bluuebunny/crossref_metadata_2025 huggingface dataset:
A genome for gnetophytes and early evolution of seed plants
Authors: Wan Tao , Liu Zhi-Ming , Li Ling-Fei , Leitch Andrew R. , Leitch Ilia J. , Lohaus Rolf , Liu Zhong-Jian , Xin Hai-Ping , Gong Yan-Bing , Liu Yang , Wang Wen-Cai , Chen Ling-Yun , Yang Yong , Kelly Laura J. , Yang Ji , Huang Jin-Ling , Li Zhen , Liu Ping , Zhang Li , Liu Hong-Mei , Wang Hui , Deng Shu-Han , Liu Meng , Li Ji , Ma Lu , Liu Yan , Lei Yang , Xu Wei , Wu Ling-Qing , Liu Fan , Ma Qian , Yu Xin-Ran , Jiang Zhi , Zhang Guo-Qiang , Li Shao-Hua , Li Rui-Qiang , Zhang Shou-Zhou , Wang Qing-Feng , Van de Peer Yves , Zhang Jin-Bo , Wang Xiao-Ming
Published: January 2018

Gnetophytes are an enigmatic gymnosperm lineage comprising three genera, Gnetum, Welwitschia and Ephedra, which are morphologically distinct from all other seed plants. Their distinctiveness has triggered much debate as to their origin, evolution and phylogenetic placement among seed plants. To increase our understanding of the evolution of gnetophytes, and their relation to other seed plants, we report here a high-quality draft genome sequence for Gnetum montanum, the first for any gnetophyte. By using a novel genome assembly strategy to deal with high levels of heterozygosity, we assembled >4 Gb of sequence encoding 27,491 protein-coding genes. Comparative analysis of the G. montanum genome with other gymnosperm genomes unveiled some remarkable and distinctive genomic features, such as a diverse assemblage of retrotransposons with evidence for elevated frequencies of elimination rather than accumulation, considerable differences in intron architecture, including both length distribution and proportions of (retro) transposon elements, and distinctive patterns of proliferation of functional protein domains. Furthermore, a few gene families showed Gnetum-specific copy number expansions (for example, cellulose synthase) or contractions (for example, Late Embryogenesis Abundant protein), which could be connected with Gnetum’s distinctive morphological innovations associated with their adaptation to warm, mesic environments. Overall, the G. montanum genome enables a better resolution of ancestral genomic features within seed plants, and the identification of genomic characters that distinguish Gnetum from other gymnosperms.
Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface
Authors: Probst Alexander J. , Ladd Bethany , Jarett Jessica K. , Geller-McGrath David E. , Sieber Christian M. K. , Emerson Joanne B. , Anantharaman Karthik , Thomas Brian C. , Malmstrom Rex R. , Stieglmeier Michaela , Klingl Andreas , Woyke Tanja , Ryan M. Cathryn , Banfield Jillian F.
Published: January 2018

An enormous diversity of previously unknown bacteria and archaea has been discovered recently, yet their functional capacities and distributions in the terrestrial subsurface remain uncertain. Here, we continually sampled a CO2-driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test the hypothesis that stratified, sandstone-hosted aquifers sampled over three phases of the eruption cycle have microbial communities that differ both in membership and function. Genome-resolved metagenomics, single-cell genomics and geochemical analyses confirmed this hypothesis and linked microorganisms to groundwater compositions from different depths. AutotrophicCandidatus“Altiarchaeum sp.” and phylogenetically deep-branching nanoarchaea dominate the deepest groundwater. A nanoarchaeon with limited metabolic capacity is inferred to be a potential symbiont of theCa. “Altiarchaeum”. Candidate Phyla Radiation bacteria are also present in the deepest groundwater and they are relatively abundant in water from intermediate depths. During the recovery phase of the geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication rates. AutotrophicSulfurimonassustained by aerobic sulfide oxidation and with the capacity for N2fixation dominate the shallow aquifer. Overall, 104 different phylum-level lineages are present in water from these subsurface environments, with uncultivated archaea and bacteria partitioned to the deeper subsurface.
Silicon based mid-IR super absorber using hyperbolic metamaterial
Authors: Desouky Mai , Mahmoud Ahmed M. , Swillam Mohamed A.
Published: January 2018

Perfect absorbers are indispensable components for energy harvesting applications. While many absorbers have been proposed, they encounter inevitable drawbacks including bulkiness or instability over time. The urge for CMOS compatible absorber that can be integrated for on chip applications requires further investigation. We theoretically demonstrate Silicon (Si) based mid IR super absorber with absorption (A) reaching 0.948. Our structure is composed of multilayered N-doped Si/ Si hyperbolic metamaterial (HMM) integrated with sub-hole Si grating. Our proposed structure has tunable absorption peak that can be tuned from 4.5 µm to 11 µm through changing the grating parameters. We also propose two grating designs integrated with N-doped Si/ Si HMM that can achieve wide band absorption. The first grating design is based on Si grating incorporating different holes’ height with (A) varying between 0.83 and 0.97 for wavelength from 5 µm to 7 µm. The second grating design is based on Si grating with variable holes’ diameter; the latter shows broad band absorption with the maximum (A) reaching 0.97. We also show that our structure is omnidirectional. We propose an all Si based absorber which demonstrates a good candidate for thermal harvesting application.
Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression
Authors: Parada Carolina Angelica , Osbun Joshua , Kaur Sumanpreet , Yakkioui Youssef , Shi Min , Pan Catherine , Busald Tina , Karasozen Yigit , Gonzalez-Cuyar Luis Francisco , Rostomily Robert , Zhang Jing , Ferreira Manuel
Published: January 2018

There is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. Differentially regulated pathways were characteristic of high-grade meningiomas. Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. These results demonstrate AKAP12 as a central regulator of meningioma aggressiveness with a possible role in progression.
Probing the folding pathway of a consensus serpin using single tryptophan mutants
Authors: Yang Li , Irving James A. , Dai Weiwen , Aguilar Marie-Isabel , Bottomley Stephen P.
Published: January 2018

Conserpin is an engineered protein that represents the consensus of a sequence alignment of eukaryotic serpins: protease inhibitors typified by a metastable native state and a structurally well-conserved scaffold. Previously, this protein has been found to adopt a native inhibitory conformation, possess an atypical reversible folding pathway and exhibit pronounced resistance to inactivation. Here we have designed a version of conserpin, cAT, with the inhibitory specificity of α1-antitrypsin, and generated single-tryptophan variants to probe its folding pathway in more detail. cAT exhibited similar thermal stability to the parental protein, an inactivation associated with oligomerisation rather a transition to the latent conformation, and a native state with pronounced kinetic stability. The tryptophan variants reveal the unfolding intermediate ensemble to consist of an intact helix H, a distorted helix F and ‘breach’ region structurally similar to that of a mesophilic serpin intermediate. A combination of intrinsic fluorescence, circular dichroism, and analytical gel filtration provide insight into a highly cooperative folding pathway with concerted changes in secondary and tertiary structure, which minimises the accumulation of two directly-observed aggregation-prone intermediate species. This functional conserpin variant represents a basis for further studies of the relationship between structure and stability in the serpin superfamily.
msgbsR: An R package for analysing methylation-sensitive restriction enzyme sequencing data
Authors: Mayne Benjamin T. , Leemaqz Shalem Y. , Buckberry Sam , Rodriguez Lopez Carlos M. , Roberts Claire T. , Bianco-Miotto Tina , Breen James
Published: January 2018

Genotyping-by-sequencing (GBS) or restriction-site associated DNA marker sequencing (RAD-seq) is a practical and cost-effective method for analysing large genomes from high diversity species. This method of sequencing, coupled with methylation-sensitive enzymes (often referred to as methylation-sensitive restriction enzyme sequencing or MRE-seq), is an effective tool to study DNA methylation in parts of the genome that are inaccessible in other sequencing techniques or are not annotated in microarray technologies. Current software tools do not fulfil all methylation-sensitive restriction sequencing assays for determining differences in DNA methylation between samples. To fill this computational need, we present msgbsR, an R package that contains tools for the analysis of methylation-sensitive restriction enzyme sequencing experiments. msgbsR can be used to identify and quantify read counts at methylated sites directly from alignment files (BAM files) and enables verification of restriction enzyme cut sites with the correct recognition sequence of the individual enzyme. In addition, msgbsR assesses DNA methylation based on read coverage, similar to RNA sequencing experiments, rather than methylation proportion and is a useful tool in analysing differential methylation on large populations. The package is fully documented and available freely online as a Bioconductor package (https://bioconductor.org/packages/release/bioc/html/msgbsR.html).
Synthesis of organic aerogels with tailorable morphology and strength by controlled solvent swelling following Hansen solubility
Authors: Tripathi Anurodh , Parsons Gregory N. , Khan Saad A. , Rojas Orlando J.
Published: January 2018

We introduce a generalized approach to synthesize aerogels that allows remarkable control over its mechanical properties. The Hansen solubility parameters are used to predict and regulate the swelling properties of the precursor gels and, consequently, to achieve aerogels with tailored density and mechanical properties. As a demonstration, crosslinked organogels were synthesized from cellulose esters to generate aerogels. By determination of Hansen’s Relative Energy Difference, it was possible to overcome the limitations of current approaches that solely rely on the choice of precursor polymer concentration to achieve a set of aerogel properties. Hence, from a given concentration, aerogels were produced in a range of mass densities, from 25 to 113 mg/cm3. Consequently, it was possible to tailor the stiffness, toughness and compressive strength of the aerogels, in the ranges between 14–340, 4–103 and 22–373 kPa, respectively. Additionally, unidirectional freeze-drying introduced pore alignment in aerogels with honeycomb morphologies and anisotropy. Interestingly, when the swelling of the polymeric gel was arrested in a non-equilibrium state, it was possible to gain additional control of the property space. The proposed method is a novel and generic solution to achieving full control of aerogel development, which up to now has been an intractable challenge.
Perivascular Spaces Segmentation in Brain MRI Using Optimal 3D Filtering
Authors: Ballerini Lucia , Lovreglio Ruggiero , Valdés Hernández Maria del C. , Ramirez Joel , MacIntosh Bradley J. , Black Sandra E. , Wardlaw Joanna M.
Published: January 2018

Perivascular Spaces (PVS) are a feature of Small Vessel Disease (SVD), and are an important part of the brain’s circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. We used ordered logit models and visual rating scales as alternative ground truth for Frangi filter parameter optimization and evaluation. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N = 20) and patients who previously had mild to moderate stroke (N = 48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated well with neuroradiological assessments (Spearman’s ρ = 0.74, p < 0.001), supporting the potential of our proposed method.
Hypomagnesemia and clinical benefits of anti-EGFR monoclonal antibodies in wild-type KRAS metastatic colorectal cancer: a systematic review and meta-analysis
Authors: Hsieh Meng-Chiao , Wu Chun-Feng , Chen Chun-Wei , Shi Chung-Sheng , Huang Wen-Shih , Kuan Feng-Che
Published: January 2018

Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47–0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53–0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30–2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62–0.98; HR: 0.60; 95% CI: 0.40–0.90; HR: 0.62; 95% CI: 0.41–0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.
The Effect of a Slowly Rocking Bed on Sleep
Authors: Omlin Ximena , Crivelli Francesco , Näf Monika , Heinicke Lorenz , Skorucak Jelena , Malafeev Alexander , Fernandez Guerrero Antonio , Riener Robert , Achermann Peter
Published: January 2018

Rocking movements appear to affect human sleep. Recent research suggested a facilitated transition from wake to sleep and a boosting of slow oscillations and sleep spindles due to lateral rocking movements during an afternoon nap. This study aimed at investigating the effect of vestibular stimulation on sleep onset, nocturnal sleep and its potential to increase sleep spindles and slow waves, which could influence memory performance. Polysomnography was recorded in 18 males (age: 20–28 years) during three nights: movement until sleep onset (C1), movement for 2 hours (C2), and one baseline (B) without motion. Sleep dependent changes in memory performance were assessed with a word-pair learning task. Although subjects preferred nights with vestibular stimulation, a facilitated sleep onset or a boost in slow oscillations was not observed. N2 sleep and the total number of sleep spindles increased during the 2 h with vestibular stimulation (C2) but not over the entire night. Memory performance increased over night but did not differ between conditions. The lack of an effect might be due to the already high sleep efficiency (96%) and sleep quality of our subjects during baseline. Nocturnal sleep in good sleepers might not benefit from the potential facilitating effects of vestibular stimulation.
Comparative transcriptome analysis reveals molecular response to salinity stress of salt-tolerant and sensitive genotypes of indica rice at seedling stage
Authors: Wang Jun , Zhu Jinyan , Zhang Yadong , Fan Fangjun , Li Wenqi , Wang Fangquan , Zhong Weigong , Wang Cailin , Yang Jie
Published: January 2018

Abiotic stresses, such as salinity, greatly threaten the growth and productivity of plants. Rice (Oryza sativa L.) is one of the most important food crops, as well as a monocot model for genomic research. To obtain a global view of the molecular response to salinity stress, we conducted a leaf transcriptome analysis on rice seedlings. Two cultivars of rice subspecies indica, including the salt-tolerant genotype Xian156 and the salt-sensitive genotype IR28, were used in the present study. Eighteen RNA libraries were obtained from these two genotypes at three timepoints (0 h, 48 h and 72 h) after applying salinity stress. We obtained the reference-guided assembly of the rice transcriptome, which resulted in 1,375 novel genes, including 1,371 annotated genes. A comparative analysis between genotypes and time points showed 5,273 differentially expressed genes (DEGs), of which 286 DEGs were only found in the tolerant genotype. The Disease resistance response protein 206 and TIFY 10 A were differentially expressed, which were validated by quantitative real-time PCR. The differentially expressed genes identified through the mRNA transcriptome, along with the structure, provide a revealing insight into rice molecular response to salinity stress and underlie the salinity tolerance mechanism between genotypes.
The “weak” interdependence of infrastructure systems produces mixed percolation transitions in multilayer networks
Authors: Liu Run-Ran , Eisenberg Daniel A. , Seager Thomas P. , Lai Ying-Cheng
Published: January 2018

Previous studies of multilayer network robustness model cascading failures via a node-to-node percolation process that assumes “strong” interdependence across layers–once a node in any layer fails, its neighbors in other layers fail immediately and completely with all links removed. This assumption is not true of real interdependent infrastructures that have emergency procedures to buffer against cascades. In this work, we consider a node-to-link failure propagation mechanism and establish “weak” interdependence across layers via a tolerance parameter α which quantifies the likelihood that a node survives when one of its interdependent neighbors fails. Analytical and numerical results show that weak interdependence produces a striking phenomenon: layers at different positions within the multilayer system experience distinct percolation transitions. Especially, layers with high super degree values percolate in an abrupt manner, while those with low super degree values exhibit both continuous and discontinuous transitions. This novel phenomenon we call mixed percolation transitions has significant implications for network robustness. Previous results that do not consider cascade tolerance and layer super degree may be under- or over-estimating the vulnerability of real systems. Moreover, our model reveals how nodal protection activities influence failure dynamics in interdependent, multilayer systems.
A Neuro-Musculo-Skeletal Model for Insects With Data-driven Optimization
Authors: Guo Shihui , Lin Juncong , Wöhrl Toni , Liao Minghong
Published: January 2018

Simulating the locomotion of insects is beneficial to many areas such as experimental biology, computer animation and robotics. This work proposes a neuro-musculo-skeletal model, which integrates the biological inspirations from real insects and reproduces the gait pattern on virtual insects. The neural system is a network of spiking neurons, whose spiking patterns are controlled by the input currents. The spiking pattern provides a uniform representation of sensory information, high-level commands and control strategy. The muscle models are designed following the characteristic Hill-type muscle with customized force-length and force-velocity relationships. The model parameters, including both the neural and muscular components, are optimized via an approach of evolutionary optimization, with the data captured from real insects. The results show that the simulated gait pattern, including joint trajectories, matches the experimental data collected from real ants walking in the free mode. The simulated character is capable of moving at different directions and traversing uneven terrains.
Terahertz Dispersion Characteristics of Super-aligned Multi-walled Carbon Nanotubes and Enhanced Transmission through Subwavelength Apertures
Authors: Wang Yue , Duan Guangwu , Zhang Liying , Ma Lihua , Zhao Xiaoguang , Zhang Xin
Published: January 2018

The terahertz (THz) dielectric properties of super-aligned multi-walled carbon nanotube (MWCNT) films were characterized in the frequency range from 0.1 to 2.5 THz with terahertz time-domain spectroscopy. The refractive index, effective permittivity, and conductivity were retrieved from the measured transmission spectra with THz incident wave polarized parallel and perpendicular to the orientation of carbon nanotubes (CNTs), and a high degree of polarization dependence was observed. The Drude-Lorentz model combined with Maxwell-Garnett effective medium theory was employed to explain the experimental results, revealing an obvious metallic behavior of the MWCNT films. Moreover, rectangular aperture arrays were patterned on the super-aligned MWCNT films with laser-machining techniques, and the transmission measurement demonstrated an extraordinarily enhanced transmission characteristic of the samples with incident wave polarized parallel to the orientation of the CNTs. Surface plasmon polaritons were employed to explain the extraordinarily enhanced transmission with high accuracy, and multi-order Fano profile was applied to model the transmission spectra. A high degree of agreement was exhibited among the experimental, numerical, and theoretical results.
The mechanistic link between health and gut microbiota diversity
Authors: Larsen Olaf F. A. , Claassen Eric
Published: January 2018

Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that higher diversity within such a network indeed leads to more efficient systems and redundancy. Our results quantitatively support earlier hypothetical considerations on gut microbiota richness with respect to these parameters. Our simulations show that higher species diversity leads to higher resilience within small microbiological ecosystems, like being present in the gut microbiota. This notion should provide an ingredient when developing new interventional strategies within the domain of microbiota management.
Impact of thickness variation on structural, dielectric and piezoelectric properties of (Ba,Ca)(Ti,Zr)O3 epitaxial thin films
Authors: Ion Valentin , Craciun Floriana , Scarisoreanu Nicu D. , Moldovan Antoniu , Andrei Andreea , Birjega Ruxandra , Ghica Corneliu , Di Pietrantonio Fabio , Cannata Domenico , Benetti Massimiliano , Dinescu Maria
Published: January 2018

It is shown that the dielectric and piezoelectric properties of Ba(Ti0.8Zr0.2)O3-x(Ba0.7Ca0.3)TiO3(x = 0.45) (BCTZ 45) epitaxial thin films have a nontrivial dependence on film thickness. BCTZ 45 epitaxial films with different thicknesses (up to 400 nm) have been deposited on SrTiO3by pulsed laser deposition and investigated by different combined techniques: conventional and off-axis X-ray diffraction, high resolution transmission electron microscopy and dielectric and piezoforce microscopy. The changes occurring in epitaxial films when their thickness increases have been attributed to a partial relaxation of misfit strain, driving the induced tetragonal symmetry in very thin films to the original rhombohedral symmetry of the bulk material in the thickest film, which influences directly and indirectly the dielectric and piezoelectric properties.
Using Transfer Function Analysis to develop biologically and economically efficient restoration strategies
Authors: Bialic-Murphy Lalasia , Gaoue Orou G. , Knight Tiffany
Published: January 2018

Rare species across taxonomic groups and biomes commonly suffer from multiple threats and require intensive restoration, including population reintroduction and threat control. Following reintroduction, it is necessary to identify what level of threat control is needed for species to persist over time. Population reintroduction and threat control are time intensive and costly. Thus, it is pragmatic to develop economically efficient restoration strategies. We combined transfer function analysis and economic cost analysis to evaluate the effects of biologically meaningful increases in demographic processes on the persistence of a reintroduced population of a Hawaii endemic long-lived shrub, Delissea waianaeensis. We show that an increase in fertility by 0.419 following the suppression of non-native rodents or an increase by 0.098 in seedling growth following the suppression of invasive molluscs would stabilize the population (i.e., λ = 1). Though a greater increase in fertility than seedling growth was needed for the reintroduced population to persist over time, increasing fertility by suppressing rodents was the most cost effective restoration strategy. Our study emphasizes the importance of considering the effects of large increases in plant vital rates in population projections and incorporating the economic cost of management actions in demographic models when developing restoration plans for endangered species.
Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth
Authors: Larasati Yonika Arum , Yoneda-Kato Noriko , Nakamae Ikuko , Yokoyama Takashi , Meiyanto Edy , Kato Jun-ya
Published: January 2018

Curcumin has been reported to exhibit anti-tumorigenic activity; however, since its precise actions remain unclear, its effects are considered to be deceptive. In the present study, we confirmed the anti-tumorigenic effects of curcumin on CML-derived leukemic cells in a xenograft model and in vitro culture system. In vitro pull-down and mass analyses revealed a series of enzymes (carbonyl reductase, glutathione-S-transferase, glyoxalase, etc.) that function in a reactive oxygen species (ROS) metabolic pathway as curcumin-binding targets, the expression of which was up-regulated in human leukemia. Curcumin increased ROS levels over the threshold in leukemic cells, and the antioxidant, glutathione (GSH) and overexpression of curcumin-binding enzymes partially mitigated the up-regulation of ROS and growth inhibition caused by curcumin. These results show that curcumin specifically inhibits tumor growth by increasing ROS levels over the threshold through the miscellaneous inhibition of ROS metabolic enzymes. Curcumin has potential in therapy to regulate ROS levels in tumor cells, thereby controlling tumor growth.
X-Ray Dark-field Imaging to Depict Acute Lung Inflammation in Mice
Authors: Hellbach Katharina , Meinel Felix G. , Conlon Thomas M. , Willer Konstantin , Yaroshenko Andre , Velroyen Astrid , Braunagel Margarita , Auweter Sigrid , Reiser Maximilian F. , Eickelberg Oliver , Pfeiffer Franz , Yildirim Ali Ö.
Published: January 2018

The aim of this study was to evaluate the feasibility of early stage imaging of acute lung inflammation in mice using grating-based X-ray dark-field imaging in vivo. Acute lung inflammation was induced in mice by orotracheal instillation of porcine pancreatic elastase. Control mice received orotracheal instillation of PBS. Mice were imaged immediately before and 1 day after the application of elastase or PBS to assess acute changes in pulmonary structure due to lung inflammation. Subsequently, 6 mice from each group were sacrificed and their lungs were lavaged and explanted for histological analysis. A further 7, 14 and 21 days later the remaining mice were imaged again. All images were acquired with a prototype grating-based small-animal scanner to generate dark-field and transmission radiographs. Lavage confirmed that mice in the experimental group had developed acute lung inflammation one day after administration of elastase. Acute lung inflammation was visible as a striking decrease in signal intensity of the pulmonary parenchyma on dark-field images at day 1. Quantitative analysis confirmed that dark-field signal intensity at day 1 was significantly lower than signal intensities measured at the remaining timepoints, confirming that acute lung inflammation can be depicted in vivo with dark-field radiography.
Cultural effects on computational metrics of spatial and temporal context
Authors: Wright Nicholas D. , Grohn Jan , Song Chen , Rees Geraint , Lawson Rebecca P.
Published: January 2018

The concept of “prediction error” - the difference between what occurred and was expected - is key to understanding the cognitive processes of human decision making. Expectations have to be learned so the concept of prediction error critically depends on context, specifically thetemporalcontext of probabilistically related events and their changes across time (i.e. volatility). While past research suggests context differently affects some cognitive processes in East Asian and Western individuals, it is currently unknown whether this extends to computationally-grounded measures of learning and prediction error. Here we compared Chinese and British nationals in an associative learning task that quantifies behavioural effects of prediction error, and—through a hierarchical Bayesian learning model—also captures how individuals learn about probabilistic relationships and their volatility. For comparison, we also administered a psychophysical task, the tilt illusion, to assess cultural differences in susceptibility tospatialcontext. We found no cultural differences in the effect of spatial context on perception. In the domain of temporal context there was no effect of culture on sensitivity to prediction error, or learning about volatility, but some suggestion that Chinese individuals may learn more readily about probabilistic relationships.
Synergistic Anti-tumour Effects of Quercetin and Oncolytic Adenovirus expressing TRAIL in Human Hepatocellular Carcinoma
Authors: Zou Hai , Zheng Yong-fa , Ge Wei , Wang Shi-bing , Mou Xiao-zhou
Published: January 2018

The combination of oncolytic adenoviruses and specific chemotherapy agents is fast emerging as a novel therapeutic approach for resistan the patocellular carcinoma (HCC) cells. A detailed analysis of the network between adenovirus and chemotherapeutic agents can help design an effective strategy to combat HCC. We sought to investigate whether a combined treatment of ZD55-TRAIL and quercetin can have an enhanced cell-killing effect on HCC cells. In-vitro experiments showed that quercetin can enhance ZD55-TRAIL mediated growth inhibition and apoptosis in HCC cells. In addition, we showed that quercetin reduced ZD55-TRAIL mediated NF-κB activation and down-regulated its downstream targets, which in turn promoted the pro-apoptotic action of ZD55-TRAIL. Furthermore, in-vivo experiments in mice injected with HuH-7 cells resulted in significantly greater reduction in tumour growth and volume following combined ZD55-TRAIL and quercetin treatment. In conclusion, we demonstrated that quercetin could sensitize human HCC cells to apoptosis via ZD55-TRAIL in-vitro and in-vivo and presented ZD55-TRAIL and quercetin combination as a suitable anti-HCC therapy.
High expression of SMARCA4 or SMARCA2 is frequently associated with an opposite prognosis in cancer
Authors: Guerrero-Martínez Jose A. , Reyes Jose C.
Published: January 2018

The gene encoding the ATPase of the chromatin remodeling SWI/SNF complexesSMARCA4(BRG1) is often mutated or silenced in tumors, suggesting a role as tumor suppressor. Nonetheless, recent reports show requirement of SMARCA4 for tumor cells growth. Here, we performed a computational meta-analysis using gene expression, prognosis, and clinicopathological data to clarify the role of SMARCA4 and the alternative SWI/SNF ATPase SMARCA2 (BRM) in cancer. We show that while theSMARCA4gene is mostly overexpressed in tumors,SMARCA2is almost invariably downexpressed in tumors. HighSMARCA4expression was associated with poor prognosis in many types of tumors, including liver hepatocellular carcinoma (LIHC), and kidney renal clear cell carcinoma (KIRC). In contrast, highSMARCA2expression was associated with good prognosis. We compared tumors with high versus low expression ofSMARCA4orSMARCA2in LIHC and KIRC cohorts from The Cancer Genome Atlas. While a high expression ofSMARCA4is associated with aggressive tumors, a high expression ofSMARCA2is associated with benign differentiated tumors, suggesting that SMARCA4 and SMARCA2 play opposite roles in cancer. Our results demonstrate that expression ofSMARCA4andSMARCA2have a high prognostic value and challenge the broadly accepted general role of SMARCA4 as a tumor suppressor.
Diverse patterns of molecular changes in the mechano-responsiveness of focal adhesions
Authors: Malik-Sheriff Rahuman S. , Imtiaz Sarah , Grecco Hernán E. , Zamir Eli
Published: January 2018

Focal adhesions anchor contractile actin fibers with the extracellular matrix, sense the generated tension and respond to it by changing their morphology and composition. Here we ask how this mechanosensing is enabled at the protein-network level, given the modular assembly and multitasking of focal adhesions. To address this, we applied a sensitive 4-color live cell imaging approach, enabling monitoring patterns of molecular changes in single focal adhesions. Co-imaging zyxin, FAK, vinculin and paxillin revealed heterogeneities in their responses to Rho-associated kinase (ROCK)-mediated perturbations of actomyosin contractility. These responses were rather weakly correlated between the proteins, reflecting diverse compositional changes in different focal adhesions. This diversity is partially attributable to the location of focal adhesions, their area, molecular content and previous contractility perturbations, suggesting that integration of multiple local cues shapes differentially focal adhesion mechano-responsiveness. Importantly, the compositional changes upon ROCK perturbations exhibited distinct paths in different focal adhesions. Moreover, the protein exhibiting the strongest response to ROCK perturbations varied among different focal adhesions. The diversity in response patterns is plausibly enabled by the modular mode of focal adhesions assembly and can provide them the needed flexibility to perform multiple tasks by combining optimally a common set of multifunctional components.
Prevalence and Risk Factors of self-reported dry eye in Brazil using a short symptom questionnaire
Authors: Castro Julia Silvestre de , Selegatto Iara Borin , Castro Rosane Silvestre de , Miranda Eliana C. M. , de Vasconcelos José Paulo Cabral , de Carvalho Keila Monteiro , Arieta Carlos Eduardo Leite , Alves Monica
Published: January 2018

To evaluate dry eye prevalence and investigate associated risk factors in Brazil by applying a short questionnaire of symptoms and risk factors. A cross-sectional study of 3,107 participants from all the five different geopolitical regions of Brazil. Overall prevalence of dry eye in this study population was 12.8%. Dry eye previous diagnosis was reported by 10.2% and presence of severe symptoms in 4.9%. Logistic regression analysis confirmed some significantly risk factors, such as female sex (Odds Ratio (OR) 1.74; 95% Confidence Interval (CI): 1.12–1.93), age ≥60 year-old (OR 2.00; 95%CI: 1.44–2.77), history of ocular surgery (OR 1.84; 95%CI: 1.30–2.60), contact lens wear (OR 1.93; 95%CI: 1.36–2.73), cancer treatment (OR 3.03; 95%CI: 1.36–6.59), computer use >6 hours per day (OR 1.77; 95%CI: 1.36–2.31), antidepressants (OR 1.61; 95%CI: 1.12–2.31) and anti-allergy (OR 2.11; 95%CI: 1.54–2.89) medications. Nevertheless, when stratified by regions, each one had its own significant factors and inherent characteristics. This is the first study about prevalence and risk factors of dry eye in a large population sample from all regions of Brazil. Dry eye is a common condition in the Brazilian population and prevalence rates varies substantially in the different geographic regions of the country, possibly reflecting climate and socioeconomic discrepancies.
Stacking change in MoS2 bilayers induced by interstitial Mo impurities
Authors: Cortés Natalia , Rosales Luis , Orellana Pedro A. , Ayuela Andrés , González Jhon W.
Published: January 2018

We use a theoretical approach to reveal the electronic and structural properties of molybdenum impurities between MoS2 bilayers. We find that interstitial Mo impurities are able to reverse the well-known stability order of the pristine bilayer, because the most stable form of stacking changes from AA’ (undoped) into AB’ (doped). The occurrence of Mo impurities in different positions shows their split electronic levels in the energy gap, following octahedral and tetrahedral crystal fields. The energy stability is related to the accommodation of Mo impurities compacted in hollow sites between layers. Other less stable configurations for Mo dopants have larger interlayer distances and band gaps than those for the most stable stacking. Our findings suggest possible applications such as exciton trapping in layers around impurities, and the control of bilayer stacking by Mo impurities in the growth process.
All Sequential Dip-Coating Processed Perovskite Layers from an Aqueous Lead Precursor for High Efficiency Perovskite Solar Cells
Authors: Adnan Muhammad , Lee Jae Kwan
Published: January 2018

A novel, sequential method of dip-coating a ZnO covered mesoporous TiO2 electrode was performed using a non-halide lead precursor in an aqueous system to form a nanoscale perovskite film. The introduction of a ZnO interfacial layer induced significant adsorption in the non-halide lead precursor system. An efficient successive solid-state ion exchange and reaction process improved the morphology, crystallinity, and stability of perovskite solar cells. Improved surface coverage was achieved using successive ionic layer adsorption and reaction processes. When all sequential dipping conditions were controlled, a notable power conversion efficiency of 12.41% under standard conditions (AM 1.5, 100 mW·cm−2) was achieved for the perovskite solar cells fabricated from an aqueous non-halide lead precursor solution without spin-casting, which is an environmentally benign and low-cost manufacturing processes.
β-Sitosterol targets Trx/Trx1 reductase to induce apoptosis in A549 cells via ROS mediated mitochondrial dysregulation and p53 activation
Authors: Rajavel Tamilselvam , Packiyaraj Pandian , Suryanarayanan Venkatesan , Singh Sanjeev Kumar , Ruckmani Kandasamy , Pandima Devi Kasi
Published: January 2018

β-Sitosterol (BS), a major bioactive constituent present in plants and vegetables has shown potent anticancer effect against many human cancer cells, but the underlying mechanism remain elusive on NSCLC cancers. We found that BS significantly inhibited the growth of A549 cells without harming normal human lung and PBMC cells. Further, BS treatment triggered apoptosis via ROS mediated mitochondrial dysregulation as evidenced by caspase-3 & 9 activation, Annexin-V/PI positive cells, PARP inactivation, loss of MMP, Bcl-2-Bax ratio alteration and cytochrome c release. Moreover, generation of ROS species and subsequent DNA stand break were found upon BS treatment which was reversed by addition of ROS scavenger (NAC). Indeed BS treatment increased p53 expression and its phosphorylation at Ser15, while silencing the p53 expression by pifithrin-α, BS induced apoptosis was reduced in A549 cells. Furthermore, BS induced apoptosis was also observed in NCI-H460 cells (p53 wild) but not in the NCI-H23 cells (p53 mutant). Down-regulation of Trx/Trx1 reductase contributed to the BS induced ROS accumulation and mitochondrial mediated apoptotic cell death in A549 and NCI-H460 cells. Taken together, our findings provide evidence for the novel anti-cancer mechanism of BS which could be developed as a promising chemotherapeutic drug against NSCLC cancers.
Comparison of plants with C3 and C4 carbon fixation pathways for remediation of polycyclic aromatic hydrocarbon contaminated soils
Authors: Sivaram Anithadevi Kenday , Logeshwaran Panneerselvan , Subashchandrabose Suresh R. , Lockington Robin , Naidu Ravi , Megharaj Mallavarapu
Published: January 2018

The phytoremediation technique has been demonstrated to be a viable option for the remediation of polycyclic aromatic hydrocarbons (PAHs) contaminated sites. This study evaluated the potential applicability of plants with C3 and C4 carbon fixation pathways for the phytoremediation of recalcitrant high molecular weight (HMW) PAHs contaminated soil. A 60 and 120-day greenhouse study was conducted which showed higher degradation of HMW PAHs in soil grown with C4 plants when compared to C3 plants. Also, no PAHs were detected in the maize cobs, sunflower, wallaby, and Sudan grass seeds at the end of the experiment. The effect of plants in modifying the microbial community and dynamics in the rhizosphere was also examined by measuring soil biochemical properties such as dehydrogenase activity and water-soluble phenols. The results demonstrate a substantial difference in the microbial populations between planted and unplanted soils, which in turn facilitate the degradation of PAHs. To the best of our knowledge, this study for the first time evaluated the phytoremediation efficacy through the A. cepa cyto- and genotoxicity assay which should be considered as an integral part of all remediation experiments.
Comparison of proximal versus distal upper-limb robotic rehabilitation on motor performance after stroke: a cluster controlled trial
Authors: Hsieh Yu-wei , Lin Keh-chung , Wu Ching-yi , Shih Tsai-yu , Li Ming-wei , Chen Chia-ling
Published: January 2018

This study examined the treatment efficacy of proximal-emphasized robotic rehabilitation by using the InMotion ARM (P-IMT) versus distal-emphasized robotic rehabilitation by using the InMotion WRIST (D-IMT) in patients with stroke. A total of 40 patients with stroke completed the study. They received P-IMT, D-IMT, or control treatment (CT) for 20 training sessions. Primary outcomes were the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scale. Secondary outcomes were the Motor Activity Log (MAL) and wrist-worn accelerometers. The differences on the distal FMA, total MRC, distal MRC, and MAL quality of movement scores among the 3 groups were statistically significant (P = 0.02 to 0.05). Post hoc comparisons revealed that the D-IMT group significantly improved more than the P-IMT group on the total MRC and distal MRC. Furthermore, the distal FMA and distal MRC improved more in the D-IMT group than in the CT group. Our findings suggest that distal upper-limb robotic rehabilitation using the InMotion WRIST system had superior effects on distal muscle strength. Further research based on a larger sample is needed to confirm long-term treatment effects of proximal versus distal upper-limb robotic rehabilitation.
Large-scale intact glycopeptide identification by Mascot database search
Authors: Bollineni Ravi Chand , Koehler Christian Jeffrey , Gislefoss Randi Elin , Anonsen Jan Haug , Thiede Bernd
Published: January 2018

Workflows capable of determining glycopeptides in large-scale are missing in the field of glycoproteomics. We present an approach for automated annotation of intact glycopeptide mass spectra. The steps in adopting the Mascot search engine for intact glycopeptide analysis included: (i) assigning one letter codes for monosaccharides, (ii) linearizing glycan sequences and (iii) preparing custom glycoprotein databases. Automated annotation of both N- and O-linked glycopeptides was proven using standard glycoproteins. In a large-scale study, a total of 257 glycoproteins containing 970 unique glycosylation sites and 3447 non-redundant N-linked glycopeptide variants were identified in 24 serum samples. Thus, a single tool was developed that collectively allows the (i) elucidation of N- and O-linked glycopeptide spectra, (ii) matching glycopeptides to known protein sequences, and (iii) high-throughput, batch-wise analysis of large-scale glycoproteomics data sets.
Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas
Authors: Wagner Vivian P. , Martins Manoela D. , Martins Marco A. T. , Almeida Luciana O. , Warner Kristy A. , Nör Jacques E. , Squarize Cristiane H. , Castilho Rogerio M.
Published: January 2018

Malignancies from the salivary glands are rare and represent 11% of all cancers from the oropharyngeal anatomical area. Mucoepidermoid Carcinomas (MEC) is the most common malignancy from the salivary glands. Low survival rates of high-grade Mucoepidermoid Carcinomas (MEC) are particularly associated with the presence of positive lymph nodes, extracapsular lymph node spread, and perineural invasion. Most recently, the presence of cancer stem cells (CSC), and the activation of the NFκB signaling pathway have been suggested as cues for an acquired resistance phenotype. We have previously shown that NFκB signaling is very active in MEC tumors. Herein, we explore the efficacy of NFκB inhibition in combination with class I and II HDAC inhibitor to deplete the population of CSC and to destroy MEC tumor cells. Our finding suggests that disruption of NFκB signaling along with the administration of HDAC inhibitors constitute an effective strategy to manage MEC tumors.
Possible role of chondroitin sulphate and glucosamine for primary prevention of colorectal cancer. Results from the MCC-Spain study
Authors: Ibáñez-Sanz Gemma , Díez-Villanueva Anna , Vilorio-Marqués Laura , Gracia Esther , Aragonés Nuria , Olmedo-Requena Rocío , Llorca Javier , Vidán Juana , Amiano Pilar , Nos Pilar , Fernández-Tardón Guillermo , Rada Ricardo , Chirlaque María Dolores , Guinó Elisabet , Dávila-Batista Verónica , Castaño-Vinyals Gemma , Pérez-Gómez Beatriz , Mirón-Pozo Benito , Dierssen-Sotos Trinidad , Etxeberria Jaione , Molinuevo Amaia , Álvarez-Cuenllas Begoña , Kogevinas Manolis , Pollán Marina , Moreno Victor
Published: January 2018

A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28–0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47–1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62–0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.