bluuebunny/crossref_metadata_2025 huggingface dataset:
Predator hunting mode and host plant quality shape attack‐abatement patterns of predation risk in an insect herbivore
Authors: Stephan Jörg G. , Low Matthew , Stenberg Johan A. , Björkman Christer
Published: November 2016

Group formation reduces individual predation risk when the proportion of prey taken per predator encounter declines faster than the increase in group encounter rate (attack‐abatement). Despite attack‐abatement being an important component of group formation ecology, several key aspects have not been empirically studied, that is, interactions with the hunting mode of the predator and how these relationships are modified by local habitat quality. In 79 cage trials, we examined individual egg predation risk in different‐sized egg clutches from the blue willow beetlePhratora vulgatissimafor two predators with different hunting modes (consumption of full group [Orthotylus marginalis] vs. part group [Anthocoris nemorum]). Because these predators also take nutrients from plant sap, we could examine how the quality of alternative food sources (high‐ vs. low‐quality host plant sap) influenced attack‐abatement patterns in the presence of different hunting strategies. For theO. marginalispredator, individual egg predation risk was largely independent of group size. ForA. nemorum, egg predation risk clearly declined with increasing group size. However, approximately one‐third of the grouping benefit was lost to an increase in group detectability. There were clear differences in attack‐abatement patterns between plants with high‐ vs. low‐quality sap. WhenO. marginaliswas the predator, there was no clear change in attack‐abatement in relation to host plant quality. However, forA. nemorumthere was a clear reduction in overall predation risk and a stronger attack‐abatement pattern with increasing group size when plant sap quality increased. This implies that the relative benefits of prey grouping behavior for any species might show diurnal or seasonal changes as other aspects of resource/habitat quality change for the focal predator. Modulation of attack‐abatement by bottom‐up effects such as plant‐based food resources is yet to be incorporated into general theory, despite the ubiquity of omnivorous predators and with omnivory being important for shaping food webs, ecosystem functions, and in biological control. Thus, ongoing refinement of attack‐abatement theory by focusing on bottom‐up vs. top‐down processes could have significant impacts on many important contemporary fields of study.
Sensitivity of coral recruitment to subtle shifts in early community succession
Authors: Doropoulos Christopher , Roff George , Visser Mart‐Simone , Mumby Peter J.
Published: November 2016

Community succession following disturbance depends on positive and negative interactions, the strength of which change along environmental gradients. To investigate how early succession affects coral reef recovery, we conducted an 18‐month experiment in Palau, using recruitment tiles and herbivore exclusion cages. One set of reefs has higher wave exposure and had previously undergone a phase shift to macroalgae following a major typhoon, whereas the other set of reefs have lower wave exposure and did not undergo a macroalgal phase shift. Similar successional trajectories were observed at all sites when herbivores were excluded: turf algae dominated early succession, followed by shifts to foliose macroalgae and heterotrophic invertebrates. However, trajectories differed in the presence of herbivores. At low wave exposure reefs, herbivores promoted coralline algae and limited turf and encrusting fleshy algae in crevice microhabitats, facilitating optimal coral recruitment. Under medium wave exposure, relatively higher but still low coverage of turf and encrusting fleshy algae (15–25%) found in crevice microhabitats inhibited coral recruitment, persisting throughout multiple recruitment events. Our results indicate that altered interaction strength in different wave environments following disturbance can drive subtle changes in early succession that cascade to alter secondary succession to coral recruitment and system recovery.
Effects of dispersal and environmental heterogeneity on the replacement and nestedness components of β‐diversity
Authors: Gianuca Andros T. , Declerck Steven A. J. , Lemmens Pieter , De Meester Luc
Published: November 2016

Traditionally metacommunity studies have quantified the relative importance of dispersal and environmental processes on observed β‐diversity. Separating β‐diversity into its replacement and nestedness components and linking such patterns to metacommunity drivers can provide richer insights into biodiversity organization across spatial scales. It is often very difficult to measure actual dispersal rates in the field and to define the boundaries of natural metacommunities. To overcome those limitations, we revisited an experimental metacommunity dataset to test the independent and interacting effects of environmental heterogeneity and dispersal on each component of β‐diversity. We show that the balance between the replacement and nestedness components of β‐diversity resulting from eutrophication changes completely depending on dispersal rates. Nutrient enrichment negatively affected local zooplankton diversity and generated a pattern of β‐diversity derived from nestedness in unconnected, environmentally heterogeneous landscapes. Increasing dispersal erased the pattern of nestedness, whereas the replacement component gained importance. In environmentally homogeneous metacommunities, dispersal limitation created community dissimilarity via species replacement whereas the nestedness component remained low and unchanged across dispersal levels. Our study provides novel insights into how environmental heterogeneity and dispersal interact and shape metacommunity structure.
Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
Authors: Rossignol Patrick , Girerd Nicolas , Bakris George , Vardeny Orly , Claggett Brian , McMurray John J.V. , Swedberg Karl , Krum Henry , van Veldhuisen Dirk J. , Shi Harry , Spanyers Sean , Vincent John , Fay Renaud , Lamiral Zohra , Solomon Scott D. , Zannad Faiez , Pitt Bertram
Published: November 2016

Aims

Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow‐up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain.

Methods and results

Results of the EMPHASIS‐HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K+ <4.0 mmol/L) and the risk of cardiovascular death or hospitalization for HF (primary endpoint). Median follow‐up was 21 months. Baseline hypokalaemia and hypokalaemia during follow‐up were common occurrences (19.6% and 40.6%, respectively). Hypokalaemia during follow‐up was associated with worse outcomes in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.05–1.52, P = 0.01] without evidence of interaction with eplerenone. In contrast, baseline hypokalaemia was associated with outcomes in the placebo group (HR 1.37, 95% CI 1.05–1.79, P = 0.02) but not in the eplerenone group (HR 0.87, 95% CI 0.62–1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone was found to be more protective in patients with baseline hypokalaemia vs. patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30–0.64, P < 0.0001 vs. 0.69, 95% CI 0.57–0.83, P = 0.0001; P for interaction = 0.04). In patients without baseline hypokalaemia, eplerenone use decreased the rate of hypokalaemia during follow‐up (HR 0.69, 95% CI 0.59–0.80, P < 0.001). A potassium level >4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6–51.4%) of the eplerenone treatment effect (P = 0.04).

Conclusion

In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.
Changes in fatty acid profile and chemical composition of meagre (Argyrosomus regius) fed with different lipid and selenium levels
Authors: Simões Tiago , Fonseca Sthelio B. , Augusto Ana , Granada Luana , Ozório Rodrigo O.A. , Gonçalves José F.M. , Pascoal Leonardo A.F. , Silva José H.V. , Lemos Marco F.L.
Published: November 2016

This study aimed to evaluate changes in body composition, specially muscle and liver fatty acid profile in meagre (Argyrosomus regius) fed with different dietary lipid sources and levels, with or without selenium supplementation. Six hundred meagre were fed twice a day, 6 days per week, with eight experimental diets for 60 days. Diets were a combination of fish oil or a vegetable blend (45% linseed + 35% rapeseed + 20% soybean oil), at 12 or 17% of oil and 0 or 1 mg/kg of organic selenium, in a 2 × 2 × 2 factorial design. The whole body protein and lipid content were affected by the dietary oil source. Fish oil diets increased long‐chain (LC) PUFAs content in the edible tissues, while vegetable oil‐based diets increased short‐chain (SC) PUFAs. Vegetable oil diet tended to decrease the fish protein content. A higher lipid liver content was observed in meagre fed the vegetable oil blend. The results also suggested the ability of meagre to convert SC‐PUFA to LC‐PUFA when the vegetable oil is included in their diet. The possibility for partial substitution of fish oil by vegetable oil in meagre diets, resulting in lower dependence of fish oil in meagre farming, is also demonstrated here.

Practical applications: The growing importance of aquaculture for basic food supply, and the urge for cost‐effective and sustainable feeds that maintain or even increase fish quality, makes the search for alternatives to common feeds a route of upmost importance, as the vegetable oil here addressed. SC‐PUFA and LC‐PUFA contents of the studied tissues increased with diets supplemented with 17% oil level, which may ultimately add more value to this farmed species. These results indicate the possibility of the partial substitution of fish oil by vegetable oil in meagre diets, resulting in lower dependence on fish oil for fish farming.

Meagre were fed with different dietary lipid sources and levels, with or without selenium supplementation, in a total of eight experimental diets during 60 days, in a 2 × 2 × 2 factorial design. Fish oil diet increases HUFAs and vegetable oil diet increases PUFAs in body composition. There is great potential for partial substitution of fish oil by vegetable oil in meagre (Argyrosomus regius) diets, resulting in lower dependence of fish oil in meagre farming.
Double extraction of olive oil in large oil mills of Southern Italy: Effects on extraction efficiency, oil quality, and economy of the process
Authors: Di Giovacchino Luciano , Preziuso Serena Maria , Di Serio Maria Gabriella , Mucciarella Maria Regina , Di Loreto Giuseppina , Lanza Barbara
Published: November 2016

In recent years, in Italy, some large oil mills, equipped with centrifugal decanter at high loading capacity have adopted the complex diagram of the double extraction of oil and, in addition, have been supplied with suitable machine to recover part of stone fragments from olive pomace with the aim to reduce the costs. Our experimental tests were carried out in a large oil mill, located in Apulia region, which processes olives of Olea europaea L. “Coratina” cultivar by double centrifugation of olive pastes prepared by using the double crushing (millstones and metallic crusher) or the single crushing (metallic crusher). The results showed that the oil yield of the first extraction was high (between 85 and 86%), regardless to the method used for olive crushing. The quality of virgin olive oil of the first extraction was extra virgin with some differences due to the different batches of olives and, in part, also to the used crushing methods. The oil of the second extraction was recovered in a low quantity (0.3 kg/100 kg olives) and its composition was not normal only for the percentage of triterpene dialcohols. The recovery of stone fragments was satisfying (about 0.13 t/t olives) and helped to significantly increase the income of oil mill.

Practical applications: The double extraction of oil, by the centrifugation system, and the recovery of SF allow to reduce the costs of olive processing in medium‐big sized oil mills. The second centrifugation, which permits to recover about 3 kg of oil/t of olives, and the recovery of SF, suitable to sell as fuel, allow to increase the income of oil mill.

The double extraction of oil, by the centrifugation system and the recovery of olive stone fragments (SF) allow to reduce the costs of olive processing in medium‐big sized oil mills. The second centrifugation, which permits to recover about 3 kg of oil/t of olives, and the recovery of SF, suitable to sell as fuel, allow to increase the income of oil mill.
Synthesis of Heterocycle‐Bridged Peptidic Macrocycles through 1,3‐Diyne Transformations
Authors: Verlinden Steven , Ballet Steven , Verniest Guido
Published: November 2016

Macrocyclic tetrapeptide analogues containing a 1,3‐diyne moiety were synthesized by a Glaser–Hay‐type macrocyclization. The obtained 1,3‐diyne was evaluated as a handle to introduce heterocycles into the macrocyclic structure. It was shown that the macrocyclic 1,3‐diynes were successfully transformed into various heterocycles by nucleophilic attack of (bis)nucleophiles to the diyne moiety. Treatment with NaHS or H2O as nucleophiles gave rise to 2,5‐bridged thiophenes or furans, whereas the use of hydrazines and hydroxylamine gave rise to the corresponding pyrazole‐ and isoxazole‐containing macrocycles. In addition, a thermoreversible Diels–Alder cycloaddition of a cyclopeptidic bridged furan was demonstrated.
Aromatic Claisen Rearrangements of Benzyl Ketene Acetals: Conversion of Benzylic Alcohols to (ortho‐Tolyl)acetates
Authors: Burns Jed M. , Krenske Elizabeth H. , McGeary Ross P.
Published: November 2016

Claisen rearrangements of benzyl vinyl ethers are much less facile than those of aliphatic allyl vinyl ethers, and their synthetic utility has remained relatively unexplored. A one‐pot procedure is reported for the generation and Claisen rearrangement of benzyl vinyl ethers that contain an activating α‐alkoxy substituent on the vinyl group. A [3,3]‐sigmatropic mechanism was supported by trapping of the intermediate isotoluene in an intramolecular Alder–ene reaction.
Ti‐Catalyzed Synthesis of Exocyclic Allenes on Oxygen Heterocycles
Authors: Padial Natalia M. , Hernández‐Cervantes Carmen , Muñoz‐Bascón Juan , Roldán‐Molina Esther , García‐Martínez Mireya , Ruiz‐Muelle Ana Belén , Rosales Antonio , Álvarez‐Corral Míriam , Muñoz‐Dorado Manuel , Rodríguez‐García Ignacio , Oltra J. Enrique
Published: November 2016

A general method for the straightforward synthesis of exocyclic allenes on five‐, six‐, seven‐, and eight‐membered oxygen heterocycles is described. A Barbier‐type titanocene(III)‐catalyzed cyclization of propargyl halides with a pendant carbonyl group is the key step of the process. This reaction is compatible with many functional groups, and can be smoothly carried out under neutral and mild conditions at room temperature.
Performance and selectivity of cationic nanoparticle pseudo‐stationary phases in electrokinetic chromatography
Authors: McGettrick Julie R. , Williamson Nathan H. , Sutton Adam T. , Palmer Christopher P.
Published: November 2016

Electrokinetic chromatography (EKC) is a powerful analytical technique that uses an ionic pseudo‐stationary phase (PSP) to separate neutral compounds. Although anionic surfactants are the most common choice for PSP, cationic latex nanoparticles are an attractive alternative. Reversible addition‐fragmentation chain transfer (RAFT) polymerization was used to synthesize several types of diblock copolymers that self‐assemble into latex nanoparticles, which were characterized by a variety of techniques including diffusion NMR. The performance of each nanoparticle as a PSP was studied by using a homologous series of ketones and linear solvation energy relationships (LSER) analysis. A cationic homopolymer coating was found to be necessary to prevent band broadening caused by analyte interactions with nanoparticles adsorbed to the capillary surface. No significant difference in methylene selectivity or LSER parameters was observed between nanoparticles with different cationic shells, but differences were observed between nanoparticles with different hydrophobic cores. Cationic latex nanoparticles behaved more like anionic latex nanoparticles than like cationic surfactants, suggesting that selectivity is primarily driven by the hydrophobic portion of a PSP. Cationic latex nanoparticles in combination with a homopolymer cationic capillary coating are an excellent choice for EKC analyses where an anodic electroosmotic flow is required.
Lessons for the NFL from Workers’ Compensation
Authors: Diana Richard
Published: November 2016

In the article “A Proposal to Address NFL Club Doctors’ Conflicts of Interest and to Promote Player Trust,” Glenn Cohen et al. write, “The [NFL's] current structure forces club doctors to have obligations to two parties—the club and the player—and to make difficult judgments about when one party's interests must yield to another's.” I can understand why some might be suspicious about bias in the current NFL medical system, in which the club doctors have a professional duty to put their player‐patients’ best interests first yet are employed by clubs, which have a primary goal of winning football games. It is my opinion, however, that neither the club nor the player needs to be sacrificed. I base this opinion partly on my experience as an NFL player in the early 1980s, partly on several years as team physician for the Boston Red Sox, and partly on my twenty‐three‐years of experience as a physician with the Connecticut Workers’ Compensation medical system, which supposes that physicians can be fair to both workers and employers.
Hepatitis C virus infection triggers a tumor‐like glutamine metabolism
Authors: Lévy Pierre L. , Duponchel Sarah , Eischeid Hannah , Molle Jennifer , Michelet Maud , Diserens Gaëlle , Vermathen Martina , Vermathen Peter , Dufour Jean‐Francois , Dienes Hans‐Peter , Steffen Hans‐Michael , Odenthal Margarete , Zoulim Fabien , Bartosch Birke
Published: November 2016

Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV‐infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense, and neoplastic transformation. Transcript levels of glutaminolytic factors were quantified in Huh7.5 cells or primary human hepatocytes infected with the Japanese fulminant hepatitis 1 HCV strain as well as in biopsies of chronic HCV patients. Nutrient deprivation, biochemical analysis, and metabolite quantification were performed with HCV–infected Huh7.5 cells. Furthermore, short hairpin RNA vectors and small molecule inhibitors were used to investigate the dependence of HCV replication on metabolic changes. We show that HCV modulates the transcript levels of key enzymes of glutamine metabolism in vitro and in liver biopsies of chronic HCV patients. Consistently, HCV infection increases glutamine use and dependence. We finally show that inhibiting glutamine metabolism attenuates HCV infection and the oxidative stress associated with HCV infection. Conclusion: Our data suggest that HCV establishes glutamine dependence, which is required for viral replication, and, importantly, that glutamine addiction is a hallmark of tumor cells. While HCV induces glutaminolysis to create an environment favorable for viral replication, it predisposes the cell to transformation. Glutaminolytic enzymes may be interesting therapeutic targets for prevention of hepatocarcinogenesis in chronic hepatitis C. (Hepatology 2017;65:789‐803).
Cancer risks after solid organ transplantation and after long‐term dialysis
Authors: Hortlund Maria , Arroyo Mühr Laila Sara , Storm Hans , Engholm Gerda , Dillner Joakim , Bzhalava Davit
Published: November 2016

Immunosuppression involves an inability to control virus infections and increased incidence of virus‐associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent. To provide a reliable and generalizable estimate, with high statistical power and long follow‐up time, we assessed cancer risks using comprehensive, population‐based registries in two different countries and from two different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long‐term dialysis patients (LDPs)). National registries in Denmark and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated. We found highly similar results, both for the two different countries and for the two different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non‐melanoma skin cancer (NMSC), non‐Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n = 2,142, 95% CI, 3.4–3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8–3.1] in Denmark and 1.6 [n = 1,713, 95% CI, 1.5–1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n = 994, 95% CI, 42–47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8–45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7–5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression‐related susceptibility to viral infections.
STEAMPUNK SYSTEM OF SYSTEMS ENGINEERING: A CASE STUDY OF SUCCESSFUL SYSTEM OF SYSTEMS ENGINEERING IN 19TH CENTURY BRITAIN
Authors: Kemp Duncan , Evans Rhianne
Published: November 2016

This article presents a case study of the Great British railway as it developed from over 300 individual railways, through a complex system of systems (SoS) to its eventual integration into a single railway. This evolution took place from the 1830s to the early 1950s. The case study focusses on the critical period from 1840 to 1860 when the railways collaborated to form a system of systems. The article evaluates the effectiveness of three current SoS frameworks at identifying the factors that enabled the SoS to operate. Much like the artistic and literary genre of Steampunk, this case study is a mixture of familiar SoS concepts and approaches in an unfamiliar Victorian setting
SYSTEMS THEORY AS A CONCEPTUAL FOUNDATION FOR SYSTEM OF SYSTEMS ENGINEERING
Authors: Keating Charles B. , Katina Polinpapilinho F. , Bradley Joseph M. , Pyne James C.
Published: November 2016

Systems theory (ST) can provide the developing systems of systems engineering (SoSE) field and practice with a strong conceptual foundation. ST is presented as a taken for granted set of axioms and corresponding propositions that explain the phenomena, patterns, and tendencies of complex systems. The results of ST are observable in the behavior and performance of systems. We argue that ST offers a critical grounding for the future development and practice of SoSE. Our exploration examines the necessity, contributions, and implications of ST as an influential conceptual foundation to accelerate and guide SoSE development and practice.
ENGINEERING THE VIRTUAL OR COLLABORATIVE SOS
Authors: Eric Honour
Published: November 2016

The largest, most complex, and most prevalent systems of systems (SoS) are virtual or collaborative in nature. In such a SoS, there is no central authority to perform systems engineering. Yet, the virtual or collaborative SoS does grow, adapt, and evolve in response to the needs of the many stakeholders. Changes in the SoS happen because of many changes in the constituent systems (CS), with each change occurring when the CS owners deem it useful to change. The systems engineering activities in the CS can be used to guide and affect the SoS through a collaborative and competitive environment in which each CS systems engineer seeks to optimize the SoS behavior for their own purposes. This requires a different approach to the systems engineering activities, in which greater emphasis is on the higher‐level analysis, architecting, and quantification. This paper describes the modified systems engineering approach, showing how to engineer the SoS from within the scope of a CS.
DESIGNING FOR INTERUSABILITY: METHODOLOGICAL RECOMMENDATIONS FOR THE SYSTEMS ENGINEER GLEANED THROUGH AN EXPLORATION OF THE CONNECTED FITNESS TECHNOLOGIES SPACE
Authors: Woodrow W. Winchester
Published: November 2016

The current shift from singular (standalone; non‐connected) product or system design to the design of product ecosystems (interconnected smart or Internet‐of‐things products or devices such as connected fitness technologies) is challenging human‐systems integration activities. Of particular concern is designing for interusability, the user experience (inclusive of the usability) of interconnected systems. While interusability is of growing concern, little concrete design guidance (methods) exists. This paper, through a synthesis of the interdisciplinary work in this emerging area, offers the systems engineer a set of methodological recommendations in designing for interusability that underpin upstream product development process or front‐end development activities. These recommendations, specifically supporting the conceive stage of the generic product development process, include: 1) using robust tools and approaches such as storytelling in understanding & capturing user needs; 2) leveraging appropriate interoperability standards particularly those supporting architectural design; and 3) engaging user experience tools and approaches such as personas, to convey and champion interusability design considerations through downstream product development process activities. Moreover, this paper calls for more active systems engineering and engineering management disciplinary involvement in advancing both an understanding of interusability, and the development of analogous methods and approaches.
FasL and the NKG2D receptor are required for the secretion of the Tag7/PGRP‐S–Hsp70 complex by the cytotoxic CD8+ lymphocytes
Authors: Sashchenko Lidia P. , Romanova Elena A. , Ivanova Olga K. , Sharapova Tatiana N. , Yashin Denis V.
Published: November 2016

Tag7 (PGRP‐S or PGLYRP1), while possessing an antimicrobial activity, also exhibits an antitumor effect when in complex with the major heat shock protein Hsp70. The cytotoxic Tag7‐Hsp70 complex is secreted by lymphocytes after interaction with the HLA‐negative tumors. Previously, we have shown that IL‐2 induces formation of the CD4+ and CD8+ cytotoxic subpopulations of human lymphocytes, which kill tumor cells through the FasL‐Fas interaction. Here, we show that only the CD8+ T cells are able to secrete the Tag7‐Hsp70 complex. For its secretion the same proteins on the surface of the lymphocytes and target cells, which are involved in the contact lysis, are necessary as well. The interaction of Fas receptor with FasL leads to an activation of the Tag7‐Hsp70 complex in the lymphocyte membrane fraction, and here FasL acts as a receptor that induces intracellular signaling in lymphocytes. An interaction of the MicA stress ligand with the NKG2D receptor is necessary for the release of this cytotoxic complex. It is possible, that CD8+ T lymphocytes interacting with a target cell can both carry out the contact killing of these cells and to secrete the cytotoxic factor. © 2016 IUBMB Life, 69(1):30–36, 2017
Sensitivity and accuracy of hybrid fluorescence‐mediated tomography in deep tissue regions
Authors: Rosenhain Stefanie , Al Rawashdeh Wa'el , Kiessling Fabian , Gremse Felix
Published: November 2016

Fluorescence‐mediated tomography (FMT) enables noninvasive assessment of the three‐dimensional distribution of near‐infrared fluorescence in mice. The combination with micro‐computed tomography (µCT) provides anatomical data, enabling improved fluorescence reconstruction and image analysis. The aim of our study was to assess sensitivity and accuracy of µCT‐FMT under realistic in vivo conditions in deeply‐seated regions. Accordingly, we acquired fluorescence reflectance images (FRI) and µCT‐FMT scans of mice which were prepared with rectal insertions with different amounts of fluorescent dye. Default and high‐sensitivity scans were acquired and background signal was analyzed for three FMT channels (670 nm, 745 nm, and 790 nm). Analysis was performed for the original and an improved FMT reconstruction using the µCT data.

While FRI and the original FMT reconstruction could detect 100 pmol, the improved FMT reconstruction could detect 10 pmol and significantly improved signal localization. By using a finer sampling grid and increasing the exposure time, the sensitivity could be further improved to detect 0.5 pmol. Background signal was highest in the 670 nm channel and most prominent in the gastro‐intestinal tract and in organs with high relative amounts of blood. In conclusion, we show that µCT‐FMT allows sensitive and accurate assessment of fluorescence in deep tissue regions.

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Potential urinary biomarkers of nephrotoxicity in cyclophosphamide‐treated rats investigated by NMR‐based metabolic profiling
Authors: Lim Sa Rang , Hyun Sun‐Hee , Lee Seul Gi , Kim Jin‐Young , Kim So‐Hyun , Park Sang‐Jin , Moon Kyoung‐Sik , Sul Donggeun , Kim Dong Hyun , Choi Hyung‐Kyoon
Published: November 2016

The anticancer‐drug cyclophosphamide (CP) is known to have nephrotoxicity. The aim of this study was to identify urinary biomarkers indicating CP‐induced nephrotoxicity. We investigated the urine metabolic profiles using nuclear magnetic resonance spectrometry of rats administered with single high‐doses of CP (0, 30, and 100 mg/kg body weight) and daily low‐doses over a 4‐week period (0, 1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2‐oxoglutarate, citrate, hippurate, formate, valine, and alanine for short‐term and 2‐oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and lysine for long‐term were selected as potential biomarkers. Pathway‐enrichment analysis suggested that the urinary metabolism of CP is related to valine, leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate, and glutamate metabolism, with high pathway impact. The potential biomarkers obtained in this study could be used to monitor CP‐induced nephrotoxicity relative to dose and treatment time.
Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function
Authors: Mittal Rahul , Debs Luca H. , Nguyen Desiree , Patel Amit P. , Grati M'hamed , Mittal Jeenu , Yan Denise , Eshraghi Adrien A. , Liu Xue Zhong
Published: November 2016

Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710–2721, 2017. © 2016 Wiley Periodicals, Inc.
Roles of Multifunctional COP9 Signalosome Complex in Cell Fate and Implications for Drug Discovery
Authors: Li Ping , Xie Longxiang , Gu Yinzhong , Li Jiang , Xie Jianping
Published: November 2016

The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis, has also been demonstrated to be important in proteolysis, cellular signal transduction and cell cycle regulation in various eukaryotic organisms. This review mainly summarizes the roles of CSN in cell cycle regulation, signal transduction and apoptosis, and its potential as diagnostic biomarkers, drug targets for cancer and infectious diseases. J. Cell. Physiol. 232: 1246–1253, 2017. © 2016 Wiley Periodicals, Inc.
APCI as an innovative ionization mode compared with EI and CI for the analysis of a large range of organophosphate esters using GC‐MS/MS
Authors: Halloum Wafaa , Cariou Ronan , Dervilly‐Pinel Gaud , Jaber Farouk , Le Bizec Bruno
Published: November 2016

Organophosphate esters (OPEs) are chemical compounds incorporated into materials as flame‐proof and/or plasticizing agents. In this work, 13 non‐halogenated and 5 halogenated OPEs were studied. Their mass spectra were interpreted and compared in terms of fragmentation patterns and dominant ions via various ionization techniques [electron ionization (EI) and chemical ionization (CI) under vacuum and corona discharge atmospheric pressure chemical ionization (APCI)] on gas chromatography coupled to mass spectrometry (GC‐MS). The novelty of this paper relies on the investigation of APCI technique for the analysis of OPEs via favored protonation mechanism, where the mass spectra were mostly dominated by the quasi‐molecular ion [M + H]+. The EI mass spectra were dominated by ions such as [H4PO4]+, [M–R]+, [M–Cl]+, and [M–Br]+, and for some non‐halogenated aryl OPEs, [M]+● was also observed. The CI mass spectra in positive mode were dominated by [M + H]+ and sometimes by [M–R]+, while in negative mode, [M–R]− and more particularly [X]‐ and [X2]‐● were mainly observed for the halogenated OPEs. Both EI and APCI techniques showed promising results for further development of instrumental method operating in selective reaction monitoring mode.

Instrumental detection limits by using APCI mode were 2.5 to 25 times lower than using EI mode for the non‐brominated OPEs, while they were determined at 50‐100 times lower by the APCI mode than by the EI mode, for the two brominated OPEs. The method was applied to fish samples, and monitored transitions by using APCI mode showed higher specificity but lower stability compared with EI mode. The sensitivity in terms of signal‐to‐noise ratio varying from one compound to another. Copyright © 2016 John Wiley & Sons, Ltd.
Quantitative structure‐activity relationship and molecular docking revealed a potency of anti‐hepatitis C virus drugs against human corona viruses
Authors: Elfiky Abdo A. , Mahdy Samah M. , Elshemey Wael M.
Published: November 2016

A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti‐HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure‐Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX‐184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK‐0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV.
EBV infection is prevalent in the adenoid and palatine tonsils in adults
Authors: Seishima Noriko , Kondo Satoru , Wakisaka Naohiro , Kobayashi Eiji , Imoto Tomoko , Moriyama‐Kita Makiko , Nakanishi Yosuke , Endo Kazuhira , Murono Shigeyuki , Sugimoto Hisashi , Hatano Miyako , Ueno Takayoshi , Yoshizaki Tomokazu
Published: November 2016

Epstein‐Barr virus (EBV) is associated with the pathogenesis of several diseases in both adults and children. However, there have been no reports on the prevalence and amount of EBV in the adenoids of adults; thus, it is important to investigate these in the adenoids and tonsils of adults and children. In this study, 67 patients who underwent tonsillectomy or adenotonsillectomy were included and divided into two groups: adults aged ≥ 16 years (n = 35) and children aged <16 years (n = 32). Patients’ adenoid and tonsil tissues were analyzed using quantitative polymerase chain reaction for EBV DNA. EBV was detected in 26 (74%) adenoids and 25 (71%) tonsils among the adult group and was detected 21 (66%) adenoids and 20 (63%) tonsils in the child group. There was no significant difference in EBV DNA prevalence between the adenoids and tonsils for each group. However, there was a significant correlation between EBV DNA load in the adenoids and tonsils of the same individual in both groups (r = 0.579, P < 0.01, adult group; r = 0.919, P < 0.01, child group). In conclusion, EBV infection is prevalent in the adenoids and tonsils in adults and children. These results indicate that EBV continuously reside in the nasopharyngeal region after primal infection and may develop several diseases.
The role of the miR‐17–92 cluster in neurogenesis and angiogenesis in the central nervous system of adults
Authors: Yang Ping , Cai Linghu , Zhang Guan , Bian Zhiqun , Han Gaofeng
Published: November 2016

It is well known that neurogenesis is not the only concern for the fully functional recovery after brain or spinal cord injury, as it has been shed light on the critical role of angiogenesis in improving neurological functional recovery. Angiogenesis and neurogenesis coordinately interact with each other in the developing and adult brain, during which they may respond to similar mediators and receptors, in which they share a common posttranscriptional regulator: the miR‐17–92 cluster. The miR‐17–92 cluster was initially described as an oncogene and was later demonstrated to drive key physiological and pathological responses during development and diseases respectively. It has been reported that the miR‐17–92 cluster regulates both neurogenesis and angiogenesis. The miR‐17–92 cluster modulates neural progenitor cells proliferation not only during development but also during neurological disorders such as stroke. It has also been shown that the endothelial miR‐17–92 cluster regulates angiogenesis during embryonic stage and adulthood. In this review, we have discussed the actions of the miR‐17–92 cluster in neuronal and vascular plasticity, and its potential as a novel therapeutic strategy for CNS injury. © 2016 Wiley Periodicals, Inc.
Antioxidant properties and global metabolite screening of the probiotic yeast Saccharomyces cerevisiae var. boulardii
Authors: Datta Suprama , Timson David J , Annapure Uday S
Published: November 2016

BACKGROUND

Saccharomyces cerevisiae var. boulardii is the only yeast species with probiotic properties. It is considered to have therapeutic significance in gastrointestinal disorders. In the present study, a comparative physiological study between this yeast and Saccharomyces cerevisiae (BY4742) was performed by evaluating two prominent traits of probiotic species, responses to different stress conditions and antioxidant capacity. A global metabolite profile was also developed aiming to identify which therapeutically important secondary metabolites are produced.

RESULTS

Saccharomyces cerevisiae var. boulardii showed no significant difference in growth patterns but greater stress tolerance compared to S. cerevisiae. It also demonstrated a six‐ to 10‐fold greater antioxidant potential (judged by the 1,1‐diphenyl‐2‐picrylhydrazyl assay), with a 70‐fold higher total phenolic content and a 20‐fold higher total flavonoid content in the extracellular fraction. These features were clearly differentiated by principal component analysis and further indicated by metabolite profiling. The extracellular fraction of the S. cerevisiae var. boulardii cultures was found to be rich in polyphenolic metabolites: vanillic acid, cinnamic acid, phenyl ethyl alcohol (rose oil), erythromycin, amphetamine and vitamin B6, which results in the antioxidant capacity of this strain.

CONCLUSION

The present study presents a new perspective for differentiating the two genetically related strains of yeast, S. cerevisiae and S. cerevisiae var. boulardii by assessing their metabolome fingerprints. In addition to the correlation of the phenotypic properties with the secretory metabolites of these two yeasts, the present study also emphasizes the potential to exploit S. cerevisiae var. boulardii in the industrial production of these metabolites. © 2016 Society of Chemical Industry
Qualitative and quantitative analysis of multiple components for quality control of Deng‐Zhan‐Sheng‐Mai capsules by ultra high performance liquid chromatography tandem mass spectrometry method coupled with chemometrics
Authors: Jiang Pin , Lu Yan , Chen Daofeng
Published: November 2016

Deng‐Zhan‐Sheng‐Mai capsules are a well‐known traditional Chinese patent medicine that was developed in China for the treatment of ischemic stroke. Its quality control focuses on Erigerontis Herba but ignores the contributions of Ginseng Radix et Rhizoma, Schisandrae Chinensis Fructus, and Ophiopogonis Radix. To improve the quality standards for this medicine, this work reports the application of a systematic ultra high performance liquid chromatography tandem mass spectrometric method coupled with chemometrics. Three qualitative and quantitative parameters are established for the evaluation of quality: chemical profiling, the relationship between the contents of 18 compounds and the antioxidant activity, and chemometric analysis. A total of 55 compounds, including 20 phenolic acids, 10 flavonoids, 15 saponins, and 10 lignans, were identified. The method for the quantitative determination of the aforementioned 18 compounds was validated. The limit of quantification ranged from 0.13 to 9.60 ng/mL. The overall recoveries ranged from 95.31 to 103.54%. Hierarchical cluster analysis and principal component analysis were applied to the data of 18 components in ten batches of samples. Nine compounds, including scutellarin, 3,5‐O‐dicaffeoylquinic acid, 4,5‐O‐dicaffeoylquinic acid, ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ophiopogonin D, schisandrin, and schisandrol B, are suggested as chemical markers for evaluating the quality.
Indirect Exposure to Captivity Details Is Not Related to Posttraumatic Stress Symptoms Among the Spouses and Offspring of Former Prisoners of War
Authors: Zerach Gadi , Solomon Zahava
Published: November 2016

Indirect exposure to the aversive details of the primary victim's traumatic event(s) has been introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5; American Psychiatric Association, 2013) as a new event criterion (Criterion A4). However, this new criterion has been criticized for its significant emphasis on the exposure to trauma “details” or trauma narrative. This study assessed the associations between reported exposure to details about captivity and posttraumatic stress symptoms (PTSS) among 2 groups of family members of former prisoners of war (ex‐POWs): spouses (n = 115) and adult offspring (n = 78). Results show that in both groups exposure to details regarding captivity was not significantly related to the severity of total PTSS and specifically, high levels of exposure to captivity details were related to lower avoidance symptoms among ex‐POWs' spouses. Among offspring, exposure to paternal behaviors stemming from the fathers' posttraumatic stress disorder was related to PTSS, above and beyond negative life events, quality of relationship with the father, and exposure to captivity details (R2 = .34). These results suggest that behavioral displays of the fathers' posttraumatic symptoms, rather than the recounting of trauma‐related details, is related to PTSS among ex‐POWs' offspring.
Bioengineering pediatric scaffold‐free auricular cartilaginous constructs
Authors: Akbari Pedram , Waldman Stephen D. , Cushing Sharon L. , Papsin Blake C. , Propst Evan J. , Weber Joanna F. , Yeger Herman , Farhat Walid A.
Published: November 2016

Objective

The use of exogenous materials as scaffolds in cartilage tissue engineering has limited the clinical application of resultant constructs due to the risk of postoperative complications. In an effort to minimize such complications, we aim to generate human, scaffold‐free auricular cartilaginous constructs.

Study Design

Laboratory study using pediatric auricular cartilage.

Methods

Remnant, normal pediatric auricular cartilage samples that would have otherwise been discarded were collected and digested to free cells. Harvested cells were cultured and expanded in vitro for two passages and plated as micromass cultures. The culture medium was replaced with a chemically defined chondrogenic medium, and cellular monolayers surrounding micromass cultures were continuously scraped off. Constructs were allowed to mature for a period of 8 weeks.

Results

Micromass constructs showed mechanical stability and structurally resembled native auricular tissue, with a perichondrium‐like layer of cells surrounding the inner cartilaginous zone. Constructs accumulated equivalent sulphated glycosaminoglycan and 50% of collagen content compared to native auricular cartilage by mass, while displaying 156% more cellularity.

Conclusions

High‐density micromass cultures of pediatric auricular chondrocytes can generate stable cartilaginous constructs following prolonged chondrogenic inductions in vitro. This technique is an essential step toward the development of three‐dimensional constructs to recreate clinically applicable auricular cartilaginous constructs.

Level of Evidence

NA. Laryngoscope, 127:E153–E158, 2017