organisms 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

Based 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

Cryptic 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.
MicroRNA miR-509 Regulates ERK1/2, the Vimentin Network, and Focal Adhesions by Targeting Plk1
Authors: Liao Guoning , Wang Ruping , Rezey Alyssa C. , Gerlach Brennan D. , Tang Dale D.
Published: August 2018

Polo-like kinase 1 (Plk1) has been implicated in mitosis, cytokinesis, and proliferation. The mechanisms that regulate Plk1 expression remain to be elucidated. It is reported that miR-100 targets Plk1 in certain cancer cells. Here, treatment with miR-100 did not affect Plk1 protein expression in human airway smooth muscle cells. In contrast, treatment with miR-509 inhibited the expression of Plk1 in airway smooth muscle cells. Exposure to miR-509 inhibitor enhanced Plk1 expression in cells. Introduction of miR-509 reduced luciferase activity of a Plk1 3′UTR reporter. Mutation of miR-509 targeting sequence in Plk1 3′UTR resisted the reduction of the luciferase activity. Furthermore, miR-509 inhibited the PDGF-induced phosphorylation of MEK1/2 and ERK1/2, and cell proliferation without affecting the expression of c-Abl, a tyrosine kinase implicated in cell proliferation. Moreover, we unexpectedly found that vimentin filaments contacted paxillin-positive focal adhesions. miR-509 exposure inhibited vimentin phosphorylation at Ser-56, vimentin network reorganization, focal adhesion formation, and cell migration. The effects of miR-509 on ERK1/2 and vimentin were diminished in RNAi-resistant Plk1 expressing cells treated with miR-509. Taken together, these findings unveil previously unknown mechanisms that miR-509 regulates ERK1/2 and proliferation by targeting Plk1. miR-509 controls vimentin cytoskeleton reorganization, focal adhesion assembly, and cell migration through Plk1.
Geriatric nutritional risk index predicts prognosis after hepatectomy in elderly patients with hepatitis B virus-related hepatocellular carcinoma
Authors: Li Lei , Wang Haiqing , Yang Jian , Jiang Li , Yang Jiayin , Wu Hong , Wen Tianfu , Yan Lvnan
Published: August 2018

Geriatric nutritional risk index (GNRI) is a novel and useful screening tool for evaluating nutritional status in elderly in-patients. We aimed to investigate whether the preoperative GNRI could be a predictive factor for outcomes in patients over 65 years of age with a diagnosis of hepatocellular carcinoma (HCC). We retrospectively enrolled 261 consecutive HCC patients after hepatectomy and classified them into four risk groups based on the GNRI values: high risk (GNRI, <82), moderate risk (GNRI, 82–92), low risk (GNRI, 92–98), and normal (GNRI, >98). We found that the lower GNRI value was significantly associated with severe postoperative complications (P < 0.001) and liver failure (P < 0.001). By multivariate logistic regression analysis, high risk- and moderate risk GNRI groups were identified as independent risk factors for postoperative serve complications and liver failure. Multivariate Cox regression analysis revealed preoperative GNRI (P < 0.001) adversely affected overall survival. In conclusion, preoperative GNRI could predict severe postoperative complications included liver failure, and the lower GNRI value was associated with worse overall survival after hepatectomy in elderly HCC patients.
Thermal photodynamic therapy increases apoptosis and reactive oxygen species generation in cutaneous and mucosal squamous cell carcinoma cells
Authors: Austin Evan , Koo Eugene , Jagdeo Jared
Published: August 2018

Thermal photodynamic therapy (PDT) is an emerging modality to optimize treatment of pre-cancerous squamous cell carcinoma (SCC) lesions, known as actinic keratoses. Thermal PDT involves heating the tissue, skin, or mucosa above normal skin temperature during 5-aminolevulinic (5-ALA) incubation and irradiating with blue light, which leads to cell apoptosis and reactive oxygen species (ROS) generation. To our knowledge, thermal PDT has not been studied for the treatment of cutaneous or mucosal SCC. We incubated two SCC cell lines with 5-ALA for 30 minutes at temperatures between 21 °C and 42 °C and then irradiated cells with 1000 seconds of blue light. We measured changes in apoptosis, necrosis, and ROS. At 36 °C, there was a dose-dependent increase in apoptosis and ROS generation. Thermal incubation of 5-ALA at 39° and 42 °C followed by blue light increased cell apoptosis and ROS generation compared to untreated control samples incubated at the same temperatures. Thermal PDT may represent a new treatment option for cutaneous and mucosal SCC cancer. Thermal PDT is associated with an increase in SCC cellular apoptosis and is associated with an upregulation in ROS. Clinical trials are required to determine optimal thermal PDT treatment parameters and efficacy for cutaneous and mucosal SCC.