bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk
Authors: Hamilton Gillian , Harris Sarah E. , Davies Gail , Liewald David C. , Tenesa Albert , Payton Antony , Horan Michael A. , Ollier William E.R. , Pendleton Neil ,   the Genetic and Environmental Risk for Alzheimer's Disease (GERAD1) Consortium, Starr John M. , Porteous David , Deary Ian J.
Published: June 2012

The β‐amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aβ‐degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four‐SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE ε4 allele (P = 0.00035, odds ratio = 1.61). In LBC1936, we identified a significant association between a different two‐SNP ECE1 intragenic haplotype and non‐verbal reasoning in individuals lacking the APOE ε4 allele (P = 0.00036, β = −0.19). Both results showed a trend towards significance after permutation (0.05 < P < 0.10). A follow‐up cognitive genetic study evaluated the association of ECE1 SNPs in three additional cohorts of non‐demented older people. Meta‐analysis of the four cohorts identified the significant association (Z < 0.05) of SNPs in the ECE‐1b promoter with non‐verbal reasoning scores, particularly in individuals lacking the APOE ε4 allele. Our genetic findings are not wholly consistent. Nonetheless, the AD associated intronic haplotype is linked to the 338A variant of known ECE1b promoter variant, 338C>A (rs213045). We observed significantly less expression from the 338A variant in two human neuroblastoma cell lines and speculate that this promoter may be subject to tissue‐specific regulation. © 2012 Wiley Periodicals, Inc.
A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis‐linked SOD1 mutants
Authors: Fujisawa Takao , Homma Kengo , Yamaguchi Namiko , Kadowaki Hisae , Tsuburaya Naomi , Naguro Isao , Matsuzawa Atsushi , Takeda Kohsuke , Takahashi Yuji , Goto Jun , Tsuji Shoji , Nishitoh Hideki , Ichijo Hidenori
Published: June 2012

Objective:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by the selective loss of upper and lower motoneurons. Although >100 different Cu, Zn superoxide dismutase (SOD1) mutations have been identified in ALS patients, it remains controversial whether all of them are disease‐causative mutations. Therefore, it is necessary to develop molecular mechanism‐based diagnosis and treatment of ALS caused by SOD1 mutations.

Methods:

We previously reported that 3 pathogenic mutations of SOD1 cause chronic endoplasmic reticulum (ER) stress by inducing the binding of SOD1 to Derlin‐1, a component of the ER homeostatic machinery. Here, we systematically analyzed 132 SOD1 mutants and found that most have a constitutively exposed Derlin‐1–binding region (DBR) that is occluded in the wild‐type protein. To develop the novel molecular mechanism‐based antibody that can specifically recognize the aberrant structure of toxic SOD1 mutants, we generated the monoclonal antibody against the DBR.

Results:

MS785, a monoclonal antibody generated against the DBR, distinguished most ALS‐causative SOD1 mutants from both wild‐type and nontoxic mutants. Moreover, MS785 recognized endogenous SOD1 in B lymphocytes derived from 14 ALS patients carrying SOD1 mutations but not from 11 healthy controls.

Interpretation:

This is the first study to address the common property of all ALS‐causative SOD1 mutants. MS785 is the first molecular mechanism‐based antibody that was shown to be able to distinguish ALS‐linked toxic SOD1 mutants from both wild‐type and nontoxic mutants. MS785 may thus become an innovative tool for the diagnosis of ALS. ANN NEUROL 2012;72:739–749
Modulating the physical properties of sunflower oil and sorbitan monopalmitate‐based organogels
Authors: Behera Beauty , Sagiri Sai S. , Pal Kunal , Srivastava Anand
Published: June 2012

The present study deals with the modulation of the sunflower oil (SO) and sorbitan monopalmitate (SM) organogels using water. The gels were prepared by heating either SO–SM mixture or SO–SM–water mixture at 60°C and subsequently cooling the mixture to room temperature. The gels were characterized by microscopy (light and electron), Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), differential thermal analysis, rheometry, pH, dc impedance, hemocompatibility, and antimicrobial studies. The gels without water (G) were found to be pale yellow in color while gels containing water (GW) were white in color. Both types of gels were thermoreversible in nature. The microscopic analysis revealed that clusters of rod‐shaped tubules were responsible in the formation of network. GW also showed the presence of water droplets encapsulated within the networked structure. FTIR studies indicated the presence of intermolecular hydrogen bonding, responsible for gel formation. Gel‐to‐sol transition temperatures (Tgs) of the GW gels were higher than G gels, which might be accounted to the higher crystallinity of the GW gels. XRD studies confirmed the higher crystallinity of the GW gels. The gels showed pseudoplastic flow behavior and were hemocompatible in nature. Ciprofloxacin‐loaded gels showed good anti‐microbial properties against Bacillus subtilis. Based on the preliminary results, the developed gels may be used as delivery vehicles for various bioactive agents. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Correlation between body composition and risk factors for cardiovascular disease and metabolic syndrome
Authors: Chuang Hai‐Hua , Li Wen‐Cheng , Sheu Bor‐Fuh , Liao Shu‐Chen , Chen Jau‐Yuan , Chang Ko‐Chen , Tsai Yi‐Wen
Published: June 2012

Body mass index (BMI) is an important diagnostic tool for determining obesity; however, while BMI reflects the influence of body height over body weight, it does not reveal body fat percentage (BF%). We explored whether BF% correlated with risk factors for cardiovascular disease and metabolic syndrome and whether metabolically obese, normal weight people were at risk for these diseases. A total of 2,867 healthy volunteers participated in this study. Blood pressure, height, weight, waist circumference, BMI, BF%, lipid profile, fasting glucose, uric acid, and lifestyle factors were collected from healthy subjects during their annual health examinations. In both males and females, BF% correlated positively with BMI and waist circumference. Participants were divided into three groups according to BF% and data were compared between groups. The results suggest that BF% correlates with risk factors for cardiovascular disease and metabolic syndrome for both men and women, and that BF% may be a useful predictor of risk, particularly in metabolically obese, normal weight individuals. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
A navigation mesh for dynamic environments
Authors: van Toll Wouter G. , Cook Atlas F. , Geraerts Roland
Published: June 2012

Games and simulations frequently model scenarios where obstacles move, appear, and disappear in an environment. A city environment changes as new buildings and roads are constructed, and routes can become partially blocked by small obstacles many times in a typical day. This paper studies the effect of using local updates to repair only the affected regions of a navigation mesh in response to a change in the environment. The techniques are inspired by incremental methods for Voronoi diagrams. The main novelty of this paper is that we show how to maintain a 2D or 2.5D navigation mesh in an environment that contains dynamic polygonal obstacles. Experiments show that local updates are fast enough to permit real‐time updates of the navigation mesh. Copyright © 2012 John Wiley & Sons, Ltd.
Quantum Dot‐Based Screening System for Discovery of G Protein‐Coupled Receptor Agonists
Authors: Lee Junghan , Kwon Yong‐Jun , Choi Youngseon , Kim Hi Chul , Kim Keumhyun , Kim JinYeop , Park Sun , Song Rita
Published: June 2012

Cellular imaging has emerged as an important tool to unravel biological complexity and to accelerate the drug‐discovery process, including cell‐based screening, target identification, and mechanism of action studies. Recently, semiconductor nanoparticles known as quantum dots (QDs) have attracted great interest in cellular imaging applications due to their unique photophysical properties such as size, tunable optical property, multiplexing capability, and photostability. Herein, we show that QDs can also be applied to assay development and eventually to high‐throughput/content screening (HTS/HCS) for drug discovery. We have synthesized QDs modified with PEG and primary antibodies to be used as fluorescent probes for a cell‐based HTS system. The G protein‐coupled receptor (GPCR) family is known to be involved in most major diseases. We therefore constructed human osteosarcoma (U2OS) cells that specifically overexpress two types of differently tagged GPCRs: influenza hemagglutinin (HA) peptide‐tagged κ‐opioid receptors (κ‐ORs) and GFP‐tagged A3 adenosine receptors (A3AR). In this study, we have demonstrated that 1) anti‐HA antibody‐conjugated QDs could specifically label HA‐tagged κ‐ORs, 2) subsequent treatment of QD‐tagged GPCR agonists allowed agonist‐induced translocation to be monitored in real time, 3) excellent emission spectral properties of QD permitted the simultaneous detection of two GPCRs in one cell, and 4) the robust imaging capabilities of the QD–antibody conjugates could lead to reproducible quantitative data from high‐content cellular images. These results suggest that the present QD‐based GPCR inhibitor screening system can be a promising platform for further drug screening applications.
Numerical Study of Split T‐Micromixers
Authors: Roudgar M. , Brunazzi E. , Galletti C. , Mauri R.
Published: June 2012

Three‐dimensional numerical simulations were performed to study the liquid flow inside split T‐type micromixers, investigating the effects of various operating and design parameters on the mixing process. While for small Reynolds numbers, the mixing efficiency of a split T‐micromixer is larger than that of a simple T‐micromixer, it was found that, when Re = 100, mixing is further enhanced by the formation of vortex pairs. This is not only a function of the flow rate, but it depends also on the geometry of the device and on the ratio between the flow rates in the inlet sub‐channels. In general, at a given flow rate, vertical splits induce a much better mixing than horizontal splits, while the reverse may occur for strongly unequal inlet flow rates.
A fair scheduling scheme based on collision statistics for cognitive radio networks
Authors: Tang Wanbin , Zhou Jing , Yu Huogen , Li Shaoqian
Published: June 2012

In cognitive radio networks (CRNs), considering the randomness of primary users' (PUs) arrival and the nonideality of spectrum sensing performed by secondary users (SUs), the collisions between PUs and SUs are unavoidable. Frequent occurrences of collisions will strongly degrade PUs' and SUs' QoS. Therefore, collision statistics, such as the average number of collisions, is a very important performance metric in CRNs. If collision statistics are not considered in the scheduling scheme of the CRNs, some SUs will meet more collisions than the others, which cause unfair experiences among the SUs. Therefore, a fair scheduling scheme based on collision statistics is proposed in this paper, which can improve fairness across all SUs. First, the number of collisions is defined as an important fairness metric for each SU, and the scheduler dynamically adjusts the priorities of the SUs by periodically counting each SU's collision number. Then, a prediction algorithm, based on the continuous‐time Markov chain model, is proposed to predict the idle probabilities of the available channels in the next slot. Considering both the priorities of the SUs and the idle probabilities of the available channels, a rational scheduling scheme will be achieved finally. Assuming the ordered hunt scheduling scheme applied by the primary system, the simulation results show that the proposed scheme can significantly improve the fairness across all SUs with little impact on spectrum utilization. Copyright © 2012 John Wiley & Sons, Ltd.
Molybdenum, Molybdenum Oxides, and their Electrochemistry
Authors: Saji Viswanathan S. , Lee Chi‐Woo
Published: June 2012

The electrochemical behaviors of molybdenum and its oxides, both in bulk and thin film dimensions, are critical because of their widespread applications in steels, electrocatalysts, electrochromic materials, batteries, sensors, and solar cells. An important area of current interest is electrodeposited CIGS‐based solar cells where a molybdenum/glass electrode forms the back contact. Surprisingly, the basic electrochemistry of molybdenum and its oxides has not been reviewed with due attention. In this Review, we assess the scattered information. The potential and pH dependent active, passive, and transpassive behaviors of molybdenum in aqueous media are explained. The major surface oxide species observed, reversible redox transitions of the surface oxides, pseudocapacitance and catalytic reduction are discussed along with carefully conducted experimental results on a typical molybdenum glass back contact employed in CIGS‐based solar cells. The applications of molybdenum oxides and the electrodeposition of molybdenum are briefly reviewed.
A Highly Active Bagasse‐Derived Solid Acid Catalyst with Properties Suitable for Production of Biodiesel
Authors: Lou Wen‐Yong , Guo Qiang , Chen Wen‐Jing , Zong Min‐Hua , Wu Hong , Smith Thomas J.
Published: June 2012

A novel bagasse‐based solid acid catalyst was successfully prepared through sulfonation of incompletely carbonized bagasse. A range of conditions for producing the catalyst were investigated, and the optimized catalyst, produced under carbonization at 648 K for 0.5 h and sulfonation at 423 K for 15 h, showed excellent catalytic activity and resulted in around 95 % yield of methyl oleate. Its activity was not only substantially greater than that of niobic acid and Amberlyst‐15, but also comparable to or superior to that of catalysts made from pure starch or glucose, respectively. Additionally, the bagasse‐derived catalyst could be repeatedly employed for at least eight cycles and still retained around 90 % of its original activity, exhibiting excellent operational stability. Furthermore, the catalyst efficiently converted waste cooking oils with 38.6 wt % free fatty acids into biodiesel and afforded a high yield of about 93.8 % within 12 h. These results clearly show that the bagasse‐derived catalyst is economic, eco‐friendly, and promising for biodiesel production from low‐cost feedstocks and may find wide applications.
Single‐cell mass cytometry adapted to measurements of the cell cycle
Authors: Behbehani Gregory K. , Bendall Sean C. , Clutter Matthew R. , Fantl Wendy J. , Nolan Garry P.
Published: June 2012

Mass cytometry is a recently introduced technology that utilizes transition element isotope‐tagged antibodies for protein detection on a single‐cell basis. By circumventing the limitations of emission spectral overlap associated with fluorochromes utilized in traditional flow cytometry, mass cytometry currently allows measurement of up to 40 parameters per cell. Recently, a comprehensive mass cytometry analysis was described for the hematopoietic differentiation program in human bone marrow from a healthy donor. The current study describes approaches to delineate cell cycle stages utilizing 5‐iodo‐2‐deoxyuridine (IdU) to mark cells in S phase, simultaneously with antibodies against cyclin B1, cyclin A, and phosphorylated histone H3 (S28) that characterize the other cell cycle phases. Protocols were developed in which an antibody against phosphorylated retinoblastoma protein (Rb) at serines 807 and 811 was used to separate cells in G0 and G1 phases of the cell cycle. This mass cytometry method yielded cell cycle distributions of both normal and cancer cell populations that were equivalent to those obtained by traditional fluorescence cytometry techniques. We applied this to map the cell cycle phases of cells spanning the hematopoietic hierarchy in healthy human bone marrow as a prelude to later studies with cancers and other disorders of this lineage. © 2012 International Society for Advancement of Cytometry
Developments in the Coordination Chemistry of Europium(II)
Authors: Garcia Joel , Allen Matthew J.
Published: June 2012

Recent advances in the coordination chemistry of Eu2+ are reviewed. Common synthetic routes for generating discrete Eu2+‐containing complexes reported since 2000 are summarized, followed by a description of the reactivity of these complexes and their applications in reduction chemistry, polymerization, luminescence, and as contrast agents for magnetic resonance imaging. Rapid development of the coordination chemistry of Eu2+ has led to an upsurge in the utilization of Eu2+‐containing complexes in synthetic chemistry, materials science, and medicine.
Use of carboxylic group functionalized magnetic nanoparticles for the preconcentration of metals in juice samples prior to the determination by capillary electrophoresis
Authors: Carpio Azahara , Mercader‐Trejo Flora , Arce Lourdes , Valcárcel Miguel
Published: June 2012

Nowadays food industry demands reliable and precise methods to resolve problems related to quality and security control. The pretreatment steps, prior to sample analysis, are necessary to extract the target analytes because of the complexities of the food samples matrices. In this work, we have studied, for the first time, the potential of carboxylic group functionalized magnetic nanoparticles to preconcentrate metals from liquid samples before CE analysis. For the extraction of metals, 10 mL of an aqueous sample containing the metal mixture was added to 2 mg carboxylic group functionalized magnetic nanoparticles. Metals retained in the nanoparticles were re‐extracted with 200 μL solution consisting of 0.8 mM 1,10‐phenanthroline and 0.04% hydroxylamine chloride at pH 2. The electrophoretic buffer used in this work to separate different metals (Co, Cu, Zn, Ni, and Cd) consisted of 30 mM hydroxylamine chloride, 0.30 mM 1,10‐phenanthroline, 80 mM urea, 15 mM ammonium chloride, and 0.1% methanol at pH 3.6. Finally, measurements were made at 270 nm. Under the optimized conditions, detection limits for Co, Zn, Cu, Ni, and Cd were 0.004, 0.003, 0.004, 0.008, and 0.009 mg L−1, respectively.
1H‐NMR‐based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors
Authors: Vázquez‐Fresno Rosa , Llorach Rafael , Alcaro Francesca , Rodríguez Miguel Ángel , Vinaixa Maria , Chiva‐Blanch Gemma , Estruch Ramon , Correig Xavier , Andrés‐Lacueva Cristina
Published: June 2012

Moderate wine consumption is associated with health‐promoting activities. An H‐NMR‐based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty‐one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24‐h urine samples were collected and analyzed by 1H‐NMR. According to the results of a one‐way ANOVA, significant markers were grouped in four categories: alcohol‐related markers (ethanol); gin‐related markers; wine‐related markers; and gut microbiota markers (hippurate and 4‐hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched‐chain amino acid (BCAA) metabolite (3‐methyl‐oxovalerate). Additionally, a possible interaction between alcohol and gut‐related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake.
Current development of microfluidic immunosensing approaches for mycotoxin detection via capillary electromigration and lateral flow technology
Authors: Li Peiwu , Zhang Zhaowei , Zhang Qi , Zhang Ning , Zhang Wen , Ding Xiaoxia , Li Ran
Published: June 2012

Mycotoxin contamination in the food chain has caused serious health issues in humans and animals. Thus, a rapid on‐site and lab‐independent detection method for mycotoxins, such as aflatoxins (AFTs), is desirable. Microfluidic chip based immunosensor technology is one of the most promising methods for fast mycotoxin assays. In this review, we cover the major microfluidic immunosensors used for mycotoxin analysis, via flow‐through (capillary electromigration) and lateral flow technology. Sample preparation from different matrices of agricultural products and foodstuffs is summarized. The choice of materials, fabrication strategies, and detection methods for microfluidic immunosensors are further discussed in detail. The sensors application in mycotoxin determination is also outlined. Finally, future challenges and opportunities are discussed.
Quantifying rainfall controls on catchment‐scale landslide erosion in Taiwan
Authors: Chen Yi‐Chin , Chang Kang‐tsung , Chiu Yu‐Jia , Lau Sze‐Man , Lee Hong‐Yuan
Published: June 2012

Landslide erosion is a dominant hillslope process and the main source of stream sediment in tropical, tectonically active mountain belts. In this study, we quantified landslide erosion triggered by 24 rainfall events from 2001 to 2009 in three mountainous watersheds in Taiwan and investigated relationships between landslide erosion and rainfall variables. The results show positive power‐law relations between landslide erosion and rainfall intensity and cumulative rainfall, with scaling exponents ranging from 2·94 to 5·03. Additionally, landslide erosion caused by Typhoon Morakot is of comparable magnitude to landslide erosion caused by the Chi‐Chi Earthquake (MW = 7·6) or 22–24 years of basin‐averaged erosion. Comparison of the three watersheds indicates that deeper landslides that mobilize soil and bedrock are triggered by long‐duration rainfall, whereas shallow landslides are triggered by short‐duration rainfall. These results suggest that rainfall intensity and watershed characteristics are important controls on rainfall‐triggered landslide erosion and that severe typhoons, like high‐magnitude earthquakes, can generate high rates of landslide erosion in Taiwan. Copyright © 2012 John Wiley & Sons, Ltd.
The Exploitation of Plant Resources by Early Homo sapiens: The Phytolith Record from Pinnacle Point 13B Cave, South Africa
Authors: Albert Rosa M. , Marean Curtis W.
Published: June 2012

The capacity to detect remnants of fire usage in archaeological sites, along with a better understanding of its use by prehistoric populations, can help us to shed light on hominin cognition, social organization, and technology. The application of phytolith studies to understand fire and its use can be widely applicable since plants typically contain phytoliths that are identifiable to different taxonomic levels. Pinnacle Point 13B (PP13B) is one of several South African Middle Stone Age (MSA) sites that shows an abundant presence of lenses of burnt material and intact hearths. Phytolith analyses at PP13B have been used to identify the types of plants used as fuel in the hearths. The phytoliths overall show high levels of alteration, and varying alteration is used to identify areas with higher alkaline conditions related to dripping water. In some areas of the site, there is excellent preservation of multicellular structures from the epidermal leaves of dicotyledonous plants, suggesting in situ structures with practically no chemical or post‐depositional alteration. A notable pattern is the abundance of dicotyledonous leaves from the rear of the cave, which might indicate specific leaf‐fuels for the fires, short‐term fire activities, or other actions such as cooking.
Night work and breast cancer: A population‐based case–control study in France (the CECILE study)
Authors: Menegaux Florence , Truong Thérèse , Anger Antoinette , Cordina‐Duverger Emilie , Lamkarkach Farida , Arveux Patrick , Kerbrat Pierre , Févotte Joëlle , Guénel Pascal
Published: June 2012

Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population‐based case‐control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99–1.64]). Odds ratios were 1.35 [1.01–1.80] in women who worked on overnight shifts, 1.40 [1.01–1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01–2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13–3.35] in women employed in night work for >4 years before their first full‐term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full‐term pregnancy.
Encapsulation of cell‐adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion
Authors: Zhang Zheng , Ni Jian , Chen Liang , Yu Lin , Xu Jianwei , Ding Jiandong
Published: June 2012

Peptides containing the sequence of arginine‐glycine‐aspartate (RGD), a famous adhesion moiety, can specifically conjugate integrins in cell membranes, and are usually applied to enhance cell adhesion after linking to solid substrates in tissue engineering or to nanoparticles in targeting delivery. This paper reveals, however, that free RGD peptides can assist in preventing tissue adhesion by blocking focal adhesion between cells and surfaces of barrier devices. In order to avoid a rapid peptide loss after straightforward injection of a peptide solution, we employed a thermosensitive injectable hydrogel composed of a biodegradable block copolymer poly(ε‐caprolactone‐co‐lactide)–poly(ethylene glycol)–poly(ε‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA) to encapsulate peptides cyclo(‐RGDfK‐). A sustainable release for one week was achieved in vitro. The rabbit model of sidewall defect and bowel abrasion was selected to examine the in vivo anti‐adhesion efficacy. It reveals a significant reduction of postoperative peritoneal adhesion in the group of RGD‐loaded PCLA–PEG–PCLA hydrogels. We interpret this excellent efficacy by the combination of two effects: first, our hydrogel affords a physical barrier to prevent adhesion between injured abdominal wall and cecum; second, the RGD molecules as integrin blockers released from the hydrogel assist the anti‐adhesion. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1599–1609, 2012.
Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle–mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1/Th2 response
Authors: Grskovic Ivan , Kutsch Anna , Frie Christian , Groma Gergely , Stermann Jacek , Schlötzer-Schrehardt Ursula , Niehoff Anja , Moss Stephen E , Rosenbaum Sabrina , Pöschl Ernst , Chmielewski Markus , Rappl Gunter , Abken Hinrich , Bateman John F , Cheah Kathryn SE , Paulsson Mats , Brachvogel Bent
Published: June 2012

Numerous biochemical studies have pointed to an essential role of annexin A5 (AnxA5), annexin A6 (AnxA6), and collagen X in matrix vesicle–mediated biomineralization during endochondral ossification and in osteoarthritis. By binding to the extracellular matrix protein collagen X and matrix vesicles, annexins were proposed to anchor matrix vesicles in the extracellular space of hypertrophic chondrocytes to initiate the calcification of cartilage. However, mineralization appears to be normal in mice lacking AnxA5 and AnxA6, whereas collagen X–deficient mice show only subtle alterations in the growth plate organization. We hypothesized that the simultaneous lack of AnxA5, AnxA6, and collagen X in vivo induces more pronounced changes in the growth plate development and the initiation of mineralization. In this study, we generated and analyzed mice deficient for AnxA5, AnxA6, and collagen X. Surprisingly, mice were viable, fertile, and showed no obvious abnormalities. Assessment of growth plate development indicated that the hypertrophic zone was expanded in Col10a1−/− and AnxA5−/−AnxA6−/−Col10a1−/− newborns, whereas endochondral ossification and mineralization were not affected in 13-day- and 1-month-old mutants. In peripheral quantitative computed tomography, no changes in the degree of biomineralization were found in femora of 1-month- and 1-year-old mutants even though the diaphyseal circumference was reduced in Col10a1−/− and AnxA5−/−AnxA6−/−Col10a1−/− mice. The percentage of naive immature IgM+/IgM+ B cells and peripheral T-helper cells were increased in Col10a1−/− and AnxA5−/−AnxA6−/−Col10a1−/− mutants, and activated splenic T cells isolated from Col10a1−/− mice secreted elevated levels of IL-4 and GM-CSF. Hence, collagen X is needed for hematopoiesis during endochondral ossification and for the immune response, but the interaction of annexin A5, annexin A6, and collagen X is not essential for physiological calcification of growth plate cartilage. Therefore, annexins and collagen X may rather fulfill functions in growth plate cartilage not directly linked to the mineralization process. © 2012 American Society for Bone and Mineral Research.
Recent trends in hip fracture rates by race/ethnicity among older US adults
Authors: Wright Nicole C , Saag Kenneth G , Curtis Jeffrey R , Smith Wilson K , Kilgore Meredith L , Morrisey Michael A , Yun Huifeng , Zhang Jie , Delzell Elizabeth S
Published: June 2012

Hip fracture incidence has declined among whites in the United States since 1995, but data on recent trends in racial and ethnic minorities are limited. The goal of this analysis was to investigate hip fracture incidence trends in racial/ethnic subgroups of older Medicare beneficiaries. We conducted a cohort study to determine annual hip fracture incidence rates from 2000 through 2009 using the Medicare national random 5% sample. Beneficiaries were eligible if they were ≥65 years of age and had 90 days of consecutive full fee-for-service Medicare coverage with no hip fracture claims. Race/ethnicity was self-reported. The incidence of hip fracture was identified using hospital diagnosis codes or outpatient diagnosis codes paired with fracture repair procedure codes. We computed age-standardized race/ethnicity-specific incidence rates and assessed trends in the rates over time using linear regression. On average, 821,475 women and 632,162 men were included in the analysis each year. Beneficiaries were predominantly white (88%), with African, Hispanic, and Asian Americans making up 8%, 1.5%, and 1.5% of the population, respectively. We identified 102,849, 4,119, 813, and 1,294 hip fractures in white, black, Asian, and Hispanic beneficiaries over the 10 years. A significant decreasing trend (p < 0.05) in hip fracture incidence from 2000-2001 to 2008-2009 was present in white women and men. Black and Asian beneficiaries experienced nonsignificant declines. Irrespective of gender, the largest rate of decline was seen in beneficiaries ≥75 years of age. The overall and age-specific rates of Hispanic women or men changed minimally over time. Hip fracture incidence rates continued to decline in recent years among white Medicare beneficiaries. Further research is needed to understand mechanisms responsible for declining rates in some and not others, as hip fractures continue to be a major problem among the elderly. © 2012 American Society for Bone and Mineral Research.
Extraction of lipids from Yarrowia Lipolytica
Authors: Milanesio Juan , Hegel Pablo , Medina‐González Yaocihuatl , Camy Séverine , Condoret Jean‐Stéphane
Published: June 2012

BACKGROUND: Microorganisms have often been considered for the production of oils and fats as an alternative to agricultural and animal resources. Extraction experiments were performed using a strain of the yeast Yarrowia lipolytica (Y. lipolytica), a high‐lipid‐content yeast. Three different methods were tested: Soxhlet extraction, accelerated solvent extraction (ASE) and supercritical carbon dioxide (SCCO2) extraction using ethanol as a co‐solvent. Also, high pressure solubility measurements in the systems ‘CO2 + yeast oil’ and ‘CO2 + ethanol + yeast oil’ were carried out.

RESULTS: The solubility experiments determined that, at the conditions of the supercritical extractor (40 °C and 20 MPa), a maximum concentration of 10 mg of yeast oil per g of solvent can be expected in pure CO2. 10% w/w of ethanol in the solvent mixture increased this value to almost 15 mg of yeast oil per g of solvent. Different pretreatments were necessary to obtain satisfactory yields in the extraction experiments. The Soxhlet and the ASE method were not able to complete the lipid extraction. The ‘SCCO2 + ethanol’ extraction curves revealed the influence of the different pretreatments on the extraction mechanism.

CONCLUSION: Evaluating the effectiveness of a given pretreatment, ASE reduced the amount of material and solvent used compared with Soxhlet. In all three cases, the best total extraction performance was obtained for the ethanol‐macerated yeast (EtM). Addition of ethanol to the solvent mixture enhanced the oil solubility. Oil can be extracted from Y. lipolytica in two different steps: a non‐selective ethanol extraction followed by TAG‐selective SCCO2 purification. © 2012 Society of Chemical Industry
Aframomum stipulatum (Gagnep) K. Schum and Aframomum giganteum (Oliv. & Hanb) K. Schum as Aroma Tincto Oleo Crops resources: essential oil, fatty acids, sterols, tocopherols, and tocotrienols composition of different fruit parts of Congo varieties
Authors: Ngakegni‐Limbili Adolphe Christian , Zebib Bachar , Cerny Muriel , Tsiba Gouolally , Elouma Ndinga Arnold Murphy , Mouloungui Zéphirin , Fourastier Isabelle , Ouamba Jean‐Maurille
Published: June 2012

BACKGROUND: Today, few known plant species provide both an essential oil (EO) and a vegetable oil (VO). Seed and husk of two Aframomum species were investigated and compared in terms of EO, fatty acids, tocopherols, and tocotrienols.

RESULTS: EO yield reaches 15.3 g kg−1 in the seeds and 3.2 g kg−1 in the husks, while VO yield is 180.0 g kg−1 in the seeds and 25.0 g kg−1 in the husks. β‐Pinene, 1,8‐cineol, α‐selinene, terpine‐4‐ol, linalool, myrtenal and β‐caryophyllene are the major compounds of seed and husk EO. Fatty acid analysis of two Aframomum species shows that oleic, linoleic, and palmitic acids were the major compounds of VO. Total sterol contents reached 4.3 g kg−1 in seed VO and 8.5 g kg−1 in husk VO. An appreciable amount of tocopherols (0.52 g kg−1) was found in seed VO.

CONCLUSION: The seed and husk oil of A. stipulatum and A. giganteum fruits are rich sources of many bioactive constituents such as fatty acids, sterols, tocopherols and tocotrienols. These tropical wild fruits can be considered as new Aroma Tincto Oleo Crops (ATOC) resources that contain both EOs and VOs. Copyright © 2012 Society of Chemical Industry
HPLC‐ESI‐MS and MS/MS structural characterization of multifucosylated N‐glycoforms of the basic proline‐rich protein IB‐8a CON1+ in human saliva
Authors: Cabras Tiziana , Boi Roberto , Pisano Elisabetta , Iavarone Federica , Fanali Chiara , Nemolato Sonia , Faa Gavino , Castagnola Massimo , Messana Irene
Published: June 2012

This study describes the characterization of the glycan moieties and the peptide backbone of six glycoforms of IB‐8a CON1+, a basic proline‐rich protein present in human saliva. MS analyses on the intact glycoproteins before and after N‐deglycosylation with PNGase F and high‐resolution MS/MS sequencing by LTQ Orbitrap XL of peptides and glycopeptides from tryptic digests allowed the structural characterization of the glycan moieties and the polypeptide backbone, as well as to establish the glycosylation site at the asparagine residue at 98th position. Five of the glycoforms carry a biantennary N‐linked glycan fucosylated in the innermost N‐acetylglucosamine of the core and showing from zero to four additional fucoses in the antennal region. The sixth glycoform carries a monoantennary monofucosylated oligosaccharide. The glycoform cluster was detected on 28 of 71 adult saliva specimens. Level of fucosylation showed interindividual variability with the major relative abundance for the trifucosylated glycoform. Nonglycosylated IB‐8a CON1+ and the variant IB‐8a CON1−, lacking of the glycosylation site, have been also detected in human saliva.
The determination and characterisation of 2‐naphthyloxycarbonyl chloride derivatised biogenic amines in pet foods
Authors: Bassanese Danielle N. , Crawford‐Clark Shona , Bowen Benjamin J. , Henderson Luke C. , Barnett Neil W. , Conlan Xavier A.
Published: June 2012

The need to monitor biogenic amines levels is essential for many areas of the food industry for two main reasons: the caustic nature and potential toxicity of these amines, and the potential to use amine levels as markers for freshness and quality in foodstuffs. Optimised analysis conditions used for the determination of biogenic amines derivatised with 2‐napthyloxycarbonyl chloride has been applied to different pet food samples to assess the effectiveness of this method for complex sample matrices. Further to this, the use of high‐resolution mass spectrometry has enabled the previously unconfirmed derivatised form of seven biogenic amines to be established. The derivatised forms identified include as mono substituted (tryptamine and histamine), bisubstituted (putrescine, cadaverine and tyramine), trisubstituted (spermidine) and tetrasubstituted (spermine). The methodology of biogenic amine determination was performed successfully to a range of pet food products highlighting the applicability to a variety of complex sample matrices.
Evaluation of common genetic variants in pre‐microRNA in susceptibility and prognosis of esophageal cancer
Authors: Umar Meenakshi , Upadhyay Rohit , Prakash Garima , Kumar Shaleen , Ghoshal Uday Chand , Mittal Balraj
Published: June 2012

Genetic variants in micro‐RNAs (miRNA) have been shown to affect progression, diagnosis, and prognosis of various malignancies; however, their role in esophageal squamous cell carcinoma (ESCC) susceptibility is controversial. Therefore, we aimed to determine role of common genetic variants in cancer related pre‐miRNA in susceptibility and survival outcome of north Indian ESCC patients. We genotyped four common polymorphisms in pre‐miRNA: mir‐196a‐2C>T, mir‐146aG>C, mir‐499T>C, and mir‐423C>A in 289 incident ESCC cases (including 153 follow‐up cases) and 309 controls using PCR/PCR RFLP‐based methods. Binary logistic regression was applied for risk estimation, while Kaplan–Meier and Cox Regression tests were performed for survival analysis. We observed that none of the pre‐miRNA genetic variants were associated with ESCC or its clinical phenotypes independently, however, combined risk genotypes of four pre‐miRNA polymorphisms increased risk of ESCC in dose–response manner (Ptrend = 0.011). Specifically, patients with 2–4 risk genotypes of pre‐miRNA polymorphisms had 1.4‐fold higher risk of ESCC compared to patients with 0–1 risk genotypes (OR = 1.43, 95% CI = 1.02–1.09, P‐value = 0.037). The risk was more pronounced in ESCC cases with upper‐third esophageal tumors. Moreover, cumulative but not independent effect of risk genotypes of pre‐miRNA polymorphisms was observed on survival outcome of ESCC patients. Cases with 2–4 risk genotypes had significantly lower median survival (11.60 vs. 30.2 months) and 2.3‐fold greater hazard of death compared to patients with 0–1 risk genotypes. In conclusion, the four studied common pre‐miRNA polymorphisms cumulatively affect susceptibility and survival of ESCC patients in north Indian population. © 2012 Wiley Periodicals, Inc.
Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson's disease
Authors: Helmchen Christoph , Pohlmann Jonas , Trillenberg Peter , Lencer Rebekka , Graf Julia , Sprenger Andreas
Published: June 2012

Patients with Parkinson's disease (PD) have difficulties in the control of self‐guided (i.e., internally driven) movements. The basal ganglia provide a nonspecific internal cue for the development of a preparatory activity for a given movement in the sequence of repetitive movements. Controversy surrounds the question of whether PD patients are capable of (1) anticipating (before an external trigger appears; i.e., anticipation) and (2) predicting movement velocity once a moving target shortly disappears from the visual scene (i.e., prediction). To dissociate between these two components, we examined internally driven (extraretinal generated) smooth pursuit eye movements in PD patients and age‐matched healthy controls by systematically varying target blanking periods of a trapezoidally moving target in four paradigms (initial blanking, midramp blanking, blanking after a short ramp, and no blanking). Compared to controls, PD patients showed (1) decreased smooth pursuit gain (without blanking), (2) deficient anticipatory pursuit (prolonged pursuit initiation latency; reduced eye velocity before target onset in the early onset blanking paradigm), and (3) preserved extraretinal predictive pursuit velocity (midramp target blanking). Deficient anticipation of future target motion was not related to either disease duration or the general motor impairment (UPDRS). We conclude that PD patients have difficulties in anticipating future target motion, which may play a role for the mechanisms involved in deficient gait initiation and termination of PD. In contrast, they remain unimpaired in their capacity of building up an internal representation of continuous target motion. This may explain the clinical advantage of medical devices that use visual motion to improve gait initiation (e.g., “PD glasses”). © 2012 Movement Disorder Society
Intraoperative x‐ray to measure distance between DBS leads: A reliability study
Authors: Verhagen Metman Leo , Pilitsis Julie G. , Stebbins Glenn T. , Bot Maarten , Bakay Roy A.E.
Published: June 2012

Background:

Many factors can jeopardize the accuracy of deep brain stimulation (DBS) lead placement. Confirmation of lead placement while the patient is still in the operating room would be advantageous. Intraoperative MRI or CT can identify placement errors, but these modalities can be cost‐ or time prohibitive. Intraoperative fluoroscopy may give information on the accuracy of the Y coordinate, but the accuracy of the X coordinate usually cannot be confirmed. When an object of known dimensions is present in the brain, such as a unilateral DBS lead, its dimensions can be used to calculate unknown distances. The objective of this study was to determine if intraoperative AP skull x‐ray accurately predicts the distance between DBS electrodes using postoperative MRI as the gold standard.

Methods:

The distance between 32 pairs of DBS leads was measured by 2 independent raters under blinded conditions on intraoperative AP x‐ray and postoperative axial and coronal MRI. Variable x‐ray magnification was accounted for using the formula: actual distance between 2 leads = (measured distance between DBS leads)/(average measured length of electrodes) × 7.5 mm.

Results:

The mean (± SD) distance on x‐ray was 22.62 ± 2.23 mm, on axial MRI 22.78 ± 1.90 mm, and on coronal MRI 22.79 ± 2.00 mm. ANOVA revealed no difference based on method (P = .887) or raters (P = .940). The intraclass correlation coefficient showed excellent interrater reliability,

Conclusions:

Intraoperative AP x‐ray accurately predicts the distance between DBS leads. The technique is especially useful when the location of the first DBS lead relative to the midline is known, such as during staged bilateral procedures or lead replacement procedures. © 2012 Movement Disorder Society
EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3‐bromopyruvate
Authors: Matsumoto Shingo , Saito Keita , Yasui Hironobu , Morris H. Douglas , Munasinghe Jeeva P. , Lizak Martin , Merkle Hellmut , Ardenkjaer‐Larsen Jan Henrik , Choudhuri Rajani , Devasahayam Nallathamby , Subramanian Sankaran , Koretsky Alan P. , Mitchell James B. , Krishna Murali C.
Published: June 2012

The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia‐sensitive drug. The small molecule 3‐bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3‐bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3‐bromopyruvate was substantially attenuated in hypoxic tumor regions (pO2 < 10 mmHg) in vivo using squamous cell carcinoma (SCCVII)‐bearing mouse model. Metabolic MRI studies using hyperpolarized 13C‐labeled pyruvate showed that monocarboxylate transporter‐1 is the major transporter for pyruvate and the analog 3‐bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter‐1 in vivo. Expression of monocarboxylate transporter‐1 was enhanced in moderately hypoxic (8–15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia‐activated drugs. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Spin‐echo magnetic resonance spectroscopic imaging at 7 T with frequency‐modulated refocusing pulses
Authors: Zhu He , Soher Brian J. , Ouwerkerk Ronald , Schär Michael , Barker Peter B.
Published: June 2012

Two approaches to high‐resolution SENSE‐encoded magnetic resonance spectroscopic imaging (MRSI) of the human brain at 7 Tesla (T) with whole‐slice coverage are described. Both sequences use high‐bandwidth radiofrequency pulses to reduce chemical shift displacement artifacts, SENSE‐encoding to reduce scan time, and dual‐band water and lipid suppression optimized for 7 T. Simultaneous B0 and transmit B1 mapping was also used for both sequences to optimize field homogeneity using high‐order shimming and determine optimum radiofrequency transmit level, respectively. One sequence (“Hahn‐MRSI”) used reduced flip angle (90°) refocusing pulses for lower radiofrequency power deposition, while the other sequence used adiabatic fast passage refocusing pulses for improved sensitivity and reduced signal dependence on the transmit‐B1 level. In four normal subjects, adiabatic fast passage‐MRSI showed a signal‐to‐noise ratio improvement of 3.2 ± 0.5 compared to Hahn‐MRSI at the same spatial resolution, pulse repetition time, echo time, and SENSE‐acceleration factor. An interleaved two‐slice Hahn‐MRSI sequence is also demonstrated to be experimentally feasible. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.