bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical alteration and preservation of sedimentary/organic nitrogen isotope signatures in a 2.7 Ga seafloor volcanic sequence
Authors: Anderson L. D. , Bebout G. E. , Izawa M. R. M. , Bridge N. J. , Banerjee N. R.
Published: November 2017

Massive to lobate volcanic flows and brecciated hyaloclastite units in the Abitibi greenstone belt allow investigation of Late Archæan seafloor alteration and associated incorporation into these rocks of nitrogen (N) biogeochemical signatures. In this suite (the Blake River Group), hyaloclastite units containing putative microbial ichnofossils are particularly enriched in large-ion lithophile elements (K, Rb, Ba, Cs), B, and Li, consistent with their having experienced the greatest fluid–rock interaction during subseafloor hydrothermal alteration. Similarly, silicate-δ18O and δ15N values for samples from the hyaloclastites show the greatest shifts from plausible magmatic values. The chemical and isotopic patterns in these tholeiitic igneous rocks greatly resemble those in modern altered seafloor basalts, consistent with the preservation of an Archæan seafloor alteration signature. The N enrichments and shifts in δ15N appear to reflect stabilization of illite and interaction with fluids carrying sedimentary/organic signatures. Enrichments of N (and the δ15N of this N) in altered glass volcanic rocks on Earth's modern and ancient seafloor point to the potential utility of N for tracing past and present biogeochemical processes in similar rocks at/near the Mars surface.
Easy and Hard Redistribution: The Political Economy of Welfare States in Latin America
Authors: Holland Alisha C. , Schneider Ben Ross
Published: November 2017

Comparative research on Latin American welfare states recently has focused on the extension of non-contributory benefits to those outside the formal labor market. This extension of benefits constitutes a major break from past exclusionary welfare regimes. Yet there also are substantial areas of continuity, especially in the contributory social-insurance system that absorbs most of welfare budgets. We develop here a framework for studying changes in Latin American welfare states that reconciles these trends. We argue that Latin American governments enjoyed an “easy” stage of welfare expansions in the 2000s, characterized by distinct political coalitions. Bottom-targeted benefits could be layered on top of existing programs and provided to wide segments of the population. But many Latin American governments are nearing the exhaustion of this social-policy model. We explore policy and coalitional challenges that hinder moves to “hard” redistribution with case studies of unemployment insurance in Chile and housing in Colombia.
The avoidance of monetary system conflict: A role for recognition theory in reconstituting the global monetary system
Authors: FELDMANN JOHN D
Published: November 2017

This article examines the ongoing conflict in the global monetary system as a struggle over norms of recognition between the US Federal Reserve and the emerging market economies. The analysis demonstrates that the Fed, though dominant actor in the global monetary system, adopts a US-centric perspective and relies upon inadequate economic constructs that misrecognise periphery members and justify a dismissal of criticisms of its monetary policy actions. The article shows how the adoption of recognition principles in reconstituting the monetary rules of the game would provide the Fed with an understanding of the political economic essentials of member countries, a greater awareness of potential harms of its monetary policy actions and the importance of cooperation in reducing conflict and mitigating episodes of monetary instability.
Social Support from Developmental Contexts and Adolescent Substance Use and Well-Being: A Comparative Study of Spain and Portugal
Authors: Jiménez-Iglesias Antonia , Camacho Inês , Rivera Francisco , Moreno Carmen , Matos Margarida Gaspar de
Published: November 2017

The aim of this study was to analyse the contribution of social support from family, friend and school (teacher and classmate) contexts in substance use (tobacco and alcohol use) and well-being (life satisfaction and health-related quality of life). Participants were 5,784 Portuguese and 22,610 Spanish adolescents aged 11 to 16 years, from the 2014 edition of the Health Behavior in School-aged Children (HBSC) study in Portugal and Spain. Results showed that for a higher life satisfaction, family (p< .001, partial η2= .032), teacher (p< .001, partial η2= .018) and classmate (p< .001, partial η2= .031) support were important in Portugal, and family (p< .001, partial η2= .056) and friend (p< .001, partial η2= .015) support in Spain. Similarly, for a better health-related quality of life, all the social support variables were relevant in Portugal (family:p< .001, partial η2= .063; teacher:p< .001, partial η2= .032; classmate:p< .001, partial η2= .054; friend:p< .001, partial η2= .034) and in Spain (family:p< .001, partial η2= .054; teacher:p< .001, partial η2= .014; classmate:p< .001, partial η2= .018; friend:p< .001, partial η2= .040). In contrast, only family support (p< .001, partial η2= .014) was relevant in Portugal for tobacco use. Therefore, social support was more relevant for adolescent well-being than for adolescent substance use, and the most relevant source of support was family support, in both Spain and Portugal.
Monolithic ultrasound fingerprint sensor
Authors: Jiang Xiaoyue , Lu Yipeng , Tang Hao-Yen , Tsai Julius M. , Ng Eldwin J. , Daneman Michael J. , Boser Bernhard E. , Horsley David A.
Published: November 2017

This paper presents a 591×438-DPI ultrasonic fingerprint sensor. The sensor is based on a piezoelectric micromachined ultrasonic transducer (PMUT) array that is bonded at wafer-level to complementary metal oxide semiconductor (CMOS) signal processing electronics to produce a pulse-echo ultrasonic imager on a chip. To meet the 500-DPI standard for consumer fingerprint sensors, the PMUT pitch was reduced by approximately a factor of two relative to an earlier design. We conducted a systematic design study of the individual PMUT and array to achieve this scaling while maintaining a high fill-factor. The resulting 110×56-PMUT array, composed of 30×43-μm2 rectangular PMUTs, achieved a 51.7% fill-factor, three times greater than that of the previous design. Together with the custom CMOS ASIC, the sensor achieves 2 mV kPa−1 sensitivity, 15 kPa pressure output, 75 μm lateral resolution, and 150 μm axial resolution in a 4.6 mm×3.2 mm image. To the best of our knowledge, we have demonstrated the first MEMS ultrasonic fingerprint sensor capable of imaging epidermis and sub-surface layer fingerprints.
Silicon CMOS architecture for a spin-based quantum computer
Authors: Veldhorst M. , Eenink H. G. J. , Yang C. H. , Dzurak A. S.
Published: November 2017

Recent advances in quantum error correction codes for fault-tolerant quantum computing and physical realizations of high-fidelity qubits in multiple platforms give promise for the construction of a quantum computer based on millions of interacting qubits. However, the classical-quantum interface remains a nascent field of exploration. Here, we propose an architecture for a silicon-based quantum computer processor based on complementary metal-oxide-semiconductor (CMOS) technology. We show how a transistor-based control circuit together with charge-storage electrodes can be used to operate a dense and scalable two-dimensional qubit system. The qubits are defined by the spin state of a single electron confined in quantum dots, coupled via exchange interactions, controlled using a microwave cavity, and measured via gate-based dispersive readout. We implement a spin qubit surface code, showing the prospects for universal quantum computation. We discuss the challenges and focus areas that need to be addressed, providing a path for large-scale quantum computing.
Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair
Authors: Qu Feini , Holloway Julianne L. , Esterhai John L. , Burdick Jason A. , Mauck Robert L.
Published: November 2017

Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue. To implement these signals in situ, we develop nanofibrous scaffolds with distinct fiber fractions that sequentially release active collagenase (to increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized and coordinated manner. We show that, when placed into a meniscal defect, the controlled release of collagenase and PDGF-AB increases cellularity at the interface and within the scaffold, as well as integration with the surrounding tissue.
Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study
Authors: Dellinger Ryan W. , Santos Santiago Roel , Morris Mark , Evans Mal , Alminana Dan , Guarente Leonard , Marcotulli Eric
Published: November 2017

NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD+ in whole blood demonstrated that NRPT significantly increases the concentration of NAD+ in a dose-dependent manner. NAD+ levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD+ levels was sustained throughout the entire 8-week trial. NAD+ levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably.
Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast
Authors: Piscuoglio Salvatore , Ng Charlotte K. Y. , Geyer Felipe C. , Burke Kathleen A. , Cowell Catherine F. , Martelotto Luciano G. , Natrajan Rachael , Popova Tatiana , Maher Christopher A. , Lim Raymond S. , Bruijn Ino de , Mariani Odette , Norton Larry , Vincent-Salomon Anne , Weigelt Britta , Reis-Filho Jorge S.
Published: November 2017

Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal elements. Here we sought to define whether histologically distinct subgroups of MBCs would be underpinned by distinct genomic and/or transcriptomic alterations. Microarray-based copy number profiling identified limited but significant differences between the distinct MBC subtypes studied here, despite the limited sample size (n = 17). In particular, we found that, compared to MBCs with chondroid or squamous cell metaplasia, MBCs with spindle cell differentiation less frequently harbored gain of 7q11.22-23 encompassing CLDN3 and CLDN4, consistent with their lower expression of claudins and their association with the claudin-low molecular classification. Microarray-based and RNA-sequencing-based gene expression profiling revealed that MBCs with spindle cell differentiation differ from MBCs with chondroid or squamous cell metaplasia on the expression of epithelial-to-mesenchymal transition-related genes, including down-regulation of CDH1 and EPCAM. In addition, RNA-sequencing revealed that the histologic patterns observed in MBCs are unlikely to be underpinned by a highly recurrent expressed fusion gene or a pathognomonic expressed mutation in cancer genes. Loss of PTEN expression or mutations affecting PIK3CA or TSC2 observed in 8/17 MBCs support the contention that PI3K pathway activation plays a role in the development of MBCs. Our data demonstrate that despite harboring largely similar patterns of gene copy number alterations, MBCs with spindle cell, chondroid and squamous differentiation are distinct at the transcriptomic level but are unlikely to be defined by specific pathognomonic genetic alterations.
Towards AI-powered personalization in MOOC learning
Authors: Yu Han , Miao Chunyan , Leung Cyril , White Timothy John
Published: November 2017

Massive Open Online Courses (MOOCs) represent a form of large-scale learning that is changing the landscape of higher education. In this paper, we offer a perspective on how advances in artificial intelligence (AI) may enhance learning and research on MOOCs. We focus on emerging AI techniques including how knowledge representation tools can enable students to adjust the sequence of learning to fit their own needs; how optimization techniques can efficiently match community teaching assistants to MOOC mediation tasks to offer personal attention to learners; and how virtual learning companions with human traits such as curiosity and emotions can enhance learning experience on a large scale. These new capabilities will also bring opportunities for educational researchers to analyse students’ learning skills and uncover points along learning paths where students with different backgrounds may require different help. Ethical considerations related to the application of AI in MOOC education research are also discussed.
Erratum: Chlamydia trachomatis neither exerts deleterious effects on spermatozoa nor impairs male fertility
Authors: Puerta Suárez Jenniffer , Sánchez Leonardo R. , Salazar Florencia C. , Saka Hector A. , Molina Rosa , Tissera Andrea , Rivero Virginia E. , Cardona Maya Walter D. , Motrich Ruben D.
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of lncRNA ANRIL in tumour cells
Authors: Zhang Dongya , Ding Liang , Li Yi , Ren Jing , Shi Guoping , Wang Yong , Zhao Shuli , Ni Yanhong , Hou Yayi
Published: November 2017

Midkine (MK) is a heparin-binding growth factor that promotes carcinogenesis and chemoresistance. The tumour microenvironment (TME) can affect chemotherapy sensitivity. However, the role of stromal-derived MK, especially in cancer-associated fibroblasts (CAFs), is unclear. Here, we confirmed that MK decreased cisplatin-induced cell death in oral squamous cell carcinoma (OSCC) cells, ovarian cancer cells and lung cancer cells. We also isolated primary CAFs (n = 3) from OSCC patients and found that CAFs secreted increased levels of MK, which abrogated cisplatin-induced cell death. Moreover, MK increased the expression of lncRNA ANRIL in the tumour cells. Normal tissues, matched tumour-adjacent tissues and OSCC tissues were analysed (n = 60) and showed that lncRNA ANRIL was indeed overexpressed during carcinogenesis and correlated with both high TNM stage and lymph node metastasis (LNM). Furthermore, lncRNA ANRIL knockdown in tumour cells inhibited proliferation, induced apoptosis and increased cisplatin cytotoxicity of the tumour cells via impairment of the drug transporters MRP1 and ABCC2, which could be restored by treatment with human MK in a caspase-3/BCL-2-dependent manner. In conclusion, we firstly describe that CAFs in the TME contribute to the high level of MK in tumours and that CAF-derived MK can promote cisplatin resistance via the elevated expression of lncRNA ANRIL.
Interplay between trauma and Pseudomonas entomophila infection in flies: a central role of the JNK pathway and of CrebA
Authors: Ragheb Ramy , Chuyen Alexandre , Torres Magali , Defaye Arnaud , Seyres Denis , Kremmer Laurent , Fernandez-Nunez Nicolas , Tricoire Hervé , Rihet Pascal , Nguyen Catherine , Röder Laurence , Perrin Laurent
Published: November 2017

In mammals, both sterile wounding and infection induce inflammation and activate the innate immune system, and the combination of both challenges may lead to severe health defects, revealing the importance of the balance between the intensity and resolution of the inflammatory response for the organism’s fitness. Underlying mechanisms remain however elusive. Using Drosophila, we show that, upon infection with the entomopathogenic bacterium Pseudomonas entomophila (Pe), a sterile wounding induces a reduced resistance and increased host mortality. To identify the molecular mechanisms underlying the susceptibility of wounded flies to bacterial infection, we analyzed the very first steps of the process by comparing the transcriptome landscape of infected (simple hit flies, SH), wounded and infected (double hit flies, DH) and wounded (control) flies. We observed that overexpressed genes in DH flies compared to SH ones are significantly enriched in genes related to stress, including members of the JNK pathway. We demonstrated that the JNK pathway plays a central role in the DH phenotype by manipulating the Jra/dJun activity. Moreover, the CrebA/Creb3-like transcription factor (TF) and its targets were up-regulated in SH flies and we show that CrebA is required for mounting an appropriate immune response. Drosophila thus appears as a relevant model to investigate interactions between trauma and infection and allows to unravel key pathways involved.
Design and applications of a clamp for Green Fluorescent Protein with picomolar affinity
Authors: Hansen Simon , Stüber Jakob C. , Ernst Patrick , Koch Alexander , Bojar Daniel , Batyuk Alexander , Plückthun Andreas
Published: November 2017

Green fluorescent protein (GFP) fusions are pervasively used to study structures and processes. Specific GFP-binders are thus of great utility for detection, immobilization or manipulation of GFP-fused molecules. We determined structures of two designed ankyrin repeat proteins (DARPins), complexed with GFP, which revealed different but overlapping epitopes. Here we show a structure-guided design strategy that, by truncation and computational reengineering, led to a stable construct where both can bind simultaneously: by linkage of the two binders, fusion constructs were obtained that “wrap around” GFP, have very high affinities of about 10–30 pM, and extremely slow off-rates. They can be natively produced inE. coliin very large amounts, and show excellent biophysical properties. Their very high stability and affinity, facile site-directed functionalization at introduced unique lysines or cysteines facilitate many applications. As examples, we present them as tight yet reversible immobilization reagents for surface plasmon resonance, as fluorescently labelled monomeric detection reagents in flow cytometry, as pull-down ligands to selectively enrich GFP fusion proteins from cell extracts, and as affinity column ligands for inexpensive large-scale protein purification. We have thus described a general design strategy to create a “clamp” from two different high-affinity repeat proteins, even if their epitopes overlap.
Invasive plants as potential food resource for native pollinators: A case study with two invasive species and a generalist bumble bee
Authors: Drossart Maxime , Michez Denis , Vanderplanck Maryse
Published: November 2017

It is now well established that invasive plants may induce drifts in the quantity and/or quality of floral resources. They are then often pointed out as a potential driver of bee decline. However, their impact on bee population remains quite unclear and still controversial, as bee responses are highly variable among species. Here, we compared the amino acid composition of pollen from three native and two invasive plant species included in diets of common pollinators in NW Europe. Moreover, the nutritional intake (i.e., pollen and amino acid intakes) ofBombus terrestriscolonies and the pollen foraging behaviour of workers (i.e., visiting rate, number of foraging trips, weight of pollen loads) were considered. We found significant differences in pollen nutrients among the studied species according to the plant invasive behaviour. We also found significant differences in pollen foraging behaviour according to the plant species, from few to several foraging trips carrying small or large pollen loads. Such behavioural differences directly impacted the pollen intake but depended more likely on plant morphology rather than on plant invasive behaviour. These results suggest that common generalist bumble bees might not always suffer from plant invasions, depending on their behavioural plasticity and nutritional requirements.
Fungal endophytes inhabiting mountain-cultivated ginseng (Panax ginseng Meyer): Diversity and biocontrol activity against ginseng pathogens
Authors: Park Young-Hwan , Kim Yoosam , Mishra Ratnesh Chandra , Bae Hanhong
Published: November 2017

Fungal endophytes isolated from mountain-cultivated ginseng (MCG, Panax ginseng Meyer) were explored for their diversity and biocontrol activity against ginseng pathogens (Alternaria panax, Botrytis cinerea, Cylindrocarpon destructans, Pythium sp. and Rhizoctonia solani). A total of 1,300 isolates were isolated from three tissues (root, stem and leaf) from MCGs grown in 24 different geographic locations in Korea. In total, 129 different fungal isolates were authenticated by molecular identification based on internal transcribed spacer (ITS) sequences. The fungal endophytes belonged to Ascomycota (81.7%), Basidiomycota (7.08%), Zygomycota (10%) and Unknown (1.15%), with 59 genera. Analysis of diversity indices across sampling sites suggested species abundance as a function of geographical and environmental factors of the locations. Shannon diversity index and richness in the different tissues revealed that root tissues are colonized more than stem and leaf tissues, and also certain fungal endophytes are tissue specific. Assessment of the ethyl acetate extracts from 129 fungal isolates for their biocontrol activity against 5 ginseng pathogens revealed that Trichoderma polysporum produces the antimcriobial metabolite against all the pathogens. This result indicates the promise of its potential usage as a biocontrol agent.
Silica formation with nanofiber morphology via helical display of the silaffin R5 peptide on a filamentous bacteriophage
Authors: Song In-Wong , Park Hyojung , Park Jung Han , Kim Hyunook , Kim Seong Hun , Yi Sung , Jaworski Justyn , Sang Byoung-In
Published: November 2017

Biological systems often generate unique and useful structures, which can have industrial relevance either as direct components or as an inspiration for biomimetic materials. For fabrication of nanoscale silica structures, we explored the use of the silaffin R5 peptide fromCylindrotheca fusiformisexpressed on the surface of the fd bacteriophage. By utilizing the biomineralizing peptide component displayed on the bacteriophage surface, we found that low concentrations (0.09 mg/mL of the R5 bacteriophage, below the concentration range used in other studies) could be used to create silica nanofibers. An additional benefit of this approach is the ability of our R5-displaying phage to form silica materials without the need for supplementary components, such as aminopropyl triethoxysilane, that are typically used in such processes. Because this method for silica formation can occur under mild conditions when implementing our R5 displaying phage system, we may provide a relatively simple, economical, and environmentally friendly process for creating silica nanomaterials.
Rama: a machine learning approach for ribosomal protein prediction in plants
Authors: Carvalho Thales Francisco Mota , Silva José Cleydson F. , Calil Iara Pinheiro , Fontes Elizabeth Pacheco Batista , Cerqueira Fabio Ribeiro
Published: November 2017

Ribosomal proteins (RPs) play a fundamental role within all type of cells, as they are major components of ribosomes, which are essential for translation of mRNAs. Furthermore, these proteins are involved in various physiological and pathological processes. The intrinsic biological relevance of RPs motivated advanced studies for the identification of unrevealed RPs. In this work, we propose a new computational method, termed Rama, for the prediction of RPs, based on machine learning techniques, with a particular interest in plants. To perform an effective classification, Rama uses a set of fundamental attributes of the amino acid side chains and applies a two-step procedure to classify proteins with unknown function as RPs. The evaluation of the resultant predictive models showed that Rama could achieve mean sensitivity, precision, and specificity of 0.91, 0.91, and 0.82, respectively. Furthermore, a list of proteins that have no annotation in Phytozome v.10, and are annotated as RPs in Phytozome v.12, were correctly classified by our models. Additional computational experiments have also shown that Rama presents high accuracy to differentiate ribosomal proteins from RNA-binding proteins. Finally, two novel proteins of Arabidopsis thaliana were validated in biological experiments. Rama is freely available at http://inctipp.bioagro.ufv.br:8080/Rama.
The association between visual function and retinal structure in chronic central serous chorioretinopathy
Authors: Sugiura Aya , Fujino Ryosuke , Takemiya Nobuko , Shimizu Kimiko , Matsuura Masato , Murata Hiroshi , Inoue Tatsuya , Obata Ryo , Asaoka Ryo
Published: November 2017

The purpose of the current study was to investigate the association between visual function and retinal structure in central serous chorioretinopathy (CSC). In 22 eyes of 22 chronic CSC patients with serous retinal detachment at the macula, retinal sensitivity was measured using MP3 microperimetry (NIDEK, Japan) and mean sensitivity within two degrees (MS2), four degrees (MS4) and six degrees (MS6), as well as foveal sensitivity (MS0), were calculated. Retinal structure was measured using optical coherence tomography (OCT, Spectralis, Heidelberg). The relationship between visual function (LogMAR best-corrected visual acuity [LogMAR VA] and MS0, MS2, MS4, MS6) and serous retinal detachment height at the fovea (SRDH), central retinal thickness (CRT), macular volume (MV) and central choroidal thickness (CCT) was investigated. There were significant negative correlations between LogMAR VA and MS0 (p = 0.016), MS2 (p = 0.049). No significant relationship was observed between LogMAR VA and SRDH (p = 0.97) although there was a significant negative correlation between SRDH and MS2 (p = 0.028), MS4 (p = 0.049), MS6 (p = 0.023). In conclusion, in CSC, serous retinal detachment was significantly correlated with retinal sensitivity measured with MP3, but not with LogMAR VA.
Exploration of Protein Unfolding by Modelling Calorimetry Data from Reheating
Authors: Mazurenko Stanislav , Kunka Antonin , Beerens Koen , Johnson Christopher M. , Damborsky Jiri , Prokop Zbynek
Published: November 2017

Studies of protein unfolding mechanisms are critical for understanding protein functions inside cells, de novo protein design as well as defining the role of protein misfolding in neurodegenerative disorders. Calorimetry has proven indispensable in this regard for recording full energetic profiles of protein unfolding and permitting data fitting based on unfolding pathway models. While both kinetic and thermodynamic protein stability are analysed by varying scan rates and reheating, the latter is rarely used in curve-fitting, leading to a significant loss of information from experiments. To extract this information, we propose fitting both first and second scans simultaneously. Four most common single-peak transition models are considered: (i) fully reversible, (ii) fully irreversible, (iii) partially reversible transitions, and (iv) general three-state models. The method is validated using calorimetry data for chicken egg lysozyme, mutated Protein A, three wild-types of haloalkane dehalogenases, and a mutant stabilized by protein engineering. We show that modelling of reheating increases the precision of determination of unfolding mechanisms, free energies, temperatures, and heat capacity differences. Moreover, this modelling indicates whether alternative refolding pathways might occur upon cooling. The Matlab-based data fitting software tool and its user guide are provided as a supplement.
Membrane insertion of the BAX core, but not latch domain, drives apoptotic pore formation
Authors: Flores-Romero Hector , Garcia-Porras Miguel , Basañez Gorka
Published: November 2017

Despite intensive research effort, how the paradigmatic proapoptotic protein BAX forms lethal apoptotic pores at the mitochondrial outer membrane (MOM) remains incompletely understood. Here, we used biophysical tools and minimalist model systems to identify the specific regions in BAX driving apoptotic pore formation, and to gain more insight into underlying mechanisms. Fluorescence mapping revealed that fully active BAX adopts a BH3-in-groove dimeric conformation in MOM-like membranes, with BAX α4-α5 helices belonging to its core domain inserting deeper into the membrane lipid bilayer than BAX α6-α8 helices belonging to its latch domain. In our reconstituted systems, antiapoptotic BCLXL formed canonical heterodimeric BH3-in-groove complexes with BAX, and blocked membrane insertion of BAX core α4-α5 helices, but not BAX latch α6-α8 helices. Moreover, poly(ethylene glycol) (PEG) conjugation (PEGylation) at multiple individual sites along the BAX core, but not latch domain, potently inhibited BAX pore-forming activity. Additional combined computational and experimental evidence revealed that the BAX core α5 helix displays a bilayer-destabilizing membrane interaction mode that is absent in BAX latch α6-α8 helices. Based on this collective set of evidence, we propose that membrane insertion of the BAX core, but not latch domain, is critical for BAX apoptotic pore formation.
A statistical image analysis framework for pore-free islands derived from heterogeneity distribution of nuclear pore complexes
Authors: Mimura Yasuhiro , Takemoto Satoko , Tachibana Taro , Ogawa Yutaka , Nishimura Masaomi , Yokota Hideo , Imamoto Naoko
Published: November 2017

Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate NPC assembly in interphase, the location of NPC assembly on the nuclear envelope is not clear. CDKs also regulate the disappearance of pore-free islands, which are nuclear envelope subdomains; this subdomain gradually disappears with increase in homogeneity of the NPC in response to CDK activity. However, a causal relationship between pore-free islands and NPC assembly remains unclear. Here, we elucidated mechanisms underlying NPC assembly from a new perspective by focusing on pore-free islands. We proposed a novel framework for image-based analysis to automatically determine the detailed ‘landscape’ of pore-free islands from a large quantity of images, leading to the identification of NPC intermediates that appear in pore-free islands with increased frequency in response to CDK activity. Comparison of the spatial distribution between simulated and the observed NPC intermediates within pore-free islands showed that their distribution was spatially biased. These results suggested that the disappearance of pore-free islands is highly related to de novo NPC assembly and indicated the existence of specific regulatory mechanisms for the spatial arrangement of NPC assembly on nuclear envelopes.
Changes in gene expression and apoptotic response in Spodoptera exigua larvae exposed to sublethal concentrations of Vip3 insecticidal proteins
Authors: Hernández-Martínez Patricia , Gomis-Cebolla Joaquín , Ferré Juan , Escriche Baltasar
Published: November 2017

The insecticidal Vip3 proteins fromBacillus thuringiensis(Bt), along with the classical Bt Cry proteins, are currently used in Bt-crops to control insect pests, since they do not share the same mode of action. Here we characterized the response ofSpodoptera exigualarvae after Vip3 challenge. The expression profile of 47 genes was analyzed in larvae challenged with three concentrations of Vip3Ca. Results showed that the up-regulated genes were mainly involved in immune response, whereas the down-regulated genes were mainly involved in the digestion process. Other mechanisms of cellular response to the damage such as apoptosis were analyzed. For this analysis, sections from the midguts were examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The nuclei of the midgut epithelial cells were stained at the highest concentration of the Vip3Ca protein and at lower concentrations of Vip3Aa in agreement with the different potency of the two proteins. In addition, apoptosis was also examined by the analysis of the expression of fivecaspasegenes. The present study shows that exposure ofS. exigualarvae to sublethal concentrations of Vip3 proteins activates different insect response pathways which trigger the regulation of some genes, APN shedding, and apoptotic cell death.
Organoids model distinct Vitamin E effects at different stages of prostate cancer evolution
Authors: Njoroge Rose N. , Unno Kenji , Zhao Jonathan C. , Naseem Anum F. , Anker Jonathan F. , McGee Warren A. , Nonn Larisa , Abdulkadir Sarki A.
Published: November 2017

Vitamin E increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) through unknown mechanisms while Selenium showed no efficacy. We determined the effects of the SELECT supplements on benign (primary), premalignant ( RWPE-1) and malignant (LNCaP) prostate epithelial organoids. While the supplements decreased proliferation and induced cell death in cancer organoids, they had no effect on the benign organoids. In contrast, Vitamin E enhanced cell proliferation and survival in the premalignant organoids in a manner that recapitulated the SELECT results. Indeed, while Vitamin E induced a pro-proliferative gene expression signature, Selenium alone or combined with Vitamin E produced an anti-proliferative signature. The premalignant organoids also displayed significant downregulation of glucose transporter and glycolytic gene expression pointing to metabolic alterations. Detached RWPE-1 cells had low ATP levels due to diminished glucose uptake and glycolysis which was rescued by Vitamin E through the activation of fatty acid oxidation (FAO). FAO inhibition abrogated the ATP rescue, diminished survival of the inner matrix detached cells, restoring the normal hollow lumen morphology in Vitamin E treated organoids. Organoid models therefore clarify the paradoxical findings from SELECT and demonstrate that Vitamin E promotes tumorigenesis in the early stages of prostate cancer evolution.
The use of microfluidic spinning fiber as an ophthalmology suture showing the good anastomotic strength control
Authors: Park DoYeun , Yong In Sung , Cho Kyong Jin , Cheng Jie , Jung Youngmee , Kim Soo Hyun , Lee Sang-Hoon
Published: November 2017

Adjusting the mechanical strength of a biomaterial to suit its intended application is very important for realizing beneficial outcomes. Microfluidic spinning fiber have been attracting attention recently due to their various advantages, but their mechanical strength has unfortunately not been a subject of concentrated research, and this lack of research has severely limited their applications. In the current work, we showed the mechanical properties of microfibers can be tuned easily and provided a mathematical explanation for how the microfluidic spinning method intrinsically controls the mechanical properties of a microfluidic spinning fiber. But we were also able to adjust the mechanical properties of such fibers in various other ways, including by using biomolecules to coat the fiber or mixing the biomolecules with the primary component of the fiber and by using a customized twisting machine to change the number of single microfiber strands forming the fiber. We used the bundle fiber as an ophthalmology suture that resulted in a porcine eye with a smoother post-operative surface than did a nylon suture. The results showed the possibility that the proposed method can solve current problems of the microfibers in practical applications, and can thus extend the range of applications of these microfibers.
An extended cluster expansion for ground states of heterofullerenes
Authors: Cheng Yun-Hua , Liao Ji-Hai , Zhao Yu-Jun , Yang Xiao-Bao
Published: November 2017

It is challenging to determine the ground states of heterofullerenes due to the numerous isomers. Taking the C60-n
B
n
heterofullerenes (1 ≤ n ≤ 4) as an example, our first-principles calculations with the isomer enumeration present the most stable structure of C57B3, which is energetically favored by 0.73 eV than the reported counterpart. It was difficult to conduct the enumeration for the isomers with n beyond 4 because of the expensive first-principle calculations. Here, we propose a nomenclature to enhance structural recognition and adopt an extended cluster expansion to describe the structural stabilities, in which the energies of the heterofullerenes with various concentrations are predicted by linear combination of the multi-body interactions. Unlike the conventional cluster expansion, the interaction parameters are derived from the enumeration of C60-n
B
n
(n = 1~4), where there are only 4 coefficients to be fitted as a function of composition for the consideration of local bonding. The cross-validation scores are 1~2 meV per atom for both C55B5 and C54B6, ensuring the ground states obtained from our model are in line with the first-principles results. With the help of the structural recognition, the extended cluster expansion could be further applied to other binary systems as an effective complement to the first-principle calculations.
The Retinol Binding Protein Receptor 2 (Rbpr2) is required for Photoreceptor Outer Segment Morphogenesis and Visual Function in Zebrafish
Authors: Shi Yi , Obert Elisabeth , Rahman Bushra , Rohrer Bärbel , Lobo Glenn P.
Published: November 2017

Vitamin A (all-trans retinol) plays critical roles in mammalian development and vision. Since vitamin A is food-derived, tissue-specific uptake and storage mechanism are needed. In the eye, uptake of RBP4-retinol is mediated by the receptor Stra6, whereas the receptor mediating RBP4 binding and retinol transport into the liver has just recently been discovered. Here we examined the role of zebrafish retinol binding protein receptor 2 (Rbpr2) for RBP4-retinol uptake in developing embryos, using eye development and vision as sensitive readouts. In cultured cells, Rbpr2 localized to membranes and promoted RBP4-retinol uptake. In larvae, Rbpr2 expression was detected in developing intestinal enterocytes and liver hepatocytes. Two rbpr2 mutant zebrafish lines, each resulting in Rbpr2 deficiency, exhibit a small eye defect, and systemic malformations including hydrocephaly and cardiac edema, phenotypes associated with vitamin A deficiency. In the retina, Rbpr2 loss resulted in shorter photoreceptor outer segments, mislocalization and decrease in visual pigments, decreased expression of retinoic acid-responsive genes and photoreceptor cell loss, overall leading to a reduction of visual function. Together, these results demonstrate that Rbpr2-mediated RBP4-retinol uptake in developing liver and intestine is necessary to provide sufficient substrate for ocular retinoid production required for photoreceptor cell maintenance and visual function.
Hydrogen mobility in the lightest reversible metal hydride, LiBeH3
Authors: Mamontov Eugene , Kolesnikov Alexander I. , Sampath Sujatha , Yarger Jeffery L.
Published: November 2017

Lithium-beryllium metal hydrides, which are structurally related to their parent compound, BeH2, offer the highest hydrogen storage capacity by weight among the metal hydrides (15.93 wt. % of hydrogen for LiBeH3). Challenging synthesis protocols have precluded conclusive determination of their crystallographic structure to date, but here we analyze directly the hydrogen hopping mechanisms in BeH2 and LiBeH3 using quasielastic neutron scattering, which is especially sensitive to single-particle dynamics of hydrogen. We find that, unlike its parent compound BeH2, lithium-beryllium hydride LiBeH3 exhibits a sharp increase in hydrogen mobility above 265 K, so dramatic that it can be viewed as melting of hydrogen sublattice. We perform comparative analysis of hydrogen jump mechanisms observed in BeH2 and LiBeH3 over a broad temperature range. As microscopic diffusivity of hydrogen is directly related to its macroscopic kinetics, a transition in LiBeH3 so close to ambient temperature may offer a straightforward and effective mechanism to influence hydrogen uptake and release in this very lightweight hydrogen storage compound.
Ozone Improves the Aromatic Fingerprint of White Grapes
Authors: Río Segade Susana , Vilanova Mar , Giacosa Simone , Perrone Irene , Chitarra Walter , Pollon Matteo , Torchio Fabrizio , Boccacci Paolo , Gambino Giorgio , Gerbi Vincenzo , Rolle Luca
Published: November 2017

Ozone, a powerful oxidative stressor, has been recently used in wine industry as sanitizing agent to reduce spoilage microflora on grapes. In this study, we evaluated ozone-induced metabolic and molecular responses during postharvest grape dehydration. Ozone increased the contents of total volatile organic compounds (VOCs), which have a great impact on the organoleptic properties of grapes and wines. Among terpenes, responsible for floral and fruity aroma, linalool, geraniol and nerol were the major aromatic markers of Moscato bianco grapes. They were significantly affected by the long-term ozone treatment, increasing their concentration in the last phases of dehydration (>20% weight loss). At molecular level, our results demonstrated that both postharvest dehydration and ozone exposure induce the biosynthesis of monoterpenes via methylerythritol phosphate (MEP) pathway and of aldehydes from lipoxygenase-hydroperoxide lyase (LOX-HPL) pathway. Therefore, transcriptional changes occurred and promoted the over-production of many important volatile compounds for the quality of white grapes.
Gas hydrate saturations estimated from pore-and fracture-filling gas hydrate reservoirs in the Qilian Mountain permafrost, China
Authors: Xiao Kun , Zou Changchun , Lu Zhenquan , Deng Juzhi
Published: November 2017

Accurate calculation of gas hydrate saturation is an important aspect of gas hydrate resource evaluation. The effective medium theory (EMT model), the velocity model based on two-phase medium theory (TPT model), and the two component laminated media model (TCLM model), are adopted to investigate the characteristics of acoustic velocity and gas hydrate saturation of pore- and fracture-filling reservoirs in the Qilian Mountain permafrost, China. The compressional wave (P-wave) velocity simulated by the EMT model is more consistent with actual log data than the TPT model in the pore-filling reservoir. The range of the gas hydrate saturation of the typical pore-filling reservoir in hole DKXX-13 is 13.0~85.0%, and the average value of the gas hydrate saturation is 61.9%, which is in accordance with the results by the standard Archie equation and actual core test. The P-wave phase velocity simulated by the TCLM model can be transformed directly into the P-wave transverse velocity in a fracture-filling reservoir. The range of the gas hydrate saturation of the typical fracture-filling reservoir in hole DKXX-19 is 14.1~89.9%, and the average value of the gas hydrate saturation is 69.4%, which is in accordance with actual core test results.
Preparation of ZnSO4·7H2O using filter cake enriched in calcium and magnesium from the process of zinc hydrometallurgy
Authors: Li Bo , Wang Xuanbing , Wei Yonggang , Wang Hua , Hu Guanglai
Published: November 2017

ZnSO4∙7H2O was prepared using a filter cake enriched in calcium and magnesium that was generated during the process of zinc hydrometallurgy. The study was optimized to obtain process parameters. The results show that the optimal acid leaching parameters are a solid-to-liquid ratio of 1:3.5, a sulfuric acid concentration of 16%, an acid leaching time of 20 min, a final pH of 4.1–4.4, a cooling and settling time of 120 min, an oxidation time of 20 min, a stirring speed of 300 r/min, a H2O2 dosage of 25 mL/L, a crystallization temperature of 20 °C, and a crystallization time of 60 min. The ZnSO4∙7H2O content in the product is 98.6%, and the zinc recovery efficiency is 97.5%. This process is characterized by simple flow and low cost, while the circulation and accumulation problems with calcium and magnesium ions in the zinc hydrometallurgy process are also solved.
Identification of novel factors enhancing recombinant protein production in multi-copy Komagataella phaffii based on transcriptomic analysis of overexpression effects
Authors: Yu Xiao-Wei , Sun Wei-Hong , Wang Ying-Zheng , Xu Yan
Published: November 2017

The methylotrophic yeast Komagataella phaffii (Pichia pastoris) has been developed into a highly successful system for heterologous protein expression in both academia and industry. However, overexpression of recombinant protein often leads to severe burden on the physiology of K. phaffii and triggers cellular stress. To elucidate the global effect of protein overexpression, we set out to analyze the differential transcriptome of recombinant strains with 12 copies and a single copy of phospholipase A2 gene (PLA2) from Streptomyces violaceoruber. Through GO, KEGG and heat map analysis of significantly differentially expressed genes, the results indicated that the 12-copy strain suffered heavy cellular stress. The genes involved in protein processing and stress response were significantly upregulated due to the burden of protein folding and secretion, while the genes in ribosome and DNA replication were significantly downregulated possibly contributing to the reduced cell growth rate under protein overexpression stress. Three most upregulated heat shock response genes (CPR6, FES1, and STI1) were co-overexpressed in K. phaffii and proved their positive effect on the secretion of reporter enzymes (PLA2 and prolyl endopeptidase) by increasing the production up to 1.41-fold, providing novel helper factors for rational engineering of K. phaffii.
A pH-induced conformational switch in a tyrosine kinase inhibitor identified by electronic spectroscopy and quantum chemical calculations
Authors: Khattab Muhammad , Wang Feng , Clayton Andrew H. A.
Published: November 2017

Tyrosine kinase inhibitors (TKIs) are a major class of drug utilised in the clinic. During transit to their cognate kinases, TKIs will encounter different pH environments that could have a major influence on TKI structure. To address this, we report UV-Vis spectroscopic and computational studies of the TKI, AG1478, as a function of pH. The electronic absorption spectrum of AG1478 shifted by 10 nm (from 342 nm to 332 nm) from acid to neutral pH and split into two peaks (at 334 nm and 345 nm) in highly alkaline conditions. From these transitions, the pKa value was calculated as 5.58 ± 0.01. To compute structures and spectra, time-dependent density functional theory (TD-DFT) calculations were performed along with conductor-like polarizable continuum model (CPCM) to account for implicit solvent effect. On the basis of the theoretical spectra, we could assign the AG1478 experimental spectrum at acidic pH to a mixture of two twisted conformers (71% AG1478 protonated at quinazolyl nitrogen N(1) and 29% AG1478 protonated at quinazolyl nitrogen N(3)) and at neutral pH to the neutral planar conformer. The AG1478 absorption spectrum (pH 13.3) was fitted to a mixture of neutral (70%) and NH-deprotonated species (30%). These studies reveal a pH-induced conformational transition in a TKI.