bluuebunny/crossref_metadata_2025 huggingface dataset:
Does stroke location predict walk speed response to gait rehabilitation?
Authors: Jones P. Simon , Pomeroy Valerie M. , Wang Jasmine , Schlaug Gottfried , Tulasi Marrapu S. , Geva Sharon , Rowe Philip J. , Chandler Elizabeth , Kerr Andrew , Baron Jean‐Claude ,   for the SWIFT‐Cast investigators
Published: November 2015

Objectives

Recovery of independent ambulation after stroke is a major goal. However, which rehabilitation regimen best benefits each individual is unknown and decisions are currently made on a subjective basis. Predictors of response to specific therapies would guide the type of therapy most appropriate for each patient. Although lesion topography is a strong predictor of upper limb response, walking involves more distributed functions. Earlier studies that assessed the cortico‐spinal tract (CST) were negative, suggesting other structures may be important.

Experimental Design: The relationship between lesion topography and response of walking speed to standard rehabilitation was assessed in 50 adult‐onset patients using both volumetric measurement of CST lesion load and voxel‐based lesion–symptom mapping (VLSM) to assess non‐CST structures. Two functional mobility scales, the functional ambulation category (FAC) and the modified rivermead mobility index (MRMI) were also administered. Performance measures were obtained both at entry into the study (3–42 days post‐stroke) and at the end of a 6‐week course of therapy. Baseline score, age, time since stroke onset and white matter hyperintensities score were included as nuisance covariates in regression models.

Principal Observations: CST damage independently predicted response to therapy for FAC and MRMI, but not for walk speed. However, using VLSM the latter was predicted by damage to the putamen, insula, external capsule and neighbouring white matter.

Conclusions

Walk speed response to rehabilitation was affected by damage involving the putamen and neighbouring structures but not the CST, while the latter had modest but significant impact on everyday functions of general mobility and gait. Hum Brain Mapp 37:689–703, 2016. © 2015 Wiley Periodicals, Inc.
PTSD Among Aboriginal and Torres Strait Islander People in Custody in Australia: Prevalence and Correlates
Authors: Heffernan Edward , Andersen Kimina , Davidson Fiona , Kinner Stuart A.
Published: November 2015

Mental disorder and trauma experiences are highly prevalent among individuals in custody; however, the impact of posttraumatic stress disorder (PTSD) on functioning is rarely considered. Indigenous Australians are incarcerated at 13 times the rate of nonindigenous Australians and report high levels of trauma exposure and psychological distress. In analysis of the largest systematic study of mental disorder among indigenous Australians in custody (N = 396), we found that the 12‐month prevalence of PTSD was high in both men (12.1%) and women (32.3%). Having PTSD was also associated with high rates of co‐occurring mental disorders (anxiety 31.2%, depression 32.8%, psychosis 24.6%, and substance use, 75.4%), lifetime suicidal ideation (50.1%), and suicide attempts (34.4%). Individuals with PTSD, compared to those without, were more likely to experience other mental disorders, OR = 2.42, 95% CI [1.12, 5.80], p = .022; lifetime suicide thoughts, OR = 2.43, 95% CI [1.34, 4.39], p = .001, and attempts, OR = 2.56, 95% CI [1.33, 4.83], p = .002; and high rates of intoxication at the time of arrest. Despite this, most (58.9%) had not accessed any form of mental health care prior to incarceration. These findings highlight the need to identify and manage PTSD in community and custodial populations.
H2AX phosphorylation level in peripheral blood mononuclear cells as an event‐free survival predictor for bladder cancer
Authors: Turinetto Valentina , Pardini Barbara , Allione Alessandra , Fiorito Giovanni , Viberti Clara , Guarrera Simonetta , Russo Alessia , Anglesio Silvia , Ruo Redda Maria Grazia , Casetta Giovanni , Cucchiarale Giuseppina , Destefanis Paolo , Oderda Marco , Gontero Paolo , Rolle Luigi , Frea Bruno , Vineis Paolo , Sacerdote Carlotta , Giachino Claudia , Matullo Giuseppe
Published: November 2015

Bladder cancer (BC) has a typical aetiology characterized by a multistep carcinogenesis due to environmental exposures, genetic susceptibility, and their interaction. Several lines of evidence suggest that DNA repair plays a role in the development and progression of BC. In particular, the study of individual susceptibility to DNA double strand breaks (DSBs) may provide valuable information on BC risk, and help to identify those patients at high‐risk of either recurrence or progression of the disease, possibly personalizing both surveillance and treatment. Among the different DSB markers, the most well characterized is phosphorylation of the histone H2AX (γ‐H2AX). We assessed any potential role of γ‐H2AX as a molecular biomarker in a case‐control study (146 cases and 146 controls) to identify individuals with increased BC risk and at high‐risk of disease recurrence or progression. We investigated γ‐H2AX levels in peripheral blood mononuclear cells before and after their exposure to ionizing radiation (IR). We did not find any significant difference among cases and controls. However, we observed a significant association between γ‐H2AX basal levels and risk of disease recurrence or progression. In particular, both BC patients as a whole and the subgroup of non‐muscle invasive BC (NMIBC) with high basal H2AX phosphorylation levels had a decreased risk of recurrence or progression (for all BC HR 0.70, 95%CI 0.52–0.94, P = 0.02; for NMIBC HR 0.68, 95%CI 0.50–0.92, P = 0.01), suggesting a protective effect of basal DSB signaling. Our data suggest that γ‐H2AX can be considered as a potential molecular biomarker to identify patients with a higher risk of BC recurrence. © 2015 Wiley Periodicals, Inc.
Expression, modulation, and clinical correlates of the autophagy protein Beclin‐1 in esophageal adenocarcinoma
Authors: Weh Katherine M. , Howell Amy B. , Kresty Laura A.
Published: November 2015

Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and mortality rates and poor survival. Efficacious preventive and treatment options are urgently needed. An increasing number of pharmacologic agents targeting cancer cell death via autophagy mechanisms are being evaluated in hopes of circumventing apoptotic and therapeutic resistance. We report for the first time, loss of Beclin‐1, a key mediator of autophagy, was significantly linked to prognostic factors in EAC. Specifically, Beclin‐1 expression loss occurred in 49.0% of EAC patients versus 4.8% of controls. There was a significant inverse correlation between loss of Beclin‐1 with histologic grade and tumor stage supporting a tumor suppressive role for Beclin‐1. Autophagy modulation linked to cell death was examined in EAC cell lines following treatment with a proanthocyanidin‐rich cranberry extract, C‐PAC, and the commonly used autophagy inducer, rapamycin. C‐PAC induced Beclin‐1‐independent autophagy in EAC cells characterized by reduced phosphorylation at serine 15 and 93, and significant cell death induction. In contrast, rapamycin‐induced autophagy resulted in concomitant, increases in total Beclin‐1 levels as well as Beclin‐1‐phosphorylation in a cell line specific manner, leading to long‐term cell survival. Furthermore, autophagic LC3‐II was induced by C‐PAC following siRNA suppression of Beclin‐1 in EAC cells. Together these data support a prognostic role of Beclin‐1 in EAC with evidence that Beclin‐dependent autophagy induction is agent specific. Future studies are necessary to fully interrogate the role autophagy plays in the progression of normal tissue to EAC and how specific agents targeting autophagic mechanisms can be efficaciously applied for cancer prevention or treatment. © 2015 Wiley Periodicals, Inc.
(p,q)‐Generalization of Szász–Mirakyan operators
Authors: Acar Tuncer
Published: November 2015

In this paper, we introduce new modifications of Szász–Mirakyan operators based on (p,q)‐integers. We first give a recurrence relation for the moments of new operators and present explicit formula for the moments and central moments up to order 4. Some approximation properties of new operators are explored: the uniform convergence over bounded and unbounded intervals is established, direct approximation properties of the operators in terms of the moduli of smoothness is obtained and Voronovskaya theorem is presented. For the particular case p = 1, the previous results for q‐Sz ász–Mirakyan operators are captured. Copyright © 2015 John Wiley & Sons, Ltd.
Bayesian sampling plans for exponential distributions with interval censored samples
Authors: Chen Lee‐Shen , Yang Ming‐Chung , Liang TaChen
Published: November 2015

This article studies the problem of designing Bayesian sampling plans (BSP) with interval censored samples. First, an algorithm for deriving the conventional BSP is proposed. The BSP is shown to possess some monotonicity. Based on the BSP and using the property of monotonicity, a new sampling plan modified by the curtailment procedure is proposed. The resulting curtailed Bayesian sampling plan (CBSP) can reduce the duration time of life test experiment, and it is optimal in the sense that its associated Bayes risk is smaller than the Bayes risk of the BSP if the cost of the duration time of life test experiment is considered. A numerical example to compute the Bayes risks of BSP and CBSP and related quantities is given. Also, a Monte Carlo simulation study is performed to illustrate the performance of the CBSP compared with the BSP. The simulation results demonstrate that our proposed CBSP has better performance because it has smaller risk. The CBSP is recommended. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 604–616, 2015
Compressive test and numerical simulation of center‐notched composite laminates with different crack configurations
Authors: Mingming Ge , Xiaoquan Cheng , Qian Zhang
Published: November 2015

Experimental and computational studies of the composite laminates with thin center notches under axial compressive loading are carried out. A series of compressive testing of the composites with different crack lengths and angles between the loading vector and 0° fiber direction were conducted. The damage mechanisms as well as load–displacement curves are obtained from the test to analyze the effects of crack dimensions on stress distribution and ultimate load. It was shown that the compressive strength of composites drastically reduces when the crack angle goes from 0° to 90°. By studying the fracture surfaces of the tested specimens, all initial cracks within the laminates are found to extend without a straight crack path until fibers fracture simultaneously. Cases that involve crack propagation are modeled for different crack dimensions with a 3D progressive damage finite element analysis using the Abaqus. Numerical simulations qualitatively reproduce the general observations made in the laboratory experiments. POLYM. COMPOS., 38:2631–2641, 2017. © 2015 Society of Plastics Engineers
Thermal and fire retardancy studies of clay‐modified unsaturated polyester/glass fiber composites
Authors: Romanzini Daiane , Cuttica Fabio , Frache Alberto , Zattera Ademir J. , Amico Sandro C.
Published: November 2015

The aim of this study was to investigate the effect of new, cation‐exchanged, and silane modified montmorillonite nanoclays fillers on thermal, mechanical and flammability characteristics of polyester/glass fiber composites in comparison with composites prepared with calcium carbonate filler. The coefficient of thermal expansion showed reduced values for silane‐modified samples. All the composites decomposed at lower temperatures in air and their degradation behavior differed from those exposed to nitrogen. The glass fibers acted as a physical barrier before combustion and the catalytic effect of the clay was less pronounced for silane‐modified samples. The peak of heat release and linear burning rate for the silane‐modified Cloisite 30B sample was reduced. However, the limiting oxygen index did not show significant changes. In general, consequent to clay addition, these composites showed improved fire performance, shorter fire duration and slower fire growth and maintained better mechanical properties than those with calcium carbonate filler. POLYM. COMPOS., 38:2743–2752, 2017. © 2015 Society of Plastics Engineers
Initiation of 2‐Hydroxyethyl Methacrylate Polymerization by Tert‐Butyl Peroxide in a Planar PECVD System
Authors: Gürsoy Mehmet , Uçar Tuba , Tosun Zahide , Karaman Mustafa
Published: November 2015

This article reports on the deposition conditions and characterization of poly(2‐hydroxyethyl methacrylate) thin films grown by initiated plasma enhanced chemical vapor deposition process. The plasma power is inductively coupled into the process chamber with a planar‐coil antenna through a quartz window, and the substrate is cooled to promote physical adsorption of monomers on its surface. The introduction of the initiator allowed for film deposition at very low plasma powers (1 W) and greatly improves the deposition rates. Fourier transform infrared (FTIR) and X‐ray photoelectron spectroscopy (XPS) analyses confirmed that the chemical functionalities of the monomers are preserved to a good extent during the depositions that were carried out at low plasma powers. The deposition kinetics of PECVD‐produced films from HEMA can be tailored by varying the substrate temperature. The apparent activation energies observed from PHEMA deposition kinetics with varying substrate temperatures are observed to be negative, which supports the hypothesis of the free radical polymerization mechanism in the PECVD PHEMA deposition.
Progress in the development of protein biomarkers of oesophageal and gastric cancers
Authors: Coghlin Caroline , Murray Graeme I.
Published: November 2015

Upper gastrointestinal cancers originating in the oesophagus and stomach often present late and have a very poor prognosis. Treatment options include surgery for localised disease but, increasingly, neoadjuvant chemotherapy and radiotherapy are being employed to improve outcome. There is often a variable response to neoadjuvant treatment between individual patients and side effects are relatively common. There is an urgent need for novel biomarkers of upper gastrointestinal cancer, not only to improve screening and early diagnosis of the oesophageal and gastric cancers when treatment options are potentially more effective, but also to accurately guide therapy in more advanced disease. The development of predictive biomarkers will also help to more effectively identify those patients that will benefit from targeted therapies. Although many promising results have been derived from these studies there remains a lack of validated clinically applicable biomarkers available for translation into routine clinical use. This review will provide an overview of the recent proteomic research on upper gastrointestinal cancer protein biomarker identification and validation. The challenges faced in the development of validated, clinically acceptable and accurate protein biomarkers will also be discussed, along with possible areas of future progress.
Soft Supramolecular Nanoparticles by Noncovalent and Host–Guest Interactions
Authors: Stoffelen Carmen , Huskens Jurriaan
Published: November 2015

Supramolecular chemistry provides a tool for the formation of highly ordered structures by means of noncovalent interactions. Soft supramolecular nanoparticles are self‐assembled nanoassemblies based on small building blocks and stabilized by basic noncovalent interactions, selective host–guest interactions, or a combination of different interaction types. This review provides an overview of the existing approaches for the formation of supramolecular nanoparticles by various types of noncovalent interactions, with a strong focus on host–guest‐mediated assemblies. The approaches are ordered based on the nature of the stabilizing supramolecular interaction, while focusing on the aspects that determine the particle structure. Where applicable, the use of these self‐assembled nanostructures as vectors in molecular diagnostics and therapeutics is described as well. The stable yet reversible nature of supramolecular interactions and their chemical flexibility offer great prospects for the development of highly engineered nanoparticles which are compatible with the complexity of living systems.
Hamlet by William Shakespeare
Authors: Brooks Jean R.
Published: November 2015

To write on Hamlet without Harold Jenkins’s great edition at one’s elbow would be absurd: my debts to it are manifold, as I am proud to acknowledge. With the growing recognition of Shakespeare’s art as reaching its fulfilment on the stage, interpretations by actors have a particular value: I am grateful for the interviews readily given me by Derek jacobi, Martin Jarvis, and jack Shepherd. For practical help in the preparation of this book, it is a pleasure to thank Dr James Gibson, and in cutting my oral draft, my husband, Professor Harold F. Brooks.
Practical Approaches to Definitive Reconstruction of Complex Abdominal Wall Defects
Authors: Latifi Rifat
Published: November 2015

With advances in abdominal surgery and the management of major trauma, complex abdominal wall defects have become the new surgical disease, and the need for abdominal wall reconstruction has increased dramatically. Subsequently, how to reconstruct these large defects has become a new surgical question. While most surgeons use native abdominal wall whenever possible, evidence suggests that synthetic or biologic mesh needs to be added to large ventral hernia repairs. One particular group of patients who exemplify “complex” are those with contaminated wounds, enterocutaneous fistulas, enteroatmospheric fistulas, and/or stoma(s), where synthetic mesh is to be avoided if at all possible. Most recently, biologic mesh has become the new standard in high‐risk patients with contaminated and dirty‐infected wounds. While biologic mesh is the most common tissue engineered used in this field of surgery, level I evidence is needed on its indication and long‐term outcomes. Various techniques for reconstructing the abdominal wall have been described, however the long‐term outcomes for most of these studies, are rarely reported. In this article, I outline current practical approaches to perioperative management and definitive abdominal reconstruction in patients with complex abdominal wall defects, with or without fistulas, as well as those who have lost abdominal domain.
Glutamate functions in stomatal closure in Arabidopsis and fava bean
Authors: Yoshida Riichiro , Mori Izumi C. , Kamizono Nobuto , Shichiri Yudai , Shimatani Tetsuo , Miyata Fumika , Honda Kenji , Iwai Sumio
Published: November 2015

Guard cells are indispensable for higher plants because they control gas exchange and water balance to maintain photosynthetic activity. The signaling processes that govern their movement are controlled by several factors, such as abscisic acid (ABA), blue light, pathogen-associated molecular patterns (PAMPs), and carbon dioxide. Herein, we demonstrated that the amino acid glutamate (Glu), a well-known mammalian neurotransmitter, functions as a novel signaling molecule in stomatal closure in both Arabidopsis and fava bean (Vicia faba L.). Pharmacological and electrophysiological analyses provided important clues for the participation of Glu-receptors, Ca2+, and protein phosphorylation during the signaling process. Genetic analyses using Arabidopsis ABA-deficient (aba2-1) and ABA-insensitive (abi1-1 and abi2-1) mutants showed that ABA is not required for Glu signaling. However, loss-of-function of the Arabidopsis gene encoding Slow Anion Channel-Associated
1 (SLAC1) and Calcium-Dependent Protein Kinase 6 (CPK6) impaired the Glu response. Moreover, T-DNA knockout mutations of the Arabidopsis Glu receptor-like gene (GLR), GLR3.5, lost their sensitivity to Glu-dependent stomatal closure. Our results strongly support functional Glu-signaling in stomatal closure and the crucial roles of GLRs in this signaling process.
Social information influences trust behaviour in adolescents
Authors: Lee Nikki C. , Jolles Jelle , Krabbendam Lydia
Published: November 2015

Trust plays an integral role in daily interactions within adolescents' social environment. Using a trust game paradigm, this study investigated the modulating influence of social information about three interaction partners on trust behaviour in adolescents aged 12–18 (N = 845). After receiving information about their interaction partners prior to the task, participants were most likely to share with a 'good' partner and rate this partner as most trustworthy. Over the course of the task all interaction partners showed similar levels of trustworthy behaviour, but overall participants continued to trust and view the good partner as more trustworthy than 'bad' and 'neutral' partners throughout the game. However, with age the ability to overcome prior social information and adapt trust behaviour improved: middle and late adolescents showed a larger decrease in trust of the good partner than early adolescents, and late adolescents were more likely to reward trustworthy behaviour from the negative partner.
Global mapping of the regulatory interactions of histone residues
Authors: Jung Inkyung , Seo Jungmin , Lee Heun-Sik , Stanton Lawrence W. , Kim Dongsup , Choi Jung Kyoon
Published: November 2015

Histone residues can serve as platforms for specific regulatory function. Here we constructed a map of regulatory associations between histone residues and a wide spectrum of chromatin regulation factors based on gene expression changes by histone point mutations in Saccharomyces cerevisiae. Detailed analyses of this map revealed novel associations. Regarding the modulation of H3K4 and K36 methylation by Set1, Set2, or Jhd2, we proposed a role for H4K91 acetylation in early Pol II elongation, and for H4K16 deacetylation in late elongation and crosstalk with H3K4 demethylation for gene silencing. The association of H3K56 with nucleosome positioning suggested that this lysine residue and its acetylation might contribute to nucleosome mobility for transcription activation. Further insights into chromatin regulation are expected from this approach.
Influence of amyloid and APOE on cognitive performance in a late middle‐aged cohort
Authors: Mielke Michelle M. , Machulda Mary M. , Hagen Clinton E. , Christianson Teresa J. , Roberts Rosebud O. , Knopman David S. , Vemuri Prashanthi , Lowe Val J. , Kremers Walter K. , Jack Clifford R. , Petersen Ronald C.
Published: November 2015

Introduction

Few studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.

Methods

We included 464 cognitively normal, test‐naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51–71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow‐up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline.

Results

Elevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test.

Discussion

Elevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.
Importance of home study visit capacity in dementia studies
Authors: Crane Paul K. , Gibbons Laura E. , McCurry Susan M. , McCormick Wayne , Bowen James D. , Sonnen Joshua , Keene C. Dirk , Grabowski Thomas , Montine Thomas J. , Larson Eric B.
Published: November 2015

Introduction

The importance of home research study visit capacity in Alzheimer's disease (AD) studies is unknown.

Methods

All evaluations are from the prospective Adult Changes in Thought study. Based on analyses of factors associated with volunteering for a new in‐clinic initiative, we analyzed AD risk factors and the relevance of neuropathologic findings for dementia comparing all data including home visits, and in‐clinic data only. We performed bootstrapping to determine whether differences were greater than expected by chance.

Results

Of the 1781 people enrolled during 1994–1996 with ≥1 follow‐up, 1369 (77%) had in‐clinic data, covering 61% of follow‐up time. In‐clinic data resulted in excluding 76% of incident dementia and AD cases. AD risk factors and the relevance of neuropathologic findings for dementia were both different with in‐clinic data.

Discussion

Limiting data collection in AD studies to research clinics alone likely reduces power and also can lead to erroneous inferences.
HOUSMAN'S SPECTRAL SHROPSHIRE
Authors: Evans Mihail
Published: November 2015

The fictional setting of the “Shropshire” of A. E. Housman's A Shropshire Lad (1894) is well known. He himself admitted to hardly having visited the county before the publication of his cycle of poems and the topography of the county in verse and actuality are often two different things. For instance, Hughley, whose steeple in the poems is a “far-known sign,” as Housman's brother Laurence discovered on a post-publication visit, is located in a valley and the remarkable spire turns out to be squat rather than soaring (Burnett, Letters 1: 90). The particular form of unreality that will be the subject of this paper is not, however, the physical backdrop of Housman's poems, imaginary or otherwise. Rather I would like to focus on the way in which the imaginative universe of Housman is populated by figures who challenge our assumptions about the boundary between the realms of the living and the dead. We might say that I will be concerned not with the epistemology of Housman's Shropshire but with its ontology, or perhaps, to use a term of Derrida's, with its “hauntology” (Specters 10, 51, 161). Indeed, my suggestion will be that far from being an untrue or fictional world, the phantasmal figures of Housman's Shropshire articulate that reality that is named, in the late work of Jacques Derrida, as the spectral. My essay will elaborate the question of the spectral as an interplay between the poems of Housman and the philosophical meditations of Derrida.
Platelet-derived CXCL12 regulates monocyte function, survival, differentiation into macrophages and foam cells through differential involvement of CXCR4–CXCR7
Authors: Chatterjee M , von Ungern-Sternberg S N I , Seizer P , Schlegel F , Büttcher M , Sindhu N A , Müller S , Mack A , Gawaz M
Published: November 2015

Platelets store and release CXCL12 (SDF-1), which governs differentiation of hematopoietic progenitors into either endothelial or macrophage-foam cells. CXCL12 ligates CXCR4 and CXCR7 and regulates monocyte/macrophage functions. This study deciphers the relative contribution of CXCR4–CXCR7 in mediating the effects of platelet-derived CXCL12 on monocyte function, survival, and differentiation. CXCL12 and macrophage migration inhibitory factor (MIF) that ligate CXCR4–CXCR7 induced a dynamic bidirectional trafficking of the receptors, causing CXCR4 internalization and CXCR7 externalization during chemotaxis, thereby influencing relative receptor availability, unlike MCP-1. In vivo we found enhanced accumulation of platelets and platelet-macrophage co-aggregates in peritoneal fluid following induction of peritonitis in mice. The relative surface expression of CXCL12, CXCR4, and CXCR7 among infiltrated monocytes was also enhanced as compared with peripheral blood. Platelet-derived CXCL12 from collagen-adherent platelets and recombinant CXCL12 induced monocyte chemotaxis specifically through CXCR4 engagement. Adhesion of monocytes to immobilized CXCL12 and CXCL12-enriched activated platelet surface under static and dynamic arterial flow conditions were mediated primarily through CXCR7 and were counter-regulated by neutralizing platelet-derived CXCL12. Monocytes and culture-derived-M1–M2 macrophages phagocytosed platelets, with the phagocytic potential of culture-derived-M1 macrophages higher than M2 involving CXCR4–CXCR7 participation. CXCR7 was the primary receptor in promoting monocyte survival as exerted by platelet-derived CXCL12 against BH3-mimetic induced apoptosis (phosphatidylserine exposure, caspase-3 activation, loss of mitochondrial transmembrane potential). In co-culture experiments with platelets, monocytes predominantly differentiated into CD163+ macrophages, which was attenuated upon CXCL12 neutralization and CXCR4/CXCR7 blocking antibodies. Moreover, OxLDL uptake by platelets induced platelet apoptosis, like other platelet agonists TRAP and collagen-related peptide (CRP). CXCL12 facilitated phagocytosis of apoptotic platelets by monocytes and M1–M2 macrophages, also promoted their differentiation into foam cells via CXCR4 and CXCR7. Thus, platelet-derived CXCL12 could regulate monocyte-macrophage functions through differential engagement of CXCR4 and CXCR7, indicating an important role in inflammation at site of platelet accumulation.
SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2
Authors: Sun R , Jiang B , Qi H , Zhang X , Yang J , Duan J , Li Y , Li G
Published: November 2015

SOX4, a member of the SOX (sex-determining region Y-related HMG box) transcription factor family, has been reported to be abnormally expressed in a wide variety of cancers, and to exert a pleiotropic function. However, its function in progression of cervical cancer (CC) remains unknown. In this study, we found that SOX4 was highly expressed in CC cells and tissues, and overexpression of SOX4 in CC CaSki cells enhanced tumor clone formation and cell proliferation, and accelerated cell cycle progress. Meanwhile, downregulation of SOX4 by shRNA in CaSki cells inhibited cell proliferation, and slowed cell cycle progress, indicating that SOX4 contributes to the development of CC. In addition, SOX4 overexpression by gene transfer reduced the sensitivity of CaSki cells in response to the chemotherapeutic drug cisplatin, and SOX4 downregulation by RNA interference increased the sensitivity of CaSki cells in response to cisplatin. Moreover, SOX4 overexpression upregulated multiple drug resistant gene ABCG2, and SOX4 downregulation inhibited ABCG2 expression. Taken together, these results suggested that SOX4 functions to modulate cancer proliferation by regulation of cell cycle, and inhibit cancer cell sensitivity to therapeutic drug via upregulation of ABCG2. Thus, SOX4 may be a target for CC chemotherapy.
Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation
Authors: Sun Jin , Wei Hui-Min , Xu Jiang , Chang Jian-Feng , Yang Zhihao , Ren Xingjie , Lv Wen-Wen , Liu Lu-Ping , Pan Li-Xia , Wang Xia , Qiao Huan-Huan , Zhu Bing , Ji Jun-Yuan , Yan Dong , Xie Ting , Sun Fang-Lin , Ni Jian-Quan
Published: November 2015

Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factor bam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs. Furthermore, overexpression of mof reduces H1 association on chromatin. In contrast, the knocking down of mof significantly rescues the GSC loss phenotype. Taken together, these results suggest that H1 functions intrinsically to promote GSC self-renewal by antagonizing MOF function. Since H1 and H4K16 acetylation are highly conserved from fly to human, the findings from this study might be applicable to stem cells in other systems.
Two-dimensional membrane as elastic shell with proof on the folds revealed by three-dimensional atomic mapping
Authors: Zhao Jiong , Deng Qingming , Ly Thuc Hue , Han Gang Hee , Sandeep Gorantla , Rümmeli Mark H
Published: November 2015

The great application potential for two-dimensional (2D) membranes (MoS2, WSe2, graphene and so on) aroused much effort to understand their fundamental mechanical properties. The out-of-plane bending rigidity is the key factor that controls the membrane morphology under external fields. Herein we provide an easy method to reconstruct the 3D structures of the folded edges of these 2D membranes on the atomic scale, using high-resolution (S)TEM images. After quantitative comparison with continuum mechanics shell model, it is verified that the bending behaviour of the studied 2D materials can be well explained by the linear elastic shell model. And the bending rigidities can thus be derived by fitting with our experimental results. Recall almost only theoretical approaches can access the bending properties of these 2D membranes before, now a new experimental method to measure the bending rigidity of such flexible and atomic thick 2D membranes is proposed.
Delaying aging is neuroprotective in Parkinson’s disease: a genetic analysis in C. elegans models
Authors: Cooper Jason F , Dues Dylan J , Spielbauer Katie K , Machiela Emily , Senchuk Megan M , Van Raamsdonk Jeremy M
Published: November 2015

Aging is the greatest risk factor for the development of Parkinson’s disease (PD). However, the role of aging in the pathogenesis of PD is not known and it is currently uncertain why the symptoms take many decades to develop when inherited mutations that cause the disease can be present from birth. We hypothesize that there are specific changes that take place during the aging process that make cells susceptible to disease-causing mutations that are well-tolerated at younger ages. If so, then interventions that increase lifespan should be beneficial in the treatment of PD. To test this hypothesis, we used the powerful genetics of C. elegans, as this worm has been used extensively in aging research. We crossed transgenic worm models of PD expressing either human mutant α-synuclein (A53T) or LRRK2 (G2019S) with the long-lived insulin-IGF1 receptor mutant, daf-2. The daf-2 mutation increased the lifespan of both PD mutants. The increase in lifespan resulting from the daf-2 mutation rescued the degeneration of dopamine neurons in both worm models of PD and importantly rescued deficits in dopamine-dependent behaviors including basal slowing, ethanol avoidance, and area-restricted searching. Increasing lifespan through daf-2 mutation also delayed the formation of small aggregates in a worm model of PD expressing α-synuclein in the body wall muscle and rescued deficits in resistance to different stresses that were present in the PD mutant worms. Overall, this work suggests that slowing down the aging process may provide an effective treatment for PD.
Structural and electrical properties of catalyst-free Si-doped InAs nanowires formed on Si(111)
Authors: Park Dong Woo , Jeon Seong Gi , Lee Cheul-Ro , Lee Sang Jun , Song Jae Yong , Kim Jun Oh , Noh Sam Kyu , Leem Jae-Young , Kim Jin Soo
Published: November 2015

We report structural and electrical properties of catalyst-free Si-doped InAs nanowires (NWs) formed on Si(111) substrates. The average diameter of Si-doped InAs NWs was almost similar to that of undoped NWs with a slight increase in height. In the previous works, the shape and size of InAs NWs formed on metallic catalysts or patterned structures were significantly changed by introducing dopants. Even though the external shape and size of the Si-doped NWs in this work were not changed, crystal structures inside the NWs were significantly changed. For the undoped InAs NWs, both zincblende (ZB) and wurzite (WZ) structures were observed in transmission-electron microscope images, where the portion of WZ structure was estimated to be more than 30%. However, only ZB was observed with an increase in stacking fault (SF) for the Si-doped NWs. The undoped and Si-doped InAs NWs were used as channels of four-point electrical measurements with Al/Ni electrodes to investigate electrical properties. The resistivity calculated from the current-voltage curve of a Si-doped InAs NW showed 1.32 × 10−3 Ωcm, which was dramatically decreased from 10.14 × 10−3 Ωcm for the undoped InAs NW. A relatively low resistivity of catalyst-free Si-doped InAs NWs was achieved without significant change in structural dimensions.
Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
Authors: Saio Tomohide , Ogura Kenji , Kumeta Hiroyuki , Kobashigawa Yoshihiro , Shimizu Kazumi , Yokochi Masashi , Kodama Kota , Yamaguchi Hiroto , Tsujishita Hideki , Inagaki Fuyuhiko
Published: November 2015

Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step to regulate their function. However, the detailed mechanisms of such dynamic regulation of the functional processes are poorly understood because of the lack of an efficient tool. We here demonstrate detailed characterization of conformational changes of MurD, a 47 kDa protein enzyme consisting of three domains, by the use of solution NMR equipped with paramagnetic lanthanide probe. Quantitative analysis of pseudocontact shifts has identified a novel conformational state of MurD, named semi-closed conformation, which is found to be the key to understand how MurD regulates the binding of the ligands. The modulation of the affinity coupled with conformational changes accentuates the importance of conformational state to be evaluated in drug design.
The accumulation mechanism of the hypoxia imaging probe “FMISO” by imaging mass spectrometry: possible involvement of low-molecular metabolites
Authors: Masaki Yukiko , Shimizu Yoichi , Yoshioka Takeshi , Tanaka Yukari , Nishijima Ken-ichi , Zhao Songji , Higashino Kenichi , Sakamoto Shingo , Numata Yoshito , Yamaguchi Yoshitaka , Tamaki Nagara , Kuge Yuji
Published: November 2015

18F-fluoromisonidazole (FMISO) has been widely used as a hypoxia imaging probe for diagnostic positron emission tomography (PET). FMISO is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of its nitro group. However, its detailed accumulation mechanism remains unknown. Therefore, we investigated the chemical forms of FMISO and their distributions in tumours using imaging mass spectrometry (IMS), which visualises spatial distribution of chemical compositions based on molecular masses in tissue sections. Our radiochemical analysis revealed that most of the radioactivity in tumours existed as low-molecular-weight compounds with unknown chemical formulas, unlike observations made with conventional views, suggesting that the radioactivity distribution primarily reflected that of these unknown substances. The IMS analysis indicated that FMISO and its reductive metabolites were nonspecifically distributed in the tumour in patterns not corresponding to the radioactivity distribution. Our IMS search found an unknown low-molecular-weight metabolite whose distribution pattern corresponded to that of both the radioactivity and the hypoxia marker pimonidazole. This metabolite was identified as the glutathione conjugate of amino-FMISO. We showed that the glutathione conjugate of amino-FMISO is involved in FMISO accumulation in hypoxic tumour tissues, in addition to the conventional mechanism of FMISO covalent binding to macromolecules.
Application of density gradient for the isolation of the fecal microbial stool component and the potential use thereof
Authors: Hevia Arancha , Delgado Susana , Margolles Abelardo , Sánchez Borja
Published: November 2015

The idea of considering the gut microbiota as a virtual human organ has led to the concept of fecal microbiota transplantation (FMT), which has recently been extremely successful in the treatment of cases of recurrentClostridium difficileinfection. Administration of safe, viable and representative fecal microbiota is crucial for FMT. To our knowledge, suitable techniques and systematic conditions for separating the fecal microbiota from stool samples have not been thoroughly investigated. In this work we show the potential to separate stool microorganisms from the rest of fecal material using a procedure with a Nycodenz® density gradient, yielding 1010viable bacteria per two grams of feces. This procedure did not affect the original microbiota composition in terms of viability, distribution and proportions, as assessed by a phylogenetic metagenomic approach. Obtaining the fecal microbiota by concentration and separation of the microorganisms from the rest of the stool components would allow the standardization of its recovery and its long-term preservation. FMT or similar microbiota restoration therapies could be used for the treatment of several disorders, or even for aesthetic purposes, so the method described in our work may contribute to the setting of the basis for the development of safe and standardized products.
Morphology and Performance of Polymer Solar Cell Characterized by DPD Simulation and Graph Theory
Authors: Du Chunmiao , Ji Yujin , Xue Junwei , Hou Tingjun , Tang Jianxin , Lee Shuit-Tong , Li Youyong
Published: November 2015

The morphology of active layers in the bulk heterojunction (BHJ) solar cells is critical to the performance of organic photovoltaics (OPV). Currently, there is limited information for the morphology from transmission electron microscopy (TEM) techniques. Meanwhile, there are limited approaches to predict the morphology /efficiency of OPV. Here we use Dissipative Particle Dynamics (DPD) to determine 3D morphology of BHJ solar cells and show DPD to be an efficient approach to predict the 3D morphology. Based on the 3D morphology, we estimate the performance indicator of BHJ solar cells by using graph theory. Specifically, we study poly (3-hexylthiophene)/[6, 6]-phenyl-C61butyric acid methyl ester (P3HT/PCBM) BHJ solar cells. We find that, when the volume fraction of PCBM is in the region 0.4 ∼ 0.5, P3HT/PCBM will show bi-continuous morphology and optimum performance, consistent with experimental results. Further, the optimum temperature (413 K) for the morphology and performance of P3HT/PCBM is in accord with annealing results. We find that solvent additive plays a critical role in the desolvation process of P3HT/PCBM BHJ solar cell. Our approach provides a direct method to predict dynamic 3D morphology and performance indicator for BHJ solar cells.
New HDAC6-mediated deacetylation sites of tubulin in the mouse brain identified by quantitative mass spectrometry
Authors: Liu Ningning , Xiong Yun , Li Shanshan , Ren Yiran , He Qianqian , Gao Siqi , Zhou Jun , Shui Wenqing
Published: November 2015

The post-translational modifications (PTMs) occurring on microtubules have been implicated in the regulation of microtubule properties and functions. Acetylated K40 of α-tubulin, a hallmark of long-lived stable microtubules, is known to be negatively controlled by histone deacetylase 6 (HDAC6). However, the vital roles of HDAC6 in microtubule-related processes such as cell motility and cell division cannot be fully explained by the only known target site on tubulin. Here, we attempt to comprehensively map lysine acetylation sites on tubulin purified from mouse brain tissues. Furthermore, mass spectrometry-based quantitative comparison of acetylated peptides from wild-type vs HDAC6 knockout mice allowed us to identify six new deacetylation sites possibly mediated by HDAC6. Thus, adding new sites to the repertoire of HDAC6-mediated tubulin deacetylation events would further our understanding of the multi-faceted roles of HDAC6 in regulating microtubule stability and cellular functions.
Effective Temperature and Universal Conductivity Scaling in Organic Semiconductors
Authors: Abdalla Hassan , van de Ruit Kevin , Kemerink Martijn
Published: November 2015

We investigate the scalability of the temperature- and electric field-dependence of the conductivity of disordered organic semiconductors to ‘universal’ curves by two different but commonly employed methods; by so-called universal scaling and by using the effective temperature concept. Experimentally both scaling methods were found to be equally applicable to the out-of-plane charge transport in PEDOT:PSS thin films of various compositions. Both methods are shown to be equivalent in terms of functional dependence and to have identical limiting behavior. The experimentally observed scaling behavior can be reproduced by a numerical nearest-neighbor hopping model, accounting for the Coulomb interaction, the high charge carrier concentration and the energetic disorder. The underlying physics can be captured in a simple empirical model, describing the effective temperature of the charge carrier distribution as the outcome of a heat balance between Joule heating and (effective) temperature-dependent energy loss to the lattice.
Ionic liquids and their bases: Striking differences in the dynamic heterogeneity near the glass transition
Authors: Grzybowska K. , Grzybowski A. , Wojnarowska Z. , Knapik J. , Paluch M.
Published: November 2015

Ionic liquids (ILs) constitute an active field of research due to their important applications. A challenge for these investigations is to explore properties of ILs near the glass transition temperature Tg, which still require our better understanding. To shed a new light on the issues, we measured ILs and their base counterparts using the temperature modulated calorimetry. We performed a comparative analysis of the dynamic heterogeneity at Tgfor bases and their salts with a simple monoatomic anion (Cl–). Each pair of ionic and non-ionic liquids is characterized by nearly the same chemical structure but their intermolecular interactions are completely different. We found that the size of the dynamic heterogeneity of ILs near Tgis considerably smaller than that established for their dipolar counterparts. Further results obtained for several other ILs near Tgadditionally strengthen the conclusion about the relatively small size of the dynamic heterogeneity of molecular systems dominated by electrostatic interactions. Our finding opens up new perspectives on designing different material properties depending on intermolecular interaction types.
Body mass index and risk of lung cancer: Systematic review and dose-response meta-analysis
Authors: Duan Peng , Hu Chunhui , Quan Chao , Yi Xianfu , Zhou Wei , Yuan Meng , Yu Tingting , Kourouma Ansoumane , Yang Kedi
Published: November 2015

Questions remain about the significance of the dose-response relationship between body mass index (BMI) and lung cancer (LC) risk. Pertinent studies were identified through a search in EMBASE and PUBMED from July 2014 until March 2015. The summary relative risk (SRR) and confidence interval (CI) were estimated. The dose-response relationship was assessed using a restricted cubic spline. The overall meta-analysis showed evidence of a nonlinear association between BMI and LC risk (Pnonlinearity < 0.001). The SRR were 0.98 (95%CI: 0.95–1.01) for 25 kg/m2, 0.91 (95%CI: 0.85–0.98) for 30 kg/m2 and 0.81 (95% CI: 0.72–0.91) for 35 kg/m2, with mild between-study heterogeneity (I2 = 5%). The results of the stratified analysis by gender were comparable to those of the overall meta-analysis. When stratified by smoking status, linear dose-response associations were observed for current smokers, ex-smokers and non-smokers (Pnonlinearity > 0.05), whereas the effects were attenuated when restricting analysis to non-smokers and at the point of 30 kg/m2, the SRR was 0.96 (95%CI: 0.86–1.07) for males and 0.95 (95%CI: 0.89–1.02) for females. This meta-analysis provides quantitative evidence that increasing BMI is a protective factor against LC. Keeping normal-to-moderate BMI should be prescribed as an evidence-based lifestyle tip for LC prevention in smokers.