bluuebunny/crossref_metadata_2025 huggingface dataset:
Tocopherols, Tocotrienols and Carotenoids in Kernel Oils Recovered from 15 Apricot (Prunus armeniaca L.) Genotypes
Authors: Górnaś Paweł , Radziejewska‐Kubzdela Elżbieta , Mišina Inga , Biegańska‐Marecik Róża , Grygier Anna , Rudzińska Magdalena
Published: March 2017

We studied the content of tocopherols, tocotrienols and carotenoids in oil extracted from the kernels of 15 apricot (Prunus armeniaca L.) genotypes and the associated oil yield of the studied samples. The oil yield in apricot kernels was in a wide range of 27.2–61.4% (w/w) dry weight basis. For each class of studied compounds (tocochromanols and carotenoids), a three‐fold difference was found between the lowest and the highest content (78.8–258.5 and 0.15–0.53 mg/100 g of oil, respectively). γ‐Tocopherol accounted for 91–94% of total tocochromanols detected in all tested samples. Lutein, zeaxanthin, β‐cryptoxanthin and β‐carotene were the main compounds among the eight different carotenoids detected in apricot kernel oils; they comprised 76–94% of the total carotenoids content, and compositions were characteristic for specific genotypes. The oil yield and content of lipophilic antioxidants in apricot kernel oils were significantly affected by the genotype. The oil yield was negatively correlated with the total amount of tocochromanols (r = −0.910) and carotenoids (r = −0.704) in apricot kernel oils.
Analysis of miscible displacement through porous media with vanishing molecular diffusion and singular wells
Authors: Droniou Jérôme , Talbot Kyle S.
Published: March 2017

This article proves the existence of solutions to a model of incompressible miscible displacement through a porous medium, with zero molecular diffusion and modelling wells by spatial measures. We obtain the solution by passing to the limit on problems indexed by vanishing molecular diffusion coefficients. The proof employs cutoff functions to excise the supports of the measures and the discontinuities in the permeability tensor, thus enabling compensated compactness arguments used by Y. Amirat and A. Ziani for the analysis of the problem with

L^{2}

wells (Amirat and Ziani, 2004 [1]). We give a novel treatment of the diffusion–dispersion term, which requires delicate use of the Aubin–Simon lemma to ensure the strong convergence of the pressure gradient, owing to the troublesome lower-order terms introduced by the localisation procedure.
Paradoxical embolism: Experiences from a single center
Authors: Zhang Hong‐Liang , Liu Zhi‐Hong , Luo Qin , Wang Yong , Zhao Zhi‐Hui , Xiong Chang‐Ming
Published: March 2017

Objective

To present our treatment experiences and the follow‐up data of patients with paradoxical embolism (PDE).

Methods

The clinical characteristics, management, and follow‐up data of all included patients who were diagnosed with PDE at Fuwai Hospital from January 1994 to October 2015 were recorded.

Results

Twelve patients were included; all had a pulmonary embolism, and 8 had deep venous thrombosis. The artery embolisms involved the cerebral artery (7 patients), renal artery (2 patients), mesentery artery (2 patients), popliteal artery (1 patient), descending aorta thrombus (1 patient), and thrombus‐straddled patent foramen ovale (PFO) (1 patient). PFO was found in 3 cases. One patient underwent thrombectomy and PFO closure; Six patients received thrombolysis; and 3 patients were implanted with a vena cava filter. Long‐term anticoagulation with warfarin was recommended for each patient. One patient died from ventricular fibrillation despite cardiopulmonary resuscitation. Eleven patients were discharged with improvements. No late mortality occurred in 8 patients with a complete follow‐up of 10.6–17.7 years. One had a recurrent deep venous thrombosis. No patient had a recurrent pulmonary or arterial embolism. Two patients changed their treatment from warfarin to aspirin; others remained on warfarin. Only 1 case had an occasional gum bleeding.

Conclusions

PDE treatment including thrombolysis, anticoagulation, and embolectomy should be individualized. We recommend long‐term anticoagulation therapy to prevent the recurrence of PDE, especially to those with an intracardiac communication or persistent risk factors for re‐thrombosis.
Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire
Authors: Jutten Roos J. , Peeters Carel F.W. , Leijdesdorff Sophie M.J. , Visser Pieter Jelle , Maier Andrea B. , Terwee Caroline B. , Scheltens Philip , Sikkes Sietske A.M.
Published: March 2017

Introduction

Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A‐IADL‐Q) was developed: a 70‐item proxy‐based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality.

Methods

Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A‐IADL‐Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD). Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum.

Results

We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the MMSE (0.72) and DAD (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia.

Discussion

The A‐IADL‐Q short version (A‐IADL‐Q‐SV) consists of 30 items and has maintained the psychometric quality of the original A‐IADL‐Q. As such, the A‐IADL‐Q‐SV is a concise measure of functional decline.
Waldenström’s macroglobulinemia masquerading as ovarian cancer with peritoneal carcinomatosis, ascites, and elevated CA-125
Authors: Eulitt Patrick , Fabian Denise , Kelly Crystal , Hemminger Jessica , William Basem M.
Published: March 2017

Waldenström’s macroglobulinemia is a rare hematology malignancy which often presents with “B symptoms,” anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström’s macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström’s macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.
Speaking to the heart: Social exclusion and reliance on feelings versus reasons in persuasion
Authors: Lu Fang‐Chi , Sinha Jayati
Published: March 2017

The authors of this study identify an alternative frame of communication for persuading people who feel socially excluded to behave in ways that benefit individual and social wellbeing, regardless of future connection possibilities. The authors suggest that socially excluded (included) consumers tend to rely on affect (cognition) in processing information, and to consequently prefer persuasive messages based on feelings (reasons). The effect occurs because people tend to ruminate about exclusionary events, which depletes self‐regulatory resources. Thus, distraction that interferes with rumination can mitigate the social exclusion effect on affective processing. The authors present findings from five studies across various paradigms promoting personal and social wellbeing (i.e., donating blood, recycling, and consuming healthful foods) and discuss the theoretical and policy implications.
Initial experience with the subcutaneous implantable cardioverter‐defibrillator in a single Japanese center
Authors: Nishii Nobuhiro , Tachibana Motomi , Morimoto Yoshimasa , Kawada Satoshi , Miyoshi Akihito , Sugiyama Hiroyasu , Nakagawa Koji , Watanabe Atsuyuki , Nakamura Kazufumi , Morita Hiroshi , Ito Hiroshi
Published: March 2017

Background

The subcutaneous implantable cardioverter‐defibrillator (S‐ICD) is recognized as a viable alternative to the transvenous ICD. The safety and efficacy of this device has been demonstrated in Western countries, but studies with S‐ICD implantation in Japanese patients have not been reported.

Methods and results

Twelve patients received an S‐ICD implant in our institute between February and September 2016. All S‐ICDs were successfully implanted without complications. One appropriate and one inappropriate therapy was identified.

Conclusions

S‐ICD implantation appears to provide a viable alternative to transvenous ICD implantation for some Japanese patients. However, we should perform careful follow‐up of patients to eliminate inappropriate therapy.
The Global Health Crisis
Authors: de Campos Thana Cristina
Published: March 2017

Proposing a new view of global justice based on natural law, this book presents a discussion of the key ethical values in contemporary medicine and health, notably in relation to neglected diseases like malaria, Ebola and Zika. The lack of treatments for such diseases point to a global health crisis. Thana Cristina de Campos provides a general framework, based on global commutative justice, for discussion of the ethical responsibilities of international stakeholders, mapping the varying duties they have, and their content and force. She also addresses the urgent need for reforms to the international legal rules on bioethics, notably the system of intellectual property rights. These ideas will be of interest to those who are looking for a more nuanced view of the human right to health than that provided by advocates in the globalist mainstream.
Degrees of Unsolvability
Authors: Lerman Manuel
Published: March 2017

Since their inception, the Perspectives in Logic and Lecture Notes in Logic series have published seminal works by leading logicians. Many of the original books in the series have been unavailable for years, but they are now in print once again. In this volume, the eleventh publication in the Perspectives in Logic series, Manuel Lerman presents a systematic study of the interaction between local and global degree theory. He introduces the reader to the fascinating combinatorial methods of recursion theory while simultaneously showing how to use these methods to prove global theorems about degrees. The intended reader will have already taken a graduate-level course in recursion theory, but this book will also be accessible to those with some background in mathematical logic and a feeling for computability. It will prove a key reference to enable readers to easily locate facts about degrees and it will direct them to further results.
Generalized fluid theory including non-Maxwellian kinetic effects
Authors: Izacard Olivier
Published: March 2017

The results obtained by the plasma physics community for the validation and the prediction of turbulence and transport in magnetized plasmas come mainly from the use of very central processing unit (CPU)-consuming particle-in-cell or (gyro)kinetic codes which naturally include non-Maxwellian kinetic effects. To date, fluid codes are not considered to be relevant for the description of these kinetic effects. Here, after revisiting the limitations of the current fluid theory developed in the 19th century, we generalize the fluid theory including kinetic effects such as non-Maxwellian super-thermal tails with as few fluid equations as possible. The collisionless and collisional fluid closures from the nonlinear Landau Fokker–Planck collision operator are shown for an arbitrary collisionality. Indeed, the first fluid models associated with two examples of collisionless fluid closures are obtained by assuming an analytic non-Maxwellian distribution function (e.g. the INMDF (Izacard, O. 2016b Kinetic corrections from analytic non-Maxwellian distribution functions in magnetized plasmas. Phys. Plasmas 23, 082504) that stands for interpreted non-Maxwellian distribution function). One of the main differences with the literature is our analytic representation of the distribution function in the velocity phase space with as few hidden variables as possible thanks to the use of non-orthogonal basis sets. These new non-Maxwellian fluid equations could initiate the next generation of fluid codes including kinetic effects and can be expanded to other scientific disciplines such as astrophysics, condensed matter or hydrodynamics. As a validation test, we perform a numerical simulation based on a minimal reduced INMDF fluid model. The result of this test is the discovery of the origin of particle and heat diffusion. The diffusion is due to the competition between a growing INMDF on short time scales due to spatial gradients and the thermalization on longer time scales. The results shown here could provide the insights to break some of the unsolved puzzles of turbulence.
The Bioethicist Who Cried “Synthetic Biology”: An Analysis of the Function of Bioterrorism Predictions in Bioethics
Authors: HOLM SØREN
Published: March 2017

This article analyzes a specter that has haunted bioethics almost since its inception, namely the specter of the misuse of biotechnology by maleficent agents bent on mass destruction, or the complete eradication of human kind and life as we know it. The article provides a general account of why bioethicists cry “catastrophic bioterrorism potential” when new biotechnologies emerge, and an analysis of the arguments that flow from the prediction, especially in relation to synthetic biology.
Engaging Women: Addressing the Gender Gap in Women’s Networking and Productivity
Authors: Barnes Tiffany D. , Beaulieu Emily
Published: March 2017

Women earn 40% of new PhDs in political science; however, once they enter the profession, they have strikingly different experiences than their male counterparts—particularly in the small but influential field of political methodology. For several years, the Society for Political Methodology, with support from the National Science Foundation, has attempted to address this gender gap through the Visions in Methodology (VIM) program. VIM features an annual conference that brings women together to present and discuss their research and to participate in professional-development sessions. Do programs like VIM have the desired impact? Using an original survey of political scientists, this study provides insights into the ways that bringing women together in small-group settings like VIM might facilitate networking and enhance productivity. In particular, the study finds that women who attend the VIM conference are better networked and more productive in terms of publication.
POPULAR MAGAZINES, NEW LIBERAL DISCOURSE AND AMERICAN DEMOCRACY, 1890s–1914
Authors: Schneirov Matthew
Published: March 2017

The study of the mass circulation “popular magazine” during the Gilded Age and Progressive Era was revived during the 1990s as part of the emerging fields of gender studies, consumer studies, and the study of the new middle class. Richard Ohmann's seminal work viewed these magazines through the lens of the political economy and class relations of an emerging corporate capitalist society and explored the relationship between mass culture and the political economy of capitalism. This paper reexamines the connection between a national mass culture, the new middle class, and an emerging corporate capitalist society through the lens of post-structuralist discourse theory. Corporate capitalism is conceptualized as in part a discourse, the new liberalism, which incorporated or rearticulated populist and socialist discourses and in doing so temporarily won the consent of the capitalist class, middle classes, and segments of the working class. Through the pages of popular magazines readers were offered pieces of a new discourse that embraced corporations rather than the “free market,” women's entry into public life, and new constructions of the self. During the muckraking era, elements of socialism and populism were integrated into mainstream American culture. Overall, the essay argues that a discourse perspective on popular magazines can open up new perspectives on corporate capitalism and the new liberalism. While corporate capitalism marked the decline of the producer–republican tradition, it also marked the emergence of an American social democratic tradition, a mixture of capitalist and socialist social formations.
IL-15 sustains IL-7R-independent ILC2 and ILC3 development
Authors: Robinette Michelle L. , Bando Jennifer K. , Song Wilbur , Ulland Tyler K. , Gilfillan Susan , Colonna Marco
Published: March 2017

The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra−/− mice. Il7ra−/− ILC2 primarily express an ST2− phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra−/− siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra−/− ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling.
USP9X regulates centrosome duplication and promotes breast carcinogenesis
Authors: Li Xin , Song Nan , Liu Ling , Liu Xinhua , Ding Xiang , Song Xin , Yang Shangda , Shan Lin , Zhou Xing , Su Dongxue , Wang Yue , Zhang Qi , Cao Cheng , Ma Shuai , Yu Na , Yang Fuquan , Wang Yan , Yao Zhi , Shang Yongfeng , Shi Lei
Published: March 2017

Defective centrosome duplication is implicated in microcephaly and primordial dwarfism as well as various ciliopathies and cancers. Yet, how the centrosome biogenesis is regulated remains poorly understood. Here we report that the X-linked deubiquitinase USP9X is physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. We demonstrate that USP9X is an integral component of centrosome and is required for centrosome biogenesis. Loss-of-function of USP9X impairs centrosome duplication and gain-of-function of USP9X promotes centrosome amplification and chromosome instability. Significantly, USP9X is overexpressed in breast carcinomas, and its level of expression is correlated with that of CEP131 and higher histologic grades of breast cancer. Indeed, USP9X, through regulation of CEP131 abundance, promotes breast carcinogenesis. Our experiments identify USP9X as an important regulator of centrosome biogenesis and uncover a critical role for USP9X/CEP131 in breast carcinogenesis, supporting the pursuit of USP9X/CEP131 as potential targets for breast cancer intervention.
Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats
Authors: Song Ji Wei , Li Kun , Liang Zhuo Wen , Dai Chen , Shen Xue Feng , Gong Yu Ze , Wang Shuang , Hu Xue Yu , Wang Zhe
Published: March 2017

Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.
Problems with visual statistical learning in developmental dyslexia
Authors: Sigurdardottir Heida Maria , Danielsdottir Hilda Bjork , Gudmundsdottir Margret , Hjartarson Kristjan Helgi , Thorarinsdottir Elin Astros , Kristjánsson Árni
Published: March 2017

Previous research shows that dyslexic readers are impaired in their recognition of faces and other complex objects, and show hypoactivation in ventral visual stream regions that support word and object recognition. Responses of these brain regions are shaped by visual statistical learning. If such learning is compromised, people should be less sensitive to statistically likely feature combinations in words and other objects, and impaired visual word and object recognition should be expected. We therefore tested whether people with dyslexia showed diminished capability for visual statistical learning. Matched dyslexic and typical readers participated in tests of visual statistical learning of pairs of novel shapes that frequently appeared together. Dyslexic readers on average recognized fewer pairs than typical readers, indicating some problems with visual statistical learning. These group differences were not accounted for by differences in intelligence, ability to remember individual shapes, or spatial attention paid to the stimuli, but other attentional problems could play a mediating role. Deficiencies in visual statistical learning may in some cases prevent appropriate experience-driven shaping of neuronal responses in the ventral visual stream, hampering visual word and object recognition.
Quantitative chromatin proteomics reveals a dynamic histone post-translational modification landscape that defines asexual and sexual Plasmodium falciparum parasites
Authors: Coetzee Nanika , Sidoli Simone , van Biljon Riëtte , Painter Heather , Llinás Manuel , Garcia Benjamin A. , Birkholtz Lyn-Marie
Published: March 2017

Gene expression in Plasmodia integrates post-transcriptional regulation with epigenetic marking of active genomic regions through histone post-translational modifications (PTMs). To generate insights into the importance of histone PTMs to the entire asexual and sexual developmental cycles of the parasite, we used complementary and comparative quantitative chromatin proteomics to identify and functionally characterise histone PTMs in 8 distinct life cycle stages of P. falciparum parasites. ~500 individual histone PTMs were identified of which 106 could be stringently validated. 46 individual histone PTMs and 30 co-existing PTMs were fully quantified with high confidence. Importantly, 15 of these histone PTMs are novel for Plasmodia (e.g. H3K122ac, H3K27me3, H3K56me3). The comparative nature of the data revealed a highly dynamic histone PTM landscape during life cycle development, with a set of histone PTMs (H3K4ac, H3K9me1 and H3K36me2) displaying a unique and conserved abundance profile exclusively during gametocytogenesis (P < 0.001). Euchromatic histone PTMs are abundant during schizogony and late gametocytes; heterochromatic PTMs mark early gametocytes. Collectively, this data provides the most accurate, complete and comparative chromatin proteomic analyses of the entire life cycle development of malaria parasites. A substantial association between histone PTMs and stage-specific transition provides insights into the intricacies characterising Plasmodial developmental biology.
Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout
Authors: Tan Philip K. , Liu Sha , Gunic Esmir , Miner Jeffrey N.
Published: March 2017

Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics. A URAT1 binding assay using radiolabeled verinurad revealed that distinct URAT1 inhibitors benzbromarone, sulfinpyrazone and probenecid all inhibit verinurad binding via a competitive mechanism. However, mutations made within the predicted transporter substrate channel differentially altered the potency for individual URAT1 inhibitors. Overall, our results suggest that URAT1 inhibitors bind to a common site in the core of the transporter and sterically hinder the transit of uric acid through the substrate channel, albeit with vastly different potencies and with differential interactions with specific URAT1 amino acids.
TGFBI Gene Mutation Analysis of Clinically Diagnosed Granular Corneal Dystrophy Patients Prior to PTK: A Pilot Study from Eastern China
Authors: Zeng Li , Zhao Jing , Chen Yingjun , Zhao Feng , Li Meiyan , Chao-Shern Connie , Moore Tara , Marshall John , Zhou Xingtao
Published: March 2017

This study investigated the TGFBI gene mutation types in outpatients clinically diagnosed with granular corneal dystrophy (GCD) prior to phototherapeutic keratectomy (PTK), also calculated the mutation rate of subjects with normal corneas, but positive family history. Clinical GCD outpatients and consanguineous family members were enrolled in this study. Among total 42 subjects: 24 patients from 23 unrelated families had typical signs of GCD on corneas; 5 patients from 5 unrelated families had atypical signs; 13 subjects from 11 unrelated families had no corneal signs but positive family history. Using Avellino gene test kit, the TGFBI mutation detection was performed on DNA samples from all subjects. 36 subjects were detected to carry heterozygous TGFBI gene mutations. Among 24 clinical GCD patients, the proportion of R124H, R555Q, R124L, R555W and R124C were 37.5%, 16.7%, 25.0%, 20.8% and 0%, respectively, and 2 patients had been diagnosed with GCD according to the opacities thriving after LASIK (R124H) and PRK (R555W). The mutation rate of 13 subjects having no signs but positive family history was 69.2%. R124H mutation is the most prominent mutation type among GCD outpatients in Eastern China. It is recommended to conduct gene detection for patients with positive family history prior to refractive surgeries.
Alterations in erythrocyte fatty acid composition in preclinical Alzheimer’s disease
Authors: Goozee Kathryn , Chatterjee Pratishtha , James Ian , Shen Kaikai , Sohrabi Hamid R. , Asih Prita R. , Dave Preeti , Ball Bethany , ManYan Candice , Taddei Kevin , Chung Roger , Garg Manohar L. , Martins Ralph N.
Published: March 2017

Brain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65–90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a ‘base model’ comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells
Authors: Schuster Manuel , Schnell Leonie , Feigl Peter , Birkhofer Carina , Mohr Katharina , Roeder Maurice , Carle Stefan , Langer Simon , Tippel Franziska , Buchner Johannes , Fischer Gunter , Hausch Felix , Frick Manfred , Schwan Carsten , Aktories Klaus , Schiene-Fischer Cordelia , Barth Holger
Published: March 2017

Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.
G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
Authors: Pan Bin , Wang Xiangmin , Nishioka Chie , Honda Goichi , Yokoyama Akihito , Zeng Lingyu , Xu Kailin , Ikezoe Takayuki
Published: March 2017

Thrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay followed by MALDI-TOF MS and western blot analysis, and identified G-protein coupled receptor 15 (GPR15) as a binding partner of TME5. TME5 rescued growth inhibition and apoptosis caused by calcineurin inhibitor FK506 in vascular ECs isolated from wild type (WT) C57BL/6 mice. On the other hand, TME5 failed to protect ECs isolated from GPR15 knockout (GPR15 KO) mice from FK506-caused vascular injury. TME5 induced activation of extracellular signal-regulated kinase (ERK) and increased level of anti-apoptotic proteins in a GPR15 dependent manner. In addition, in vivo Matrigel plug angiogenesis assay found that TME5 stimulated angiogenesis in mice. TME5 promoted endothelial migration in vitro. Furthermore, TME5 increased production of NO in association with activated endothelial NO synthase (eNOS) in ECs. All these pro-angiogenesis functions of TME5 were abolished by knockout of GPR15. Our findings suggest that GPR15 plays an important role in mediating cytoprotective function as well as angiogenesis of TM.
Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts
Authors: Li Wenjiao , Wang Wangsheng , Zuo Rujuan , Liu Chao , Shu Qun , Ying Hao , Sun Kang
Published: March 2017

Serum amyloid A1 (SAA1) is an acute response protein, which is mainly produced by the liver, during infection. However, it remains unknown whether SAA1 can be produced in human fetal membranes where it is able to elicit events pertinent to labor initiation. We demonstrated that SAA1 was expressed in the fibroblasts and epithelium of the amnion and the trophoblasts of the chorion. Further study in human amnion fibroblasts showed that SAA1 production was augmented by interleukin-1β (IL-1β) and cortisol alone and synergistically, and SAA1 in turn induced the expression of IL-1β, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and PGE2 production. These effects of SAA1 were mediated through activation of the NF-κB, p38 and ERK1/2 pathways via the toll-like receptor 4 (TLR4). Inhibition of TLR4 attenuated not only SAA1-induced activation of NF-κB, p38 and ERK1/2 but also increases in IL-1β, IL-6 and COX-2 expression. Moreover, SAA1 expression was increased in human amnion tissue following spontaneous labor. In conclusion, this study has demonstrated for the first time that SAA1 can be produced in human fetal membranes, which can be greatly induced in the presence of proinflammatory cytokines and glucocorticoids thereby producing effects associated with parturition.
The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
Authors: Pritchard Manon F. , Powell Lydia C. , Khan Saira , Griffiths Peter C. , Mansour Omar T. , Schweins Ralf , Beck Konrad , Buurma Niklaas J. , Dempsey Christopher E. , Wright Chris J. , Rye Philip D. , Hill Katja E. , Thomas David W. , Ferguson Elaine L.
Published: March 2017

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.
The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans
Authors: dos Reis Thaila Fernanda , Nitsche Benjamin M. , de Lima Pollyne Borborema Almeida , de Assis Leandro José , Mellado Laura , Harris Steven D. , Meyer Vera , dos Santos Renato A. Corrêa , Riaño-Pachón Diego M. , Ries Laure Nicolas Annick , Goldman Gustavo H.
Published: March 2017

One of the drawbacks during second-generation biofuel production from plant lignocellulosic biomass is the accumulation of glucose, the preferred carbon source of microorganisms, which causes the repression of hydrolytic enzyme secretion by industrially relevant filamentous fungi. Glucose sensing, subsequent transport and cellular signalling pathways have been barely elucidated in these organisms. This study therefore characterized the transcriptional response of the filamentous fungus Aspergillus nidulans to the presence of high and low glucose concentrations under continuous chemostat cultivation with the aim to identify novel factors involved in glucose sensing and signalling. Several transcription factor- and transporter-encoding genes were identified as being differentially regulated, including the previously characterized glucose and xylose transporter HxtB. HxtB was confirmed to be a low affinity glucose transporter, localizing to the plasma membrane under low- and high-glucose conditions. Furthermore, HxtB was shown to be involved in conidiation-related processes and may play a role in downstream glucose signalling. A gene predicted to encode the protein kinase PskA was also identified as being important for glucose metabolism. This study identified several proteins with predicted roles in glucose metabolic processes and provides a foundation for further investigation into the response of biotechnologically important filamentous fungi to glucose.
Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow
Authors: Saino Nicola , Ambrosini Roberto , Albetti Benedetta , Caprioli Manuela , De Giorgio Barbara , Gatti Emanuele , Liechti Felix , Parolini Marco , Romano Andrea , Romano Maria , Scandolara Chiara , Gianfranceschi Luca , Bollati Valentina , Rubolini Diego
Published: March 2017

Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodicClockgene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation atClockpoly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation atClockmay be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.
Y14 governs p53 expression and modulates DNA damage sensitivity
Authors: Lu Chia-Chen , Lee Chi-Chieh , Tseng Ching-Tzu , Tarn Woan-Yuh
Published: March 2017

Y14 is a core component of the exon junction complex (EJC), while it also exerts cellular functions independent of the EJC. Depletion of Y14 causes G2/M arrest, DNA damage and apoptosis. Here we show that knockdown of Y14 induces the expression of an alternative spliced isoform of p53, namely p53β, in human cells. Y14, in the context of the EJC, inhibited aberrant exon inclusion during the splicing of p53 pre-mRNA, and thus prevent p53β expression. The anti-cancer agent camptothecin specifically suppressed p53β induction. Intriguingly, both depletion and overexpression of Y14 increased overall p53 protein levels, suggesting that Y14 governs the quality and quantity control of p53. Moreover, Y14 depletion unexpectedly reduced p21 protein levels, which in conjunction with aberrant p53 expression accordingly increased cell sensitivity to genotoxic agents. This study establishes a direct link between Y14 and p53 expression and suggests a function for Y14 in DNA damage signaling.
Bioinspired fractal electrodes for solar energy storages
Authors: Thekkekara Litty V. , Gu Min
Published: March 2017

Solar energy storage is an emerging technology which can promote the solar energy as the primary source of electricity. Recent development of laser scribed graphene electrodes exhibiting a high electrical conductivity have enabled a green technology platform for supercapacitor-based energy storage, resulting in cost-effective, environment-friendly features, and consequent readiness for on-chip integration. Due to the limitation of the ion-accessible active porous surface area, the energy densities of these supercapacitors are restricted below ~3 × 10−3 Whcm−3. In this paper, we demonstrate a new design of biomimetic laser scribed graphene electrodes for solar energy storage, which embraces the structure of Fern leaves characterized by the geometric family of space filling curves of fractals. This new conceptual design removes the limit of the conventional planar supercapacitors by significantly increasing the ratio of active surface area to volume of the new electrodes and reducing the electrolyte ionic path. The attained energy density is thus significantly increased to ~10−1 Whcm−3- more than 30 times higher than that achievable by the planar electrodes with ~95% coulombic efficiency of the solar energy storage. The energy storages with these novel electrodes open the prospects of efficient self-powered and solar-powered wearable, flexible and portable applications.
Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model
Authors: Koyama Satoshi , Matsunaga Shinji , Imanishi Masaki , Maekawa Yoichi , Kitano Hiroya , Takeuchi Hiromi , Tomita Shuhei
Published: March 2017

Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.
PG2 for patients with acute spontaneous intracerebral hemorrhage: a double-blind, randomized, placebo-controlled study
Authors: Chen Chun-Chung , Chen XianXiu , Li Tsai-Chung , Lin Hung-Lin , Chu Yen-Tze , Lee Han-Chung , Cheng Yu-Kai , Chen Der-Cherng , Tsai Shiu-Chiu , Cho Der-Yang , Hsieh Ching-Liang
Published: March 2017

PG2 is an infusible polysaccharide extracted from Astragalus membranaceus, which is a Chinese herb traditionally used for stroke treatment. We investigated the effect of PG2 on patients with spontaneous acute intracerebral hemorrhage (ICH). A total of 61 patients with acute spontaneous ICH were randomized to either the treatment group (TG, 30 patients), which received 3 doses of PG2 (500 mg, IV) per week for 2 weeks, or the control group (CG, 31 patients), which received PG2 placebo. At 84 days after PG2 administration, the percentage of patients with a good Glasgow outcome scale (GOS 4–5) score in the TG was similar to that in the CG (69.0% vs. 48.4%; p = 0.2). The percentage of good mRS scores (0–2) in the TG was similar to that in the CG (62.1% vs. 45.2%; p = 0.3). In addition, no significant differences were seen when comparing differences in the C-reactive protein, erythrocyte sedimentation rate, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α, and S100B levels between baseline and days 4, 7, and 14 after PG2 administration (all p > 0.05). The results are preliminary, necessitating a more thorough assessment.
Precise Photodynamic Therapy of Cancer via Subcellular Dynamic Tracing of Dual-loaded Upconversion Nanophotosensitizers
Authors: Chang Yulei , Li Xiaodan , Zhang Li , Xia Lu , Liu Xiaomin , Li Cuixia , Zhang Youlin , Tu Langping , Xue Bin , Zhao Huiying , Zhang Hong , Kong Xianggui
Published: March 2017

Recent advances in upconversion nanophotosensitizers (UCNPs-PS) excited by near-infrared (NIR) light have led to substantial progress in improving photodynamic therapy (PDT) of cancer. For a successful PDT, subcellular organelles are promising therapeutic targets for reaching a satisfactory efficacy. It is of vital importance for these nanophotosensitizers to reach specifically the organelles and to perform PDT with precise time control. To do so, we have in this work traced the dynamic subcellular distribution, especially in organelles such as lysosomes and mitochondria, of the poly(allylamine)-modified and dual-loaded nanophotosensitizers. The apoptosis of the cancer cells induced by PDT with the dependence of the distribution status of the nanophotosensitizers in organelles was obtained, which has provided an in-depth picture of intracellular trafficking of organelle-targeted nanophotosensitizers. Our results shall facilitate the improvement of nanotechnology assisted photodynamic therapy of cancers.
Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation
Authors: Lu Xiaozhao , Bai Danna , Liu Xiangwei , Zhou Chen , Yang Guodong
Published: March 2017

Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis.