bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress hormone response to the DEX–CRH test and its relation to psychotherapy outcome in panic disorder patients with and without agoraphobia
Authors: Wichmann Susann , Bornstein Stefan R. , Lorenz Thomas , Petrowski Katja
Published: February 2018

This study tested whether the hormonal stress response to the DEX–CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX–CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour). Repeated measures ANCOVA were conducted for the analysis of the pre-therapy hormonal response, and Pearson’s correlation analysis to test for associations with the psychotherapy outcome. Data analyses revealed large effect sizes for CBT in the clinical measures (η2 ≥ 0.321), main effects of time for cortisol and ACTH with no differences between both groups, and significant associations between cortisol release and agoraphobic cognitions for the patients. PD diagnosis had no impact on the hormonal response. However, those patients with higher cortisol release showed less improvement after CBT (significantly for agoraphobic cognitions). Clinical implications of these findings are the prediction of the therapy success from a potential endocrine correlate whose persistency (if assessed repeatedly) during the treatment may predict (non-)response to the current treatment, possibly representing a decision support for a change in treatment to avoid the continuation of an inefficient treatment.
Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism
Authors: Rose Shannon , Bennuri Sirish C. , Davis Jakeira E. , Wynne Rebecca , Slattery John C. , Tippett Marie , Delhey Leanna , Melnyk Stephan , Kahler Stephen G. , MacFabe Derrick F. , Frye Richard E.
Published: February 2018

Butyrate (BT) is a ubiquitous short-chain fatty acid (SCFA) principally derived from the enteric microbiome. BT positively modulates mitochondrial function, including enhancing oxidative phosphorylation and beta-oxidation and has been proposed as a neuroprotectant. BT and other SCFAs have also been associated with autism spectrum disorders (ASD), a condition associated with mitochondrial dysfunction. We have developed a lymphoblastoid cell line (LCL) model of ASD, with a subset of LCLs demonstrating mitochondrial dysfunction (AD-A) and another subset of LCLs demonstrating normal mitochondrial function (AD-N). Given the positive modulation of BT on mitochondrial function, we hypothesized that BT would have a preferential positive effect on AD-A LCLs. To this end, we measured mitochondrial function in ASD and age-matched control (CNT) LCLs, all derived from boys, following 24 and 48 h exposure to BT (0, 0.1, 0.5, and 1 mM) both with and without an in vitro increase in reactive oxygen species (ROS). We also examined the expression of key genes involved in cellular and mitochondrial response to stress. In CNT LCLs, respiratory parameters linked to adenosine triphosphate (ATP) production were attenuated by 1 mM BT. In contrast, BT significantly increased respiratory parameters linked to ATP production in AD-A LCLs but not in AD-N LCLs. In the context of ROS exposure, BT increased respiratory parameters linked to ATP production for all groups. BT was found to modulate individual LCL mitochondrial respiration to a common set-point, with this set-point slightly higher for the AD-A LCLs as compared to the other groups. The highest concentration of BT (1 mM) increased the expression of genes involved in mitochondrial fission (PINK1, DRP1, FIS1) and physiological stress (UCP2, mTOR, HIF1α, PGC1α) as well as genes thought to be linked to cognition and behavior (CREB1, CamKinase II). These data show that the enteric microbiome-derived SCFA BT modulates mitochondrial activity, with this modulation dependent on concentration, microenvironment redox state, and the underlying mitochondrial function of the cell. In general, these data suggest that BT can enhance mitochondrial function in the context of physiological stress and/or mitochondrial dysfunction, and may be an important metabolite that can help rescue energy metabolism during disease states. Thus, insight into this metabolic modulator may have wide applications for both health and disease since BT has been implicated in a wide variety of conditions including ASD. However, future clinical studies in humans are needed to help define the practical implications of these physiological findings.
Ulk4 regulates GABAergic signaling and anxiety-related behavior
Authors: Liu Min , Fitzgibbon Marie , Wang Yanqin , Reilly Jamie , Qian Xiaohong , O’Brien Timothy , Clapcote Steve , Shen Sanbing , Roche Michelle
Published: February 2018

Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder. The current study characterized behavior of heterozygous Ulk4
+/tm1a
mice, demonstrating that Ulk4
+/tm1a
mice displayed no schizophrenia-like behavior in acoustic startle reactivity and prepulse inhibition tests or depressive-like behavior in the Porsolt swim or tail suspension tests. However, Ulk4
+/tm1a
mice exhibited an anxiety-like behavioral phenotype in several tests. Previously identified hypo-anxious (Atp1a2, Ptn, and Mdk) and hyper-anxious (Gria1, Syngap1, and Npy2r) genes were found to be dysregulated accordingly in Ulk4 mutants. Ulk4 was found to be expressed in GABAergic neurons and the Gad67+ interneurons were significantly reduced in the hippocampus and basolateral amygdala of Ulk4
+/tm1a
mice. Transcriptome analyses revealed a marked reduction of GABAergic neuronal subtypes, including Pvalb, Sst, Cck, Npy, and Nos3, as well as significant upregulation of GABA receptors, including Gabra1, Gabra3, Gabra4, Gabra5, and Gabrb3. This is the first evidence that Ulk4 plays a major role in regulating GABAergic signaling and anxiety-like behavior, which may have implications for the development of novel anxiolytic treatments.
Walking and rolling of crystals induced thermally by phase transition
Authors: Taniguchi Takuya , Sugiyama Haruki , Uekusa Hidehiro , Shiro Motoo , Asahi Toru , Koshima Hideko
Published: February 2018

The mechanical motion of materials has been increasingly explored in terms of bending and expansion/contraction. However, the locomotion of materials has been limited. Here, we report walking and rolling locomotion of chiral azobenzene crystals, induced thermally by a reversible single-crystal-to-single-crystal phase transition. Long plate-like crystals with thickness gradient in the longitudinal direction walk slowly, like an inchworm, by repeated bending and straightening under heating and cooling cycles near the transition temperature. Furthermore, thinner, longer plate-like crystals with width gradient roll much faster by tilted bending and then flipping under only one process of heating or cooling. The length of the crystal is shortened above the transition temperature, which induces bending due to the temperature gradient to the thickness direction. The bending motion is necessarily converted to the walking and rolling locomotion due to the unsymmetrical shape of the crystal. This finding of the crystal locomotion can lead to a field of crystal robotics.
Crosstalk in concurrent repeated games impedes direct reciprocity and requires stronger levels of forgiveness
Authors: Reiter Johannes G. , Hilbe Christian , Rand David G. , Chatterjee Krishnendu , Nowak Martin A.
Published: February 2018

Direct reciprocity is a mechanism for cooperation among humans. Many of our daily interactions are repeated. We interact repeatedly with our family, friends, colleagues, members of the local and even global community. In the theory of repeated games, it is a tacit assumption that the various games that a person plays simultaneously have no effect on each other. Here we introduce a general framework that allows us to analyze “crosstalk” between a player’s concurrent games. In the presence of crosstalk, the action a person experiences in one game can alter the person’s decision in another. We find that crosstalk impedes the maintenance of cooperation and requires stronger levels of forgiveness. The magnitude of the effect depends on the population structure. In more densely connected social groups, crosstalk has a stronger effect. A harsh retaliator, such as Tit-for-Tat, is unable to counteract crosstalk. The crosstalk framework provides a unified interpretation of direct and upstream reciprocity in the context of repeated games.
Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells
Authors: Prusty Deepak K. , Adam Volker , Zadegan Reza M. , Irsen Stephan , Famulok Michael
Published: February 2018

Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2′,6′-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization. The lipidated DNA scaffolds self-assemble into spherical hybrid-nanoconstructs that specifically bind cMet. The combined features of the nanocarriers increase serum nuclease resistance, favor their import into cells presumably mediated by endocytosis, and allow selective photo-release of the chemotherapeutic into the targeted cells. cMet-expressing H1838 tumor cells specifically internalize drug-loaded nanoconstructs, and subsequent UV exposure enhances cell mortality. This modular approach thus paves the way for novel classes of powerful aptamer-based therapeutics.
Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner
Authors: Wang Yun-Qian , Wang Hao-Lian , Xu Jie , Tan Juan , Fu Lin-Na , Wang Ji-Lin , Zou Tian-Hui , Sun Dan-Feng , Gao Qin-Yan , Chen Ying-Xuan , Fang Jing-Yuan
Published: February 2018

Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
Author Correction: Hippocampal oxytocin receptors are necessary for discrimination of social stimuli
Authors: Raam Tara , McAvoy Kathleen M. , Besnard Antoine , Veenema Alexa H. , Sahay Amar
Published: February 2018

The original version of this Article contained an error in the spelling of the author Alexa H. Veenema, which was incorrectly given as Alexa Veenema. This has now been corrected in both the PDF and HTML versions of the Article.
α-cell glucokinase suppresses glucose-regulated glucagon secretion
Authors: Basco Davide , Zhang Quan , Salehi Albert , Tarasov Andrei , Dolci Wanda , Herrera Pedro , Spiliotis Ioannis , Berney Xavier , Tarussio David , Rorsman Patrik , Thorens Bernard
Published: February 2018

Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of KATP channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype.
Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients
Authors: Guéant Jean-Louis , Chéry Céline , Oussalah Abderrahim , Nadaf Javad , Coelho David , Josse Thomas , Flayac Justine , Robert Aurélie , Koscinski Isabelle , Gastin Isabelle , Filhine-Tresarrieu Pierre , Pupavac Mihaela , Brebner Alison , Watkins David , Pastinen Tomi , Montpetit Alexandre , Hariri Fadi , Tregouët David , Raby Benjamin A , Chung Wendy K. , Morange Pierre-Emmanuel , Froese D. Sean , Baumgartner Matthias R. , Benoist Jean-François , Ficicioglu Can , Marchand Virginie , Motorin Yuri , Bonnemains Chrystèle , Feillet François , Majewski Jacek , Rosenblatt David S.
Published: February 2018

The original version of this Article contained an error in the title, which was incorrectly given as 'APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'. This has now been corrected in both the PDF and HTML versions of the Article to read 'A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'.
Low-dose x-ray tomography through a deep convolutional neural network
Authors: Yang Xiaogang , De Andrade Vincent , Scullin William , Dyer Eva L. , Kasthuri Narayanan , De Carlo Francesco , Gürsoy Doğa
Published: February 2018

Synchrotron-based X-ray tomography offers the potential for rapid large-scale reconstructions of the interiors of materials and biological tissue at fine resolution. However, for radiation sensitive samples, there remain fundamental trade-offs between damaging samples during longer acquisition times and reducing signals with shorter acquisition times. We present a deep convolutional neural network (CNN) method that increases the acquired X-ray tomographic signal by at least a factor of 10 during low-dose fast acquisition by improving the quality of recorded projections. Short-exposure-time projections enhanced with CNNs show signal-to-noise ratios similar to long-exposure-time projections. They also show lower noise and more structural information than low-dose short-exposure acquisitions post-processed by other techniques. We evaluated this approach using simulated samples and further validated it with experimental data from radiation sensitive mouse brains acquired in a tomographic setting with transmission X-ray microscopy. We demonstrate that automated algorithms can reliably trace brain structures in low-dose datasets enhanced with CNN. This method can be applied to other tomographic or scanning based X-ray imaging techniques and has great potential for studying faster dynamics in specimens
Publisher Correction: Crystal Orientation Dependence of Gallium Nitride Wear
Authors: Zeng Guosong , Sun Wei , Song Renbo , Tansu Nelson , Krick Brandon A.
Published: February 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: Ambipolar field role in formation of electron distribution function in gas discharge plasma
Authors: Yuan Chengxun , Bogdanov E. A. , Kudryavtsev A. A. , Rabadanov K. M. , Zhou Zhongxiang
Published: February 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.
Voluntary locomotor activity promotes myogenic growth potential in domestic pigs
Authors: Kalbe Claudia , Zebunke Manuela , Lösel Dorothea , Brendle Julia , Hoy Steffen , Puppe Birger
Published: February 2018

Self-determined physical activity is an essential behavioural need and can vary considerably between individuals of a given species. Although locomotion is suggested as a prerequisite for adequate function of skeletal muscle, domestic pigs are usually reared under limited space allowance. The aim of our study was to investigate if a different voluntary locomotor activity leads to altered properties in the muscle structure, biochemistry and mRNA expression of selected genes involved in myogenesis and skeletal muscle metabolism. Based on a video tracking method, we assigned pigs to three categories according to their total distances walked over five observed time points: long distance, medium distance, and short distance. The microstructure and biochemistry parameters of the M. semitendinosus were unaffected by the distance categories. However, we found distance-dependent differences in the mRNA expression of the genes encoding growth (IGF2, EGF, MSTN) and transcription factors (MRF4, MYOD). In particular, the IGF2/MSTN ratio appears to be a sensitive indicator, at the molecular level, for the locomotor activity of individuals. Our results indicate that the myogenic growth potential of pigs under standard rearing conditions is triggered by their displayed voluntary locomotor activity, but the covered distances are insufficient to induce adaptive changes at the tissue level.
Visuospatial asymmetries do not modulate the cheerleader effect
Authors: Carragher Daniel J. , Lawrence Blake J. , Thomas Nicole A. , Nicholls Michael E. R.
Published: February 2018

The cheerleader effect occurs when the same individual appears to be more attractive when seen in a group, compared to alone. As observers over-attend to visual information presented in the left visual field, we investigated whether the spatial arrangement of the faces in a group would influence the magnitude of the cheerleader effect. In Experiment 1, target faces were presented twice in the centre of the display: once alone, and once in a group. Group images featured two distractor faces, which were presented in either the left or the right visual field, or on either side of the target. The location of the distractor faces did not modulate the size of the cheerleader effect, which was observed in each group configuration. In Experiment 2, we manipulated the location of the target faces, which were presented at the far left, far right, or centre of the group. Faces were again significantly more attractive in each group configuration, and the spatial location of the target face did not influence the size of the cheerleader effect. Together, our results show that the cheerleader effect is a robust phenomenon, which is not influenced by the spatial arrangement of the faces in the group.
Differentially expressed host long intergenic noncoding RNA and mRNA in HIV-1 and HIV-2 infection
Authors: Biswas Santanu , Haleyurgirisetty Mohan , Ragupathy Viswanath , Wang Xue , Lee Sherwin , Hewlett Indira , Devadas Krishnakumar
Published: February 2018

Non-coding RNAs and mRNAs have been implicated in replication, pathogenesis and host response in HIV infection. However, the impact of long intergenic non-coding RNAs (lincRNAs) on HIV-1 and HIV-2 infection is not known. In this study, we have analyzed expression profiles of lincRNAs and mRNAs in monocyte derived macrophages (MDMs) infected with HIV-1/HIV-2 using microarrays. Our study identified many differentially expressed lincRNAs and mRNAs in MDMs infected with HIV-1/HIV-2 compared to uninfected MDMs. Genes involved in glutathione metabolism and lysine degradation were differentially regulated only in HIV-1 infected MDMs. In HIV-2 infected MDMs, CUL 2, SFRS9, and RBBP4 genes were differentially expressed. Furthermore, we found that plasma levels of lincRNA: chr2: 165509129-165519404 and lincRNA: chr12: 57761837-57762303 were better indicators of HIV-1 infection while lincRNA: chr10:128586385-128592960, XLOC_001148 and lincRNA: chr5:87580664-87583451, were better indicators of HIV-2 infection. In summary, our study has demonstrated that there is substantial alteration in lincRNA and mRNA expression in response to HIV-1/HIV-2 infection. These differentially expressed lincRNAs and mRNAs could serve as prognostic and diagnostic biomarkers of HIV infection and help in the identification of new targets for therapy.
PilVax – a novel peptide delivery platform for the development of mucosal vaccines
Authors: Wagachchi Dasun , Tsai Jia-Yun C. , Chalmers Callum , Blanchett Sam , Loh Jacelyn M. S. , Proft Thomas
Published: February 2018

Peptide vaccines are an attractive strategy to engineer the induction of highly targeted immune responses and avoid potentially allergenic and/or reactogenic protein regions. However, peptides by themselves are often unstable and poorly immunogenic, necessitating the need for an adjuvant and a specialised delivery system. We have developed a novel peptide delivery platform (PilVax) that allows the presentation of a stabilised and highly amplified peptide as part of the group A streptococcus serotype M1 pilus structure (PilM1) on the surface of the non-pathogenic bacterium Lactococcus lactis. To show proof of concept, we have successfully inserted the model peptide Ova324–339 into 3 different loop regions of the backbone protein Spy0128, which resulted in the assembly of the pilus containing large numbers of peptide on the surface of L. lactis. Intranasal immunisation of mice with L. lactis PilM1-Ova generated measurable Ova-specific systemic and mucosal responses (IgA and IgG). Furthermore, we show that multiple peptides can be inserted into the PilVax platform and that peptides can also be incorporated into structurally similar, but antigenically different pilus structures. PilVax may be useful as a cost-effective platform for the development of peptide vaccines against a variety of important human pathogens.
A compact silicon grating coupler based on hollow tapered spot-size converter
Authors: Asaduzzaman Md , Bakaul Masuduzzaman , Skafidas Efstratios , Khandokar Md Rezwanul Haque
Published: February 2018

A new compact silicon grating coupler enabling fibre-to-chip light coupling at a minimized taper length is proposed. The proposed coupler, which incorporates a hollow tapered waveguide, converts the spot-size of optical modes from micro- to nano-scales by reducing the lateral dimension from 15 µm to 300 nm at a length equals to 60 µm. The incorporation of such a coupler in photonic integrated circuit causes a physical footprint as small as 81 µm × 15 µm with coupling efficiency and 3-dB coupling bandwidth as high as 72% and 69 nm respectively.
Transitions to sustainable management of phosphorus in Brazilian agriculture
Authors: Withers Paul J. A. , Rodrigues Marcos , Soltangheisi Amin , de Carvalho Teotonio S. , Guilherme Luiz R. G. , Benites Vinicius de M. , Gatiboni Luciano C. , de Sousa Djalma M. G. , Nunes Rafael de S. , Rosolem Ciro A. , Andreote Fernando D. , Oliveira Adilson de , Coutinho Edson L. M. , Pavinato Paulo S.
Published: February 2018

Brazil’s large land base is important for global food security but its high dependency on inorganic phosphorus (P) fertilizer for crop production (2.2 Tg rising up to 4.6 Tg in 2050) is not a sustainable use of a critical and price-volatile resource. A new strategic analysis of current and future P demand/supply concluded that the nation’s secondary P resources which are produced annually (e.g. livestock manures, sugarcane processing residues) could potentially provide up to 20% of crop P demand by 2050 with further investment in P recovery technologies. However, the much larger legacy stores of secondary P in the soil (30 Tg in 2016 worth over $40 billion and rising to 105 Tg by 2050) could provide a more important buffer against future P scarcity or sudden P price fluctuations, and enable a transition to more sustainable P input strategies that could reduce current annual P surpluses by 65%. In the longer-term, farming systems in Brazil should be redesigned to operate profitably but more sustainably under lower soil P fertility thresholds.
Supersaturation-controlled microcrystallization and visualization analysis for serial femtosecond crystallography
Authors: Lee Dan Bi , Kim Jong-Min , Seok Jong Hyeon , Lee Ji-Hye , Jo Jae Deok , Mun Ji Young , Conrad Chelsie , Coe Jesse , Nelson Garrett , Hogue Brenda , White Thomas A. , Zatsepin Nadia , Weierstall Uwe , Barty Anton , Chapman Henry , Fromme Petra , Spence John , Chung Mi Sook , Oh Chang-Hyun , Kim Kyung Hyun
Published: February 2018

Time-resolved serial femtosecond crystallography with X-ray free electron laser (XFEL) holds the potential to view fast reactions occurring at near-physiological temperature. However, production and characterization of homogeneous micron-sized protein crystals at high density remain a bottleneck, due to the lack of the necessary equipments in ordinary laboratories. We describe here supersaturation-controlled microcrystallization and visualization and analysis tools that can be easily used in any laboratory. The microcrystallization conditions of the influenza virus hemagglutinin were initially obtained with low reproducibility, which was improved by employing a rapid evaporation of hanging drops. Supersaturation-controlled microcrystallization was then developed in a vapor diffusion mode, where supersaturation was induced by evaporation in hanging drops sequentially for durations ranging from 30 sec to 3 min, depending on the protein. It was applied successfully to the microcrystal formation of lysozyme, ferritin and hemagglutinin with high density. Moreover, visualization and analysis tools were developed to characterize the microcrystals observed by light microscopy. The size and density distributions of microcrystals analyzed by the tools were found to be consistent with the results of manual analysis, further validated by high-resolution microscopic analyses. Our supersaturation-controlled microcrystallization and visualization and analysis tools will provide universal access to successful XFEL studies.
Sahel rainfall strength and onset improvements due to more realistic Atlantic cold tongue development in a climate model
Authors: Steinig S. , Harlaß J. , Park W. , Latif M.
Published: February 2018

The simulation of Sahel rainfall and its onset during the West African Monsoon (WAM) remains a challenge for current state-of-the-art climate models due to their persistent biases, especially in the tropical Atlantic region. Here we show that improved representation of Atlantic Cold Tongue (ACT) development is essential for a more realistic seasonal evolution of the WAM, which is due to a further inland migration of the precipitation maximum. The observed marked relationship between ACT development and Sahel rainfall onset only can be reproduced by a climate model, the Kiel Climate Model (KCM), when sufficiently high resolution in its atmospheric component is employed, enabling enhanced equatorial Atlantic interannual sea surface temperature variability in the ACT region relative to versions with coarser atmospheric resolution. The ACT/Sahel rainfall relationship in the model critically depends on the correct seasonal phase-locking of the interannual variability rather than on its magnitude. We compare the KCM results with those obtained from climate models participating in the Coupled Model Intercomparison Project phase 5 (CMIP5).
Measurement of nuclear reaction cross sections by using Cherenkov radiation toward high-precision proton therapy
Authors: Masuda Takamitsu , Kataoka Jun , Arimoto Makoto , Takabe Miho , Nishio Teiji , Matsushita Keiichiro , Miyake Tasuku , Yamamoto Seiichi , Inaniwa Taku , Toshito Toshiyuki
Published: February 2018

Monitoring the in vivo dose distribution in proton therapy is desirable for the accurate irradiation of a tumor. Although positron emission tomography (PET) is widely used for confirmation, the obtained distribution of positron emitters produced by the protons does not trace the dose distribution due to the different physical processes. To estimate the accurate dose from the PET image, the cross sections of nuclear reactions that produce positron emitters are important yet far from being sufficient. In this study, we measured the cross sections of 16O(p,x)15O, 16O(p,x)13N, and 16O(p,x)11C with a wide-energy range (approximately 5–70 MeV) by observing the temporal evolution of the Cherenkov radiation emitted from positrons generated via β+ decay along the proton path. Furthermore, we implemented the new cross sectional data into a conventional Monte Carlo (MC) simulation, so that a direct comparison was possible with the PET measurement. We confirmed that our MC results showed good agreement with the experimental data, both in terms of the spatial distributions and temporal evolutions. Although this is the first attempt at using the Cherenkov radiation in the measurements of nuclear cross sections, the obtained results suggest the method is convenient and widely applicable for high precision proton therapy.
EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells
Authors: Mimche Patrice N. , Lee Choon M. , Mimche Sylvie M. , Thapa Manoj , Grakoui Arash , Henkemeyer Mark , Lamb Tracey J.
Published: February 2018

Hepatic fibrosis is the result of an excessive wound-healing response subsequent to chronic liver injury. A feature of liver fibrogenesis is the secretion and deposition of extracellular matrix proteins by activated hepatic stellate cells (HSCs). Here we report that upregulation of EphB2 is a prominent feature of two mouse models of hepatic fibrosis and also observed in humans with liver cirrhosis. EphB2 is upregulated and activated in mouse HSCs following chronic carbon tetrachloride (CCl4) exposure. Moreover, we show that EphB2 deficiency attenuates liver fibrosis and inflammation and this is correlated with an overall reduction in pro-fibrotic markers, inflammatory chemokines and cytokines. In an in vitro system of HSCs activation we observed an impaired proliferation and sub-optimal differentiation into fibrogenic myofibroblasts of HSCs isolated from EphB2−/− mice compared to HSCs isolated from wild type mice. This supports the hypothesis that EphB2 promotes liver fibrosis partly via activation of HSCs. Cellular apoptosis which is generally observed during the regression of liver fibrogenesis was increased in liver specimens of CCl4-treated EphB2−/− mice compared to littermate controls. This data is suggestive of an active repair/regeneration system in the absence of EphB2. Altogether, our data validate this novel pro-fibrotic function of EphB2 receptor tyrosine kinase.
CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs
Authors: Kaur Sukhbir , Elkahloun Abdel G. , Arakelyan Anush , Young Lynn , Myers Timothy G. , Otaizo-Carrasquero Francisco , Wu Weiwei , Margolis Leonid , Roberts David D.
Published: February 2018

Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies. These EV subsets have similar sizes but divergent RNA contents. Apart from differences in numbers of nonannotated transcripts, CD63+, MHC1+, and CD47+EVs have similar overall contents of most noncoding RNA classes, but the relative enrichment of specific RNAs differs. The enrichment of micro-RNAs is highly divergent, and some including miR320a are selectively concentrated in CD47+EVs. Small nucleolar RNAs including SNORD116@ and SNHG10 are also selectively enriched in CD47+EVs, whereas no small nuclear RNAs are enriched in CD47+EVs. Conversely, MHC1+EVs are selectively enriched in a subset of tRNAs including TRE-CTC and TRR-CCG. This heterogeneity in RNA composition suggests multiple sorting mechanisms that direct specific RNAs into subsets of EVs that express specific surface markers.
Breastfeeding moderates FTO related adiposity: a birth cohort study with 30 years of follow-up
Authors: Horta Bernardo Lessa , Victora Cesar G. , França Giovanny V. A. , Hartwig Fernando P. , Ong Ken K. , Rolfe Emanuella de Lucia. , Magalhães Elma I. S. , Lima Natalia P. , Barros Fernando C.
Published: February 2018

This study assessed the association of breastfeeding with body composition at 30 years, among subjects who have been prospectively followed since birth in a southern Brazilian city. We also evaluated whether breastfeeding moderated the association between the rs9939609 variant in theFTOgene and adiposity. At 30 years, total and predominant breastfeeding were positively associated with lean mass index and inversely with visceral fat thickness. Among subjects breastfed for <1 month, all outcomes showed monotonically increasing values with additional copies of the A allele in theFTOgenotype (rs9939609). Associations among subjects breastfed for one month or longer tended to be in the same direction but showed lower magnitude and were less consistent; for all outcomes. Interactions had p values ≤ 0.05 for body mass index, fat mass index and waist circumference. Even among young adults, breastfeeding moderates the association between theFTOvariant rs9939609 and body composition.
Generation and characterization of a IgG monoclonal antibody specific for GM3 (NeuGc) ganglioside by immunizing β3Gn-T5 knockout mice
Authors: He Dongwei , Fan Xiaoyan , Liu Boyi , Tian Yiqing , Zhang Xiangmei , Kang Lin , Tai Yan , Liu Shuzhen , Wang Qian , Li Qingxia , Cai Jianhui
Published: February 2018

A murine monoclonal antibody (MAb-1) specific for GM3 has been generated by immunizing β3Gn-T5 knockout mice with purified GM3 ganglioside. The binding specificity of MAb-1 (IgG3 subclass) was established by an enzyme-linked immunosorbent assay (ELISA) and FACS and the antibody showed high binding specificity with GM3. Cell viability assay showed that MAb-1 significantly suppressed cell growth. Immunohistochemistry analysis revealed that MAb-1 was strongly expressed in human ovarian cancer tissues, whereas it was hardly expressed in normal tissues. Finally, antibody-dependent cellular cytotoxicity (ADCC) activities were determined by measuring lactate dehydrogenase (LDH) releasing assay and the results showed high ADCC activities in two representative ovarian cancer cell lines (OVHM and ID8). All of these data indicate that MAb-1 may be potentially used as a therapeutic antibody against ovarian cancers in clinical trials.
Broad-spectrum neutralization of avian influenza viruses by sialylated human milk oligosaccharides: in vivo assessment of 3′-sialyllactose against H9N2 in chickens
Authors: Pandey Ramesh Prasad , Kim Dae Hee , Woo Jinsuk , Song Jaeyoung , Jang Sang Ho , Kim Joon Bae , Cheong Kwang Myun , Oh Jin Sik , Sohng Jae Kyung
Published: February 2018

Two sialylated human milk oligosaccharides (SHMOs) 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) were accessed for their possible antiviral activity against six different subtypes of thirteen avian influenza (AI) viruses in vitro. 3′-SL exhibited promising antiviral activity against almost all subtypes of tested AI viruses in hemagglutination inhibition assay, whereas 6′-SL showed activity against few selected H1N1, H1N2, and H3N2 subtype strains. 3′-SL has minimum inhibitory concentration values of 15.62 mM or less in more than half of the viruses examined. 3′-SL also showed effective inactivation of H9N2 Korea isolate (A/Chicken/Korea/MS96/1996) at 12.5 mM concentration in Madin Darby Canine Kidney (MDCK) cell line. Thus, 3′-SL was further studied for in vivo study against H9N2 virus in pathogen free chicken experiment models. In vivo study exhibited improved clinical symptoms on H9N2 infected chickens when treated with 3′-SL. Moreover, treating chickens with 3′-SL resulted in complete elimination of H9N2 viruses within 24 h of virus infection (0.8 HAU of H9N2). Indirect ELISA assay confirmed complete wash-out of H9N2 viruses from the colon after neutralization by 3′-SL without entering the blood stream. These in vivo results open up possible applications of 3′-SL for the prevention of AI virus infections in birds by a simple cleansing mechanism.
Nitrogen-doped mesoporous SiC materials with catalytically active cobalt nanoparticles for the efficient and selective hydrogenation of nitroarenes
Authors: Eckardt Mirco , Zaheer Muhammad , Kempe Rhett
Published: February 2018

Mesoporous nitrogen-doped silicon carbide catalysts with integrated cobalt nanoparticles (Co@N-SiC) were synthesized by the thermal decomposition of a microphase-separated block copolymer of polycarbosilane and polyethylene. The catalysts are highly active, reusable and offer selective hydrogenation of the nitro group in the presence of hydrogenation-sensitive functional groups.
Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis
Authors: Zhou Zhike , Liang Yifan , Qu Huiling , Zhao Mei , Guo Feng , Zhao Chuansheng , Teng Weiyu
Published: February 2018

Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51–0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = −0.03, 95% CI = −0.13–0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48–0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51–1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30–0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51–0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.
Machine learning of correlated dihedral potentials for atomistic molecular force fields
Authors: Friederich Pascal , Konrad Manuel , Strunk Timo , Wenzel Wolfgang
Published: February 2018

Computer simulation increasingly complements experimental efforts to describe nanoscale structure formation. Molecular mechanics simulations and related computational methods fundamentally rely on the accuracy of classical atomistic force fields for the evaluation of inter- and intramolecular energies. One indispensable component of such force fields, in particular for large organic molecules, is the accuracy of molecule-specific dihedral potentials which are the key determinants of molecular flexibility. We show in this work that non-local correlations of dihedral potentials play a decisive role in the description of the total molecular energy—an effect which is neglected in most state-of-the-art dihedral force fields. We furthermore present an efficient machine learning approach to compute intramolecular conformational energies. We demonstrate with the example of α-NPD, a molecule frequently used in organic electronics, that this approach outperforms traditional force fields by decreasing the mean absolute deviations by one order of magnitude to values smaller than 0.37 kcal/mol (16.0 meV) per dihedral angle.
3D cellular structures and co-cultures formed through the contactless magnetic manipulation of cells on adherent surfaces
Authors: Abdel Fattah Abdel Rahman , Mishriki Sarah , Kammann Tobias , Sahu Rakesh P. , Geng Fei , Puri Ishwar K.
Published: February 2018

Label-free cell magnetic manipulations facilitate fast and new experimental setups and reveal novel observations in synthetic biology.
Kinetic Monte Carlo simulations of water ice porosity: extrapolations of deposition parameters from the laboratory to interstellar space
Authors: Clements Aspen R. , Berk Brandon , Cooke Ilsa R. , Garrod Robin T.
Published: February 2018

Using an off-lattice kinetic Monte Carlo model we reproduce experimental laboratory trends in the density of amorphous solid water (ASW) for varied deposition angle, rate and surface temperature. Extrapolation of the model to conditions appropriate to protoplanetary disks and interstellar dark clouds indicate that these ices may be less porous than laboratory ices.
A drastic influence of the anion nature and concentration on high pressure intrusion–extrusion of electrolyte solutions in Silicalite-1
Authors: Ryzhikov A. , Nouali H. , Daou T. J. , Patarin J.
Published: February 2018

Energetic performances and behavior of high-pressure intrusion–extrusion of concentrated saline solutions in MFI-type zeosil depend drastically on the anion nature.
Phase equilibrium and physical properties of biobased ionic liquid mixtures
Authors: Toledo Hijo Ariel A. C. , Maximo Guilherme J. , Cunha Rosiane L. , Fonseca Felipe H. S. , Cardoso Lisandro P. , Pereira Jorge F. B. , Costa Mariana C. , Batista Eduardo A. C. , Meirelles Antonio J. A.
Published: February 2018

Protic ionic liquid crystals (PILCs) obtained from natural sources are promising compounds due to their peculiar properties and sustainable appeal.
Sumanene: an efficient π-bowl for dihydrogen storage
Authors: Della Therese Davis , Suresh Cherumuttathu H.
Published: February 2018

The outstanding ability of sumanene, its anionic and dianionic forms and sumanene–M+ion-pair complexes (M = Li, Na, K) to bind dihydrogen has been revealed using density functional theory calculations pointing out that these systems could be employed for developing new H2storage systems.
Isolated Ni single atoms in graphene nanosheets for high-performance CO2 reduction
Authors: Jiang Kun , Siahrostami Samira , Zheng Tingting , Hu Yongfeng , Hwang Sooyeon , Stavitski Eli , Peng Yande , Dynes James , Gangisetty Mehash , Su Dong , Attenkofer Klaus , Wang Haotian
Published: February 2018

High-performance electrocatalytic CO2 reduction to CO using Ni single-atom catalyst in an anion membrane electrode assembly.
Minimum thermal conductivity in the context of diffuson-mediated thermal transport
Authors: Agne Matthias T. , Hanus Riley , Snyder G. Jeffrey
Published: February 2018

Diffuson-mediated thermal transport suggests a lower minimum thermal conductivity than phonon models.
Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies
Authors: Poongavanam Vasanthanathan , Corona Angela , Steinmann Casper , Scipione Luigi , Grandi Nicole , Pandolfi Fabiana , Di Santo Roberto , Costi Roberta , Esposito Francesca , Tramontano Enzo , Kongsted Jacob
Published: February 2018

In silicomethods identified a new class of inhibitors for HIV-1 RT RNase H and magnesium complexation study reveals the binding mode of these compounds.
Sensors for measuring subcellular zinc pools
Authors: Chabosseau Pauline , Woodier Jason , Cheung Rebecca , Rutter Guy A.
Published: February 2018

Zinc homeostasis is essential for normal cellular function, and defects in this process are associated with a number of diseases including type 2 diabetes (T2D), neurological disorders and cardiovascular disease.
Tunable clustering of magnetic nanoparticles in microgels: enhanced magnetic relaxivity by modulation of network architecture
Authors: Herman K. , Lang M. E. , Pich A.
Published: February 2018

In the present work we used microgels as colloidal containers for the loading of magnetic nanoparticles. By varying the crosslink density in the microgels, we show a non-linear enhancement of the transverse magnetization relaxation.
Few-layer NiPS3 nanosheets as bifunctional materials for Li-ion storage and oxygen evolution reaction
Authors: Dangol Raksha , Dai Zhengfei , Chaturvedi Apoorva , Zheng Yun , Zhang Yu , Dinh Khang Ngoc , Li Bing , Zong Yun , Yan Qingyu
Published: February 2018

A facile liquid-phase exfoliation strategy to explore high-yield exfoliation of NiPS3 and its anodic properties for LIBs and OER.
CdS nanosphere-decorated hollow polyhedral ZCO derived from a metal–organic framework (MOF) for effective photocatalytic water evolution
Authors: Chen Wenxia , Fang Jiasheng , Zhang Yiwei , Chen Guangliang , Zhao Shuo , Zhang Chao , Xu Ran , Bao Jiehua , Zhou Yuming , Xiang Xin
Published: February 2018

We design a new and economic noble metal-free CdS/ZnxCo3−xO4 (CdS/ZCO) nanohybrid photocatalyst using a metal–organic framework (MOF) template.
Phase and composition controlled synthesis of cobalt sulfide hollow nanospheres for electrocatalytic water splitting
Authors: Ma Xiaoya , Zhang Wei , Deng Yida , Zhong Cheng , Hu Wenbin , Han Xiaopeng
Published: February 2018

This work demonstrates the controllable synthesis of cobalt sulfide hollow nanospheres and the phase-dependent catalytic properties for the OER and HER.
Figuration of bowl-shaped π-conjugated molecules: properties and functions
Authors: Saito Masaichi , Shinokubo Hiroshi , Sakurai Hidehiro
Published: February 2018

Synthesis, properties, and functions of bowl-shaped pi-conjugated molecules including a hetero atom-doped system are reviewed.
Catalyst-free synthesis of tetrahydropyrimidines via formal [3+3]-cycloaddition of imines with 1,3,5-hexahydro-1,3,5-triazines
Authors: Chen Long , Liu Kai , Sun Jiangtao
Published: February 2018

A practical and environmentally benign synthesis of poly-substituted tetrahydropyrimidines via formal [3+3]-annulation of imines and 1,3,5-hexahydro-1,3,5-triazines under catalyst-free conditions has been developed.
An azo-coupling reaction-based surface enhanced resonance Raman scattering approach for ultrasensitive detection of salbutamol
Authors: Yu Shihua , Liu Zhigang , Zhang Jianpo , Li Hongwei , Xu Na , Yuan Xin-xin , Wu Yuqing
Published: February 2018

Azo-coupling reaction-based SERRS indirect approach for SAL detection, with a LOD of 1.0 × 10−11 M within 7 min for real samples.
SO2 enhanced desorption from basic aluminum sulfate desulphurization–regeneration solution by falling-film evaporation
Authors: Huang Kuo , Deng Xianhe , He Feiqiang
Published: February 2018

The heat and mass transfer performances of falling-film evaporation with converging–diverging tubes of different dimensions were studied.