bluuebunny/crossref_metadata_2025 huggingface dataset:
Striking against bioterrorism with advanced proteomics and reference methods
Authors: Armengaud Jean
Published: December 2016

The intentional use by terrorists of biological toxins as weapons has been of great concern for many years. Among the numerous toxins produced by plants, animals, algae, fungi, and bacteria, ricin is one of the most scrutinized by the media because it has already been used in biocrimes and acts of bioterrorism. Improving the analytical toolbox of national authorities to monitor these potential bioweapons all at once is of the utmost interest. MS/MS allows their absolute quantitation and exhibits advantageous sensitivity, discriminative power, multiplexing possibilities, and speed. In this issue of Proteomics, Gilquin et al. (Proteomics 2017, 17, 1600357) present a robust multiplex assay to quantify a set of eight toxins in the presence of a complex food matrix. This MS/MS reference method is based on scheduled SRM and high‐quality standards consisting of isotopically labeled versions of these toxins. Their results demonstrate robust reliability based on rather loose scheduling of SRM transitions and good sensitivity for the eight toxins, lower than their oral median lethal doses. In the face of an increased threat from terrorism, relevant reference assays based on advanced proteomics and high‐quality companion toxin standards are reliable and firm answers.
Controlled growth and spray deposition of silver nanowires for ITO‐free, flexible, and high brightness OLEDs
Authors: Alshammari Abdullah S. , Sam F. Laurent M. , Rozanski Lynn J. , Mills Christopher A. , Alenezi Mohammad R. , Beliatis Michail J. , Jayawardena K. D. G. Imalka , Underwood John M. , Silva S. Ravi P.
Published: December 2016

The next generation of electronic devices will require low cost materials and processing techniques that are fully compatible with flexible substrates and large area applications. Silver nanowires are promising candidates for many applications and can be processed by various solution‐based large area deposition techniques. In this work, high aspect ratio silver nanowires were synthesized via a polyol reduction of silver nitrate in the presence of a metal‐salt and a capping agent. The grown nanowires were spray coated and simply planarized with inkjet printed PEDOT:PSS to produce smooth and high performance nanocomposite electrodes suitable for industrial applications. The nanocomposite electrodes exhibit figure of merit values (σDC/σOP) of about 60, higher than the values required for industrial use (>35). High conductivity with high optical transparency was achieved by controlling the aspect ratio of the nanowires and their concentration in the films. The highly conductive and transparent electrodes were utilized to fabricate organic light emitting diodes, which exhibited high luminance (∼ 7 × 103 cd m−2) and performance comparable to a “benchmark” ITO electrode. The results show that the combination of the nanocomposite materials, together with the solution based techniques could pave the way towards flexible, solution processable, low cost, and large area device applications.

ITO‐free OLEDs fabricated using solution processed Ag NW/PEDOT:PSS nanocomposites as transparent conductive electrode. Improving the aspect ratio of the grown nanowires along with controlling their density in the films allow for highly conductive and transparent nanocomposite electrodes. These nanocomposite samples are utilized as a direct replacement for ITO in OLEDs.
Emerging biotechnologies for production of itaconic acid and its applications as a platform chemical
Authors: Saha Badal C
Published: December 2016

Recently, itaconic acid (IA), an unsaturated C5-dicarboxylic acid, has attracted much attention as a biobased building block chemical. It is produced industrially (>80 g L−1) from glucose by fermentation with Aspergillus terreus. The titer is low compared with citric acid production (>200 g L−1). This review summarizes the latest progress on enhancing the yield and productivity of IA production. IA biosynthesis involves the decarboxylation of the TCA cycle intermediate cis-aconitate through the action of cis-aconitate decarboxylase (CAD) enzyme encoded by the CadA gene in A. terreus. A number of recombinant microorganisms have been developed in an effort to overproduce it. IA is used as a monomer for production of superabsorbent polymer, resins, plastics, paints, and synthetic fibers. Its applications as a platform chemical are highlighted. It has a strong potential to replace petroleum-based methylacrylic acid in industry which will create a huge market for IA.
Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors
Authors: Yamamoto Noboru , Nokihara Hiroshi , Yamada Yasuhide , Shibata Takashi , Tamura Yosuke , Seki Yoshitaka , Honda Kazunori , Tanabe Yuko , Wakui Hiroshi , Tamura Tomohide
Published: December 2016

Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with advanced solid tumors with a life expectancy of ≥3 months. Patients were observed for 3 weeks after a single dose of nivolumab at 1, 3, 10 or 20 mg/kg, then received the same dose of nivolumab every 2 weeks until unacceptable toxicity or disease progression occurred. This study included a maximum dose of 20 mg/kg, which is the highest dose of nivolumab evaluated to date. The maximum dose was 10 mg/kg in previous studies. Results The commonest adverse drug reaction was lymphopenia, which occurred in 10 (58.8%) patients, including two (11.8%) with Grade ≥3 events. No dose-limiting toxicities (DLTs) were observed up to the maximum dose of 20 mg/kg. The area under the concentration–time curve from time 0 to the last measurable concentration was linear up to 20 mg/kg. The maximum concentration showed dose-dependency up to 10 mg/kg, but not between 10 and 20 mg/kg. One durable complete response and two partial responses were observed. Conclusions Nivolumab at doses of 1–20 mg/kg was not associated with DLTs, and it was generally well tolerated at doses of up to 20 mg/kg in Japanese patients with advanced solid tumors.
Synthesis, Characterization, and Evaluation of Ethoxylated Lauryl‐Myrisityl Alcohol Nonionic Surfactants as Wetting Agents, Anti‐Foamers, and Minimum Film Forming Temperature Reducers in Emulsion Polymer Lattices
Authors: Abd El‐Ghaffar M. A. , Sherif M. H. , Taher El‐Habab A.
Published: December 2016

Two nonionic FAEO (fatty alcohol ethoxylated) surfactants with varying solubility were obtained by the reaction of lauryl‐myrisityl alcohol (LMA) with ethylene oxide to yield lauryl‐myristyl/alcohol ethoxylated with 3 and 31 mol of ethylene oxide by changing the length of polyethylene glycol segment. The prepared surfactants, designated as LMAEO‐3 and LMAEO‐31, were characterized for their structures using spectroscopic measurements; in addition, their surface properties were investigated. The results indicated that LMAEO‐31 exhibits excellent surface activity. Evaluation of the surfactants as wetting agents, anti‐foamers, and minimum film forming temperature (MFFT) reducer in emulsion polymer lattices achieved promising results indicating high performance in the mentioned industrial applications.
Mastering the sentence
Authors: Lingard Lorelei
Published: December 2016

None
Intraoperative high‐field magnetic resonance imaging, multimodal neuronavigation, and intraoperative electrophysiological monitoring‐guided surgery for treating supratentorial cavernomas
Authors: Li Fang‐ye , Chen Xiao‐lei , Xu Bai‐nan
Published: December 2016

Objective

To determine the beneficial effects of intraoperative high‐field magnetic resonance imaging (MRI), multimodal neuronavigation, and intraoperative electrophysiological monitoring‐guided surgery for treating supratentorial cavernomas.

Methods

Twelve patients with 13 supratentorial cavernomas were prospectively enrolled and operated while using a 1.5 T intraoperative MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring. All cavernomas were deeply located in subcortical areas or involved critical areas. Intraoperative high‐field MRIs were obtained for the intraoperative “visualization” of surrounding eloquent structures, “brain shift” corrections, and navigational plan updates.

Results

All cavernomas were successfully resected with guidance from intraoperative MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring. In 5 cases with supratentorial cavernomas, intraoperative “brain shift” severely deterred locating of the lesions; however, intraoperative MRI facilitated precise locating of these lesions. During long‐term (>3 months) follow‐up, some or all presenting signs and symptoms improved or resolved in 4 cases, but were unchanged in 7 patients.

Conclusions

Intraoperative high‐field MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring are helpful in surgeries for the treatment of small deeply seated subcortical cavernomas.
A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression
Authors: Carrasquillo Minerva M. , Allen Mariet , Burgess Jeremy D. , Wang Xue , Strickland Samantha L. , Aryal Shivani , Siuda Joanna , Kachadoorian Michaela L. , Medway Christopher , Younkin Curtis S. , Nair Asha , Wang Chen , Chanana Pritha , Serie Daniel , Nguyen Thuy , Lincoln Sarah , Malphrus Kimberly G. , Morgan Kevin , Golde Todd E. , Price Nathan D. , White Charles C. , De Jager Philip L. , Bennett David A. , Asmann Yan W. , Crook Julia E. , Petersen Ronald C. , Graff‐Radford Neill R. , Dickson Dennis W. , Younkin Steven G. , Ertekin‐Taner Nilüfer
Published: December 2016

Introduction

We hypothesized that common Alzheimer's disease (AD)‐associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.

Methods

Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis.

Results

A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347‐C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta‐analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni‐corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively).

Discussion

Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome‐wide association study meta‐analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.
Dimensions of Expertise in Wine Evaluation
Authors: Ashton Robert H.
Published: December 2016

This article explores the question of what distinguishes novices from experts in wine evaluation. Is it experts’ superior sensory abilities related to taste and smell, their superior cognitive abilities related to knowledge and memory, or a combination of both—and if a combination, which of the two dimensions of expertise, sensory or cognitive, seems to be more important? I address these issues by considering what has been learned in the past 30+ years from research concerning the sensory and cognitive dimensions of expertise in wine evaluation. The research examines expert/novice differences at both the chemical component level (detecting, discriminating among, and describing wine-relevant chemical components) and the holistic level (hedonic evaluation of wine as an integrated manifestation of its components). (JEL Classification: C93)
Making Circles of Steel and Castles of Vanity Possible: The Cold War in theLongue Duréeof “Modernity”
Authors: Bodden Michael H.
Published: December 2016

Alfred McCoy's paper offers a masterful analysis of the way in which the Philippines, and more generally Southeast Asia, were used as base and laboratory for extending US dominance—its hegemony—in the twentieth century, and in particular the Cold War era and its aftermath. He offers a succinct summary of the way in which US organs of global domination—the National Security Council, the CIA, the Defense Department—worked throughout the developing world and in Europe to ensure compliant, anti-communist regimes during the Cold War period, which also meant that more than once the United States was thwarting democracy in a number of locales and thus casting its own ideology of democratic progress and prosperity into doubt.
Temporal and spatial trends in stranding records of cetaceans on the Irish coast, 2002–2014
Authors: McGovern Barry , Culloch Ross M. , O'Connell Michael , Berrow Simon
Published: December 2016

Using Irish strandings data collected between 2002 and 2014, seasonal and annual trends in the number of strandings for all strandings identified to species level (N = 1480), and for the five most frequently reported species: common dolphin (25.7% of records), harbour porpoise (22.2%), long-finned pilot whale (8.8%), striped dolphin (6.9%) and bottlenose dolphin (6.9%) were investigated. With the exception of bottlenose dolphins, there was a significant linear increase in the number of strandings across years for all species and for all strandings collectively, that were identified to species-level. Only common dolphins demonstrated a significant increase in the proportion of records relative to all other strandings, which may be indicative of a real rise in the number of strandings of this species. Common dolphins and harbour porpoises showed a similar significant difference in monthly strandings, with more strandings occurring during the earlier months of the year. Significant differences in the gender of stranded animals were found in common, striped, bottlenose and Atlantic white-sided dolphins and sperm and pygmy sperm whales. Live and mass stranding events were primarily comprised of pelagic species. Most strandings occurred on the south and west coasts, with two hotspots for live and mass strandings identified. The patterns and trends identified are discussed in relation to the caveats in interpreting strandings data. Specifically to Ireland, the findings highlight the urgent need to build on the current volunteer reporting network and augment this comprehensive dataset with post-mortem examinations to better understand the cause of the trends identified. The importance of strandings data in informing conservation and management guidelines of these species’ is discussed.
Activity of two extracts of Cynanchum paniculatum against Ichthyophthirius multifiliis theronts and tomonts
Authors: JI-HONG WEN , YAN-LI WANG , YU-HUA LIU , JI-YUAN ZHANG , ZE-HONG LI
Published: December 2016

The present study aims to evaluate the antiparasitic activity of active components from Cynanchum paniculatum against Ichthyophthirius multifiliis. The antiparasitic activities of two bioassay-guided fractionationated compounds from C. paniculatum identified as Cynatratoside-A and Cynanversicoside C, by comparing spectral data (NMR and ESI-MS) with literature values, were evaluated by in vitro assay. These showed that both could kill theronts of I. multifiliis at a concentration of 10·0 mg L−1, with the median effective concentration (EC50) values of 4·6 mg L−1 and 5·2 mg L−1 for Cynatratoside-A and Cynanversicoside C, respectively. Encysted tomonts were killed at concentrations of 8·0 mg L−1 with both compounds. In vivo experiments demonstrated that fish treated with both compounds at 15·0 mg L−1 carried significantly fewer parasites than controls (P < 0·05). There were no mortalities among treated fish group compared with 75% mortality of untreated fish. Cynatratoside-A and Cynanversicoside C are therefore potential candidate drugs for use against I. multifiliis.
Two's a crowd? Crowding effect in a parasitic castrator drives differences in reproductive resource allocation in singlevsdouble infections
Authors: FONG CAITLIN R. , MORON NANCY A. , KURIS ARMAND M.
Published: December 2016

The ‘crowding effect’ is a result of competition by parasites within a host for finite resources. Typically, the severity of this effect increases with increasing numbers of parasites within a host and manifests in reduced body size and thus fitness. Evidence for the crowding effect is mixed – while some have found negative effects, others have found a positive effect of increased parasite load on parasite fitness. Parasites are consumers with diverse trophic strategies reflected in their life history traits. These distinctions are useful to predict the effects of crowding. We studied a parasitic castrator, a parasite that usurps host reproductive energy and renders the host sterile. Parasitic castrators typically occur as single infections within hosts. With multiple parasitic castrators, we expect strong competition and evidence of crowding. We directly assess the effect of crowding on reproductive success in a barnacle population infected by a unique parasitic castrator,Hemioniscus balani,an isopod parasite that infects and blocks reproduction of barnacles. We find (1) strong evidence of crowding in double infections, (2) increased frequency of double infections in larger barnacle hosts with more resources and (3) perfect compensation in egg production, supporting strong space limitation. Our results document that the effects of crowding are particularly severe for this parasitic castrator, and may be applicable to other castrators that are also resource or space limited.
External Resources and Indiscriminate Violence
Authors: Zhukov Yuri M.
Published: December 2016

Within a single conflict, the scale of government violence against civilians can vary greatly—from mass atrocities in one village to eerie restraint in the next. This article argues that the scale of anticivilian violence depends on a combatant's relative dependence on local and external sources of support. External resources make combatants less dependent on the local population, yet create perverse incentives for how the population is to be treated. Efforts by the opposition to interdict the government's external resources can reverse this effect, making the government more dependent on the local population. The article tests this relationship with disaggregated archival data on German-occupied Belarus during World War II. It finds that Soviet partisan attacks against German personnel provoked reprisals against civilians but that attacks against railroads had the opposite effect. Where partisans focused on disrupting German supply lines rather than killing Germans, occupying forces conducted fewer reprisals, burned fewer houses, and killed fewer people.
ESTIMATING THE QUADRATIC VARIATION SPECTRUM OF NOISY ASSET PRICES USING GENERALIZED FLAT-TOP REALIZED KERNELS
Authors: Varneskov Rasmus Tangsgaard
Published: December 2016

This paper analyzes a generalized class of flat-top realized kernel estimators for the quadratic variation spectrum, that is, the decomposition of quadratic variation into integrated variance and jump variation. The underlying log-price process is contaminated by additive noise, which consists of two orthogonal components to accommodate α-mixing dependent exogenous noise and an asymptotically non-degenerate endogenous correlation structure. In the absence of jumps, the class of estimators is shown to be consistent, asymptotically unbiased, and mixed Gaussian at the optimal rate of convergence, n1/4. Exact bounds on lower-order terms are obtained, and these are used to propose a selection rule for the flat-top shrinkage. Bounds on the optimal bandwidth for noise models of varying complexity are also provided. In theoretical and numerical comparisons with alternative estimators, including the realized kernel, the two-scale realized kernel, and a bias-corrected pre-averaging estimator, the flat-top realized kernel enjoys a higher-order advantage in terms of bias reduction, in addition to good efficiency properties. The analysis is extended to jump-diffusions where the asymptotic properties of a flat-top realized kernel estimate of the total quadratic variation are established. Apart from a larger asymptotic variance, they are similar to the no-jump case. Finally, the estimators are used to design two classes of (medium) blocked realized kernels, which produce consistent, non-negative estimates of integrated variance. The blocked estimators are shown to have no loss either of asymptotic efficiency or in the rate of consistency relative to the flat-top realized kernels when jumps are absent. However, only the medium blocked realized kernels achieve the optimal rate of convergence under the jump alternative.
The Lessons of Effective Altruism
Authors: Rubenstein Jennifer C.
Published: December 2016

Carol Sue Snowden worked for thirty years as a librarian at the Columbus Metropolitan Library in Columbus, Ohio. She led a quiet, frugal life, spending money mostly on books, which were her passion. When she died, she donated the money she had saved—over $1 million—to the Columbus library and seven local schools. Most of us would look upon this generosity with admiration, but according to a new movement called Effective Altruism (EA), Snowden got it wrong. While she was right to donate her money, she should have instead directed it to an organization that does the most good overall.
Factors associated with influenza vaccine uptake in older adults living in the community in Singapore
Authors: ANG L. W. , CUTTER J. , JAMES L. , GOH K. T.
Published: December 2016

In Singapore, influenza vaccination is recommended for persons at higher risk of complications of seasonal influenza, including those with chronic medical conditions and the elderly (individuals aged ⩾65 years). We investigated the factors associated with influenza vaccine uptake based on a nationally representative sample of community-dwelling adults aged>50 years. The data for this study were obtained from the National Health Surveillance Survey (NHSS) 2013. The association between influenza vaccine uptake and socio-demographic and health-related variables was analysed using univariable and multivariable logistic regression models. Of 3700 respondents aged ⩾50 years in the NHSS, 15·2% had received seasonal influenza vaccination in the past year. Older age, single marital status and economic inactivity were the socio-demographic variables independently associated with vaccine uptake. Health-related factors which were predictive of influenza vaccine uptake were sufficient total physical activity, better self-rated health, having at least one medical condition at risk of influenza complications and a regular family doctor/general practitioner. Influenza vaccine uptake in community-dwelling older adults was low. Our findings are of relevance in the formulation of public health policies and targeted health promotion strategies to increase vaccine uptake in this population group.
The Demographics and Education of Emergency Medical Services (EMS) Professionals: A National Longitudinal Investigation
Authors: Bentley Melissa A. , Shoben Abigail , Levine Roger
Published: December 2016

Objectives

The objectives of this study were to assess longitudinal and cross-sectional changes in Emergency Medical Technician (EMT)-Basics and Paramedics: (1) demographics, (2) employment characteristics, and (3) initial Emergency Medical Services (EMS) education.

Methods

These data were collected between 1999 and 2008 employing survey techniques aimed at collecting valid data. A random, stratified sample was utilized to allow results to be generalizable to the nationally certified EMS population. Survey weights that were adjusted for each stratum’s response were estimated. Weighted percentages, averages for continuous variables, and 95% confidence intervals (CIs) were calculated. Significant changes over time were noted when the CIs did not overlap.

Results

In all 10 years of data collection, the proportion of EMT-Paramedics who were male was greater than the proportion of EMT-Basics who were male. A substantial proportion of respondents performed EMS services for more than one agency: between 39.8% and 43.5% of EMT-Paramedics and 18.4% and 22.4% of EMT-Basic respondents reported this. The most common type of employer for both EMT-Basics and EMT-Paramedics was fire-based organizations. About one-third of EMT-Basics (32.3%-40.1%) and almost one-half of EMT-Paramedics (43.1%-45.3%) reported that these organizations were their main EMS employer. Rural areas (<25,000 residents) were the most common practice settings for EMT-Basics (52.1%-63.7%), while more EMT-Paramedics worked in urban settings (65.2%-77.7%).

Conclusions

This analysis serves as a useful baseline to measure future changes in the EMS profession. This study described the demographic and work-life characteristics of a cohort of nationally certified EMT-Basics and Paramedics over a 10-year period. This analysis also summarized initial EMS education changes over time.

BentleyMA, ShobenA, LevineR. The demographics and education of Emergency Medical Services (EMS) professionals: a national longitudinal investigation. Prehosp Disaster Med. 2016;31(Suppl. 1):s18–s29.
Mortality at Music Festivals: Academic and Grey Literature for Case Finding
Authors: Turris Sheila A. , Lund Adam
Published: December 2016

Objective

Deaths at music festivals are not infrequently reported in the media; however, the true mortality burden is difficult to determine as the deaths are not yet systematically documented in the academic literature.

Methods

This was a literature search for case examples using academic and gray literature sources, employing both retrospective and prospective searches of media sources from 1999-2014.

Results

The gray literature documents a total of 722 deaths, including traumatic (594/722; 82%) and non-traumatic (128/722; 18%) causes. Fatalities were caused by trampling (n=479), motor-vehicle-related (n=39), structural collapses (n=28), acts of terror (n=26), drowning (n=8), assaults (n=6), falls (n=5), hanging (n=2), and thermal injury (n=2). Non-traumatic deaths included overdoses (n=96/722; 13%), environmental causes (n=8/722; 1%), natural causes (n=10/722; 1%), and unknown/not reported (n=14/722; 2%). The majority of non-trauma-related deaths were related to overdose (75%).

The academic literature documents trauma-related deaths (n=368) and overdose-related deaths (n=12). One hundred percent of the trauma-related deaths reported in the academic literature also were reported in the gray literature (n=368). Mortality rates cannot be reported as the total attendance at events is not known.

Conclusions

The methodology presented in this manuscript confirms that deaths occur not uncommonly at music festivals, and it represents a starting point in the documentation and surveillance of mortality.

TurrisSA, LundA. Mortality at music festivals: academic and grey literature for case finding. Prehosp Disaster Med. 2017;32(1):58–63.
Society of Pediatric Psychology Diversity Award: Training Underrepresented Minority Students in Psychology
Authors: Mitchell Monica J. , Crosby Lori E.
Published: December 2016

Improving diversity, particularly among trainees and professionals from underrepresented ethnic minority backgrounds, has been a long-stated goal for the field of psychology. Research has provided strategies and best practices, such as ensuring cultural sensitivity and relevance in coursework, clinical and research training, promoting a supportive and inclusive climate, providing access to cultural and community opportunities, and increasing awareness and cultural competence among professionals ( Rogers & Molina, 2006 ). Despite this, the rates of psychologists from ethnically diverse and underrepresented minority (URM) backgrounds remain low and few published studies have described programmatic efforts to increase diversity within the field. This article describes the INNOVATIONS training model, which provides community and culturally related research experiences, graduate-school-related advising, and mentoring to high school and college students. The article also examines how the model may support enrollment of URM students in doctoral programs in psychology. Findings indicate that INNOVATIONS supported students’ transition from high school and college to graduate programs (with approximately 75% of students enrolling in master’s and doctoral programs). INNOVATIONS also supported students, including those from URM backgrounds, enrolling in doctoral programs (41.7%). Students who were trained in the research assistant track were most likely to enroll in psychology doctoral programs, perhaps as a result of the intensive time and training committed to research and clinical experiences. Data support the importance of research training for URM students pursuing psychology graduate study and the need to ensure cultural relevance of the training. Implications for clinical and pediatric psychology are discussed.
Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation
Authors: Tripathi Madhulika , Zhang Cheng Wu , Singh Brijesh Kumar , Sinha Rohit Anthony , Moe Kyaw Thu , DeSilva Deidre Anne , Yen Paul Michael
Published: December 2016

Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.
Sensitivity of hematopoietic stem cells to mitochondrial dysfunction by SdhD gene deletion
Authors: Bejarano-García José Antonio , Millán-Uclés África , Rosado Iván V , Sánchez-Abarca Luís Ignacio , Caballero-Velázquez Teresa , Durán-Galván María José , Pérez-Simón José Antonio , Piruat José I
Published: December 2016

It is established that hematopoietic stem cells (HSC) in the hypoxic bone marrow have adapted their metabolism to oxygen-limiting conditions. This adaptation includes suppression of mitochondrial activity, induction of anerobic glycolysis, and activation of hypoxia-inducible transcription factor 1α (Hif1α)-dependent gene expression. During progression of hematopoiesis, a metabolic switch towards mitochondrial oxidative phosphorylation is observed, making this organelle essential for determining cell fate choice in bone marrow. However, given that HSC metabolism is essentially oxygen-independent, it is still unclear whether functional mitochondria are absolutely required for their survival. To assess the actual dependency of these undifferentiated cells on mitochondrial function, we have performed an analysis of the hematopoiesis in a mouse mutant, named SDHD-ESR, with inducible deletion of the mitochondrial protein-encoding SdhD gene. This gene encodes one of the subunits of the mitochondrial complex II (MCII). In this study, we demonstrate that, in contrast to what has been previously established, survival of HSC, and also myeloid and B-lymphoid progenitors, depends on proper mitochondrial activity. In addition, gene expression analysis of these hematopoietic lineages in SDHD-ESR mutants calls into question the proposed activation of Hif1α in response to MCII dysfunction.
Correction: Corrigendum: Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues
Authors: Scheller Erica L. , Doucette Casey R. , Learman Brian S. , Cawthorn William P. , Khandaker Shaima , Schell Benjamin , Wu Brent , Ding Shi-Ying , Bredella Miriam A. , Fazeli Pouneh K. , Khoury Basma , Jepsen Karl J. , Pilch Paul F. , Klibanski Anne , Rosen Clifford J. , MacDougald Ormond A.
Published: December 2016

Nature Communications 6: Article number: 7808 (2015); Published: 6 August 2015; Updated: 8 December 2016 In Figure 3 of this Article, marrow adipose tissue volumes (in panels b and c) and adipocyte numbers (in panel g) were calculated incorrectly. In Fig. 3b,c, regional MAT volumes in the ‘GP to T/FJ’ group were normalized incorrectly to both regional marrow volume and total marrow volume instead of normalizing to total marrow volume only.
Collisions in outer space produced an icosahedral phase in the Khatyrka meteorite never observed previously in the laboratory
Authors: Bindi Luca , Lin Chaney , Ma Chi , Steinhardt Paul J.
Published: December 2016

We report the first occurrence of an icosahedral quasicrystal with composition Al62.0(8)Cu31.2(8)Fe6.8(4), outside the measured equilibrium stability field at standard pressure of the previously reported Al-Cu-Fe quasicrystal (AlxCuyFez, with x between 61 and 64, y between 24 and 26, z between 12 and 13%). The new icosahedral mineral formed naturally and was discovered in the Khatyrka meteorite, a recently described CV3 carbonaceous chondrite that experienced shock metamorphism, local melting (with conditions exceeding 5 GPa and 1,200 °C in some locations), and rapid cooling, all of which likely resulted from impact-induced shock in space. This is the first example of a quasicrystal composition discovered in nature prior to being synthesized in the laboratory. The new composition was found in a grain that has a separate metal assemblage containing icosahedrite (Al63Cu24Fe13), currently the only other known naturally occurring mineral with icosahedral symmetry (though the latter composition had already been observed in the laboratory prior to its discovery in nature). The chemistry of both the icosahedral phases was characterized by electron microprobe, and the rotational symmetry was confirmed by means of electron backscatter diffraction.
Oxytocin improves synchronisation in leader-follower interaction
Authors: Gebauer L. , Witek M. A. G. , Hansen N. C. , Thomas J. , Konvalinka I. , Vuust P.
Published: December 2016

The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member – i.e. one was following another who was leading/self-pacing – dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner’s behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.
Ultrafast Method for Selective Design of Graphene Quantum Dots with Highly Efficient Blue Emission
Authors: Kang Suk Hyun , Mhin Sungwook , Han Hyuksu , Kim Kang Min , Jones Jacob L. , Ryu Jeong Ho , Kang Ju Seop , Kim Shin Hee , Shim Kwang Bo
Published: December 2016

Graphene quantum dots (GQDs) have attractive properties and potential applications. However, their various applications are limited by a current synthetic method which requires long processing time. Here, we report a facile and remarkably rapid method for production of GQDs exhibiting excellent optoelectronic properties. We employed the pulsed laser ablation (PLA) technique to exfoliate GQDs from multi-wall carbon nanotube (MWCNTs), which can be referred to as a pulsed laser exfoliation (PLE) process. Strikingly, it takes only 6 min to transform all MWCNTs precursors to GQDs by using PLE process. Furthermore, we could selectively produce either GQDs or graphene oxide quantum dots (GOQDs) by simply changing the organic solvents utilized in the PLE processing. The synthesized GQDs show distinct blue photoluminescence (PL) with excellent quantum yield (QY) up to 12% as well as sufficient brightness and resolution to be suitable for optoelectronic applications. We believe that the PLE process proposed in this work will further open up new routes for the preparation of different optoelectronic nanomaterials.
EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm
Authors: Kim Seong Gon , Harwani Mrudul , Grama Ananth , Chaterji Somali
Published: December 2016

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.
Novel Design of Iridium Phosphors with Pyridinylphosphinate Ligands for High-Efficiency Blue Organic Light-emitting Diodes
Authors: Wu Zheng-Guang , Jing Yi-Ming , Lu Guang-Zhao , Zhou Jie , Zheng You-Xuan , Zhou Liang , Wang Yi , Pan Yi
Published: December 2016

Due to the high quantum efficiency and wide scope of emission colors, iridium (Ir) (III) complexes have been widely applied as guest materials for OLEDs (organic light-emitting diodes). Contrary to well-developed Ir(III)-based red and green phosphorescent complexes, the efficient blue emitters are rare reported. Like the development of the LED, the absence of efficient and stable blue materials hinders the widely practical application of the OLEDs. Inspired by this, we designed two novel ancillary ligands of phenyl(pyridin-2-yl)phosphinate (ppp) and dipyridinylphosphinate (dpp) for efficient blue phosphorescent iridium complexes (dfppy)2Ir(ppp) and (dfppy)2Ir(dpp) (dfppy = 2-(2,4-difluorophenyl)pyridine) with good electron transport property. The devices using the new iridium phosphors display excellent electroluminescence (EL) performances with a peak current efficiency of 58.78 cd/A, a maximum external quantum efficiency of 28.3%, a peak power efficiency of 52.74 lm/W and negligible efficiency roll-off ratios. The results demonstrated that iridium complexes with pyridinylphosphinate ligands are potential blue phosphorescent materials for OLEDs.
GSK-3β controls NF-kappaB activity via IKKγ/NEMO
Authors: Medunjanin Senad , Schleithoff Lisa , Fiegehenn Christian , Weinert Soenke , Zuschratter Werner , Braun-Dullaeus Ruediger C.
Published: December 2016

The NF-κB signaling pathway is central for the innate immune response and its deregulation is found in multiple disorders such as autoimmune, chronic inflammatory and metabolic diseases. IKKγ/NEMO is essential for NF-κB activation and NEMO dysfunction in humans has been linked to so-called progeria syndromes, which are characterized by advanced ageing due to age-dependent inflammatory diseases. It has been suggested that glycogen synthase kinase-3β (GSK-3β) participates in NF-κB regulation but the exact mechanism remained incompletely understood. In this study, we identified NEMO as a GSK-3β substrate that is phosphorylated at serine 8, 17, 31 and 43 located within its N-terminal domain. The kinase forms a complex with wild-type NEMO while point mutations of NEMO at the specific serines abrogated GSK-3β binding and subsequent phosphorylation of NEMO resulting in its destabilization. However, K63-linked polyubiquitination was augmented in mutated NEMO explaining an increased binding to IKKα and IKKβ. Even IκBα was found degraded. Still, TNFα-stimulated NF-κB activation was impaired pointing towards an un-controlled signalling process. Our data suggest that GSK-3β is critically important for ordered NF-κB signalling through modulation of NEMO phosphorylation.
From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2
Authors: Sheikh Taimoor I. , Ausió Juan , Faghfoury Hannah , Silver Josh , Lane Jane B. , Eubanks James H. , MacLeod Patrick , Percy Alan K. , Vincent John B.
Published: December 2016

Mutations in the MECP2 gene cause Rett syndrome (RTT). MeCP2 binds to chromocentric DNA through its methyl CpG-binding domain (MBD) to regulate gene expression. In heterozygous females the variable phenotypic severity is modulated by non-random X-inactivation, thus making genotype-phenotype comparisons unreliable. However, genotype-phenotype correlations in males with hemizygousMECP2 mutations can provide more accurate insights in to the true biological effect of specific mutations. Here, we compared chromatin organization and binding dynamics for twelve MeCP2 missense mutations (including two novel and the five most common MBD missense RTT mutations) and identifiedacorrelation with phenotype in hemizygous males. We observed impaired interaction of MeCP2-DNA for mutations around the MBD-DNA binding interface, and defective chromatin clustering for distal MBD mutations. Furthermore, binding and mobility dynamics show a gradient of impairment depending on the amino acid properties and tertiary structure within the MBD. Interestingly, a wide range of phenotypic/clinical severity, ranging from neonatal encephalopathy to mild psychiatric abnormalities were observed and all are consistent with our functional/molecular results. Overall, clinical severity showed a direct correlation with the functional impairment of MeCP2. These mechanistic and phenotypic correlations of MeCP2 mutations will enable improved and individualized diagnostics, and may lead to personalized therapeutic interventions.
A New Synergetic Nanocomposite for Dye Degradation in Dark and Light
Authors: V. Lakshmi Prasanna , Rajagopalan Vijayaraghavan
Published: December 2016

Environmental hazard caused due to the release of dyes in effluents is a concern in many countries. Among the various methods to combat this problem, Advanced Oxidation Process, in which semiconductor photocatalysts are used, is considered the most effective one. These materials release Reactive Oxygen Species (ROS) such as hydroxyl radical and superoxide in suspension that degrade the dyes into non-toxic minerals. However, this process requires visible or UV light for activation. Hence, there is a need to develop materials that release ROS, both in the absence and in the presence of light, so that the efficiency of dye removal is enhanced. Towards this objective, we have designed and synthesized a new nanocomposite ZnO2/polypyrrole which releases ROS even in the dark. The ROS released in the dark and in light were estimated by standard methods. It is to be noted that ZnO2 degrades the dye only under UV light but not in dark or in the presence of visible light. We propose the mechanism of dye degradation in dark and light. The synergically coupled nanocomposite of ZnO2/ppy is the first example that degrades dyes in the dark, through advanced oxidation process without employing additional reagents.
Aphids transform and detoxify the mycotoxin deoxynivalenol via a type II biotransformation mechanism yet unknown in animals
Authors: De Zutter N. , Audenaert K. , Arroyo-Manzanares N. , De Boevre M. , Van Poucke C. , De Saeger S. , Haesaert G. , Smagghe G.
Published: December 2016

Biotransformation of mycotoxins in animals comprises phase I and phase II metabolisation reactions. For the trichothecene deoxynivalenol (DON), several phase II biotransformation reactions have been described resulting in DON-glutathiones, DON-glucuronides and DON-sulfates made by glutathione-S-transferases, uridine-diphosphoglucuronyl transferases and sulfotransferases, respectively. These metabolites can be easily excreted and are less toxic than their free compounds. Here, we demonstrate for the first time in the animal kingdom the conversion of DON to DON-3-glucoside (DON-3G) via a model system with plant pathogenic aphids. This phase II biotransformation mechanism has only been reported in plants. As the DON-3G metabolite was less toxic for aphids than DON, this conversion is considered a detoxification reaction. Remarkably, English grain aphids (Sitobion avenae) which co-occur with the DON producer Fusarium graminearum on wheat during the development of fusarium symptoms, tolerate DON much better and convert DON to DON-3G more efficiently than pea aphids (Acyrthosiphon pisum), the latter being known to feed on legumes which are no host for F. graminearum. Using a non-targeted high resolution mass spectrometric approach, we detected DON-diglucosides in aphids probably as a result of sequential glucosylation reactions. Data are discussed in the light of an eventual co-evolutionary adaptation of S. avenae to DON.