bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical and in vitro degradation behavior of magnesium‐bioactive glass composites prepared by SPS for biomedical applications
Authors: Dutta Sourav , Devi K. Bavya , Gupta Sanjay , Kundu Biswanath , Balla Vamsi Krishna , Roy Mangal
Published: April 2018

In order to make magnesium (Mg) a successful candidate for fracture fixation devices, it is imperative to control the corrosion rate and enhance its elastic modulus. In the present work, we have prepared bioactive glass (BG) reinforced magnesium composite using spark plasma sintering (SPS). Simultaneous application of heat and pressure during SPS decreased the softening point of BG (600°C), allowing it to coat the Mg particles partially. As a result, BG was found along the Mg particle boundaries, which was confirmed by elemental mapping. Addition of BG improved microhardness and elastic modulus of Mg‐BG composites. Corrosion behavior was studied by hydrogen evolution and immersion corrosion in phosphate buffered saline (PBS). After 64 h of immersion, Mg‐10 wt % BG composite showed highest corrosion resistance. Quantitative micro‐computed tomography (micro‐CT) results indicated porosity increase in Mg‐BG composites during immersion. The maximum increase in porosity (1.66%) was noticed for pure Mg while the minimum for Mg‐10 wt % BG composite. MG63 cell‐material interactions, using extract method, showed good cytocompatibility for Mg‐10 wt % BG composite. The concentration of Mg ion in cell culture media was measured using atomic absorption spectroscopy after 24 h immersion of Mg/BG composites. The results indicated that using BG as reinforcement and SPS as sintering method; we can prepare corrosion resistant and high modulus Mg‐BG composites that can be used for fabricating bone fracture fixation plates. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 352–365, 2019.
Acidic and alkaline chemicals’ influence on a tricalcium silicate‐based dental biomaterial
Authors: Neelakantan Prasanna , Berger Todd , Primus Carolyn , Shemesh Hagay , Wesselink Paul R.
Published: April 2018

Bioactive hydraulic tricalcium silicate materials are commonly used in several dental procedures. Mineral Trioxide Aggregate (MTA) is one such material, which is used in a variety of clinical applications, the most recent of which is root canal sealing material, during which, the MTA potentially comes in contact with remnants of the chemical agents used for disinfecting root canals. The effects of commonly used root canal irrigating solutions on MTA have not been investigated in depth, thus far. The aim of this study was to determine the effect of five common chemical agents used in root canal preparation (sodium hypochlorite/NaOCl, ethylene diaminetetraacetic acid/EDTA, mixture of sodium hypochlorite and etidronic acid/NaOCl + EA, mixture of EDTA and Chlorhexidine/QMix, or saline) on a commercial tricalcium silicate (MTA Plus). Samples were analyzed using scanning electron microscopy with energy dispersive spectroscopy, X‐ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy and Inductively coupled plasma techniques to see effects of phases formed and calcium ion release. Specimens immersed in NaOCl and NaOCl + EA had strong peaks for calcium hydroxide, but materials exposed to EDTA and QMix had lesser XRD peaks for calcium hydroxide. The calcium hydroxide peak in the XRD indicates hydration of tricalcium silicate and formation of amorphous calcium silicate hydrate. Calcium released from samples immersed in EDTA and NaOCl was less than in NaOCl + EA and QMix solutions. Fewer calcium phosphate crystals and less calcium hydroxide were observed with the samples in NaOCl, EDTA and QMix, which could have an important impact as it negatively influences the bioactivity. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 377–387, 2019.
Novel, cost‐effective, Cu‐doped calcium silicate nanoparticles for bone fracture intervention: Inherent bioactivity andin vivoperformance
Authors: Mabrouk Mostafa , ElShebiney Shaimaa A. , Kenawy Sayed H. , El‐Bassyouni Gehan T. , Hamzawy Esmat MA
Published: April 2018

Copper (Cu)‐doped calcium silicate nanoparticles were synthesized by a wet precipitation method as economical bone fracture filler. The aim was to improve the overall physicochemical properties, bioactivity, and biological performance of the bone fracture filler prepared herein. The synthesized nanoparticles were evaluated using X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FT‐IR), and transmission electron microscopy (TEM). The bioactivity of the prepared nanoparticles was investigated after immersion in simulated body fluid (SBF) by means of inductively coupled plasma (ICP), SEM coupled with energy dispersive X‐rays (EDX), and FTIR. The size and bioactivity of the prepared nanoparticles after 15 days of immersion in SBF was dependent on the Cu concentrations. The fracture healing ability of the fabricated nanoparticles on adult aged male Wistar rats was enhanced by the presence of copper. All the obtained results are of high relevance for fabricating improved Cu‐doped calcium silicate nanoparticles (∼50 nm) as low cost bone fracture filler. In addition, thein vivostudy presented complete healing of the tibiae bone with normal architecture of bone tissue specifically calcium silicate nanoparticles doped with 3% and 5% Cu. Hence, the presence of copper is a promising tactic for improving the biological properties of calcium silicate. Therefore, the designed nanoparticles have huge potential for the treatment of bone fractures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 388–399, 2019.
Enhancement of electrochemical properties of niobium‐doped LiFePO4/C synthesized by sol–gel method
Authors: Jiang Ao , Wang Xinlu , Gao Musen , Wang Jinxian , Liu Guixia , Yu Wensheng , Zhang Hongbo , Dong Xiangting
Published: April 2018

LiFePO4/C and LiFe1–xNb
xPO4/C composites were synthesized using a sol–gel method. The influence of niobium doping on the constitution, morphology, and electrochemical properties of the samples was studied in detail. X‐Ray diffraction patterns indicate that appropriate Nb doping does not alter seriously the structure of LiFePO4. Electrochemical characterization of the electrodes showed that the Li‐ion batteries based on LiFe1–xNb
xPO4/C electrode exhibited better charge/discharge performance than those based on LiFePO4/C. The LiFe0.95Nb0.05PO4/C‐based cell had the specific capacity of 157, 121, and 85 mAh/g at 0.2, 2, and 5 C, respectively, in comparison with 126, 94, and 52 mAh/g for the LiFePO4/C cell. The results show that the addition of niobium promotes the electrochemical performance of the materials especially at high charge/discharge rates of the battery.
Fluorescence quenching study of humic‐fraction‐modified silica gel in a solid state after association with a variety of pesticidal analytes in hexane and acetonitrile
Authors: Gao Yu‐Xuan , Chen Shushi
Published: April 2018

In this paper, we investigate the fluorescence quenching of acidic humic‐fraction‐modified silica gel in the solid state after association with a variety of pesticidal analytes in hexane and acetonitrile. The percentage of fluorescence quenching is found to be dependent on the contact time and linearly on the number of moles of analyte involved in the association process. However, any π–π complexation interaction arising from the acidic aromatic ring on the analyte due to the derivatization of a bulky electron‐withdrawing group is not observed. Also, any mechanism leading to adsorption or any quenching process occurring as a result of the steric hindrance obtained by a theoretical interaction simulation is not observed. The Fourier transform infrared (FTIR) data and simulation results, instead, suggest that electron‐rich atoms on the analyte, such as oxygen, sulfur, nitrogen, and phosphorus, are responsible for fluorescence quenching, following dipole–dipole interaction with the humic‐fraction‐modified adsorbent.
Urgently Yours: Temporal Communication Norms and Psychological Distance
Authors: Kaju Alex , Maglio Sam J.
Published: April 2018

Communicators have at their disposal an ever‐increasing variety of modalities by which to transmit messages. Do the prominent norms attached to different communication modalities contain information in and of themselves? The present investigation considers this question through the lens of text messages and emails, hypothesized to confer different normative information about urgency. Text messages (vs. emails)—or any communication inferred by receivers to have been sent with greater urgency—cause the content of those messages to seem, in the eyes of receivers, closer in time (Study 1), closer in space (Study 2), and more likely to occur (Study 3). Moderation and mediation analyses confirm the role of urgency underlying the relationship between modality and distance. We provide evidence for these effects in a series of laboratory studies together with a field study in which real text messages and emails impact not only inferred distance but also a behavior deriving therefrom. Theoretical and practical implications highlight the importance, for both researchers and practitioners, of understanding how the medium of communication can shape interpretation of the message.
Melioration revisited: a systematic replication of Vaughan (1981)
Authors: Bland Vikki J. , Cowie Sarah , Elliffe Douglas , Podlesnik Christopher A.
Published: April 2018

Organisms that behave so as to forfeit a relatively higher overall rate of reinforcement in favor of a relatively lower rate are said to engage in suboptimal choice. Suboptimal choice has been linked with maladaptive behavior in humans. Melioration theory offers one explanatory framework for suboptimal choice. Melioration theory suggests behavior is controlled by differences in local reinforcer rates between alternatives. Vaughan (1981) arranged two experimental conditions in which maximizing the overall rate of reinforcement required behavior that was compatible, or incompatible, with melioration. Vaughan found pigeons allocated more time to a locally richer alternative even when doing so resulted in suboptimal choice. However, Vaughan did not show whether these effects could systematically reverse and did not provide within‐session data to show that choice across short time spans remains under the control of differences in local reinforcer rates. The present study used pigeons to replicate and extend Vaughan's findings. We investigated shifts in overall‐ and within‐session choice across repeated conditions, according to arranged local contingencies. Behavior systematically followed changes in local contingencies for most pigeons. Within‐session data suggests that, providing differences in local reinforcer rates are discriminated, pigeons will allocate more time to a locally richer alternative, even if this leads to suboptimal choice. These findings facilitate the more confident use of similar procedures that investigate how melioration contributes to suboptimal choice.
How ecological communities respond to artificial light at night
Authors: Sanders Dirk , Gaston Kevin J.
Published: April 2018

Many ecosystems worldwide are exposed to artificial light at night (ALAN), from streetlights and other sources, and a wide range of organisms has been shown to respond to this anthropogenic pressure. This raises concerns about the consequences for major ecosystem functions and their stability. However, there is limited understanding of how whole ecological communities respond to ALAN, and this cannot be gained simply by making predictions from observed single species physiological, behavioral, or ecological responses. Research needs to include an important building block of ecological communities, namely the interactions between species that drive ecological and evolutionary processes in ecosystems. Here, we summarize current knowledge about community responses to ALAN and illustrate different pathways and their impact on ecosystem functioning and stability. We discuss that documentation of the impact of ALAN on species interaction networks and trait distributions provides useful tools to link changes in community structure to ecosystem functions. Finally, we suggest several approaches to advance research that will link the diverse impact of ALAN to changes in ecosystems.
Uterine and eggshell modifications associated with the evolution of viviparity in South American water snakes (Helicopsspp.)
Authors: Braz Henrique B. , Almeida‐Santos Selma M. , Murphy Christopher R. , Thompson Michael B.
Published: April 2018

The evolution of viviparity requires eggshell thinning to bring together the maternal uterus and extraembryonic membranes to form placentae for physiological exchanges. Eggshell thinning likely involves reduced activity of the uterine glands that secrete it. We tested these hypotheses by comparing the uterine and eggshell structure and histochemistry among oviparous and viviparous water snakes (Helicops) using phylogenetic methods. Eggshell thinning occurred convergently in all three origins of viviparity inHelicopsand was accomplished by the loss of the mineral layer and thinning of the shell membrane. Uterine glands secrete the shell membrane in both oviparous and viviparousHelicops. These glands increase during vitellogenesis regardless of the reproductive mode, but they always reach smaller sizes in viviparous forms. As there is no phylogenetic signal in eggshell thickness and gland dimensions, we conclude that interspecific differences are related to reproductive mode and not phylogeny. Therefore, our results support the hypothesis that eggshell thinning is associated with the evolution of viviparity and that such thinning result from a reduction in gland size in viviparous taxa. Interestingly, the shell membrane thickness of viviparous females of the reproductively bimodalHelicops angulatusis intermediate between their oviparous and viviparous congeners. Thus, although eggshell thinning is required by the evolution of viviparity, a nearly complete loss of this structure is not. However, uterine gland dimensions are similar across viviparousHelicops. Fewer glands or their functional repurposing may explain the thinner shell membrane in viviparous species ofHelicopsin comparison to viviparous females of the bimodalH. angulatus.
Tomojiro Nagai, founder of the Association of the Medical Practitioners (Jicchi ika no tame no kai) in Japan
Authors: Matsumura Shinji , Ishibashi Yukishige
Published: April 2018

Obituary: Tomojiro Nagai, founder of the Association of the Medical Practitioners (Jicchi‐ika no tame no kai) in Japan.
MiR‐21 ameliorates age‐associated skin wound healing defects in mice
Authors: Long Shuang , Zhao Na , Ge Lan , Wang Guojian , Ran Xinze , Wang Junping , Su Yongping , Wang Tao
Published: April 2018

Background

The cellular and molecular mechanisms responsible for the age‐associated delay of cutaneous wound healing are still not well understood. Previous studies have shown that miR‐21 plays key roles during skin wound healing. We presumed that dysregulation of miR‐21 may be involved in age‐associated defects in wound healing and that miR‐21 may be one potential therapeutic target by which to ameliorate wound defects in elderly subjects.

Methods

Circular full thickness excisional wounds were made on the dorsal skin of young (2‐month‐old) and aged (12‐month‐old) female mice. The wound healing rates were quantified and compared between wild‐type and miR‐21 knock‐in mice. Both histologic and morphometric analyses of the wounds were evaluated. Furthermore, the expression patterns of miR‐21 during wound healing in both young and aged mice were assessed by in situ hybridization. The effects of topical miR‐21 overexpression on wound healing in aged mice were estimated by both wound closure quantification and histological analyses.

Results

Aged miR‐21 knock‐in female mice showed significantly improved wound healing compared to their wild‐type counterparts with respect to mature granulation tissue, smaller wound width and thinner epidermis. The expression patterns of miR‐21 showed that miR‐21 levels were insufficient for repairing granulation tissue in aged mice. Intradermal injection of miR‐21 plasmid around wounds could upregulate miR‐21 levels during wound healing and ameliorate age‐associated skin wound defects.

Conclusions

The results of the present study reveal that the upregulation of miR‐21 levels could improve wound repair in aged mice, which suggests that a therapeutic strategy targeting miR‐21 expression in age‐associated wound healing may be feasible.
Preoperative criterion identifying a low‐risk group for lymph node metastasis in intrahepatic cholangiocarcinoma
Authors: Yoh Tomoaki , Hatano Etsuro , Seo Satoru , Terajima Hiroaki , Uchida Yoichiro , Taura Kojiro , Yasuchika Kentaro , Uemoto Shinji
Published: April 2018

Background

Imaging study cannot identify patients with potential low‐risk for lymph node (LN) metastasis in intrahepatic cholangiocarcinoma (ICC). The purpose of this study was to identify a low‐risk group for LN metastasis in ICC using preoperatively available factors.

Methods

Data from 127 consecutive patients, who underwent curative intent surgery for ICC at Kyoto University Hospital and Kitano Hospital between 2002 and 2016, were retrospectively analyzed. By using only preoperative data, multiple linear regression model for predicting LN metastasis was developed.

Results

Forty‐three patients exhibited LN metastasis (33.9%). Serum CA19‐9 levels ≥37 IU/ml, ICC with hilar invasion, and LN swelling were identified as independent preoperative predictors of LN metastasis. The prediction model for LN metastasis using these three factors revealed good discrimination (area under the receiver operating characteristics curve 0.874, P < 0.001). Negative for all three factors (i.e. CA19‐9 levels <37 IU/ml, peripheral ICC and no LN swelling) identified 35 patients (27.6%) as a low‐risk group, with the false negative rate of 2.3%.

Conclusions

We proposed a preoperative criterion for predicting LN metastasis, giving rise to the identification of ICC patients who showed a low‐risk of LN metastasis.
Molecular Substantiation and Drug Efficacy of Relatively High Molecular Weight S‐BINOLs; Appraised as Breast Cancer Medication and PI3Kinase Inhibitors
Authors: Muralidharan Vivek Panyam , Alagumuthu Manikandan , Arumugam Sivakumar , Iyer Sathiyanarayanan Kulathu
Published: April 2018

Relatively high molecular weight S‐BINOLs with substituted functional groups were synthesized, and structures were elucidated by FTIR, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and HRMS. As a preliminary step, the compounds were docked into the active site of phosphoinositide3‐kinase (PI3Kinase) (Protein Data Bank ID: 2IUG) that is a crucial regulator of apoptosis or programmed cell death. To ensure the PI3Kinase inhibition, because it was predicted as the most suitable bioactivity of these compounds, a competitive ELISA PI3Kinase inhibition study was carried out. Compounds 3, 4a, 4b, and 6 were assessed for cytotoxicity/antiproliferative effects on MCF‐7 (breast cancer) and HCT116 (colon cancer) cell lines. In the docking studies, excellent binding affinities of 3, 4a, 4b, and 6 (−11.36, −14.52, −14.86, and −21.76 kcal/mol, respectively) and the inhibitory constants (ki) (4.75 nM, 81.64 pM, 78.23 pM, and 14.24 pM, respectively) encouraged us to carry out anticancer studies further. Excellent inhibitory values were obtained in the range of 82–90% relative activity and IC50 range of 5–12 nM. In the cytotoxicity, the relative inhibition activity was remarkably found high in MCF‐7 cell lines as 89.14% (6), 82.18% (4b), 80.46% (3), and 74.78% (4a) with the IC50 range of 0.02–0.18 μM. No compounds were found inactive for the proposed activity in this study. The Structure Activity Relationship studies prove that compounds 3, 4a, 4b, and 6 are specific PI3Kinase inhibitors with the competence to cure breast cancers.
Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease
Authors: Abdala-Valencia Hiam , Coden Mackenzie E , Chiarella Sergio E , Jacobsen Elizabeth A , Bochner Bruce S , Lee James J , Berdnikovs Sergejs
Published: April 2018

Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial–mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

Review on the two-way communication between tissue and eosinophils, discussing eosinophil heterogeneity in the framework of biological processes occurring in different tissue states.
Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques relies on a PLD2–CD36 functional interdependence
Authors: Ganesan Ramya , Henkels Karen M , Wrenshall Lucile E , Kanaho Yasunori , Di Paolo Gilbert , Frohman Michael A , Gomez-Cambronero Julian
Published: April 2018

The uptake of cholesterol carried by low-density lipoprotein (LDL) is tightly controlled in the body. Macrophages are not well suited to counteract the cellular consequences of excess cholesterol leading to their transformation into “foam cells,” an early step in vascular plaque formation. We have uncovered and characterized a novel mechanism involving phospholipase D (PLD) in foam cell formation. Utilizing bone marrow-derived macrophages from genetically PLD deficient mice, we demonstrate that PLD2 (but not PLD1)-null macrophages cannot fully phagocytose aggregated oxidized LDL (Agg-Ox-LDL), which was phenocopied with a PLD2-selective inhibitor. We also report a role for PLD2 in coupling Agg-oxLDL phagocytosis with WASP, Grb2, and Actin. Further, the clearance of LDL particles is mediated by both CD36 and PLD2, via mutual dependence on each other. In the absence of PLD2, CD36 does not engage in Agg-Ox-LDL removal and when CD36 is blocked, PLD2 cannot form protein–protein heterocomplexes with WASP or Actin. These results translated into humans using a GEO database of microarray expression data from atheroma plaques versus normal adjacent carotid tissue and observed higher values for NFkB, PLD2 (but not PLD1), WASP, and Grb2 in the atheroma plaques. Human atherectomy specimens confirmed high presence of PLD2 (mRNA and protein) as well as phospho-WASP in diseased arteries. Thus, PLD2 interacts in macrophages with Actin, Grb2, and WASP during phagocytosis of Agg-Ox-LDL in the presence of CD36 during their transformation into “foam cells.” Thus, this study provides new molecular targets to counteract vascular plaque formation and atherogenesis.
Kindlin-3 negatively regulates the release of neutrophil extracellular traps
Authors: Xu Zhen , Ni Beiwen , Cao Zhongyuan , Zielonka Jacek , Gao Juan , Chen Fangyuan , Kalyanaraman Balaraman , White Gilbert C , Ma Yan-Qing
Published: April 2018

Neutrophils fight infections by generating reactive oxygen species (ROS) and extracellular traps (NETs). However, how neutrophils modulate ROS/NET generation is mechanistically unclear. Kindlin-3, an essential integrin activator expressed in hematopoietic cells, is required to support integrin-mediated neutrophil recruitment during inflammation. Here, we report a novel role of kindlin-3 in regulating ROS/NET generation in neutrophils. When overexpressing kindlin-3 in neutrophil-like differentiated HL-60 cells (HL-60N), ROS/NET generation from these cells were significantly suppressed. Interestingly, overexpression of a kindlin-3 mutant that is defective for interacting with integrins in HL-60N cells still inhibited ROS/NET generation, suggesting that the role of kindlin-3 in inhibiting ROS/NET signaling may be independent of its binding to integrins. Consistently, knockdown of kindlin-3 in HL-60N cells led to enhanced ROS/NET generation. In addition, bone marrow neutrophils isolated from kindlin-3-deficient mice showed elevated ROS/NET generation when compared with WT counterparts. As expected, overexpression of exogenous kindlin-3 in mouse neutrophils could suppress NET release ex vivo and in vivo. Collectively, these results demonstrate that kindlin-3 in neutrophils is involved in modulating the ROS/NET signaling, providing a novel mechanism for fine-tuning neutrophil behaviors during inflammation.

Kindlin-3 is a novel regulator for fine-tuning the generation of ROS/NETs in neutrophils during inflammation.
miRNA regulation of innate immunity
Authors: Momen-Heravi Fatemeh , Bala Shashi
Published: April 2018

MicroRNAs (miRNAs) are small noncoding RNA and are pivotal posttranscriptional regulators of both innate and adaptive immunity. They act by regulating the expression of multiple immune genes, thus, are the important elements to the complex immune regulatory network. Deregulated expression of specific miRNAs can lead to potential autoimmunity, immune tolerance, hyper-inflammatory phenotype, and cancer initiation and progression. In this review, we discuss the contributory pathways and mechanisms by which several miRNAs influence the development of innate immunity and fine-tune immune response. Moreover, we discuss the consequence of deregulated miRNAs and their pathogenic implications.
PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma
Authors: Wille Christoph , Eiseler Tim , Langenberger Sven-Thorben , Richter Julia , Mizuno Kensaku , Radermacher Peter , Knippschild Uwe , Huber-Lang Markus , Seufferlein Thomas , Paschke Stephan
Published: April 2018

Neutrophils are important mediators of the innate immune defense and of the host response to a physical trauma. Because aberrant infiltration of injured sites by neutrophils was shown to cause adverse effects after trauma, we investigated how neutrophil infiltration could be modulated at the cellular level. Our data indicate that protein kinase D (PKD) is a vital regulator of neutrophil transmigration. PKD phosphorylates the Cofilin-phosphatase Slingshot-2L (SSH-2L). SSH-2L in turn dynamically regulates Cofilin activity and actin polymerization in response to a chemotactic stimulus for neutrophils, for example, fMLP. Here, we show that inhibition of PKD by two specific small molecule inhibitors results in broad, unrestricted activation of Cofilin and strongly increases the F-actin content of neutrophils even under basal conditions. This phenotype correlates with a significantly impaired neutrophil deformability as determined by optical stretcher analysis. Consequently, inhibition of PKD impaired chemotaxis as shown by reduced extravasation of neutrophils. Consequently, we demonstrate that transendothelial passage of both, neutrophil-like NB4 cells and primary PMNs recovered from a hemorrhagic shock trauma model was significantly reduced. Thus, inhibition of PKD may represent a promising modulator of the neutrophil response to trauma.

Protein Kinase D coordinates actin polymerization, neutrophil deformability and transendothelial migration via its substrate Slingshot2 and Cofilin.
Monocyte function in patients with myelodysplastic syndrome
Authors: Pollyea Daniel A , Hedin Brenna R , O’Connor Brian P , Alper Scott
Published: April 2018

Myelodysplastic syndrome (MDS) is a malignant hematopoietic stem cell disorder that frequently evolves into acute myeloid leukemia (AML). Patients with MDS are prone to infectious complications, in part due to the presence of severe neutropenia and/or neutrophil dysfunction. However, not all patients with neutropenia become infected, suggesting that other immune cells may compensate in these patients. Monocytes are also integral to immunologic defense; however, much less is known about monocyte function in patients with MDS. In the current study, we monitor the composition of peripheral blood monocytes and several aspects of monocyte function in MDS patients, including HLA-DR expression, LPS-induced inflammatory cytokine production, and phagocytosis. We find that monocytes from MDS patients exhibit relatively normal innate immune functions compared to monocytes from healthy control subjects. We also find that HLA-DR expression is moderately increased in monocytes from MDS patients. These results suggest that monocytes could compensate for other immune deficits in MDS patients to help fight infection. We also find that the range of immune functions in monocytes from MDS patients correlates with several key clinical parameters, including blast cell count, monocyte count, and revised International Prognostic Scoring System score, suggesting that disease severity impacts monocyte function in MDS patients.

Monocytes from patients with Myelodysplastic Syndrome exhibit relatively normal immune function and could contribute to infection control in these patients.
Editorial: Cancer, drugs, and bugs—Bacteriotherapy on the rise?
Authors: Adamczyk Alexandra , Westendorf Astrid M
Published: April 2018

Discussion on how the gut microbiota orchestrates immune responses during cancer therapies and how targeting the microbiota can prevent chemotherapy-induced toxicity.
Fipronil recognition by the FA1 site of human serum albumin
Authors: Ascenzi Paolo , Leboffe Loris , Toti Daniele , Polticelli Fabio , Trezza Viviana
Published: April 2018

Fipronil is a broad‐spectrum pesticide widely used in agriculture, horticulture, and forestry. Because fipronil can cause a variety of toxic effects in animals and humans, its use is authorized as a pesticide in veterinary medicinal products for pets, but not for the treatment of livestock animals whose products are intended for consumption. Recently, however, the presence of fipronil residues has been detected in the eggs and meat of layer hens from farms located in different European countries. Given the relevance of fipronil toxicity for human health, it is important to gain information concerning its fate in the human body, including its binding mode to human serum albumin (HSA), the most abundant protein in plasma. Here, the inhibition of heme‐Fe(III) binding to the fatty acid site 1 (FA1) of HSA by fipronil is reported. Docking simulations support functional data, indicating that the FA1 site is the preferential cleft for fipronil recognition by HSA. The affinity of fipronil for HSA (Kf = 1.9 × 10−6 M, at pH 7.3, and 20.0°C) may be relevant in vivo. Indeed, HSA could play a pivotal role in fipronil transport and scavenging, thus reducing the pesticide‐free plasmatic levels, with consequent reduced systemic toxicity. In turn, fipronil binding to the FA1 site of HSA could impair the recognition of endogenous and exogenous molecules.
Study on a 65‐mer peptide mimetic enzyme with GPx and SOD dual function
Authors: Yin Juxin , Zhuang Jianjian , Lv Shaowu , Mu Ying
Published: April 2018

Excessive reactive oxygen species (ROS) levels are harmful to the body. The peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant enzymes for preventing ROS‐induced damage. Se‐CuZn‐65P is an enzyme mimetic with dual GPx and SOD antioxidant function. However, currently, its production is mainly based on the cysteine auxotrophic expression technique, which is inefficient, expensive, and time consuming. In this study, we combined protein engineering and the chemical mutation method to synthesize Se‐CuZn‐65P. The DNA sequence encoding the 65 amino acid peptide with the desired sequence transformations to incorporate the SOD and the GPx catalytic sites was cloned and expressed in a soluble protein expression vector. The protein yield increased up to 152 mg/L, which is 10 times higher than in previous studies. The SOD and GPx activity of Se‐CuZn‐65P was high (1181 U/mg and 753 U/μmol, respectively). The binding constant of glutathione was 5.6 × 104 L·mol−1, which shows that Se‐CuZn‐65P efficiently catalyzed hydrogen peroxide reduction by glutathione. Mitochondrial damage experiments confirmed the double protective role of the Se‐CuZn‐65P peptide and demonstrated functional synergy between the SOD and the GPx domains, which indicates its potential to be used in the treatment of ROS‐related diseases. Our research may give a new thought to increase the yield of mimic.
Improving lymph node characterization in staging malignant lymphoma using first‐order ADC texture analysis from whole‐body diffusion‐weighted MRI
Authors: De Paepe Katja N. , De Keyzer Frederik , Wolter Pascal , Bechter Oliver , Dierickx Daan , Janssens Ann , Verhoef Gregor , Oyen Raymond , Vandecaveye Vincent
Published: April 2018

Background

Correct staging and treatment initiation in malignant lymphoma depends on accurate lymph node characterization. However, nodal assessment based on conventional and diffusion‐weighted (DWI) MRI remains challenging, particularly in smaller nodes.

Purpose

To evaluate first‐order apparent diffusion coefficient (ADC) texture parameters compared to mean ADC for lymph node characterization in non‐Hodgkin lymphoma (NHL) using whole‐body DWI (WB‐DWI).

Study Type

Retrospective.

Population

Twenty‐eight patients with NHL.

Field Strength/Sequence

3T whole‐body DWI using two b‐values (0–1000 s/mm2).

Assessment

Regions of interest were drawn on the three most hyperintense lymph nodes on b1000‐images, irrespective of size, in all nodal body regions. Diagnostic performance of mean ADC (ADCmean) was compared with first‐order ADC texture parameters: standard deviation (ADCstdev), kurtosis (ADCkurt), and skewness (ADCskew). Additional subanalyses focused on the accuracy of ADCmean and ADC texture parameters in different lymph node volumes and nodal regions.

Statistical Tests

Benign and malignant nodes were compared using Mann–Whitney U‐tests with 18‐Fluoro‐deoxyglucose positron emission tomography computed tomography and bone marrow biopsy as reference standard. Receiver operating characteristic analyses were performed to determine cutoff values and calculate sensitivity, specificity, accuracy, and positive and negative predictive value (PPV, NPV).

Results

ADCmean (P = 0.008), ADCskew and ADCkurt differed significantly between benign and malignant nodes (P < 0.001), while ADCstdev didn't (P = 0.21). ADCskew was the best discriminating parameter, with 79% sensitivity, 86% specificity, 83% accuracy, 85% PPV, and 81% NPV. In every volume category, ADCskew yielded the highest accuracy (88% in 0–25th percentile volume, 75% in 25th–75th percentile, 93% in 75–100th percentile). On a per‐region basis, ADCskew accuracy varied 13.6% between nodal regions, while ADCmean, ADCkurt, and ADCstdev showed interregional variation of 17.4%, 20.3%, and 14.9%, respectively.

Data Conclusion

First‐order ADC texture analysis with WB‐DWI improved lymph node characterization compared to ADCmean. ADCskew was the most accurate and robust discriminatory parameter over all lymph node volumes and nodal body regions.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:897–906.
Modified breath‐hold compressed‐sensing 3D MR cholangiopancreatography with a small field‐of‐view and high resolution acquisition: Clinical feasibility in biliary and pancreatic disorders
Authors: Zhu Liang , Xue Huadan , Sun Zhaoyong , Qian Tianyi , Weiland Elisabeth , Kuehn Bernd , Asbach Patrick , Hamm Bernd , Jin Zhengyu
Published: April 2018

Background

Compressed‐sensing (CS) accelerated 3D MR cholangiopancreatography (MRCP) could be acquired in both navigator‐triggered (NT) and breath‐hold (BH) mode, but the latter has been considered inferior in depicting pancreatic duct and diagnosing pancreatic duct‐related diseases.

Purpose

To prospectively evaluate the clinical feasibility of a modified 3D BH‐CS‐MRCP prototype protocol with small field‐of‐view (FOV) and higher spatial resolution, and to compare its performance to the original BH‐CS‐MRCP and NT‐CS‐MRCP.

Study Type

Prospective cohort study.

Population

Eighty‐two patients with suspected pancreaticobiliary diseases (46 male, median age, 55 years, range, 16–79 years), including seven noncooperative patients.

Field Strength/Sequence

3T, CS‐MRCP.

Assessment

Three protocols were performed in random order in each patient. Acquisition time of each protocol was recorded. Image quality, background suppression, duct visibility, and diagnostic confidence with duct anatomic variations and duct‐related pathologies were rated on a 5‐point scale by two blinded radiologists independently.

Statistical Tests

The Wilcoxon signed‐rank test was used to compare the intraindividual difference. Interobserver agreement was determined using kappa coefficients. The diagnostic performance was calculated using receiver operating characteristic curves.

Results

Acquisition time was 17 seconds for both BH‐CS‐MRCP protocols, and 127.5 ± 36.9 seconds for NT‐CS‐MRCP. In 75 cooperative patients, the incidence of major artifacts was low for all protocols (5.3–8.0%). Background suppression was similar with the two BH‐CS‐MRCP protocols (3.67 ± 0.77 for original BH‐CS‐MRCP and 3.70 ± 0. 57 for modified BH‐CS‐MRCP, respectively), both inferior to the NT‐CS‐MRCP protocol (4.41 ± 0.68, P < 0.001 for both). Modified BH‐CS‐MRCP and NT‐CS‐MRCP depicted pancreatic duct and second‐level branches of biliary duct better than original BH‐CS‐MRCP (all P < 0.01). The diagnostic performance for detecting bile duct abnormalities was similar for all protocols (P = 0.53–0.87), whereas for detecting pancreatic duct abnormalities, modified BH‐CS‐MRCP and NT‐CS‐MRCP had significantly better performance compared to original BH‐CS‐MRCP (both P < 0.01). In seven noncooperative patients, NT‐CS‐MRCP had superior image quality than both BH protocols (both P < 0.01).

Data Conclusion

Modified BH‐CS‐MRCP is feasible for pancreatic and biliary disorders. NT‐CS‐MRCP might be more useful in noncooperative patients.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:1389–1399.
Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats
Authors: Gupta Sangeetha , Upadhayay Deepti , Sharma Uma , Jagannathan Naranamangalam R. , Gupta Yogendra Kumar
Published: April 2018

Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post‐MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post‐reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post‐reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.
Differences in Creative Problem‐Solving Preferences Across Occupations
Authors: Puccio Gerard J. , Miller Blair , Acar Selcuk
Published: April 2018

FourSight theory contends that individuals show preferences for the mental operations rooted in the creative process. The four fundamental preferences measured by FourSight are Clarifiers, Ideators, Developers, and Implementers. The present study examined the extent to which certain occupations reflect a proclivity for these four creative‐process preferences. Guided by Holland's theory of vocational choice, hypothesized relationships were formulated for the link between FourSight theory and 17 occupations. For example, it was predicted that those who work in finance would show a significant bias toward the Clarifier preference. Of the 17 hypothesized relationships between FourSight and occupation, statistical analysis of the FourSight preferences for 20,784 individuals showed support for 12 predictions and partial support for two of the hypothesized relationships. These findings clearly demonstrate that particular occupations engage specific creative‐process preferences. Future investigations might wish to examine the degree to which the interaction between work and creative‐thinking preferences predicts creative performance, satisfaction, stress, and turnover.
Effects of methyl jasmonate on plant growth and leaf properties
Authors: Li Cui , Wang Peng , Menzies Neal W. , Lombi Enzo , Kopittke Peter M.
Published: April 2018

Exogenous application of methyl jasmonate (MeJA) can induce anatomical and chemical changes that are components of defence responses in plants. Particularly, MeJA is well‐known to increase leaf trichome density to protect against insect herbivory, but surprisingly little is known about the effects of MeJA on other leaf properties and plant growth. Using sunflower (Helianthus annuus), tomato (Solanum lycopersicum), and soybean (Glycine max) treated with 0.0, 0.1, 0.5, 1.0, and 2.5 mM MeJA, we examined changes in leaf trichome density, stomatal density, cuticle thickness, cuticle composition, plant height, and biomass production. For all three plant species, MeJA (especially at the higher concentrations) caused significant decreases in plant height (up to 39%) and biomass (up to 79%). MeJA caused substantial increases in leaf trichome density (being 1.3–3.5‐times higher) in all three species, with the magnitude of these effects increasing with MeJA concentration. However, we also observed that MeJA resulted in significant changes in cuticle composition and thickness, and stomatal density, although the magnitude of these changes was smaller relative to changes in trichome density. Specifically, high concentrations of MeJA increased the relative content of phenolic compounds and cutin in leaf cuticle while decreasing the relative content of polysaccharide. The changes in stomatal density varied with plant species and MeJA concentration. Also, MeJA increased cuticle thickness in tomato but decreased that in sunflower and soybean. Thus, studies investigating MeJA should also consider the importance of changes in other leaf properties and plant growth.
Seasonal variation of macro and micronutrients in blades and petioles of Vitis vinifera L. cv. Mencía and Sousón
Authors: Cancela Javier J. , Fandiño María , González Xesús P. , Rey Benjamín J. , Mirás-Avalos José M.
Published: April 2018

In the case of grapevine (Vitis vinifera L.), leaf blade and petioles at different sampling times are used for nutritional diagnosis and planning fertilization practices. However, reference values for each nutrient depend on the scion‐rootstock combination. In this sense, the current study aimed at determining the reliability of leaf blade and petiole for diagnosis at different phenological stages and, also, of the period of validity, around flowering and veraison, in which the nutrient concentrations obtained could be compared with reference values. The study was carried out in three vineyards (two planted with cv. Mencía and one with cv. Sousón) within the Ribeira Sacra Designation of Origin (NW Spain). Blades and petioles were collected throughout a growth season (2014) and total concentrations of ten essential elements were determined in both tissues. In general, petioles showed greater variability between replicates for P, K, Ca, Mg, and Zn, while N, Fe, Mn, Cu, and B presented greater variability in blades. Differences between consecutive sampling dates suggest that references for flowering were valid until fruit‐set. Furthermore, blade and petiole references at the beginning of veraison were valid until the advanced ripening stage for most nutrients, with the exception of N, P, and Zn. The seasonal variation of the concentrations in both tissues confirmed the need for reference values for each phenological stage and tissue.
Isolation and identification of rapeseed (Brassica napus) cultivars for potential higher and lower Cd accumulation
Authors: Zhang Xian Duo , Wang Ye , Li Hai Bo , Yang Zhi Min
Published: April 2018

Cadmium (Cd) as a non‐essential toxic metal has become one of the seriously environmental problems. Overload of Cd into plant shoots, particularly the addible parts (i.e., grains), jeopardizes crop production and food safety. Isolating and identifying genotypic variations in Cd accumulation of rapeseed (Brassica napus) cultivars is an efficient approach for phytoremediation and developing lower Cd‐accumulating plants. In this study, a trial was conducted under natural condition in Nanjing, China, from 2014 to 2017, and identified 64 rapeseed cultivars collected from the areas of Gui Zhou province. Rapeseed grew under moderate Cd exposure (5 mg kg−1) for 5 months, and shoots were harvested for Cd quantification. A great variation of total Cd concentrations in shoots, ranking from 0.16 to 17.03 mg Cd kg−1, was found. Following the initial examination of all cultivars, two sets of plants with high (#138 and #177) and low (#208 and #244) Cd concentrations were further investigated. Throughout the growth period, cultivars #138 and #177 accumulated more Cd during vegetative (30, 60, and 120 d) and late developmental (180 d) stages than cultivars #208 and #244. The higher Cd concentration in shoots of #138 and #177 was associated with the higher Cd concentration in xylem sap, suggesting the greater capability of Cd translocation from roots to shoots. Compared to #208 and #244, Cd exposure moderately reduced zinc and iron concentrations in some tissues of #138 and #177, whereas the manganese and magnesium concentrations showed no change. Although #138 and #177 cultivars accumulated more Cd in their shoots, no Cd toxicity was detected. Moreover, both #138 and #177 cultivars had a similar biomass to #208 or #244. These results suggest that #138 and #177 rapeseeds are tolerant to Cd stress.