bluuebunny/crossref_metadata_2025_split huggingface dataset:
When Obligate Partners Melt Down
Authors: Moran Nancy A. 
Published: November 2016

ABSTRACT
Insect hosts derive benefits from their obligate symbionts, including nutrient supplementation and the ability to colonize otherwise inhospitable niches. But long-term symbionts sometimes also limit the ecological range of their hosts; in particular, they are often more temperature sensitive than the hosts themselves. Even small increases in average temperature, comparable to those occurring under current conditions of climate change, can kill symbionts and, with them, their hosts. In some cases, limitations imposed by obligate symbionts may help to counter the spread of invasive pests, but they also contribute to contractions in populations and geographic ranges of invertebrate species.
Siderophores: More than Stealing Iron
Authors: Behnsen Judith , Raffatellu Manuela 
Published: November 2016

ABSTRACT

Siderophores are small molecular iron chelators that are produced by microbes and whose most notable function is to sequester iron from the host and provide this essential metal nutrient to microbes. Recent studies have proposed additional, noncanonical roles for siderophores, including the acquisition of noniron metals and modulation of host functions. Recently, Holden et al. (V. I. Holden, P. Breen, S. Houle, C. M. Dozois, and M. A. Bachman, mBio 7:e01397-16, 2016,
http://dx.doi.org/10.1128/mBio.01397-16
) showed that siderophores secreted by
Klebsiella pneumoniae
during lung infection induce stabilization of the transcription factor HIF-1α, increase the expression of proinflammatory cytokines in the lung, and promote dissemination of
K. pneumoniae
to the spleen. Thus, their study demonstrated novel roles for siderophores
in vivo
, beyond iron sequestration. The interaction of siderophores with host cells further promotes the pathogenicity of
K. pneumoniae
and is likely relevant for other pathogens that also secrete siderophores in the host.
Cooperative Evolutionary Strategy between the Bacteriome and Mycobiome
Authors: Ghannoum Mahmoud 
Published: November 2016

ABSTRACT
Nonhealing chronic wounds are all unique in origin and circumstance, and attempting to isolate a single etiology for the failure of a wound to heal is daunting. Wounds represent complex systems of multispecies fungal and bacterial biofilms. The survival strategies of interactive microbial communities have led to cooperative evolutionary strategies that culminate in biofilm formation. In microbial dysbiosis, biofilms are beneficial to both bacterial and fungal communities but detrimental to the host. Fungi benefit by a surge in their virulence factors, while bacteria become tolerant to antibacterials as a consequence of living under the protective umbrella of the biofilm matrix. This interkingdom cooperation negatively impacts the host, as the fungi and bacteria produce extracellular enzymes that inflict tissue damage, leading to an increase in proinflammatory cytokines, which results in oxidative damage and apoptotic cell death.
Cross-sectional survey of the amount of free sugars and calories in carbonated sugar-sweetened beverages on sale in the UK
Authors: Hashem Kawther M , He Feng J , Jenner Katharine H , MacGregor Graham A 
Published: November 2016

ObjectivesTo investigate the free sugars and calorie content of carbonated sugar-sweetened beverages (CSSB) available in the main UK supermarkets.Study designWe carried out a cross-sectional survey in 2014 of 169 CSSB.MethodsThe free sugars (sugars g/100 mL) and calorie (kcal/100 mL) were collected from product packaging and nutrient information panels of CSSB available in 9 main UK supermarkets.ResultsThe average free sugars content in CSSB was 30.1±10.7 g/330 mL, and 91% of CSSB would receive a ‘red’ (high) label for sugars per serving. There was a large variation in sugars content between different flavours of CSSB and within the same type of flavour ranging from 3.3 to 52.8 g/330 mL. On average, ginger beer (38.5±9.9 g/330 mL) contained the highest amounts of sugars and ginger ale (22.9±7.7 g/330 mL) contained the lowest. Cola flavour is the most popular flavour in the UK with an average free sugars content of 35.0±1.1 g/330 mL. On average, the supermarket own brand contained lower levels of sugars than branded products (27.9±10.6 vs 31.6±10.6 g/330 mL, p=0.02). The average calorie content in CSSB was 126.1±43.5 kcal/330 mL. Cola flavour had a calorie content of 143.5±5.2 kcal/330 mL. Among the 169 products surveyed, 55% exceeded the maximum daily recommendation for free sugars intake (30 g) per 330 mL.ConclusionsFree sugars content of CSSB in the UK is high and is a major contributor to free sugars intake. There is a wide variation in the sugars content of CSSB and even within the same flavour of CSSB. These findings demonstrate that the amount of free sugars added to CSSB can be reduced without technical issues, and there is an urgent need to set incremental free sugars reduction targets. A reduction in sugars content and overall CSSB consumption will be very beneficial in reducing obesity, type 2 diabetes and dental caries.
Excellent low-frequency sound absorption of radial membrane acoustic metamaterial
Authors: Gao Nansha , Wu Jiu Hui , Hou Hong , Yu Lie 
Published: November 2016

This paper proposes a new radial membrane acoustic metamaterial (RMAM) structure, wherein a layer membrane substrate is covered with a rigid ring (polymethyl methacrylate frame and aluminum lump). The dispersion relationships, transmission spectra and displacement fields of the eigenmodes of this radial membrane acoustic metamaterial are studied with FEM. In contrast to the traditional radial phononic crystals (RPCs), the proposed structures can open bandgaps (BGs) in lower frequency range (0–300 Hz). Simulation results show that the physical mechanism behind the bandgaps is the coupling effects between the rotational vibration of aluminum lump and the transverse vibration of membrane. Geometrical parameters which can adjust the bandgaps’ widths or positions are analyzed. Finally, we investigate the axial sound transmission loss of this acoustic metamaterial structure, and discuss the effects of factor loss, membrane thickness and the number of layers of unit cell on the axial sound transmission loss. Dynamic effective density proves the accuracy of the FEM results. This kind of structure has potential application in pipe or circular ring structure for damping/noise reduction.
Production of nearly monodisperse Fe3O4 and Fe@Fe3O4 nanoparticles in aqueous medium and their surface modification for biomedical applications
Authors: Tegafaw Tirusew , Xu Wenlong , Lee Sang Hyup , Chae Kwon Seok , Chang Yongmin , Lee Gang Ho 
Published: November 2016

Iron (Fe)-based nanoparticles are extremely valuable in biomedical applications owing to their low toxicity and high magnetization values at room temperature. In this study, we synthesized nearly monodisperse iron oxide (Fe3O4) and Fe@Fe3O4 (core: Fe, shell: Fe3O[Formula: see text] nanoparticles in aqueous medium under argon flow and then, coated them with various biocompatible ligands and silica. In this study, eight types of surface-modified nanoparticles were investigated, namely, Fe3O4@PAA (PAA = polyacrylic acid; [Formula: see text] of PAA = 5100 amu and 15,000 amu), Fe3O4@PAA–FA (FA = folic acid; [Formula: see text] of PAA = 5100 amu and 15,000 amu), Fe3O4@PEI–fluorescein (PEI = polyethylenimine; [Formula: see text] of PEI = 1300 amu), Fe@Fe3O4@PEI ([Formula: see text] of PEI = 10,000 amu), Fe3O4@SiO2 and Fe@Fe3O4@SiO2 nanoparticles. We characterized the prepared surface-modified nanoparticles using high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) absorption spectroscopy, a superconducting quantum interference device (SQUID), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL) spectroscopy and confocal microscopy. Finally, we measured the cytotoxicity of the samples. The results indicate that the surface-modified nanoparticles are biocompatible and are potential candidates for various biomedical applications.
Dysregulation of Rab37-Mediated Cross-talk between Cancer Cells and Endothelial Cells via Thrombospondin-1 Promotes Tumor Neovasculature and Metastasis
Authors: Tzeng Hong-Tai , Tsai Chung-Han , Yen Yi-Ting , Cheng Hung-Chi , Chen Yi-Chieh , Pu Shih-Wen , Wang Yu-Shiuan , Shan Yan-Shen , Tseng Yau-Lin , Su Wu-Chou , Lai Wu-Wei , Wu Li-Wha , Wang Yi-Ching 
Published: November 2016

Abstract
Purpose: Accumulating evidence indicates that factors secreted by cancer epithelial cells shape the tumor microenvironment to promote cancer invasion and metastasis. Recent studies also shed light on alterations of Rab small GTPase–mediated exocytosis in tumorigenesis. However, the mechanisms for Rab-mediated exocytosis in tumor microenvironment remain elusive. We aimed to investigate the interplay between Rab37-mediated exocytosis and tumor microenvironment, focusing on endothelial cell motility and angiogenesis.
Experimental Design: We performed fluorescence IHC for Rab37, thrombospondin-1 (TSP1, an antiangiogenesis factor), and angiogenesis marker CD31 in 183 surgically resected esophageal squamous cell carcinoma (ESCC) patient samples. Cell migration, invasion, angiogenesis, and tumor metastasis were measured.
Results: ESCC patients with low expression of Rab37 or TSP1 significantly correlated with high CD31 expression and were associated with worse progression-free survival. The multivariate Cox regression analysis showed that concordant low expression of both Rab37 and TSP1 was an independent prognostic factor of ESCC patients. Rab37-mediated exocytosis of TSP1 led to the inhibition of neovasculature in vitro and in vivo. Secreted TSP1 from cancer cells with Rab37 exocytic function inhibited the p-FAK/p-paxillin/p-ERK migration signaling in both cancer epithelial cells and their surrounding endothelial cells. Dysfunction of Rab37 or loss of TSP1 abrogated the suppressive effects on angiogenesis and metastasis.
Conclusions: Our findings suggest that Rab37-mediated TSP1 secretion in cancer cells suppresses metastasis and angiogenesis via a cross-talk with endothelial cells and reveal a novel component of the vesicular exocytic machinery in tumor microenvironment and tumor progression. Dysregulation of Rab37/TSP1 axis has clinical implications for prognosis prediction. Clin Cancer Res; 23(9); 2335–45. ©2016 AACR.
Combinatorial Drug Screening Identifies Ewing Sarcoma–specific Sensitivities
Authors: Radic-Sarikas Branka , Tsafou Kalliopi P. , Emdal Kristina B. , Papamarkou Theodore , Huber Kilian V. M. , Mutz Cornelia , Toretsky Jeffrey A. , Bennett Keiryn L. , Olsen Jesper V. , Brunak Søren , Kovar Heinrich , Superti-Furga Giulio 
Published: November 2016

Abstract
Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma–specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1. We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1–dependent manner. Mol Cancer Ther; 16(1); 88–101. ©2016 AACR.
Near Infrared Photoimmunotherapy in a Transgenic Mouse Model of Spontaneous Epidermal Growth Factor Receptor (EGFR)-expressing Lung Cancer
Authors: Nakamura Yuko , Ohler Zoe Weaver , Householder Deborah , Nagaya Tadanobu , Sato Kazuhide , Okuyama Shuhei , Ogata Fusa , Daar Dagane , Hoa Tieu , Choyke Peter L. , Kobayashi Hisataka 
Published: November 2016

Abstract
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by a sensitive photoabsorber following exposure to NIR light. Most studies of NIR-PIT have been performed in xenograft models of cancer. The purpose of this study was to evaluate the therapeutic effects of NIR-PIT in a transgenic model of spontaneous lung cancer expressing human EGFR (hEGFR-TL). Mice were separated into 3 groups for the following treatments: (1) no treatment (control); (2) 150 μg of photoabsorber, IR700, conjugated to panitumumab, an antibody targeting EGFR [antibody–photoabsorber conjugate (APC)] intravenously (i.v.) only; (3) 150 μg of APC i.v. with NIR light administration. Each treatment was performed every week up to three weeks. MRI was performed 1 day before and 3, 6, 13, 20, 27, and 34 days after first NIR-PIT. The relative volume of lung tumors was calculated from the tumor volume at each MRI time point divided by the initial volume. Steel test for multiple comparisons was used to compare the tumor volume ratio with that of control. Tumor volume ratio was inhibited significantly in the NIR-PIT group compared with control group (P &lt; 0.01 at all time points). In conclusion, NIR-PIT effectively treated a spontaneous lung cancer in a hEGFR-TL transgenic mouse model. MRI successfully monitored the therapeutic effects of NIR-PIT. Mol Cancer Ther; 16(2); 408–14. ©2016 AACR.
Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction
Authors: Michael Gibson C. , Korjian Serge , Tricoci Pierluigi , Daaboul Yazan , Yee Megan , Jain Purva , Alexander John H. , Steg P. Gabriel , Lincoff A. Michael , Kastelein John J.P. , Mehran Roxana , D’Andrea Denise M. , Deckelbaum Lawrence I. , Merkely Bela , Zarebinski Maciej , Ophuis Ton Oude , Harrington Robert A. 
Published: November 2016

Background:
Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein–mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction.

Methods:
The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy).

Results:
A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar.

Conclusions:
Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT02108262.
Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial)
Authors: Sposato Luciano A. , Cohen Geoffrey , Wardlaw Joanna M. , Sandercock Peter , Lindley Richard I. , Hachinski Vladimir , von Kummer Rudiger , von Heijne Anders , Bradey Nick , Peeters Andre , Cala Lesley , Adami Alessandro , Morris Zoe , Farrall Andrew , Potter Gillian 
Published: November 2016

Background and Purpose—
In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging.

Methods—
We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation.

Results—
Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33−2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial.

Conclusions—
We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes.

Clinical Trial Registration—

URL:
http://www.isrctn.com
. Unique identifier: ISRCTN25765518.
Quantifying the Eddy–Jet Feedback Strength of the Annular Mode in an Idealized GCM and Reanalysis Data
Authors: Ma Ding , Hassanzadeh Pedram , Kuang Zhiming 
Published: November 2016

Abstract
A linear response function (LRF) that relates the temporal tendency of zonal-mean temperature and zonal wind to their anomalies and external forcing is used to accurately quantify the strength of the eddy–jet feedback associated with the annular mode in an idealized GCM. Following a simple feedback model, the results confirm the presence of a positive eddy–jet feedback in the annular mode dynamics, with a feedback strength of 0.137 day−1 in the idealized GCM. Statistical methods proposed by earlier studies to quantify the feedback strength are evaluated against results from the LRF. It is argued that the mean-state-independent eddy forcing reduces the accuracy of these statistical methods because of the quasi-oscillatory nature of the eddy forcing. Assuming the mean-state-independent eddy forcing is sufficiently weak at the low-frequency limit, a new method is proposed to approximate the feedback strength as the regression coefficient of low-pass-filtered eddy forcing onto the low-pass-filtered annular mode index. When time scales longer than 200 days are used for the low-pass filtering, the new method produces accurate results in the idealized GCM compared to the value calculated from the LRF. The estimated feedback strength in the southern annular mode converges to 0.121 day−1 in reanalysis data using the new method. This work also highlights the significant contribution of medium-scale waves, which have periods less than 2 days, to the annular mode dynamics. Such waves are filtered out if eddy forcing is calculated from daily mean data. The present study provides a framework to quantify the eddy–jet feedback strength in GCMs and reanalysis data.
The Energetics of Southern Ocean Upwelling
Authors: Hogg Andrew McC. , Spence Paul , Saenko Oleg A. , Downes Stephanie M. 
Published: November 2016

AbstractThe ocean’s meridional overturning circulation is closed by the upwelling of dense, carbon-rich waters to the surface of the Southern Ocean. It has been proposed that upwelling in this region is driven by strong westerly winds, implying that the intensification of Southern Ocean winds in recent decades may have enhanced the rate of upwelling, potentially affecting the global overturning circulation. However, there is no consensus on the sensitivity of upwelling to winds or on the nature of the connection between Southern Ocean processes and the global overturning circulation. In this study, the sensitivity of the overturning circulation to changes in Southern Ocean westerly wind stress is investigated using an eddy-permitting ocean–sea ice model. In addition to a suite of standard circulation metrics, an energy analysis is used to aid dynamical interpretation of the model response. Increased Southern Ocean wind stress enhances the upper cell of the overturning circulation through creation of available potential energy in the Southern Hemisphere, associated with stronger upwelling of deep water. Poleward shifts in the Southern Ocean westerlies lead to a complicated transient response, with the formation of bottom water induced by increased polynya activity in the Weddell Sea and a weakening of the upper overturning cell in the Northern Hemisphere. The energetic consequences of the upper overturning cell response indicate an interhemispheric connection to the input of available potential energy in the Northern Hemisphere.