bluuebunny/crossref_metadata_2025 huggingface dataset:
Product recall as a way of responsible management of a firm: The roles of corporate social responsibility and board members' sense of ownership
Authors: Oh Hannah , Bae John , Kim Sang‐Joon , Choi Ryan
Published: February 2019

This paper employs a new perspective for viewing product recall as a way to responsibly manage a firm with a record of corporate social responsibility (CSR) engagement. Firms known for their past CSR performance are assumed to be responsible in recalling defective products when a product‐harm crisis occurs. We examine whether the cumulated CSR efforts increase the likelihood of engaging in a voluntary product recall. To further reinforce the perspective, we examine whether the relationship still holds under performance pressure. In addition, this study examines the moderating effect of board characteristics that give a sense of ownership to board members (e.g., a family member of a founder, holding block shares, and voting power) in increasing socially responsible firms' engagement in the voluntary recall. The hypotheses were tested using a sample of 592 public firms in the United States from 2001 to 2014.
Hair cortisol in the perinatal period mediates associations between maternal adversity and disrupted maternal interaction in early infancy
Authors: Nyström‐Hansen Maja , Andersen Marianne S. , Khoury Jennifer E. , Davidsen Kirstine , Gumley Andrew , Lyons‐Ruth Karlen , MacBeth Angus , Harder Susanne
Published: February 2019

Existing literature points to the possibility that cortisol could be one link between maternal adversity and poorer parenting quality, but most studies have examined salivary cortisol concentrations rather than hair cortisol concentrations. The current study examined hair cortisol concentration (HCC) during the third trimester of pregnancy as a mediator between maternal adversity indicators (childhood abuse, severe mental illness, symptomatic functioning) and maternal caregiving behavior at 4 months postpartum. Forty‐four women participated in the study: 30 with severe mental disorders, and 14 nonclinical controls. HCC was assessed during the third trimester of pregnancy (HCC‐P) and at 4 months postpartum (HCC‐4M). Sexual, physical, and emotional abuse were assessed by the Adverse Childhood Experiences Study Questionnaire. Maternal disrupted interaction was reliably coded from mother–infant video interactions during a Still‐Face Procedure. Mediation models indicated that maternal HCC‐P and HCC‐4M mediated associations between maternal psychopathology (severe mental illness, symptomatic functioning) and maternal disrupted interaction at 4 months. Maternal HCC at 4 months also mediated associations between experienced childhood abuse and overall disrupted interaction. Our findings indicate that HCC may be a potential early biomarker for future caregiving challenges among mothers with severe mental illness and histories of childhood abuse.
Rainfall partitioning varies across a forest age chronosequence in the southernAppalachianMountains
Authors: Brantley Steven T. , Miniat Chelcy F. , Bolstad Paul V.
Published: February 2019

Evaporation of precipitation from plant surfaces, or interception, is a major component of the global water budget. Interception has been measured and/or modelled across a wide variety of forest types; however, most studies have focused on mature, second‐growth forests, and few studies have examined interception processes across forest age classes. We present data on two components of interception, total canopy interception (Ei) and litter interception—that is, Oi + Oehorizon layers—(Eff), across a forest age chronosequence, from 2 years since harvest to old growth. We used precipitation, throughfall, and stemflow collectors to measure total rainfall (P) and estimateEi; and collected litter biomass and modelled litter wetting and drying to estimate evaporative loss from litter. CanopyEi,Pminus throughfall, increased rapidly with forest age and then levelled off to a maximum of 21% ofPin an old‐growth site. Stemflow also varied across stands, with the highest stemflow (~8% ofP) observed in a 12‐year‐old stand with high stem density. ModelledEffwas 4–6% ofPand did not vary across sites. Total stand‐level interception losses (Ei + Eff) were best predicted by stand age (R2 = 0.77) rather than structural parameters such as basal area (R2 = 0.49) or leaf area (R2 < 0.01). Forest age appears to be an important driver of interception losses from forested mountain watersheds even when stand‐level structural variables are similar. These results will contribute to our understanding of water budgets across the broader matrix of forest ages that characterize the modern forest landscape.
Single Laser Shot Photoinduced Phase Transition of Rubidium Manganese Hexacyanoferrate Investigated by X‐ray Diffraction
Authors: Azzolina Giovanni , Collet Eric , Mariette Céline , Cammarata Marco , Trzop Elzbieta , Sander Mathias , Levantino Matteo , Nakagawa Kosuke , Tokoro Hiroko , Ohkoshi Shin‐ichi , Bertoni Roman
Published: February 2019

We have studied by X‐ray diffraction the phase transition of microcrystals of rubidium manganese hexacyanoferrate, for which combined electron transfer and structural reorganization are responsible for a change of magnetic properties. The Rb0.94Mn[Fe(CN)6]0.98·2.5H2O system undergoes a phase transition between the tetragonal phase FeII(S = 0)–CN–MnIII(S = 2) and the cubic FeIII(S = 1/2)–CN–MnII(S = 5/2) phases. The thermal equilibrium phase transition shows a broad regime of bistability, responsible for the appearance of a thermal hysteresis in the approximate 185–300 K temperature range. We used a deposited film to study by X‐ray diffraction the switching from the tetragonal phase to the cubic phase, induced inside the thermal hysteresis by a single laser shot of tuneable power. Compared to previous measurements using local probes, our results show that the ns laser pulse induces a stable long‐range ordered cubic phase when conversion is partial or complete.
A Molybdenum Carbide Nanotubes Modified Electrode as the Functionalized Sensing Platform for Electrochemical Detection of Dopamine
Authors: Li Ke , Han Yanchao , Li Jing , Xing Huanhuan , Chen Lei , Li Guang , Zhu Xiaoqing , Wang Erkang
Published: February 2019

In this work, molybdenum carbide (Mo2C) nanotubes were prepared via the self‐degradable template method and high‐temperature calcination, and then were successfully used to modify glassy carbon electrode (CGE) for the high‐sensitivity determination of dopamine (DA) without the inference of ascorbic acid(AA) and uric acid (UA). The surface morphology of Mo2C nanotubes has been investigated by scanning electron microscope (SEM) and transmission electron microscope (TEM). Owing to the enhanced electron transfer rate and high surface area of Mo2C, the modified electrode not only exhibits very excellent electrochemical performance for DA, but also has good analytical performance for DA in the mixture with AA and UA through differential pulse voltammetry (DPV), which can be applied for DA detection with wide linear range(0.005–50 μmol L−1) and low detection limit 0.001 μmol L−1. The modified electrode has been applied to detect DA in DA hydrochloride injection by using standard adding method with satisfactory results.
Electrochemical Biosensor for Sensitive Quantification of Glyphosate in Maize Kernels
Authors: Cahuantzi‐Muñoz Selene L. , González‐Fuentes Miguel A. , Ortiz‐Frade Luis A. , Torres Eduardo , Ţălu Ştefan , Trejo G. , Méndez‐Albores Alia
Published: February 2019

A graphite‐epoxy electrode (GE) modified with multiwalled carbon nanotubes (MWCNTs) and horseradish peroxidase (GE/MWCNTs‐HRP) was used to build a glyphosate biosensor whose performance in aqueous solutions depends on the enzyme activity. For the biosensor preparation, MWCNTs were deposited onto the GE surface by electrophoresis using an oxidative treatment (H2SO4/HNO3) in presence of cetyl tributylammonium bromide (CTAB) as a cationic surfactant. The surfactant was further removed from the MWCNTs surface by dipping the electrode in an EtOH/HCl solution. The physical immobilization of HRP and therefore the glyphosate sensing capabilities was tested at pH 4 where the herbicide exhibits one only species. Circular dichroism studies suggested that the secondary structure of HRP changes as a result of its interaction with glyphosate and that this change is intensified by the combination of glyphosate and H2O2, which may explain the decrease of the enzyme catalytic activity with the increase of glyphosate concentration. The glyphosate quantification in doped‐maize kernels was highly reproducible and exhibits detection and quantification limits of 1.32 pM and 1.63 pM respectively. The biosensor is also characterized by a high recovery (100 %) and precision (coefficient of variation <1 %) and can be employed in presence of interfering substances such as chlorpyrifos (an organophosphate pesticide) and starch.
Development of bedforms due to waves blocked by a counter current
Authors: Chatterjee Debasmita , Ghosh Subir , Mazumder Bijoy S. , Sarkar Kaushik
Published: February 2019

Experiments are conducted in a laboratory flume on the propagation of a surface wave against unidirectional flow with a sediment bed. This article presents the spatial variation of bedforms induced by the wave‐blocking phenomenon by a suitably tuned uniform fluid flow and a counter‐propagating wave. The occurrence of wave‐blocking is confirmed by finding a critical wave frequency in a particular flow discharge in which the waves are effectively blocked and is established using the linear dispersion relation. The purpose of this work is to identify wave‐blocking and its influence on the development of bedforms over the sediment bed. Interestingly bedform signatures are observed at a transition of bedforms in three zones, with asymmetric ripples having a steeper slope downstream face induced by the incoming current, followed by flat sand bars beneath the wave‐blocking zone and more symmetric ripples below the wave‐dominated region at the downstream. This phenomenon suggests that the sediment bed is segmented into three different regions of bed geometry along the flow. The deviations of mean flows, Reynolds stresses, turbulent kinetic energy, and power spectral density due to the wave‐blocking phenomenon are presented along the non‐uniform flow over sediment bed. The bottom shear stress, bed roughness and stochastic nature of the bedform features are also discussed. The results are of relevance to engineers and geoscientists concerned with contemporary process as well as those interested in the interpretation of palaeoenvironmental conditions from fossil bedforms. © 2019 John Wiley & Sons, Ltd.
Application of steam explosion in oil extraction of camellia seed (Camellia oleifera Abel.) and evaluation of its physicochemical properties, fatty acid, and antioxidant activities
Authors: Zhang Shanying , Pan Yong‐Gui , Zheng Lili , Yang Yang , Zheng Xiaoyan , Ai Binling , Xu Zhimin , Sheng Zhanwu
Published: February 2019

This study evaluated the physicochemical properties of oils extracted from steam‐exploded camellia seed (Camellia oleifera Abel.). Steam pressure, resident time, fatty acid composition, total phenolics, tocopherol, squalene, and sterol contents, and volatile compounds were determined. 1H NMR and FTIR spectra were performed for the structure of camellia seed oil. This study has found the highest yield of oil was 86.56% and was obtained when steam explosion pretreatment was at 1.6 MPa 30 s. Oil extracted by steam explosion pretreatment exhibited favorable physicochemical properties and stronger antioxidant activities compared to untreated oil. The compositions of fatty acid were similar between treated and untreated camellia seed oil. According to the 1H NMR and FTIR analyses, the functional groups of the oils were not significantly affected by the steam explosion pretreatment. Furans such as 2‐pentyl‐furan, 2‐furanmethanol, and 3‐methyl‐furan were produced from stream‐exploded camellia seed. Scanning electron microscopy revealed that steam explosion pretreatment efficiently promoted the release of oil by destroying the cell structure of camellia seed. Therefore, steam explosion can be an effective method for the camellia seed oil extraction.
Bacterial content and associated risk factors influencing the quality of bulk tank milk collected from dairy cattle farms in Mandalay Region
Authors: Naing Ye Wint , Wai Soe Soe , Lin Thant Nyi , Thu Wink Phyo , Htun Lat Lat , Bawm Saw , Myaing Tin Tin
Published: February 2019

To investigate the bacterial content and risk factors associated with the hygienic quality of raw milk, a cross‐sectional study was conducted in four townships of Mandalay Region, Myanmar. From April to October 2017, bulk tank milk samples (n = 233) were collected from 233 dairy cattle farms located in Tada‐U, Pyin Oo Lwin, Meiktila, and Patheingyi Townships. From each farm, approximately 100 ml of bulk tank milk was collected and examined for bacterial content. Total bacterial count (TBC) and coliform count (CC) in milk samples were determined using milk agar and violet red bile agar. Of 233 milk samples, 68.2% (159/233) showed TBC higher than 1.0 × 105 cfu/ml, and 78.4% (183/233) showed CC higher than 100 cfu/ml. The mean value of TBC among 233 farms was 2.55 × 107 cfu/ml, ranging from 6.0 × 103 to 3.0 × 109 cfu/ml, whereas the mean value of CC was 1.59 × 105 cfu/ml, ranging from 10 to 8.4 × 106 cfu/ml. TBC tended to increase as CC increased in milk samples. The number of precautionary measures for milking operation, choice of cleaning materials, training experience of the farmers, cleanliness score of milking cows, and CMT scores of milk were significantly associated (p < 0.05) with TBC in bulk tank milk. Similarly, the number of precautionary measures for milking operation, choice of cleaning materials, training experience of the farmers, cleanliness scores of milking cows, CMT scores of milk samples, herd size, and type of milking practice showed significant association (p < 0.05) with CC in bulk tank milk. The effects of these potential risk factors should be minimized, farmers should be trained properly, and technical support should be provided, so that the quality of raw milk produced in Myanmar can be improved.
Energy Infrastructure Rebuilding Should Reflect Current Technologies
Authors: DeCotis Paul A.
Published: February 2019

In an earlier column in these pages, note was made of the numerous studies pointing to the need for significant investment in our energy infrastructure.
The relationship between the frequency of number‐puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over
Authors: Brooker Helen , Wesnes Keith A. , Ballard Clive , Hampshire Adam , Aarsland Dag , Khan Zunera , Stenton Rob , Megalogeni Maria , Corbett Anne
Published: February 2019

Objective

Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number‐puzzle use is related to cognitive function in older adults.

Methods

Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self‐reported frequency of performing number puzzles. Two cognitive‐test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups.

Results

Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant.

Conclusions

This study has identified a close relationship between frequency of number‐puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.
The hippocampal code for space in Mongolian gerbils
Authors: Mankin Emily A. , Thurley Kay , Chenani Alireza , Haas Olivia V. , Debs Luca , Henke Josephine , Galinato Melissa , Leutgeb Jill K. , Leutgeb Stefan , Leibold Christian
Published: February 2019

Large parts of our knowledge about the physiology of the hippocampus in the intact brain are derived from studies in rats and mice. While many of those findings fit well to the limited data available from humans and primates, there are also marked differences, for example, in hippocampal oscillation frequencies and in the persistence of theta oscillations. To test whether the distinct sensory specializations of the visual and auditory system of primates play a key role in explaining these differences, we recorded basic hippocampal physiological properties in Mongolian gerbils, a rodent species with high visual acuity, and good low‐frequency hearing, similar to humans. We found that gerbils show only minor differences to rats regarding hippocampal place field activity, theta properties (frequency, persistence, phase precession, theta compression), and sharp wave ripple events. The only major difference between rats and gerbils was a considerably higher degree of head direction selectivity of gerbil place fields, which may be explained by their visual system being able to better resolve distant cues. Thus, differences in sensory specializations between rodent species only affect hippocampal circuit dynamics to a minor extent, which implies that differences to other mammalian lineages, such as bats and primates, cannot be solely explained by specialization in the auditory or visual system.
[2.2.2.2](2,7)‐1‐Bromonaphthalenophane from a Desymmetrized Building Block Bearing Electrophilic and Masked Nucleophilic Functionalities
Authors: Cai Guangke , Chatterjee Shreyam , Hisaki Ichiro , Tobe Yoshito
Published: February 2019

In search of 2,7‐ethylene‐bridged naphthalenophanes with desymmetrized naphthalene cores as inherently chiral cyclophanes, nucleophilic substitution of 1‐bromo‐7‐(bromomethyl)‐2‐[(trimethylsilyl)methyl]naphthalene, a desymmetrized building block bearing an electrophilic group (CH2Br) and a masked nucleophilic functionality (CH2TMS) which can be activated by fluoride anion, was examined. As a result, in contrast to the case of parent naphthalenophanes wherein the smallest [2.2]naphthalenophane was obtained as the major product, only [2.2.2.2](2,7)‐1‐bromonaphthalenophane was obtained albeit in low yields, whereas the corresponding [2.2]‐ or [2.2.2]naphthalenophanes were not obtained. Though the [2.2.2.2]‐1‐bromonaphthalenophane can adopt four idealized geometries of different symmetry, among which three are inherently chiral, theoretical calculations predict that three conformers have almost equal energy and may equilibrate in solution. The X‐ray crystallographic study shows that it adopts a C2 conformation with anti,anti,anti orientation of the C−Br bonds at least as a major component in crystal.
MicroRNA‐365 promotes the contractile phenotype of venous smooth muscle cells and inhibits neointimal formation in rat vein grafts
Authors: Cao Bo‐Jun , Zhu Lei , Wang Xiao‐Wen , Zou Rong‐Jiang , Lu Zhi‐Qian
Published: February 2019

The high rate of autologous vein graft failure caused by neointimal hyperplasia remains an unresolved issue in the field of cardiovascular surgery; therefore, it is important to explore new methods for protecting against neointimal hyperplasia. MicroRNA‐365 has been reported to inhibit the proliferation of vascular smooth muscle cells (SMCs). This study aimed to test whether adenovirus‐mediated miR‐365 was able to attenuate neointimal formation in rat vein grafts. We found that miR‐365 expression was substantially reduced in vein grafts following engraftment. In vitro, overexpression of miR‐365 promoted smooth muscle‐specific gene expression and inhibited venous SMC proliferation and migration. Consistent with this, overexpression of miR‐365 in a rat vein graft model significantly reduced grafting‐induced neointimal formation and effectively improved the hemodynamics of the vein grafts. Mechanistically, we identified that cyclin D1 as a potential downstream target of miR‐365 in vein grafts. Specially, to increase the efficiency of miR‐365 gene transfection, a 30% poloxamer F‐127 gel containing 0.25% trypsin was mixed with adenovirus and spread around the vein grafts to increase the adenovirus contact time and penetration. We showed that adenovirus‐mediated miR‐365 attenuated venous SMC proliferation and migration in vitro and effectively inhibited neointimal formation in rat vein grafts. Restoring expression of miR‐365 is a potential therapeutic approach for the treatment of vein graft failure. © 2019 IUBMB Life, 2019
Effect of chronic exposure to inorganic arsenic on intestinal cells
Authors: Chiocchetti Gabriela M. , Vélez Dinoraz , Devesa Vicenta
Published: February 2019

Chronic exposure to inorganic arsenic (As)—As(III) + As(V)—is associated with type 2 diabetes, vascular diseases and various types of cancer. Although the oral route is the main way of exposure to inorganic As, the adverse gastrointestinal effects produced by chronic exposure are not well documented. The aim of the present study is to evaluate the effect of chronic exposure to As(III) on the intestinal epithelium. For this purpose, NCM460 cells, non‐transformed epithelial cells from the human colon, were exposed to As(III) (0.01‐0.2 mg/L) for 6 months and monitored for acquisition of a tumor‐like phenotype. Secretion of matrix metalloproteinases, histone modifications (H3 acetylation), hyperproliferation capacity, formation of floating spheres, anchorage‐independent growth, release of cytokine interleukin‐8 and expression of relevant genes in colon tumorigenesis were assessed. The results show a maintained proinflammatory response from the beginning, with an increase in interleukin‐8 secretion (≤570%). Downregulation of CDX1 and CDX2 was also observed. After 14 weeks of exposure, cells presented marked increases in matrix metalloproteinase‐2 secretion and histone modifications. As(III)‐treated cells were hyperproliferative, grew in low‐serum media and were able to form free‐floating spheres. Overall, these data suggest that exposure of human colon epithelial cells to As(III) facilitates acquisition of transformed cell characteristics.
Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold
Authors: Hosseini Fatemeh Sadat , Saburi Ehsan , Enderami Seyed Ehsan , Ardeshirylajimi Abdolreza , Bagherabad Matineh Barati , Marzouni Hadi Zare , Ghoraeian Pegah , Soleimanifar Fatemeh
Published: February 2019

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT‐MSCs), and after characterization cultured on the PES‐PANI scaffold and culture plate. Electron microscopic and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT‐MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real‐time reverse‐transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT‐MSCs was significantly increased when grown on PES‐PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES‐PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.
Downregulation of miroRNA‐141 mediates acquired resistance to trastuzumab and is associated with poor outcome in breast cancer by upregulating the expression of ERBB4
Authors: Han Guodong , Qiu Ni , Luo Kai , Liang Hongling , Li Hongsheng
Published: February 2019

Background

microRNAs are involved in the control of cell growth and apoptosis; they also play an essential role in resistance towards trastuzumab, in breast cancer. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease.

Methods

Real‐time polymerase chain reaction (RT‐PCR) was performed to identify the virtual microRNA (miRNA) involved in breast cancer cells resistant to trastuzumab. RT‐PCR and Western blot analysis were carried out to study the effects of microRNA‐141 (miR‐141) on ERBB2, ERBB4 and AKT production. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenylterazolium bromide assay and flow cytometry analysis was carried out to examine the effect of miR‐141 on cell proliferation and apoptosis via ERBB4.

Result

According to RT‐PCR results, only miR‐141 and miR‐375 among miR‐141, miR‐375, miR‐16, miR‐155, miR‐217 and miR‐205 were downregulated in trastuzumab‐resistant cells. Trastuzumab‐resistant cells displayed higher levels of ERBB4 and p‐AKT as well as showing a higher growth rate and a lower apoptosis rate. Online software programs were used, which identified ERBB4 as a gene targeted by miR‐141 with a highly conserved binding site for miR‐141 located within the ERBB4 3′‐untranslated region. In trastuzumab‐resistant cells, miR‐141 and shERBB4 reduced ERBB4 and p‐AKT levels; ERBB2 and total AKT levels in miR‐141 and shERBB4 groups showed no significant difference. Anti‐miR‐141 was upregulated ERBB4 and p‐AKT levels in parental cell and had no obvious effect on ERBB2 and total AKT levels. Finally, miR‐141 upregulated viability of the cells, which was restored by shERBB4, miR‐141 and shERBB4 inhibited proliferation, and enhanced apoptosis of trastuzumab‐resistant cells. miR‐141 inhibitor caused an evident increase in proliferation and an obvious decrease in apoptosis of parental cells.

Conclusion

Knockdown of miR‐141 causes overexpression of ERBB4, which is involved in trastuzumab resistance in breast cancer cells. This study has implications that miR‐141 as well as its target, ERBB4, as a potential target for treating trastuzumab‐resistant breast cancers.
Myricetin relieves LPS‐induced mastitis by inhibiting inflammatory response and repairing the blood–milk barrier
Authors: Kan Xingchi , Liu Bingrun , Guo Wenjin , Wei Libin , Lin Yuanqing , Guo Yingcheng , Gong Qian , Li Yanwei , Xu Dianwen , Cao Yu , Huang Bingxu , Dong Aiwen , Ma He , Fu Shoupeng , Liu Juxiong
Published: February 2019

Mastitis, an inflammation of mammary gland, is a serious disease that affects the health of dairy cows around the world. Myricetin, a flavonoid from Bayberry, has been reported to suppress various inflammatory response. The aim of this study was to evaluate the effect of myricetin on lipopolysaccharide (LPS)‐induced in vivo and in vitro mastitis model and clarify the underlying mechanism. In vivo experiments, myricetin attenuated the severity of inflammatory lesion and neutrophil infiltration. Moreover, myricetin pretreatment induced a significant decrease in the activity of myeloperoxidase (MPO) and the production of TNF‐α, IL‐6, and IL‐1β triggered by LPS. Myricetin pretreatment could also increase the integrity of the blood–milk barrier and upregulate the tight junction proteins in LPS‐induced mice mastitis. In vitro, myricetin inhibited LPS‐induced inflammatory response in mice mammary epithelial cells (mMECs). In the further mechanism studies, we found that the anti‐inflammatory effect of myricetin was mediated by inhibiting LPS‐induced phosphorylation of AKT, IKK‐α, IκB‐α, and P65 in vivo and in vitro. Collectively, these data suggested that myricetin effectively ameliorated the inflammatory response by inhibiting the AKT/IKK/NF‐κB signaling pathway and repairing the integrity of blood–milk barrier in LPS‐induced mice mastitis.
The effect of anodal/cathodal biphasic electrical stimulation on insulin release
Authors: Siegel David , Baca Serapio M. , Thompson David C. , Huntsman Molly M. , Mower Morton M. , Ross David
Published: February 2019

We studied the effects of electrical stimulation on insulin release from rat insulinoma (INS‐1) cells. The anodal/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage‐ and stimulation duration‐dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Basal and ACBPS‐induced insulin secretion could be inhibited by mitochondrial poisons and calcium channel blockers, indicating that insulin release was dependent on adenosine triphosphate (ATP) and the influx of calcium. ACBPS parameters that released insulin caused no detectable plasma membrane damage or cytotoxicity, although temporary morphological changes could be observed immediately after ACBPS. ACBPS did not alter the plasma membrane transmembrane potential but did cause pronounced uptake of MitoTracker Red into the mitochondrial membrane, indicating an increased mitochondrial membrane potential. While the ATP:ADP ratio after ACBPS did not change, the guanosine triphosphate (GTP) levels increased and increased GTP levels have previously been associated with insulin release in INS‐1 cells. These results provide evidence that ACBPS can have significant biological effects on cells. In the case of INS‐1 cells, ACBPS promotes insulin release without causing cytotoxicity.
Anti‐inflammatory effects of resolvins in diabetic nephropathy: Mechanistic pathways
Authors: Yaribeygi Habib , Atkin Stephen L. , Simental‐Mendía Luis E. , Barreto George E. , Sahebkar Amirhossein
Published: February 2019

The incidence of diabetes mellitus is growing rapidly. The exact pathophysiology of diabetes is unclear, but there is increasing evidence of the role of the inflammatory response in both developing diabetes as well as its complications. Resolvins are naturally occurring polyunsaturated fatty acids that are found in fish oil and sea food that have been shown to possess anti‐inflammatory actions in several tissues including the kidneys. The pathways by which resolvins exert this anti‐inflammatory effect are unclear. In this review we discuss the evidence showing that resolvins can suppress inflammatory responses via at least five molecular mechanisms through inhibition of the nucleotide‐binding oligomerization domain protein 3 inflammasome, inhibition of nuclear factor κB molecular pathways, improvement of oxidative stress, modulation of nitric oxide synthesis/release and prevention of local and systemic leukocytosis. Complete understanding of these molecular pathways is important as this may lead to the development of new effective therapeutic strategies for diabetes and diabetic nephropathy.
4β‐Hydroxycholesterol as an Endogenous Biomarker for CYP3A Activity: Literature Review and Critical Evaluation
Authors: Penzak Scott R. , Rojas‐Fernandez Carlos
Published: February 2019

A number of cytochrome P450 (CYP)3A phenotyping probes have been used to characterize the drug interaction potential of new molecular entities; of these, midazolam has emerged as the gold standard. Recently, plasma 4β‐hydroxycholesterol (4β‐OHC), the metabolite of CYP3A‐mediated cholesterol metabolism, has been championed as an endogenous biomarker for CYP3A, particularly during chronic conditions where CYP3A activity is altered by disease and in long‐term treatment studies where midazolam administration is not optimal. Multiple studies in humans have shown that 4β‐OHC can qualitatively differentiate among weak, moderate, and potent CYP3A induction when an inducer, typically rifampin, is administered for up to 2 weeks. Conversely, longer durations of CYP3A inhibitor administration (≥1 month) appear to be necessary to differentiate among weak, moderate, and potent CYP3A inhibitors. A number of studies have reported statistically significant linear relationships between 4β‐OHC plasma concentrations (and 4β‐OHC:cholesterol ratios) and midazolam clearance. However, sufficiently powered studies assessing the ability of 4β‐OHC or 4β‐OHC:cholesterol ratios to measure CYP3A activity (ie, predictive performance) have not been conducted to date. Additional limitations associated with 4β‐OHC phenotyping include inability to detect acute changes in CYP3A activity, uncertainty with regard to its intestinal formation, ambiguity surrounding the role of CYP3A5 in its metabolism, and lack of clarity regarding the role of transporters in its disposition. As such, the data do not support the use of 4β‐OHC or 4β‐OHC:cholesterol ratios as an endogenous biomarker for CYP3A activity.
A case of gastric carcinoma with lymphoid stroma diagnosed by an endoscopic ultrasound‐guided fine‐needle biopsy
Authors: Tanabe Hiroki , Ando Katsuyoshi , Sutoh Daisuke , Ohta Katsuhisa , Ohdaira Hironori , Suzuki Yutaka , Fujiya Mikihiro , Okumura Toshikatsu
Published: February 2019

Endoscopic ultrasound‐guided sampling is indicated to achieve an accurate diagnosis of subepithelial lesions of the stomach when a standard biopsy fails. Gastric carcinoma with lymphoid stroma (GCLS) is located under the epithelial layer with dense lymphocytic infiltration, making a pathological diagnosis by a biopsy difficult. We herein report a case of the pathological diagnosis of GCLS using an endoscopic ultrasound‐guided fine‐needle biopsy. The patient underwent distal gastrectomy and was diagnosed with Epstein‐Barr virus‐negative cancer.
ART adherence and viral suppression are high among most non‐pregnant individuals with early‐stage, asymptomatic HIV infection: an observational study from Uganda and South Africa
Authors: Haberer Jessica E , Bwana Bosco M , Orrell Catherine , Asiimwe Stephen , Amanyire Gideon , Musinguzi Nicholas , Siedner Mark J , Matthews Lynn T , Tsai Alexander C , Katz Ingrid T , Bell Kathleen , Kembabazi Annet , Mugisha Stephen , Kibirige Victoria , Cross Anna , Kelly Nicola , Hedt‐Gauthier Bethany , Bangsberg David R
Published: February 2019

Introduction

The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support.

Methods

From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 < 200 cells/μL). Socio‐behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically.

Results

Adherence data were available for 869 participants: 322 (37%) early/non‐pregnant, 199 (23%) early/pregnant and 348 (40%) late/non‐pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non‐pregnant versus early/pregnant or late/non‐pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non‐pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking.

Discussion

ART adherence among non‐pregnant individuals with early‐stage infection is as high or higher than with late‐stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late‐stage infection in South Africa and highlight the need for differentiated care delivery.
The trafficking protein JFC1 regulates Rac1-GTP localization at the uropod controlling neutrophil chemotaxis and in vivo migration
Authors: Ramadass Mahalakshmi , Johnson Jennifer L , Marki Alex , Zhang Jinzhong , Wolf Dennis , Kiosses William B , Pestonjamasp Kersi , Ley Klaus , Catz Sergio D
Published: February 2019

Neutrophil chemotaxis is essential in responses to infection and underlies inflammation. In neutrophils, the small GTPase Rac1 has discrete functions at both the leading edge and in the retraction of the trailing structure at the cell’s rear (uropod), but how Rac1 is regulated at the uropod is unknown. Here, we identified a mechanism mediated by the trafficking protein synaptotagmin-like 1 (SYTL1 or JFC1) that controls Rac1-GTP recycling from the uropod and promotes directional migration of neutrophils. JFC1-null neutrophils displayed defective polarization and impaired directional migration to N-formyl-methionine-leucyl-phenylalanine in vitro, but chemoattractant-induced actin remodeling, calcium signaling and Erk activation were normal in these cells. Defective chemotaxis was not explained by impaired azurophilic granule exocytosis associated with JFC1 deficiency. Mechanistically, we show that active Rac1 localizes at dynamic vesicles where endogenous JFC1 colocalizes with Rac1-GTP. Super-resolution microscopy (STORM) analysis shows adjacent distribution of JFC1 and Rac1-GTP, which increases upon activation. JFC1 interacts with Rac1-GTP in a Rab27a-independent manner to regulate Rac1-GTP trafficking. JFC1-null cells exhibited Rac1-GTP accumulation at the uropod and increased tail length, and Rac1-GTP uropod accumulation was recapitulated by inhibition of ROCK or by interference with microtubule remodeling. In vivo, neutrophil dynamic studies in mixed bone marrow chimeric mice show that JFC1−/− neutrophils are unable to move directionally toward the source of the chemoattractant, supporting the notion that JFC1 deficiency results in defective neutrophil migration. Our results suggest that defective Rac1-GTP recycling from the uropod affects directionality and highlight JFC1-mediated Rac1 trafficking as a potential target to regulate chemotaxis in inflammation and immunity.
Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner
Authors: Li Tianyang , Yang Yang , Song Hongxiao , Li Haijun , Cui An , Liu Yanhou , Su Lishan , Crispe Ian Nicholas , Tu Zhengkun
Published: February 2019

NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL-12 and IL-18, and innate immune stimuli such as ligation of TLRs. The secretion of IL-18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL-18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL-18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38/PI3K/AKT pathway, and that the activated NK cells mediate HSC death in a TRAIL-involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38/PI3K/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression.
Illinois Tool Works: Making a big impact with small‐wins strategy
Authors: Pangarkar Nitin
Published: February 2019

Game‐changing business strategies grab headlines, but also often fail to live up to stakeholders' expectations. In pursuit of these ambitious approaches, companies may lose sight of the benefit of carefully planned, frequent small gains that, over time, result in exceptional performance. As implemented at Illinois Tool Works, an American Fortune 500 firm, this small‐wins strategy is grounded in decentralization, operational excellence based on simplicity, customer‐focused innovation, and acquisitions. The firm's experiences offer other companies wishing to follow suit a four‐point agenda for getting the most from continual small gains.
Augmentation of chronic rotator cuff healing using adipose‐derived stem cell‐seeded human tendon‐derived hydrogel
Authors: Kaizawa Yukitoshi , Franklin Austin , Leyden Jacinta , Behn Anthony W. , Tulu Ustun S. , Sotelo Leon Daniel , Wang Zhen , Abrams Geoffrey D. , Chang James , Fox Paige M.
Published: February 2019

Rotator cuff (RTC) repair outcomes are unsatisfactory due to the poor healing capacity of the tendon bone interface (TBI). In our preceding study, tendon hydrogel (tHG), which is a type I collagen rich gel derived from human tendons, improved biomechanical properties of the TBI in a rat chronic RTC injury model. Here we investigated whether adipose‐derived stem cell (ASC)‐seeded tHG injection at the repair site would further improve RTC healing. Rats underwent bilateral supraspinatus tendon detachment. Eight weeks later injured supraspinatus tendons were repaired with one of four treatments. In the control group, standard transosseous suture repair was performed. In the ASC, tHG, tHGASC groups, ASC in media, tHG, and ASC‐seeded tHG were injected at repair site after transosseous suture repair, respectively. Eight weeks after repair, the TBI was evaluated biomechanically, histologically, and via micro CT. Implanted ASCs were detected in ASC and tHGASC groups 7 weeks after implantation. ACS implantation improved bone morphometry at the supraspinatus insertion on the humerus. Injection of tHG improved biomechanical properties of the repaired TBI. RTC healing in tHGASC group was significantly better than control but statistically equivalent to the tHG group based on biomechanical properties, fibrocartilage area at the TBI, and bone morphometry at the supraspinatus insertion. In a rat RTC chronic injury model, no biomechanical advantage was gained with ASC augmentation of tHG. Clinical Significance: Tendon hydrogel augmentation with adipose derived stem cells does not significantly improve TBI healing over tHG alone in a chronic rotator cuff injury model. © 2019 Orthopaedic Research Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Functional Brush Poly(2‐ethyl‐2‐oxazine)s: Synthesis by CROP and RAFT, Thermoresponsiveness and Grafting onto Iron Oxide Nanoparticles
Authors: Klein Tobias , Parkin Joshua , de Jongh Patrick A. J. M. , Esser Lars , Sepehrizadeh Tara , Zheng Gang , De Veer Michael , Alt Karen , Hagemeyer Christoph E. , Haddleton David M. , Davis Thomas P. , Thelakkat Mukundan , Kempe Kristian
Published: February 2019

Brush polymers are highly functional polymeric materials combining the properties of different polymer classes and have found numerous applications, for example, in nanomedicine. Here, the synthesis of functional phosphonate‐ester‐bearing brush polymers based on poly(2‐oxazine)s is reported through a combination of cationic ring‐opening polymerization (CROP) of 2‐ethyl‐2‐oxazine and reversible addition‐fragmentation chain transfer (RAFT) polymerization. In this way, a small library of well‐defined (Đ ≤ 1.17) poly(oligo(2‐ethyl‐2‐oxazine) methacrylate) P(OEtOzMA)n brushes with tunable lower critical solution temperature (LCST) behavior and negligible cell toxicity is prepared. Upon deprotection, the phosphonic acid end‐group of the P(OEtOzMA)n brush enables the successful grafting‐onto iron oxide nanoparticles (IONPs). Colloidal stability of the particle suspension in combination with suitable magnetic resonance imaging (MRI) relaxivities demonstrates the potential of these particles for future applications as negative MRI contrast agents.
Accreditation in a differentiated duopoly
Authors: Grepperud Sverre , Mathisen Terje Andreas , Pedersen Pål Andreas
Published: February 2019

Accreditation is increasingly important worldwide; however, some industries have higher accreditation rates than others. We suggest a duopoly model to discuss how market characteristics affect the incentive for firms to seek accreditation. The discussion relates to the effects accreditation might have on the costs and demands in the markets, the degree of product differentiation (addressing both substitutable and complementary goods), type of competition (various Cournot and Bertrand games), and welfare for society. It follows that markets with high accreditation rates are either characterized by fierce competition (price competition in substitutable goods) or by a high degree of coordination (complementarity).
Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy
Authors: Arnst Kinsie E , Banerjee Souvik , Chen Hao , Deng Shanshan , Hwang Dong‐Jin , Li Wei , Miller Duane D
Published: February 2019

Microtubule (MT)‐targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Newer generations of developed drugs attack these problems and alternative approaches such as the development of dual tubulin and kinase inhibitors are being investigated. This approach offers the potential to show increased efficacy and lower toxicities. This review covers different categories of MT‐targeting agents, recent advances in dual inhibitors, and current challenges for this drug target.
Methylation of HIF3A promoter CpG islands contributes to insulin resistance in gestational diabetes mellitus
Authors: Zhang Yinghong , Chen Yangyang , Qu Hongmei , Wang Yuanli
Published: February 2019

Background

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance during pregnancy, and will lead to high risk of diabetes even after pregnancy. Hypoxia‐inducible factor (HIF) family proteins are transcriptional factors that are highly correlated with methylation, which might be involved in the regulation of GDM.

Methods

Baseline clinical characteristics of the GDM patients and healthy women were analyzed. Omental tissue from GDM patients and control groups were collected and detected for the expression levels of HIF1A, HIF2A, and HIF3A. The CpG islands of HIF3A promoter were predicted by “methprimer” software, and the methylation level of CpG islands was detected by bisulfite sequencing PCR.

Results

HIF3A was downregulated in the omental tissue from GDM patients, whereas HIF1A and HIF2A were not affected. Furthermore, HIF3A expression was positively correlated with levels of estrogen receptor α (ESR1) and solute carrier family 2 member 4 (SLC2A4). Moreover, CpG islands of HIF3A promoter were highly methylated in GDM patients. In addition, methylation level of CpG islands could be upregulated by Estradiol (E2) treatment, since high dose of E2 reduced HIF3A mRNA expression in 3T3‐L1 adipocytes.

Conclusion

Our findings demonstrate that the expression level of HIF3A, but not HIF1A or HIF2A, is downregulated in GDM patients. The methylation status of HIF3A promoter region is highly correlated with GDM, which could be a novel therapeutic target for GDM treatment.