bluuebunny/crossref_metadata_2025 huggingface dataset:
A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV
Authors: OhAinle Molly , Helms Louisa , Vermeire Jolien , Roesch Ferdinand , Humes Daryl , Basom Ryan , Delrow Jeffrey J , Overbaugh Julie , Emerman Michael
Published: December 2018

Interferon (IFN) inhibits HIV replication by inducing antiviral effectors. To comprehensively identify IFN-induced HIV restriction factors, we assembled a CRISPR sgRNA library of Interferon Stimulated Genes (ISGs) into a modified lentiviral vector that allows for packaging of sgRNA-encoding genomes in trans into budding HIV-1 particles. We observed that knockout of Zinc Antiviral Protein (ZAP) improved the performance of the screen due to ZAP-mediated inhibition of the vector. A small panel of IFN-induced HIV restriction factors, including MxB, IFITM1, Tetherin/BST2 and TRIM5alpha together explain the inhibitory effects of IFN on the CXCR4-tropic HIV-1 strain, HIV-1LAI, in THP-1 cells. A second screen with a CCR5-tropic primary strain, HIV-1Q23.BG505, described an overlapping, but non-identical, panel of restriction factors. Further, this screen also identifies HIV dependency factors. The ability of IFN-induced restriction factors to inhibit HIV strains to replicate in human cells suggests that these human restriction factors are incompletely antagonized.

Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
Authors: Bhattacharya Debadrita , Rothstein Megan , Azambuja Ana Paula , Simoes-Costa Marcos
Published: December 2018

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.
Prøvestikking ved Melkefoss, Sør-Varanger, Finnmark, 2006
Authors: Skandfer Marianne
Published: December 2018

Report (in Norwegian) on test-pitting at Melkefoss, Pasvik, Sør-Varanger municipality, Finnmark in 2006. Includes background, methods, observations, interpretations and AMS dates. Illustrated and with references. Related publications:Skandfer, M. 2012 "House Structures and Social Identification in Finnmark, Arctic Norway 2400 BC - AD 300." In Damm, Charlotte and Saarikiivi, Janne (eds.): Networks, Interaction and Emerging Identities in Fennoscandia and Beyond. Papers from the Conference held in Tromsø, Norway, October 13-16 2009. Suomalais-Ugrilainen Seura / Finno-Ugrian Society 2012 pp. 155-176 (2017-06-12) Related reports: http://doi.org/10.7557/7.4334http://doi.org/10.7557/7.4311http://doi.org/10.7557/7.4313
Rapport fra registreringer i Karasjok og Kautokeino kommuner, Finnmark, 2012
Authors: Skandfer Marianne
Published: December 2018

Archaeological survey report. Related publications:Skandfer, M., Blankholm, H. P. and Hood, B. (eds) Archaeological Perspectives on Hunter-Gatherer Landscapes and Resource Management in Interior North Norway. Equinox Publishing, Sheffield. Related reports:http://doi.org/10.7557/7.4335http://doi.org/10.7557/7.4333http://doi.org/10.7557/7.4331http://doi.org/10.7557/7.4324http://doi.org/10.7557/7.4325http://doi.org/10.7557/7.4328
Registreringer Kautokeino, Karasjok og Tana kommuner i forbindelse med post-doktorprosjekt i arkeologi 2006–2007
Authors: Skandfer Marianne
Published: December 2018

Archaeological survey report. Surveys conducted in Kautokeino, Karasjok and Tana municipalities, aiming at identifying semi-subterranean house-pits. Related publication: Blankholm, H. P. and Skandfer, M. (in press) House Pits in the Northern Interior. In: Skandfer, M., Blankholm, H. P. and Hood, B. (eds) Archaeological Perspectives on Hunter-Gatherer Landscapes and Resource Management in Interior North Norway. Equinox Publishing, Sheffield. (Chapter 12)Related reports:http://doi.org/10.7557/7.4332http://doi.org/10.7557/7.4334http://doi.org/10.7557/7.4335http://doi.org/10.7557/7.4311http://doi.org/10.7557/7.4312http://doi.org/10.7557/7.4313http://doi.org/10.7557/7.4314
The Selfer, Personality in a Virtual Paradigm
Authors: Salinas Mercado Esteban , González-González Alejandro
Published: December 2018

In view of the emerging behaviors facilitated by digital innovations, this article proposes an insight of the development of identity in the virtual paradigm. The task is to inscribe the selfie phenomenon in an exploratory manner within a pertinent theoretical framework that allows apprehending its aspects in terms of value and relationships. Using a qualitative ethnomethodology (Semantic Analysis Based on Images), it’s sought to locate certain narrative of the body in a context of interdisciplinary exchange in relation to a hypothetical category; namely the Selfer. Compiled sources derived from psychoanalysis, psychology, sociology, cybernetics etc. offer to inscribe these new phenomena into theories of mediation and the Subject. The ethnomethodology employed here considers selfie-narrative as a deployment of the body image. The interest lies in understanding motivations and consequences as individuals and societies through discursive consciousness. A group of three components were derived from the collected data: Self, The Ideal Virtual Collective Self (IVCS) and the Symptom. The results are presented as a narrative analysis of the participants’ discourse. This study considers selfies as trans-aesthetic objects with notable elicitation of self-impressions, based on a critical analysis of the participants’ testimonies. The findings of this study are relevant in a social context in terms of exploring the effect of selfies on mental health, psycho-dynamics and semiology.
'Overcoming' the 'Battlefield of the Mind'
Authors: Claydon Elizabeth Anna , Whitehouse-Hart Joanne
Published: December 2018

This article offers a psychoanalytically informed discursive analysis of the teachings of two leading Christian digital evangelists in the field of Christian ‘Self-help’ texts: Joyce Meyer and Joel Osteen. Meyer and Osteen both have global popularity and multimedia presences. Influenced by psychosocial theory, we combine linguistic analysis with the ideas of Kleinian and post-Kleinian object relations. Exploring Meyer’s and Osteen’s media usage, we argue that digital and online tools have enhanced their connective ability with their immense audiences. It is argued that such discursive spaces create new psychosocial possibilities and contradictions for their messages of emotional health and self-governance through a combination of scripture and psychological approaches common in secular self-help communication. Both preachers focus on changing ‘language’ and ‘thought’, employing techniques and scripture that require the believer to excessively self-focus, and this process revolves emotionally around the construction of images of an omnipotent, good God and the mind as a spiritual battleground between ‘good’ objects (God) and ‘bad’ (Satan).
Investigating More Effective and Less Effective EFL Learners’Attitudes and Motivational Orientation
Authors: Yousefi Halvaei Mohammadreza , Akbar Ansarin Ali
Published: December 2018

The present study investigated the differences in attitudes and motivation between more effective and less effective learners studying at the first year of graduate university program. Based on this aim, first, the researcher developed the three-part 35-item attitude-motivation questionnaire of the present study based on the AMTB developed by Gardner (1985). Second, he selected 441 students (224 male & 217 female) studying at the first year of their graduate program at universities in East Azarbayjan province (Iran) as the participants of the study. Third, he administered the questionnaire of the study to the selected participants and asked them to complete it. Finally, he analyzed the data of the study in order to answer the mentioned research questions. The chi-square test was utilized to analyze the collected data of the study. The results of the study showed that there were significant differences between more effective and less effective learners’ attitudes and motivation. Based on the results of the study, it was argued that, the EFL syllabus designers and teachers should help the learners to become aware of their attitudes, and motivational orientations. Furthermore, they should make an effort to tailor classroom materials and classroom teaching to the EFL learners’ individual differences.
Density-dependent changes in the distribution of Southern Right Whales (Eubalaena australis) in the breeding ground Peninsula Valdés
Authors: Sueyro Nicolas , Crespo Enrique Alberto , Arias Magdalena , Coscarella Mariano Alberto
Published: December 2018

Background

The Southern Right Whale (Eubalaena australis) population of the South–western Atlantic Ocean is recovering. In the breeding ground of Peninsula Valdés, as a consequence of the population growth, expansion to new areas by some types of groups and a change in the habitat use patterns at the coastal area were recorded.

Methods

We analysed information gathered from aerial surveys conducted along the coast of Peninsula Valdés in 15 years of effective sampling in a 19-year span. These surveys were divided into four periods (1999–2000; 2004–2007; 2008–2012 and 2013–2016) and estimated the density of whales in a 620 km of coast divided into segments of five km.

Results

The density of the whales increased to near three whales per km2(averaged over each period) in the high-density areas. When this mean number was reached, the significant changes in density in the adjacent areas were detected in the following period. These changes were a decrease in density in the high-density areas and an increase of density in the low-density areas.

Discussion

We propose that a threshold in density elicits a response in habitat use, with theMother-calfpairs remaining in the area, while theothergroups are displaced to new areas.
Genetic analysis reveals FinnishFormica fennicapopulations do not form a separate genetic entity fromF. exsecta
Authors: Hakala Sanja Maria , Seppä Perttu , Heikkilä Maria , Punttila Pekka , Sorvari Jouni , Helanterä Heikki
Published: December 2018

CoptoformicaMüller, 1923 is a subgenus ofFormicaLinnaeus, 1758 that consists of c. a dozen species of ants that typically inhabit open grassy habitats and build small nest mounds. The most recent addition to the group isFormica fennicaSeifert, 2000. The description was based on morphological characters, but the species status has not been confirmed by molecular methods. In this study, we use thirteen DNA microsatellite markers and a partial mitochondrial COI gene sequence to assess the species status ofF. fennica, by comparing the genetic variation among samples identified asF. fennicaand six other borealFormica (Coptoformica)species. Most of the species studied form separate, discontinuous clusters in phylogenetic and spatial analyses with only little intraspecific genetic variation. However, both nuclear and mitochondrial markers fail to separate the species pairF. exsectaNylander, 1846 andF. fennicadespite established morphological differences. The genetic variation within theF. exsecta/fennicagroup is extensive, but reflects spatial rather than morphological differences. FinnishF. fennicapopulations studied so far should not be considered a separate species, but merely a morph ofF. exsecta.
JacLy: a Jacobian-based method for the inference of metabolic interactions from the covariance of steady-state metabolome data
Authors: Khatibipour Mohammad Jafar , Kurtoğlu Furkan , Çakır Tunahan
Published: December 2018

Reverse engineering metabolome data to infer metabolic interactions is a challenging research topic. Here we introduce JacLy, a Jacobian-based method to infer metabolic interactions of small networks (<20 metabolites) from the covariance of steady-state metabolome data. The approach was applied to two different in silico small-scale metabolome datasets. The power of JacLy lies on the use of steady-state metabolome data to predict the Jacobian matrix of the system, which is a source of information on structure and dynamic characteristics of the system. Besides its advantage of inferring directed interactions, its superiority over correlation-based network inference was especially clear in terms of the required number of replicates and the effect of the use of priori knowledge in the inference. Additionally, we showed the use of standard deviation of the replicate data as a suitable approximation for the magnitudes of metabolite fluctuations inherent in the system.
Urbanization, environmental stabilization and temporal persistence of bird species: a view from Latin America
Authors: Leveau Lucas Matías
Published: December 2018

Background

A scarcely studied consequence of urbanization is the effect of temporal stabilization of the environment on bird communities. This alteration is thought to dampen environmental variations between day and night, seasons and years, promoting a temporal persistence of bird composition in urban areas. The aim of this study was to review current evidence of temporal stabilization of biotic and abiotic factors in urban environments and the potential effects of such stabilization on temporal variation of bird species presence at different temporal scales.

Methods

I selected the literature by searching published articles and book chapters using Scopus and Google scholar. I only included articles that compared the temporal variation of bird composition or resources between different levels of urbanization.

Results

In general, there is evidence of temporal stabilization of abiotic and biotic factors at the three time scales considered. At the diurnal scale, the main factor considered was artificial light in the context of light pollution. At the seasonal and interannual scales, several case studies found a smaller temporal variation of primary productivity in urban than in natural and rural areas. Bird species composition showed more stabilization in urban environments at the three temporal scales: (1) several case studies reported bird activity at night, associated with artificial light; (2) studies in urban parks and along urbanization gradients showed smaller seasonal variation of bird composition in the more urbanized areas; and (3) in general, case studies along urbanization gradients showed smaller interannual variation of bird composition in the more urbanized areas, although some studies showed no relationships or opposite trends than expected.

Discussion

The published evidence suggests that urban areas dampen the natural cycles at several temporal scales. The stabilization of biotic and abiotic factors, such as light, temperature, food and habitat structure, is desynchronized from natural diurnal, seasonal and interannual cycles. However, there is a dearth of long-term comparisons of bird composition and studies that simultaneously analyze the relationship between resources and bird composition stabilization at the seasonal and interannual scales. More research is needed in the Southern hemisphere, where there is a lack of studies dealing with the seasonal and interannual variations of primary productivity along urbanization gradients and nocturnal activity of bird species. A future research agenda should include differentiation of spatial and temporal homogenization of avifaunas.
Conservation implications of primate trade in China over 18 years based on web news reports of confiscations
Authors: Ni Qingyong , Wang Yu , Weldon Ariana , Xie Meng , Xu Huailiang , Yao Yongfang , Zhang Mingwang , Li Ying , Li Yan , Zeng Bo , Nekaris K.A.I.
Published: December 2018

Primate species have been increasingly threatened by legal and illegal trade in China, mainly for biomedical research or as pets and traditional medicine, yet most reports on trade from China regard international trade. To assess a proxy for amount of national primate trades, we quantified the number of reports of native primate species featuring in unique web news reports from 2000 to 2017, including accuracy of their identification, location where they were confiscated or rescued, and their condition upon rescue. To measure temporal trends across these categories, the time span was divided into three sections: 2000–2005, 2006–2011 and 2012–2017. A total of 735 individuals of 14 species were reported in 372 news reports, mostly rhesus macaques (n= 165, 22.5%,Macaca mulatta) and two species of slow lorises (n= 487, 66.3%,Nycticebusspp.). During the same period, live individuals of rhesus macaques were recorded 206 times (70,949 individuals) in the Convention on International Trade in Endangered Species of Wild Fauna and Flora Trade Database, whereas slow lorises were only recorded four times (nine individuals), indicating that the species originated illegally from China or were illegally imported into China. Due to their rescued locations in residential areas (n= 211, 56.7%), most primates appeared to be housed privately as pets. A higher proportion of ‘market’ rescues during 2006–2011 (χ2= 8.485, df= 2,p= 0.014), could be partly attributed to an intensive management on wildlife markets since the outbreak of severe acute respiratory syndrome (SARS) in 2003. More than half (68.3%, 502 individuals) of the primate individuals were unhealthy, injured or dead when rescued. Thus, identification and welfare training and capacity-building should be provided to husbandry and veterinary professionals, as well as education to the public through awareness initiatives. The increase in presence of some species, especially slow lorises, with a declining population in restricted areas, also suggests the urgent need for public awareness about the illegal nature of keeping these taxa as pets.
Modelling of the SDF-1/CXCR4 regulated in vivo homing of therapeutic mesenchymal stem/stromal cells in mice
Authors: Jin Wang , Liang Xiaowen , Brooks Anastasia , Futrega Kathryn , Liu Xin , Doran Michael R. , Simpson Matthew J. , Roberts Michael S. , Wang Haolu
Published: December 2018

Background

Mesenchymal stem/stromal cells (MSCs) are a promising tool for cell-based therapies in the treatment of tissue injury. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a significant role in directing MSC homing to sites of injury. However in vivo MSC distribution following intravenous transplantation remains poorly understood, potentially hampering the precise prediction and evaluation of therapeutic efficacy.

Methods

A murine model of partial ischemia/reperfusion (I/R) is used to induce liver injury, increase the hepatic levels of SDF-1, and study in vivo MSC distribution. Hypoxia-preconditioning increases the expression of CXCR4 in human bone marrow-derived MSCs. Quantitative assays for human DNA using droplet digital PCR (ddPCR) allow us to examine the in vivo kinetics of intravenously infused human MSCs in mouse blood and liver. A mathematical model-based system is developed to characterize in vivo homing of human MSCs in mouse models with SDF-1 levels in liver and CXCR4 expression on the transfused MSCs. The model is calibrated to experimental data to provide novel estimates of relevant parameter values.

Results

Images of immunohistochemistry for SDF-1 in the mouse liver with I/R injury show a significantly higher SDF-1 level in the I/R injured liver than that in the control. Correspondingly, the ddPCR results illustrate a higher MSC concentration in the I/R injured liver than the normal liver. CXCR4 is overexpressed in hypoxia-preconditioned MSCs. An increased number of hypoxia-preconditioned MSCs in the I/R injured liver is observed from the ddPCR results. The model simulations align with the experimental data of control and hypoxia-preconditioned human MSC distribution in normal and injured mouse livers, and accurately predict the experimental outcomes with different MSC doses.

Discussion

The modelling results suggest that SDF-1 in organs is an effective in vivo attractant for MSCs through the SDF-1/CXCR4 axis and reveal the significance of the SDF-1/CXCR4 chemotaxis on in vivo homing of MSCs. This in vivo modelling approach allows qualitative characterization and prediction of the MSC homing to normal and injured organs on the basis of clinically accessible variables, such as the MSC dose and SDF-1 concentration in blood. This model could also be adapted to abnormal conditions and/or other types of circulating cells to predict in vivo homing patterns.
Early‐onset colorectal cancer in young individuals
Authors: Mauri Gianluca , Sartore‐Bianchi Andrea , Russo Antonio‐Giampiero , Marsoni Silvia , Bardelli Alberto , Siena Salvatore
Published: December 2018

Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early‐onset CRC are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon‐sided location of the primary tumor. Among EO‐CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO‐CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, heredity and outcome of treatments of EO‐CRC, and provide considerations for future perspectives.
Printable Fabrication of a Fully Integrated and Self‐Powered Sensor System on Plastic Substrates
Authors: Lin Yuanjing , Chen Jiaqi , Tavakoli Mohammad Mahdi , Gao Yuan , Zhu Yudong , Zhang Daquan , Kam Matthew , He Zhubing , Fan Zhiyong
Published: December 2018

Wearable and portable devices with desirable flexibility, operational safety, and long cruising time, are in urgent demand for applications in wireless communications, multifunctional entertainments, personal healthcare monitoring, etc. Herein, a monolithically integrated self‐powered smart sensor system with printed interconnects, printed gas sensor for ethanol and acetone detection, and printable supercapacitors and embedded solar cells as energy sources, is successfully demonstrated in a wearable wristband fashion by utilizing inkjet printing as a proof‐of‐concept. In such a “wearable wristband”, the harvested solar energy can either directly drive the sensor and power up a light‐emitting diode as a warning signal, or can be stored in the supercapacitors in a standby mode, and the energy released from supercapacitors can compensate the intermittency of light illumination. To the best of our knowledge, the demonstration of such a self‐powered sensor system integrated onto a single piece of flexible substrate in a printable and additive manner has not previously been reported. Particularly, the printable supercapacitors deliver an areal capacitance of 12.9 mF cm−2 and the printed SnO2 gas sensor shows remarkable detection sensitivity under room temperature. The printable strategies for device fabrication and system integration developed here show great potency for scalable and facile fabrication of a variety of wearable devices.
Laser‐Scribed Graphene Oxide Electrodes for Soft Electroactive Devices
Authors: Kuhnel Djen T. , Rossiter Jonathan M. , Faul Charl F. J.
Published: December 2018

Inherently soft electroactive devices will enable a range of novel applications in biomedical, wearable, and robotics technology. In this area, dielectric elastomers (DEs) are particularly promising electromechanical transducers. One major challenge for DEs and other soft devices is the fabrication and precise patterning of thin stretchable conductors. Conventional methods such as pad printing and spray deposition require prefabricated molds or stencils, and inkjet printing relies on organic solvents to tune the rheology of inks. Here, laser‐scribed graphene oxide (LSGO) is proposed to fabricate patterned, stretchable electrodes for DE actuators (DEAs). The method uses a low‐cost laser engraver that can produce arbitrary patterns with 0.1 mm resolution. The process is green (free of organic solvents) and does not require molds or stencils. DEAs with regular and complex LSGO electrodes are fabricated and characterized. In a direct comparison with DEAs made using conductive carbon grease as electrode material, LSGO DEAs show higher maximum actuation strain. Areal strain of 8.8% is observed in a planar LSGO DEA with patterned electrodes.
A novel Core–Shell structured CuIn@SiO2 catalyst for CO2 hydrogenation to methanol
Authors: Shi Zhisheng , Tan Qingqing , Wu Dongfang
Published: December 2018

CO2 hydrogenation is one of the most promising processes in response to energy crisis and greenhouse gas emission. There is, however, still a lack of a highly efficient and sustainable catalyst for this reaction. In this study, a novel low‐cost core–shell structured CuIn@SiO2 catalyst is prepared by a solvothermal method and used for catalyzing CO2 hydrogenation to methanol. A significant interaction exists between Cu and In, promoting Cu dispersion and reducibility, Cu2In alloy and oxygen vacancy formation. Moreover, plenty of interfacial sites are formed between Cu2In and In2O3, which further enhances CO2 adsorption and activation. CuIn@SiO2, therefore, shows not only a satisfactory catalytic stability due to core–shell formation but also an excellent catalytic performance. 9.8% CO2 conversion, 78.1% CH3OH selectivity, and 13.7 ·h−1·gcat−1 CH3OH space–time yield are obtained at the space velocity of 20,000 mL·gcat−1·h−1. CuIn@SiO2 possesses a great potential as catalyst for CO2 hydrogenation in a moderate condition in industry. © 2018 American Institute of Chemical Engineers AIChE J, 65: 1047–1058, 2019
Dual‐phase membrane reactor for hydrogen separation with high tolerance to CO2 and H2S impurities
Authors: Cai Lili , Hu Shiqing , Cao Zhongwei , Li Hongbo , Zhu Xuefeng , Yang Weishen
Published: December 2018

Catalytic membrane reactors based on oxygen‐permeable membranes are recently studied for hydrogen separation because their hydrogen separation rates and separation factors are comparable to those of Pd‐based membranes. New membrane materials with high performance and good tolerance to CO2 and H2S impurities are highly desired. In this work, a new membrane material Ce0.85Sm0.15O1.925–Sr2Fe1.5Mo0.5O6‐δ (SDC–SFM) was prepared for hydrogen separation. It exhibits high conductivities at low oxygen partial pressures, which is benefit to electron transfer and ion diffusion. A high hydrogen separation rate of 6.6 mL cm−2 min−1 was obtained on a 0.5‐mm‐thick membrane coated with Ni/SDC catalyst at 900°C. The membrane reactor was operated steadily for 532 h under atmospheres containing CO2 and H2S impurities. Various characterizations reveal that SDC–SFM has good stability in the membrane reactor for hydrogen separation. All facts confirm that SDC–SFM is promising for hydrogen separation in practical applications. © 2018 American Institute of Chemical Engineers AIChE J, 65: 1088–1096, 2019
Directed Evolution Empowered Redesign of Natural Proteins for the Sustainable Production of Chemicals and Pharmaceuticals
Authors: Bornscheuer Uwe T. , Hauer Bernhard , Jaeger Karl Erich , Schwaneberg Ulrich
Published: December 2018

Directed evolution has advanced into a standard industrial “tool” to tailor naturally occurring proteins for a variety of biotechnological applications, thus enabling product valorization and bringing societal benefits across industrial sectors. Examples are sustainable enzymatic production processes for chemicals, pharmaceuticals, or applications in the food, feed, and laundry industries. In essence, directed evolution has contributed to sustainable industrial processes that fuel the transition from a fossil‐based economy to a biobased economy utilizing renewable resources. Phage display technologies represent a comparable breakthrough that allow for the directed evolution of binding proteins by physical coupling between a phenotype and the respective genotype, thus enabling the identification of highly selective antibodies for a broad variety of applications in diagnostics and therapy.
Preparation, characterization and catalytic application of molybdenum Schiff‐base complex immobilized on silica‐coated Fe3O4 as a reusable catalyst for the synthesis of pyranopyrazole derivatives
Authors: Hamrahian Seyedeh Aghigh , Salehzadeh Sadegh , Rakhtshah Jamshid , Haji babaei Farshid , Karami Niloofar
Published: December 2018

A recoverable molybdenum Schiff‐base complex immobilized on silica‐coated Fe3O4 nanoparticles was prepared and characterized. This superparamagntic nanocatalyst, which is separable using an external magnet, can be used as an efficient catalyst for the promotion of the synthesis of pyranopyrazole derivatives. A variety of desired products were obtained in high to excellent yields within short times. In comparison with other catalysts employed in the condensation of various aromatic aldehydes, malononitrile and 3‐methyl‐1‐phenyl‐2‐ pyrazoline‐5‐one, the present catalyst showed a much higher activity in terms of mild conditions and short reaction time. The catalyst can be reused for several times without significant loss of activity.
Chondroitin sulfate inhibits secretion of TNF and CXCL8 from human mast cells stimulated by IL‐33
Authors: Gross Amanda R. , Theoharides Theoharis C.
Published: December 2018

Glycosaminoglycans (GAGs) are linear, highly negatively charged carbohydrate chains present in connective tissues. Chondroitin sulfate (CS) and heparin (Hep) are also found in the numerous secretory granules of mast cells (MC), tissue immune cells involved in allergic and inflammatory reactions. CS and Hep may inhibit secretion of histamine from rat connective tissue MC, but their effect on human MC remains unknown. Human LAD2 MC were pre‐incubated with CS, Hep, or dermatan sulfate (DS) before being stimulated by either the peptide substance P (SP, 2 μM) or the cytokine IL‐33 (10 ng/mL). Preincubation with CS had no effect on MC degranulation stimulated by SP, but inhibited TNF (60%) and CXCL8 (45%) secretion from LAD2 cells stimulated by IL‐33. Fluorescein‐conjugated CS (CS‐F) was internalized by LAD2 cells only at 37 °C, but not 4 °C, indicating it occurred by endocytosis. DS and Hep inhibited IL‐33‐stimulated secretion of TNF and CXCL8 to a similar extent as CS. None of the GAGs tested inhibited IL‐33‐stimulated gene expression of either TNF or CXCL8. There was no effect of CS on ionomycin‐stimulated calcium influx. There was also no effect of CS on surface expression of the IL‐33 receptor, ST2. Neutralization of the hyaluronan receptor CD44 did not affect the internalization of CS‐F. The findings in this article show that CS inhibits secretion of TNF and CXCL8 from human cultured MC stimulated by IL‐33. CS could be formulated for systemic or topical treatment of allergic or inflammatory diseases, such as atopic dermatitis, cutaneous mastocytosis, and psoriasis. © 2018 BioFactors, 45(1):49–61, 2019
Effect of high fat diet on NF‐кB microRNA146a negative feedback loop in ovalbumin‐sensitized rats
Authors: Akhavanakbari Godrat , Babapour Behzad , Alipour Mohammad Reza , Keyhanmanesh Rana , Ahmadi Mahdi , Aslani Mohammad Reza
Published: December 2018

The present study aimed to investigate the role of microRNA‐146a and its adapter proteins [interleukin‐1 receptor‐associated kinase 1 (IRAK1) and tumor necrosis factor (TNF) receptor‐associated factor 6 (TRAF6)] in the pathogenesis of ovalbumin (OVA)‐sensitized rats in association with the diet‐induced obesity condition. Twenty male Wistar rats were divided into four groups: control with normal diet (ND), OVA‐sensitized with normal diet (S + ND), high‐fat diet (HFD), and OVA‐sensitized with high‐fat diet (S + HFD). All the animals were fed for 8 weeks with standard pelts or high‐fat diet, and were then sensitized and challenged with OVA or saline for another 4 weeks. The tracheal responsiveness to methacholine, serum protein levels, and lipid profile levels was measured by the ELISA method. Moreover, the gene expression level of microRNA‐146a (miR‐146a) was measured in the lung tissue of the rats using the real‐time PCR method. Maximum response to methacholin increased in the S + HFD group in compared with ND, S + ND, and HFD groups (P < 0.05 to P < 0.001). Moreover, in the S + HFD group the mRNA expression levels of miRNA‐146a increased in the lung tissue (P < 0.001). In addition, the protein analysis results showed that IRAK1, TRAF6, NF‐kB, and IL‐1β protein levels were high in the S + HFD group compared to the ND and HFD groups; however, in compared with the S + ND group, only the IL‐1β protein level was higher in the S + HFD group (P < 0.05). These results suggest that a defect in the NF‐kB–miR‐146a negative feedback loop may be involved in the pathogenesis of obesity associated with OVA‐sensitized condition. © 2018 BioFactors, 45(1):75–84, 2019
Development and validation of a rapid and sensitive UPLC–MS/MS assay for the quantification of tofacitinib in human plasma
Authors: Bharwad Kirtikumar D. , Shah Priyanka A. , Shrivastav Pranav S. , Singhal Puran
Published: December 2018

A highly sensitive, selective and rapid ultra‐performance liquid chromatography–tandem mass spectrometry method has been developed for the quantification of a Janus kinase (JAK) inhibitor, tofacitinib (TOF). The assay employed liquid–liquid extraction with methyl‐tert butyl ether to extract tofacitinib and tofacitinib‐13C3 15 N (as internal standard) from human plasma. The samples were analyzed on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column using acetonitrile and 10.0 mm ammonium acetate, pH 4.5 (75:25, v/v) as the mobile phase within 1.4 min. The precursor/product ion transitions were monitored at m/z 313.3/149.2 and 317.4/149.2 for tofacitinib and tofacitinib‐13C3 15 N, respectively, in the positive electrospray ionization mode. The calibration curves were linear (r2 ≥ 0.9978) across the concentration range of 0.05–100 ng/mL. The mean extraction recovery of tofacitinib across quality controls was 98.6%. The intra‐ and inter‐batch precision (CV) and accuracy ranged from 2.1–5.1 and 96.2–103.1%, respectively. All validation results complied well with the current guidelines. The method is amenable to high sample throughput and was applied to determine TOF plasma concentration in a pharmacokinetic study with 12 healthy Indian subjects after oral administration of 5 mg tablets.
Diffuse tibiofemoral cartilage change prior to the development of accelerated knee osteoarthritis: Data from the osteoarthritis initiative
Authors: Harkey Matthew S. , Davis Julie E. , Lu Bing , Price Lori Lyn , Eaton Charles B. , Lo Grace H. , Barbe Mary F. , Ward Robert J. , Zhang Ming , Liu Shao‐Hsien , Lapane Kate L. , MacKay James W. , McAlindon Timothy E. , Driban Jeffrey B.
Published: December 2018

We compared the spatial distribution of tibiofemoral cartilage change between individuals who will develop accelerated knee osteoarthritis (KOA) versus typical onset of KOA prior to the development of radiographic KOA. We conducted a longitudinal case–control analysis of 129 individuals from the Osteoarthritis Initiative. We assessed the percent change in tibiofemoral cartilage on magnetic resonance images at 36 informative locations from 2 to 1 year prior to the development of accelerated (n = 44) versus typical KOA (n = 40). We defined cartilage change in the accelerated and typical KOA groups at 36 informative locations based on thresholds of cartilage percent change in a no KOA group (n = 45). We described the spatial patterns of cartilage change in the accelerated KOA and typical KOA groups and performed a logistic regression to determine if diffuse cartilage change (predictor; at least half of the tibiofemoral regions demonstrating change in multiple informative locations) was associated with KOA group (outcome). There was a non‐significant trend that individuals with diffuse tibiofemoral cartilage change were 2.2 times more likely to develop accelerated knee OA when compared with individuals who develop typical knee OA (OR [95% CI] = 2.2 [0.90–5.14]. Adults with accelerated or typical KOA demonstrate heterogeneity in spatial distribution of cartilage thinning and thickening. These results provide preliminary evidence of a different spatial pattern of cartilage change between individuals who will develop accelerated versus typical KOA. These data suggest there may be different mechanisms driving the early structural disease progression between accelerated versus typical KOA. Clin. Anat. 32:369–378, 2019. © 2018 Wiley Periodicals, Inc.
Comparing Web‐Based and Traditional Career Interventions With Elementary Students: An Experimental Study
Authors: Cerrito Julie A. , Trusty Jerry , Behun Richard Joseph
Published: December 2018

Although research acknowledges the importance of the formative years of childhood in career development, there is a disconnection between theory and practice in elementary school counseling settings. This study compared a web‐based career guidance intervention with a traditional career guidance intervention by measuring the effects each one has on the career development progression of 4th‐ and 5th‐grade students. Using a pretest−posttest comparison group experimental design, the authors randomly assigned students to either the experimental group (web‐based) or the comparison group (traditional). Results showed significant interactions between group and time for 2 of the 4 subscales examined in the study. Research implications and best practices for infusing career development interventions into the elementary school counseling curriculum are discussed.
Functionalized Silver‐Ion‐Mediated α‐dC/β‐dC Hybrid Base Pairs with Exceptional Stability: α‐d‐5‐Iodo‐2′‐Deoxycytidine and Its Octadiynyl Derivative in Metal DNA
Authors: Müller Sebastian Lars , Zhou Xinglong , Leonard Peter , Korzhenko Oxana , Daniliuc Constantin , Seela Frank
Published: December 2018

Silver‐mediated α‐dC–Ag+–β‐dC hybrid base pairs decorated with 5‐iodo‐ or 5‐octadiynyl residues are well accommodated in duplex DNA. A strong Tm increase and favorable thermodynamic data for duplex DNA were observed after addition of silver ions. The phenomenon is particularly obvious when both nucleobases of the base pairs are functionalized. Neither the position of the base pair, nor the type of 5‐substituent had a negative influence. On the contrary, functionalization of conventional silver‐mediated β‐dC–Ag+–β‐dC homo base pairs showed a negative impact induced by the bulky substituents. To this end, cytosine modified 12‐mer oligodeoxynucleotides were prepared by solid‐phase synthesis employing new α‐anomeric 2′‐deoxycytidine phosphoramidites. A multigram scale synthesis was developed for 5‐iodo‐α‐d‐2′‐deoxycytidine (1) employing the direct glycosylation of cytosine with Hoffer's α‐d‐halogenose followed by separation of anomeric DMT nucleosides. Regarding base‐pair stability and functionalization silver‐mediated α/β‐dC hybrid base pairs were found to be superior to β/β‐dC homo pairs. According to their extraordinary properties, they might find applications in DNA diagnostics, material science, or nanotechnology.
Metal‐Organic Framework Derived Hierarchical Co/C@V2O3 Hollow Spheres as a Thin, Lightweight, and High‐Efficiency Electromagnetic Wave Absorber
Authors: Zhou Chenhui , Wu Chen , Liu Dong , Yan Mi
Published: December 2018

Developing high‐efficiency electromagnetic (EM) wave absorbing materials with light weight, thin thickness, and wide absorption bandwidth is highly desirable for ever‐developing electronic and telecommunication devices. Herein, hierarchical metal–organic framework (MOF)‐derived Co/C@V2O3 hollow spheres were designed and synthesized through a facile hydrothermal, precipitation, and pyrolysis method. The composite exhibits both excellent impedance matching and light weight due to the rational combination of hollow V2O3 spheres and porous Co/C. Additionally, multiple components enable a large dielectric and magnetic loss of the composite, giving rise to enhanced EM wave absorption performance with a maximum reflection loss (RL) of −40.1 dB and a broad effective absorption bandwidth (RL < −10 dB) of 4.64 GHz at a small thickness of 1.5 mm. This work provides insights into the design of hierarchical hollow and porous composites as thin and lightweight EM wave absorbers with efficient absorption, which can also be extended to energy storage, catalysis, and sensing.
The prevalence of human papillomavirus in oropharyngeal cancer is increasing regardless of sex or race, and the influence of sex and race on survival is modified by human papillomavirus tumor status
Authors: Faraji Farhoud , Rettig Eleni M. , Tsai Hua‐Ling , El Asmar Margueritta , Fung Nicholas , Eisele David W. , Fakhry Carole
Published: December 2018

Background

The purpose of this study was to evaluate the influence of sex and race/ethnicity upon prevalence trends of human papillomavirus (HPV) in oropharyngeal cancer (OPC) and survival after OPC.

Method

This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with OPC between 2010 and 2015. Outcomes were HPV status of tumor specimens and overall survival. Sex‐ and race‐stratified trends in HPV prevalence were estimated using generalized linear modeling. The influence of sex, race, and HPV tumor status on overall survival was compared by Kaplan‐Meier method and Cox Proportional Hazards models.

Results

This analysis included 20,886 HPV‐positive and 10,364 HPV‐negative OPC patients. The prevalence of HPV‐positive tumors was higher among men (70.6%) than women (56.3%) and increased significantly over time at a rate of 3.5% and 3.2% per year among men and women, respectively. The prevalence of HPV‐positive tumors was highest among whites (70.2%), followed by Hispanics (61.3%), Asians (55.8%), and blacks (46.3%). Blacks and Hispanics experienced significantly more rapid increases in prevalence of HPV‐positive tumors over time compared with whites (6.5% vs 5.6% vs 3.2% per year, respectively). In HPV‐positive OPC, neither sex nor race/ethnicity was associated with survival among patients with HPV‐positive OPC. In contrast, for HPV‐negative OPC, risk of death was significantly higher for women versus men (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.08‐1.26) and blacks versus whites (aHR, 1.21; 95% CI, 1.10‐1.33).

Conclusion

The prevalence of HPV‐positive tumors is increasing for all sex and race/ethnicity groups in the United States. Sex and race are independently associated with survival for HPV‐negative but not HPV‐positive OPC.
C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer
Authors: McFarland Daniel C. , Shaffer Kelly , Breitbart William , Rosenfeld Barry , Miller Andrew H.
Published: December 2018

Background

Depression is highly prevalent in lung cancer. Although there is a known association between inflammation and depression, this relationship has not been examined in patients with lung cancer who undergo treatment with immune and other targeted drug therapies. Peripheral blood C‐reactive protein (CRP), a marker of systemic inflammation, may help identify metastatic lung cancer patients with inflammation‐associated depression.

Method

Patients with metastatic lung cancer undergoing treatment were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS). Inflammation (CRP and CRP cutoffs ≥1 and ≥3 mg/mL) and demographic and treatment variables were analyzed for association with depression.

Results

One hundred nine consecutive participants exhibited an average plasma CRP concentration of 1.79 mg/mL (median, 0.75 mg/mL [standard deviation, 2.5 mg/mL), and 20.7% had a CRP concentration of ≥3.0 mg/mL; 23.9% met depression screening criteria (HADS ≥8). A log transformation of CRP was significantly correlated with depression severity (r = 0.47, P < .001). CRP was the only covariate to predict depression severity (P = .008) in a multivariate model including lung cancer disease subtype and type of systemic treatment. Receiver operating characteristic analysis indicated that CRP had moderate predictive accuracy in identifying elevated depression (area under the curve = 0.74). A cutoff of CRP ≥3.0 generated high specificity (88%) but identified only 50% of those with elevated depression.

Conclusion

Elevated CRP is associated with depression in patients with metastatic lung cancer. Thus, CRP may identify a subset of lung cancer patients with inflammation‐induced depression and may be useful in predicting response to treatments that target inflammation or its downstream mediators on the brain.
Oligometastatic prostate cancer: Reality or figment of imagination?
Authors: Foster Corey C. , Weichselbaum Ralph R. , Pitroda Sean P.
Published: December 2018

The term “oligometastatic prostate cancer” refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the “better‐than‐expected,” retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate‐specific membrane antigen‐targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk‐stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis‐directed therapy, future efforts should focus on conducting high‐quality, prospective trials with much‐needed molecular correlative studies.