bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Aeroplane Struts
Authors: Barling W. H. , Webb H. A.
Published: February 2017

The failure of struts under end load is due to two causes, crushing, due to direct compression, and excessive bending, due to elastic instability. In a general way we may say that the end portions of the strut tend to fail by crushing and the middle portion tends to fail by bending, but we cannot make a rule to decide where the middle portion ends and the end portions begin, because both causes are really operating simultaneously all along the strut, and we can only form a vague impression of their relative importance at various sections of the strut. A parallel strut, for instance, unless it is very short, will fail by bending at or near the middle, and the end portions will show no signs of crushing; so we may fairly infer that weight can be saved in a solid wooden strut without much loss of strength by tapering the ends; and that on the whole the efficiency of a strut, as measured by the ratio of crippling end load to weight or (resistance + m weight) where m* is a fraction, can be improved by tapering.
A Note on the “Inflow” Theory of the Airscrew
Authors: Riach M. A. S.
Published: February 2017

The following note has been written partly by way of a commentary upon Dr. H. C. Watt's recent article, in the July number of the Aëronautical Journal, entitled, “ A Note on the Theories of Screw Propulsion,” and partly by way of an explanation of the apparent inconsistency of the “inflow” theory of the airscrew.

Consider an element of a propeller blade situated at a radius of x from the boss centre of the propeller and having an angle of ϕ between the chord line of the blade section and the plane of rotation. The form of the blade section is considered to be that of an aerofoil, of which the characteristics are known from wind channel experiments upon a model of the same geometrical form (Fig. I).

We wish to apply these wind channel data to the propeller blade element with rigorous consistency, i.e., as far as the two respective régimes of the propeller and the aerofoil permit.
On the Flight of Albatrosses and Gannets
Authors: Hankin E. H.
Published: February 2017

I owe the greater part of the following information about the flight of the albatross to Captain E. H. Gordon, of the P. and O. ss. Company. He has studied these birds during numerous voyages, both on steamers and sailing ships. He has seen them near Cape Horn, the Cape, off the south coast of Australia, and at many other places.
Lehrenden- und studierenden-zentrierte Lehre messen
Authors: Wibbecke Gerald , Wibbecke Anna-Lena , Kahmann Janine , Kadmon Martina
Published: February 2017

Zusammenfassung. Es besteht ein Bedarf an wissenschaftlich geprüften Beobachtungsinstrumenten zum Lehrverhalten an Hochschulen. Diese Arbeit stellt einen Beobachtungsbogen für Lehrveranstaltungen vor (BEO-LV), der lehrenden- und studierendenzentrierte Lehrhandlungen erfassen kann. Um bei den Lehrenden die Akzeptanz für die Datenerhebungen zu erhöhen, soll dieser gleichzeitig für didaktische Rückmeldungen genutzt werden. Zur psychometrischen Überprüfung des BEO-LV werden zwei Untersuchungen dargestellt: (1) Die Beurteilendenübereinstimmung und Interraterreliabilität in Lehrveranstaltungen erwiesen sich in einer Beobachtungsstudie als zufriedenstellend. (2) Die Überprüfung der Beurteilendenübereinstimmung und der internen Validität in einer Videostudie ergab zufriedenstellende Ergebnisse für Beobachtende mit fortgeschrittenen didaktischen Kenntnissen. Die Ergebnisse zeigen, dass der BEO-LV zur Messung des Lehrverhaltens eingesetzt werden kann. Voraussetzung für gute psychometrische Ergebnisse ist eine ausführliche Einarbeitung in die operationalen Definitionen der Beobachtungsitems.
Unterrichtsstörungen aus Lehrer- und Schülersicht
Authors: Wettstein Alexander , Ramseier Erich , Scherzinger Marion , Gasser Luciano
Published: February 2017

Zusammenfassung. Unterrichtsstörungen belasten sowohl Lehrpersonen als auch Schülerinnen und Schüler. Gleichzeitig ist davon auszugehen, dass Lehrpersonen und Lernende Störungen anders wahrnehmen. Mit einem Fragebogen wurden Unterrichtsstörungen, Beziehung und Klassenführung an 83 Klassen mehrperspektivisch aus Sicht der Klassenlehrperson (N = 83), einer ausgewählten Fachlehrperson (N = 83) und der Schülerinnen und Schüler (N = 1290) erfasst. Die Daten wurden in einem Multitrait-Multimethod-Design ausgewertet. Die Ergebnisse weisen auf eine sehr hohe Reliabilität der aggregierten Schülerurteile hin. In der Einschätzung dreier Formen von Unterrichtsstörungen korrelierten die Schülerurteile im Durchschnitt zu .44 mit der Einschätzung der Klassenlehrperson und zu .54 mit der Einschätzung der Fachlehrperson. In der Einschätzung ihrer Beziehung stimmten die Lehrpersonen und Schülerinnen und Schüler nur schwach (.38 und .23), bzw. für Klassenführung (.09 und -.07) gar nicht überein. Lehrpersonen und Lernende erleben den Unterricht aus einer rollenspezifischen Subjektivität jeweils anders. Für Lehrpersonen ist es entscheidend, auch die Perspektive der Schülerinnen und Schüler einzunehmen und eigene Anteile an Störungen kritisch zu reflektieren.
Integrating Topographic Imaging into Geoscience Field Courses
Authors: Pratt-Sitaula Beth , Crosby Benjamin , Crosby Christopher
Published: February 2017

Using TLS and Structure from Motion (SfM) Photogrammetry in Undergraduate Field Education; Cardwell, Montana, 16–19 August 2016
Targeting A2 adenosine receptors in cancer
Authors: Allard David , Turcotte Martin , Stagg John
Published: February 2017

Tumor cells use various ways to evade anti‐tumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine‐generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate anti‐tumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro‐angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer. We discuss recent pre‐clinical studies and summarize the different mechanisms‐of‐action of adenosine‐targeting drugs. We also review the rationale for combining inhibitors of the adenosine pathway with other anticancer therapies such immune checkpoint inhibitors, tumor vaccines, chemotherapy and adoptive T cell therapy.
Scanning tunnelling spectroscopy as a probe of multi-Q magnetic states of itinerant magnets
Authors: Gastiasoro Maria N. , Eremin Ilya , Fernandes Rafael M. , Andersen Brian M.
Published: February 2017

The combination of electronic correlations and Fermi surfaces with multiple nesting vectors can lead to the appearance of complex multi-Q magnetic ground states, hosting unusual states such as chiral density waves and quantum Hall insulators. Distinguishing single-Q and multi-Q magnetic phases is however a notoriously difficult experimental problem. Here we propose theoretically that the local density of states (LDOS) near a magnetic impurity, whose orientation may be controlled by an external magnetic field, can be used to map out the detailed magnetic configuration of an itinerant system and distinguish unambiguously between single-Q and multi-Q phases. We demonstrate this concept by computing and contrasting the LDOS near a magnetic impurity embedded in three different magnetic ground states relevant to iron-based superconductors—one single-Q and two double-Q phases. Our results open a promising avenue to investigate the complex magnetic configurations in itinerant systems via standard scanning tunnelling spectroscopy, without requiring spin-resolved capability.
Relation between NOD2 genotype and changes in innate signaling in Crohn’s disease on mRNA and miRNA levels
Authors: Chen Yun , Salem Mohammad , Boyd Mette , Bornholdt Jette , Li Yuan , Coskun Mehmet , Seidelin Jakob Benedict , Sandelin Albin , Nielsen Ole Haagen
Published: February 2017

Crohn’s disease is associated with an altered innate immune response of pathogenic importance. This altered response can be associated to loss-of-function polymorphisms in the NOD2 (nucleotide-binding oligomerization domain-containing protein 2) gene, but also changes in transcriptional and post-transcriptional regulatory layers, including microRNA activity. Here, we characterized the link between NOD2 genotype and inflammatory-mediated changes in innate signaling by studying transcriptional and post-transcriptional activity in response to NOD2-agonist muramyl dipeptide in monocytes from healthy controls, and Crohn’s disease patients with and without NOD2 loss-of-function polymorphisms. We measured the expression of genes and microRNAs in monocytes from these subjects after stimulation with muramyl dipeptide. Gene expression profiles mainly distinguished the actual muramyl dipeptide response, but not the genotype. A hyper-responsive phenotype was found in Crohn’s disease patients without NOD2 mutations, characterized by upregulated cytokine receptors and general downregulation of microRNA expression. Conversely, microRNA expression could identify genotype-specific differences between subject groups but exhibited little change upon muramyl dipeptide treatment. Only two microRNAs showed muramyl dipeptide-induced response, including miR-155, which was found to regulate multiple genes and whose host gene was one of the highest muramyl dipeptide responders. miR-155 was upregulated in Crohn’s disease patients with NOD2 mutations following lipopolysaccharide and Escherichia coli treatment, but the upregulation was substantially reduced upon muramyl dipeptide treatment. While Crohn’s disease patients with NOD2 mutations on average showed a reduced muramyl dipeptide response, the cohort exhibited large individual variance: a small subset had inflammatory responses almost comparable to wild-type patients on both gene and miR-155 regulatory levels.
Examining brain structures associated with dispositional envy and the mediation role of emotional intelligence
Authors: Xiang Yanhui , Zhao Sasa , Wang Hanlin , Wu Qihan , Kong Feng , Mo Lei
Published: February 2017

Dispositional envy is distinguished by definition and neurally from episodic envy. While the neural correlates of episodic envy have been evaluated by specific tasks in previous studies, little is known about the structural neural basis of dispositional envy. In this study, we investigated the structural neural basis of dispositional envy underlying individual differences across two independent samples comprising a total of 100 young healthy adults. Firstly, 73 subjects’ data (sample 1) was analyzed, and we assessed the association between regional gray matter volume (rGMV) and dispositional envy using voxel-based morphometry (VBM). Furthermore, we explored the role of emotional intelligence in the association between GMV and dispositional envy. VBM indicated that dispositional envy was positively correlated with GMV in the left dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG). We also found that emotional intelligence partially mediated the association between DLPFC volume and dispositional envy. These results were replicated in another independent sample (Sample 2, n = 27). These results provide the first evidence that dispositional envy exhibits a structural neural correlation with the DLPFC and STG, and give a neutral explanation for why individuals with high emotional intelligence exhibit less envy.
Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington’s disease
Authors: Bragg Robert M. , Coffey Sydney R. , Weston Rory M. , Ament Seth A. , Cantle Jeffrey P. , Minnig Shawn , Funk Cory C. , Shuttleworth Dominic D. , Woods Emily L. , Sullivan Bonnie R. , Jones Lindsey , Glickenhaus Anne , Anderson John S. , Anderson Michael D. , Dunnett Stephen B. , Wheeler Vanessa C. , MacDonald Marcy E. , Brooks Simon P. , Price Nathan D. , Carroll Jeffrey B.
Published: February 2017

We investigated the appearance and progression of disease-relevant signs in the B6.HttQ111/+ mouse, a genetically precise model of the mutation that causes Huntington’s disease (HD). We find that B6.HttQ111/+ mice are healthy, show no overt signs of central or peripheral inflammation, and no gross motor impairment as late as 12 months of age. Behaviorally, we find that 4–9 month old B6.HttQ111/+ mice have normal activity levels and show no clear signs of anxiety or depression, but do show clear signs of reduced motivation. The neuronal density, neuronal size, synaptic density and number of glia is normal in B6.HttQ111/+ striatum, the most vulnerable brain region in HD, up to 12 months of age. Despite this preservation of the synaptic and cellular composition of the striatum, we observe clear progressive, striatal-specific transcriptional dysregulation and accumulation of neuronal intranuclear inclusions (NIIs). Simulation studies suggest these molecular endpoints are sufficiently robust for future preclinical studies, and that B6.HttQ111/+ mice are a useful tool for modeling disease-modifying or neuroprotective strategies for disease processes before the onset of overt phenotypes.
eUnaG: a new ligand-inducible fluorescent reporter to detect drug transporter activity in live cells
Authors: Yeh Johannes T.-H. , Nam Kwangho , Yeh Joshua T.-H. , Perrimon Norbert
Published: February 2017

The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds. This sensor can be used in live cells to measure transporter activity, as excretion of BR depends on ABC and SLC transporters. Applying eUnaG in functional RNAi screens, we characterize l(2)03659 as a Drosophila multidrug resistant-associated ABC transporter.
Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease
Authors: Hubmacher Dirk , Schneider Michael , Berardinelli Steven J. , Takeuchi Hideyuki , Willard Belinda , Reinhardt Dieter P. , Haltiwanger Robert S. , Apte Suneel S.
Published: February 2017

Secreted metalloproteases have diverse roles in the formation, remodeling, and the destruction of extracellular matrix. Recessive mutations in the secreted metalloprotease ADAMTS17 cause ectopia lentis and short stature in humans with Weill-Marchesani-like syndrome and primary open angle glaucoma and ectopia lentis in dogs. Little is known about this protease or its connection to fibrillin microfibrils, whose major component, fibrillin-1, is genetically associated with ectopia lentis and alterations in height. Fibrillin microfibrils form the ocular zonule and are present in the drainage apparatus of the eye. We show that recombinant ADAMTS17 has unique characteristics and an unusual life cycle. It undergoes rapid autocatalytic processing in trans after its secretion from cells. Secretion of ADAMTS17 requires O-fucosylation and its autocatalytic activity does not depend on propeptide processing by furin. ADAMTS17 binds recombinant fibrillin-2 but not fibrillin-1 and does not cleave either. It colocalizes to fibrillin-1 containing microfibrils in cultured fibroblasts and suppresses fibrillin-2 (FBN2) incorporation in microfibrils, in part by transcriptional downregulation of Fbn2 mRNA expression. RNA in situ hybridization detected Adamts17 expression in specific structures in the eye, skeleton and other organs, where it may regulate the fibrillin isoform composition of microfibrils.
Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells
Authors: Ma Jun , Li Xinyu , Su Yongwei , Zhao Jianyun , Luedtke Daniel A. , Epshteyn Valeria , Edwards Holly , Wang Guan , Wang Zhihong , Chu Roland , Taub Jeffrey W. , Lin Hai , Wang Yue , Ge Yubin
Published: February 2017

Acute myeloid leukemia (AML) continues to be a challenging disease to treat, thus new treatment strategies are needed. In this study, we investigated the antileukemic effects of ATR inhibition alone or combined with cytarabine in AML cells. Treatment with the ATR-selective inhibitor AZ20 caused proliferation inhibition in AML cell lines and primary patient samples. It partially abolished the G2 cell cycle checkpoint and caused DNA replication stress and damage, accompanied by CDK1-independent apoptosis and downregulation of RRM1 and RRM2. AZ20 synergistically enhanced cytarabine-induced proliferation inhibition and apoptosis, abolished cytarabine-induced S and G2/M cell cycle arrest, and cooperated with cytarabine in inducing DNA replication stress and damage in AML cell lines. These key findings were confirmed with another ATR-selective inhibitor AZD6738. Therefore, the cooperative induction of DNA replication stress and damage by ATR inhibition and cytarabine, and the ability of ATR inhibition to abrogate the G2 cell cycle checkpoint both contributed to the synergistic induction of apoptosis and proliferation inhibition in AML cell lines. Synergistic antileukemic interactions between AZ20 and cytarabine were confirmed in primary AML patient samples. Our findings provide insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML.
Plasma cell treatment device Plasma-on-Chip: Monitoring plasma-generated reactive species in microwells
Authors: Oh Jun-Seok , Kojima Shinya , Sasaki Minoru , Hatta Akimitsu , Kumagai Shinya
Published: February 2017

We have developed a plasma cell treatment device called Plasma-on-Chip that enables the real-time monitoring of a single cell culture during plasma treatment. The device consists of three parts: 1) microwells for cell culture, 2) a microplasma device for generating reactive oxygen and nitrogen species (RONS) for use in cell treatment, and 3) through-holes (microchannels) that connect each microwell with the microplasma region for RONS delivery. Here, we analysed the delivery of the RONS to the liquid culture medium stored in the microwells. We developed a simple experimental set-up using a microdevice and applied in situ ultraviolet absorption spectroscopy with high sensitivity for detecting RONS in liquid. The plasma-generated RONS were delivered into the liquid culture medium via the through-holes fabricated into the microdevice. The RONS concentrations were on the order of 10–100 μM depending on the size of the through-holes. In contrast, we found that the amount of dissolved oxygen was almost constant. To investigate the process of RONS generation, we numerically analysed the gas flow in the through-holes. We suggest that the circulating gas flow in the through-holes promotes the interaction between the plasma (ionised gas) and the liquid, resulting in enhanced RONS concentrations.
Depurinized milk downregulates rat thymus MyD88/Akt/p38 function, NF-κB-mediated inflammation, caspase-1 activity but not the endonuclease pathway: in vitro/in vivo study
Authors: Kocic Gordana , Veljkovic Andrej , Kocic Hristina , Colic Miodrag , Mihajlovic Dusan , Tomovic Katarina , Stojanovic Svetlana , Smelcerovic Andrija
Published: February 2017

The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes,in vitroAnnexin-V-FITC/PI assay was performed. Significant decreases in the thymus wet weight, thymocyte MyD88, Akt-1/phospho-Akt-1 kinase, p38/phospho-p38, NF-κB, caspase-1 activity and CD4+/CD8+ antigen expression were obtained, especially in the DP milk group. The activity of thymocyte alkaline and acid DNase increased in the DP but not in the UHT milk group. The level of IL-6 significantly decreased in DP milk treated group, while the level of total TGF-β and IL-6 increased in UHT milk group. Significant differences in hematological parameters were obtained in commercial milk fed group. Observed results about prevention of experimental diabetes in DP pretreated groups may suggest that purine compounds, uric acid and other volatile toxic compounds of commercial milk may suppress oral tolerance, probably via IL-6 and TGF-β cytokine effects.
Griseofulvin impairs intraerythrocytic growth of Plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study
Authors: Smith Clare M. , Jerkovic Ante , Truong Thy Thuc , Foote Simon J. , McCarthy James S. , McMorran Brendan J.
Published: February 2017

Griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome P450-mediated production of N-methyl protoporphyrin IX (N-MPP). N-MPP is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage Plasmodium falciparum. Novel drugs against Plasmodium are needed to achieve malaria elimination. Thus, we investigated whether griseofulvin shows anti-plasmodial activity. We observed that the intraerythrocytic growth of P. falciparum is inhibited in red blood cells pretreated with griseofulvin in vitro. Treatment with 100 μM griseofulvin was sufficient to prevent parasite growth and induce the production of N-MPP. Inclusion of the ferrochelatase substrate PPIX blocked the inhibitory activity of griseofulvin, suggesting that griseofulvin exerts its activity through the N-MPP-dependent inhibition of ferrochelatase. In an ex-vivo study, red blood cells from griseofulvin-treated subjects were refractory to the growth of cultured P. falciparum. However, in a clinical trial griseofulvin failed to show either therapeutic or prophylactic effect in subjects infected with blood stage P. falciparum. Although the development of griseofulvin as an antimalarial is not warranted, it represents a novel inhibitor of P. falciparum growth and acts via the N-MPP-dependent inhibition of ferrochelatase.
Structure of an octameric form of the minichromosome maintenance protein from the archaeon Pyrococcus abyssi
Authors: Cannone Giuseppe , Visentin Silvia , Palud Adeline , Henneke Ghislaine , Spagnolo Laura
Published: February 2017

Cell division is a complex process that requires precise duplication of genetic material. Duplication is concerted by replisomes. The Minichromosome Maintenance (MCM) replicative helicase is a crucial component of replisomes. Eukaryotic and archaeal MCM proteins are highly conserved. In fact, archaeal MCMs are powerful tools for elucidating essential features of MCM function. However, while eukaryotic MCM2-7 is a heterocomplex made of different polypeptide chains, the MCM complexes of manyArchaeaform homohexamers from a single gene product. Moreover, some archaeal MCMs are polymorphic, and both hexameric and heptameric architectures have been reported for the same polypeptide. Here, we present the structure of the archaeal MCM helicase fromPyrococcus abyssiin its single octameric ring assembly. To our knowledge, this is the first report of a full-length octameric MCM helicase.
Synthesis, Fungicidal Activity, and Structure Activity Relationship of β-Acylaminocycloalkylsulfonamides against Botrytis cinerea
Authors: Liu Chun-Hui , Chen Xiao-Yuan , Qin Pei-Wen , Qi Zhi-Qiu , Ji Ming-Shan , Liu Xing-Yu , Babu P. Vijaya , Li Xing-Hai , Cui Zi-Ning
Published: February 2017

In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents.
N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment
Authors: Ghayor Chafik , Gjoksi Bebeka , Dong Jing , Siegenthaler Barbara , Caflisch Amedeo , Weber Franz E.
Published: February 2017

N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA’s potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an ‘inactive’ drug-delivery vehicle.
Integrin α5β1 expression on dopaminergic neurons is involved in dopaminergic neurite outgrowth on striatal neurons
Authors: Izumi Yasuhiko , Wakita Seiko , Kanbara Chisato , Nakai Toshie , Akaike Akinori , Kume Toshiaki
Published: February 2017

During development, dopaminergic neurons born in the substantia nigra extend their axons toward the striatum. However, the mechanisms by which the dopaminergic axons extend the striatum to innervate their targets remain unclear. We previously showed that paired-cultivation of mesencephalic cells containing dopaminergic neurons with striatal cells leads to the extension of dopaminergic neurites from the mesencephalic cell region to the striatal cell region. The present study shows that dopaminergic neurites extended along striatal neurons in the paired-cultures of mesencephalic cells with striatal cells. The extension of dopaminergic neurites was suppressed by the pharmacological inhibition of integrin α5β1. Using lentiviral vectors, short hairpin RNA (shRNA)-mediated knockdown of integrin α5 in dopaminergic neurons suppressed the neurite outgrowth to the striatal cell region. In contrast, the knockdown of integrin α5 in non-dopaminergic mesencephalic and striatal cells had no effect. Furthermore, overexpression of integrin α5 in dopaminergic neurons differentiated from embryonic stem cells enhanced their neurite outgrowth on striatal cells. These results indicate that integrin α5β1 expression on dopaminergic neurons plays an important role in the dopaminergic neurite outgrowth on striatal neurons.
The dynamic mechanism of noisy signal decoding in gene regulation
Authors: Liu Peijiang , Wang Haohua , Huang Lifang , Zhou Tianshou
Published: February 2017

Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation. In addition, we find that the input noise can induce stochastic focusing in a regulation-dependent manner. These results reveal not only the dynamic mechanism of noisy signal decoding in gene regulation but also the essential role of external noise in controlling gene expression levels.
Targeting the molecular chaperone SlyD to inhibit bacterial growth with a small molecule
Authors: Kumar Amit , Balbach Jochen
Published: February 2017

Molecular chaperones are essential molecules for cell growth, whereby they maintain protein homeostasis. Because of their central cellular function, bacterial chaperones might be potential candidates for drug targets. Antimicrobial resistance is currently one of the greatest threats to human health, with gram-negative bacteria being of major concern. We found that a Cu2+ complex readily crosses the bacterial cell wall and inhibits SlyD, which is a molecular chaperone, cis/trans peptidyl prolyl isomerise (PPIase) and involved in various other metabolic pathways. The Cu2+ complex binds to the active sites of SlyD, which suppresses its PPIase and chaperone activities. Significant cell growth retardation could be observed for pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). We anticipate that rational development of drugs targeting molecular chaperones might help in future control of pathogenic bacterial growth, in an era of rapidly increasing antibiotic resistance.
ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
Authors: Zhang Rong , Knapp Michael , Suzuki Kentaro , Kajioka Daiki , Schmidt Johanna M. , Winkler Jonas , Yilmaz Öznur , Pleschka Michael , Cao Jia , Kockum Christina Clementson , Barker Gillian , Holmdahl Gundela , Beaman Glenda , Keene David , Woolf Adrian S. , Cervellione Raimondo M. , Cheng Wei , Wilkins Simon , Gearhart John P. , Sirchia Fabio , Di Grazia Massimo , Ebert Anne-Karolin , Rösch Wolfgang , Ellinger Jörg , Jenetzky Ekkehart , Zwink Nadine , Feitz Wout F. , Marcelis Carlo , Schumacher Johannes , Martinón-Torres Federico , Hibberd Martin Lloyd , Khor Chiea Chuen , Heilmann-Heimbach Stefanie , Barth Sandra , Boyadjiev Simeon A. , Brusco Alfredo , Ludwig Michael , Newman William , Nordenskjöld Agneta , Yamada Gen , Odermatt Benjamin , Reutter Heiko
Published: February 2017

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10−08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10−19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.
Comparative study of the gut microbiome potentially related to milk protein in Murrah buffaloes (Bubalus bubalis) and Chinese Holstein cattle
Authors: Zhang Jiachao , Xu Chuanbiao , Huo Dongxue , Hu Qisong , Peng Qiannan
Published: February 2017

Previous studies suggested a close relationship between ruminant gut microbes and the mammary gland. In this study, shotgun metagenomic sequencing was used to reveal the differences in the intestinal microbiome potentially related to milk components in Murrah buffaloes and Chinese Holstein cattle. A PCoA based on the weighted Unifrac distances showed an apparent clustering pattern in the structure of intestinal microbiota between buffalo and cattle. We could attribute the structural difference to the genera of Sutterella, Coprococcus and Dorea. A further analysis of microbial functional features revealed that the biosynthesis of amino acids (including lysine, valine, leucine and isoleucine), lipopolysaccharide biosynthesis and cofactor/vitamin biosynthesis were enriched in the buffalo. In contrast, dairy cattle had higher levels of pyruvate metabolism and carbon fixation in photosynthetic organisms. A further correlation analysis based on different milk components and the typical microbiome uncovered a significant positive correlation between milk protein and the microbial biosynthesis of amino acids, which was also positively correlated in the genera of Parabacteroides, Dorea and Sutterella. This study will expand our understanding of the intestinal microbiome of buffalo and cattle as representative ruminants, as well as provide new views about how to improve the production and nutritional qualities of animal milk.
Millitesla magnetic field effects on the photocycle of an animal cryptochrome
Authors: Sheppard Dean M. W. , Li Jing , Henbest Kevin B. , Neil Simon R. T. , Maeda Kiminori , Storey Jonathan , Schleicher Erik , Biskup Till , Rodriguez Ryan , Weber Stefan , Hore P. J. , Timmel Christiane R. , Mackenzie Stuart R.
Published: February 2017

Drosophila have been used as model organisms to explore both the biophysical mechanisms of animal magnetoreception and the possibility that weak, low-frequency anthropogenic electromagnetic fields may have biological consequences. In both cases, the presumed receptor is cryptochrome, a protein thought to be responsible for magnetic compass sensing in migratory birds and a variety of magnetic behavioural responses in insects. Here, we demonstrate that photo-induced electron transfer reactions in Drosophila melanogaster cryptochrome are indeed influenced by magnetic fields of a few millitesla. The form of the protein containing flavin and tryptophan radicals shows kinetics that differ markedly from those of closely related members of the cryptochrome–photolyase family. These differences and the magnetic sensitivity of Drosophila cryptochrome are interpreted in terms of the radical pair mechanism and a photocycle involving the recently discovered fourth tryptophan electron donor.
Metagenomic survey of the taxonomic and functional microbial communities of seawater and sea ice from the Canadian Arctic
Authors: Yergeau Etienne , Michel Christine , Tremblay Julien , Niemi Andrea , King Thomas L. , Wyglinski Joanne , Lee Kenneth , Greer Charles W.
Published: February 2017

Climate change has resulted in an accelerated decline of Arctic sea ice since 2001 resulting in primary production increases and prolongation of the ice-free season within the Northwest Passage. The taxonomic and functional microbial community composition of the seawater and sea ice of the Canadian Arctic is not very well known. Bacterial communities from the bottom layer of sea ice cores and surface water from 23 locations around Cornwallis Island, NU, Canada, were extensively screened. The bacterial 16S rRNA gene was sequenced for all samples while shotgun metagenomics was performed on selected samples. Bacterial community composition showed large variation throughout the sampling area both for sea ice and seawater. Seawater and sea ice samples harbored significantly distinct microbial communities, both at different taxonomic levels and at the functional level. A key difference between the two sample types was the dominance of algae in sea ice samples, as visualized by the higher relative abundance of algae and photosynthesis-related genes in the metagenomic datasets and the higher chlaconcentrations. The relative abundance of various OTUs and functional genes were significantly correlated with multiple environmental parameters, highlighting many potential environmental drivers and ecological strategies.
Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle
Authors: Vernetti Lawrence , Gough Albert , Baetz Nicholas , Blutt Sarah , Broughman James R. , Brown Jacquelyn A. , Foulke-Abel Jennifer , Hasan Nesrin , In Julie , Kelly Edward , Kovbasnjuk Olga , Repper Jonathan , Senutovitch Nina , Stabb Janet , Yeung Catherine , Zachos Nick C. , Donowitz Mark , Estes Mary , Himmelfarb Jonathan , Truskey George , Wikswo John P. , Taylor D. Lansing
Published: February 2017

Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media. MPS models representing the major absorption, metabolism and clearance organs (the jejunum, liver and kidney) were evaluated, along with skeletal muscle and neurovascular models. Three compounds were evaluated for organ-specific processing: terfenadine for pharmacokinetics (PK) and toxicity; trimethylamine (TMA) as a potentially toxic microbiome metabolite; and vitamin D3. We show that the organ-specific processing of these compounds was consistent with clinical data, and discovered that trimethylamine-N-oxide (TMAO) crosses the blood-brain barrier. These studies demonstrate the potential of human MPS for multi-organ toxicity and absorption, distribution, metabolism and excretion (ADME), provide guidance for physically coupling MPS, and offer an approach to coupling MPS with distinct media and perfusion requirements.
Structural white matter and functional connectivity alterations in patients with shoulder apprehension
Authors: Zanchi Davide , Cunningham Gregory , Lädermann Alexandre , Ozturk Mehmet , Hoffmeyer Pierre , Haller Sven
Published: February 2017

Previous functional magnetic resonance imaging (fMRI) findings indicate that shoulder apprehension is more complex than a pure mechanical problem of the shoulder, showing a direct modification in functional brain networks associated with motor inhibition and emotional regulation. The current study extends these findings by investigating further structural alterations in patients with shoulder apprehension compared to controls. 14 aged patients with shoulder apprehension (27.3 ± 2.0 years) and 10 matched healthy controls (29.6 ± 1.3 years) underwent clinical and fMRI examination including fMRI and diffusion tensor imaging (DTI). Tract-based spatial statistics procedure was used to analyze white matter (WM) alterations. Functional images were analyzed investigating resting state network connectivity. DTI results were correlated with different shoulder clinical scores and functional connectivity networks. Fractional anisotropy (FA), representing white matter integrity, is increased in the left internal capsule and partially in the thalamus in patients compared to controls. Moreover, FA correlates negatively with simple shoulder test (SST) scores (p < .05) and positively with a functional connectivity network qualitatively replicating previous results (p < .01). This study extends previous findings, showing that in addition to functional changes, structural white matter changes are also present in patients with shoulder apprehension.
A microneedle biosensor for minimally-invasive transdermal detection of nerve agents
Authors: Mishra Rupesh K. , Vinu Mohan A. M. , Soto Fernando , Chrostowski Robert , Wang Joseph
Published: February 2017

A microneedle array based biosensor for minimally invasive electrochemical monitoring of organophosphate (OP) nerve agents under the skin.
Elucidating light-induced charge accumulation in an artificial analogue of methane monooxygenase enzymes using time-resolved X-ray absorption spectroscopy
Authors: Moonshiram Dooshaye , Picón Antonio , Vazquez-Mayagoitia Alvaro , Zhang Xiaoyi , Tu Ming-Feng , Garrido-Barros Pablo , Mahy Jean-Pierre , Avenier Frédéric , Aukauloo Ally
Published: February 2017

Probing the light-induced two electron transfer processes at a diiron(iii,iii) multimolecular photocatalytic system.
Iron(ii)-catalyzed sulfur directed C(sp3)–H bond amination/C–S cross coupling reaction
Authors: Duan Fang-Fang , Song Shi-Qian , Xu Run-Sheng
Published: February 2017

An efficient iron(ii)-catalyzed sulfur directed C(sp3)–H bond amination/C–S cross coupling reaction has been developed, and the mechanism corresponds to a Fe(ii)/Fe(iii) catalytic cycle.
Spin-polarized transport in graphene nanoribbons with Rashba spin–orbit interaction: the effects of spatial symmetry
Authors: Zhang Qingtian , Chan K. S. , Li Jingbo
Published: February 2017

The spin polarization can be largely enhanced by breaking the spatial symmetries of ideal graphene nanoribbons with Rashba SOI.
Jones oxidation of glycerol catalysed by small gold clusters
Authors: Pembere Anthony M. , Luo Zhixun
Published: February 2017

We present here a joint theoretical and experimental study on the oxidation reactivity of glycerol catalysed by chemically pure small Au clusters in the absence and presence of H2O2.
The properties and behavior of α-pinene secondary organic aerosol particles exposed to ammonia under dry conditions
Authors: Bell David M. , Imre Dan , T. Martin Scot , Zelenyuk Alla
Published: February 2017

Chemical transformations and aging of secondary organic aerosol (SOA) particles can alter their physical and chemical properties, including particle morphology.
Insights into acid dissociation of HCl and HBr with internal electric fields
Authors: Boda Manjusha , Naresh Patwari G.
Published: February 2017

A critical electric field exerted by the solvent on the ionizable group leads to acid dissociation.
An autonomous lab on a chip for space flight calibration of gravity-induced transcellular calcium polarization in single-cell fern spores
Authors: Park J. , Salmi M. L. , Wan Salim W. W. A. , Rademacher A. , Wickizer B. , Schooley A. , Benton J. , Cantero A. , Argote P. F. , Ren M. , Zhang M. , Porterfield D. M. , Ricco A. J. , Roux S. J. , Rickus J. L.
Published: February 2017

A device designed for space flight measures the longest continuous observation of a plant cell's calcium response to hypergravity made to date.
Phased peristaltic micropumping for continuous sampling and hardcoded droplet generation
Authors: Nightingale Adrian M. , Evans Gareth W. H. , Xu Peixiang , Kim Byung Jae , Hassan Sammer-ul , Niu Xize
Published: February 2017

We describe a highly robust method to generate droplets using peristaltically-pumped anti-phased oil/aqueous flows with droplet size, frequency and composition specifiable in the pump design.
Understanding the microscopic binding mechanism of hydroxylated and sulfated polybrominated diphenyl ethers with transthyretin by molecular docking, molecular dynamics simulations and binding free energy calculations
Authors: Cao Huiming , Sun Yuzhen , Wang Ling , Zhao Chunyan , Fu Jianjie , Zhang Aiqian
Published: February 2017

The binding of TTR with sulfated-PBDEs and OH-PBDEs shows different molecular recognition mechanisms.
Synthesis of thiospinel CuCo2S4and CuCo2S4/reduced-graphene oxide nanohybrids as highly effective catalysts for the Sonogashira reaction
Authors: Hashemi Fath Roghayeh , Hoseini S. Jafar
Published: February 2017

Thiospinel CuCo2S4and CuCo2S4/reduced-graphene oxide nanohybrids were first synthesized through a simple solvothermal approach. These nanohybrids were then used as non-phosphine catalysts for the Sonogashira reaction in water.
Novel triazole-modified chitosan@nickel nanoparticles: efficient and recoverable catalysts for Suzuki reaction
Authors: Hajipour Abdol R. , Abolfathi Parisa
Published: February 2017

The synthesis of triazole-modified chitosan@nickel catalyst through the click reaction of azide-functionalized chitosan with an alkynated imino-thiophene ligand for Suzuki–Miyaura coupling reactions.
Self-supported rectangular CoP nanosheet arrays grown on a carbon cloth as an efficient electrocatalyst for the hydrogen evolution reaction over a variety of pH values
Authors: Yan Xiao-yu , Devaramani Samrat , Chen Jing , Shan Duo-liang , Qin Dong-dong , Ma Qin , Lu Xiao-quan
Published: February 2017

In this study, we reported rectangular CoP nanosheet (NS) arrays on carbon cloth (CoP NS/CC) prepared via a concise two-step synthetic method.
Enhanced magnetic anisotropy in a tellurium-coordinated cobalt single-ion magnet
Authors: Yao Xiao-Nan , Yang Mu-Wen , Xiong Jin , Liu Jia-Jia , Gao Chen , Meng Yin-Shan , Jiang Shang-Da , Wang Bing-Wu , Gao Song
Published: February 2017

Fine-tuning of the ligand field of a series of four-coordinate Co(ii) SIMs, yielding the first tellurium-coordinated SIM.
Directed assembly of a high surface area 2D metal–organic framework displaying the augmented “kagomé dual” (kgd-a) layered topology with high H2and CO2uptake
Authors: Spanopoulos Ioannis , Tsangarakis Constantinos , Barnett Sarah , Nowell Harriot , Klontzas Emmanuel , Froudakis George E. , Trikalitis Pantelis N.
Published: February 2017

A high surface area layered MOF withkgd-atopology, based on a nanosized and highly aromatic hexagonal linker, shows high H2and CO2uptake.
The synthesis of unsymmetric diamides through Rh-catalyzed selective C–H bond activation of amides with isocyanates
Authors: Yu Xiaoli , Wang Duo-Sheng , Xu Zhaojun , Yang Bobin , Wang Dawei
Published: February 2017

Synthetic and mechanistic studies on Rh-catalyzed C–H activation of amides with isocyanates, resulting in one of the unsymmetric diamine products showing promising anti-cancer activity.
Synthesis and characterization of metallo-supramolecular polymers from thiophene-based unimers bearing pybox ligands
Authors: Hladysh Sviatoslav , Václavková Daniela , Vrbata David , Bondarev Dmitrij , Havlíček David , Svoboda Jan , Zedník Jiří , Vohlídal Jiří
Published: February 2017

A series of novel metallo-supramolecular polymers was prepared, based on 2,6-bis(2-oxazolinyl)pyridine chelating groups bridged with thiophene, bithiophene and thienothiophene as a linker, beginning from commercially available (chelidamic) acid.
Polymorphism of a hexadecane–heptadecane binary system in nanopores
Authors: Sui Jian , Zhang Shi Qi , Zhai Min , Tian Fang , Zhang Jian , Lan Xiao Zheng
Published: February 2017

Phase behaviors of a hexadecane–heptadecane (n-C16H34–C17H36, C16–C17) binary system in the bulk and in nanopores of controlled porous glasses (CPGs) are investigated using differential scanning calorimetry (DSC) and temperature-dependent powder X-ray diffraction (XRD).
Synthesis and photophysical properties of phenanthroimidazole–triarylborane dyads: intriguing ‘turn-on’ sensing mediated by fluoride anions
Authors: You Dong Kyun , Lee Seon Hee , Lee Ji Hye , Kwak Sang Woo , Hwang Hyonseok , Lee Junseong , Chung Yongseog , Park Myung Hwan , Lee Kang Mun
Published: February 2017

Phenanthroimidazole-based triarylborane compounds with an N-phenyl or N-biphenyl bridge were prepared and these compounds show ratiometrical ‘turn-on’ response in PL spectra upon fluoride binding to the borane moiety.