bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory cytokine profiles in eyes with primary angle-closure glaucoma
Authors: Wang Yayi , Chen Shida , Liu Yaoming , Huang Wenbin , Li Xinyi , Zhang Xiulan
Published: November 2018

Acute primary angle-closure (APAC) eyes show an early ‘acute inflammatory’ condition, while the inflammation condition has not been fully elucidated in the development of primary angle-closure glaucoma (PACG). To evaluate the roles of inflammatory cytokines in the pathogenesis of PACG, this cross-sectional study involved 40 eyes of 32 PACG patients who required trabeculectomy and 24 eyes of 24 patients who required cataract surgery. The aqueous humor samples were collected at the time of surgery. Fifteen inflammatory cytokines were detected using the multiplex bead immunoassay technique, and the clinical information was recorded for the correlation analysis. Eight of the 15 cytokines were all detectable in both groups, including granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, and vascular endothelial growth factor (VEGF). When compared with the cataract patients, the MCP-3, MDC, and VEGF levels were elevated in the PACG patients, while the MCP-1 and MIP-1β levels were decreased. However, the G-CSF, IL-6, and IL-8 levels were similar between the two groups. The MCP-1 concentration was elevated accordingly as the disease progressed in the PACG patients. Our results suggest the PACG eyes retained a ‘mild inflammation’ condition in the aqueous humor, and MCP-1 may play an important role in the progression of this disease.
Research on passivity based control strategy of power conversion system used in the energy storage system
Authors: Li Jianguo , Lv Xiuping , Zhao Biao , Zhang Yajing , Zhang Qiaojie , Wang Jiuhe
Published: November 2018

This study proposes a practical control strategy of passivity based control (PBC) of the power conversion system (PCS) used in the energy storage system. First, the differential equations based on the Kirchhoff voltage and current laws are listed in the study, and the mathematical model in Euler–Lagrange form is also given. On the basis of the PBC theory, the system passivity of the PCS is demonstrated, the implementation of differential equations based on the damping injection principle is deduced, and simulation results in SIMULINK are also given. The PBC strategy has the advantages of high stability globally in a nonlinear system, and strong robustness to the system parameters deviation and external interference. Finally, a PCS prototype of 10 kW, which is made up of ac–dc converter and dc–dc converter, is built and the experimental results verify the correctness and effectivity of the proposed solution.
Implementation of wireless MEMS sensor network for detection of gait events
Authors: Bora Dhruba Jyoti , Kumar Neelesh , Dutta Ritushree
Published: November 2018

MEMS based wireless sensor network (WSN) for real‐time human health monitoring is promising in home‐based rehabilitation. It requires effective integration of a number of MEMS sensors and their placement on the human body to create a wireless body area network for continuous and timely monitoring of various biophysical parameters. This study attempts to develop an XBee‐based WSN for real‐time monitoring of human gait. Traditionally, the optical motion systems were used for gait analysis but they suffer from certain limitations such as the development of the complex algorithm and constrains in the work space. In comparison to the optical system, the attractive benefits of MEMS‐based sensor systems are small size and low cost. Magnetic field angular rate and gravity sensor system can perform a complete analysis of the human gait. The sensor modules were developed using the inertial sensors mainly accelerometer and gyro sensor. LabVIEW software is used for data acquisition from the body sensor nodes and gait analysis. Biometrics Lab System is used as the standard system for calibration of data obtained from sensors. The joint angle range of motion was calculated using both the systems. The advantage of the proposed system is that it facilitates wireless transmission of gait parameters (joint angle measurement) for easy monitoring of human gait in various rehabilitation programmes.
Toxicity, morphological and structural properties of chitosan‐coated Bi2O3–Bi(OH)3 nanoparticles prepared via DC arc discharge in liquid: a potential nanoparticle‐based CT contrast agent
Authors: Mohammadi Mohsen , Tavajjohi Atiyeh , Ziashahabi Azin , Pournoori Negin , Muhammadnejad Samad , Delavari Hamid , Poursalehi Reza
Published: November 2018

In this study, Bi2O3 nanoparticles were employed as computed tomography (CT) contrast agents. In this regard, X‐ray attenuation of Bi2O3 nanoparticles, prepared via DC arc discharge in water, was investigated. In addition, the optical, structural, morphology and cytotoxicity properties of afforded nanoparticles were also studied. The electric arc discharge was done via bismuth electrodes in a water medium. Then, to stabilise Bi2O3 nanoparticles, chitosan molecule was cross linked via glutaraldehyde around Bi2O3 nanoparticles. X‐ray diffraction analysis demonstrated the monoclinic structure and field emission‐scanning electron microscopy images clarified the average size of Bi2O3 as 40 nm. Fourier transform infrared analysis proved chitosan band formation around Bi2O3 nanoparticles. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay revealed no considerable toxicity after 72 h. Finally, X‐ray CT of chitosan‐coated Bi2O3 nanoparticles and Iohexol was carried out at concentrations of 1–6 mg/ml. The CT number of chitosan‐coated Bi2O3 nanoparticles measured 16, 30, 49, 66, 75 and 85, as well as, respective numbers for Iohexol were 5, 14, 25, 34, 44 and 57. Therefore, it displayed that X‐ray attenuation of chitosan‐coated Bi2O3 nanoparticle was more in comparison with Iohexol at the same concentrations. Eventually, the results demonstrated that chitosan‐coated Bi2O3 nanoparticles are a suitable candidate for commercial iodine contrast agent substitution.
Fabrication of antimony doped tin oxide nanopowders as an advanced electrode material for supercapacitors
Authors: Zhang Jie , Sun Yudong , Xu Jiasheng
Published: November 2018

The antimony doped tin oxide (Sb‐SnO2, ATO) nanopowders have been synthesised via a facile co‐precipitation method using absolute methanol as a solvent at room temperature and followed by a calcination process. The calcination process of fabricated ATO from precursor is investigated by thermogravimetric analysis (TGA). The crystallite phase and morphological structure of ATO powder are examined by the X‐ray diffraction and scanning electron microscopy. ATO material consisting of numerous sphere‐like nanoparticles with the diameter of 40–60 nm were further measured by electrochemical workstation, exhibiting the ATO nanostructure is an high‐conductivity electrode material with highly reversible features, good specific capacitance and good capacitance retention. The specific capacitance of the ATO electrode material shows 158.2 F g−1 at current density of 1 A g−1, and specific capacitance retention remained 72% when the current density increases up to 10 A g−1, indicating the ATO nanostructures materials can be considered as a promising electrode material for supercapacitors.
Pulsating low-mass white dwarfs in the frame of new evolutionary sequences
Authors: Calcaferro Leila M. , Córsico Alejandro H. , Althaus Leandro G. , Romero Alejandra D. , Kepler S. O.
Published: November 2018

Context. Some low-mass white-dwarf (WD) stars with H atmospheres currently being detected in our galaxy, show long-period g(gravity)-mode pulsations, and comprise the class of pulsating WDs called extremely low-mass variable (ELMV) stars. At present, it is generally believed that these stars have thick H envelopes. However, from stellar evolution considerations, the existence of low-mass WDs with thin H envelopes is also possible.

Aims. We present a thorough asteroseismological analysis of ELMV stars on the basis of a complete set of fully evolutionary models that represents low-mass He-core WD stars harboring a range of H envelope thicknesses. Although there are currently nine ELMVs, here we only focus on those that exhibit more than three periods and whose periods do not show significant uncertainties.

Methods. We considered g-mode adiabatic pulsation periods for low-mass He-core WD models with stellar masses in the range [0.1554–0.4352] M⊙, effective temperatures in the range [6000–10 000] K, and H envelope thicknesses in the interval −5.8 ≲ log(MH/M⋆)≲ −1.7. We explore the effects of employing different H-envelope thicknesses on the adiabatic pulsation properties of low-mass He-core WD models, and perform period-to-period fits to ELMV stars to search for a representative asteroseismological model.

Results. We found that the mode-trapping effects of g modes depend sensitively on the value of MH, with the trapping cycle and trapping amplitude larger for thinner H envelopes. We also found that the asymptotic period spacing, ΔΠa, is longer for thinner H envelopes. Finally, we found asteroseismological models (when possible) for the stars under analysis, characterized by canonical (thick) and by thin H envelope. The effective temperature and stellar mass of these models are in agreement with the spectroscopic determinations.

Conclusions. The fact that we have found asteroseismological solutions with H envelopes thinner than canonical gives a suggestion of the possible scenario of formation of these stars. Indeed, in the light of our results, some of these stars could have been formed by binary evolution through unstable mass loss.
Schmerztherapie beim Hund mit Curcuma longa L.
Authors: Thoonsen Yvonne
Published: November 2018

Curcumin ist die am besten charakterisierte Komponente aus dem Rhizom von Curcuma longa L., die eine Vielzahl von Wirkungen auf den Säugetierorganismus ausübt. Ihre antioxidativen und entzündungshemmenden Eigenschaften sind von großem Interesse und eröffnen einiges an Potenzial. Insbesondere für ältere multimorbide Hundepatienten stellt Curcumin eine wertvolle, wirkungsvolle, nebenwirkungsarme sowie auch praktisch adjuvante Therapie in Kombination mit anderen Analgetika dar. Zudem unterstützt und schützt sie zusätzlich das wichtigste Entgiftungsorgan des Organismus – die Leber – und könnte auch aufgrund seiner neuroprotektiven Wirkung bei Alzheimer-Demenz eine begleitende bzw. vorbeugende Therapieoption beim Kognitiven Dysfunktionssyndrom des Hundes darstellen. Der palliative Einsatz ggf. hochdosierten Curcumins bei Tumorerkrankungen könnte ebenfalls sinnvoll sein. Ernsthafte Studien zu Curcuma longa L., seinen Zubereitungen, Dosierungen und beim Tier sind gefordert.
Acute Effect of Active and Passive Static Stretching on Elastic Modulus of the Hamstrings
Authors: Nakao Gakuto , Taniguchi Keigo , Katayose Masaki
Published: November 2018

The purpose of this study was to investigate differences in the acute effects of passive knee extension (PKE) and active knee extension (AKE) stretching on the shear elastic modulus of the hamstrings. In 20 healthy men, maximum knee extension (maximum range of motion [ROM]) and shear elastic modulus of the hamstrings (biceps femoris long head, semitendinosus, semimembranosus) were measured before (Pre) and after (Post) AKE and PKE stretching. The maximum ROM during stretching was measured. In both stretching methods, maximum ROM increased and the shear elastic modulus decreased (p<0.01), but no difference was found between the procedures. No significant difference was observed in the maximum ROM during stretching between the procedures (p=0.06). The shear elastic modulus was significantly lower in the biceps femoris long head and semimembranosus than in the semitendinosus muscle (p<0.05). Static stretching with PKE and AKE stretching showed an increase in maximum ROM and a decrease in hamstring elasticity, but no difference was found between the methods. Both stretching protocols were effective for reducing elasticity of the biceps femoris long head and semimembranosus.
An Azirine Strategy for the Synthesis of Alkyl 4-Amino-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates
Authors: Khlebnikov Alexander , Funt Liya , Tomashenko Olesya , Novikov Mikhail
Published: November 2018

1-(3,3,3-Trifluoro-2,2-dihydroxypropyl)pyridin-1-ium bromide serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted aminopyrroles based on the 2H-azirine ring expansion strategy. The primary products, 3-aryl-2-(methoxycarbonyl)-4-(pyridin-1-ium-1-yl)-5-(trifluoromethyl)pyrrol-1-ides, can be hydrogenated by H2/PtO2 to form alkyl 3-aryl-4-(piperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates and transformed into alkyl 4-amino-3-aryl-1-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates via methylation/hydrazinolysis.
A Breath of Fresh Air
Authors: Jain Pratik , Chunawala Aafreen
Published: November 2018

Asthma affects individuals of all ages, from childhood into adulthood. Taking preventive measures is essential for asthmatic patients, as the recurrence of attacks is a major discomfort and stressor. Here, we will examine two cases of bronchial asthma from the practices of conscientious students who have learned under Dr. Rajan Sankaran. Here, the authors demonstrate the ease in which neo-homeopaths can also emulate Dr. Sankaran's various approaches and techniques of case taking and analysis, and also how to apply these very techniques to find a carefully selected medicine that brings a successful cure. Homeopathic remedies become ‘a breath of fresh air’ for these patients and provide long-term relief of symptoms, both physically and mentally.
The ADA-EASD patient-centered guidelines for management of hyperglycemia: Are they patient-centered enough?
Authors: Kalra Sanjay , Bantwal Ganapathy , John Mathew
Published: November 2018

Background: The American diabetes association (ADA) and European association for the study of diabetes (EASD) recently issued an updated position statement on the management of hyperglycemia in type 2 diabetes. The choice of nomenclature of these guidelines is refreshing as it highlights a patient-centered approach to managing diabetes.

Discussion: This debate looks at these guidelines through the prism of patient-centeredness, it tries to assess if the authors of the ADA-EASD position statement have been able to “walk the talk” with respect to the patient-centered approach that they advocate.

Conclusion: We conclude that the guidelines can be made more patient-centered, by emphasizing psychosocial and psychiatric comorbidity of diabetes, ethno pharmacy, and patient-friendly insulin regimes and oral fixed dose combinations, in a culturally competent, globally acceptable manner.
Social norms and farm animal protection
Authors: Delon Nicolas
Published: November 2018

Social change is slow and difficult. Social change for animals is formidably slow and difficult. Advocates and scholars alike have long tried to change attitudes and convince the public that eating animals is wrong. The topic of norms and social change for animals has been neglected, which explains in part the relative failure of the animal protection movement to secure robust support reflected in social and legal norms. Moreover, animal ethics has suffered from a disproportionate focus on individual attitudes and behavior at the expense of collective behavior, social change, and empirical psychology. If what we want to change is behavior on a large scale, norms are important tools. This article reviews an account of social norms that provides insights into the possibility and limitations of social change for animals, approaching animal protection as a problem of reverse social engineering. It highlights avenues for future work from this neglected perspective.
Cs0.33WO3 as a high-performance transparent solar radiation shielding material for windows
Authors: Xu Qiyan , Xiao Lihua , Ran Jingyu , Tursun Rabigul , Zhou Guangdong , Deng Lianli , Tang Dongsheng , Shu Qunwei , Qin Jingyun , Lu Guosong , Peng Ping
Published: November 2018

The optical properties of Cs0.33WO3 were analyzed based on experimental results reported in the literature. Its potential for use as a transparent energy-saving filter was evaluated using theoretical optical results. The results showed that Cs0.33WO3 exhibits excellent near-infrared radiation reflectance/absorption and high transmissivity of visible light, so it is ideal for use as a solar radiative filter for windows. In addition, Cs0.33WO3 provides perfect solar radiation shielding, suggesting that this material could be applied for compacted filters and nanoparticle-dispersed coatings. Two types of Cs0.33WO3 filters exhibited more than 80% transmissivity of visible light and excellent solar radiation shielding performance. This research work indicates that the doping of the Cs ion into hex-WO3 induces a persistent n-type electronic conductivity with metal-like characteristics and dramatically enhances near-infrared radiation absorption while maintaining excellent visible light transparency.
The origin of enhanced magnetodielectric effect in Y3-xYbxFe5O12 ceramics
Authors: Huang Yu Hui , Xu Zu Zhao , Liu Xiao Qiang , Li Juan , Wu Yong Jun
Published: November 2018

In this work, dielectric and magnetic behaviors, as well as magnetodielectric (MD) effect of Yb-substituted yttrium iron garnet (Y3-xYbxFe5O12) ceramics, have been studied systematically. Three dielectric relaxations are detected from the temperature spectrums, which can be attributed to the charge carries hopping between Fe2+ and Fe3+, inhomogeneous structure, and conduction, respectively. All the samples exhibit ferrimagnetic behaviors at room temperature and the saturation magnetization (Ms) increases first and then decreases with increasing Yb-substitution. The variation of Ms can be viewed as a comprehensive effect of superexchange interaction of Fe1-O-Fe2 and double exchange interaction between Fe2+ and Fe3+ ions. The room-temperature MD effect of Y3-xYbxFe5O12 ceramics measured at 15 kOe and 1 MHz are −1.11%, −1.33%, −2.04%, −1.48%, and −1.57%, for x = 0, 0.5, 1, 2, and 3, respectively. With the analysis of XPS spectra, the origin of enhanced MD effect has been investigated, and it is mainly caused by the response of local dipoles (Fe2+-Fe3+) under applied magnetic field.
Rare-earth high entropy alloys with hexagonal close-packed structure
Authors: Qiao J. W. , Bao M. L. , Zhao Y. J. , Yang H. J. , Wu Y. C. , Zhang Y. , Hawk J. A. , Gao M. C.
Published: November 2018

The formation of octonary DyErGdHoLuScTbY and senary DyGdHoLaTbY and ErGdHoLaTbY high-entropy alloys (HEAs) with the hexagonal close-packed (HCP) structure was reported in this study. Experiments using scanning electron microscopy and x-ray diffraction confirmed the single HCP solid solution in the as-cast state for these three HEAs if the presence of minor rare-earth oxides due to contamination from processing is ignored. The measured compressive yield stress values for these HEAs at room temperature are 245, 205, and 360 MPa for the ErGdHoLaTbY, DyGdHoLaTbY, and DyErGdHoLuScTbY HEAs, respectively. The corresponding solid solution strengthening contributions for these HEAs were estimated using a simple elastic model, and the resulting contributions were 28 MPa, 27 MPa, and 42 MPa for the three aforementioned HEAs.
A TPD-based determination of the graphite interlayer cohesion energy
Authors: Weippert Jürgen , Hauns Jakob , Bachmann Julian , Böttcher Artur , Yao Xuelin , Yang Bo , Narita Akimitsu , Müllen Klaus , Kappes Manfred M.
Published: November 2018

Temperature Programmed Desorption (TPD) spectroscopy was used to determine the binding energies of polycyclic aromatic hydrocarbons CnHm (22 ≤ n ≤ 60) with highly oriented pyrolytic graphite. These energies were then used to estimate the dispersive graphite interlayer cohesion by means of a refined extrapolation method proposed by Björk et al. This yields a cohesion energy of 44.0 ± 3.8 meV per carbon atom. We discuss some limits of the TPD-based approach and contrast our values with previous determinations of the interlayer cohesion energy of graphite.
Generalized Schrödinger equations with energy-dependent potentials: Formalism and applications
Authors: Schulze-Halberg Axel , Yeşiltaş Özlem
Published: November 2018

The quantum mechanical formalism for systems featuring energy-dependent potentials is extended to systems governed by generalized Schrödinger equations that include the position-dependent mass case. Modified versions of the probability density and the probability current lead to adjustments in the scalar product and the norm. Our results are applied to several systems, including energy-dependent modifications of the Mathews-Lakshmanan oscillator and the generalized Swanson system.
Fluctuations and Mixing State of an Aqueous Solution of the Ionic Liquid Tetrabutylphosphonium Trifluoroacetate around the Critical Point
Authors: Nitta Ayako , Morita Takeshi , Ohno Hiroyuki , Nishikawa Keiko
Published: November 2018

Aqueous solutions of ionic liquids have unique mixing states. Fluctuations are useful for understanding the inhomogeneity of the mixing states. In this study, an aqueous solution of tetrabutylphosphonium trifluoroacetate, ([P4,4,4,4]CF3COO), which exhibits a lower-critical-solution-temperature-type phase transition, was investigated. Focussing on the concentration and temperature range near the critical point, the fluctuations were evaluated by combining three kinds of experimentally obtained data: small-angle X-ray scattering intensity, partial molar volumes, and isothermal compressibility. Using Kirkwood–Buff integrals, individual density fluctuations of water and [P4,4,4,4]CF3COO were calculated, and these suggested that a large number of water molecules hydrated [P4,4,4,4]CF3COO ion pairs, and the hydrated ion pairs aggregated near the critical point. The relationship between the mesoscopic fluctuations and the macroscopic phase transition was clarified by drawing counter maps of the fluctuations in the phase diagrams.
Imaginative Order from Reasonable Chaos: Conformation-Driven Activity and Reactivity in Exploring Protein–Ligand Interactions
Authors: Moore Alexander F. , Newman David J. , Ranganathan Shoba , Liu Fei
Published: November 2018

Sir Derek Barton’s seminal work on steroid conformational analysis opened up a new era of enquiry into how the preferred conformation of any molecule could have profound effects on its physical–chemical properties and activities. Conformation-based effects on molecular activity and reactivity continue to manifest, with one key area of investigation currently focussed on conformational entropy in driving protein–ligand interactions. Carrying on from Barton’s initial insight on natural product conformational properties, new questions now address how conformational flexibility within a bioactive natural product structural framework (reasonable chaos), can be directed to confer dynamically new protein–ligand interactions beyond the basic lock–key model (imaginative order). Here we summarise our work on exploring conformational diversity from fluorinated natural product fragments, and how this approach of conformation-coupled diversity-oriented synthesis can be used to iteratively derive ligands with enhanced specificity against highly homologous protein domains. Our results demonstrate that the conformation entropic states of highly conserved protein domains differ significantly, and this conformational diversity, beyond primary sequence analysis, can be duly captured and exploited by natural-product derived ligands with complementary conformational dynamics for enhancing recognition specificity in drug lead discovery.
Differences in hydraulic traits of grapevine rootstocks are not conferred to a common Vitis vinifera scion
Authors: Barrios-Masias Felipe H. , Knipfer Thorsten , Walker M. Andrew , McElrone Andrew J.
Published: November 2018

Cultivars of grapevine are commonly grafted onto rootstocks to improve resistance against biotic and abiotic stress, however, it is not clear whether known differences in hydraulic traits are conferred from rootstocks to a common scion. We recently found that Vitis riparia and Vitis champinii differed in drought-induced embolism susceptibility and repair, which was related to differences in root pressure generation after rewatering (Knipfer et al. 2015). In the present study, we tested whether these and other physiological responses to drought are conferred to a common V. vinifera scion (Cabernet Sauvignon) grafted on V. riparia and V. champinii rootstocks. We measured xylem embolism formation/repair using in vivo microCT imaging, which was accompanied with analysis of leaf gas exchange, osmotic adjustment and root pressure. Our data indicate that differences in scion physiological behaviour for both rootstock combinations were negligible, suggesting that the sensitivity of Cabernet Sauvignon scion to xylem embolism formation/repair, leaf gas exchange and osmotic adjustment is unaffected by either V. riparia or V. champinii rootstock in response to drought stress.
Movement of juvenile barramundi (Lates calcarifer) through a cone ramp fishway at a modified coastal wetland in central Queensland, Australia
Authors: Power Trent , Moore Matthew , McCann Jack
Published: November 2018

Barramundi (Lates calcarifer) often migrate from marine to fresh water as juveniles. In March 2018a relatively large number of small juveniles (<100mm) were recorded moving through a fishway on a tidal interface barrier in central Queensland, Australia. This is in contrast to the few documented observations of transitional movements, which involved mostly larger juveniles (250–400mm).
Quantitation of class IA PI3Ks in mice reveals p110-free-p85s and isoform-selective subunit associations and recruitment to receptors
Authors: Tsolakos N. , Durrant T. N. , Chessa T. , Suire S. M. , Oxley D. , Kulkarni S. , Downward J. , Perisic O. , Williams R. L. , Stephens L. , Hawkins P. T.
Published: November 2018

Significance

The class IA PI3Ks, comprised of regulatory (p85α/p85β/p55γ) and catalytic (p110α/β/δ) subunits, which make the signaling lipid PIP
3
, constitute a key node in signaling. Many factors underlie their numerous cellular roles and large investments in the creation of PI3K-inhibitors. The existence of heterodimeric-isoforms (at least nine) with distinct distributions and properties and the often-debated existence of “p110-free-regulatory-subunits” as modulators provide the system with flexibility, redundancy and isoform-selective functions. Despite the scale of this endeavour, many of the system’s “rules of engagement” are unknown. Here we demonstrate preferential subunit associations, clarify the existence of “p110-free-regulatory-subunits”, show that they have properties that could allow them to modulate pathway activity, and reveal mechanisms that allow selective activation of PI3Kα and β by receptors.
MARCH3 attenuates IL-1β–triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI
Authors: Lin Heng , Gao Deng , Hu Ming-Ming , Zhang Man , Wu Xiao-Xia , Feng Lu , Xu Wen-Hua , Yang Qing , Zhong Xuan , Wei Jin , Xu Zhi-Sheng , Zhang Hong-Xia , Song Ze-Min , Zhou Qian , Ye Wen , Liu Ying , Li Shu , Shu Hong-Bing
Published: November 2018

Significance

Infection of pathogenic microbes induces the body to produce cytokines, which are mediators of inflammation. IL-1β plays central roles in the initiation of inflammatory and immune responses. In this study, we identified MARCH3 protein, which negatively regulates IL-1β–triggered signaling and inflammatory response by mediating K48-linked polyubiquitination of IL-1RI at lysine 409 and its lysosomal degradation. Our findings reveal a mechanism for how IL-1β–triggered inflammatory response is attenuated by down-regulation of IL-1β receptor.
pH-dependent thermodynamic intermediates of pHLIP membrane insertion determined by solid-state NMR spectroscopy
Authors: Otieno Sarah A. , Hanz Samuel Z. , Chakravorty Bianca , Zhang Anqi , Klees Lukas M. , An Ming , Qiang Wei
Published: November 2018

Significance

The pH low insertion peptide (pHLIP) inserts into membrane under mild acidity, forming a transmembrane α-helix. For applications, pHLIP can (
i
) detect local acidosis in vivo (e.g., for cancer imaging) and (
ii
) translocate polar, otherwise membrane-impermeable, cargos across membrane, which has far-reaching implications in research and medicine. Although the initial and end states of pHLIP insertion (at pH ≥ 7 and ≤5.3, respectively) are well known, how pHLIP interacts with membrane at the intervening pH values, which are most relevant to tumor acidity in vivo, is not clear. Here we use solid-state NMR spectroscopy to establish the distinct intermediate states that exist at the intervening pH values. Such understanding may improve pHLIP technology in the future.
The CD4−CD8−MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+MAIT cell pool
Authors: Dias Joana , Boulouis Caroline , Gorin Jean-Baptiste , van den Biggelaar Robin H. G. A. , Lal Kerri G. , Gibbs Anna , Loh Liyen , Gulam Muhammad Yaaseen , Sia Wan Rong , Bari Sudipto , Hwang William Y. K. , Nixon Douglas F. , Nguyen Son , Betts Michael R. , Buggert Marcus , Eller Michael A. , Broliden Kristina , Tjernlund Annelie , Sandberg Johan K. , Leeansyah Edwin
Published: November 2018

Significance

Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells recognizing microbial riboflavin metabolites presented by the monomorphic MR1 molecule. Here, we show that the CD8+CD4−and CD8−CD4−subpopulations of human MAIT cells represent transcriptionally and phenotypically discrete subsets with distinct functional profiles. Furthermore, T cell receptor repertoire analysis, as well as MAIT cell data based on human fetal tissues, umbilical cord blood, and culture systems indicate that the CD8−CD4−subset may derive from the main CD8+CD4−MAIT cell pool. Thus, MAIT cells, a major antimicrobial effector T cell population in humans, segregate into two functionally distinct but developmentally related subsets separated by the expression of CD8. This functional difference may have significant implications in infectious and inflammatory diseases.
Wrapping up the fats—a structure of the lipid droplet biogenesis protein seipin
Authors: Bohnert Maria
Published: November 2018

The lipid droplet (LD) biogenesis protein seipin is crucial for formation of normal LDs, but its exact functional role has been enigmatic. In this issue, Sui et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201809067) report the cryo­–electron microscopy structure of seipin, which provides novel insights into how seipin might mediate LD formation.
3-Chlorodiphenylamine activates cardiac troponin by a mechanism distinct from bepridil or TFP
Authors: Tikunova Svetlana B. , Cuesta Andres , Price Morgan , Li Monica X. , Belevych Natalya , Biesiadecki Brandon J. , Reiser Peter J. , Hwang Peter M. , Davis Jonathan P.
Published: November 2018

Despite extensive efforts spanning multiple decades, the development of highly effective Ca2+ sensitizers for the heart remains an elusive goal. Existing Ca2+ sensitizers have other targets in addition to cardiac troponin (cTn), which can lead to adverse side effects, such as hypotension or arrhythmias. Thus, there is a need to design Ca2+-sensitizing drugs with higher affinity and selectivity for cTn. Previously, we determined that many compounds based on diphenylamine (DPA) were able to bind to a cTnC–cTnI chimera with moderate affinity (Kd ∼10–120 µM). Of these compounds, 3-chlorodiphenylamine (3-Cl-DPA) bound most tightly (Kd of 10 µM). Here, we investigate 3-Cl-DPA further and find that it increases the Ca2+ sensitivity of force development in skinned cardiac muscle. Using NMR, we show that, like the known Ca2+ sensitizers, trifluoperazine (TFP) and bepridil, 3-Cl-DPA is able to bind to the isolated N-terminal domain (N-domain) of cTnC (Kd of 6 µM). However, while the bulky molecules of TFP and bepridil stabilize the open state of the N-domain of cTnC, the small and flexible 3-Cl-DPA molecule is able to bind without stabilizing this open state. Thus, unlike TFP, which drastically slows the rate of Ca2+ dissociation from the N-domain of isolated cTnC in a dose-dependent manner, 3-Cl-DPA has no effect on the rate of Ca2+ dissociation. On the other hand, the affinity of 3-Cl-DPA for a cTnC–TnI chimera is at least an order of magnitude higher than that of TFP or bepridil, likely because 3-Cl-DPA is less disruptive of cTnI binding to cTnC. Therefore, 3-Cl-DPA has a bigger effect on the rate of Ca2+ dissociation from the entire cTn complex than TFP and bepridil. Our data suggest that 3-Cl-DPA activates the cTn complex via a unique mechanism and could be a suitable scaffold for the development of novel treatments for systolic heart failure.
Condition-specific series of metabolic sub-networks and its application for gene set enrichment analysis
Authors: Tran Van Du T , Moretti Sébastien , Coste Alix T , Amorim-Vaz Sara , Sanglard Dominique , Pagni Marco
Published: November 2018

Motivation

Genome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism’s metabolism, yet their integration to achieve biological insight remains challenging.

Results

We investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO.

Availability and implementation

The metaboGSE R package is available at https://CRAN.R-project.org/package=metaboGSE.

Supplementary information

Supplementary data are available at Bioinformatics online.
PAVOOC: designing CRISPR sgRNAs using 3D protein structures and functional domain annotations
Authors: Schaefer Moritz , Clevert Djork-Arné , Weiss Bertram , Steffen Andreas
Published: November 2018

Single-guide RNAs (sgRNAs) targeting the same gene can significantly vary in terms of efficacy and specificity. PAVOOC (Prediction And Visualization of On- and Off-targets for CRISPR) is a web-based CRISPR sgRNA design tool that employs state of the art machine learning models to prioritize most effective candidate sgRNAs. In contrast to other tools, it maps sgRNAs to functional domains and protein structures and visualizes cut sites on corresponding protein crystal structures. Furthermore, PAVOOC supports homology-directed repair template generation for genome editing experiments and the visualization of the mutated amino acids in 3D.

Availability and implementation

PAVOOC is available under https://pavooc.me and accessible using modern browsers (Chrome/Chromium recommended). The source code is hosted at github.com/moritzschaefer/pavooc under the MIT License. The backend, including data processing steps, and the frontend are implemented in Python 3 and ReactJS, respectively. All components run in a simple Docker environment.

Supplementary information

Supplementary data are available at Bioinformatics online.
Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
Authors: Elhaik Eran , Ryan Desmond M
Published: November 2018

Motivation

In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug’s efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups.

Results

Pair Matcher (PaM) addresses stratification bias by optimizing pairing assignments a priori and/or a posteriori to the trial using both genetic and demographic criteria. Using simulated and real datasets, we show that PaM identifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on competing methods, including the commonly used principal component analysis (PCA). Homogenizing the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the trial or genetic study. PaM’s ancestral inferences also allow characterizing responders and developing a precision medicine approach to treatment.

Availability and implementation

PaM is freely available via Rhttps://github.com/eelhaik/PAM and a web-interface at http://elhaik-matcher.sheffield.ac.uk/ElhaikLab/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Local rewiring algorithms to increase clustering and grow a small world
Authors: Alstott Jeff , Klymko Christine , Pyzza Pamela B , Radcliffe Mary
Published: November 2018

Many real-world networks have high clustering among vertices: vertices that share neighbours are often also directly connected to each other. A network’s clustering can be a useful indicator of its connectedness and community structure. Algorithms for generating networks with high clustering have been developed, but typically rely on adding or removing edges and nodes, sometimes from a completely empty network. Here, we introduce algorithms that create a highly clustered network by starting with an existing network and rearranging edges, without adding or removing them; these algorithms can preserve other network properties even as the clustering increases. They rely on local rewiring rules, in which a single edge changes one of its vertices in a way that is guaranteed to increase clustering. This greedy step can be applied iteratively to transform a random network into a form with much higher clustering. Additionally, the algorithms presented grow a network’s clustering faster than they increase its path length, meaning that network enters a regime of comparatively high clustering and low path length: a small world. These algorithms may be a basis for how real-world networks rearrange themselves organically to achieve or maintain high clustering and small-world structure.
Negative Self-perception of Aging and Mortality in Very Old Chinese Adults: The Mediation Role of Healthy Lifestyle
Authors: Zhang Xin , Kamin Stefan T , Liu Songqi , Fung Helene H , Lang Frieder R
Published: November 2018

Objectives

Previous literature has consistently shown a positive association between negative self-perception of aging and mortality in middle-aged and older adults. However, two questions remain unsolved: (a) whether such association holds among very old people (i.e., the fourth age) and (b) the potential mediators that could contribute to the positive association. This study sought to fill in the research gap by examining the association between self-perception of aging and mortality in a group of very old Chinese participants (i.e., aged over 78 years).

Methods

Four waves of data across a span of 8 years (2000–2008) were obtained from the Chinese Longitudinal Healthy Longevity Survey, which measured a total of 9,683 participants’ negative self-perception of aging, survival status, cognitive functioning, diet, as well as other demographic information.

Results

Latent growth models with survival analysis were conducted, and the results replicated previous findings indicating an association between negative self-perceptions of aging and reduced survival. Moreover and more importantly, a potential mediator—healthy lifestyle (e.g., eating fresh vegetables and fruits, exercising regularly, and no smoking)—was identified, such that older adults with more negative self-perception of aging tended to engage in less healthy lifestyle, which could lead to increased risk of mortality.

Discussion

The findings provided support for a longitudinal behavioral pathway of health, linking negative perceptions of aging to mortality, and also yielded important practical implications for older adults to reach longevity.
Genomes of trombidid mites reveal novel predicted allergens and laterally transferred genes associated with secondary metabolism
Authors: Dong Xiaofeng , Chaisiri Kittipong , Xia Dong , Armstrong Stuart D , Fang Yongxiang , Donnelly Martin J , Kadowaki Tatsuhiko , McGarry John W , Darby Alistair C , Makepeace Benjamin L
Published: November 2018

Background

Trombidid mites have a unique life cycle in which only the larval stage is ectoparasitic. In the superfamily Trombiculoidea (“chiggers”), the larvae feed preferentially on vertebrates, including humans. Species in the genus Leptotrombidium are vectors of a potentially fatal bacterial infection, scrub typhus, that affects 1 million people annually. Moreover, chiggers can cause pruritic dermatitis (trombiculiasis) in humans and domesticated animals. In the Trombidioidea (velvet mites), the larvae feed on other arthropods and are potential biological control agents for agricultural pests. Here, we present the first trombidid mites genomes, obtained both for a chigger, Leptotrombidium deliense, and for a velvet mite, Dinothrombium tinctorium.

Results

Sequencing was performed using Illumina technology. A 180 Mb draft assembly for D. tinctorium was generated from two paired-end and one mate-pair library using a single adult specimen. For L. deliense, a lower-coverage draft assembly (117 Mb) was obtained using pooled, engorged larvae with a single paired-end library. Remarkably, both genomes exhibited evidence of ancient lateral gene transfer from soil-derived bacteria or fungi. The transferred genes confer functions that are rare in animals, including terpene and carotenoid synthesis. Thirty-seven allergenic protein families were predicted in the L. deliense genome, of which nine were unique. Preliminary proteomic analyses identified several of these putative allergens in larvae.

Conclusions

Trombidid mite genomes appear to be more dynamic than those of other acariform mites. A priority for future research is to determine the biological function of terpene synthesis in this taxon and its potential for exploitation in disease control.
On the numerical solution of a class of systems of linear matrix equations
Authors: Simoncini Valeria
Published: November 2018

We consider the solution of systems of linear matrix equations in two or three unknown matrices. For dense problems we derive algorithms that determine the numerical solution by only involving matrices of the same size as those in the original problem, thus requiring low computational resources. For large and structured systems we show how the problem properties can be exploited to design effective algorithms with low memory and operation requirements. Numerical experiments illustrate the performance of the new methods.
Anti-OspA DNA-Encoded Monoclonal Antibody Prevents Transmission of Spirochetes in Tick Challenge Providing Sterilizing Immunity in Mice
Authors: Wang Yang , Esquivel Rianne , Flingai Seleeke , Schiller Zachary A , Kern Aurélie , Agarwal Sangya , Chu Jacqueline , Patel Ami , Sullivan Katherine , Wise Megan C , Broderick Kate E , Hu Linden , Weiner David B , Klempner Mark S
Published: November 2018

We recently developed anti-OspA human immunoglobulin G1 monoclonal antibodies (HuMAbs) that are effective in preventing Borrelia transmission from ticks in a murine model. Here, we investigated a novel approach of DNA-mediated gene transfer of HuMAbs that provide protection against Lyme disease. Plasmid DNA-encoded anti-OspA HuMAbs inoculated in mice achieved a serum antibody concentration of >6 μg/mL. Among mice injected with DNA-encoded monoclonal antibodies, 75%–77% were protected against an acute challenge by Borrelia-infected ticks. Our results represent the first demonstration of employing DNA transfer as a delivery system for antibodies that block transmission of Borrelia in animal models.
Circulating Neutrophil Extracellular Traps and Neutrophil Activation Are Increased in Proportion to Disease Severity in Human Malaria
Authors: Kho Steven , Minigo Gabriela , Andries Benediktus , Leonardo Leo , Prayoga Pak , Poespoprodjo Jeanne R , Kenangalem Enny , Price Ric N , Woodberry Tonia , Anstey Nicholas M , Yeo Tsin W
Published: November 2018

Background

Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.

Methods

In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria; asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia; and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity.

Results

In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection.

Conclusions

Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.
Computational acoustic musicology
Authors: Boren Braxton B
Published: November 2018

While the challenge of historical reconstruction of past musical performances is not a fully solved problem, not all the elements are equally unknown, or of equal magnitude. Despite some uncertainty about the interpretation of individual performers on specific dates, scholarship can still inform other factors of greater perceptual importance, leading to a good approximation of historical performances. In addition to performance style and period instruments, computer simulations make it possible to also account for the acoustics of the period performance space. In addition, the most accurate reconstruction should simulate the room’s acoustics in real time for the performers, thus retaining the feedback mechanisms of room response on performance practice.