bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Complications of Laparoscopic and Conventional Appendectomy Reported to the Finnish Patient Insurance Centre
Authors: Kotaluoto Sannamari , Pauniaho Satu‐Liisa K. , Helminen Mika T. , Sand Juhani A. , Rantanen Tuomo K.
Published: October 2015

Background

Appendectomy is considered a safe operation, the related complications being minor. Negative exploration is an accepted procedure to avoid complications of appendicitis. Treatment with antibiotics is under debate as a primary treatment for appendicitis. The aim of this study was to collect and analyze detailed information on complications and morbidity related to appendectomy using the information of the nationwide Patient Insurance Association (PIA) database and to study the incidence of patient claims and compensated injuries related to appendectomy in Finland.

Methods

Patients’ claims from 1990 to 2010 were collected from the PIA register. Complications were classified using the accordion severity grading system. Severe complications were selected for more detailed analyses. Laparoscopic and open surgeries were compared. Factors related to compensated claims were assessed. For statistical analysis, Fisher’s exact test, logistic multivariate regression, and the Mann–Kendall function were used.

Results

Appendectomy complications leading to a patient insurance claim in Finland are rare (0.2 %). The rate of patients’ claims after laparoscopic surgery was higher than after open surgery (p < 0.001), but the rate of compensated claims was equal. During the study period, complications after laparoscopic procedures more often led to additional surgery or organ failure (p = 0.03). Of the patients with a compensated injury, only 57 % had appendicitis. Preoperative computed tomography was used in only 6 % of these cases.

Conclusions

Patient injuries and claims regarding severe complications after appendectomy are rare. The complications related to laparoscopic appendectomy were more severe than those of open surgery.
Improving phosphorus use efficiency in agriculture: opportunities for breeding
Authors: van de Wiel Clemens C. M. , van der Linden C. Gerard , Scholten Olga E.
Published: October 2015

Phosphorus (P) is often an important limiting factor for crop yields, but rock phosphate as fertilizer is a non-renewable resource and expected to become scarce in the future. High P input levels in agriculture have led to environmental problems. One of the ways to tackle these issues simultaneously is improving phosphorus use efficiency (PUE) of the crops through breeding. In this review, we describe plant architectural and physiological traits important for PUE. Subsequently, we discuss efficient methods of screening for PUE traits. We address targeted cultivation methods, including solid and hydroponic systems, as well as testing methods, such as image analysis systems, and biomass and photosynthesis measurements. Genetic variation for PUE traits has been assessed in many crops, and genetics of PUE has been studied by quantitative trait loci (QTL) analyses and genome-wide association study. A number of genes involved in the plant’s response to low P have been characterized. These genes include transcription factors, and genes involved in signal transduction, hormonal pathways, sugar signalling, P saving metabolic pathways, and in P scavenging, including transporters and metabolites and/or ATP-ases mobilizing P in the soil. In addition, the role of microorganisms promoting PUE of plants, particularly arbuscular mycorrhizal fungi is discussed. An overview is given of methods for selecting for optimal combinations of plant and fungal genotypes, and their genetics, incl. QTLs and genes involved. In conclusion, significant progress has been made in selecting for traits for PUE, developing systems for the difficult but highly relevant root phenotyping, and in identifying QTLs and genes involved.
Social Autonomy and Heteronomy in the Age of ICT: The Digital Pharmakon and the (Dis)Empowerment of the General Intellect
Authors: Lemmens Pieter
Published: October 2015

‘The art of living with ICTs (information and communication technologies)’ today not only means finding new ways to cope, interact and create new lifestyles on the basis of the new digital (network) technologiesindividually, as ‘consumer-citizens’. It also means inventing new modes of living, producing and, not in the least place, strugglingcollectively, as workers and producers. As the so-called digital revolution unfolds in the context of a neoliberal cognitive and consumerist capitalism, its ‘innovations’ are predominantly employed to modulate and control both production processes and consumer behavior in view of the overall goal of extracting surplus value. Today, the digital networks overwhelmingly destroy social autonomy, instead engendering increasing social heteronomy and proletarianization. Yet it is these very networks themselves, as technicalpharmakain the sense of French ‘technophilosopher’ Bernard Stiegler, that can be employed as no other to struggle against this tendency. This paper briefly explores this possibility by reflecting upon current diagnoses of our ‘technological situation’ by some exemplary post-operaist Marxists from a Stieglerian, pharmacological perspective.
Immunization Coverage in Migrant School Children Along the Thailand-Myanmar Border
Authors: Kaji Aiko , Parker Daniel M. , Chu Cindy S. , Thayatkawin Wipa , Suelaor Jiraporn , Charatrueangrongkun Rachai , Salathibuppha Kloloi , Nosten Francois H. , McGready Rose
Published: October 2015

The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health.
Grain Boundary Segregation of Rare-Earth Elements in Magnesium Alloys
Authors: Robson Joseph D. , Haigh Sarah J. , Davis Bruce , Griffiths David
Published: October 2015

Small additions of rare-earth (RE) elements have been shown to have a powerful effect in modifying the texture of wrought magnesium alloys, giving a highly beneficial effect in improving their formability. Recent work has shown that segregation of RE atoms to grain boundaries is important in producing this texture change. In this work, two Mg-RE systems have been studied Mg-Y and Mg-Nd using high-resolution scanning transmission electron microscopy that permits both imaging and elemental analysis with a spatial resolution of better than 0.1 nm. The Mg-Y alloy, where the solubility and level of addition are relatively high, showed the RE texture change effect. This was accompanied by clustering of Y on the grain boundaries, consistent with previous studies of the Mg-Gd system. The Mg-Nd alloy, where the solubility and level of addition are relatively low, showed no texture change and no segregation. In this case, impurity elements binding the RE into insoluble particles, rendering it ineffective. The results are analyzed by modifying a previous model for the solute drag effect on boundaries expected due to the RE additions. This predicts that both Gd and Y will strongly inhibit boundary motion, with Gd being approximately twice as effective as Y.
Novel Synthesized Gemini Surfactant as Corrosion Inhibitor for Carbon Steel in HCl Solution
Authors: Zhang Ting , Pan Zhongwen , Gao Haixia
Published: October 2015

A quaternary ammonium gemini surfactant containing an ester spacer, namely (diethylhexanedioate)diyl‐α,ω‐bis(dimethyl myristyl ammonium bromide) (14‐DEHA‐14) was synthesized using a two‐step procedure with dimethyl hexanedioate, dimethylaminoethanol, and 1‐bromotetradecane. The chemical structure of the compound was confirmed by infrared (IR) spectrum, 1H nuclear magnetic resonance (NMR), and elemental analysis. The critical micelle concentration was determined by conductivity and tensiometry measurements, and its inhibition effect on corrosion of carbon steel in dilute (1.0 M) hydrochloric acid solution was investigated by weight loss measurements. The results show that the synthesized gemini surfactant acts as an excellent corrosion inhibitor in 1.0 M HCl solution. The adsorption of the inhibitor via chemical adsorption onto the carbon steel surface obeyed the Langmuir adsorption isotherm. A possible corrosion mechanism of the compound is discussed in relation to the calculated thermodynamic parameters and adsorption isotherm.
The hip in arthrogryposis
Authors: Bradish Christopher
Published: October 2015

Pathology

Hip dislocation is seen in approximately 30 % of children with amyoplasia and approximately 50 % of these will be bilateral.

Treatment

Closed reduction is rarely successful. Open reduction is indicated for unilateral dislocations and for the majority of bilateral dislocations. Reduction is recommended via a medial approach.

Results

A long-term satisfactory outcome can be achieved but with some loss of hip range of movement.
The power of parallel structure
Authors: Watling Chris
Published: October 2015

None
Imaging neuroinflammation in multiple sclerosis using TSPO-PET
Authors: Airas Laura , Rissanen Eero , Rinne Juha O.
Published: October 2015

Conventional MR imaging (MRI) techniques form the cornerstone of multiple sclerosis (MS) diagnostics and clinical follow-up today. MRI is sensitive in demonstrating focal inflammatory lesions and diffuse atrophy. However, especially in progressive MS, there is increasingly widespread diffuse pathology also outside the plaques, often related to microglial activation and neurodegeneration. This cannot be detected using conventional MRI. Positron emission tomography (PET) imaging using 18-kDa translocator protein (TSPO) binding radioligands has recently shown promise as a tool to detect this diffuse pathology in vivo, and for the first time allows one to follow its development longitudinally. It is becoming evident that the more advanced the MS disease is, the more pronounced is microglial activation. PET imaging allows the detection of MS-related pathology at molecular level in vivo. It has potential to enable measurement of effects of new disease-modifying drugs aimed at reducing neurodegeneration and neuroinflammation. PET imaging could thus be included in the design of future clinical trials of progressive MS. There are still technical issues related to the quality of TSPO radioligands and post-processing methodology, and comparison of studies from different PET centres is challenging. In this review, we summarise the main evidence supporting the use of TSPO-PET as a tool to explore the diffuse inflammation in MS.
Applications of species accumulation curves in large‐scale biological data analysis
Authors: Deng Chao , Daley Timothy , Smith Andrew
Published: October 2015

The species accumulation curve, or collector’s curve, of a population gives the expected number of observed species or distinct classes as a function of sampling effort. Species accumulation curves allow researchers to assess and compare diversity across populations or to evaluate the benefits of additional sampling. Traditional applications have focused on ecological populations but emerging large‐scale applications, for example in DNA sequencing, are orders of magnitude larger and present new challenges. We developed a method to estimate accumulation curves for predicting the complexity of DNA sequencing libraries. This method uses rational function approximations to a classical non‐parametric empirical Bayes estimator due to Good and Toulmin [Biometrika, 1956, 43, 45–63]. Here we demonstrate how the same approach can be highly effective in other large‐scale applications involving biological data sets. These include estimating microbial species richness, immune repertoire size, and k‐mer diversity for genome assembly applications. We show how the method can be modified to address populations containing an effectively infinite number of species where saturation cannot practically be attained. We also introduce a flexible suite of tools implemented as an R package that make these methods broadly accessible.
SMIM1 is a type II transmembrane phosphoprotein and displays the Vel blood group antigen at its carboxyl‐terminus
Authors: Arnaud Lionel , Kelley Liam P. , Helias Virginie , Cartron Jean-Pierre , Ballif Bryan A.
Published: October 2015

Disruption of SMIM1, encoding small integral membrane protein 1, is responsible for the Vel‐negative blood type, a rare but clinically‐important blood type. However, the exact nature of the Vel antigen and how it is presented by SMIM1 are poorly understood. Using mass spectrometry we found several sites of phosphorylation in the N‐terminal region of SMIM1 and we found the initiating methionine of SMIM1 to be acetylated. Flow cytometry analyses of human erythroleukemia cells expressing N‐ or C‐terminally Flag‐tagged SMIM1, several point mutants of SMIM1, and a chimeric molecule between Kell and SMIM1 demonstrated that SMIM1 carries the Vel antigen as a type II membrane protein with a predicted C‐terminal extracellular domain of only 3–12 amino acids.
Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients
Authors: Deon Marion , Sitta Angela , Faverzani Jessica L. , Guerreiro Gillian B. , Donida Bruna , Marchetti Desirèe P. , Mescka Caroline P. , Ribas Graziela S. , Coitinho Adriana S. , Wajner Moacir , Vargas Carmen R.
Published: October 2015

Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro‐inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid—PLA and phenylacetic acid—PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di‐tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin‐6 and interleukin‐1β, both significantly increased in these patients, provide evidence that the pro‐inflammatory state occurs. Besides, interleukin‐1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin‐6 and interleukin‐10, an anti‐inflammatory cytokine. Di‐tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro‐oxidant and pro‐inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.
Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study
Authors: Hu Y.-D. , Xiang Y.-T. , Fang J.-X. , Zu S. , Sha S. , Shi H. , Ungvari G. S. , Correll C. U. , Chiu H. F. K. , Xue Y. , Tian T.-F. , Wu A.-S. , Ma X. , Wang G.
Published: October 2015

Background

While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).

Method

Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.

Results

By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.

Conclusions

Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.
Design, analysis, and control of a cable-driven parallel platform with a pneumatic muscle active support
Authors: Zhao Xingwei , Zi Bin , Qian Lu
Published: October 2015

The neck is an important part of the body that connects the head to the torso, supporting the weight and generating the movement of the head. In this paper, a cable-driven parallel platform with a pneumatic muscle active support (CPPPMS) is presented for imitating human necks, where cable actuators imitate neck muscles and a pneumatic muscle actuator imitates spinal muscles, respectively. Analyzing the stiffness of the mechanism is carried out based on screw theory, and this mechanism is optimized according to the stiffness characteristics. While taking the dynamics of the pneumatic muscle active support into consideration as well as the cable dynamics and the dynamics of the Up-platform, a dynamic modeling approach to the CPPPMS is established. In order to overcome the flexibility and uncertainties amid the dynamic model, a sliding mode controller is investigated for trajectory tracking, and the stability of the control system is verified by a Lyapunov function. Moreover, a PD controller is proposed for a comparative study. The results of the simulation indicate that the sliding mode controller is more effective than the PD controller for the CPPPMS, and the CPPPMS provides feasible performances for operations under the sliding mode control.
Forecasting Congressional Elections Using Facebook Data
Authors: MacWilliams Matthew C.
Published: October 2015

Facebook constantly tracks the growth of each congressional candidate’s fan base and the number of people engaging with candidates online. These Facebook metrics comprise a rich dataset that theoretically may capture the effectiveness of campaigns in building participatory support as well as their potential to mobilize support. When added to electoral fundamentals similar to those used in national-election forecasting, can Facebook data be used to develop a reliable model for predicting vote-percentage outcomes of individual congressional contests? The results of an exploratory investigation reveal that fan participation and mobilization metrics tracked by Facebook produced surprisingly accurate election predictions in the 2012 US Senate races studied. The question remains, however, whether these results are a “flash in the 2012 pan” or an indication that using Facebook statistics to measure campaign effectiveness is a new tool that scholars can use to forecast the outcome of congressional campaigns.
I Approve This Candidate: The Strategic Use of Ad Endorsements in the 2008 Election
Authors: Paul Newly , York Chance
Published: October 2015

Contextual and strategic factors that influence the use of endorsements in political advertisements represent an underexplored area of the scholarly literature, resulting in a gap between the art and science of campaigning and the advertising-effects literature. This article uses data from the Wisconsin Ad Project to study endorsements in ads aired during the 2008 election cycle. We show that endorsements are used strategically by campaigns and that four factors—candidate characteristics, campaign characteristics, ad format, and timing—affect whether an ad containing an endorsement is aired. Specifically, endorsements are more likely to appear in positive ads, are primarily used by incumbents and female candidates, are less likely to appear in competitive races, and tend to air less frequently as a campaign progresses.
Flipping the Introductory American Politics Class: Student Perceptions of the Flipped Classroom
Authors: Jenkins Shannon
Published: October 2015

Much attention has been centered on the use of emerging technologies in higher education, including flipped classes. However, widespread admiration for and adoption of these innovations seems to be occurring at a much faster pace than the assessment and evaluation of them. Questions about student performance in and perception of flipped classes remain unanswered, so more research is needed. This study examines student perceptions of a partially flipped Introduction to American Politics course. In general, the results indicate that students preferred the partially flipped format, although (1) it is not clear that students would prefer a fully flipped course, and (2) some aspects of the flipped format worked better than others.
Composite particles with magnetic properties, near-infrared excitation, and far-red emission for luminescence-based oxygen sensing
Authors: Scheucher Elisabeth , Wilhelm Stefan , Wolfbeis Otto S. , Hirsch Thomas , Mayr Torsten
Published: October 2015

Oxygen sensing, magnetic, and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing, baking, and grinding procedure. Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission. The composite particles are excited with near infrared (NIR) laser light (980 nm). The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission (<750 nm) using an inert mediator dye and a platinated benzoporphyrin dye. This concept combines the advantages of NIR excitation and far-red emissive indicator dyes, offering minimized auto-fluorescence and enhanced membrane permeability. Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles, which enables easy manipulation and separation of the particles by the application of an external magnetic field.
Observation of a phononic Mollow triplet in a multimode hybrid spin-nanomechanical system
Authors: Pigeau B. , Rohr S. , Mercier de Lépinay L. , Gloppe A. , Jacques V. , Arcizet O.
Published: October 2015

Reminiscent of the bound character of a qubit’s dynamics confined on the Bloch sphere, the observation of a Mollow triplet in the resonantly driven qubit fluorescence spectrum represents one of the founding signatures of quantum electrodynamics. Here we report on its observation in a hybrid spin-nanomechanical system, where a nitrogen-vacancy spin qubit is magnetically coupled to the vibrations of a silicon carbide nanowire. A resonant microwave field turns the originally parametric hybrid interaction into a resonant process, where acoustic phonons are now able to induce transitions between the dressed qubit states, leading to synchronized spin-oscillator dynamics. We further explore the vectorial character of the hybrid coupling to the bidimensional deformations of the nanowire. The demonstrated microwave assisted synchronization of the spin-oscillator dynamics opens novel perspectives for the exploration of spin-dependent forces, the key ingredient for quantum state transfer.
Spectromicroscopic insights for rational design of redox-based memristive devices
Authors: Baeumer Christoph , Schmitz Christoph , Ramadan Amr H. H. , Du Hongchu , Skaja Katharina , Feyer Vitaliy , Müller Philipp , Arndt Benedikt , Jia Chun-Lin , Mayer Joachim , De Souza Roger A. , Michael Schneider Claus , Waser Rainer , Dittmann Regina
Published: October 2015

The demand for highly scalable, low-power devices for data storage and logic operations is strongly stimulating research into resistive switching as a novel concept for future non-volatile memory devices. To meet technological requirements, it is imperative to have a set of material design rules based on fundamental material physics, but deriving such rules is proving challenging. Here, we elucidate both switching mechanism and failure mechanism in the valence-change model material SrTiO3, and on this basis we derive a design rule for failure-resistant devices. Spectromicroscopy reveals that the resistance change during device operation and failure is indeed caused by nanoscale oxygen migration resulting in localized valence changes between Ti4+ and Ti3+. While fast reoxidation typically results in retention failure in SrTiO3, local phase separation within the switching filament stabilizes the retention. Mimicking this phase separation by intentionally introducing retention-stabilization layers with slow oxygen transport improves retention times considerably.
High-performance mussel-inspired adhesives of reduced complexity
Authors: Ahn B. Kollbe , Das Saurabh , Linstadt Roscoe , Kaufman Yair , Martinez-Rodriguez Nadine R. , Mirshafian Razieh , Kesselman Ellina , Talmon Yeshayahu , Lipshutz Bruce H. , Israelachvili Jacob N. , Waite J. Herbert
Published: October 2015

Despite the recent progress in and demand for wet adhesives, practical underwater adhesion remains limited or non-existent for diverse applications. Translation of mussel-inspired wet adhesion typically entails catechol functionalization of polymers and/or polyelectrolytes, and solution processing of many complex components and steps that require optimization and stabilization. Here we reduced the complexity of a wet adhesive primer to synthetic low-molecular-weight catecholic zwitterionic surfactants that show very strong adhesion (∼50 mJ m−2) and retain the ability to coacervate. This catecholic zwitterion adheres to diverse surfaces and self-assembles into a molecularly smooth, thin (<4 nm) and strong glue layer. The catecholic zwitterion holds particular promise as an adhesive for nanofabrication. This study significantly simplifies bio-inspired themes for wet adhesion by combining catechol with hydrophobic and electrostatic functional groups in a small molecule.
NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass
Authors: Elmsjö A , Rosqvist F , Engskog M K R , Haglöf J , Kullberg J , Iggman D , Johansson L , Ahlström H , Arvidsson T , Risérus U , Pettersson C
Published: October 2015

Background:

Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation.

Methods:

In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation.

Results:

We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies.

Conclusion:

A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.
Deletion of murine Arv1 results in a lean phenotype with increased energy expenditure
Authors: Lagor W R , Tong F , Jarrett K E , Lin W , Conlon D M , Smith M , Wang M Y , Yenilmez B O , McCoy M G , Fields D W , O'Neill S M , Gupta R , Kumaravel A , Redon V , Ahima R S , Sturley S L , Billheimer J T , Rader D J
Published: October 2015

Background:

ACAT-related enzyme 2 required for viability 1 (ARV1) is a putative lipid transporter of the endoplasmic reticulum that is conserved across eukaryotic species. The ARV1 protein contains a conserved N-terminal cytosolic zinc ribbon motif known as the ARV1 homology domain, followed by multiple transmembrane regions anchoring it in the ER. Deletion of ARV1 in yeast results in defective sterol trafficking, aberrant lipid synthesis, ER stress, membrane disorganization and hypersensitivity to fatty acids (FAs). We sought to investigate the role of Arv1 in mammalian lipid metabolism.

Methods:

Homologous recombination was used to disrupt the Arv1 gene in mice. Animals were examined for alterations in lipid and lipoprotein levels, body weight, body composition, glucose tolerance and energy expenditure.

Results:

Global loss of Arv1 significantly decreased total cholesterol and high-density lipoprotein cholesterol levels in the plasma. Arv1 knockout mice exhibited a dramatic lean phenotype, with major reductions in white adipose tissue (WAT) mass and body weight on a chow diet. This loss of WAT is accompanied by improved glucose tolerance, higher adiponectin levels, increased energy expenditure and greater rates of whole-body FA oxidation.

Conclusions:

This work identifies Arv1 as an important player in mammalian lipid metabolism and whole-body energy homeostasis.
Epstein–Barr virus LMP1 induces focal adhesions and epithelial cell migration through effects on integrin-α5 and N-cadherin
Authors: Wasil L R , Shair K H Y
Published: October 2015

Epstein–Barr virus (EBV) is a γ-herpesvirus associated with human epithelial and B-cell malignancies. The EBV latent membrane protein (LMP) 1 is expressed in nasopharyngeal carcinoma (NPC) and promotes oncogenic intracellular signaling mechanisms. LMP1 also promotes a pro-migratory phenotype through potential effects on cell surface proteins, as expression of LMP1 induces an epithelial–mesenchymal transition (EMT) in epithelial cell lines. In this study, LMP1 was examined for potential effects on cadherin and integrin surface interactions, and assessed for biological effects on adhesion and motility to fibronectin. Expression of LMP1 in the non-tumorigenic epithelial cell line MCF10a induced an EMT-associated cadherin switch. The induced N-cadherin was ligated and localized to the cell surface as determined by triton-solubility and immunofluorescence assays. In addition, LMP1 induced the assembly of focal adhesions (FAs) with increased production of fibronectin in MCF10a and NP460hTERT-immortalized nasopharyngeal cells. Biochemical enrichment of fibronectin-associated proteins indicated that LMP1 selectively promoted the recruitment of integrin-α5 and Src family kinase proteins to FA complexes. Neutralizing antibodies to N-cadherin and integrin-α5, but not integrin-αV, blocked the adhesion and transwell motility of MCF10a cells to fibronectin induced by LMP1. LMP1-induced transwell motility was also decreased by Src inhibition with the PP2 kinase inhibitor and short hairpin RNAs. These studies reveal that LMP1 has multiple mechanisms to promote the adhesive and migratory properties of epithelial cells through induction of fibronectin and modulation of cell surface interactions involving integrin-α5 and N-cadherin, which may contribute to the metastatic potential of NPC.
Nodes-and-connections RNAi knockdown screening: identification of a signaling molecule network involved in fulvestrant action and breast cancer prognosis
Authors: Miyoshi N , Wittner B S , Shioda K , Hitora T , Ito T , Ramaswamy S , Isselbacher K J , Sgroi D C , Shioda T
Published: October 2015

Although RNA interference (RNAi) knockdown screening of cancer cell cultures is an effective approach to predict drug targets or therapeutic/prognostic biomarkers, interactions among identified targets often remain obscure. Here, we introduce the nodes-and-connections RNAi knockdown screening that generates a map of target interactions through systematic iterations of in silico prediction of targets and their experimental validation. An initial RNAi knockdown screening of MCF-7 human breast cancer cells targeting 6560 proteins identified four signaling molecules required for their fulvestrant-induced apoptosis. Signaling molecules physically or functionally interacting with these four primary node targets were computationally predicted and experimentally validated, resulting in identification of four second-generation nodes. Three rounds of further iterations of the prediction–validation cycle generated third, fourth and fifth generation of nodes, completing a 19-node interaction map that contained three predicted nodes but without experimental validation because of technical limitations. The interaction map involved all three members of the death-associated protein kinases (DAPKs) as well as their upstream and downstream signaling molecules (calmodulins and myosin light chain kinases), suggesting that DAPKs play critical roles in the cytocidal action of fulvestrant. The in silico Kaplan–Meier analysis of previously reported human breast cancer cohorts demonstrated significant prognostic predictive power for five of the experimentally validated nodes and for three of the prediction-only nodes. Immunohistochemical studies on the expression of 10 nodal proteins in human breast cancer tissues not only supported their prognostic prediction power but also provided statistically significant evidence of their synchronized expression, implying functional interactions among these nodal proteins. Thus, the Nodes-and-Connections approach to RNAi knockdown screening yields biologically meaningful outcomes by taking advantage of the existing knowledge of the physical and functional interactions between the predicted target genes. The resulting interaction maps provide useful information on signaling pathways cooperatively involved in clinically important features of the malignant cells, such as drug resistance.
Pharmacologically targeted NMDA receptor antagonism by NitroMemantine for cerebrovascular disease
Authors: Takahashi Hiroto , Xia Peng , Cui Jiankun , Talantova Maria , Bodhinathan Karthik , Li Wenjun , Saleem Sofiyan , Holland Emily A. , Tong Gary , Piña-Crespo Juan , Zhang Dongxian , Nakanishi Nobuki , Larrick James W. , McKercher Scott R. , Nakamura Tomohiro , Wang Yuqiang , Lipton Stuart A.
Published: October 2015

Stroke and vascular dementia are leading causes of morbidity and mortality. Neuroprotective therapies have been proposed but none have proven clinically tolerated and effective. While overstimulation of N-methyl-d-aspartate-type glutamate receptors (NMDARs) is thought to contribute to cerebrovascular insults, the importance of NMDARs in physiological function has made this target, at least in the view of many in ‘Big Pharma,’ ‘undruggable’ for this indication. Here, we describe novel NitroMemantine drugs, comprising an adamantane moiety that binds in the NMDAR-associated ion channel that is used to target a nitro group to redox-mediated regulatory sites on the receptor. The NitroMemantines are both well tolerated and effective against cerebral infarction in rodent models via a dual allosteric mechanism of open-channel block and NO/redox modulation of the receptor. Targeted S-nitrosylation of NMDARs by NitroMemantine is potentiated by hypoxia and thereby directed at ischemic neurons. Allosteric approaches to tune NMDAR activity may hold therapeutic potential for cerebrovascular disorders.
Microwave axial dielectric properties of carbon fiber
Authors: Hong Wen , Xiao Peng , Luo Heng , Li Zhuan
Published: October 2015

Randomly distributed carbon fibers (CFs) reinforced epoxy resin composites are prepared by the pouring method, the dielectric properties of CF composites with different fiber content and length have been performed in the frequency range from 8.2 to 12.4 GHz. The complex permittivity of the composite increases with the fiber length, which is attributed to the decrease of depolarization field and increases with the volume fraction, which is attributed to the increase of polarization. A formula, based on the theory of Reynolds-Hugh, is proposed to calculate the effective permittivity of CF composites and validated by the experiments. The proposed formula is further applied to derive the axial permittivity of CF and analyze the effect of fiber length on the axial permittivity.
Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells
Authors: Ojima Takuma , Shibata Eri , Saito Shiho , Toyoda Masashi , Nakajima Hideki , Yamazaki-Inoue Mayu , Miyagawa Yoshitaka , Kiyokawa Nobutaka , Fujimoto Jun-ichiro , Sato Toshinori , Umezawa Akihiro
Published: October 2015

Glycosphingolipids (GSLs) are glycoconjugates that function as mediators of cell adhesion and modulators of signal transduction. Some well-defined markers of undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are glycoconjugates, such as SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. However, Comprehensive GSL profiles of hiPSCs have not yet been elucidated. The global images of GSLs from the parental cells, hiPSCs and differentiated cells revealed that there are parental cell-independent specific glycolipids, including Globo H (fucosyl-Gb5Cer) and H type1 antigen (fucosyl-Lc4Cer) that are novel markers for undifferentiated hiPSCs. Interestingly, undifferentiated hiPSCs expressed H type 1 antigen, specific for blood type O, regardless of the cells’ genotypes. Thus, in this study, we defined the dynamics of GSL remodeling during reprogramming from parental cell sets to iPSC sets and thence to iPSC-neural cells.
Phase Transformation in Tantalum under Extreme Laser Deformation
Authors: Lu C.-H. , Hahn E. N. , Remington B. A. , Maddox B. R. , Bringa E. M. , Meyers M. A.
Published: October 2015

The structural and mechanical response of metals is intimately connected to phase transformations. For instance, the product of a phase transformation (martensite) is responsible for the extraordinary range of strength and toughness of steel, making it a versatile and important structural material. Although abundant in metals and alloys, the discovery of new phase transformations is not currently a common event and often requires a mix of experimentation, predictive computations and luck. High-energy pulsed lasers enable the exploration of extreme pressures and temperatures, where such discoveries may lie. The formation of a hexagonal (omega) phase was observed in recovered monocrystalline body-centered cubic tantalum of four crystallographic orientations subjected to an extreme regime of pressure, temperature and strain-rate. This was accomplished using high-energy pulsed lasers. The omega phase and twinning were identified by transmission electron microscopy at 70 GPa (determined by a corresponding VISAR experiment). It is proposed that the shear stresses generated by the uniaxial strain state of shock compression play an essential role in the transformation. Molecular dynamics simulations show the transformation of small nodules from body-centered cubic to a hexagonal close-packed structure under the same stress state (pressure and shear).
Fluorescence polarization measures energy funneling in single light-harvesting antennas—LH2 vs conjugated polymers
Authors: Camacho Rafael , Tubasum Sumera , Southall June , Cogdell Richard J. , Sforazzini Giuseppe , Anderson Harry L. , Pullerits Tõnu , Scheblykin Ivan G.
Published: October 2015

Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ε). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ε = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET.
Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae
Authors: Zowawi Hosam M. , Forde Brian M. , Alfaresi Mubarak , Alzarouni Abdulqadir , Farahat Yasser , Chong Teik-Min , Yin Wai-Fong , Chan Kok-Gan , Li Jian , Schembri Mark A. , Beatson Scott A. , Paterson David L.
Published: October 2015

Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-blaOXA-181 mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.
The Scaling of Human Contacts and Epidemic Processes in Metapopulation Networks
Authors: Tizzoni Michele , Sun Kaiyuan , Benusiglio Diego , Karsai Márton , Perra Nicola
Published: October 2015

We study the dynamics of reaction-diffusion processes on heterogeneous metapopulation networks where interaction rates scale with subpopulation sizes. We first present new empirical evidence, based on the analysis of the interactions of 13 million users on Twitter, that supports the scaling of human interactions with population size with an exponent γ ranging between 1.11 and 1.21, as observed in recent studies based on mobile phone data. We then integrate such observations into a reaction- diffusion metapopulation framework.Weprovide an explicit analytical expression for the global invasion threshold which sets a critical value of the diffusion rate below which a contagion process is not able to spread to a macroscopic fraction of the system. In particular, we consider the Susceptible-Infectious-Recovered epidemic model. Interestingly, the scaling of human contacts is found to facilitate the spreading dynamics. This behavior is enhanced by increasing heterogeneities in the mobility flows coupling the subpopulations. Our results show that the scaling properties of human interactions can significantly affect dynamical processes mediated by human contacts such as the spread of diseases, ideas and behaviors.
Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein
Authors: Janowska Maria K. , Wu Kuen-Phon , Baum Jean
Published: October 2015

Pathology in Parkinson’s disease is linked to self-association of α-Synuclein (αS) into pathogenic oligomeric species and highly ordered amyloid fibrils. Developing effective therapeutic strategies against this debilitating disease is critical and βS, a pre-synaptic protein that co-localizes with αS, can act as an inhibitor of αS assembly. Despite the potential importance of βS as an inhibitor of αS, the nature, location and specificity of the molecular interactions between these two proteins is unknown. Here we use NMR paramagnetic relaxation enhancement experiments, to demonstrate that βS interacts directly with αS in a transient dimer complex with high specificity and weak affinity. Inhibition of αS by βS arises from transient αS/βS heterodimer species that exist primarily in head- to- tail configurations while αS aggregation arises from a more heterogeneous and weaker range of transient interactions that include both head-to-head and head-to-tail configurations. Our results highlight that intrinsically disordered proteins can interact directly with one another at low affinity and that the transient interactions that drive inhibition versus aggregation are distinct by virtue of their plasticity and specificity.