bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic (Alkyl)(Amino)Carbene Complexes of Rhodium and Nickel and Their Steric and Electronic Parameters
Authors: Paul Ursula S. D. , Sieck Carolin , Haehnel Martin , Hammond Kai , Marder Todd B. , Radius Udo 
Published: July 2016

AbstractN‐heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAACmethyl, which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands.
Measurement and Characterization of Apoptosis by Flow Cytometry
Authors: Telford William , Tamul Karen , Bradford Jolene 
Published: July 2016

AbstractApoptosis is an important mechanism in cell biology, playing a critical regulatory role in virtually every organ system. It has been particularly well characterized in the immune system, with roles ranging from immature immune cell development and selection to down‐regulation of the mature immune response. Apoptosis is also the primary mechanism of action of anti‐cancer drugs. Flow cytometry has been the method of choice for analyzing apoptosis in suspension cells for more than 25 years. Numerous assays have been devised to measure both the earliest and latest steps in the apoptotic process, from the earliest signal‐transduction events to the late morphological changes in cell shape and granularity, proteolysis, and chromatin condensation. These assays are particularly powerful when combined into multicolor assays determining several apoptotic characteristics simultaneously. The multiparametric nature of flow cytometry makes this technology particularly suited to measuring apoptosis. In this unit, we will describe the four main techniques for analyzing caspase activity in apoptotic cells, combined with annexin V and cell permeability analysis. These relatively simple multiparametric assays are powerful techniques for assessing cell death. © 2016 by John Wiley & Sons, Inc.
Fabry Disease Biomarkers: Analysis of Urinary Lyso‐Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry
Authors: Lavoie Pamela , Boutin Michel , Abaoui Mona , Auray‐Blais Christiane 
Published: July 2016

AbstractFabry disease is an X‐linked lysosomal storage disorder caused by the absence or reduction of the enzyme α‐galactosidase A activity. Currently, globotriaosylsphingosine (lyso‐Gb3) and globotriaosylceramide (Gb3) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso‐Gb3 and seven structurally related analogs. A solid‐phase extraction process is performed, then lyso‐Gb3 and its analogs are analyzed simultaneously with an internal standard by ultra‐performance liquid chromatography (UPLC) coupled to a tandem mass spectrometry (MS/MS) system. This methodology can be useful for the diagnosis of Fabry patients, including patients with cardiac variant mutations, but also to monitor the efficacy of therapeutic interventions, considering that lyso‐Gb3 analogs are more elevated than lyso‐Gb3 itself in urine. © 2016 by John Wiley & Sons, Inc.
Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells
Authors: Wang Liheng , Egli Dieter , Leibel Rudolph L. 
Published: July 2016

AbstractThe hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate‐like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2.1+ hypothalamic progenitors. Subsequent incubation with BDNF induces the differentiation and maturation of pro‐opiomelanocortin and neuropeptide Y neurons, which are major cell types in the arcuate hypothalamus. These neurons have molecular and cellular characteristics consistent with arcuate neurons. © 2016 by John Wiley & Sons, Inc.
Tandem Mass Spectrometry Quantitation of Lyso‐Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients
Authors: Boutin Michel , Lavoie Pamela , Abaoui Mona , Auray‐Blais Christiane 
Published: July 2016

AbstractFabry disease is an X‐linked lysosomal storage disorder, caused by a deficit in α‐galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso‐Gb3), globotriaosylceramide (Gb3), and galabiosylceramide (Ga2) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso‐Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso‐Gb3 with different chemical modifications on the sphingosine chain (−C2H4, −H2, +O, +H2O, +H2O2, and +H2O3). An ultra‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated for the multiplex analysis of lyso‐Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed‐mode strong cation exchange (MCX) cartridges. An in‐house synthesized N‐glycinated lyso‐Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso‐Gb3 and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley & Sons, Inc.
CRISPR/Cas9‐Based Multiplex Genome Editing in Monocot and Dicot Plants
Authors: Ma Xingliang , Liu Yao‐Guang 
Published: July 2016

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9‐mediated genome targeting system has been applied to a variety of organisms, including plants. Compared to other genome‐targeting technologies such as zinc‐finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs), the CRISPR/Cas9 system is easier to use and has much higher editing efficiency. In addition, multiple “single guide RNAs” (sgRNAs) with different target sequences can be designed to direct the Cas9 protein to multiple genomic sites for simultaneous multiplex editing. Here, we present a procedure for highly efficient multiplex genome targeting in monocot and dicot plants using a versatile and robust CRISPR/Cas9 vector system, emphasizing the construction of binary constructs with multiple sgRNA expression cassettes in one round of cloning using Golden Gate ligation. We also describe the genotyping of targeted mutations in transgenic plants by direct Sanger sequencing followed by decoding of superimposed sequencing chromatograms containing biallelic or heterozygous mutations using the Web‐based tool DSDecode. © 2016 by John Wiley & Sons, Inc.
CRISPR‐Cas9‐Guided Genome Engineering in C. elegans
Authors: Kim Hyun‐Min , Colaiácovo Monica P. 
Published: July 2016

AbstractThe CRISPR (clustered regularly interspaced short palindromic repeats)–Cas (CRISPR‐associated) system is successfully being used for efficient and targeted genome editing in various organisms, including the nematode C. elegans. Recent studies have developed various CRISPR‐Cas9 approaches to enhance genome engineering via two major DNA double‐strand break repair pathways: non‐homologous end joining and homologous recombination. Here we describe a protocol for Cas9‐mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning, as well as injection methods required for delivering Cas9, sgRNAs, and repair template DNA into the C. elegans germline. © 2016 by John Wiley & Sons, Inc.
Associations between bedtime and nighttime parenting and infant cortisol in the first year
Authors: Philbrook Lauren E. , Teti Douglas M. 
Published: July 2016

AbstractWe examined how maternal care within the bedtime and nighttime contexts influences infant cortisol levels and patterning. Eighty‐two mothers (Mage = 29.4 years) and infants participated in a longitudinal study when infants were 3, 6, and 9 months old. At each time point, bedtime and nighttime parenting were recorded and infant cortisol at bedtime and the following morning was analyzed. Multilevel model analyses showed that infants had lower cortisol levels when mothers were more emotionally available at bedtime, and infants whose mothers responded more often to their non‐distressed cues had lower cortisol levels on average. Less co‐sleeping and more maternal responses to infant distress were linked to healthier cortisol patterning. By shedding light on parenting qualities and behaviors that influence infant cortisol, these results indicate avenues for intervention and suggest the utility of studying parenting in infant sleep contexts.
Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE Pro™ — United States, 2013
Authors: Chatham‐Stephens Kevin , Taylor Ethel , Chang Arthur , Peterson Amy , Daniel Johnni , Martin Colleen , Deuster Patricia , Noe Rebecca , Kieszak Stephanie , Schier Josh , Klontz Karl , Lewis Lauren 
Published: July 2016

In September 2013, the Hawaii Department of Health (HDOH) was notified of seven adults who developed acute hepatitis after taking OxyELITE Pro™, a weight loss and sports dietary supplement. CDC assisted HDOH with their investigation, then conducted case‐finding outside of Hawaii with FDA and the Department of Defense (DoD).We defined cases as acute hepatitis of unknown etiology that occurred from April 1, 2013, through December 5, 2013, following exposure to a weight loss or muscle‐building dietary supplement, such as OxyELITE Pro™. We conducted case‐finding through multiple sources, including data from poison centers (National Poison Data System [NPDS]) and FDA MedWatch.We identified 40 case‐patients in 23 states and two military bases with acute hepatitis of unknown etiology and exposure to a weight loss or muscle building dietary supplement. Of 35 case‐patients who reported their race, 15 (42.9%) reported white and 9 (25.7%) reported Asian. Commonly reported symptoms included jaundice, fatigue, and dark urine. Twenty‐five (62.5%) case‐patients reported taking OxyELITE Pro™. Of these 25 patients, 17 of 22 (77.3%) with available data were hospitalized and 1 received a liver transplant. NPDS and FDA MedWatch each captured seven (17.5%) case‐patients.Improving the ability to search surveillance systems like NPDS and FDA MedWatch for individual and grouped dietary supplements, as well as coordinating case‐finding with DoD, may benefit ongoing surveillance efforts and future outbreak responses involving adverse health effects from dietary supplements. This investigation highlights opportunities and challenges in using multiple sources to identify cases of suspected supplement associated adverse events. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Perceived collective continuity and attitudes toward outgroups
Authors: Warner Ruth H. , Kent Ana H. , Kiddoo Kristin L. 
Published: July 2016

AbstractIn a series of six studies, we examined the role that perceived collective continuity (PCC) plays in intergroup attitudes. While the extant literature focuses on attitudes toward ingroups, the current studies chose to expand upon this research by concentrating on three types of outgroups (national, religious, and organizational). Results indicated that for groups perceived as neutral or positive, increased PCC was associated with more positive attitudes, while for enemy groups, increased PCC was associated with more negative attitudes. Entitativity played a mediating role such that as the outgroup was perceived as more continuous, it was also seen as more entitative. Higher entitativity led to less negative attitudes toward a past ally but more negative attitudes toward a past enemy. Results held whether past conflict and PCC were measured or manipulated, further supporting our findings. PCC has negative or positive implications for judgments of outgroups depending on intergroup history. Copyright © 2016 John Wiley & Sons, Ltd.
Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging
Authors: Ghosh Shampa , Sinha Jitendra Kumar , Raghunath Manchala 
Published: July 2016

AbstractDNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson‐Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717–721, 2016
Income and Democracy: A Smooth Varying Coefficient Redux
Authors: Lundberg Alexander L. , Huynh Kim P. , Jacho‐Chávez David T. 
Published: July 2016

SummaryAcemoglu et al. (American Economic Review 2008; 98: 808–842) find no effect of income on democracy when controlling for fixed effects in a dynamic panel model. Work by Moral‐Benito and Bartolucci (Economics Letters 2012; 117: 844–847) and Cervellati et al. (American Economic Review 2014; 104: 707–719) suggests that the original model might have been misspecified and proposes alternative specifications instead. We formally test these parametric specifications by implementing Lee's (Journal of Econometrics 2014; 178: 146–166) dynamic panel test of linear parametric specifications against a general class of nonlinear alternatives robustly and reject all these specifications. However, using a more flexible model proposed by Cai and Li (Econometric Theory 2008; 24: 1321–1342) we find that the relationship between income and democracy appears to be mediated by education, but results are not statistically significant. Copyright © 2016 John Wiley & Sons, Ltd.
Do Serum Creatinine Levels Show Clinically Significant Fluctuations on Serial Determinations on the Siemens Advia 1800 Analyzer?
Authors: Levitan Daniel , Harper Aaron E. , Sun Yi , Scarpa Carniello Jose V. , Momeni Amir , Kagan Joshua , Alexis Herol , Eid Ikram , Harris Loretta , Marshal Barbara , Tafani Edlira , Pincus Matthew 
Published: July 2016

BackgroundThe goal of this work was to determine whether there are clinically significant fluctuations in the level of serum creatinine on serial determinations, especially in the borderline range (1.1–1.3 mg/dl), after specimen storage.MethodsSixty‐one serum samples were analyzed. They were divided into three categories based on the initial serum creatinine measurement: low (≤1.0 mg/dl), borderline (1.1–1.3 mg/dl), and high (≥1.4 mg/dl). The specimens were stored at 4°C and run on the Siemens Advia 1800 chemistry analyzer on days 1, 3, and 11.ResultsStatistical comparisons of the three groups were made using the unpaired t‐test, yielding a two‐tailed P‐value for each group comparison. The P‐values ranged from 0.0829 to 0.3892, indicating no statistically significant difference between the standard deviations of each group.ConclusionsMild‐to‐moderate fluctuations in precision occur in successive serum creatinine determinations. The overwhelming majority of these fluctuations should not affect clinical decision making.
Cardiac cachexia: hic et nunc
Authors: Loncar Goran , Springer Jochen , Anker Markus , Doehner Wolfram , Lainscak Mitja 
Published: July 2016

AbstractCardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.
Proteomic evidence of methanotrophy in methane‐enriched hypolimnetic lake water
Authors: Ullrich Nina , Casper Peter , Otto Andreas , Gessner Mark O. 
Published: July 2016

AbstractFreshwaters have recently been recognized as important sources of methane emitted to the atmosphere, and microbial methane oxidation at the oxic/anoxic interface is a key process controlling these emissions. We applied proteomics to determine enzyme expression patterns of methanotrophs in response to methane enrichment of lake water. In a small‐scale incubation experiment with natural bacterial communities we compared enzymes involved in methane metabolism between control and methane‐enriched hypolimnetic water simulating high (∼1 mM) and low (∼0.001 mM) methane concentrations at oxyclines in lakes. Methane was effectively consumed when the supply was high, reducing oxygen levels from 0.40 mM (12.9 mg L−1) to 0.09 mM (3.0 mg L−1), well below those in the controls. The dominant key enzyme of microbial methane oxidation, particulate methane monooxygenase, was identified in both enriched and control flasks, whereas enzymes potentially involved in methane metabolism via the RuMP pathway and serine cycle were essentially restricted to the enriched flasks. All enzymes had best sequence matches with type I methanotrophs, whereas no indication of type II or type X methanotrophs was found, even though four enzymes of the serine cycle were identified. Overall, our proteomic analysis provides convincing evidence that a suite of genes required for methanotrophy are quickly expressed when the presence of both methane and oxygen creates conditions characteristic of oxyclines in lakes.
Triolimus: A Multi‐Drug Loaded Polymeric Micelle Containing Paclitaxel, 17‐AAG, and Rapamycin as a Novel Radiosensitizer
Authors: Tomoda Keishiro , Tam Yu Tong , Cho Hyunah , Buehler Darya , Kozak Kevin R. , Kwon Glen S. 
Published: July 2016

Triolimus is a multi‐drug loaded polymeric micelle containing paclitaxel (PTX), 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 × 10−9m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 × 10−9m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17‐AAG (P/17) >17‐AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17‐AAG/RAP at 15/15/7.5 mg kg−1) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17‐AAG/RAP at 60/60/30 mg kg−1) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited.
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Transverse relaxation and flip angle mapping: Evaluation of simultaneous and independent methods using multiple spin echoes
Authors: McPhee Kelly C. , Wilman Alan H. 
Published: July 2016

PurposeTo evaluate transverse relaxation (T2) and flip angle maps derived from signal pathway modeling of multiple spin echoes using simultaneous or independent T2 and flip angle fitting.MethodsWe examined different approaches to indirect and stimulated echo compensated T2 relaxometry from multiple spin echoes to evaluate both T2 and flip angle accuracy in simulation, phantom, and human brain. Signal pathways were modeled with or without independent flip angle maps using either Bloch simulations, or Extended Phase Graph (EPG) with Fourier or Shinnar‐Le Roux approximation of slice profiles.ResultsSlice‐selective decay curves differ substantially between models. Inaccurate flip angles are obtained with EPG methods, although T2 values are relatively accurate. Providing measured flip angles to EPG methods yields erroneous T2. Bloch methods improve both T2 and flip angle results. Simultaneous fitting can suffer from flip angle redundancy yielding multiple T2 solutions, particularly in low signal‐to‐noise ratio cases.ConclusionEPG fitting provides reasonably accurate T2, but is limited by poor accuracy in resulting flip angles, and T2 errors increase when flip angles are provided. Bloch simultaneous fitting of T2 and flip angle provides excellent results, but can be limited by multiple solutions which can be overcome by including a flip angle map. Magn Reson Med 77:2057–2065, 2017. © 2016 International Society for MagneticResonance in Medicine