bluuebunny/crossref_metadata_2025 huggingface dataset:
NPTX2 promotes colorectal cancer growth and liver metastasis by the activation of the canonical Wnt/β-catenin pathway via FZD6
Authors: Xu Chunjie , Tian Guangang , Jiang Chunhui , Xue Hanbing , Kuerbanjiang Manzila , Sun Longci , Gu Lei , Zhou Hong , Liu Ye , Zhang Zhigang , Xu Qing
Published: March 2019

Accumulating evidence from clinical and epidemiological studies has highlighted the close correlation between the individual risk of cancer and nervous system diseases. The expression of neuronal pentraxin 2 (NPTX2) is absent in Alzheimer’s disease, anxiety, and depression. Herein, we found that NPTX2 mRNA and protein expression was significantly upregulated in colorectal carcinoma (CRC). NPTX2 expression level gradually increased with CRC progression and was closely associated with poor prognosis. In vitro and in vivo studies demonstrated that NPTX2 promoted CRC proliferation and metastasis through the activation of the Wnt/β-catenin signaling pathway. As NPTX2 receptors are absent on CRC cells, NPTX2 was shown to physically interact with frizzled class receptor 6 (FZD6) to promote β-catenin translocation into the cell nucleus, resulting in an increase in the expression of MYC, cyclin D1, snail, and N-cadherin along with a decrease in the expression of E-cadherin. Knockdown of FZD6 expression with a small-interfering RNA almost completely reversed the proliferative effects of NPTX2 on CRC development. In conclusion, NPTX2, a molecule related to nervous system diseases, promotes CRC cell proliferation and metastasis through the activation of the Wnt/β-catenin pathway via direct interaction with FZD6.
The whole transcriptome and proteome changes in the early stage of myocardial infarction
Authors: Li Yanfei , Wang Cuiping , Li Tingting , Ma Linlin , Fan Fangzhou , Jin Yueling , Shen Junwei
Published: March 2019

As the most severe manifestation of coronary artery disease, myocardial infarction (MI) is a complex and multifactorial pathophysiologic process. However, the pathogenesis that underlies MI remains unclear. Here, we generated a MI mouse model by ligation of the proximal left anterior descending coronary artery. The transcriptome and proteome, at different time points after MI, were detected and analysed. Immune-related pathways, cell cycle-related pathways, and extracellular matrix remodelling-related pathways were significantly increased after MI. Not only innate immune cells but also adaptive immune cells participated in the early stage of MI. Proteins that functioned in blood agglutination, fibrinolysis, secretion, and immunity were significantly changed after MI. Nppa, Serpina3n, and Anxa1, three secreted proteins that can easily be detected in blood, were significantly changed after MI. Our discoveries not only reveal the molecular and cellular changes in MI but also identify potential candidate biomarkers of MI for clinical diagnosis or treatment.
Publisher Correction: Capturing variation impact on molecular interactions in the IMEx Consortium mutations data set
Authors:   IMEx Consortium contributing authors, Khadake J. , Meldal B. , Panni S. , Thorneycroft D. , van Roey K. , Abbani S. , Salwinski L. , Pellegrini M. , Iannuccelli M. , Licata L. , Cesareni G. , Roechert B. , Bridge A. , Ammari M. G. , McCarthy F. , Broackes-Carter F. , Campbell N. H. , Melidoni A. N. , Rodriguez-Lopez M. , Lovering R. C. , Jagannathan S. , Chen C. , Lynn D. J. , Ricard-Blum S. , Mahadevan U. , Raghunath A. , del-Toro N. , Duesbury M. , Koch M. , Perfetto L. , Shrivastava A. , Ochoa D. , Wagih O. , Piñero J. , Kotlyar M. , Pastrello C. , Beltrao P. , Furlong L. I. , Jurisica I. , Hermjakob H. , Orchard S. , Porras P.
Published: March 2019

In the original HTML version of this Article, the order of authors within the author list was incorrect. The IMEx Consortium contributing authors were incorrectly listed as the last author and should have been listed as the first author. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
Microbial abundance, activity and population genomic profiling with mOTUs2
Authors: Milanese Alessio , Mende Daniel R , Paoli Lucas , Salazar Guillem , Ruscheweyh Hans-Joachim , Cuenca Miguelangel , Hingamp Pascal , Alves Renato , Costea Paul I , Coelho Luis Pedro , Schmidt Thomas S. B. , Almeida Alexandre , Mitchell Alex L , Finn Robert D. , Huerta-Cepas Jaime , Bork Peer , Zeller Georg , Sunagawa Shinichi
Published: March 2019

Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites).
Discovery of key whole-brain transitions and dynamics during human wakefulness and non-REM sleep
Authors: Stevner A. B. A. , Vidaurre D. , Cabral J. , Rapuano K. , Nielsen S. F. V. , Tagliazucchi E. , Laufs H. , Vuust P. , Deco G. , Woolrich M. W. , Van Someren E. , Kringelbach M. L.
Published: March 2019

The modern understanding of sleep is based on the classification of sleep into stages defined by their electroencephalography (EEG) signatures, but the underlying brain dynamics remain unclear. Here we aimed to move significantly beyond the current state-of-the-art description of sleep, and in particular to characterise the spatiotemporal complexity of whole-brain networks and state transitions during sleep. In order to obtain the most unbiased estimate of how whole-brain network states evolve through the human sleep cycle, we used a Markovian data-driven analysis of continuous neuroimaging data from 57 healthy participants falling asleep during simultaneous functional magnetic resonance imaging (fMRI) and EEG. This Hidden Markov Model (HMM) facilitated discovery of the dynamic choreography between different whole-brain networks across the wake-non-REM sleep cycle. Notably, our results reveal key trajectories to switch within and between EEG-based sleep stages, while highlighting the heterogeneities of stage N1 sleep and wakefulness before and after sleep.
MMS observations of electron scale magnetic cavity embedded in proton scale magnetic cavity
Authors: Liu H. , Zong Q.-G. , Zhang H. , Xiao C. J. , Shi Q. Q. , Yao S. T. , He J. S. , Zhou X.-Z. , Pollock C. , Sun W. J. , Le G. , Burch J. L. , Rankin R.
Published: March 2019

Magnetic cavities (sometimes referred to as magnetic holes) at electron kinetic scale are thought to be one of the extremely small intermittent structures formed in magnetized turbulent plasmas, where the turbulence energy cascaded down to electron scale may finally be dissipated and consequently energize the electrons. However, the geometry and formation of these structures remain not definitively resolved. Here we discuss an electron scale magnetic cavity embedded in a proton scale magnetic cavity observed by the MMS spacecraft in the magnetosheath. By applying an innovative particle sounding technique, we directly depict the boundary of the electron scale magnetic cavity and uncover the geometry. We find that this structure is nearly circular with a radius of 10.0 km and its formation is due to the diamagnetic current. Investigation of the electron scale structure is only recently made possible by the high spatial and temporal resolution provided by MMS observations.
A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome
Authors: Wiberg Akira , Ng Michael , Schmid Annina B. , Smillie Robert W. , Baskozos Georgios , Holmes Michael V. , Künnapuu K. , Mägi R. , Bennett David L. , Furniss Dominic
Published: March 2019

Carpal tunnel syndrome (CTS) is a common and disabling condition of the hand caused by entrapment of the median nerve at the level of the wrist. It is the commonest entrapment neuropathy, with estimates of prevalence ranging between 5–10%. Here, we undertake a genome-wide association study (GWAS) of an entrapment neuropathy, using 12,312 CTS cases and 389,344 controls identified in UK Biobank. We discover 16 susceptibility loci for CTS with p < 5 × 10−8. We identify likely causal genes in the pathogenesis of CTS, including ADAMTS17, ADAMTS10 and EFEMP1, and using RNA sequencing demonstrate expression of these genes in surgically resected tenosynovium from CTS patients. We perform Mendelian randomisation and demonstrate a causal relationship between short stature and higher risk of CTS. We suggest that variants within genes implicated in growth and extracellular matrix architecture contribute to the genetic predisposition to CTS by altering the environment through which the median nerve transits.
Single-shot on-chip spectral sensors based on photonic crystal slabs
Authors: Wang Zhu , Yi Soongyu , Chen Ang , Zhou Ming , Luk Ting Shan , James Anthony , Nogan John , Ross Willard , Joe Graham , Shahsafi Alireza , Wang Ken Xingze , Kats Mikhail A. , Yu Zongfu
Published: March 2019

Miniaturized spectrometers have significant potential for portable applications such as consumer electronics, health care, and manufacturing. These applications demand low cost and high spectral resolution, and are best enabled by single-shot free-space-coupled spectrometers that also have sufficient spatial resolution. Here, we demonstrate an on-chip spectrometer that can satisfy all of these requirements. Our device uses arrays of photodetectors, each of which has a unique responsivity with rich spectral features. These responsivities are created by complex optical interference in photonic-crystal slabs positioned immediately on top of the photodetector pixels. The spectrometer is completely complementary metal–oxide–semiconductor (CMOS) compatible and can be mass produced at low cost.
Modulation of recombination zone position for quasi-two-dimensional blue perovskite light-emitting diodes with efficiency exceeding 5%
Authors: Li Zhenchao , Chen Ziming , Yang Yongchao , Xue Qifan , Yip Hin-Lap , Cao Yong
Published: March 2019

In recent years, substantial progress has been made in developing perovskite light-emitting diodes with near-infrared, red and green emissions and over 20% external quantum efficiency. However, the development of perovskite light-emitting diodes with blue emission remains a great challenge, which retards further development of full-color displays and white-light illumination based on perovskite emissive materials. Here, firstly, through composition and dimensional engineering, we prepare quasi-two-dimensional perovskite thin films with improved blue emission, taking advantages of reduced trap density and enhanced photoluminescence quantum yield. Secondly, we find a vertically non-uniform distribution of perovskite crystals in the PEDOT:PSS/perovskite hybrid film. Through modulating the position of the recombination zone, we activate the majority of quasi-two-dimensional perovskite crystals, and thus demonstrate the most efficient blue perovskite light-emitting diode to date with emission peak at 480 nm, record luminance of 3780 cd m−2 and record external quantum efficiency of 5.7%.
Non-saturating quantum magnetization in Weyl semimetal TaAs
Authors: Zhang Cheng-Long , Wang C. M. , Yuan Zhujun , Xu Xitong , Wang Guangqiang , Lee Chi-Cheng , Pi Li , Xi Changying , Lin Hsin , Harrison Neil , Lu Hai-Zhou , Zhang Jinglei , Jia Shuang
Published: March 2019

Detecting the spectroscopic signatures of relativistic quasiparticles in emergent topological materials is crucial for searching their potential applications. Magnetometry is a powerful tool for fathoming electrons in solids, by which a clear method for discerning relativistic quasiparticles has not yet been established. Adopting the probes of magnetic torque and parallel magnetization for the archetype Weyl semimetal TaAs in strong magnetic field, we observed a quasi-linear field dependent effective transverse magnetization and a non-saturating parallel magnetization when the system enters the quantum limit. Distinct from the saturating magnetic responses for non-relativistic quasiparticles, the non-saturating signals of TaAs in strong field is consistent with our newly developed magnetization calculation for a Weyl fermion system in an arbitrary angle. Our results establish a high-field thermodynamic method for detecting the magnetic response of relativistic quasiparticles in topological materials.
Deep convolutional neural networks for accurate somatic mutation detection
Authors: Sahraeian Sayed Mohammad Ebrahim , Liu Ruolin , Lau Bayo , Podesta Karl , Mohiyuddin Marghoob , Lam Hugo Y. K.
Published: March 2019

Accurate detection of somatic mutations is still a challenge in cancer analysis. Here we present NeuSomatic, the first convolutional neural network approach for somatic mutation detection, which significantly outperforms previous methods on different sequencing platforms, sequencing strategies, and tumor purities. NeuSomatic summarizes sequence alignments into small matrices and incorporates more than a hundred features to capture mutation signals effectively. It can be used universally as a stand-alone somatic mutation detection method or with an ensemble of existing methods to achieve the highest accuracy.
Publisher Correction: Mathematical model of hemodynamic mechanisms and consequences of glomerular hypertension in diabetic mice
Authors: Mahato Hari Shankar , Ahlstrom Christine , Jansson-Löfmark Rasmus , Johansson Ulrika , Helmlinger Gabriel , Hallow K. Melissa
Published: March 2019

The original version of this Article had an incorrect Article number of 2, an incorrect Volume of 5 and an incorrect Publication year of 2019. These errors have now been corrected in the PDF and HTML versions of the Article.
Metagenomics and the development of viral water quality tools
Authors: Bibby Kyle , Crank Katherine , Greaves Justin , Li Xiang , Wu Zhenyu , Hamza Ibrahim A. , Stachler Elyse
Published: March 2019

Human exposure to pathogenic viruses in environmental waters results in a significant global disease burden. Current microbial water quality monitoring approaches, mainly based on fecal indicator bacteria, insufficiently capture human health impacts posed by pathogenic viruses in water. The emergence of the ‘microbiome era’ and high-throughput metagenome sequencing has led to the discovery of novel human-associated viruses, including both pathogenic and commensal viruses in the human microbiome. The discovery of novel human-associated viruses is often followed by their detection in wastewater, highlighting the great diversity of human-associated viruses potentially present in the water environment. Novel human-associated viruses provide a rich reservoir to develop viral water quality management tools with diverse applications, such as regulating wastewater reuse and monitoring agricultural and recreational waters. Here, we review the pathway from viral discovery to water quality monitoring tool, and highlight select human-associated viruses identified by metagenomics and subsequently detected in the water environment (namely Bocavirus, Cosavirus, CrAssphage, Klassevirus, and Pepper Mild Mottle Virus). We also discuss research needs to enable the application of recently discovered human-associated viruses in water quality monitoring, including investigating the geographic distribution, environmental fate, and viability of potential indicator viruses. Examples suggest that recently discovered human pathogens are likely to be less abundant in sewage, while other human-associated viruses (e.g., bacteriophages or viruses from food) are more abundant but less human-specific. The improved resolution of human-associated viral diversity enabled by metagenomic tools provides a significant opportunity for improved viral water quality management tools.
Approaching the potential of model-data comparisons of global land carbon storage
Authors: Wu Zhendong , Hugelius Gustaf , Luo Yiqi , Smith Benjamin , Xia Jianyang , Fensholt Rasmus , Lehsten Veiko , Ahlström Anders
Published: March 2019

Carbon storage dynamics in vegetation and soil are determined by the balance of carbon influx and turnover. Estimates of these opposing fluxes differ markedly among different empirical datasets and models leading to uncertainty and divergent trends. To trace the origin of such discrepancies through time and across major biomes and climatic regions, we used a model-data fusion framework. The framework emulates carbon cycling and its component processes in a global dynamic ecosystem model, LPJ-GUESS, and preserves the model-simulated pools and fluxes in space and time. Thus, it allows us to replace simulated carbon influx and turnover with estimates derived from empirical data, bringing together the strength of the model in representing processes, with the richness of observational data informing the estimations. The resulting vegetation and soil carbon storage and global land carbon fluxes were compared to independent empirical datasets. Results show model-data agreement comparable to, or even better than, the agreement between independent empirical datasets. This suggests that only marginal improvement in land carbon cycle simulations can be gained from comparisons of models with current-generation datasets on vegetation and soil carbon. Consequently, we recommend that model skill should be assessed relative to reference data uncertainty in future model evaluation studies.
Quantized spin pump on helical edge states of a topological insulator
Authors: Wang Mei-Juan , Wang Jun , Liu Jun-Feng
Published: March 2019

We report a theoretical study of the quantized spin pump in a traditional quantum pump device that is based on the helical edge states of a quantum spin Hall insulator. By introducing two time-dependent magnetizations out of phase as the pumping parameters, we found that when the Fermi energy resides in the energy gap opened by magnetization, an integer number of charges or spins can be pumped out in a pumping cycle and ascribed to the possible topological interface state born in between the two pumping potentials. The quantized pump current can be fully spin-polarized, spin-unpolarized, or pure spin current while its direction can be abruptly reversed by some system parameters such as the pumping phase and local gate voltage. Our findings may shed light on generation of a quantized spin pump.
Non-conventional Ce:YAG nanostructures via urea complexes
Authors: Armetta Francesco , Saladino Maria Luisa , Giordano Cristina , Defilippi Chiara , Marciniak Łukasz , Hreniak Dariusz , Caponetti Eugenio
Published: March 2019

Ce:YAG nanostructures (Ce:YAG = Cerium in Yttrium Aluminium Garnet), easy to control and shape, have been prepared via templating approach using natural and synthetic materials (i.e. paper, cotton wool and glass wool) previously soaked with a gel-like metals precursor and then thermally treated to achieve the wished morphology. The final material, otherwise difficult to process, can be easily moulded, it is lightweight, portable and forms, at the nanoscale, homogeneous layers of interconnected but not agglomerated nanoparticles (15 ± 5 nm). Using the same synthetic route, called Urea-Glass-Route, but in absence of a template, extremely pure Ce:YAG nanoparticle (45 ± 5 nm) can be also prepared, highly crystalline and well-defined in size and shape. Both structural and optical properties of the final materials were investigated, showing high optical quality. The support allows the production of a multifunctional material with mouldable shape and potential lighting application for large structures combining the strength, chemical durability, fire resistance, and translucency of glass fibres. Last, but not least, the synthetic path also allows an easy scaling up of the process: the first, key step for practical application of nanosized rare-earth doped YAG on large scale.
Direct imaging of the recruitment and phosphorylation of S6K1 in the mTORC1 pathway in living cells
Authors: Ahmed Abdullah R. , Owens Raymond J. , Stubbs Christopher D. , Parker Anthony W. , Hitchman Richard , Yadav Rahul B. , Dumoux Maud , Hawes Chris , Botchway Stanley W.
Published: March 2019

Knowledge of protein signalling pathways in the working cell is seen as a primary route to identifying and developing targeted medicines. In recent years there has been a growing awareness of the importance of the mTOR pathway, making it an attractive target for therapeutic intervention in several diseases. Within this pathway we have focused on S6 kinase 1 (S6K1), the downstream phosphorylation substrate of mTORC1, and specifically identify its juxtaposition with mTORC1. When S6K1 is co-expressed with raptor we show that S6K1 is translocated from the nucleus to the cytoplasm. By developing a novel biosensor we demonstrate in real-time, that phosphorylation and de-phosphorylation of S6K1 occurs mainly in the cytoplasm of living cells. Furthermore, we show that the scaffold protein raptor, that typically recruits mTOR substrates, is not always involved in S6K1 phosphorylation. Overall, we demonstrate how FRET-FLIM imaging technology can be used to show localisation of S6K1 phosphorylation in living cells and hence a key site of action of inhibitors targeting mTOR phosphorylation.
Prediction of future cognitive impairment among the community elderly: A machine-learning based approach
Authors: Na Kyoung-Sae
Published: March 2019

The early detection of cognitive impairment is a key issue among the elderly. Although neuroimaging, genetic, and cerebrospinal measurements show promising results, high costs and invasiveness hinder their widespread use. Predicting cognitive impairment using easy-to-collect variables by non-invasive methods for community-dwelling elderly is useful prior to conducting such a comprehensive evaluation. This study aimed to develop a machine learning-based predictive model for future cognitive impairment. A total of 3424 community elderly without cognitive impairment were included from the nationwide dataset. The gradient boosting machine (GBM) was exploited to predict cognitive impairment after 2 years. The GBM performance was good (sensitivity = 0.967; specificity = 0.825; and AUC = 0.921). This study demonstrated that a machine learning-based predictive model might be used to screen future cognitive impairment using variables, which are commonly collected in community health care institutions. With efforts of enhancing the predictive performance, such a machine learning-based approach can further contribute to the improvement of the cognitive function in community elderly.
Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model
Authors: Peng Chiung Chi , Chen Chang-Yu , Chen Chang-Rong , Chen Chang-Jui , Shen Kun-Hung , Chen Kuan-Chou , Peng Robert Y.
Published: March 2019

Bicalutamide (Bic) is frequently used in androgen deprivation therapy (ADT) for treating prostate cancer. ADT-induced hypogonadism was reported to have the potential to lead to acute kidney injury (AKI). ADT was also shown to induce bladder fibrosis via induction of the transforming growth factor (TGF)-β level. We hypothesized that Bic can likely induce renal fibrosis. To understand this, a cell model was used to explore expressions of relevant profibrotic proteins. Results indicated that Bic initiated multiple apoptotic and fibrotic pathways, including androgen deprivation, downregulation of the androgen receptor → phosphatidylinositol-3-kinase → Akt pathway, upregulation of the extrinsic apoptotic pathway- tumor necrosis factor α →  nuclear factor κB → caspase-3, increased expressions of fibrosis-related proteins including platelet-derived growth factor β, fibronectin and collagen IV, and enhanced cell migration. The endoplasmic reticular stress pathway and smooth muscle actin were unaffected by Bic. Co-treatment with testosterone was shown to have an anti-apoptotic effect against Bic, suggesting a better outcome of Bic therapy if administered with an appropriate testosterone intervention. However, since Bic was found to inhibit the membrane transport and consumption rates of testosterone, a slightly larger dose of testosterone is recommended. In conclusion, these pathways can be considered to be pharmaceutically relevant targets for drug development in treating the adverse effects of Bic.
A unique and threatened deep water coral-bivalve biotope new to the Mediterranean Sea offshore the Naples megalopolis
Authors: Taviani Marco , Angeletti Lorenzo , Cardone Frine , Montagna Paolo , Danovaro Roberto
Published: March 2019

The Gulf of Naples is an example of the most beautiful and biodiverse marine regions of the Mediterranean Sea and of the most impacted areas in terms of industrial activities, large contaminated areas, resource exploitation, infrastructures at sea and maritime transportation. We conducted Remotely Operated Vehicle surveys in the Dohrn Canyon in the Tyrrhenian Sea at approximately 12 NM off Naples metropolitan area, and revealed a hotspot of deep-sea benthic biodiversity of sessile fauna at ca. 400 m depth. The hard bottoms are characterized by a high abundance of charismatic species, such as the habitat forming cold-water corals (CWC) Madrepora oculata, Lophelia pertusa, Desmophyllum dianthus in association with the large size bivalves Acesta excavata and Neopycnodonte zibrowii. This CWC-bivalve co-occurrence represents a novel biotope for the Mediterranean Sea, which coexists with the evidence of severe anthropogenic threats, such as illegal dumping and fishery malpractices that were visually documented during the survey. We recommend the adoption of specific protection measures to preserve these unique deep-sea assemblages showing the uncommon co-existence of such a number of deep-sea species in a single habitat.
NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma
Authors: Dang Hien , Pomyen Yotsawat , Martin Sean P. , Dominguez Dana A. , Yim Sun Young , Lee Ju-Seog , Budhu Anuradha , Shah Ashesh P. , Bodzin Adam S. , Wang Xin Wei
Published: March 2019

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification or translocation alone. We demonstrate the utility of the NDMT gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of gene signatures, such as the NDMT signature, offers patients access to personalized risk assessments, which may be utilized to direct future care.
Evidence of age-related improvement in the foraging efficiency of Adélie penguins
Authors: Lescroël Amélie , Ballard Grant , Massaro Melanie , Dugger Katie , Jennings Scott , Pollard Annie , Porzig Elizabeth , Schmidt Annie , Varsani Arvind , Grémillet David , Ainley David
Published: March 2019

Age variation in reproductive performance is well-documented but the mechanisms underlying this variation remain unclear. Foraging efficiency is likely to be a key source of demographic variation as it determines the amount of energy that can be invested in fitness-related activities. Evidence of age-related changes in the foraging efficiency of adult seabirds is scarce and inconsistent. We investigated the effects of age on the foraging efficiency of breeding Adélie penguins, a relatively short-lived seabird species, in order to gain a broader perspective on the processes driving variation in ageing rates. We found support for a positive effect of age, either linear or levelling off at old ages, on both our proxies for daily catch rate and catch per unit effort. Across all age classes, males were more performant foragers than females. We found no strong evidence for differing ageing patterns between sexes or individual quality levels, and no evidence for senescence. We infer that continuous individual improvement could be responsible for a larger amount of the variation in foraging efficiency with age at our study site, compared with selective disappearance of underperforming phenotypes. The different results reported by other studies highlight the need to conduct longitudinal studies across a range of species in different environments.
Independent and combined effects of diethylhexyl phthalate and polychlorinated biphenyl 153 on sperm quality in the human and dog
Authors: Sumner Rebecca N. , Tomlinson Mathew , Craigon Jim , England Gary C. W. , Lea Richard G.
Published: March 2019

A temporal decline in human and dog sperm quality is thought to reflect a common environmental aetiology. This may reflect direct effects of seminal chemicals on sperm function and quality. Here we report the effects of diethylhexyl phthalate (DEHP) and polychlorinated biphenyl 153 (PCB153) on DNA fragmentation and motility in human and dog sperm. Human and dog semen was collected from registered donors (n = 9) and from stud dogs (n = 11) and incubated with PCB153 and DEHP, independently and combined, at 0x, 2x, 10x and 100x dog testis concentrations. A total of 16 treatments reflected a 4 × 4 factorial experimental design. Although exposure to DEHP and/or PCB153 alone increased DNA fragmentation and decreased motility, the scale of dose-related effects varied with the presence and relative concentrations of each chemical (DEHP.PCB interaction for: DNA fragmentation; human p < 0.001, dog p < 0.001; Motility; human p < 0.001, dog p < 0.05). In both human and dog sperm, progressive motility negatively correlated with DNA fragmentation regardless of chemical presence (Human: P < 0.0001, r = −0.36; dog P < 0.0001, r = −0.29). We conclude that DEHP and PCB153, at known tissue concentrations, induce similar effects on human and dog sperm supporting the contention of the dog as a sentinel species for human exposure.
Merits and pitfalls of conventional and covalent docking in identifying new hydroxyl aryl aldehyde like compounds as human IRE1 inhibitors
Authors: Carlesso Antonio , Chintha Chetan , Gorman Adrienne M. , Samali Afshin , Eriksson Leif A.
Published: March 2019

IRE1 is an endoplasmic reticulum (ER) bound transmembrane bifunctional kinase and endoribonuclease protein crucial for the unfolded protein response (UPR) signaling pathway. Upon ER stress, IRE1 homodimerizes, oligomerizes and autophosphorylates resulting in endoribonuclease activity responsible for excision of a 26 nucleotide intron from the X-box binding protein 1 (XBP1) mRNA. This unique splicing mechanism results in activation of the XBP1s transcription factor to specifically restore ER stress. Small molecules targeting the reactive lysine residue (Lys907) in IRE1α’s RNase domain have been shown to inhibit the cleavage of XBP1 mRNA. Crystal structures of murine IRE1 in complex with covalently bound hydroxyl aryl aldehyde (HAA) inhibitors show that these molecules form hydrophobic interactions with His910 and Phe889, a hydrogen bond with Tyr892 and an indispensable Schiff-base with Lys907. The availability of such data prompted interest in exploring structure-based drug design as a strategy to develop new covalently binding ligands. We extensively evaluated conventional and covalent docking for drug discovery targeting the catalytic site of the RNase domain. The results indicate that neither computational approach is fully successful in the current case, and we highlight herein the potential and limitations of the methods for the design of novel IRE1 RNase binders.
Corrosion mechanism and kinetics of Al-Zn coating deposited by arc thermal spraying process in saline solution at prolong exposure periods
Authors: Lee Han-Seung , Singh Jitendra Kumar , Ismail Mohamed A. , Bhattacharya Chinmoy , Seikh Asiful H. , Alharthi Nabeel , Hussain Raja Rizwan
Published: March 2019

Steel structures significantly degrades owing to corrosion especially in coastal and industrial areas where significant amounts of aggressive ions are present. Therefore, anodic metals such as Al and Zn are used to protect steel. In the present study, we provide insights for the corrosion mechanism and kinetics of Al-Zn pseudo alloy coating deposited on mild steel plate via an arc thermal spraying process in 3.5 wt.% NaCl solution in terms of its improved corrosion resistance properties at prolonged exposure durations. Electrochemical studies including open circuit potential (OCP) and electrochemical impedance spectroscopy (EIS) on the deposited coating at longer exposure durations revealed enhanced corrosion resistance properties while the morphology of corrosion products through field emission-scanning electron microscopy (FE-SEM) indicated their compactness and adherence. Furthermore, atomic force microscopy (AFM) confirmed reduced roughness when compared with that of unexposed coating. Additionally, X-ray diffraction (XRD) and Raman spectroscopy results confirmed the formation of protective, adherent, and sparingly soluble Simonkolleite (Zn5(OH)8Cl2.H2O) after 55 d of exposure in 3.5 wt.% NaCl solution. A schematic is proposed that explains the corrosion process of Al–Zn pseudo alloy coating in 3.5 wt.% NaCl solution from the deposition of coating and initiation of corrosion to longer exposure durations.
Adsorption of Methylene Blue and Pb2+ by using acid-activated Posidonia oceanica waste
Authors: Elmorsi Randa R. , El-Wakeel Shaimaa T. , Shehab El-Dein Waleed A. , Lotfy Hesham R. , Rashwan Wafaa E. , Nagah Mohammed , Shaaban Seham A. , Sayed Ahmed Sohair A. , El-Sherif Iman Y. , Abou-El-Sherbini Khaled S.
Published: March 2019

Dead leaves of seagrassPosidonia oceanicawere activated by using one mol L−1acetic acid and used as an eco-adsorbent for the removal of methylene blue (MB) and Pb2+from aqueous solutions. The seagrass was characterized by chemical and physical measurements that confirmed the acid-activation of seagrass. The favourable conditions for MB and Pb2+adsorption onto the activated seagrass (SGa) were determined to be a pH range of 2–12 and ≥6, an adsorbent dosage of 3.0 and 0.5 g L−1, respectively, and a shaking time of 30 min, which are suitable for a wide range of wastewaters. The equilibrium data were analysed using the Langmuir, Freundlich and Dubinin-Raduskavich-Kaganer (DRK) adsorption isotherm models. The Freundlich and DRK models best describe the adsorption processes of MB and Pb2+, on SGawith capacities of 2681.9 and 631.13 mg g−1, respectively. The adsorption isotherm fitting and thermodynamic studies suggest that the adsorption mechanism of MB may combine electrostatic and physical multilayer adsorption processes, in which MB may be present as monomers as well as dimers and trimers which were confirmed from UV spectroscopy whereas Pb2+is chemically adsorbed onto SGa. The pseudo-2nd-order kinetic model was utilized to investigate the kinetics of adsorption processes. The removal process was successfully applied for MB-spiked brackish waste water from Manzala Lake, Egypt, with removal efficiencies of 91.5–99.9%.
Efficient $${\boldsymbol{A}}{\boldsymbol{u}}{({\boldsymbol{C}}{\boldsymbol{N}})}_{{\bf{2}}}^{-{\bf{1}}}$$ adsorption using peach stone-derived granular activated carbon
Authors: Maponga Tayengwa Christopher , Mahamadi Courtie
Published: March 2019

Agricultural wastes have attracted attention as alternative precursors for the production of granular activated carbon. Using batch sorption studies, we demonstrated that granular activated carbon prepared through chemical activation using zinc chloride followed by physical activation in nitrogen environment at high temperatures can effectively adsorb aurocyanide from solution. Furthermore, gold recovery process using the granular activated carbon was amenable to optimization of adsorption parameters such as carbon dosage, initial aurocyanide concentration and contact time. These results may open new fronts on the application of low-cost granular activated carbon, particularly in the carbon-in-pulp metallurgical process.
Probing the effects of nonannular lipid binding on the stability of the calcium pump SERCA
Authors: Espinoza-Fonseca L. Michel
Published: March 2019

The calcium pump SERCA is a transmembrane protein that is critical for calcium transport in cells. SERCA resides in an environment made up largely by the lipid bilayer, so lipids play a central role on its stability and function. Studies have provided insights into the effects of annular and bulk lipids on SERCA activation, but the role of a nonannular lipid site in the E2 intermediate state remains elusive. Here, we have performed microsecond molecular dynamics simulations to probe the effects of nonannular lipid binding on the stability and structural dynamics of the E2 state of SERCA. We found that the structural integrity and stability of the E2 state is independent of nonannular lipid binding, and that occupancy of a lipid molecule at this site does not modulate destabilization of the E2 state, a step required to initiate the transition toward the competent E1 state. We also found that binding of the nonannular lipid does not induce direct allosteric control of the intrinsic functional dynamics the E2 state. We conclude that nonannular lipid binding is not necessary for the stability of the E2 state, but we speculate that it becomes functionally significant during the E2-to-E1 transition of the pump.
Priority Attachment: a Comprehensive Mechanism for Generating Networks
Authors: Morzy Mikołaj , Kajdanowicz Tomasz , Kazienko Przemysław , Miebs Grzegorz , Rusin Arkadiusz
Published: March 2019

We claim that networks are created according to the priority attachment mechanism. We introduce a simple model, which uses the priority attachment to generate both synthetic and close to empirical networks. Priority attachment is a mechanism, which generalizes previously proposed mechanisms, such as small world creation or preferential attachment, but we also observe its presence in a range of real-world networks. In this paper, we show that by using priority attachment we can generate networks of very diverse topologies, as well as re-create empirical ones. An additional advantage of the priority attachment mechanism is an easy interpretation of the latent processes of network formation. We substantiate our claims by performing numerical experiments on both synthetic and empirical networks. The two main contributions of the paper are: the development of the priority attachment mechanism, and the design of Priority Rank: a simple network generative model based on the priority attachment mechanism.
Characterisation of novel-cell-wall LysM-domain proteins LdpA and LdpB from the human pathogenic fungus Aspergillus fumigatus
Authors: Muraosa Yasunori , Toyotome Takahito , Yahiro Maki , Kamei Katsuhiko
Published: March 2019

Aspergillus fumigatus, a filamentous fungus that is ubiquitous in the environment, causes several human pulmonary disorders, including chronic and acute invasive infections and allergic diseases. Lysin motif (LysM) is a small protein domain that binds chitin, a major component of fungal cell wall polysaccharides. Several secreted LysM-domain proteins without catalytic function (LysM effectors) have been identified. They act as virulence factors in plant pathogenic fungi by preventing the immune response induced by chitin; however, LysM proteins in mammalian pathogenic fungi remain largely unexplored. We describe two novel LysM-domain proteins, LdpA and LdpB, in A. fumigatus. Functional analyses of single and double knockouts revealed no significant effects on cell wall chitin content, cell wall integrity, fungal morphology and fungal growth. Fluorescent signals from LdpA-green fluorescent protein (GFP) and LdpB-GFP were observed in cell wall and extracellular matrix. In a mouse model of invasive pulmonary aspergillosis, survival did not differ between ΔldpA/B and wild-type infection; however, further studies are required to reveal their functions in fungal−host interactions.
Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease
Authors: Yemni Eman Al , Monies Dorota , Alkhairallah Thamer , Bohlega Saeed , Abouelhoda Mohamed , Magrashi Amna , Mustafa Abeer , AlAbdulaziz Basma , Alhamed Mohamed , Baz Batoul , Goljan Ewa , Albar Renad , Jabaan Amjad , Faquih Tariq , Subhani Shazia , Ali Wafa , Shinwari Jameela , Al-Mubarak Bashayer , Al-Tassan Nada
Published: March 2019

Genetic studies of the familial forms of Parkinson’s disease (PD) have identified a number of causative genes with an established role in its pathogenesis. These genes only explain a fraction of the diagnosed cases. The emergence of Next Generation Sequencing (NGS) expanded the scope of rare variants identification in novel PD related genes. In this study we describe whole exome sequencing (WES) genetic findings of 60 PD patients with 125 variants validated in 51 of these cases. We used strict criteria for variant categorization that generated a list of variants in 20 genes. These variants included loss of function and missense changes in 18 genes that were never previously linked to PD (NOTCH4,BCOR, ITM2B,HRH4,CELSR1,SNAP91,FAM174A,BSN,SPG7,MAGI2,HEPHL1,EPRS,PUM1,CLSTN1,PLCB3,CLSTN3,DNAJB9andNEFH) and 2 genes that were previously associated with PD (EIF4G1andATP13A2). These genes either play a critical role in neuronal function and/or have mouse models with disease related phenotypes. We highlightNOTCH4as an interesting candidate in which we identified a deleterious truncating and a splice variant in 2 patients. Our combined molecular approach provides a comprehensive strategy applicable for complex genetic disorders.
Large-scale data from wearables reveal regional disparities in sleep patterns that persist across age and sex
Authors: Ong Ju Lynn , Tandi Jesisca , Patanaik Amiya , Lo June C. , Chee Michael W. L.
Published: March 2019

Prior reports on geographical differences in sleep duration have relied on samples collected at different time points with a variety of subjective instruments. Using sleep data from a total of 553,559 nights from 23,680 Fitbit users (aged 15–80y), we found objective evidence for regional disparities in sleep duration of 32–43 min between Oceanian and East Asian users on weekdays. This was primarily driven by later bedtimes in East Asians. Although users in all countries extended sleep on weekends, East Asians continued to sleep less than their Oceanian counterparts. Women generally slept more than men, and older users slept less than younger users. Reasons for shorter sleep duration in East Asians on both weekdays and weekends, across the lifespan and in both sexes remain to be investigated.
The homotopic connectivity of the functional brain: a meta-analytic approach
Authors: Mancuso Lorenzo , Costa Tommaso , Nani Andrea , Manuello Jordi , Liloia Donato , Gelmini Gabriele , Panero Melissa , Duca Sergio , Cauda Franco
Published: March 2019

Homotopic connectivity (HC) is the connectivity between mirror areas of the brain hemispheres. It can exhibit a marked and functionally relevant spatial variability, and can be perturbed by several pathological conditions. The voxel-mirrored homotopic connectivity (VMHC) is a technique devised to enquire this pattern of brain organization, based on resting state functional connectivity. Since functional connectivity can be revealed also in a meta-analytical fashion using co-activations, here we propose to calculate the meta-analytic homotopic connectivity (MHC) as the meta-analytic counterpart of the VMHC. The comparison between the two techniques reveals their general similarity, but also highlights regional differences associated with how HC varies from task to rest. Two main differences were found from rest to task: (i) regions known to be characterized by global hubness are more similar than regions displaying local hubness; and (ii) medial areas are characterized by a higher degree of homotopic connectivity, while lateral areas appear to decrease their degree of homotopic connectivity during task performance. These findings show that MHC can be an insightful tool to study how the hemispheres functionally interact during task and rest conditions.
Insights into the complex role of GRAS transcription factors in the arbuscular mycorrhiza symbiosis
Authors: Hartmann Rico M. , Schaepe Sieke , Nübel Daniel , Petersen Arne C. , Bertolini Martina , Vasilev Jana , Küster Helge , Hohnjec Natalija
Published: March 2019

To improve access to limiting nutrients, the vast majority of land plants forms arbuscular mycorrhizal (AM) symbioses with Glomeromycota fungi. We show here that AM-related GRAS transcription factors from different subgroups are upregulated during a time course of mycorrhization. Based on expression studies in mutants defective in arbuscule branching (ram1-1, with a deleted MtRam1 GRAS transcription factor gene) or in the formation of functional arbuscules (pt4-2, mutated in the phosphate transporter gene MtPt4), we demonstrate that the five AM-related GRAS transcription factor genes MtGras1, MtGras4, MtGras6, MtGras7, and MtRad1 can be differentiated by their dependency on MtRAM1 and MtPT4, indicating that the network of AM-related GRAS transcription factors consists of at least two regulatory modules. One module involves the MtRAM1- and MtPT4-independent transcription factor MtGRAS4 that activates MtGras7. Another module is controlled by the MtRAM1- and MtPT4-dependent transcription factor MtGRAS1. Genome-wide expression profiles of mycorrhized MtGras1 knockdown and ram1-1 roots differ substantially, indicating different targets. Although an MtGras1 knockdown reduces transcription of AM-related GRAS transcription factor genes including MtRam1 and MtGras7, MtGras1 overexpression alone is not sufficient to activate MtGras genes. MtGras1 knockdown roots display normal fungal colonization, with a trend towards the formation of smaller arbuscules.
The nest fungus of the lower termite Reticulitermes labralis
Authors: Ye Chenxu , Li Jing , Ran Yuehua , Rasheed Humaira , Xing Lianxi , Su Xiaohong
Published: March 2019

Fitness-determining interactions with fungi have often been considered a by-product of social evolution in insects. In higher termites, the mutualistic association between the basidiomycete genus Termitomyces and Macrotermitinae is well known. However, whether and how lower termites use fungi is unclear. Here, we found a large amount of brown sclerotium-forming fungi in egg piles of the lower termite Reticulitermes labralis and identified the sclerotia as Fibulorhizoctonia sp. There was a significant difference in morphology between the sclerotia and the termite eggs. The workers of R. labralis and R. chinensis actively gathered the sclerotia into the egg piles within their nests, whereas the workers of R. aculabialis did not gather sclerotia outside their nests. None of the sclerotia in the egg piles germinated in the presence of workers. However, the sclerotia germinated in the absence of workers, and then the hyphae killed the termite eggs. The data from cellulase activity demonstrated that Fibulorhizoctonia sp. was able to exhaustively digest cellulose into glucose.We confirmed for the first time that the workers carrying the sclerotia into the piles of eggs is not due to mistaking the sclerotia for their eggs and that the workers of R. labralis may be able to select favourite fungi.