bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary iron and calcium intakes during pregnancy are associated with lower risk of prematurity, stillbirth and neonatal mortality among women in Tanzania
Authors: Mosha Dominic , Liu Enju , Hertzmark Ellen , Chan Grace , Sudfeld Christopher , Masanja Honorati , Fawzi Wafaie
Published: November 2016

Objective

Prematurity, stillbirth and other adverse birth outcomes remain major concerns in resource-limited settings. Poor dietary intake of micronutrients during pregnancy has been associated with increased risk of adverse outcomes. We determined the relationships between dietary Fe and Ca intakes during pregnancy and risks of adverse birth outcomes among HIV-negative women.

Design

Women’s diet was assessed through repeated 24 h diet recalls in pregnancy. Mean intakes of total Fe, Fe from animal sources and Ca during pregnancy were examined in relation to adverse birth outcomes and neonatal mortality. Women were prescribed daily Fe supplements as per standard perinatal care.

Setting

Dar es Salaam, Tanzania.

Subjects

A cohort of 7634 pregnant women.

Results

Median (interquartile range) daily dietary intake of total Fe, animal Fe and Ca was 11·9 (9·3–14·7), 0·5 (0–1·1) and 383·9 (187·4–741·2) mg, respectively. Total Fe intake was significantly associated with reduced risk of stillbirth (trend over quartiles, P=0·010). Animal Fe intake was significantly associated with reduced risk of preterm birth and extreme preterm birth. Animal Fe intake was inversely related to neonatal mortality risk; compared with women in the lowest intake quartile, those in the top quartile were 0·51 times as likely to have neonatal death (95 % CI 0·33, 0·77). Higher Ca intake was associated with reduced risk of preterm birth (relative risk; 95 % CI: 0·76; 0·65, 0·88) and extreme preterm birth (0·63; 0·47, 0·86). Women in the highest Ca intake quartile had reduced risk of neonatal mortality (0·59; 0·37, 0·92).

Conclusions

Daily dietary Fe and Ca intakes among pregnant women are very low. Improvement of women’s diet quality during gestation is likely to improve the risks of adverse birth outcomes.
How should realism and hope be combined in physician–patient communication at the end of life? An online focus-group study among participants with and without a Muslim background
Authors: Oosterveld-Vlug Mariska G. , Francke Anneke L. , Pasman H. Roeline W. , Onwuteaka-Philipsen Bregje D.
Published: November 2016

Objective:

Maintaining false hope may result in prolonged curative aggressive treatments until the very last stage of life. In this study, we sought to explore how people think that realistic and hopeful information should best be combined in physician–patient communications at the end of life.

Method:

During a period of 15 days, participants of five online focus groups (OFGs) could log in onto a closed discussion site and offer responses to several topics. A variety of people participated: patients, older people, relatives, and healthcare professionals with and without a Muslim background. Participants with a Muslim background constituted a separate group, because previous research indicated that they might have distinct views on good end-of-life care and communication. Transcripts were analyzed following the principles of thematic analysis.

Results:

Participants from all focus groups preferred that physicians provide realistic information in an empathic way, stating that the patient would never be left on his own and that withholding curative treatment was not equal to withholding care, explicitly asking how the patient could be helped during the time remaining, and involving other professionals in the care process and communications. As such, physicians could support patients' transition from “hope for a cure” to “hope for a good death.” Muslims specified the way they wished to receive realistic information: first from a relative, and not by using the term “incurable illness,” but rather by informing the patient that they had no remaining curative treatments available.

Significance of results:

Realism and hope are not necessarily mutually exclusive and can be combined when providing realistic information in a delicate and culturally sensitive way. This study provides suggestions on how physicians can do so. Communication skills training as well as anchoring knowledge of the diversity of cultural and religious views into physicians' education could improve end-of-life communication.
The Use of ‘Macro’ Legal Analysis in the Understanding and Development of Global Environmental Governance
Authors: Turner Stephen J.
Published: November 2016

This article examines the manner in which ‘macro’ legal analysis can potentially assist in overcoming some of the issues that are faced in the understanding and development of global environmental governance (GEG). It argues that the analysis of law through separate and distinct disciplines – such as environmental law, trade law, corporate law, and human rights law – results in what this article refers to as ‘micro’ legal analysis. As such, it contends that this can have the effect of creating obstacles in the development of coherent and effective legal and policy choices related to the protection of the environment. It illustrates these arguments with examples of practical problems that have arisen from the separation of legal issues in practice and provides the theoretical underpinnings, based on the critique of international lawyers, for the application of ‘macro’ legal analysis. In other words, it argues for a form of analysis that would consider the entire range of relevant legal disciplines in a unitary process. It then provides a methodology for the development and application of ‘macro’ legal analysis in relation to environmental issues. Finally, it considers the potential that this approach could have within the field of GEG and comments on the implications that it could have for the way in which lawyers are trained in the future.
Frightened by an Old Scarecrow: The Remarkable Resilience of Demand Characteristics
Authors: Sharpe Donald , Whelton William J.
Published: November 2016

More than 50 years ago, the idea of demand characteristics was introduced by Martin Orne in a widely cited American Psychologist article. Through the 1960s and the mid-1970s, numerous studies were conducted investigating the role of demand characteristics in a variety of research areas. Demand characteristics faded from researchers’ attention in the late 1970s, relegated to brief descriptions in research methods textbooks. The present article traces the origins of and battles fought over demand characteristics during its heyday. Evidence is provided that suggests demand characteristics experienced a rebirth in the 1980s and it remains a widely referenced idea up to today. Demand characteristics reflect perennial concerns about the difficulties of and limitations to doing research with humans, concerns that often surface in the periodic crises that confront psychology. The types of problems that animated the crisis of confidence associated with demand characteristics in the 1970s form one dimension of the current replication crisis. Reinterpretation of this current replication crisis and a new direction for experimental research with human subjects are derived from this review of demand characteristics.
Stiffening of sickle cell trait red blood cells under simulated strenuous exercise conditions
Authors: Xu Zhensong , Zheng Yi , Wang Xian , Shehata Nadine , Wang Chen , Xie Shaorong , Sun Yu
Published: November 2016

The higher risk of vaso-occlusion events and sudden death for sickle-cell trait (SCT) athletes has been speculatively ascribed to SCT red blood cell (RBC) stiffening during strenuous exercise. However, the microenvironmental changes that could induce the stiffening of SCT RBCs are unknown. To address this question, we measured the mechanical properties of and changes in SCT RBCs under deoxygenated and acidic environments, which are two typical conditions present in the circulation of athletes undertaking strenuous exercise. The results reveal that SCT RBCs are inherently stiffer than RBCs from non-SCT healthy subjects, and a lower pH further stiffens the SCT cells. Furthermore, at both normal and low pH levels, deoxygenation was found to not be the cause of the stiffness of SCT RBCs. This study confirms that the stiffening of SCT RBCs occurs at a low pH and implies that SCT RBC stiffening could be responsible for vaso-occlusion in SCT athletes during strenuous exercise.
Highly durable organic electrode for sodium-ion batteries via a stabilized α-C radical intermediate
Authors: Wu Shaofei , Wang Wenxi , Li Minchan , Cao Lujie , Lyu Fucong , Yang Mingyang , Wang Zhenyu , Shi Yang , Nan Bo , Yu Sicen , Sun Zhifang , Liu Yao , Lu Zhouguang
Published: November 2016

It is a challenge to prepare organic electrodes for sodium-ion batteries with long cycle life and high capacity. The highly reactive radical intermediates generated during the sodiation/desodiation process could be a critical issue because of undesired side reactions. Here we present durable electrodes with a stabilized α-C radical intermediate. Through the resonance effect as well as steric effects, the excessive reactivity of the unpaired electron is successfully suppressed, thus developing an electrode with stable cycling for over 2,000 cycles with 96.8% capacity retention. In addition, the α-radical demonstrates reversible transformation between three states: C=C; α-C·radical; and α-C− anion. Such transformation provides additional Na+ storage equal to more than 0.83 Na+ insertion per α-C radical for the electrodes. The strategy of intermediate radical stabilization could be enlightening in the design of organic electrodes with enhanced cycling life and energy storage capability.
Growing three-dimensional biomorphic graphene powders using naturally abundant diatomite templates towards high solution processability
Authors: Chen Ke , Li Cong , Shi Liurong , Gao Teng , Song Xiuju , Bachmatiuk Alicja , Zou Zhiyu , Deng Bing , Ji Qingqing , Ma Donglin , Peng Hailin , Du Zuliang , Rümmeli Mark Hermann , Zhang Yanfeng , Liu Zhongfan
Published: November 2016

Mass production of high-quality graphene with low cost is the footstone for its widespread practical applications. We present herein a self-limited growth approach for producing graphene powders by a small-methane-flow chemical vapour deposition process on naturally abundant and industrially widely used diatomite (biosilica) substrates. Distinct from the chemically exfoliated graphene, thus-produced biomorphic graphene is highly crystallized with atomic layer-thickness controllability, structural designability and less noncarbon impurities. In particular, the individual graphene microarchitectures preserve a three-dimensional naturally curved surface morphology of original diatom frustules, effectively overcoming the interlayer stacking and hence giving excellent dispersion performance in fabricating solution-processible electrodes. The graphene films derived from as-made graphene powders, compatible with either rod-coating, or inkjet and roll-to-roll printing techniques, exhibit much higher electrical conductivity (∼110,700 S m−1 at 80% transmittance) than previously reported solution-based counterparts. This work thus puts forward a practical route for low-cost mass production of various powdery two-dimensional materials.
An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy
Authors: Chen Yichao , Xia Rui , Huang Yixian , Zhao Wenchen , Li Jiang , Zhang Xiaolan , Wang Pengcheng , Venkataramanan Raman , Fan Jie , Xie Wen , Ma Xiaochao , Lu Binfeng , Li Song
Published: November 2016

Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models.
Co-designing a scalable quantum computer with trapped atomic ions
Authors: Brown Kenneth R , Kim Jungsang , Monroe Christopher
Published: November 2016

The first generation of quantum computers are on the horizon, fabricated from quantum hardware platforms that may soon be able to tackle certain tasks that cannot be performed or modelled with conventional computers. These quantum devices will not likely be universal or fully programmable, but special-purpose processors whose hardware will be tightly co-designed with particular target applications. Trapped atomic ions are a leading platform for first-generation quantum computers, but they are also fundamentally scalable to more powerful general purpose devices in future generations. This is because trapped ion qubits are atomic clock standards that can be made identical to a part in 1015, and their quantum circuit connectivity can be reconfigured through the use of external fields, without modifying the arrangement or architecture of the qubits themselves. In this forward-looking overview, we show how a modular quantum computer with thousands or more qubits can be engineered from ion crystals, and how the linkage between ion trap qubits might be tailored to a variety of applications and quantum-computing protocols.
Phase transitions and self-organized criticality in networks of stochastic spiking neurons
Authors: Brochini Ludmila , de Andrade Costa Ariadne , Abadi Miguel , Roque Antônio C. , Stolfi Jorge , Kinouchi Osame
Published: November 2016

Phase transitions and critical behavior are crucial issues both in theoretical and experimental neuroscience. We report analytic and computational results about phase transitions and self-organized criticality (SOC) in networks with general stochastic neurons. The stochastic neuron has a firing probability given by a smooth monotonic function Φ(V) of the membrane potential V, rather than a sharp firing threshold. We find that such networks can operate in several dynamic regimes (phases) depending on the average synaptic weight and the shape of the firing function Φ. In particular, we encounter both continuous and discontinuous phase transitions to absorbing states. At the continuous transition critical boundary, neuronal avalanches occur whose distributions of size and duration are given by power laws, as observed in biological neural networks. We also propose and test a new mechanism to produce SOC: the use of dynamic neuronal gains – a form of short-term plasticity probably located at the axon initial segment (AIS) – instead of depressing synapses at the dendrites (as previously studied in the literature). The new self-organization mechanism produces a slightly supercritical state, that we called SOSC, in accord to some intuitions of Alan Turing.
Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth
Authors: Chin Peck Yin , Dorian Camilla L. , Hutchinson Mark R. , Olson David M. , Rice Kenner C. , Moldenhauer Lachlan M. , Robertson Sarah A.
Published: November 2016

Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (−)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed E. coli. Local induction by E. coli of inflammatory cytokine genes Il1b, Il6, Tnf and Il10 in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.
Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin
Authors: Engels Christina , Schwab Clarissa , Zhang Jianbo , Stevens Marc J. A. , Bieri Corinne , Ebert Marc-Olivier , McNeill Kristopher , Sturla Shana J. , Lacroix Christophe
Published: November 2016

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.
TALEN-mediated knock-in via non-homologous end joining in the crustacean Daphnia magna
Authors: Nakanishi Takashi , Kato Yasuhiko , Matsuura Tomoaki , Watanabe Hajime
Published: November 2016

Transcription activator-like effector nucleases (TALENs) are versatile tools that enable the insertion of DNA into different organisms. Here, we confirmed TALEN-mediated knock-in via non-homologous end joining in the crustacean Daphnia magna, a model organism for ecological and toxicological genomics. We tested two different TALENs, ey1 TALEN and ey2 TALEN, both of which target the eyeless locus. The donor DNA plasmid, harbouring the H2B-GFP reporter gene, was designed to contain both TALEN target sites and was co-injected with each TALEN mRNA into eggs. The ey1 TALEN and ey2 TALEN constructs both resulted in H2B-GFP expression in Daphnia with a germline transmission efficiency of 3%. Of the three transgenic animals generated, two had donor DNA at the targeted genomic site, which suggested concurrent cleavage of the injected plasmid DNA and genome DNA. The availability of such tools that are capable of targeted knock-in of foreign genes will be extremely useful for advancing the knowledge of gene function and contribute to an increased understanding of functional genomics in Daphnia.
Children’s Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease
Authors: Li Pengyuan , Li Tao , Gu Qiuyun , Chen Xiaomin , Li Jiahui , Chen Xiashi , Chen Yan , Zhang Danwei , Gao Rong , He Zhenjian , Zhu Xun , Zhang Wangjian , Hao Yuantao , Zhang Dingmei
Published: November 2016

Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children’s caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children’s 257 samples (98 children’s caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children’s caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children’s caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities.
Neovestitol, an isoflavonoid isolated from Brazilian red propolis, reduces acute and chronic inflammation: involvement of nitric oxide and IL-6
Authors: Franchin Marcelo , Colón David F. , da Cunha Marcos G. , Castanheira Fernanda V. S. , Saraiva André L. L. , Bueno-Silva Bruno , Alencar Severino M. , Cunha Thiago M. , Rosalen Pedro L.
Published: November 2016

Isoflavonoids have been largely studied due to their distinct biological activities identified thus far. Herein, we evaluated the activity of neovestitol, an isoflavonoid isolated from Brazilian red propolis, in acute and chronic inflammation. As for acute inflammation, we found that neovestitol reduced neutrophil migration, leukocyte rolling and adhesion, as well as expression of ICAM-1 in the mesenteric microcirculation during lipopolysaccharide-induced acute peritonitis. No changes were observed in the levels of TNF-α, CXCL1/KC and CXCL2/MIP-2 upon pretreatment with neovestitol. The administration of an inducible nitric oxide synthase (iNOS) inhibitor abolished the inhibitory effects of neovestitol in neutrophil migration and ICAM-1 expression. Nitrite levels increased upon treatment with neovestitol. No effects of neovestitol were observed on the chemotaxis of neutrophils in vitro. As for chronic inflammation, neovestitol also reduced the clinical score and joint damage in a collagen-induced arthritis model. There was no change in the frequency of IL-17-producing TCD4+ cells. In addition, pretreatment with neovestitol reduced the levels of IL-6. These results demonstrate a potential anti-inflammatory activity of neovestitol, which may be useful for therapeutic purposes and/or as a nutraceutical.
Water-soluble acacetin prodrug confers significant cardioprotection against ischemia/reperfusion injury
Authors: Liu Hui , Yang Lei , Wu Hui-Jun , Chen Kui-Hao , Lin Feng , Li Gang , Sun Hai-Ying , Xiao Guo-Sheng , Wang Yan , Li Gui-Rong
Published: November 2016

The morbidity and mortality of patients with ischemic cardiomyopathy resulted from ischemia/reperfusion injury are very high. The present study investigates whether our previously synthesized water-soluble phosphate prodrug of acacetin was cardioprotective against ischemia/reperfusion injury in anin vivorat model. We found that intravenous administration of acacetin prodrug (10 mg/kg) decreased the ventricular arrhythmia score and duration, reduced ventricular fibrillation and infarct size, and improved the impaired heart function induced by myocardial ischemia/reperfusion injury in anesthetized rats. The cardioprotective effects were further confirmed with the parent compound acacetin in anex vivorat regional ischemia/reperfusion heart model. Molecular mechanism analysis revealed that acacetin prevented the ischemia/reperfusion-induced reduction of the anti-oxidative proteins SOD-2 and thioredoxin, suppressed the release of inflammation cytokines TLR4, IL-6 and TNFα, and decreased myocyte apoptosis induced by ischemia/reperfusion. Our results demonstrate the novel evidence that acacetin prodrug confer significantin vivocardioprotective effect against ischemia/reperfusion injury by preventing the reduction of endogenous anti-oxidants and the release of inflammatory cytokines, thereby inhibiting cardiomyocytes apoptosis, which suggests that the water-soluble acacetin prodrug is likely useful in the future as a new drug candidate for treating patients with acute coronary syndrome.
Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin
Authors: Hu Bang-li , Shi Cheng , Lei Rong-e , Lu Dong-hong , Luo Wei , Qin Shan-yu , Zhou You , Jiang Hai-xing
Published: November 2016

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. β-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced β-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of β-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while β-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of β-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of β-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of β-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and β-catenin pathway.
A microfluidic device for measuring cell migration towards substrate-bound and soluble chemokine gradients
Authors: Schwarz Jan , Bierbaum Veronika , Merrin Jack , Frank Tino , Hauschild Robert , Bollenbach Tobias , Tay Savaş , Sixt Michael , Mehling Matthias
Published: November 2016

Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue.
Engineering of Escherichia coli for direct and modulated biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer using unrelated carbon sources
Authors: Srirangan Kajan , Liu Xuejia , Tran Tam T. , Charles Trevor C. , Moo-Young Murray , Chou C. Perry
Published: November 2016

While poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] is a biodegradable commodity plastic with broad applications, its microbial synthesis is hindered by high production costs primarily associated with the supplementation of related carbon substrates (e.g. propionate or valerate). Here we report construction of engineered Escherichia coli strains for direct synthesis of P(3HB-co-3HV) from an unrelated carbon source (e.g. glucose or glycerol). First, an E. coli strain with an activated sleeping beauty mutase (Sbm) operon was used to generate propionyl-CoA as a precursor. Next, two acetyl-CoA moieties or acetyl-CoA and propionyl-CoA were condensed to form acetoacetyl-CoA and 3-ketovaleryl-CoA, respectively, by functional expression of β-ketothiolases from Cupriavidus necator (i.e. PhaA and BktB). The resulting thioester intermediates were channeled into the polyhydroxyalkanoate (PHA) biosynthetic pathway through functional expression of acetoacetyl-CoA reductase (PhaB) for thioester reduction and PHA synthase (PhaC) for subsequent polymerization. Metabolic engineering of E. coli host strains was further conducted to enhance total PHA content and the 3-hydroxyvaleryl (3HV) monomer fraction in the copolymer. Using a selection of engineered E. coli strains for batch cultivation with an unrelated carbon source, we achieved high-level P(3HB-co-3HV) production with the 3HV monomer fraction ranging from 3 to 19 mol%, demonstrating the potential industrial applicability of these whole-cell biocatalysts.
Recombinant spider silk from aqueous solutions via a bio-inspired microfluidic chip
Authors: Peng Qingfa , Zhang Yaopeng , Lu Li , Shao Huili , Qin Kankan , Hu Xuechao , Xia Xiaoxia
Published: November 2016

Spiders achieve superior silk fibres by controlling the molecular assembly of silk proteins and the hierarchical structure of fibres. However, current wet-spinning process for recombinant spidroins oversimplifies the natural spinning process. Here, water-soluble recombinant spider dragline silk protein (with a low molecular weight of 47 kDa) was adopted to prepare aqueous spinning dope. Artificial spider silks were spun via microfluidic wet-spinning, using a continuous post-spin drawing process (WS-PSD). By mimicking the natural spinning apparatus, shearing and elongational sections were integrated in the microfluidic spinning chip to induce assembly, orientation of spidroins, and fibril structure formation. The additional post-spin drawing process following the wet-spinning section partially mimics the spinning process of natural spider silk and substantially contributes to the compact aggregation of microfibrils. Subsequent post-stretching further improves the hierarchical structure of the fibres, including the crystalline structure, orientation, and fibril melting. The tensile strength and elongation of post-treated fibres reached up to 510 MPa and 15%, respectively.
Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs
Authors: Li Feng , Cheng Liang , Murphy Christopher M. , Reszka-Blanco Natalia J. , Wu Yaxu , Chi Liqun , Hu Jianming , Su Lishan
Published: November 2016

Chronic Hepatitis B Virus (HBV) infection is generally not curable with current anti-viral drugs. Virus rebounds after stopping treatment from the stable HBV covalently-closed-circular DNA (cccDNA). The development of drugs that directly target cccDNA is hampered by the lack of robust HBV cccDNA models. We report here a novel HBV cccDNA technology that will meet the need. We engineered a minicircle HBV cccDNA with a Gaussia Luciferase reporter (mcHBV-GLuc cccDNA), which serves as a surrogate to measure cccDNA activity. The mcHBV-GLuc cccDNA was easily produced in bacteria, and it formed minichromosomes as HBV cccDNA episome DNA does when it was transfected into human hepatocytes. Compared to non-HBV minicircle plasmids, mcHBV-GLuc cccDNA showed persistent HBV-GLuc activity and HBx-dependent gene expression. Importantly, the mcHBV-GLuc cccDNA showed resistance to interferons (IFN) treatment, indicating its unique similarity to HBV cccDNA that is usually resistant to long-term IFN treatment in chronic HBV patients. Most importantly, GLuc illuminates cccDNA as a surrogate of cccDNA activity, providing a very sensitive and quick method to detect trace amount of cccDNA. The mcHBV-GLuc cccDNA model is independent of HBV infection, and will be valuable for investigating HBV cccDNA biology and for developing cccDNA-targeting drugs.
Anti-tumor activity of SL4 against breast cancer cells: induction of G2/M arrest through modulation of the MAPK-dependent p21 signaling pathway
Authors: Wang Li-Hui , Jiang Xiao-Rui , Chen Guo-Liang , Guo Wei , Zhang Jing-Yuan , Cui Li-Juan , Li Hua-Huan , Li Meng , Liu Xing , Yang Jing-Yu , Wu Chun-Fu
Published: November 2016

SL4, a chalcone-based compound, has been shown to retard tumor invasion and angiogenesis by suppressing HIF1 activity and to induce apoptosis by promoting ROS release. Here, we report that SL4 is able to inhibit the proliferation of different types of breast cancer cell in vitro and in vivo by inducing G2/M cell cycle arrest. Our results showed that SL4 exhibited strong anti-proliferative activity in several human breast cancer cell lines, with IC50 values lower than 1.3 μM. Further studies indicated that SL4 induced G2/M arrest in these cell lines. Mechanistically, SL4 reduces the expression of cyclin A2 and cdc25C and decreases the activity of the cdc2/cyclin B1 complex. Notably, SL4 treatment resulted in an obvious increase in p21 mRNA and protein levels through activation of MAPK signaling pathways, but not the TGF-β pathway. SP600125 and PD98059, specific inhibitors of JNK kinase and ERK kinase, significantly blocked the SL4-induced G2/M phase arrest and upregulation of p21. Furthermore, SL4 suppressed the growth of established breast tumors in nude mice through upregulation of p21 and downregulation of cdc25C, and displayed a good safety profile. Taken together, these findings demonstrate the potential value of SL4 as a novel multi-target anti-tumor drug candidate.
Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity
Authors: Latif-Hernandez Amira , Shah Disha , Ahmed Tariq , Lo Adrian C. , Callaerts-Vegh Zsuzsanna , Van der Linden Annemie , Balschun Detlef , D’Hooge Rudi
Published: November 2016

Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model of neurodegenerative brain disease. Complementary techniques were combined to examine the consequences of QA injection into medial prefrontal cortex (mPFC) of C57BL6 mice. In accordance with the NMDAR-mediated synapto- and neurotoxic action of QA, we found an initial increase in excitability and an augmentation of hippocampal long-term potentiation, converting within two weeks into a reduction and impairment, respectively, of these processes. QA-induced mPFC excitotoxicity impaired behavioral flexibility in a reversal variant of the hidden-platform Morris water maze (MWM), whereas regular, extended MWM training was unaffected. QA-induced mPFC damage specifically affected the spatial-cognitive strategies that mice use to locate the platform during reversal learning. These behavioral and cognitive defects coincided with changes in cortical functional connectivity (FC) and hippocampal neuroplasticity. FC between various cortical regions was assessed by resting-state fMRI (rsfMRI) methodology, and mice that had received QA injection into mPFC showed increased FC between various cortical regions. mPFC and hippocampus (HC) are anatomically as well as functionally linked as part of a cortical network that controls higher-order cognitive functions. Together, these observations demonstrate the central functional importance of rodent mPFC as well as the validity of QA-induced mPFC damage as a preclinical rodent model of the early stages of neurodegeneration.
A rapid, automated surface protein profiling of single circulating exosomes in human blood
Authors: Kibria Golam , Ramos Erika K. , Lee Katelyn E. , Bedoyan Sarah , Huang Simo , Samaeekia Ravand , Athman Jaffre J. , Harding Clifford V. , Lötvall Jan , Harris Lyndsay , Thompson Cheryl L. , Liu Huiping
Published: November 2016

Circulating exosomes provide a promising approach to assess novel and dynamic biomarkers in human disease, due to their stability, accessibility and representation of molecules from source cells. However, this potential has been stymied by lack of approaches for molecular profiling of individual exosomes, which have a diameter of 30–150 nm. Here we report a rapid analysis approach to evaluate heterogeneous surface protein expression in single circulating exosomes from human blood. Our studies show a differential CD47 expression in blood-derived individual circulating exosomes that is correlated with breast cancer status, demonstrating a great potential of individual exosome profiles in biomarker discovery. The sensitive and high throughput platform of single exosome analysis can also be applied to characterizing exosomes derived from other patient fluids.
Possible existence of optical communication channels in the brain
Authors: Kumar Sourabh , Boone Kristine , Tuszyński Jack , Barclay Paul , Simon Christoph
Published: November 2016

Given that many fundamental questions in neuroscience are still open, it seems pertinent to explore whether the brain might use other physical modalities than the ones that have been discovered so far. In particular it is well established that neurons can emit photons, which prompts the question whether these biophotons could serve as signals between neurons, in addition to the well-known electro-chemical signals. For such communication to be targeted, the photons would need to travel in waveguides. Here we show, based on detailed theoretical modeling, that myelinated axons could serve as photonic waveguides, taking into account realistic optical imperfections. We propose experiments, both in vivo and in vitro, to test our hypothesis. We discuss the implications of our results, including the question whether photons could mediate long-range quantum entanglement in the brain.
Targeted in vivo delivery of EGFR siRNA inhibits ovarian cancer growth and enhances drug sensitivity
Authors: Satpathy Minati , Mezencev Roman , Wang Lijuan , McDonald John F.
Published: November 2016

A functionalized nanohydrogel siRNA delivery system and a mouse model of serous ovarian cancer were used to test predictions from previous cell line studies that knockdown of EGFR (epidermal growth factor receptor) may be of clinical significance in the treatment of epithelial tumors especially with respect to the enhancement of platinum based therapies. Our results support these predictions and suggest that targeted delivery of EGFR siRNA may be an effective strategy for the treatment of ovarian and other epithelial tumors associated with elevated levels of EGFR and especially those demonstrating resistance to platinum-based therapies.
Decreased preoperative serum 25-Hydroxyvitamin D levels in colorectal cancer are associated with systemic inflammation and serrated morphology
Authors: Väyrynen Juha P. , Mutt Shivaprakash J. , Herzig Karl-Heinz , Väyrynen Sara A. , Kantola Tiina , Karhu Toni , Karttunen Tuomo J. , Klintrup Kai , Mäkelä Jyrki , Mäkinen Markus J. , Tuomisto Anne
Published: November 2016

Deficiency of vitamin D is associated with increased risk of several types of cancer including colorectal cancer (CRC). However, factors contributing to low levels of 25-hydroxyvitamin D [25(OH)D] in CRC are not clear. Therefore, in this study serum 25(OH)D levels in 117 CRC patients and 86 controls were analyzed and correlated with the clinicopathological data including morphological subtype (serrated or conventional), quantity of tumor infiltrating immune cells, levels of systemic inflammatory markers, and disease outcome. We found that the patients had lower serum 25(OH)D levels compared to the controls. Interestingly, among the patients mismatch repair deficiency, serrated morphology, and high body mass index associated with lowest serum 25(OH)D levels. In addition, patients operated in summer or autumn had higher serum 25(OH)D levels. Furthermore, serum 25(OH)D levels inversely correlated with several systemic inflammatory markers, e.g. serum C reactive protein, but did not associate with prognosis. Mechanism leading to vitamin D deficiency in these patients are not clear but could be related to the effects of systemic inflammation. Longitudinal studies are warranted to assess vitamin D deficiency as a potential risk factor for serrated colorectal polyps and adenocarcinoma.
Sustained synchronized neuronal network activity in a human astrocyte co-culture system
Authors: Kuijlaars Jacobine , Oyelami Tutu , Diels Annick , Rohrbacher Jutta , Versweyveld Sofie , Meneghello Giulia , Tuefferd Marianne , Verstraelen Peter , Detrez Jan R. , Verschuuren Marlies , De Vos Winnok H. , Meert Theo , Peeters Pieter J. , Cik Miroslav , Nuydens Rony , Brône Bert , Verheyen An
Published: November 2016

Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer’s disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells. However, the differentiation process and growth conditions of hiPSC-derived neurons are non-trivial. In order to study neuronal network formation and (mal)function in a fully humanized system, we have established an in vitro co-culture model of hiPSC-derived cortical neurons and human primary astrocytes that recapitulates neuronal network synchronization and connectivity within three to four weeks after final plating. Live cell calcium imaging, electrophysiology and high content image analyses revealed an increased maturation of network functionality and synchronicity over time for co-cultures compared to neuronal monocultures. The cells express GABAergic and glutamatergic markers and respond to inhibitors of both neurotransmitter pathways in a functional assay. The combination of this co-culture model with quantitative imaging of network morphofunction is amenable to high throughput screening for lead discovery and drug optimization for neurological diseases.
Electronic hybridisation implications for the damage-tolerance of thin film metallic glasses
Authors: Schnabel Volker , Jaya B. Nagamani , Köhler Mathias , Music Denis , Kirchlechner Christoph , Dehm Gerhard , Raabe Dierk , Schneider Jochen M.
Published: November 2016

A paramount challenge in materials science is to design damage-tolerant glasses. Poisson’s ratio is commonly used as a criterion to gauge the brittle-ductile transition in glasses. However, our data, as well as results in the literature, are in conflict with the concept of Poisson’s ratio serving as a universal parameter for fracture energy. Here, we identify the electronic structure fingerprint associated with damage tolerance in thin film metallic glasses. Our correlative theoretical and experimental data reveal that the fraction of bonds stemming from hybridised states compared to the overall bonding can be associated with damage tolerance in thin film metallic glasses.
Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2
Authors: Saad Amine , Bijian Krikor , Qiu Dinghong , da Silva Sabrina Daniela , Marques Maud , Chang Chia-Hao , Nassour Hassan , Ramotar Dindial , Damaraju Sambasivarao , Mackey John , Bismar Tarek , Witcher Michael , Alaoui-Jamali Moulay A.
Published: November 2016

Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels. RbBP5, a subunit of the H3K4 histone methyltransferase (HMT) complex was found to interact with Fascin 1 supporting its role in H3K4me3 establishment at target genes. Moreover, we show that changes to SLC3A2 levels affect amino acid-mediated mTORC1 activation. These results reveal that Fascin 1 has a yet undiscovered nuclear function as an epigenetic modulator of genes essential for amino acid metabolism.
Preparation of preferentially exposed poison-resistant Pt(111) nanoplates with a nitrogen-doped graphene aerogel
Authors: Xie Beibei , Zhang Yong , Du Na , Li Haiping , Hou Wanguo , Zhang Renjie
Published: November 2016

A poison-resistant and highly catalytically active Pt(111) lattice on ultrathin Pt nanoplates (Pt(111)NPTs) is obtained with a dense small pore N-atom doped aerogel (NGA) with a large specific surface area and high N content.
An α-helical peptidomimetic scaffold for dynamic combinatorial library formation
Authors: Busschaert Nathalie , Thompson Sam , Hamilton Andrew D.
Published: November 2016

A novel oligobenzamide-based α-helix mimetic was designed and synthesised with either imine or hydrazone functionalities that serve both to pre-organise the side-chain vectors to mimic the i, i + 4 and i + 7 residues of an α-helix, and to allow for the facile creation of dynamic libraries.
Remote meta C–H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives
Authors: Modak Atanu , Mondal Anirban , Watile Rahul , Mukherjee Semanti , Maiti Debabrata
Published: November 2016

This discovery illustrates selective meta C–H bond activation from multiple non-equivalent C–H bonds present in medicinally relevant arylethanesulfonic acid and the 2-arylpropanoic acid moiety using weakly coordinating nitrile as a directing group.
Absolute cross-sections for DNA strand breaks and crosslinks induced by low energy electrons
Authors: Chen Wenzhuang , Chen Shiliang , Dong Yanfang , Cloutier Pierre , Zheng Yi , Sanche Léon
Published: November 2016

Absolute cross-sections (CSs) for the interaction of low energy electrons with condensed macromolecules are essential parameters to accurately model ionizing radiation induced reactions.
Collective proton transfer in ordinary ice: local environments, temperature dependence and deuteration effects
Authors: Drechsel-Grau Christof , Marx Dominik
Published: November 2016

Ordinary ice at low temperature: what about collective nuclear quantum effects in its chiral six rings?
X-ray emission spectroscopy: highly sensitive techniques for time-resolved probing of cerium reactivity under catalytic conditions
Authors: Kopelent R. , van Bokhoven J. A. , Nachtegaal M. , Szlachetko J. , Safonova O. V.
Published: November 2016

High sensitivity of X-ray emission spectroscopy based methods for in situ time-resolved quantification of Ce3+ in ceria-based catalysts and related materials.
Mechanism for the enhanced oxygen reduction reaction of La0.6Sr0.4Co0.2Fe0.8O3−δ by strontium carbonate
Authors: Li Mei , Sun Zhongti , Yang Wenqiang , Hong Tao , Zhu Zhesheng , Zhang Yanxiang , Wu Xiaojun , Xia Changrong
Published: November 2016

We demonstrate that SrCO3 can improve ORR on LSCF, solving the problem of contradicting effects of Sr surface segregation on LSCF.
Photochemical proton-coupled C–H activation: an example using aliphatic fluorination
Authors: Field Mackenzie J. , Sinha Soumalya , Warren Jeffrey J.
Published: November 2016

Excited state organic photosensitizers are investigated in the context of their ability to activate CH bonds via outer sphere electron transfer or via proton-coupled electron transfer.