bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Alternative Redox Partners and Oxidizing Agents on CYP154C8 Catalytic Activity and Product Distribution
Authors: Dangi Bikash , Park Hyun , Oh Tae‐Jin
Published: August 2018

CYP154C8 catalyzes the hydroxylation of diverse steroids, as has previously been demonstrated, by using an NADH‐dependent system including putidaredoxin and putidaredoxin reductase as redox partner proteins carrying electrons from NADH. In other reactions, CYP154C8 reconstituted with spinach ferredoxin and NADPH‐dependent ferredoxin reductase displayed catalytic activity different from that of the NADH‐dependent system. The NADPH‐dependent system showed multistep oxidation of progesterone and other substrates including androstenedione, testosterone, and nandrolone. (Diacetoxyiodo)benzene was employed to generate compound I (FeO3+), actively supporting the redox reactions catalyzed by CYP154C8. In addition to 16α‐hydroxylation, progesterone and 11‐oxoprogesterone also underwent hydroxylation at the 6β‐position in reactions supported by (diacetoxyiodo)benzene. CYP154C8 was active in the presence of high concentrations (>10 mm) of H2O2, with optimum conversion surprisingly being achieved at ≈75 mm H2O2. More importantly, H2O2 tolerance by CYP154C8 was evident in the very low heme oxidation rate constant (K) even at high concentrations of H2O2. Our results demonstrate that alternative redox partners and oxidizing agents influence the catalytic efficiency and product distribution of a cytochrome P450 enzyme. More importantly, these choices affected the type and selectivity of reaction catalyzed by the P450 enzyme.
A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation
Authors: Johnson Oleta T. , Kaur Tanpreet , Garner Amanda L.
Published: August 2018

Proteins containing intrinsic disorder often form secondary structure upon interaction with a binding partner. Modulating such structures presents an approach for manipulating the resultant functional outcomes. Translational repressor protein 4E‐BP1 is an example of an intrinsically disordered protein that forms an α‐helix upon binding to its protein ligand, eIF4E. Current biophysical methods for analyzing binding‐induced structural changes are low‐throughput, require large amounts of sample, or are extremely sensitive to signal interference by the ligand itself. Herein, we describe the discovery and development of a conditionally fluorescent 4E‐BP1 peptide that reports structural changes of its helix in high‐throughput format. This reporter peptide is based on conditional quenching of fluorescein by thioamides. In this case, fluorescence signal increases as the peptide becomes more ordered. Conversely, destabilization of the α‐helix results in decreased fluorescence signal. The low concentration and low volume of peptide required make this approach amenable for high‐throughput screening to discover ligands that alter peptide secondary structure.
Ligand‐Driven Conformational Dynamics Influences Selectivity of UbiX
Authors: Żaczek Szymon , Kowalska Justyna , Dybala‐Defratyka Agnieszka
Published: August 2018

Up until now, it has remained elusive as to why the flavin prenyltransferase UbiX requires dimethylallyl monophosphate (DMAP) as one of its cosubstrates instead of dimethylallyl pyrophosphate (DMAPP), even though the former is not used in metabolic pathways, while the latter is a common isoprenoid precursor. Herein, mainly on the basis of molecular dynamics (MD) simulations, we demonstrate that the selectivity of UbiX may be governed by its conformational dynamics. The hydrogen‐bonding network of UbiX does not facilitate a proper encompassing of DMAPP. This induces significant conformational changes of the enzyme that result mostly in unreactive trajectories, whereas DMAP remains at a catalytically competent position throughout the performed simulations. Within the presented study, we provide a justification for the atypical selectivity of UbiX.
Ter‐cell, A New Target for Hepatocellular Carcinoma Therapy
Authors: Cen Xiaohong , Cheng Kui
Published: August 2018

Hepatocellular carcinoma (HCC), a malignancy of the liver, has become the second most lethal cause of cancer death globally. Recently, scientists discovered that a splenic erythroblast‐like cell induced by the primary tumor, termed Ter‐cell, promoted HCC progression and metastasis. These findings shed light on the inhibition of Ter‐cell or artemin that can serve as a new therapeutic target for HCC.
Postpartum eruption of enoxaparin‐induced erythema multiforme
Authors: Schadler Eric D. , Joyce Joel C. , Haugen Reshma N.
Published: August 2018

Key Clinical Message

Enoxaparin is a commonly used hospital medication and in rare instances may result in development of erythema multiforme. Management of these patients can be challenging. Physicians must maintain a high index of suspicion and consider the indication for enoxaparin therapy prior to withdrawal of the medication.
Biocatalyzed C−C Bond Formation for the Production of Alkaloids
Authors: Patil Mahesh D. , Grogan Gideon , Yun Hyungdon
Published: August 2018

Traditional methods of chemical synthesis of alkaloids exhibit various problems such as lack of enantioselectivity, the use of toxic chemical and intermediates, and multiple numbers of synthetic steps. Consequently, various enzymatic methods for the formation of C−C bonds in the alkaloid skeleton have been developed. Herein, we report advances achieved in the enzymatic or chemo‐enzymatic synthesis of pharmaceutically important alkaloids that employ three C−C bond forming enzymes: two Pictet‐Spenglerases and the oxidative C−C bond forming flavoenzyme Berberine Bridge Enzyme. Protein engineering studies, improving the substrate scope of these enzymes, and thereby leading to the synthesis of non‐natural alkaloids possessing higher or newer pharmacological activities, are also discussed. Furthermore, the integration of these biocatalysts with other enzymes, in multi‐enzymatic cascades for the enantioselective synthesis of alkaloids, is also reviewed. Current results suggest that these enzymes hold great promise for the generation of C−C bonds in the selective synthesis of alkaloid compounds possessing diverse pharmacological properties.
Synthesis of 2,5‐Disubstituted Pyrrolidine Alkaloids via A One‐Pot Cascade Using Transaminase and Reductive Aminase Biocatalysts
Authors: Costa Bruna Z. , Galman James L. , Slabu Iustina , France Scott P. , Marsaioli Anita J. , Turner Nicholas J.
Published: August 2018

A multi‐enzymatic cascade process involving transaminases (TAs) and reductive aminases (RedAms) to produce enantiomerically pure 2,5‐disubstituted pyrrolidine alkaloids from their respective 1,4‐diketones is reported. Several TAs were screened and the best results for diketone monoamination were obtained with an R‐selective TA from Mycobacterium chlorophenicum and with an S‐selective TA from Bacillus megaterium. Pyrroline reduction was best performed by a reductive aminase from Ajellomyces dermatitidis (AdRedAm). Finally, a biocatalytic one‐pot cascade was implemented using the aforementioned enzymes and a variety of 2‐methyl‐5‐alkylpyrrolidines were produced with high (>99 %) conversion, diastereomeric and enantiomeric excess values.
Fluorescent Molecular Rotors for Viscosity Sensors
Authors: Lee Seung‐Chul , Heo Jeongyun , Woo Hee Chul , Lee Ji‐Ah , Seo Young Hun , Lee Chang‐Lyoul , Kim Sehoon , Kwon O‐Pil
Published: August 2018

Invited for the cover of this issue is the collaborative work of the groups of O‐Pil Kwon (Ajou University), Chang‐Lyoul Lee (Advanced Photonics Research Institute, APRI/Gwangju Institute of Science and Technology, GIST), and Sehoon Kim (Korea Institute of Science and Technology, KIST). The cover image illustrates the viscosity‐sensitive fluorescent behavior of fluorescent molecular rotors (FMRs) in various viscous media. The intensity of the FMRs increases with decreasing speed of the rotor; this is portrayed as the waterwheel in the cover image. When the waterwheel slowly rotates in winter (high viscosity media), FMR—portrayed as the house in the image—shows strong fluorescent‐light illumination (left‐hand side of the image). In contrast, the right‐hand side of image depicts decreasing fluorescence intensity with increasing rotation of the waterwheel (low viscosity media). Read the full text of the article at 10.1002/chem.201801389.
Neuroarchitecture of the dung beetle central complex
Authors: el Jundi Basil , Warrant Eric J. , Pfeiffer Keram , Dacke Marie
Published: August 2018

Despite their tiny brains, insects show impressive abilities when navigating over short distances during path integration or during migration over thousands of kilometers across entire continents. Celestial compass cues often play an important role as references during navigation. In contrast to many other insects, South African dung beetles rely exclusively on celestial cues for visual reference during orientation. After finding a dung pile, these animals cut off a piece of dung from the pat, shape it into a ball and roll it away along a straight path until a suitable place for underground consumption is found. To maintain a constant bearing, a brain region in the beetle's brain, called the central complex, is crucially involved in the processing of skylight cues, similar to what has already been shown for path‐integrating and migrating insects. In this study, we characterized the neuroanatomy of the sky‐compass network and the central complex in the dung beetle brain in detail. Using tracer injections, combined with imaging and 3D modeling, we describe the anatomy of the possible sky‐compass network in the central brain. We used a quantitative approach to study the central‐complex network and found that several types of neuron exhibit a highly organized connectivity pattern. The architecture of the sky‐compass network and central complex is similar to that described in insects that perform path integration or are migratory. This suggests that, despite their different orientation behaviors, this neural circuitry for compass orientation is highly conserved among the insects.
Early life trauma increases threat response of peri‐weaning rats, reduction of axo‐somatic synapses formed by parvalbumin cells and perineuronal net in the basolateral nucleus of amygdala
Authors: Santiago Adrienne N. , Lim Kayla Y. , Opendak Maya , Sullivan Regina M. , Aoki Chiye
Published: August 2018

Early life trauma is a risk factor for life‐long disorders related to emotional processing, but knowledge underlying its enduring effect is incomplete. This study was motivated by the hypothesis that early life trauma increases amygdala‐dependent threat responses via reduction in inhibition by parvalbumin (PV) interneurons and perineuronal nets (PNN) supporting PV cells, thus increasing excitability of the basolateral amygdala (BLA). From postnatal day (PN) 8–12, rat pups of both sexes were reared under normal bedding or under insufficient nest‐building materials to induce maternal‐to‐infant maltreatment trauma (Scarcity‐Adversity Model, SAM). At weaning age of PN23, the SAM group exhibited increased threat responses to predator odor. The SAM‐induced increase in threat response was recapitulated in normally reared PN22–23 rats that were unilaterally depleted of PNN in the BLA by the enzymes, chondroitinase‐ABC plus hyaluronidase at PN19–20. Light and electron microscopic analysis of the BLA revealed that anterior‐to‐mid levels of SAM group's BLAs exhibited decreased PNN intensity and decreased axo‐somatic synapses between PV‐to‐principal pyramidal‐like neurons and PV‐to‐PV. PV and PNN densities (cells/mm2) in the BLA of both control (CON) and SAM groups were still low at PN12 and SAM delayed the ontogenetic rise of PV intensity and PNN density. Moreover, PV cell density in the anterior‐to‐mid BLA correlated negatively with threat response of CON animals, but not for SAM animals. Thus, reduction of PNN‐supported, PV‐mediated somatic inhibition of pyramidal cells provides a mechanistic support for the enduring effect of early life maltreatment manifested as increasing innate threat response at weaning.
A Dynamic Biomaterial Based on a 2‐Nitrobenzyl Derivative with a tert‐Butyl Substituent at the Benzyl Position: Rapid Response and Minimized Phototoxicity
Authors: Yamamoto Shota , Ikegami Hiroki , Yamaguchi Kazuo , Nakanishi Jun
Published: August 2018

The front cover artwork is provided by the group of Prof. Jun Nakanishi at the International Center for Materials Nanoarchitectonics (WPI‐MANA), National Institute for Materials Science (NIMS). The image shows photo‐induced cell migration behavior on a dynamic cell culture platform based on 2‐nitrobenzyl ester with different benzyl substituents. Read the full text of the Communication at10.1002/cptc.201800087.
Reporting on supply chain sustainability: Measurement using item response theory
Authors: Fernandes Sheila Mendes , Bornia Antonio Cezar
Published: August 2018

The purpose of this article is to measure the level of reporting about supply chain sustainability using item response theory (IRT). IRT allows inserting items and their respondents into a single scale and creating interpretable scales. An instrument composed of 24 items was prepared and applied to 345 sustainability reports from companies in 21 sectors of the Brazilian economy. It used Samejima's gradual response model to construct a scale to measure the level of reporting on supply chain sustainability. As a result, five interpretable levels were identified in the scale constructed (Minimum, Low, Medium, Medium High and High). The reporting about the supply chain in most of the sustainability reports analyzed (48.41%) is concentrated at the scale's lowest or minimum level: 24.93% are at the second or low level, 2.61% are at the medium level, and only 0.29% of the reports are at the high level of the scale.
Corporate social responsibility information and involvement strategies in controversial industries
Authors: Vollero Agostino , Conte Francesca , Siano Alfonso , Covucci Claudia
Published: August 2018

This paper assesses how companies belonging to controversial and non‐controversial industries differ in their adoption of corporate social responsibility (CSR) information and involvement strategies. Drawing on legitimacy and stakeholder theories, a thematic content analysis of the websites of companies listed in the Dow Jones Sustainability Word Index is used to establish a set of measures for CSR communication strategies aimed at fostering stakeholder engagement. Companies in controversial industries are found to be more likely to adopt a CSR information strategy than those in non‐controversial industries but do not attempt to create stakeholder involvement. The results highlight the importance for communication managers in controversial organizations of considering information strategies as a meta‐level of engagement and of implementing an involvement strategy to mitigate the level of controversy. The study offers a wider conceptualization of the business activities of controversial industries and contributes to the debate on stakeholder engagement for organizational legitimacy.
Glial Cell Expansion Coincides with Neural Circuit Formation in the Developing Auditory Brainstem
Authors: Brandebura Ashley N. , Morehead Michael , Heller Daniel T. , Holcomb Paul , Kolson Douglas R. , Jones Garrett , Mathers Peter H. , Spirou George A.
Published: August 2018

Neural circuit formation involves maturation of neuronal, glial and vascular cells, as well as cell proliferation and cell death. A fundamental understanding of cellular mechanisms is enhanced by quantification of cell types during key events in synapse formation and pruning and possessing qualified genetic tools for cell type‐specific manipulation. Acquiring this information in turn requires validated cell markers and genetic tools. We quantified changing proportions of neurons, astrocytes, oligodendrocytes, and microglia in the medial nucleus of the trapezoid body (MNTB) during neural circuit development. Cell type‐specific markers, light microscopy and 3D virtual reality software, the latter developed in our laboratory, were used to count cells within distinct cell populations at postnatal days (P)3 and P6, bracketing the period of nerve terminal growth and pruning in this system. These data revealed a change from roughly equal numbers of neurons and glia at P3 to a 1.5:1 ratio of glia to neurons at P6. PCNA and PH3 labeling revealed that proliferation of oligodendrocytes contributed to the increase in glial cell number during this timeframe. We next evaluated Cre driver lines for selectivity in labeling cell populations. En1‐Cre was specific for MNTB neurons. PDGFRα‐Cre and Aldh1L1‐Cre, thought to be mostly specific for oligodendrocyte lineage cells and astrocytes, respectively, both labeled significant numbers of neurons, oligodendrocytes, and astrocytes and are non‐specific genetic tools in this neural system.
Glycine‐modified growth hormone secretagogues identified in seized doping material
Authors: Gajda Paulina Marta , Holm Niels Bjerre , Hoej Lars Jakobsen , Rasmussen Brian Schou , Dalsgaard Petur Weihe , Reitzel Lotte Ask , Linnet Kristian
Published: August 2018

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.
RELT negatively regulates the early phase of the T‐cell response in mice
Authors: Choi Beom K. , Kim Seon‐Hee , Kim Young H. , Lee Don G. , Oh Ho S. , Han Chungyong , Kim Yu I. , Jeon Yoon , Lee Ho , Kwon Byoung S.
Published: August 2018

RELT (tumor necrosis factor receptor superfamily member 19‐like, TNFRSF19L) is a TNFR superfamily member that is primarily expressed in immune cells and lymphoid tissues, but whose immunological function is not well‐defined. Here, we show that RELT is expressed by naive T cells and DCs, and their activation or maturation decreases RELT expression. Using RELT knockout (RELT−/−) mice, we demonstrate that RELT deficiency selectively promotes the homeostatic proliferation of CD4+ T cells but not CD8+ T cells, and enhances anti‐tumor CD8+ T‐cell responses. We also demonstrate, using an adoptive transfer model in which RELT is knocked‐out in either the transferred transgenic CD8+ T cells or the recipient melanoma‐bearing mice, that RELT on multiple immune cells limits the hyper‐response of tumor‐specific CD8+ T cells. Hyper‐responsiveness of RELT‐deficient T cells was induced by promoting their proliferation. Taken together, our findings suggest that RELT acts as a negative regulator that controls the early phase of T‐cell activation probably by promoting T‐cell apoptosis.
Disposable Electrochemical Sensor for Rapid Determination of Ethyl Xanthate in the Mining Industry
Authors: Pedre Ignacio , Battaglini Fernando , González Graciela A.
Published: August 2018

Xanthate is a widely used reagent in sulfide mineral flotation. A simple and reliable method is presented for the direct monitoring of xanthate in flotation baths and their effluents, as a tool for their reconditioning, and reducing their environmental impact. For this purpose, screen‐printed graphite electrodes (SPE) were modified with a polyelectrolyte‐surfactant matrix which was able to adsorb the xanthate, whose concentration is determined by electrochemical impedance spectroscopy (EIS) following the change in the electron transfer resistance of ferrocyanide after a pre‐oxidation treatment. Linear ranges from 0.25 to 1 μM and 15 to 100 μM were determined for effluents and flotation baths, respectively. A mechanism for the electron transfer process is proposed based on Quartz crystal microbalance, IR and cyclic voltammetry studies.
Associations between dimensions of anorexia nervosa and obsessive–compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa
Authors: Levinson Cheri A. , Zerwas Stephanie C. , Brosof Leigh C. , Thornton Laura M. , Strober Michael , Pivarunas Bernadette , Crowley James J. , Yilmaz Zeynep , Berrettini Wade H. , Brandt Harry , Crawford Steven , Fichter Manfred M. , Halmi Katherine A. , Johnson Craig , Kaplan Allan S. , La Via Maria , Mitchell James , Rotondo Alessandro , Woodside D. Blake , Kaye Walter H. , Bulik Cynthia M.
Published: August 2018

Objective

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders.

Method

In path analyses (N = 732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator.

Results

When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status.

Conclusions

Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.
Antioxidant properties, ACE/renin inhibitory activities of pigeon pea hydrolysates and effects on systolic blood pressure of spontaneously hypertensive rats
Authors: Olagunju Aderonke I. , Omoba Olufunmilayo S. , Enujiugha Victor N. , Alashi Adeola M. , Aluko Rotimi E.
Published: August 2018

Legumes are rich sources of protein in human diet and their consumption has been associated with the prevention of chronic diseases attributable to their bioactive components. Pigeon pea (Cajanus cajan) is an underutilized legume with relatively high protein content (~24%). Protein hydrolysates were prepared from pea isolate by enzymatic hydrolysis using pepsin and pancreatin. Hydrolysates were evaluated for their amino acid composition, antioxidant properties, in vitro and in vivo antihypertensive properties. The hydrolysates had high hydrophobic amino acids, especially isoleucine, phenylalanine, and leucine. Pepsin‐pancreatin‐hydrolyzed pea protein (PPHPp) showed significantly higher ability to scavenge DPPH˙ while pancreatin‐hydrolyzed pea protein (PPHPa) had higher ˙OH, ABTS˙+ scavenging, Fe3+ reducing and linoleic acid peroxidation inhibition. PPHPp exhibited superior angiotensin‐converting enzyme inhibition (61.82%) while PPHPa showed higher renin inhibition (14.28%). PPHPp exhibited strong antihypertensive effect, showing an instantaneous systolic blood pressure lowering effect (−26.12 mmHg) within 2‐h post‐oral administration. Pigeon pea protein hydrolysate (especially from pancreatin digest) could therefore, be a promising source of bioactive peptides and potential ingredient for formulation of functional foods against oxidative stress and hypertension.
Lexical learning in a new language leads to neural pattern similarity with word reading in native language
Authors: Li Huiling , Qu Jing , Chen Chuansheng , Chen Yanjun , Xue Gui , Zhang Lei , Lu Chengrou , Mei Leilei
Published: August 2018

Previous neuroimaging studies have suggested similar neural activations for word reading in native and second languages. However, such similarities were qualitatively determined (i.e., overlapping activation based on traditional univariate activation analysis). In this study, using representational similarity analysis and an artificial language training paradigm, we quantitatively computed cross‐language neural pattern similarity to examine the modulatory effect of proficiency in the new language. Twenty‐four native Chinese speakers were trained to learn 30 words in a logographic artificial language for 12 days and scanned while performing a semantic decision task after 4‐day training and after 12‐day training. Results showed that higher proficiency in the new language was associated with higher cross‐language pattern similarity in select regions of the reading network.
Glucocorticoid-Induced Insulin Resistance in Men Is Associated With Suppressed Undercarboxylated Osteocalcin
Authors: Parker Lewan , Lin Xuzhu , Garnham Andrew , McConell Glenn , Stepto Nigel K , Hare David L , Byrnes Elizabeth , Ebeling Peter R , Seeman Ego , Brennan-Speranza Tara C , Levinger Itamar
Published: August 2018

In mice, glucocorticoid-induced insulin resistance occurs largely through impaired osteoblast function and decreased circulating undercarboxylated osteocalcin (ucOC). Whether these mechanisms contribute to glucocorticoid-induced insulin resistance in humans has yet to be established. In addition, the effects of glucocorticoids on the exercise-induced increase in circulating ucOC and insulin sensitivity are also unknown. We hypothesized that acute glucocorticoid treatment would lead to basal and postexercise insulin resistance in part through decreased circulating ucOC and ucOC-mediated skeletal muscle protein signaling. Nine healthy men completed two separate cycling sessions 12 hours after ingesting either glucocorticoid (20 mg prednisolone) or placebo (20 mg Avicel). The homeostatic model assessment was used to assess basal insulin sensitivity and a 2-hour euglycemic–hyperinsulinemic clamp was commenced 3 hours after exercise to assess postexercise insulin sensitivity. Serum ucOC and skeletal muscle protein signaling were measured. Single-dose glucocorticoid ingestion increased fasting glucose (27%, p < 0.01) and insulin (83%, p < 0.01), and decreased basal insulin sensitivity (−47%, p < 0.01). Glucocorticoids reduced insulin sensitivity after cycling exercise (−34%, p < 0.01), reduced muscle GPRC6A protein content (16%, p < 0.05), and attenuated protein phosphorylation of mTORSer2481, AktSer374, and AS160Thr642 (59%, 61%, and 50%, respectively; all ps < 0.05). Serum ucOC decreased (−24%, p < 0.01) which correlated with lower basal insulin sensitivity (r = 0.54, p = 0.02), lower insulin sensitivity after exercise (r = 0.72, p < 0.05), and attenuated muscle protein signaling (r = 0.48–0.71, p < 0.05). Glucocorticoid-induced basal and postexercise insulin resistance in humans is associated with the suppression of circulating ucOC and ucOC-linked protein signaling in skeletal muscle. Whether ucOC treatment can offset glucocorticoid-induced insulin resistance in human subjects requires further investigation. © 2018 American Society for Bone and Mineral Research.
Efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in elderly patients with chronic hepatitis C virus infection
Authors: Elbaz Tamer , Abdo Mahmoud , Omar Heba , Hassan Essam A. , Zaghloul Amr M. , Abdel‐Samiee Mohamed , Moustafa Ahmed , Qawzae Abdallah , Gamil Mostafa , Esmat Gamal
Published: August 2018

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver‐related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon‐free direct‐acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.
Exploring the vertical accretion of ornithogenic sediments from the Xisha Islands, South China Sea, by seabird subfossils
Authors: Xu Liqiang , Zhao Jinjun , Wu Libin , Chen Lin , Liu Xiaodong
Published: August 2018

Reef islands of the Xisha Islands, South China Sea, were formed during the mid–late Holocene. However, the vertical accretion of ornithogenic sediments of the islands is not well understood owing to a lack of precise dating. Here we present an analysis of seven of the Xisha Islands, and reconstruct their accumulation history based on radiocarbon analysis of seabird subfossils. From Clam‐based age–depth models, a universal development mode of the Xisha Islands is hypothesized. The mean accumulation rate of guano sediments on the Xisha Islands in the late Holocene was 1.02 ± 0.42 mm a−1. The sum of the deposition rate of coral sands and the rate of ornithogenic accumulation is lower than or close to the current rate of sea level rise in the Xisha Islands, implying a potential threat to the islands’ safety. This study also provides robust evidence for a sequence of island development associated with seabirds.
Experimental and theoretical study of Raman scattering spectra of ternary chalcogenides Tl4HgI6, Tl4HgBr6, and TlHgCl3
Authors: Yukhymchuk Volodymyr O. , Dzhagan Volodymyr M. , Mazur Nazar V. , Parasyuk Oleg V. , Khyzhun Oleg Y. , Luzhnyi Ivan V. , Yaremko Anatoliy M. , Valakh Mykhailo Ya. , Litvinchuk Alexander P.
Published: August 2018

The results of a comprehensive experimental and theoretical study of Raman scattering of Tl4HgI6, Tl4HgBr6, and TlHgCl3 ternary chalcogenides are presented. Phonon mode assignment to the specific lattice eigenmodes is achieved via comparison of experimental data with the results of first principle lattice dynamics calculations. Both experimental data and theoretical calculations allow to confirm that Tl4HgBr6 crystals belong to the non‐centrosymmetric space group P4nc, whereas Tl4HgI6 to the centrosymmetric space group P4/mnc.
Separation and determination of microRNAs by high‐speed capillary sieving electrophoresis
Authors: Wang Wei , Cai Xiaoyu , Lin Ping , Bai Ruiguang
Published: August 2018

In this work, high‐speed capillary sieving electrophoresis with laser‐induced fluorescence detection was applied to simultaneously determine three microRNAs. A developed manual sample introduction device for the high‐speed capillary electrophoresis system was applied to perform sample injection. Strategies, including field‐amplified sample injection and electrokinetic injection, were studied to improve the detection sensitivity. Under the optimal conditions, the limit of detection for DNA‐159 could be lowered to 5.10 × 10−12 mol/L. In order to achieve enough separation resolution, two DNA probes were designed to have extra sequences that acted as the drag tails. Under the optimized conditions, the three DNA probes and the complexes of microRNA‐156, microRNA‐159, and microRNA‐166 could be completely separated within 3.2 min in background electrolyte (pH 8.7) containing 2.0% m/m polyvinyl pyrrolidone and 0.4% m/m hydroxyethyl cellulose. The limits of detection for the three microRNAs were 0.051, 0.11, and 0.25 nmol/L, respectively. Then the method was applied to analyze the microRNAs spiked in the samples extracted from banana leaves. The recoveries ranged from 114.3 to 121.1% (n = 3). The results showed that the method developed in this work was an effective means for microRNA assay.
Recent advances of online coupling of sample preparation techniques with ultra high performance liquid chromatography and supercritical fluid chromatography
Authors: Liang Yanshan , Zhou Ting
Published: August 2018

Ultra high performance liquid chromatography and supercritical fluid chromatography techniques are favored because of their high efficiency and fast analysis speed. Although many sample preparation techniques have been coupled with common liquid chromatography online, the online coupling of sample preparation with the two popular chromatography techniques have gained increasing attention owing to the increasing requirements of efficiency and sensitivity. In this review, we have discussed and summarized the recent advances of the online coupling of sample preparation with ultra high performance liquid chromatography and supercritical fluid chromatography techniques. The main sample preparation techniques that have been coupled with ultra high performance liquid chromatography online are solid‐phase extraction and in‐tube solid‐phase microextraction, while solid‐phase extraction and supercritical fluid extraction are the main techniques that have been coupled with supercritical fluid chromatography online. Especially, the strategies for online coupling of sample preparation with chromatography techniques were summarized. Typical applications and growing trends of the online coupling techniques were also discussed in detail. With the increasing demands of improving the efficiency, throughput, and analytical capability toward complex samples of the analysis methods, online coupling of sample preparation with chromatography techniques will acquire further development.
2′‐Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76
Authors: Singhal Jyotsana , Chikara Shireen , Horne David , Salgia Ravi , Awasthi Sanjay , Singhal Sharad S.
Published: August 2018

Consumption of citrus‐fruits is associated with reduced incidence of breast cancer (BC), the most common cancer diagnosed in women across the globe. In this study, we investigated the anticancer potential of 2‐Hydroxyflavanone (2HF) in BC. 2HF, a citrus‐bioflavonoid, has demonstrated anticancer properties in various cancers, but its anticancer role in BC has not been well studied. We investigated the in vitro and in vivo growth inhibitory effects of 2HF in an array of BC lines and in xenograft mouse models of ER‐positive and HER2‐positive BC cells. Compared to control, 2HF treatment reduced cell viability and suppressed migratory and invasive potential of BC cells, while, no growth inhibitory effects were observed in non‐tumorigenic breast epithelial cells. Further, 2HF inhibited the expression of RLIP76, a stress‐defensive and anti‐apoptotic protein, which is over‐expressed in BC cells and simultaneously reduced proliferation of BC cells. Nude mice bearing MCF7 or SKBR3 BC cells xenografts treated with either 2HF or targeting RLIP76 by RLIP76‐antisense or RLIP76‐antibody treatment had significantly lower tumor‐weight as compared to corresponding controls. In addition, Western‐blotting and immunohistochemical analysis of tumor tissue from control and treatment group mice showed that 2HF decreased protein expression levels of RLIP76, and the decrease was similar to those seen following RLIP76‐antisense treatment. Furthermore, 2HF decreased expression of Ki67, CD31, vimentin, inhibited phosphorylation of Akt and expression of survivin and Bcl2, and increased levels of Bax, E‐cadherin, and cleaved‐PARP. Therefore, our results indicate that 2HF may suppress BC growth in vitro and in vivo by targeting RLIP76, and may serve as a potential adjuvant treatment in BC patients.
Pseudodifferential equations, wave factorization, and related problems
Authors: Vasilyev Vladimir B.
Published: August 2018

We consider a model elliptic pseudodifferential equation in a special canonical domains of a multidimensional space. Using a special representation for an elliptic symbol, we give the formula for a general solution of such an equation and choose additional conditions under which this boundary value problem has a unique solution in appropriate Sobolev‐Slobodetskii spaces. Also, we introduce some transmutation operators that help us in constructing the solution.
New exact solutions to extended (3 + 1)‐dimensional Jimbo‐Miwa equations by using bilinear forms
Authors: Kaur Lakhveer , Wazwaz Abdul‐Majid
Published: August 2018

In this work, we investigate extended (3 + 1)‐dimensional Jimbo‐Miwa equations by locating movable critical points with the aid of Painlevé analysis. We construct bilinear forms through using truncated Painlevé expansions along with the Bell polynomials approach. The proposed approach provides enough freedom to construct solutions that may be related to large variety of real physical phenomena, and in addition, this approach enriches the solution structure. Abundant exact solutions involving various arbitrary constants are furnished in uniform manner by using test function. The obtained solutions are entirely new and different from those reported in the literature.
The Prevention of Lower Urinary Tract Symptoms (PLUS) in girls and women: Developing a conceptual framework for a prevention research agenda
Authors: Brady Sonya S. , Bavendam Tamara G. , Berry Amanda , Fok Cynthia S. , Gahagan Sheila , Goode Patricia S. , Hardacker Cecilia T. , Hebert‐Beirne Jeni , Lewis Cora E. , Lewis Jessica B. , Kane Low Lisa , Lowder Jerry L. , Palmer Mary H. , Wyman Jean F. , Lukacz Emily S. ,   For the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium
Published: August 2018

Aims

The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium was established by the National Institutes of Health in 2015 to expand research beyond the detection and treatment of lower urinary tract symptoms (LUTS) to the promotion and preservation of bladder health and prevention of LUTS in girls and women. While many multi‐disciplinary scientific networks focus on pelvic floor dysfunction and LUTS, the PLUS Consortium stands alone in its focus on prevention. This article describes the PLUS approach to developing a conceptual framework to guide the Consortium's initial prevention research agenda.

Methods

The conceptual framework was informed by traditional social ecological models of public health, biopsychosocial models of health, Glass and McAtee's Society‐Behavior‐Biology Nexus, and the World Health Organization's conceptual framework for action on the social determinants of health.

Results

The PLUS conceptual framework provides a foundation for developing prevention interventions that have the greatest likelihood of promoting and preserving bladder health among diverse populations.

Conclusions

PLUS Consortium work is premised on the notion that programs, practices, and policies designed to promote health will have optimal impact if the conceptual foundation upon which efforts are based is comprehensive and informed by multiple disciplines. The PLUS conceptual framework is broadly applicable to domains of health that have historically focused on the treatment of illness and symptoms rather than the promotion of health. It is also applicable to domains of health that have been examined from a predominantly biological or social ecological perspective, without integration of both perspectives.
Early History of Home Parenteral Nutrition: From Hospital to Home
Authors: Hurt Ryan T. , Steiger Ezra
Published: August 2018

Technologic advances in the past century have led to the ability to safely deliver parenteral nutrition (PN) to hospitalized patients. Key breakthroughs included the development of saline and glucose infusions, infusion pumps, macronutrients (lipids, dextrose, and amino acids), and central venous catheters. In the 1960s, centrally delivered PN was performed in short‐term hospitalized patients by Lincoln James Lawson (North Staffordshire Royal Infirmatory, United Kingdom) and long‐term patients by Stanley Dudrick (University of Pennsylvania, United States). These early studies showed that a system was needed that would allow patients with intestinal failure to be discharged from the hospital and receive home PN (HPN). In the late 1960s and early 1970s, Belding Scribner, Maurice Shils, Khursheed Jeejeebhoy, Marvin Ament, Dudrick, and their teams discharged patients from the hospital who then self‐administered HPN. Shortly after these early cases of HPN, multidisciplinary centers were established first in North America, and later in Europe, to manage these complex cases. The current article describes the patients treated by these early HPN pioneers, in addition to subsequent case series reported by them and others.
The Population Cost‐Effectiveness of Weight Watchers with General Practitioner Referral Compared with Standard Care
Authors: Lymer Sharyn , Schofield Deborah , Cunich Michelle , Lee Crystal Man Ying , Fuller Nicholas , Caterson Ian , Colagiuri Stephen
Published: August 2018

Objective

This study aimed to assess population‐level cost‐effectiveness of the Weight Watchers (WW) program with doctor referral compared with standard care (SC) for Australian adults with overweight and obesity.

Methods

The target population was Australian adults ≥ 20 years old with BMI ≥ 27 kg/m2, whose obesity status was subsequently modeled for 2015 to 2025. A microsimulation model (noncommunicable disease model [NCDMod]) was used to assess the incremental cost‐effectiveness of WW compared with SC. A health system perspective was taken, and outcomes were measured by obesity cases averted in 2025, BMI units averted for 2015 to 2025, and quality‐adjusted life years for 2015 to 2025. Univariate sensitivity testing was used to measure variations in the model parameters.

Results

The WW intervention resulted in 60,445 averted cases of obesity in 2025 (2,311 more cases than for SC), extra intervention costs of A$219 million, and cost savings within the health system of A$17,248 million (A$82 million more than for SC) for 2015 to 2025 compared with doing nothing. The modeled WW had an incremental cost‐effectiveness ratio of A$35,195 in savings per case of obesity averted in 2025. WW remained dominant over SC for the different scenarios in the sensitivity analysis.

Conclusions

The WW intervention represents good value for money. The WW intervention needs serious consideration in a national package of obesity health services.
Correlates of Weight‐Loss Methods Among Young Adults in Canada
Authors: Raffoul Amanda , Hammond David
Published: August 2018

Objective

The aim of this study was to examine the prevalence of various weight‐loss behaviors among young adults in Canada and differences in the use of these methods by demographic characteristics, health literacy, and perceived body size.

Methods

Data from the 2016 wave of the Canada Food Study were used, which collected self‐reported information from 3,000 young adults in five cities. Linear regression models were conducted to investigate correlates of the number and type of weight‐loss methods used across the following four categories: dietary changes, physical activity, assisted weight‐loss methods, and unhealthy behaviors.

Results

In the past 12 months, more than half of respondents reported a weight‐loss attempt, and nearly one‐fifth engaged in an unhealthy weight‐loss method. The risk of engaging in a greater number of weight‐loss behaviors across categories was higher for women, nonbinary‐gendered individuals, and individuals who perceived themselves as having overweight or obesity. Respondents with lower health literacy engaged in a significantly greater number of unhealthy methods.

Conclusions

Many young adults use healthier weight‐loss strategies, but a concerning number use multiple and/or unhealthy weight‐loss methods as well. Furthermore, there are subgroup differences in weight‐loss method engagement, which holds significance for public health efforts aiming to improve weight‐related behaviors.
Finding Adequate Scale for Obesity Care
Authors: Kahan Scott , Kyle Theodore K.
Published: August 2018

See accompanying article, pg. 1261.
Crystalline structure, dielectric, and mechanical properties of simultaneously biaxially stretched polyvinylidene fluoride film
Authors: Lu Hongchao , Li Li
Published: August 2018

Biaxially stretched films have balanced properties in the film plane compared with uniaxially stretched films, thus having wider potential applications. In this paper, the simultaneously biaxial stretching (BO) technology had been applied to poly (vinylidene fluoride) (PVDF) melt extrusion film, and the crystalline structure, dielectric, and mechanical properties of the BOPVDF films were investigated. The results showed that during the simultaneous BO process, the applied stress on the film led to the alignment of PVDF chains into the crystals and the formation of all‐trans planar zigzag (TTT) conformation, thus increasing the relative content of β phase and the crystallinity of BOPVDF films, as well as the dielectric response. When the stretching ratio was 2.0 × 2.0, the dielectric constant of the film reached the maximum, ie, ~12, and the dielectric loss was minimum, ie, ~0.02. At the same time, the mechanical properties of the stretched films were significantly improved and reached the maximum tensile strength with 3.5 × 3.5 draw ratio, ie, 90 MPa.
Stable, nanometer‐thick oxygen‐containing plasma polymer films suited for enhanced biosensing
Authors: Hegemann Dirk , Indutnyi Ivan , Zajíčková Lenka , Makhneva Ekaterina , Farka Zdeněk , Ushenin Yuriy , Vandenbossche Marianne
Published: August 2018

Stable surface functionalization is required in many applications such as in biosensing. For this purpose, hydrocarbon‐based plasma polymer films (PPFs) were investigated by controlling cross‐linking and film structure at the nanoscale, while functional groups were incorporated using a CO2/C2H4 low pressure plasma. In particular, an oxygen‐rich termination layer of 1 nm (top layer) was gradually deposited onto a more cross‐linked PPF (base layer) with varying thickness (<20 nm) yielding highly stable yet functional a‐C:H:O films as compared to conventional oxygen‐rich PPFs. Such stabilized nano‐layers provided a homogeneous functionalization of Au‐coated (flat) biochips as used for immunosensing as well as of nanostructured Au‐coated surfaces explored for enhanced biosensing. The used periodic grating coated by the highly stable a‐C:H:O nano‐layer can be adjusted to the required environmental refractive index range yielding a distinct sensitivity enhancement for biosensing.