bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer
Authors: Vallières Martin , Kay-Rivest Emily , Perrin Léo Jean , Liem Xavier , Furstoss Christophe , Aerts Hugo J. W. L. , Khaouam Nader , Nguyen-Tan Phuc Felix , Wang Chang-Shu , Sultanem Khalil , Seuntjens Jan , El Naqa Issam
Published: August 2017

Quantitative extraction of high-dimensional mineable data from medical images is a process known as radiomics. Radiomics is foreseen as an essential prognostic tool for cancer risk assessment and the quantification of intratumoural heterogeneity. In this work, 1615 radiomic features (quantifying tumour image intensity, shape, texture) extracted from pre-treatment FDG-PET and CT images of 300 patients from four different cohorts were analyzed for the risk assessment of locoregional recurrences (LR) and distant metastases (DM) in head-and-neck cancer. Prediction models combining radiomic and clinical variables were constructed via random forests and imbalance-adjustment strategies using two of the four cohorts. Independent validation of the prediction and prognostic performance of the models was carried out on the other two cohorts (LR: AUC = 0.69 and CI = 0.67; DM: AUC = 0.86 and CI = 0.88). Furthermore, the results obtained via Kaplan-Meier analysis demonstrated the potential of radiomics for assessing the risk of specific tumour outcomes using multiple stratification groups. This could have important clinical impact, notably by allowing for a better personalization of chemo-radiation treatments for head-and-neck cancer patients from different risk groups.
Diel CO2 cycles reduce severity of behavioural abnormalities in coral reef fish under ocean acidification
Authors: Jarrold Michael D. , Humphrey Craig , McCormick Mark I. , Munday Philip L.
Published: August 2017

Elevated CO2 levels associated with ocean acidification (OA) have been shown to alter behavioural responses in coral reef fishes. However, all studies to date have used stable pCO2 treatments, not considering the substantial diel pCO2 variation that occurs in shallow reef habitats. Here, we reared juvenile damselfish, Acanthochromis polyacanthus, and clownfish, Amphiprion percula, at stable and diel cycling pCO2 treatments in two experiments. As expected, absolute lateralization of A. polyacanthus and response to predator cue of Am. percula were negatively affected in fish reared at stable, elevated pCO2 in both experiments. However, diel pCO2 fluctuations reduced the negative effects of OA on behaviour. Importantly, in experiment two, behavioural abnormalities that were present in fish reared at stable 750 µatm CO2 were largely absent in fish reared at 750 ± 300 µatm CO2. Overall, we show that diel pCO2 cycles can substantially reduce the severity of behavioural abnormalities caused by elevated CO2. Thus, past studies may have over-estimated the impacts of OA on the behavioural performance of coral reef fishes. Furthermore, our results suggest that diel pCO2 cycles will delay the onset of behavioural abnormalities in natural populations.
Schisandrin B regulates lipid metabolism in subcutaneous adipocytes
Authors: Kwan Hiu Yee , Wu Jiahui , Su Tao , Chao Xiao-Juan , Yu Hua , Liu Bin , Fu Xiuqiong , Tse Anfernee Kai Wing , Chan Chi Leung , Fong Wang Fun , Yu Zhi-ling
Published: August 2017

Subcutaneous adipocytes in obese subjects have a lower sensitivity to catecholamine-induced lipolysis and a higher sensitivity to insulin anti-lipolytic effects compared to adipocytes in other adipose depots. Therefore, increasing lipolysis in subcutaneous adipocytes coupled with enhanced fatty acid oxidation may be an anti-obesity strategy. Schisandrin B (Sch B) is one of the most abundant active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis which is a commonly prescribed Chinese medicinal herb. We found that Sch B reduced glycerolipid contents in 3T3-L1 adipocytes and subcutaneous adipocytes dissected from DIO mice. Sch B also activated hormone sensitive lipase (HSL) and increased lipolysis in these adipocyte in a protein kinase A-dependent manner. Interestingly, Sch B increased fatty acid oxidation gene expressions in these adipocytes, implying an increase in fatty acid oxidation after treatment. In in vivo model, we found that Sch B increased HSL phosphorylation, reduced glycerolipid levels and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes in the DIO mice. More importantly, Sch B significantly reduced the subcutaneous adipocyte sizes, subcutaneous adipose tissue mass and body weight of the mice. Our study provides scientific evidence to suggest a potential therapeutic function of Sch B or Schisandra chinensis seed containing Sch B in reducing obesity.
The Tomato DOF Daily Fluctuations 1, TDDF1 acts as flowering accelerator and protector against various stresses
Authors: Ewas Mohamed , Khames Eman , Ziaf Khurram , Shahzad Raheel , Nishawy Elsayed , Ali Farhan , Subthain Hizar , Amar Mohamed H. , Ayaad Mohamed , Ghaly Omran , Luo Jie
Published: August 2017

Adaptation to environmental changes is an important fitness trait for crop development. Photoperiod is an essential factor in seasonal control of flowering time. Sensing of day-length requires an interaction between the Photoperiod and the endogenous rhythms that is controlled by plant circadian clock. Thus, circadian clock is a critical regulator and internal molecular time-keeping mechanism, controlling key agricultural traits in crop plants such as the ability to adjust their growth and physiology to anticipate diurnal environmental changes. Here, we describe the gene Tomato Dof Daily Fluctuations 1 (TDDF1), which is involved in circadian regulation and stress resistance. Large daily oscillations in TDDF1 expression were retained after transferring to continuous dark (DD) or light (LL) conditions. Interestingly, overexpressing TDDF1 induce early flowering in tomato through up-regulation of the flowering-time control genes, moreover, by protein-protein interaction with the floral inducer SFT gene. Notably, overexpressing TDDF1 in tomato was associated with chlorophyll overaccumulation by up-regulating the related biosynthetic genes. TDDF1 expression results in improved drought, salt, various hormones stress tolerance alongwith resistance to late blight caused by Phytophthora infestans. This study can be a distinctive strategy to improve other economically important crops.
Effect of non-linearity of a predictor on the shape and magnitude of its receiver-operating-characteristic curve in predicting a binary outcome
Authors: Ho Kwok M.
Published: August 2017

Area under a receiver-operating-characteristic (AUROC) curve is widely used in medicine to summarize the ability of a continuous predictive marker to predict a binary outcome. This study illustrated how a U-shaped or inverted U-shaped continuous predictor would affect the shape and magnitude of its AUROC curve in predicting a binary outcome by comparing the ROC curves of the worst first 24-hour arterial pH values of 9549 consecutive critically ill patients in predicting hospital mortality before and after centering the predictor by its mean or median. A simulation dataset with an inverted U-shaped predictor was used to assess how this would affect the shape and magnitude of the AUROC curve. An asymmetrical U-shaped relationship between pH and hospital mortality, resulting in an inverse-sigmoidal ROC curve, was observed. The AUROC substantially increased after centering the predictor by its mean (0.611 vs 0.722, difference = 0.111, 95% confidence interval [CI] 0.087–0.135), and was further improved after centering by its median (0.611 vs 0.745, difference = 0.133, 95%CI 0.110–0.157). A sigmoidal-shaped ROC curve was observed for an inverted U-shaped predictor. In summary, a non-linear predictor can result in a biphasic-shaped ROC curve; and centering the predictor can reduce its bias towards null predictive ability.
Response of soil microbial community to application of biochar in cotton soils with different continuous cropping years
Authors: Han Guangming , Lan Jiayang , Chen Quanqiu , Yu Cui , Bie Shu
Published: August 2017

The bacterial community in soils of cotton that have continuously been cropped for 2 years, 6 years, 11 years and 14 years and treated with biochar (B0, 0 t·ha−1; B1, 12.5 t·ha−1; and B2, 20 t·ha−1) was investigated using next-generation sequencing. Of the 45 bacterial genera (relative abundance ratio of genera greater than 0.3%), 21 genera were affected (p < 0.05) by the biochar treatment, whereas 20 genera were affected by the continuous cropping. Between the soils that have been continuously cropped for 2 years and 14 years, 12 different genera were significantly observed (p < 0.05), and 6 genera belonged to the phylum Acidobacteria. The relative abundance of Sphingomonas and Pseudomonas in the biochar-treated soils was significantly higher than that in the soil without biochar treatment (p < 0.05), and the relative abundance of Sphingomonas and Pseudomonas in soils that have been continuously cropped for 2 years and 6 years was significantly higher than that in the soils continuously cropped for 11 years and 14 years (p < 0.05). The results suggest that the biochar application has a significant impact on the soil bacterial community, which may improve the microbial diversity of continuous cropping systems in cotton soils.
A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis
Authors: Díaz-Jiménez David , Núñez Lucía , De la Fuente Marjorie , Dubois-Camacho Karen , Sepúlveda Hugo , Montecino Martín , Torres-Riquelme Alejandro , García-González Paulina , Chnaiderman Jonás , Vossenkamper Anna , MacDonald Thomas T. , Simian Daniela , González María-Julieta , Cidlowski John A. , Quera Rodrigo , Hermoso Marcela A.
Published: August 2017

The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression. Serum ST2 levels and genetic variants in the IL1RL1 distal promoter were examined by ELISA and PCR sequencing in UC patients receiving corticosteroids. Glucocorticoid-mediated ST2 production was evaluated in intestinal mucosa cultures. Molecular regulation of glucocorticoid-mediated ST2 was assessed by RT-qPCR, ChIP assay and luciferase reporter assay. Dexamethasone effect on ST2 transcript expression was analyzed in leukocytes and related to IL1RL1 variants. Sequencing of a distal IL1RL1 promoter region demonstrated that SNPs rs6543115(C) and rs6543116(A) are associated with increased sST2 in UC patients on corticosteroids. Dexamethasone up-regulated sST2 transcription through interaction with the glucocorticoid-response element (GRE) carrying rs6543115(C) variant. Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression.
Prolonged AT1R activation induces CaV1.2 channel internalization in rat cardiomyocytes
Authors: Hermosilla Tamara , Encina Matías , Morales Danna , Moreno Cristian , Conejeros Carolina , Alfaro-Valdés Hilda M. , Lagos-Meza Felipe , Simon Felipe , Altier Christophe , Varela Diego
Published: August 2017

The cardiac L-type calcium channel is a multi-subunit complex that requires co-assembling of the pore-forming subunit CaV1.2 with auxiliary subunits CaVα2δ and CaVβ. Its traffic has been shown to be controlled by these subunits and by the activation of various G-protein coupled receptors (GPCR). Here, we explore the consequences of the prolonged activation of angiotensin receptor type 1 (AT1R) over CaV1.2 channel trafficking. Bioluminescence Resonance Energy Transfer (BRET) assay between β-arrestin and L-type channels in angiotensin II-stimulated cells was used to assess the functional consequence of AT1R activation, while immunofluorescence of adult rat cardiomyocytes revealed the effects of GPCR activation on CaV1.2 trafficking. Angiotensin II exposure results in β-arrestin1 recruitment to the channel complex and an apparent loss of CaV1.2 immunostaining at the T-tubules. Accordingly, angiotensin II stimulation causes a decrease in L-type current, Ca2+ transients and myocyte contractility, together with a faster repolarization phase of action potentials. Our results demonstrate that prolonged AT1R activation induces β-arrestin1 recruitment and the subsequent internalization of CaV1.2 channels with a half-dose of AngII on the order of 100 nM, suggesting that this effect depends on local renin-angiotensin system. This novel AT1R-dependent CaV1.2-trafficking modulation likely contributes to angiotensin II-mediated cardiac remodeling.
Single, but not dual, attention facilitates statistical learning of two concurrent auditory sequences
Authors: Daikoku Tatsuya , Yumoto Masato
Published: August 2017

When we are exposed to a novel stimulus sequence, we can learn the sequence by extracting a statistical structure that is potentially embedded in the sequence. This mechanism is called statistical learning, and is considered a fundamental and domain-general process that is innate in humans. In the real-world environment, humans are inevitably exposed to auditory sequences that often overlap with one another, such as speech sound streams from multiple speakers or entangled melody lines generated by multiple instruments. The present study investigated how single and dual attention modulates brain activity, reflecting statistical learning when two auditory sequences were presented simultaneously. The results demonstrated that the effect of statistical learning had more pronounced neural activity when listeners paid attention to only one sequence and ignored the other, rather than paying attention to both sequences. Biased attention may thus be an essential strategy when learners are exposed to multiple information streams.
Free mate choice does not influence reproductive success in humans
Authors: Sorokowski Piotr , Groyecka Agata , Karwowski Maciej , Manral Upma , Kumar Amit , Niemczyk Agnieszka , Marczak Michalina , Misiak Michał , Sorokowska Agnieszka , Huanca Thomas , Conde Esther , Wojciszke Bogdan , Pawłowski Bogusław
Published: August 2017

The effect of free mate choice on the relative magnitude of fitness benefits has been examined among various species. The majority of the data show significant fitness benefits of mating with partners of an individual’s own choice, highlighting elevated behavioral compatibility between partners with free mate choice. Similarities between humans and other species that benefit from free mate choice led us to hypothesize that it also confers reproductive benefits in Homo sapiens. To test this hypothesis, we conducted a study among three indigenous societies—the Tsimane’, Yali, and Bhotiya—who employ natural birth control. In all three samples, we compared the marriages arranged by parents with the non-arranged ones in terms of number of offspring. Here, we show that there were no significant relationships between type of marriage and the total number of alive children and number of dead children among the three sampled groups. The presented study is the first to date to examine the fitness benefits of free mate choice in humans. In discussion we present limitations of our research and discuss the possibility of love having a beneficial influence in terms of the number of offspring.
Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells
Authors: Thirstrup Kenneth , Dächsel Justus C. , Oppermann Felix S. , Williamson Douglas S. , Smith Garrick P. , Fog Karina , Christensen Kenneth V.
Published: August 2017

Genetic variation in the leucine-rich repeat kinase 2 (LRRK2) gene is associated with risk of familial and sporadic Parkinson’s disease (PD). To support clinical development of LRRK2 inhibitors as disease-modifying treatment in PD biomarkers for kinase activity, target engagement and kinase inhibition are prerequisite tools. In a combined proteomics and phosphoproteomics study on human peripheral mononuclear blood cells (PBMCs) treated with the LRRK2 inhibitor Lu AF58786 a number of putative biomarkers were identified. Among the phospho-site hits were known LRRK2 sites as well as two phospho-sites on human Rab10 and Rab12. LRRK2 dependent phosphorylation of human Rab10 and human Rab12 at positions Thr73 and Ser106, respectively, was confirmed in HEK293 and, more importantly, Rab10-pThr73 inhibition was validated in immune stimulated human PBMCs using two distinct LRRK2 inhibitors. In addition, in non-stimulated human PBMCs acute inhibition of LRRK2 with two distinct LRRK2 inhibitor compounds reduced Rab10-Thr73 phosphorylation in a concentration-dependent manner with apparent IC50’s equivalent to IC50’s on LRRK2-pSer935. The identification of Rab10 phosphorylated at Thr73 as a LRRK2 inhibition marker in human PBMCs strongly support inclusion of assays quantifying Rab10-pThr73 levels in upcoming clinical trials evaluating LRRK2 kinase inhibition as a disease-modifying treatment principle in PD.
Air stable black phosphorous in polyaniline-based nanocomposite
Authors: Fonsaca Jéssica E. S. , Domingues Sergio H. , Orth Elisa S. , Zarbin Aldo J. G.
Published: August 2017

The greatest challenge regarding black phosphorus (BP) comes as a result of its fast degradation when exposed to ambient conditions, which has overshadowed its applications. Herein, we report a simple and efficient route towards overcoming BP deterioration by preparing a nanocomposite with the conducting polymer polyaniline (PANI). The liquid/liquid interfacial method was employed to produce transparent, freestanding and transferable thin film of BP covered by PANI, with high stability under ambient atmosphere, up to 60 days. Otherwise, the uncapped exfoliated neat BP degraded in solely 3 days under the same conditions. Characterization data show that PANI covers efficiently the BP flakes, indicating favorable interactions between the components. The results presented here can be considered a breakthrough for employing BP as thin film in different technological applications, considering the properties of BP itself or taking advantage of synergistically combining the properties of both components.
Cranial biomechanics in basal urodeles: the Siberian salamander (Salamandrella keyserlingii) and its evolutionary and developmental implications
Authors: Zhou Zupeng , Fortuny Josep , Marcé-Nogué Jordi , Skutschas Pavel P.
Published: August 2017

Developmental changes in salamander skulls, before and after metamorphosis, affect the feeding capabilities of these animals. How changes in cranial morphology and tissue properties affect the function of the skull are key to decipher the early evolutionary history of the crown-group of salamanders. Here, 3D cranial biomechanics of the adultSalamandrella keyserlingiiwere analyzed under different tissue properties and ossification sequences of the cranial skeleton. This helped unravel that: (a) Mechanical properties of tissues (as bone, cartilage or connective tissue) imply a consensus between the stiffness required to perform a function versus the fixation (and displacement) required with the surrounding skeletal elements. (b) Changes on the ossification pattern, producing fontanelles as a result of bone loss or failure to ossify, represent a trend toward simplification potentially helping to distribute stress through the skull, but may also imply a major destabilization of the skull. (c) Bone loss may be originated due to biomechanical optimization and potential reduction of developmental costs. (d) Hynobiids are excellent models for biomechanical reconstruction of extinct early urodeles.
Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets
Authors: Obst Lieselotte , Göde Sebastian , Rehwald Martin , Brack Florian-Emanuel , Branco João , Bock Stefan , Bussmann Michael , Cowan Thomas E. , Curry Chandra B. , Fiuza Frederico , Gauthier Maxence , Gebhardt René , Helbig Uwe , Huebl Axel , Hübner Uwe , Irman Arie , Kazak Lev , Kim Jongjin B. , Kluge Thomas , Kraft Stephan , Loeser Markus , Metzkes Josefine , Mishra Rohini , Rödel Christian , Schlenvoigt Hans-Peter , Siebold Mathias , Tiggesbäumker Josef , Wolter Steffen , Ziegler Tim , Schramm Ulrich , Glenzer Siegfried H. , Zeil Karl
Published: August 2017

We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions.
Metagenomic evidence of stronger effect of stylo (legume) than bahiagrass (grass) on taxonomic and functional profiles of the soil microbial community
Authors: Zhou Yang , Zhu Honghui , Fu Shenglei , Yao Qing
Published: August 2017

Plants are key determinants of soil microbial community (SMC). Legumes and grasses are distinct groups in various ecosystems; however, how they differentially shape SMC structure and functioning has yet to be explored. Here, we investigate SMC in soils grown with stylo (legume) or bahiagrass (grass). Soil metagenomic sequencing indicates that Archaea was more abundant in unplanted soils than in planted soils, and that stylo selected higher abundance of fungi than bahiagrass. When the stylo soils enriched Streptomyces, Frankia, Mycobacterium and Amycolatopsis, the bahiagrass soils enriched Sphingomonas and Sphingobium. NMDS reveals that the legume shaped SMC more greatly than the grass (P < 0.004). SMC functional profiles (KEGG and CAZy) were also greatly altered by plants with the legume being more effective (P < 0.000 and P < 0.000). The abundant microbial taxa contributed to the main community functions, with Conexibacter, Sphingomonas, and Burkholderia showing multifunctionality. Moreover, soil chemical property showed much higher direct effect on SMC structure and functional profiles than soil extracts, although the soil total nitrogen and some compounds (e.g. heptadecane, 1-pentadecyne and nonanoic acid) in soil extracts were best correlated with SMC structure and functional profiles. These findings are the first to suggest that legume species shape SMC more greatly than grass species.
Optimal achieved blood pressure for patients with stable coronary artery disease
Authors: Huang Chin-Chou , Leu Hsin-Bang , Yin Wei-Hsian , Tseng Wei-Kung , Wu Yen-Wen , Lin Tsung-Hsien , Yeh Hung-I , Chang Kuan-Cheng , Wang Ji-Hung , Wu Chau-Chung , Chen Jaw-Wen
Published: August 2017

We aimed to investigate the ideal achieved blood pressure (BP) in ethnic Chinese patients with stable coronary artery disease (CAD) in Taiwan. A total of 2,045 patients (age 63.5 ± 11.9 years, 1,722 male [84.2%]) with stable CAD who had undergone percutaneous coronary interventions were enrolled. The achieved systolic BP was 130.6 ± 17.7 mmHg and diastolic BP was 74.9 ± 12.0 mmHg. In 12 months, patients with systolic BP < 120 mmHg and systolic BP ≥ 160 mmHg had increased risk of total cardiovascular events when compared to those with systolic BP 120–139 mmHg. In 24 months, patients with systolic BP < 120 mmHg and systolic BP ≥ 160 mmHg had increased risk of total cardiovascular events when compared to those with systolic BP 120–139 mmHg; patients with diastolic BP < 70 mmHg had increased risk of total cardiovascular events when compared to those with diastolic BP 70–79 mmHg. In conclusion, systolic BP < 120 mmHg and ≥160 mmHg or diastolic BP < 70 mmHg is associated with increased cardiovascular events, supporting that the optimal BP control should also be justified for stable CAD in non-western cohorts.
Entropy spikes as a signature of Lifshitz transitions in the Dirac materials
Authors: Tsaran V. Yu. , Kavokin A. V. , Sharapov S. G. , Varlamov A. A. , Gusynin V. P.
Published: August 2017

We demonstrate theoretically that the characteristic feature of a 2D system undergoing N consequent Lifshitz topological transitions is the occurrence of spikes of entropy per particle s of a magnitude ±ln2/(J − 1/2) with 2 ≤ J ≤ N at low temperatures. We derive a general expression for s as a function of chemical potential, temperature and gap magnitude for the gapped Dirac materials. Inside the smallest gap, the dependence of s on the chemical potential exhibits a dip-and-peak structure in the temperature vicinity of the Dirac point. The spikes of the entropy per particles can be considered as a signature of the Dirac materials. These distinctive characteristics of gapped Dirac materials can be detected in transport experiments where the temperature is modulated in gated structures.
Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome
Authors: Lee So-Hyun , Nam Tai-Seung , Li Wenting , Kim Jung Ha , Yoon Woong , Choi Yoo-Duk , Kim Kun-Hee , Cai Hua , Kim Min Jung , Kim Changsoo , Choy Hyon E. , Kim Nacksung , Chay Kee Oh , Kim Myeong-Kyu , Choi Seok-Yong
Published: August 2017

COACH syndrome is an autosomal recessive developmental disorder, a subtype of Joubert syndrome and related disorders, characterized by cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Although mutations in TMEM67 (transmembrane protein 67)/MKS3 (Meckel-Gruber syndrome, type 3) were reported to cause COACH syndrome, this causality has not verified by functional studies. In a 20-year-old Korean man, we found cerebellar ataxia, isolated elevation in serum γ-glutamyl transpeptidase (γ-GTP) activity, oligophrenia, the molar tooth sign (MTS) in the brain MR images and congenital hepatic fibrosis (CHF). Two novel compound heterozygous mutations were found in TMEM67 in the patient: i) missense mutation (c.395 G > C and p.Gly132Ala) in exon 3, and ii) deletion in exon 26 (c.2758delT and p.Tyr920ThrfsX40). Western blotting showed that the p.Tyr920ThrfsX40 mutation accelerates turnover of the TMEM67 protein. Although wild-type human TMEM67 RNA rescued phenotypes of zebrafish embryos injected with anti-sense oligonucleotide morpholinos against tmem67, the two human TMEM67 RNAs individually harboring the two mutations did not. Finally, Wnt signaling, but not Hedgehog signaling, was suppressed in tmem67 morphants. To the best of our knowledge, this is the first report verifying the causality between COACH syndrome and TMEM67, which will further our understanding of molecular pathogenesis of the syndrome.
Inert Gas Deactivates Protein Activity by Aggregation
Authors: Zhang Lijuan , Zhang Yuebin , Cheng Jie , Wang Lei , Wang Xingya , Zhang Meng , Gao Yi , Hu Jun , Zhang Xuehua , Lü Junhong , Li Guohui , Tai Renzhong , Fang Haiping
Published: August 2017

Biologically inert gases play important roles in the biological functionality of proteins. However, researchers lack a full understanding of the effects of these gases since they are very chemically stable only weakly absorbed by biological tissues. By combining X-ray fluorescence, particle sizing and molecular dynamics (MD) simulations, this work shows that the aggregation of these inert gases near the hydrophobic active cavity of pepsin should lead to protein deactivation. Micro X-ray fluorescence spectra show that a pepsin solution can contain a high concentration of Xe or Kr after gassing, and that the gas concentrations decrease quickly with degassing time. Biological activity experiments indicate a reversible deactivation of the protein during this gassing and degassing. Meanwhile, the nanoparticle size measurements reveal a higher number of “nanoparticles” in gas-containing pepsin solution, also supporting the possible interaction between inert gases and the protein. Further, MD simulations indicate that gas molecules can aggregate into a tiny bubble shape near the hydrophobic active cavity of pepsin, suggesting a mechanism for reducing their biological function.
Involvement of mTOR-autophagy in the selection of primitive mesenchymal stem cells in chitosan film 3-dimensional culture
Authors: Chiu Hsiao-Ying , Tsay Yeou-Guang , Hung Shih-Chieh
Published: August 2017

Mesenchymal stem cells (MSCs) in conventional monolayer culture are heterogeneous and contain a significant portion of senescent cells. MSCs cultured on chitosan film form 3-dimenional spheres, increase in stemness and differentiation capability; however, the underlying mechanisms remain elusive. We first demonstrate chitosan film culture induces apoptosis at 2 days, with specificity in late senescent cells. Especially in senescent cells, chitosan film culture activates mTOR, which activates S6K/S6/4E-BP1 to enhance fibronection synthesis and peripheral dead cell attachment, and phosphorylates ULK1 at S757 to further inactivate ULK1, LC3A and autophagy, thereby inducing apoptosis. Combination of chitosan film culture with mTOR inhibition prevents peripheral dead cell attachment, thereby further increasing pluripotent gene expression, in vitro osteogenesis and in vivo bone formation. These data successfully figure out the role of mTOR signaling in chitosan film culture and develop a method by combination of rapamycin treatment for promoting stemness and differentiation capability in MSCs.
Analyses of Mitogenome Sequences Revealed that Asian Citrus Psyllids (Diaphorina citri) from California Were Related to Those from Florida
Authors: Wu Fengnian , Kumagai Luci , Cen Yijing , Chen Jianchi , Wallis Christopher M. , Polek MaryLou , Jiang Hongyan , Zheng Zheng , Liang Guangwen , Deng Xiaoling
Published: August 2017

Asian citrus psyllid (ACP, Diaphorina citri Kuwayama) transmits “Candidatus Liberibacter asiaticus” (CLas), an unculturable alpha-proteobacterium associated with citrus Huanglongbing (HLB). CLas has recently been found in California. Understanding ACP population diversity is necessary for HLB regulatory practices aimed at reducing CLas spread. In this study, two circular ACP mitogenome sequences from California (mt-CApsy, ~15,027 bp) and Florida (mt-FLpsy, ~15,012 bp), USA, were acquired. Each mitogenome contained 13 protein coding genes, 2 ribosomal RNA and 22 transfer RNA genes, and a control region varying in sizes. The Californian mt-CApsy was identical to the Floridian mt-FLpsy, but different from the mitogenome (mt-GDpsy) of Guangdong, China, in 50 single nucleotide polymorphisms (SNPs). Further analyses were performed on sequences in cox1 and trnAsn regions with 100 ACPs, SNPs in nad1-nad4-nad5 locus through PCR with 252 ACP samples. All results showed the presence of a Chinese ACP cluster (CAC) and an American ACP cluster (AAC). We proposed that ACP in California was likely not introduced from China based on our current ACP collection but somewhere in America. However, more studies with ACP samples from around the world are needed. ACP mitogenome sequence analyses will facilitate ACP population research.
PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer
Authors: Mjos Siv , Werner Henrica M. J. , Birkeland Even , Holst Frederik , Berg Anna , Halle Mari K. , Tangen Ingvild L. , Kusonmano Kanthida , Mauland Karen K. , Oyan Anne M. , Kalland Karl-Henning , Lewis Aurélia E. , Mills Gordon B. , Krakstad Camilla , Trovik Jone , Salvesen Helga B. , Hoivik Erling A.
Published: August 2017

Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer.
De novo design of antibody complementarity determining regions binding a FLAG tetra-peptide
Authors: Entzminger Kevin C. , Hyun Jeong-min , Pantazes Robert J. , Patterson-Orazem Athena C. , Qerqez Ahlam N. , Frye Zach P. , Hughes Randall A. , Ellington Andrew D. , Lieberman Raquel L. , Maranas Costas D. , Maynard Jennifer A.
Published: August 2017

Computational antibody engineering efforts to date have focused on improving binding affinities or biophysical characteristics. De novo design of antibodies binding specific epitopes could greatly accelerate discovery of therapeutics as compared to conventional immunization or synthetic library selection strategies. Here, we employed de novo complementarity determining region (CDR) design to engineer targeted antibody–antigen interactions using previously described in silico methods. CDRs predicted to bind the minimal FLAG peptide (Asp–Tyr–Lys–Asp) were grafted onto a single-chain variable fragment (scFv) acceptor framework. Fifty scFvs comprised of designed heavy and light or just heavy chain CDRs were synthesized and screened for peptide binding by phage ELISA. Roughly half of the designs resulted in detectable scFv expression. Four antibodies, designed entirely in silico, bound the minimal FLAG sequence with high specificity and sensitivity. When reformatted as soluble antigen-binding fragments (Fab), these clones expressed well, were predominantly monomeric and retained peptide specificity. In both formats, the antibodies bind the peptide only when present at the amino-terminus of a carrier protein and even conservative peptide amino acid substitutions resulted in a complete loss of binding. These results support in silico CDR design of antibody specificity as an emerging antibody engineering strategy.
Evidence for rangewide panmixia despite multiple barriers to dispersal in a marine mussel
Authors: Lourenço Carla R. , Nicastro Katy R. , McQuaid Christopher D. , Chefaoui Rosa M. , Assis Jorge , Taleb Mohammed Z. , Zardi Gerardo I.
Published: August 2017

Oceanographic features shape the distributional and genetic patterns of marine species by interrupting or promoting connections among populations. Although general patterns commonly arise, distributional ranges and genetic structure are species-specific and do not always comply with the expected trends. By applying a multimarker genetic approach combined with Lagrangian particle simulations (LPS) we tested the hypothesis that oceanographic features along northeastern Atlantic and Mediterranean shores influence dispersal potential and genetic structure of the intertidal musselPerna perna. Additionally, by performing environmental niche modelling we assessed the potential and realized niche ofP.pernaalong its entire native distributional range and the environmental factors that best explain its realized distribution.Perna pernashowed evidence of panmixia across >4,000 km despite several oceanographic breaking points detected by LPS. This is probably the result of a combination of life history traits, continuous habitat availability and stepping-stone dynamics. Moreover, the niche modelling framework depicted minimum sea surface temperatures (SST) as the major factor shapingP.pernadistributional range limits along its native areas. Forthcoming warming SST is expected to further change these limits and allow the species to expand its range polewards though this may be accompanied by retreat from warmer areas.
Endolysin LysEF-P10 shows potential as an alternative treatment strategy for multidrug-resistant Enterococcus faecalis infections
Authors: Cheng Mengjun , Zhang Yufeng , Li Xinwei , Liang Jiaming , Hu Liyuan , Gong Pengjuan , Zhang Lei , Cai Ruopeng , Zhang Hao , Ge Jinli , Ji Yalu , Guo Zhimin , Feng Xin , Sun Changjiang , Yang Yongjun , Lei Liancheng , Han Wenyu , Gu Jingmin
Published: August 2017

Phage-derived lysins can hydrolyse bacterial cell walls and show great potential for combating Gram-positive pathogens. In this study, the potential of LysEF-P10, a new lysin derived from a isolated Enterococcus faecalis phage EF-P10, as an alternative treatment for multidrug-resistant E. faecalis infections, was studied. LysEF-P10 shares only 61% amino acid identity with its closest homologues. Four proteins were expressed: LysEF-P10, the cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain (LysEF-P10C), the putative binding domain (LysEF-P10B), and a fusion recombination protein (LysEF-P10B-green fluorescent protein). Only LysEF-P10 showed highly efficient, broad-spectrum bactericidal activity against E. faecalis. Several key functional residues, including the Cys-His-Asn triplet and the calcium-binding site, were confirmed using 3D structure prediction, BLAST and mutation analys. We also found that calcium can switch LysEF-P10 between its active and inactive states and that LysEF-P10B is responsible for binding E. faecalis cells. A single administration of LysEF-P10 (5 μg) was sufficient to protect mice against lethal vancomycin-resistant Enterococcus faecalis (VREF) infection, and LysEF-P10-specific antibody did not affect its bactericidal activity or treatment effect. Moreover, LysEF-P10 reduced the number of Enterococcus colonies and alleviated the gut microbiota imbalance caused by VREF. These results indicate that LysEF-P10 might be an alternative treatment for multidrug-resistant E. faecalis infections.
Discovery of human-like L-asparaginases with potential clinical use by directed evolution
Authors: Rigouin Coraline , Nguyen Hien Anh , Schalk Amanda M. , Lavie Arnon
Published: August 2017

L-asparaginase is a chemotherapy drug used to treat acute lymphoblastic leukemia (ALL). The main prerequisite for clinical efficacy of L-asparaginases is micromolar KM for asparagine to allow for complete depletion of this amino acid in the blood. Since currently approved L-asparaginases are of bacterial origin, immunogenicity is a challenge, which would be mitigated by a human enzyme. However, all human L-asparaginases have millimolar KM for asparagine. We recently identified the low KM guinea pig L-asparaginase (gpASNase1). Because gpASNase1 and human L-asparaginase 1 (hASNase1) share ~70% amino-acid identity, we decided to humanize gpASNase1 by generating chimeras with hASNase1 through DNA shuffling. To identify low KM chimeras we developed a suitable bacterial selection system (E. coli strain BW5Δ). Transforming BW5Δ with the shuffling libraries allowed for the identification of several low KM clones. To further humanize these clones, the C-terminal domain of gpASNase1 was replaced with that of hASNase1. Two of the identified clones, 63N-hC and 65N-hC, share respectively 85.7% and 87.1% identity with the hASNase1 but have a KM similar to gpASNase1. These clones possess 100–140 fold enhanced catalytic efficiency compared to hASNase1. Notably, we also show that these highly human-like L-asparaginases maintain their in vitro ALL killing potential.
Predicting hidden bulk phases from surface phases in bilayered Sr3Ru2O7
Authors: Rivero Pablo , Jin Rongying , Chen Chen , Meunier Vincent , Plummer E. W. , Shelton William
Published: August 2017

The ability to predict hidden phases under extreme conditions is not only crucial to understanding and manipulating materials but it could also lead to insight into new phenomena and novel routes to synthesize new phases. This is especially true for Ruddlesden-Popper perovskite phases that possess interesting properties ranging from superconductivity and colossal magnetoresistance to photovoltaic and catalytic activities. In particular, the physical properties of the bilayer perovskite Sr3Ru2O7 at the surface are intimately tied to the rotation and tilt of the RuO6 octahedra. To take advantage of the extra degree of freedom associated with tilting we have performed first principles hybrid density functional simulations of uniaxial pressure applied along the c-axis of bulk Sr3Ru2O7 where we find that the octahedra become tilted, leading to two phase transitions. One is a structural transition at $$\simeq $$
≃
1.5 GPa, and the other is from a ferromagnetic (FM) metal to an antiferromagnetic (AFM) insulator at $$\simeq $$
≃
21 GPa whose AFM spin configuration is different from the AFM state near the FM ground state.
An ab initio study on noble gas inserted halogenated acetylene: HNgCCX (Ng = Kr and Xe; X = halogen)
Authors: Huang Zhengguo , Li Yuying , Wang Xiaohong
Published: August 2017

Although HNgCCX (Ng = Kr and Xe; X = F and Cl) have been identified in cryogenic matrices, similar Br and I analogues have not been prepared so far. In this paper, the nature of HNgCCX (Ng = Kr and Xe; X = F, Cl, Br and I) have been investigated by ab initio methods. The main characteristic absorption peak of HNgCCX is thevH-Ng, which decreases as X varies from F to I. Moreover, the H-Xe bond is stronger than the H-Kr bond. ThevC≡CandvC-Xexhibit red- and blue-shift characters, respectively, especially the C-X bond is abnormal blue-shift halogen bond. AIM results show that the H-Ng bond is essentially covalent bond and the covalent character of H-Xe bond is underestimated, and the trend of the covalent character is C-Cl > C-Br > C-F > C-I. Although HNgCCX is instable thermodynamically with respect to Ng + HCCX, it is kinetically stable with respect to the two-/three-body channels due to the relatively larger energy barriers. The three-body channels of HNgCCX is the main decomposition channel, and the kinetically stability of HXeCCX is more than its Kr analogues. This study is helpful for the preparation of new HNgCCX in cryogenic matrices.
Transcriptome analysis reveals the host selection fitness mechanisms of the Rhizoctonia solani AG1IA pathogen
Authors: Xia Yuan , Fei Binghong , He Jiayu , Zhou Menglin , Zhang Danhua , Pan Linxiu , Li Shuangcheng , Liang Yueyang , Wang Lingxia , Zhu Jianqing , Li Ping , Zheng Aiping
Published: August 2017

Rhizoctonia solaniAG1IA is a major generalist pathogen that causes sheath blight. Its genome, which was the first to be sequenced from theRhizoctoniagenus, may serve as a model for studying pathogenic mechanisms. To explore the pathogen-host fitness mechanism of sheath-blight fungus, a comprehensive comparative transcriptome ecotype analysis ofR. solaniAG1IA isolated from rice, soybean and corn during infection was performed. Special characteristics in gene expression, gene ontology terms and expression of pathogenesis-associated genes, including genes encoding secreted proteins, candidate effectors, hydrolases, and proteins involved in secondary metabolite production and the MAPK pathway, were revealed. Furthermore, as an important means of pathogenic modulation, diverse alternative splicing of key pathogenic genes inRhizoctonia solaniAG1IA during infections of the abovementioned hosts was uncovered for the first time. These important findings of key factors in the pathogenicity ofR. solaniAG1IA ecotypes during infection of various hosts explain host preference and provide novel insights into the pathogenic mechanisms and host-pathogen selection. Furthermore, they provide information on the fitness ofRhizoctonia, a severe pathogen with a wide host range.
Modelling viscoacoustic wave propagation with the lattice Boltzmann method
Authors: Xia Muming , Wang Shucheng , Zhou Hui , Shan Xiaowen , Chen Hanming , Li Qingqing , Zhang Qingchen
Published: August 2017

In this paper, the lattice Boltzmann method (LBM) is employed to simulate wave propagation in viscous media. LBM is a kind of microscopic method for modelling waves through tracking the evolution states of a large number of discrete particles. By choosing different relaxation times in LBM experiments and using spectrum ratio method, we can reveal the relationship between the quality factor Q and the parameter τ in LBM. A two-dimensional (2D) homogeneous model and a two-layered model are tested in the numerical experiments, and the LBM results are compared against the reference solution of the viscoacoustic equations based on the Kelvin-Voigt model calculated by finite difference method (FDM). The wavefields and amplitude spectra obtained by LBM coincide with those by FDM, which demonstrates the capability of the LBM with one relaxation time. The new scheme is relatively simple and efficient to implement compared with the traditional lattice methods. In addition, through a mass of experiments, we find that the relaxation time of LBM has a quantitative relationship with Q. Such a novel scheme offers an alternative forward modelling kernel for seismic inversion and a new model to describe the underground media.
Full-field 3D shape measurement of discontinuous specular objects by direct phase measuring deflectometry
Authors: Liu Yue , Huang Shujun , Zhang Zonghua , Gao Nan , Gao Feng , Jiang Xiangqian
Published: August 2017

Abstarct

With the advent of intelligent manufacturing, phase measuring deflectometry (PMD) has been widely studied for the measurement of the three-dimensional (3D) shape of specular objects. However, existing PMDs cannot measure objects having discontinuous specular surfaces. This paper presents a new direct PMD (DPMD) method that measures the full-field 3D shape of complicated specular objects. A mathematical model is derived to directly relate an absolute phase map to depth data, instead of the gradient. Two relevant parameters are calibrated using a machine vision-based method. On the basis of the derived model, a full-field 3D measuring system was developed. The accuracy of the system was evaluated using a mirror with known positions along an accurate translating stage. The 3D shape of a monolithic multi-mirror array having multiple specular surfaces was measured. Experimental results show that the proposed DPMD method can obtain the full-field 3D shape of specular objects having isolated and/or discontinuous surfaces accurately and effectively.
Highly sensitive electrochemical detection of mercuric ions based on sequential nucleic acid amplification and guanine nanowire formation
Authors: Xie Shunbi , Tang Ying , Tang Dianyong
Published: August 2017

This work reported a strategy of combining enzyme/DNAzyme amplification and guanine nanowires to develop a bioassay for Hg2+ detection.
A novel supramolecular magnesoborate framework with snowflake-like channels built by unprecedented huge B69 cluster cages
Authors: Wang Jia-Jia , Yang Guo-Yu
Published: August 2017

A novel magnesoborate with a 3D supramolecular framework has been made under solvothermal conditions, showing wonderful snowflake-like motif channels assembled from unprecedented B69 cluster cage units.