bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Analysis of Natural‐Product‐Like Macrocycles by Tandem Oxidation/Oxa‐Conjugate Addition Reactions
Authors: Lee Hyunji , Sylvester Kayla , Derbyshire Emily R. , Hong Jiyong
Published: March 2019

As traditional small‐molecule drug discovery programs focus on a relatively narrow range of chemical space, most human proteins are viewed as unreachable targets. Consequently, there is a strong interest in expanding the chemical space in drug discovery beyond traditional small molecules. Here, a strategy for the preparation of a broad natural‐product‐like macrocyclic library by using the tandem allylic oxidation/oxa‐conjugate addition and macrocyclization reactions is reported. Cheminformatic analyses demonstrate that this tetrahydropyran‐containing macrocyclic library shows a significant overlap with natural products in the chemical space. This approach can be used for designing libraries that may probe more deeply into natural‐product‐like space.
Anticancer IrIII–Aspirin Conjugates for Enhanced Metabolic Immuno‐Modulation and Mitochondrial Lifetime Imaging
Authors: Wu Xiao‐Wen , Zheng Yue , Wang Fang‐Xin , Cao Jian‐Jun , Zhang Hang , Zhang Dong‐Yang , Tan Cai‐Ping , Ji Liang‐Nian , Mao Zong‐Wan
Published: March 2019

The chemo‐anti‐inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated IrIII complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti‐inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long‐lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase‐dependent apoptosis and caspase‐independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial‐targeting and immunomodulatory activities is feasible to develop multifunctional metal‐based anticancer agents.
Developing Bicatalytic Cascade Reactions: Ruthenium‐catalyzed Hydrogen Generation From Methanol
Authors: Agapova Anastasiya , Junge Henrik , Beller Matthias
Published: March 2019

A novel state‐of‐the‐art bicatalytic system for hydrogen generation from aqueous methanol at low temperature and base concentration is described. Applying two molecularly defined ruthenium complexes A and B3 for methanol dehydrogenation at the same time under the same conditions, a synergistic effect is observed. This behavior is explained by the increase of the dehydrogenation of formic acid, which is formed as an intermediate, by the second catalyst B3.
A Molecular Torsion Balance Study: A Nearby Anionic Group Exerts Little Influence on Hydrophobic Interactions between Nonpolar Surfaces
Authors: Ling Xiujun , Wilcox Craig S.
Published: March 2019

Polar groups have a solvent ordering effect on water and therefore may affect hydrophobic binding energies for nearby lipophilic surfaces. This would mean that determinations of excess surface free energy association energies require consideration of nearby polar functional groups. This paper reports results of a study to measure this possible effect. It was concluded from the models used here that an anionic polar group nearby a hydrophobic surface has little or no effect on the magnitude of hydrophobic association.
An empirical saddlepoint approximation based method for smoothing survival functions under right censoring
Authors: Jeganathan Pratheepa , Randrianampy Noroharivelo V. , Paige Robert L. , Trindade A. Alexandre
Published: March 2019

The Kaplan–Meier (KM) estimator is ubiquitously used for estimating survival functions, but it provides only a discrete approximation at the observation times and does not deliver a proper distribution if the largest observation is censored. Using KM as a starting point, we devise an empirical saddlepoint approximation‐based method for producing a smooth survival function that is unencumbered by choice of tuning parameters. The procedure inverts the moment generating function (MGF) defined through a Riemann–Stieltjes integral with respect to an underlying mixed probability measure consisting of the discrete KM mass function weights and an absolutely continuous exponential right‐tail completion. Uniform consistency, and weak and strong convergence results are established for the resulting MGF and its derivatives, thus validating their usage as inputs into the saddlepoint routines. Relevant asymptotic results are also derived for the density and distribution function estimates. The performance of the resulting survival approximations is examined in simulation studies, which demonstrate a favourable comparison with the log spline method (Kooperberg & Stone, 1992) in small sample settings. For smoothing survival functions we argue that the methodology has no immediate competitors in its class, and we illustrate its application on several real data sets.The Canadian Journal of Statistics47: 238–261; 2019 © 2019 Statistical Society of Canada
Comparison of nylon‐flocked swab and Dacron swab cytology for anal HSIL detection in transgender women and gay, bisexual, and other men who have sex with men
Authors: Wiley Dorothy J. , Hsu Hilary K. , Ganser Martha A. , Brook Jenny , Elashoff David A. , Moran Matthew G. , Young Stephen A. , Joste Nancy E. , Mitsuyasu Ronald , Darragh Teresa M. , Morris David H. , Martínez‐Maza Otoniel M. , Detels Roger , Rao Jian Yu , Bolan Robert K. , Shigeno Eric T. , Rodriguez Ernesto
Published: March 2019

Background

An anal histological high‐grade squamous intraepithelial lesion (hHSIL) is an anal cancer precursor. Experts recommend Dacron swab anal cytology as a primary screen for anal hHSILs, especially among human immunodeficiency virus–infected and –uninfected men who have sex with men (MSM). Studies have shown that Dacron cytology inaccurately predicts anal hHSILs and results in unnecessary diagnostic procedures. Nylon‐flocked (NF) swabs have been shown to trap pathogens and cells well. Thus, this study compared test characteristics of anal cytology using NF and Dacron swab collection protocols to predict anal hHSILs.

Methods

A single‐visit, randomized clinical trial compared NF and Dacron swab anal cytology specimens to predict high‐resolution anoscopy and biopsy–diagnosed anal hHSILs. Data for 326 gay men, bisexual men, other MSM, and male‐to‐female transgender women contributed descriptive and tabular statistics with which unadjusted and fully adjusted logistic regression models were constructed. The models estimated the odds of hHSILs, test accuracy (area under the curve [AUC]) and sensitivity, and specificity as well as the positive and negative predictive values of abnormal NF and Dacron cytology for predicting hHSILs.

Results

In the fully adjusted model, the sensitivities for NF and Dacron cytology were nearly equal (48% vs 47%), but the specificity was higher with NF cytology (76% vs 69%). Comparisons of the areas under receiver operating characteristic curves showed that NF cytology alone predicted hHSILs better than the covariate model (AUC, 0.69 vs 0.63; P = .02), but NF and Dacron cytology comparisons showed no statistically significant differences (AUC, 0.69 vs 0.67; P = .3).

Conclusions

NF cytology and Dacron cytology provide modest sensitivity, but NF cytology has higher specificity and accuracy, and this is important for lowering the costs of population‐based screening.
Same, same but different: Attention bias for food cues in adults and adolescents with anorexia nervosa
Authors: Werthmann Jessica , Simic Mima , Konstantellou Anna , Mansfield Phoebe , Mercado Daniela , van Ens Welmoed , Schmidt Ulrike
Published: March 2019

Objective

Attention processing for food may be biased in people with Anorexia Nervosa (AN). However, previous studies have had inconsistent results. This is likely to be due to indirect assessment of attention, which does not inform on the underlying attention processes, and/or the heterogeneity of participants across studies, testing either adults or adolescents with AN, that is, people at very different developmental and illness stages.

Method

Eye‐tracking was employed as a direct assessment of attention during a visual probe task with food versus non‐food pictures. Attention bias for food was measured in 39 adults and 34 adolescents with AN and in 53 adults and 31 adolescents without AN.

Results

All participants had a direction bias for food, specifically for high‐calorie food. However, adults with AN subsequently avoided maintaining attention on food versus non‐food cues, compared to adults without AN. Adolescents with or without AN demonstrated increased attention maintenance on food versus non‐food cues, and, contrary to our hypothesis, did not differ in their attention bias for food cues. Accordingly, adults with AN differed significantly from adolescents with AN in attention maintenance for food cues: while adolescents with AN showed significantly increased attention maintenance on food stimuli, adults avoided maintaining attention on food cues.

Discussion

Adults with AN may apply attention strategies to facilitate restrictive eating. This strategy is absent in adolescents with AN. This difference in food‐related attention bias between adolescents and adults with AN suggests that attention biases develop over time as the illness progresses.
The accuracy of ecological flow metrics derived using a physics‐based distributed rainfall–runoff model in the Great Plains, USA
Authors: Worthington Thomas A. , Brewer Shannon K. , Vieux Baxter , Kennen Jonathan
Published: March 2019

The development of a hydrologic foundation, essential for advancing our understanding of flow‐ecology relationships, was developed using the high‐resolution physics‐based distributed rainfall–runoff model Vflo in a semi‐arid region. We compared the accuracy and bias associated with flow metrics that were generated using Vflo, gauge data, and drainage area ratios at both a daily and monthly time step in the Canadian River basin, USA. First, we calibrated and applied bias correction to the Vflo model to simulate streamflow at ungauged catchment locations. Next, flow metrics were calculated using simulated and observed data from stream gauge locations. We found discharge predictions using Vflo were more accurate than drainage area ratios. General correspondence between predicted discharge and the gauge data was apparent; however, flow metrics calculated using the Vflo output did not accurately represent flow variability. Results from the Vflo model showed systematic discharge over‐predictions in the upper basin and isolated over‐predictions in the lower basin, likely due to hail events and sparse rainfall data across the large catchment. Goodness‐of‐fit statistics (Nash–Sutcliffe efficiency, root‐mean square error, and the coefficient of variation) indicated the drainage area ratio and Vflo were more accurate at a monthly rather than daily time step, even after quantile mapping. This finding limits the number of streamflow metrics available to develop ecological models, but more importantly, the coarser resolution may hinder our understanding of ecological processes that occur at a submonthly time step. Our approach provides a framework for selecting flow metrics that best represent hydrologic patterns across a large semi‐arid catchment with the necessary accuracy to address the ecological questions of interest.
GC‐MS Characterization of Cyclic Fatty Acid Monomers and Isomers of Unsaturated Fatty Acids Formed During the Soybean Oil Heating Process
Authors: Cherif Ammar , Boukhchina Sadok , Angers Paul
Published: March 2019

In this work, the possibility of formation and isolation of cyclic fatty acid monomers (CFAM) from polyunsaturated fatty acids via prolonged heat treatment of soybean oil are studied. The structures of CFAM are determined using Gas chromatography‐Mass spectrometry (GC‐MS) of their 4, 4‐dimethyloxazoline (DMOX) derivatives, the yield of derivatization is 98%. Among CFAM, the cyclohexyl fatty acids with ring from C12 to C17 and the cyclohexneyl with ring from C10 to C15 formed acid are detected by GC‐MS. The new cyclopentyl with ring at C14 position or between C13 to C17 are detected from linoleic acid. Also, the variation of major fatty acids composition of soybean oil during heated treatment at 150, 180, 210, and 240 °C for 60 h are analyzed. The results indicate that after heating, soybean oil contains four isomers of conjugated linoleic acid (CLA), four isomers of C18:1 and four isomers of C18:3. The heating process, the enrichment steps, and CFAM concentration can modify the profile of CFAM and permit the emergence of new compounds, which can be useful to know the edible oil structural changes during the phases of extraction and analysis.

Practical Applications: When heated at high temperature for a long time, soybean oil undergoes isomerization and cyclization reactions. In fact, CFAM structures with five and six membered carbon rings are identified from heated oil. A new mass spectrum of the CFAM derivative from the intramolecular C18:2 cyclization is also described. Although CFAM are present at very low concentrations in heated oils, these compounds are the most toxic metabolites produced in soybean oil heated at high temperature. In addition to the four isomers of conjugated linoleic acid, four isomers of C18:1 and four of C18:3 are detected during the heating process. The data clearly show that it is necessary to avoid heating the soybean oil to a temperature above 210 °C for a period of more than 60 h which can minimize the production of CFAM.

The gap of 68 amu between the molecular ion (333) and m/z 265 indicate the location of cyclopentyl ring at C14, which is first determined in heated soybean oil.
A New Cationic Functionalized Pillar[5]arene and Applications for Adsorption of Anionic Dyes
Authors: Tian Huasheng , Wang Chunyu , Li Haiying , Deng Rong , Li Runan , Meguellati Kamel
Published: March 2019

Herein, we report a new kind of cationic pillar[5]arene‐based monofunctionalized compound which exists in different conformations in chloroform (pseudorotaxane) and DMSO (open form). This molecule can self‐assemble into vesicles in water and can potentially load negatively charged molecules such as congo red dye in water. The use of these positively charged nanoparticles can be extended to a broad range of applications.
A new approach for traffic matrix estimation in high load computer networks based on graph embedding and convolutional neural network
Authors: Emami Mohsen , Akbari Reza , Javidan Reza , Zamani Ali
Published: March 2019

In computer networks, transmitted traffic between origin‐destination nodes has been considered a crucial factor in traffic engineering applications. To date, measuring the traffic directly in high load networks is difficult due to high computational costs. On the other hand, accurate estimation of network traffic by means of link load measurements and routing information is currently a challenging problem. In this paper, we propose a new approach to estimate end‐to‐end traffic, inspired by graph embedding. In the proposed approach, we consider a computer network as a time‐varying graph. Our model provides explicit routing information to a convolutional neural network estimator via link load measurements and network topological structure. When explicit routing information is provided, the learning model is only expected to embed the relations between link loads into a traffic estimation vector, instead of figuring out the routing paths. The experimental results showed that the proposed approach outperforms similar estimators in terms of lower estimation error and better tracking the fluctuations.
Change of proteolysis and sensory profile during ripening of Cheddar‐style cheese as influenced by a microbial rennet from rice wine
Authors: Zhao Xiao , Zheng Zhe , Zhang Jian , Sarwar Abid , Aziz Tariq , Yang Zhennai
Published: March 2019

To test the potential of a novel microbial rennet isolated from traditional fermented rice wine for cheese making, Cheddar‐style cheese made with this enzyme was studied for changes in composition, proteolysis, and sensory profile during 90 days of ripening in comparison with a control cheese made with a commercial rennet. The initial proteolysis assay of the microbial rennet on milk proteins indicated a notable increase in the hydrolysis of casein components (α‐, β‐, and κ‐caseins) but no effect on whey proteins upon increasing the concentration of the enzyme. Correspondingly, compared to cheese made with commercial rennet, the use of the microbial rennet in Cheddar‐style cheese resulted in significantly higher primary and secondary proteolysis in the later stages of ripening (60–90 days ripening) and thus a softer texture and the formation of more volatile compounds and free amino acids (FAAs) despite its lower moisture content (41.7%, w/w). Though the cheese made with the microbial rennet was found to contain bitter‐taste FAAs (1,000 mg/100 g), the combined effect of other‐taste FAAs, including sweet (231 mg/100 g), umami (225 mg/100 g), and tasteless (361 mg/100 g) FAAs, in the cheese attenuated the bitter taste of the cheese. This analysis was in accordance with the sensory evaluation, which showed no significantly different sensory scoring between the cheeses made with the microbial and commercial rennets. The present study demonstrated a novel approach to evaluate the bitter taste of ripened cheese. The results of this study suggest the potential of the microbial rennet from rice wine to serve as a new source of milk‐clotting agents in cheese making.
Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study
Authors: Minonzio J-G , Bochud N , Vallet Q , Ramiandrisoa D , Etcheto A , Briot K , Kolta S , Roux C , Laugier P
Published: March 2019

Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = -0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.
Identify the critical protein‐coding genes and long noncoding RNAs in cardiac myxoma
Authors: Cheng Nan , Wu Yuanbin , Zhang Huajun , Guo Yi , Cui Huimin , Wei Shixiong , Zhao Yuancheng , Wang Rong
Published: March 2019

Cardiac myxoma (CM) is the most common benign cardiac tumor which is mostly sporadic. Increasing evidence show that protein‐coding genes (PCGs) and long noncoding RNAs (lncRNAs) play important roles in the pathology processes of multiple cancers. However, the functional roles and regulatory mechanisms of RNAs interaction in CM are still unclear. In this study, we investigated three pairs of surgically excised CM by high throughput sequencing and screened a set of PCGs and lncRNAs which were differentially expressed and could serve as expression markers in CM. By constructing protein‐protein interactions (PPI) and lncRNA‐mRNA coexpressing network, we screened out a CM‐related hub lncRNA‐mRNA modules, which were enriched in different pathways such as MAPK and TGF‐beta whose imbalance were validated by q‐PCR. In addition, we identified a specific dysregulated competing endogenous RNA (ceRNA) network in CM by integrating lncRNA‐miRNA‐mRNA interactions. These results will help us to understand the interaction mechanisms of RNAs in CM and provide novel PCGs and lncRNAs as potential therapeutic targets for CM.
Retracted: Downregulated microRNA‐135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3‐kinase/AKT signaling pathway via phosphatidylinositol 3‐kinase regulatory subunit 2
Authors: Qu Yuan , Zhang Yu‐Ping , Wu Jing , Jie Li‐Gang , Deng Jia‐Xin , Zhao Dong‐Bao , Yu Qing‐Hong
Published: March 2019

Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA‐135a (miR‐135a) on the SFs involved in RA by mediating the phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3‐kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR‐135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual‐luciferase reporter gene assay. Subsequently, high miR‐135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR‐135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR‐135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR‐135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR‐135a might be a potential target in the treatment of RA.
Prolonged elevated levels of c‐kit+ progenitor cells after a myocardial infarction by beta 2 adrenergic receptor priming
Authors: Finan Amanda , Demion Marie , Sicard Pierre , Guisiano Morgane , Bideaux Patrice , Monceaux Kevin , Thireau Jérôme , Richard Sylvain
Published: March 2019

Endogenous progenitor cells may participate in cardiac repair after a myocardial infarction (MI). The beta 2 adrenergic receptor (ß2‐AR) pathway induces proliferation of c‐kit+ cardiac progenitor cells (CPC) in vitro. We investigated if ß2‐AR pharmacological stimulation could ameliorate endogenous CPC‐mediated regeneration after a MI. C‐kit+ CPC ß1‐AR and ß2‐AR expression was evaluated in vivo and in vitro. A significant increase in the percentage of CPCs expressing ß1‐AR and ß2‐AR was measured 7 days post‐MI. Accordingly, 24 hrs of low serum and hypoxia in vitro significantly increased CPC ß2‐AR expression. Cell viability and differentiation assays validated a functional role of CPC ß2‐AR. The effect of pharmacological activation of ß2‐AR was studied in C57 mice using fenoterol administered in the drinking water 1 week before MI or sham surgery or at the time of the surgery. MI induced a significant increase in the percentage of c‐kit+ progenitor cells at 7 days, whereas pretreatment with fenoterol prolonged this response resulting in a significant elevated number of CPC up to 21 days post‐MI. This increased number of CPC correlated with a decrease in infarct size. The immunofluorescence analysis of the heart tissue for proliferation, apoptosis, macrophage infiltration, cardiomyocytes surface area, and vessel density showed significant changes on the basis of surgery but no benefit due to fenoterol treatment. Cardiac function was not ameliorated by fenoterol administration when evaluated by echocardiography. Our results suggest that ß2‐AR stimulation may improve the cardiac repair process by supporting an endogenous progenitor cell response but is not sufficient to improve the cardiac function.
Activation of α7‐nAChRs protects SH‐SY5Y cells from 1‐methyl‐4‐phenylpyridinium‐induced apoptotic cell death via ERK/p53 signaling pathway
Authors: Xu Shi , Yang Beibei , Tao Tingting , Zhang Ji , Liu Yun , Hu Jun , Fan Yi , Zhang Guangdong
Published: March 2019

Epidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7‐nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7‐nAChRs; the mechanisms underlying how α7‐nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7‐nAChR agonist PNU‐282987, we first confirmed that their addition to SH‐SY5Y cells challenged with 1‐methyl‐4‐phenylpyridinium (MPP+) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU‐282987 showed the neuroprotective antiapoptotic effects via activating the α7‐nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7‐nAChRs in SH‐SY5Y cells and found that suppressing α7‐nAChR expression diminished the antiapoptotic effects of nicotine and PNU‐282987, not the toxic effects of MPP+. Moreover, α7‐nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU‐282987 on the phosphorylated extracellular signal‐regulated kinase (ERK), not c‐Jun amino‐terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7‐nAChRs and suggest that α7‐nAChR agonists may be validated as novel treatments for PD.
Loss of PKC mu function induces cytoskeletal defects in mouse oocyte meiosis
Authors: Zhang Yu , Wu Lan‐Lan , Wan Xiang , Wang Hong‐Hui , Li Xiao‐Han , Pan Zhen‐Nan , Sun Shao‐Chen
Published: March 2019

Cytoskeleton which includes microtubule and actin filaments plays important roles during mammalian oocyte maturation. In the present study, we showed that protein kinase C mu (PKC mu) was one potential key molecule which affected cytoskeleton dynamics in mouse oocytes. Our results showed that PKC mu expressed and localized at the poles of the spindle during oocyte maturation, and PKC mu expression reduced in the oocytes from 6‐month‐old mice or 24 hr in vitro culture. We knocked down the expression of PKC mu in oocytes using morpholino injection to explore the relationship between PKC mu and subcellular structure defects. The loss of PKC mu reduced oocyte maturation competence, showing with decreased polar body extrusion rate and increased rate of symmetric division. Further analysis indicated that PKC mu decrease caused the spindle organization defects, and this could be confirmed by the decreased tubulin acetylation level. Moreover, we found that PKC mu affected the phosphorylation level of cofilin for actin assembly, which further affected cytoplasmic actin distribution and spindle positioning. In summary, our data indicated that PKC mu is one key factor for oocyte maturation through its roles on the spindle organization and actin filament distribution.
Activation of β‐catenin in Col2‐expressing chondrocytes leads to osteoarthritis‐like defects in hip joint
Authors: Xia Chenjie , Wang Pinger , Fang Liang , Ge Qinwen , Zou Zhen , Dong Rui , Zhang Peng , Shi Zhenyu , Xu Rui , Zhang Lei , Luo Chen , Ying Jun , Xiao Luwei , Shen Jie , Chen Di , Tong Peijian , Jin Hongting
Published: March 2019

Although osteoarthritis (OA) in the hip joint is a common and debilitating degenerative disease, the precise molecular mechanisms underlying its pathological process remains unclear. This study sets out to investigate whether β‐catenin plays a critical role in hip OA pathogenesis. Here, we showed overexpressed β‐catenin protein in human OA cartilage tissues. Then, we analyzed β‐cat(ex3)Col2ER mice, in which β‐catenin gene was conditionally activated in femoral head chondrocytes. At 2 months of age, β‐cat(ex3)Col2ER mice already showed a phenotype of severe cartilage degeneration in the femoral head. More changes observed in β‐cat(ex3)Col2ER mice with age included subchondral sclerosis and osteophyte formation along joint margins, resembling a hip OA phenotype in humans. In addition, cartilage degradation and chondrocyte apoptosis as the results of β‐catenin activation possibly contributed to this hip OA‐like phenotype. Overall our findings provide direct evidence about the importance of β‐catenin in hip OA pathogenesis.
Using a variant of coverslip hypoxia to visualize tumor cell alterations at increasing distances from an oxygen source
Authors: Arocena Miguel , Landeira Mercedes , Di Paolo Andrés , Silva Alejandro , Sotelo‐Silveira José , Fernández Ariel , Alonso Julia
Published: March 2019

Early stages in tumor development involve growth in confined spaces, where oxygen diffusion is limited and metabolic waste products accumulate. This hostile microenvironment imposes strong selective pressures on tumor cells, leading eventually to the survival and expansion of aggressive subclones that condition further tumor evolution. To model features of this microenvironment in vitro, a diffusional barrier can be introduced in the form of a coverslip placed on top of cells, a method termed coverslip hypoxia. Using a variant of this method, with larger volume between coverslip and cells and with oxygen diffusion occurring only through a small hole in the center of the coverslip, we have visualized alterations in LNCaP tumor cells as a function of their distance to the oxygen source at the center. We observed remarkable morphological changes in LNCaP cells as the distance from the center increases, with cells becoming highly spread, displaying dynamic membrane protrusions and occasionally adopting a migratory phenotype. Concomitantly, cells farther from the center displayed marked increases in the hypoxia marker hypoxyprobe, whereas extracellular pH decreased in the same direction. Cells with altered morphology displayed prominent increases in fibrillar actin, as well as swollen mitochondria with distorted cristae and accumulation of neutral lipid‐containing intracellular vesicles. These results show that an in vitro microenvironment that models diffusional barriers encountered by tumors in situ can have profound effects on tumor cells. The coverslip hypoxia variant we describe can be used to characterize in vitro the response of tumor cells to environmental conditions that play crucial roles in early tumor development.
Long noncoding RNA SBF2‐AS1 promotes colorectal cancer proliferation and invasion by inhibiting miR‐619‐5p activity and facilitating HDAC3 expression
Authors: Chen Gang , Gu Yue , Han Peng , Li Zhong , Zhao Jin‐Lu , Gao Mei‐Zhuo
Published: March 2019

Evidence, demonstrating long noncoding RNAs (lncRNAs) as critical players in cancer, remains to increase. lncRNA SBF2‐AS1 was reported to be involved in several cancers, such as hepatocellular carcinoma. However, the role of SBF2‐AS1 in colorectal cancer (CRC) is unknown. We showed lncRNA SBF2‐AS1 expression was growing in CRC samples, especially in advanced cases. Accordingly, SBF2‐AS1 possesses higher expression in CRC cell lines than in normal cell line. Moreover, SBF2‐AS1 high expression indicated a low survival rate. Functionally, SBF2‐AS1 knockdown suppressed the proliferation, migration, and invasion of CRC cells. In terms of mechanism, SBF2‐AS1 upregulation restrained the activity of miR‐619‐5p and led to overexpression of HDAC3. Importantly, downregulation of miR‐619‐5p or HDAC3 overexpression reversed SBF2‐AS1‐silencing‐caused suppression on proliferation and metastasis. Summarily, our findings elucidated a crucial role of SBF2‐AS1 as a miR‐619‐5p sponge, shedding novel light on lncRNA‐related prognostics.
Modelling supply chain adaptation for disruptions: An empirically grounded complex adaptive systems approach
Authors: Zhao Kang , Zuo Zhiya , Blackhurst Jennifer V.
Published: March 2019

Through the development and usage of an agent‐based model, this article investigates firms' adaptive strategies against disruptions in a supply chain network. Viewing supply chain networks as complex adaptive systems, we first construct and analyze a real‐world supply chain network among 2,971 firms spanning 90 industry sectors. We then develop an agent‐based simulation to show how the model of firms' adaptive behaviors can leverage competition relationships within a supply chain network. The simulation also models how disruptions propagate in the supply chain network through cascading failures. With the simulation, we seek to understand if a firm's adaptive behaviors can reduce the impact of disruptions in supply chain networks. Therefore, we propose, evaluate, and analyze two types of adaptive strategies a firm can leverage to reduce the negative effects of supply chain network disruptions. First, we deploy in our model a reactive strategy, which restructures the network in response to a disruption event among first‐tier suppliers. Next, we develop and propose proactive strategies, which are used when a distant disruption is observed but has not yet hit the focal firm. We discuss the implications related to how and when firms can improve their resilience against supply disruptions by leveraging adaptive strategies.
Revisiting the complex adaptive systems paradigm: Leading perspectives for researching operations and supply chain management issues
Authors: Nair Anand , Reed‐Tsochas Felix
Published: March 2019

This paper presents a conceptual model for a renewed consideration of the complex adaptive systems (CAS) perspective in operations and supply chain management research. A literature review identifies the approaches taken in published research to examine issues such as complexity, adaptation, and emergent behavior. We present a revised conceptual framework that offers directions for embracing key tenets from CAS research so as to gain deeper insights into pertinent issues within the field. We introduce the articles that are part of this special issue and highlight how these articles relate to the conceptual framework proposed in the paper. We also propose some methodological directions that can help in undertaking rigorous investigations of some important aspects that have theoretical and managerial significance.
The Association Between Negative Trauma‐Related Cognitions and Pain‐Related Functional Status Among Veterans With Posttraumatic Stress Disorder and Alcohol Use Disorder
Authors: Curry Inga , Malaktaris Anne L. , Lyons Robert , Herbert Matthew S. , Norman Sonya B.
Published: March 2019

Among veterans with posttraumatic stress disorder (PTSD), alcohol use disorders (AUDs) are highly prevalent. Furthermore, PTSD frequently co‐occurs with chronic pain (CP), and CP is associated with an increased risk of AUD. Pain‐related beliefs and appraisals are significantly associated with poorer pain‐related functional status, yet few studies have examined negative trauma‐related cognitions and their impact on pain‐related functional disability in veterans with co‐occurring PTSD and AUD. Accordingly, we examined the association between negative trauma‐related cognitions and pain severity and pain disability in 137 veterans seeking treatment for PTSD and AUD. Using hierarchical multiple linear regression, we found that higher levels of negative trauma‐related cognitions (e.g., “I am completely incompetent”) were associated with a higher level of pain severity, after controlling for PTSD symptom severity and frequency of alcohol use, total R2 = .07, ΔR2 = .06. Additionally, as hypothesized, we found that higher levels of negative trauma‐related cognitions were associated with higher levels of pain disability, after controlling for PTSD symptom severity, frequency of alcohol use, and pain severity, total R2 = .46, ΔR2 = .03. Given that negative trauma‐related cognitions contributed to pain severity and pain disability, even when controlling for PTSD severity and frequency of alcohol use, future studies should explore the potential impact of interventions that address negative trauma‐related cognitions (e.g., prolonged exposure or cognitive processing therapy) on pain severity and disability.
Observations at backyard bird feeders influence the emotions and actions of people that feed birds
Authors: Dayer Ashley A. , Rosenblatt Connor , Bonter David N. , Faulkner Holly , Hall Richard J. , Hochachka Wesley M. , Phillips Tina B. , Hawley Dana M.
Published: March 2019

Backyard bird feeding is one of the most common ways people engage with wildlife in many parts of the world. Given its scale, it can have profound consequences for the ecology of feeder birds and their behaviour. While previous work has primarily explored socio‐demographic factors associated with bird feeding, how observations of nature at backyard feeders (e.g. changes in feeder bird abundance, interaction with natural enemies and weather) influence people's propensity to feed birds remain largely unknown.

We examined the association between peoples’ observations at their backyard feeders and their emotions and behaviours related to providing food to birds. We conducted an online survey of a subset of United States participants in Project FeederWatch, a large‐scale citizen science project.

Overwhelmingly, respondents (n = 1,176) reported taking actions, such as managing predators or maintaining feeders, in response to observable natural factors (e.g. increased incidence of disease, the presence of predators, increased bird abundance). Additionally, respondents described a variety of emotional responses to the scenarios of depredation or disease at their feeders, some of which (particularly anger) had a small association with whether a respondent would take action in response. Respondents generally believed that their bird feeding benefits backyard birds (e.g. by improving overwinter survival and overall health), and indicated that natural factors (e.g. bird abundance, disease prevalence) and abiotic factors (i.e. cold temperature) had more of an influence on how much they feed birds than internal constraints such as time and money.

These findings suggest that human behaviour with respect to bird feeding is coupled to observations of nature, which could lead to feedbacks between provisioning intensity and ecological dynamics. Overall, our results have important implications for bird conservation and for understanding the potential benefits that humans receive from provisioning birds.

A plain language summary is available for this article.
Silicon Nanoparticles Prepared by Plasma‐Assisted Ablative Synthesis: Physical Properties and Potential Biomedical Applications
Authors: Kargina Yulia V. , Perepukhov Aleksandr M. , Kharin Aleksandr Yu. , Zvereva Elena A. , Koshelev Anatolii V. , Zinovyev Sergei V. , Maximychev Aleksandr V. , Alykova Alida F. , Sharonova Nina V. , Zubov Vitalii P. , Gulyaev Mikhail V. , Pirogov Yurii A. , Vasiliev Aleksandr N. , Ischenko Anatolii A. , Timoshenko Viktor Yu.
Published: March 2019

Silicon (Si) nanoparticles (NPs) with small (10−3–10−1 at%) content of iron oxide (Fe2O3) are prepared by plasma‐assisted ablative synthesis. Powders of the prepared Si‐iron oxide (SIO) NPs are investigated by means of the transmission electron microscopy, Raman spectroscopy, electron paramagnetic resonance, and magnetic susceptibility measurements. Aqueous suspensions of the NPs are studied by using dynamic light scattering and nuclear magnetic resonance technique. The longitudinal and transverse relaxation times of protons in aqueous suspensions of the NPs are found to be dependent on the iron content. The stronger decrease of the proton relaxation is detected for the samples with higher iron content. Magnetic resonance imaging (MRI) experiments show that SIO NPs have properties of the MRI contrast agent and it is confirmed by in vivo experiments with cancer tumor. Aqueous suspensions of SIO NPs are explored as sensitizers of electromagnetic radio frequency hyperthermia and the highest heating rate is observed for the NPs with smaller hydrodynamic size (≈50 nm). The obtained results indicate possible ways for applications of SIO NPs in the MRI diagnostics and mild therapy of cancer.
Gadolinium Metallofullerene‐Based Activatable Contrast Agent for Tumor Signal Amplification and Monitoring of Drug Release
Authors: Wang Sheng , Zhou Zijian , Wang Zhantong , Liu Yijing , Jacobson Orit , Shen Zheyu , Fu Xiao , Chen Zhi‐Yi , Chen Xiaoyuan
Published: March 2019

Activatable imaging probes are promising to achieve increased signal‐to‐noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion‐associated potential long‐term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH‐responsive polymer and gadolinium metallofullerene (GMF). This GMF‐based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH‐responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic‐to‐hydrophilic conversion of the pH‐responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.
Behavior of Sweet Potato Starch After Spray‐Drying Under Different Pretreatment Conditions
Authors: dos Santos Thais Paes Rodrigues , Franco Célia Maria Landi , Mischan Martha Maria , Leonel Magali
Published: March 2019

There are a lot of potential uses of sweet potato as a source of starch in food and other industries. Pregelatinization, a physical modification that confers properties of interest for several industrial applications, is a way to expand the use of this starch. Processing conditions have significant impact on the properties of modified starch and therefore, the effects of the concentration of starch and preheating temperature on the physical properties of spray dried starch in this study are evaluated. This study is carried out by applying a central rotational compound experimental design to test two independent variables, starch concentration and preheating temperature, and consisted of a total of 11 treatments. Results showed that the granule size, gelatinization temperature, and breakdown viscosity are significantly affected by the preheating temperature. Besides this, preheating temperature and starch concentration also influenced the crystallinity percentage, enthalpy change, gelatinization degree, retrogradation properties, and final viscosity. The final products showed lower crystallinity percentage, enthalpy change, and onset and peak dissociation temperature, as well as, higher peak gelatinization temperature, retrogradation rates, swelling power, and solubility, independent of processing conditions, when compared with native sweet potato starch. Partially pregelatinized starch with high viscosity and resistance to heating under agitation can be obtained under the process conditions consisting of up to 8% starch concentration and a preheating temperature of 60 °C. These acquired properties can potentially boost the use of sweet potato starch in food industries.
Characteristics of Flour and Starch Isolated from Red Rice Subjected to Different Drying Conditions
Authors: Ramos Adriano H. , Rockenbach Bruno A. , Ferreira Cristiano D. , Gutkoski Luiz C. , de Oliveira Maurício
Published: March 2019

Drying is a method used to reduce grain moisture and prolong safe storage. The objective of the study is to evaluate the changes in red rice flour and starch submitted to sun‐drying, continuous drying at 40 °C, continuous drying at 100 °C and intermittent drying. In general, the significant changes are found in continuous drying at 100 °C, followed by intermittent drying, continuous drying at 40 °C and sun‐drying. Continuous drying at 100 °C reduces starch extraction yield and increases residual protein, leading to starch with dark reddish stains. At higher temperatures, increases in TO and relative crystallinity and lower solubility, swelling power, ΔT occur. The flour gel presents higher values when intermittent drying is applied, differing from the starch gel, which higher hardness found at continuous drying method at 40 °C probably due to the macromolecules from rice pericarp. According to the increase in grain drying temperature, there are reductions in final viscosity and setback in the starch and increases in final viscosity and setback in the flour, attributed mainly to the high amount of protein. The parameters of RVA and texture demonstrates that the higher purity of the starch promotes a gel with greater stability in refrigeration.