bluuebunny/crossref_metadata_2025 huggingface dataset:
Weed Control with Non-Selective Herbicides in Soybean (Glycine max) Stale Seedbed Culture
Authors: Lanie Andrew J. , Griffin James L. , Vidrine P. Roy , Reynolds Daniel B.
Published: January 2018

Barnyardgrass and morningglory control POST with glufosinate at 840 g a.i./ha 28 d after treatment was 79 to 85% and 83 to 90%, respectively, when no more than 35 d elapsed between initial spring soil tillage and herbicide application. For the same rate of glufosinate, prickly sida and hemp sesbania were controlled 68 and 92%, respectively. Comparable barnyardgrass control was obtained with glufosinate at 560 and 840 g/ha, which was greater than at 420 g/ha. Hemp sesbania control was similar for all rates of glufosinate. In comparison, paraquat at 1050 g a.i./ha controlled 40 to 65% barnyardgrass, 44 to 75% morningglory, 41% prickly sida, and 92% hemp sesbania. With 840 g a.i./ha glyphosate and SC-0224, barnyardgrass, morningglory, prickly sida, and hemp sesbania were controlled 55 to 89%, 55 to 81%, 45 to 61%, and 56 to 68%, respectively. Soybean yield was 5.8, 7.6, 6.0, and 5.9 times greater than the nontreated check for 1050 g/ha paraquat and 840 g/ha glufosinate, glyphosate, and SC-0224, respectively.
Friedlander–Keller ray expansions and scalar wave reflection at canonically perturbed boundaries
Authors: TEW R.H.
Published: January 2018

This paper concerns the reflection of high-frequency, monochromatic linear waves of wavenumber k(≫ 1) from smooth boundaries which are O(k−1/2) perturbations away from either a specified near-planar boundary or else from a given smooth, two-dimensional curve of general O(1) curvature. For each class of perturbed boundary, we will consider separately plane and cylindrical wave incidence, with general amplitude profiles of each type of incident field. This interfacial perturbation scaling is canonical in the sense that a ray approach requires a modification to the standard WKBJ ‘ray ansatz’ which, in turn, leads to a leading-order amplitude (or ‘transport’) equation which includes an extra term absent in a standard application of the geometrical theory of diffraction. This extra term is unique to this scaling, and the afore-mentioned modification that is required is an application of a generalised type of ray expansion first posed by F. G. Friedlander and J. B. Keller (1955 Commun. Pure Appl. Math.6, 387–394).
Erythromelalgia
Authors: Klein-Weigel Peter Franz , Volz Theresa Sophie , Richter Jutta Gisela
Published: January 2018

Abstract. Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning. Between the pain episodes, the affected skin areas are usually asymptomatic, but there are patients with typical features of acrocyanosis and/or Raynaud’s phenomenon preceding or occurring in between the episodes of erythromelalgia. Diagnosis is made by ascertaining the typical clinical features. Thereafter, the differentiation between primary and secondary forms should be made. Genetic testing is recommended, especially in premature cases and in cases of family clustering in specialized genetic institutions after genetic counselling. Multimodal therapeutic intervention aims toward attenuation of pain and improvement of the patient’s quality of life. For this purpose, a wide variety of nonpharmacological approaches and pharmacological substances for topical and systemic use have been proposed, which are usually applied individually in a step-by-step approach. Prognosis mainly depends on the underlying condition and the ability of the patients and their relatives to cope with the disease.

Keywords: Erythromelalgia, erythermalgia, genetic pain syndrome, vascular acrosyndrome, chronic pain syndrome, small fibre polyneuropathy
The fungus that came in from the cold: dry rot’s pre-adapted ability to invade buildings
Authors: Balasundaram S V , Hess J , Durling M B , Moody S C , Thorbek L , Progida C , LaButti K , Aerts A , Barry K , Grigoriev I V , Boddy L , Högberg N , Kauserud H , Eastwood D C , Skrede I
Published: January 2018

Many organisms benefit from being pre-adapted to niches shaped by human activity, and have successfully invaded man-made habitats. One such species is the dry rot fungus Serpula lacrymans, which has a wide distribution in buildings in temperate and boreal regions, where it decomposes coniferous construction wood. Comparative genomic analyses and growth experiments using this species and its wild relatives revealed that S. lacrymans evolved a very effective brown rot decay compared to its wild relatives, enabling an extremely rapid decay in buildings under suitable conditions. Adaptations in intracellular transport machineries promoting hyphal growth, and nutrient and water transport may explain why it is has become a successful invader of timber in houses. Further, we demonstrate that S. lacrymans has poor combative ability in our experimental setup, compared to other brown rot fungi. In sheltered indoor conditions, the dry rot fungus may have limited encounters with other wood decay fungi compared to its wild relatives. Overall, our analyses indicate that the dry rot fungus is an ecological specialist with poor combative ability against other fungi.
Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway
Authors: Li Jianshuang , Lu Di , Dou Hong , Liu Huadie , Weaver Kevin , Wang Wenjun , Li Jiada , Yeh Edward T.H. , Williams Bart O. , Zheng Ling , Yang Tao
Published: January 2018

The development, growth, and renewal of skeletal tissues rely on the function of osteochondroprogenitors (OCPs). Protein sumoylation/desumoylation has emerged as a pivotal mechanism for stem cell/progenitor homeostasis, and excessive sumoylation has been associated with cell senescence and tissue aging, but its role in regulating OCP function is unclear. Here we show that postnatal loss of the desumoylase SUMO1/sentrin-specific peptidase 6 (SENP6) causes premature aging. OCP-specific SENP6 knockout mice exhibit smaller skeletons, with elevated apoptosis and cell senescence in OCPs and chondrocytes. In Senp6
‒/‒
cells, the two most significantly elevated pathways are p53 signaling and senescence-associated secreted phenotypes (SASP), and Trp53 loss partially rescues the skeletal and cellular phenotypes caused by Senp6 loss. Furthermore, SENP6 interacts with, desumoylates, and stabilizes TRIM28, suppressing p53 activity. Our data reveals a crucial role of the SENP6–p53 axis in maintaining OCP homeostasis during skeletal development.
Ancient environmental DNA reveals shifts in dominant mutualisms during the late Quaternary
Authors: Zobel Martin , Davison John , Edwards Mary E. , Brochmann Christian , Coissac Eric , Taberlet Pierre , Willerslev Eske , Moora Mari
Published: January 2018

DNA-based snapshots of ancient vegetation have shown that the composition of high-latitude plant communities changed considerably during the late Quaternary. However, parallel changes in biotic interactions remain largely uninvestigated. Here we show how mutualisms involving plants and heterotrophic organisms varied during the last 50,000 years. During 50–25 ka BP, a cool period featuring stadial-interstadial fluctuations, arbuscular mycorrhizal and non-N-fixing plants predominated. During 25-15 ka BP, a cold, dry interval, the representation of ectomycorrhizal, non-mycorrhizal and facultatively mycorrhizal plants increased, while that of N-fixing plants decreased further. From 15 ka BP, which marks the transition to and establishment of the Holocene interglaciation, representation of arbuscular mycorrhizal plants decreased further, while that of ectomycorrhizal, non-mycorrhizal, N-fixing and wind-pollinated plants increased. These changes in the mutualist trait structure of vegetation may reflect responses to historical environmental conditions that are without current analogue, or biogeographic processes, such as spatial decoupling of mutualist partners.
Maturation of the gut microbiome and risk of asthma in childhood
Authors: Stokholm Jakob , Blaser Martin J. , Thorsen Jonathan , Rasmussen Morten A. , Waage Johannes , Vinding Rebecca K. , Schoos Ann-Marie M. , Kunøe Asja , Fink Nadia R. , Chawes Bo L. , Bønnelykke Klaus , Brejnrod Asker D. , Mortensen Martin S. , Al-Soud Waleed Abu , Sørensen Søren J. , Bisgaard Hans
Published: January 2018

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.
Understanding the physical metallurgy of the CoCrFeMnNi high-entropy alloy: an atomistic simulation study
Authors: Choi Won-Mi , Jo Yong Hee , Sohn Seok Su , Lee Sunghak , Lee Byeong-Joo
Published: January 2018

Although high-entropy alloys (HEAs) are attracting interest, the physical metallurgical mechanisms related to their properties have mostly not been clarified, and this limits wider industrial applications, in addition to the high alloy costs. We clarify the physical metallurgical reasons for the materials phenomena (sluggish diffusion and micro-twining at cryogenic temperatures) and investigate the effect of individual elements on solid solution hardening for the equiatomic CoCrFeMnNi HEA based on atomistic simulations (Monte Carlo, molecular dynamics and molecular statics). A significant number of stable vacant lattice sites with high migration energy barriers exists and is thought to cause the sluggish diffusion. We predict that the hexagonal close-packed (hcp) structure is more stable than the face-centered cubic (fcc) structure at 0 K, which we propose as the fundamental reason for the micro-twinning at cryogenic temperatures. The alloying effect on the critical resolved shear stress (CRSS) is well predicted by the atomistic simulation, used for a design of non-equiatomic fcc HEAs with improved strength, and is experimentally verified. This study demonstrates the applicability of the proposed atomistic approach combined with a thermodynamic calculation technique to a computational design of advanced HEAs.
High resolution NanoSIMS imaging of deuterium distributions in 316 stainless steel specimens after fatigue testing in high pressure deuterium environment
Authors: McMahon Greg , Miller Bryan D. , Burke M. Grace
Published: January 2018

It is irrefutable that the presence of hydrogen reduces the mechanical performance of many metals and alloys used for structural components. Several mechanisms of hydrogen-assisted cracking (HAC) of steels have been postulated. The direct evidence of the mechanisms by which hydrogen embrittles these materials has remained elusive. This is by virtue of our difficulty to directly observe the hydrogen distribution at spatial resolutions less than 100 nm and analysis volumes greater than 1 × 109atoms at microstructural features such as grain boundaries, dislocations, twins, stacking faults and sub-micron inclusions that are all potential hydrogen trapping sites postulated to be responsible for the degradation of mechanical performance. Here, we report on an experimental methodology combining an elaborate fatigue testing protocol in an enriched gaseous deuterium environment with NanoSIMS (secondary ion mass spectrometry) imaging for detection of deuterium at spatial resolutions as low as 100 nm and accompanying TEM analysis. Type 316 stainless steel compact tension specimens were precharged in deuterium followed by fatigue testing at high stress ratio (0.7), low delta K (~11 MPa √m), and a frequency of 1 cycle per minute using a sawtooth waveform with a rise time of 30 s in high pressure (68.9 MPa) gaseous deuterium (99.999% purity) environment at room temperature. High resolution NanoSIMS imaging was then used to measure the deuterium distribution at the tip of and in the wake of secondary and tertiary fatigue cracks as well as at MnS inclusions. The use of deuterium eliminates the difficulties of interpreting hydrogen measurements by SIMS relating to the ubiquitous presence of hydrogen in all high vacuum systems and guarantees that deuterium measured by the NanoSIMS must be attributed to the fatigue testing protocol. This methodology has allowed us to directly observe the distribution of hydrogen in dislocation tangles ahead and in the wake of fatigue crack tips and at the interface of MnS inclusions. The protocol provides an avenue by which the path and speed with which hydrogen proceeds along its embrittling course of action may be directly followed through modifications of the fatigue testing parameters and/or alloy type and allows a means to validate at least qualitatively recently published models of enhanced hydrogen transport by dislocations.
Mechanisms of interactive specialization and emergence of functional brain circuits supporting cognitive development in children
Authors: Battista Christian , Evans Tanya M. , Ngoon Tricia J. , Chen Tianwen , Chen Lang , Kochalka John , Menon Vinod
Published: January 2018

Cognitive development is thought to depend on the refinement and specialization of functional circuits over time, yet little is known about how this process unfolds over the course of childhood. Here we investigated growth trajectories of functional brain circuits and tested an interactive specialization model of neurocognitive development which posits that the refinement of task-related functional networks is driven by a shared history of co-activation between cortical regions. We tested this model in a longitudinal cohort of 30 children with behavioral and task-related functional brain imaging data at multiple time points spanning childhood and adolescence, focusing on the maturation of parietal circuits associated with numerical problem solving and learning. Hierarchical linear modeling revealed selective strengthening as well as weakening of functional brain circuits. Connectivity between parietal and prefrontal cortex decreased over time, while connectivity within posterior brain regions, including intra-hemispheric and inter-hemispheric parietal connectivity, as well as parietal connectivity with ventral temporal occipital cortex regions implicated in quantity manipulation and numerical symbol recognition, increased over time. Our study provides insights into the longitudinal maturation of functional circuits in the human brain and the mechanisms by which interactive specialization shapes children’s cognitive development and learning.
The Role Of Parafacial Neurons In The Control Of Breathing During Exercise
Authors: Korsak Alla , Sheikhbahaei Shahriar , Machhada Asif , Gourine Alexander V. , Huckstepp Robert T. R
Published: January 2018

Neuronal cell groups residing within the retrotrapezoid nucleus (RTN) and C1 area of the rostral ventrolateral medulla oblongata contribute to the maintenance of resting respiratory activity and arterial blood pressure, and play an important role in the development of cardiorespiratory responses to metabolic challenges (such as hypercapnia and hypoxia). In rats, acute silencing of neurons within the parafacial region which includes the RTN and the rostral aspect of the C1 circuit (pFRTN/C1), transduced to express HM4D (Gi-coupled) receptors, was found to dramatically reduce exercise capacity (by 60%), determined by an intensity controlled treadmill running test. In a model of simulated exercise (electrical stimulation of the sciatic or femoral nerve in urethane anaesthetised spontaneously breathing rats) silencing of the pFRTN/C1 neurons had no effect on cardiovascular changes, but significantly reduced the respiratory response during steady state exercise. These results identify a neuronal cell group in the lower brainstem which is critically important for the development of the respiratory response to exercise and, determines exercise capacity.
Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG
Authors: Huang Yibo , Higuchi Yujiro , Kinoshita Takashi , Mitani Ai , Eshima Yasunari , Takegawa Kaoru
Published: January 2018

Endo-β-N-acetylglucosaminidase (ENGase) catalyzes hydrolysis of N-linked oligosaccharides. Although many ENGases have been characterized from various organisms, so far no fucose-containing oligosaccharides-specific ENGase has been identified in any organism. Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis. By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain. Among them, a recombinant protein purified from Escherichia coli expressing the candidate gene ORF1188 exhibited fucose-containing oligosaccharides-specific ENGase activity. The ENGase exhibited optimum activities at very acidic pHs (between pH 2.3–2.5). A BLAST search using the sequence of ORF1188 identified two fungal homologs, one in Beauveria bassiana and the other in Cordyceps militaris. Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
Multi-label Deep Learning for Gene Function Annotation in Cancer Pathways
Authors: Guan Renchu , Wang Xu , Yang Mary Qu , Zhang Yu , Zhou Fengfeng , Yang Chen , Liang Yanchun
Published: January 2018

The war on cancer is progressing globally but slowly as researchers around the world continue to seek and discover more innovative and effective ways of curing this catastrophic disease. Organizing biological information, representing it, and making it accessible, or biocuration, is an important aspect of biomedical research and discovery. However, because maintaining sophisticated biocuration is highly resource dependent, it continues to lag behind the continually being generated biomedical data. Another critical aspect of cancer research, pathway analysis, has proven to be an efficient method for gaining insight into the underlying biology associated with cancer. We propose a deep-learning-based model, Stacked Denoising Autoencoder Multi-Label Learning (SdaMLL), for facilitating gene multi-function discovery and pathway completion. SdaMLL can capture intermediate representations robust to partial corruption of the input pattern and generate low-dimensional codes superior to conditional dimension reduction tools. Experimental results indicate that SdaMLL outperforms existing classical multi-label algorithms. Moreover, we found some gene functions, such as Fused in Sarcoma (FUS, which may be part of transcriptional misregulation in cancer) and p27 (which we expect will become a member viral carcinogenesis), that can be used to complete the related pathways. We provide a visual tool (https://www.keaml.cn/gpvisual) to view the new gene functions in cancer pathways.
Publisher Correction: Acute Psychological Stress Disrupts Attentional Bias to Threat-Related Stimuli
Authors: Jiang Caihong , Buchanan Tony W. , Yao Zhuxi , Zhang Kan , Wu Jianhui , Zhang Liang
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Publisher Correction: Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain
Authors: Anderson Christopher S. , Ortega Sandra , Chaves Francisco A. , Clark Amelia M. , Yang Hongmei , Topham David J. , DeDiego Marta L.
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Publisher Correction: Paracrine interactions between mesenchymal stem cells and macrophages are regulated by 1,25-dihydroxyvitamin D3
Authors: Saldaña Laura , Vallés Gema , Bensiamar Fátima , Mancebo Francisco José , García-Rey Eduardo , Vilaboa Nuria
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids
Authors: Wammers Marianne , Schupp Anna-Kathrin , Bode Johannes G. , Ehlting Christian , Wolf Stephanie , Deenen René , Köhrer Karl , Häussinger Dieter , Graf Dirk
Published: January 2018

Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affectinglipopolysaccharide(LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such astaurolithocholic acid(TLC), on the transcriptome of human macrophages in the presence or absence of LPS. While TLC itself has almost no effect on gene expression under control conditions, this compound modulates the expression of 202 out of 865 transcripts in the presence of LPS. Interestingly, pathway analysis revealed that TLC specifically supressed the expression of genes involved in mediating pro-inflammatory effects, phagocytosis, interactions with pathogens and autophagy as well as the recruitment of immune cells, such as NK cells, neutrophils and T cells. These data indicate a broad influence of bile acids on inflammatory responses and immune functions in macrophages. These findings may contribute to the clinical observation that patients with cholestasis present a lack of response to bacterial or viral infections.
Mitochondrial network complexity emerges from fission/fusion dynamics
Authors: Zamponi Nahuel , Zamponi Emiliano , Cannas Sergio A. , Billoni Orlando V. , Helguera Pablo R. , Chialvo Dante R.
Published: January 2018

Mitochondrial networks exhibit a variety of complex behaviors, including coordinated cell-wide oscillations of energy states as well as a phase transition (depolarization) in response to oxidative stress. Since functional and structural properties are often interwinded, here we characterized the structure of mitochondrial networks in mouse embryonic fibroblasts using network tools and percolation theory. Subsequently we perturbed the system either by promoting the fusion of mitochondrial segments or by inducing mitochondrial fission. Quantitative analysis of mitochondrial clusters revealed that structural parameters of healthy mitochondria laid in between the extremes of highly fragmented and completely fusioned networks. We confirmed our results by contrasting our empirical findings with the predictions of a recently described computational model of mitochondrial network emergence based on fission-fusion kinetics. Altogether these results offer not only an objective methodology to parametrize the complexity of this organelle but also support the idea that mitochondrial networks behave as critical systems and undergo structural phase transitions.
A Gaussian extension for Diffraction Enhanced Imaging
Authors: Arfelli Fulvia , Astolfo Alberto , Rigon Luigi , Menk Ralf Hendrik
Published: January 2018

Unlike conventional x-ray attenuation one of the advantages of phase contrast x-ray imaging is its capability of extracting useful physical properties of the sample. In particular the possibility to obtain information from small angle scattering about unresolvable structures with sub-pixel resolution sensitivity has drawn attention for both medical and material science applications. We report on a novel algorithm for the analyzer based x-ray phase contrast imaging modality, which allows the robust separation of absorption, refraction and scattering effects from three measured x-ray images. This analytical approach is based on a simple Gaussian description of the analyzer transmission function and this method is capable of retrieving refraction and small angle scattering angles in the full angular range typical of biological samples. After a validation of the algorithm with a simulation code, which demonstrated the potential of this highly sensitive method, we have applied this theoretical framework to experimental data on a phantom and biological tissues obtained with synchrotron radiation. Owing to its extended angular acceptance range the algorithm allows precise assessment of local scattering distributions at biocompatible radiation doses, which in turn might yield a quantitative characterization tool with sufficient structural sensitivity on a submicron length scale.
Tribological Properties of Ultrananocrystalline Diamond Films: Mechanochemical Transformation of Sliding Interfaces
Authors: Rani Revati , Panda Kalpataru , Kumar Niranjan , Titovich Kozakov Alexey , Ivanovich Kolesnikov Vladimir , Vyacheslavovich Sidashov Andrey , Lin I-Nan
Published: January 2018

Improving the tribological properties of materials in ambient and high vacuum tribo-conditions is useful for inter-atmospheric applications. Highly-hydrogenated and less-hydrogenated ultrananocrystalline diamond (UNCD) films with distinct microstructural characteristics were deposited on Ti–6Al–4 V alloy, by optimizing the plasma conditions in the chemical vapor deposition. Both the UNCD films showed less friction coefficient in ambient atmospheric tribo-contact conditions due to the passivation. This provides chemical stability to UNCD films under the tribo-mechanical stressed conditions which limits the transferlayer formation and conversion of UNCD phase into graphitization/amorphization. However, in the high vacuum tribo-conditions, highly-hydrogenated UNCD films showed low friction value which gradually increased to the higher magnitude at longer sliding cycles. The low friction coefficient was indicative of passivation provided by the hydrogen network intrinsically present in the UNCD films. It gradually desorbs and the dangling bonds are progressively activated in the contact regime, leading to a gradual increase in the friction value. In contrast, less-hydrogenated UNCD films do not exhibit low friction regime in high vacuum conditions due to the lack of internal passivation. In this case, the conversion of UNCD to amorphized carbon structure in the wear tracks and amorphous carbon (a-C) tribofilm formation on ball scars were observed.
Xeno-free pre-vascularized spheroids for therapeutic applications
Authors: Bauman E. , Feijão T. , Carvalho D. T. O. , Granja P. L. , Barrias C. C.
Published: January 2018

Spheroid culture has gained increasing popularity, arising as a promising tool for regenerative medicine applications. Importantly, spheroids may present advantages over single-cell suspensions in cell-based therapies (CT). Unfortunately, most growth media used for spheroid culture contain animal origin-components, such as fetal bovine serum (FBS). The presence of FBS compromises the safety of CT and presents economic and ethical constraints. SCC (supplement for cell culture) is a novel xeno-free (XF) industrial cell culture supplement, derived from well-controlled pooled human plasma and processed under good manufacturing practice rules. Here, we developed a XF SCC-based formulation for 2D-culture of outgrowth endothelial cells (OEC), and then used it for generating co-culture spheroids of OEC and mesenchymal stem cells (MSC). XF MSC-OEC spheroids were characterized in detail and compared to spheroids cultured in FBS-supplemented medium. XF spheroids presented comparable integrity, size and morphology as the reference culture. The use of both media resulted in spheroids with similar structure, abundant extracellular matrix deposition and specific patterns of OEC distribution and organization. Notably, XF spheroids presented significantly enhanced angiogenic potential, both in vitro (fibrin sprouting assay) and in vivo (CAM assay). These findings are particularly promising in the context of potential therapeutic applications.
Probing the molecular basis of hERG drug block with unnatural amino acids
Authors: Macdonald Logan C. , Kim Robin Y. , Kurata Harley T. , Fedida David
Published: January 2018

Repolarization of the cardiac action potential is primarily mediated by two voltage-dependent potassium currents:IKrandIKs. The voltage-gated potassium channel that gives rise toIKr, Kv11.1 (hERG), is uniquely susceptible to high-affinity block by a wide range of drug classes. Pore residues Tyr652 and Phe656 are critical to potent drug interaction with hERG. It is considered that the molecular basis of this broad-spectrum drug block phenomenon occurs through interactions specific to the aromatic nature of the side chains at Tyr652 and Phe656. In this study, we used nonsense suppression to incorporate singly and doubly fluorinated phenylalanine residues at Tyr652 and Phe656 to assess cation-π interactions in hERG terfenadine, quinidine, and dofetilide block. Incorporation of these unnatural amino acids was achieved with minimal alteration to channel activation or inactivation gating. Our assessment of terfenadine, quinidine, and dofetilide block did not reveal evidence of a cation-π interaction at either aromatic residue, but, interestingly, shows that certain fluoro-Phe substitutions at position 652 result in weaker  drug potency.
Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis
Authors: Koseki Jun , Konno Masamitsu , Asai Ayumu , Colvin Hugh , Kawamoto Koichi , Nishida Naohiro , Sakai Daisuke , Kudo Toshihiro , Satoh Taroh , Doki Yuichiro , Mori Masaki , Ishii Hideshi
Published: January 2018

The significance of mitochondrial metabolism in cancer cells has recently been gaining attention. Among other findings, One-carbon folate metabolism has been reported to be closely associated with cellular characteristics in cancer. To study molecular targets for efficient cancer therapy, we investigated the association between the expressions of genes that code enzymes involved in one-carbon metabolism and survival rate of patients with adenocarcinomas of the colorectum and lung. Patients with high expression of genes that control the metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and ALDH1L2, have a shorter overall survival rate compared with patients with low expression of these genes. Our results revealed that these genes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism, suggesting the rationale of drug discovery in cancer medicine.
A new macrofaunal limit in the deep biosphere revealed by extreme burrow depths in ancient sediments
Authors: Cobain S. L. , Hodgson D. M. , Peakall J. , Wignall P. B. , Cobain M. R. D.
Published: January 2018

Macrofauna is known to inhabit the top few 10s cm of marine sediments, with rare burrows up to two metres below the seabed. Here, we provide evidence from deep-water Permian strata for a previously unrecognised habitat up to at least 8 metres below the sediment-water interface. Infaunal organisms exploited networks of forcibly injected sand below the seabed, forming living traces and reworking sediment. This is the first record that shows sediment injections are responsible for hosting macrofaunal life metres below the contemporaneous seabed. In addition, given the widespread occurrence of thick sandy successions that accumulate in deep-water settings, macrofauna living in the deep biosphere are likely much more prevalent than considered previously. These findings should influence future sampling strategies to better constrain the depth range of infaunal animals living in modern deep-sea sands. One Sentence Summary: The living depth of infaunal macrofauna is shown to reach at least 8 metres in new habitats associated with sand injections.
Estimating the capacity for production of formamide by radioactive minerals on the prebiotic Earth
Authors: Adam Zachary R. , Hongo Yayoi , Cleaves H. James , Yi Ruiqin , Fahrenbach Albert C. , Yoda Isao , Aono Masashi
Published: January 2018

Water creates special problems for prebiotic chemistry, as it is thermodynamically favorable for amide and phosphodiester bonds to hydrolyze. The availability of alternative solvents with more favorable properties for the formation of prebiotic molecules on the early Earth may have helped bypass this so-called “water paradox”. Formamide (FA) is one such solvent, and can serve as a nucleobase precursor, but it is difficult to envision how FA could have been generated in large quantities or accumulated in terrestrial surface environments. We report here the conversion of aqueous acetonitrile (ACN) via hydrogen cyanide (HCN) as an intermediate into FA by γ-irradiation under conditions mimicking exposure to radioactive minerals. We estimate that a radioactive placer deposit could produce 0.1‒0.8 mol FA km−2 year−1. A uraninite fission zone comparable to the Oklo reactors in Gabon can produce 0.1‒1 mol m−2 year−1, orders of magnitude greater than other scenarios of FA production or delivery for which reaching sizeable concentrations of FA are problematic. Radioactive mineral deposits may be favorable settings for prebiotic compound formation through emergent geologic processes and FA-mediated organic chemistry.
Extracellular Total Electrolyte Concentration Imaging for Electrical Brain Stimulation (EBS)
Authors: Sajib Saurav Z. K. , Lee Mun Bae , Kim Hyung Joong , Woo Eung Je , Kwon Oh In
Published: January 2018

Techniques for electrical brain stimulation (EBS), in which weak electrical stimulation is applied to the brain, have been extensively studied in various therapeutic brain functional applications. The extracellular fluid in the brain is a complex electrolyte that is composed of different types of ions, such as sodium (Na+), potassium (K+), and calcium (Ca+). Abnormal levels of electrolytes can cause a variety of pathological disorders. In this paper, we present a novel technique to visualize the total electrolyte concentration in the extracellular compartment of biological tissues. The electrical conductivity of biological tissues can be expressed as a product of the concentration and the mobility of the ions. Magnetic resonance electrical impedance tomography (MREIT) investigates the electrical properties in a region of interest (ROI) at low frequencies (below 1 kHz) by injecting currents into the brain region. Combining with diffusion tensor MRI (DT-MRI), we analyze the relation between the concentration of ions and the electrical properties extracted from the magnetic flux density measurements using the MREIT technique. By measuring the magnetic flux density induced by EBS, we propose a fast non-iterative technique to visualize the total extracellular electrolyte concentration (EEC), which is a fundamental component of the conductivity. The proposed technique directly recovers the total EEC distribution associated with the water transport mobility tensor.
Thrombospondin-1 secreted by human umbilical cord blood-derived mesenchymal stem cells rescues neurons from synaptic dysfunction in Alzheimer’s disease model
Authors: Kim Dong Hyun , Lim Hoon , Lee Dahm , Choi Soo Jin , Oh Wonil , Yang Yoon Sun , Oh Jeong Su , Hwang Hyun Ho , Jeon Hong Bae
Published: January 2018

Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs’ secretome co-cultured with Aβ42-treated mouse hippocampal neurons. Thrombospondin-1 (TSP-1), a protein secreted by hUCB-MSCs in in vitro and 5XFAD AD mouse models, was selected for study. Treatment with exogenous recombinant TSP-1 or co-cultures with hUCB-MSCs significantly increased expression of synaptic-density markers, such as synaptophysin (SYP) and post-synaptic density protein-95 (PSD-95) in Aβ42-treated mouse hippocampal neurons. Knockdown of TSP-1 expression in hUCB-MSCs through small interfering RNA (siRNA) abolished the reversal of Aβ42-induced hippocampal synaptic-density loss. We demonstrate that the rescue effect of hUCB-MSC-secreted TSP-1 was mediated by neuroligin-1 (NLGN1) or α2δ-1 receptors. Interestingly, NLGN1 and α2δ-1 expression, which was reduced in Aβ42-treated hippocampal neurons, increased in co-cultures with hUCB-MSCs or exogenous TSP-1. Together, these findings suggest that hUCB-MSCs can attenuate Aβ42-induced synaptic dysfunction by regulating TSP-1 release, thus providing a potential alternative therapeutic option for early-stage AD.
Tumor suppressor activity of miR-451: Identification of CARF as a new target
Authors: Li Ling , Gao Ran , Yu Yue , Kaul Zeenia , Wang Jia , Kalra Rajkumar S. , Zhang Zhenya , Kaul Sunil C. , Wadhwa Renu
Published: January 2018

microRNAs (miRs) have recently emerged as small non-coding regulators of gene expression. We performed a loss-of-function screening by recruiting retrovirus mediated arbitrary manipulation of genome coupled with escape of cells from 5-Aza-2′-deoxycytidine (5-Aza-dC)-induced senescence. miRNA pool from cells that emerged from 5-Aza-dC-induced senescence was subjected to miR-microarray analysis with respect to the untreated control. We identified miR-451 as one of the upregulated miRs and characterized its functional relevance to drug resistance, cell growth, tumor suppressor proteins p53 and pRb, and stress response. We report that miR-451 caused growth arrest in cells leading to their resistance to 5-Aza-dC-induced senescence. Decrease in cyclin D1, CDK4 and phosphorylated pRB supported the growth arrest in miR-451 transfected cells. We demonstrate that Collaborator of ARF (CARF) protein is a new target of miR-451 that intermediates its function in tumor suppressor and stress signaling.
Role of cobalt cations in short range antiferromagnetic Co3O4 nanoparticles: a thermal treatment approach to affecting phonon and magnetic properties
Authors: Gawali Swati R. , Gandhi Ashish Chhaganlal , Gaikwad Shrikrushna Shivaji , Pant Jayashree , Chan Ting-Shan , Cheng Chia-Liang , Ma Yuan-Ron , Wu Sheng Yun
Published: January 2018

We report the phonon and magnetic properties of various well-stabilized Co3O4 nanoparticles. The net valence in cobalt (II)/(III) cation can be obtained by subtracting the Co2+ ions in tetrahedral interstices and Co3+ ions in the octahedral interstices, respectively, which will possess spatial inhomogeneity of its magnetic moment via Co2+ in tetrahedra and Co3+ in octahedral configurations in the normal spinel structure. Furthermore, the distribution of Co2+/Co3+ governed by various external (magnetic field and temperature) and internal (particle size and slightly distorted CoO6 octahedra) sources, have led to phenomena such as a large redshift of phonon-phonon interaction and short-range magnetic correlation in the inverse spinel structure. The outcome of our study is important in terms of the future development of magnetic semiconductor spintronic devices of Co3O4.
Fis is a global regulator critical for modulation of virulence factor production and pathogenicity of Dickeya zeae
Authors: Lv Mingfa , Chen Yufan , Liao Lisheng , Liang Zhibin , Shi Zurong , Tang Yingxin , Ye Sixuan , Zhou Jianuan , Zhang Lianhui
Published: January 2018

Dickeya zeaeis the causal agent of rice foot rot disease, which has recently become a great threat to rice planting countries and regions. The pathogen produces a family of phytotoxins named zeamines that is critical for bacterial virulence, but little is known about the signaling pathways and regulatory mechanisms that govern zeamine production. In this study, we showed that a conserved transcriptional regulator Fis is involved in the regulation of zeamine production inD. zeaestrain EC1. Deletion mutants were markedly attenuated in the virulence against rice seed germination. Transcriptome and phenotype analyses showed that Fis is a potent global transcriptional regulator modulating various virulence traits, including production of extracellular enzymes and exopolysaccharides, swimming and swarming motility, biofilm formation and cell aggregation. DNA gel retardation analysis showed that Fis directly regulates the transcription of key virulence genes and the genes encoding Vfm quorum sensing system through DNA/protein interaction. Our findings unveil a key regulator associated with the virulence ofD. zeaeEC1, and present useful clues for further elucidation of the regulatory complex and signaling pathways which govern the virulence of this important pathogen.
Room temperature stable film formation of π-conjugated organic molecules on 3d magnetic substrate
Authors: Inami Eiichi , Shimasaki Mikio , Yorimitsu Hideki , Yamada Toyo Kazu
Published: January 2018

An important step toward molecule-based electronics is to realize a robust and well-ordered molecular network at room temperature. To this end, one key challenge is tuning the molecule–substrate electronic interactions that influence not only the molecular selfassembly but also the stability of the resulting structures. In this study, we investigate the film formation of π-conjugated metal-free phthalocyanine molecules on a 3d-bcc-Fe(001) whisker substrate at 300 K by using ultra-high-vacuum scanning tunneling microscopy. On bare Fe(001), hybridization between the molecular π and the Fe(001) d-states prevents the molecular assembly, resulting in the disordered patchy structures. The second- and third-layer molecules form densely packed films, while the morphologies show clear difference. The second-layer molecules partially form p(5 × 5)-ordered films with the rectangular edges aligned along the [100] and [010] directions, while the edges of the third-layer films are rounded. Remarkably, such film morphologies are stable even at 300 K. These findings suggest that the molecular self-assembly and the resulting morphologies in the second and third layers are affected by the substrate bcc(001), despite that the Fe-d states hybridize only with the first-layer molecules. The possible mechanism is discussed with the kinetic Monte Carlo simulation.
Functional Isolation of Tumor-Initiating Cells using Microfluidic-Based Migration Identifies Phosphatidylserine Decarboxylase as a Key Regulator
Authors: Chen Yu-Chih , Humphries Brock , Brien Riley , Gibbons Anne E. , Chen Yu-Ting , Qyli Tonela , Haley Henry R. , Pirone Matthew E. , Chiang Benjamin , Xiao Annie , Cheng Yu-Heng , Luan Yi , Zhang Zhixiong , Cong Jason , Luker Kathryn E. , Luker Gary D. , Yoon Euisik
Published: January 2018

Isolation of tumor-initiating cells currently relies on markers that do not reflect essential biologic functions of these cells. We proposed to overcome this limitation by isolating tumor-initiating cells based on enhanced migration, a function tightly linked to tumor-initiating potential through epithelial-to-mesenchymal transition (EMT). We developed a high-throughput microfluidic migration platform with automated cell tracking software and facile recovery of cells for downstream functional and genetic analyses. Using this device, we isolated a small subpopulation of migratory cells with significantly greater tumor formation and metastasis in mouse models. Whole transcriptome sequencing of migratory versus non-migratory cells from two metastatic breast cancer cell lines revealed a unique set of genes as key regulators of tumor-initiating cells. We focused on phosphatidylserine decarboxylase (PISD), a gene downregulated by 8-fold in migratory cells. Breast cancer cells overexpressing PISD exhibited reduced tumor-initiating potential in a high-throughput microfluidic mammosphere device and mouse xenograft model. PISD regulated multiple aspects of mitochondria, highlighting mitochondrial functions as therapeutic targets against cancer stem cells. This research establishes not only a novel microfluidic technology for functional isolation of tumor-initiating cells regardless of cancer type, but also a new approach to identify essential regulators of these cells as targets for drug development.
Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis
Authors: Tornai Tamas , Tornai David , Sipeki Nora , Tornai Istvan , Alsulaimani Rayan , Fechner Kai , Roggenbuck Dirk , Norman Gary L. , Veres Gabor , Par Gabriella , Par Alajos , Szalay Ferenc , Lakatos Peter Laszlo , Antal-Szalmas Peter , Papp Maria
Published: January 2018

Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target.