bluuebunny/crossref_metadata_2025 huggingface dataset:
Better therapy requires better response evaluation: Paving the way for minimal residual disease testing for every myeloma patient
Authors: Landgren Ola , Owen Roger G.
Published: July 2015

In 2015, there is a large body of evidence demonstrating that minimal residual disease (MRD) negativity after therapy is a powerful predictor of progression‐free survival and overall survival in multiple myeloma. On the basis of available data, we believe MRD provides a meaningful endpoint for regulatory purposes, academic studies, and a valuable prognostic evaluation of individual patients in the clinical setting. Similar to what has been shown in acute and chronic lymphocytic leukemia, based on emerging data, the prognostic impact of MRD in multiple myeloma appears to be independent of induction therapy received. This fact raises fundamental questions regarding best possible treatment strategies (e.g., fixed number of cycles versus response adapted number of cycles) as well as optimal treatment modalities (e.g., newer effective but less intense combination therapies versus high dose melphalan followed by autologous stem cell transplantation), in particular for patients newly diagnosed with multiple myeloma. © 2015 International Clinical Cytometry Society
Increased utilization, verification, and clinical implications of immunocytochemistry: Experience in a northern New England hospital
Authors: Sauter Jennifer L. , Ambaye Abiy B. , Mount Sharon L.
Published: July 2015

Background

We report our experience in utilization, verification, and clinical implications of antibodies for use in diagnostic immunocytochemistry (ICC).

Methods

A computer search identified cytology cases utilizing ICC and corresponding surgical pathology material. Alcohol‐fixed liquid based cytology (LBC) specimens were generated from surgical pathology bench specimens. ICC on LBC and immunohistochemistry on formalin fixed paraffin embedded tissue (FFPE) were performed in parallel for 71 commonly used antibodies. Cytology and corresponding surgical pathology reports were reviewed for all cases in which antibodies failed verification studies but had been used in the four years prior to implementation of our verification process.

Results

From 2007 to 2011, the number of cytology cases in which ICC was performed increased from 98 (or 5% of all non‐Pap test/nonurine cytology cases in our laboratory) to 306 (or 15%). Verification studies revealed calretinin, CD5, c‐kit/CD117, inhibin, napsin A, OCT 3/4, and PAX‐5 to be nonreliable in LBC despite consistent immunoreactivity in concurrent IHC on surgical specimens. No antibodies were found to be immunoreactive on LBC but nonreactive on FFPE. No adverse clinical outcomes resulted from the use of nonverified antibodies.

Conclusions

Utilization of ICC at our institution has increased dramatically in recent years. Our verification process confirmed reliability in the majority of antibodies, but did identify several inconsistent antibodies. Although, in our series, no adverse clinical outcomes resulted from preverification use of these inconsistent antibodies, we encourage other institutions to confirm reliability of antibodies prior to use for diagnostic ICC. Diagn. Cytopathol. 2015;43:688–695. © 2015 Wiley Periodicals, Inc.
Movement of regulatory RNA between animal cells
Authors: Jose Antony M.
Published: July 2015

Recent studies suggest that RNA can move from one cell to another and regulate genes through specific base‐pairing. Mechanisms that modify or select RNA for secretion from a cell are unclear. Secreted RNA can be stable enough to be detected in the extracellular environment and can enter the cytosol of distant cells to regulate genes. Mechanisms that import RNA into the cytosol of an animal cell can enable uptake of RNA from many sources including other organisms. This role of RNA is akin to that of steroid hormones, which cross cell membranes to regulate genes. The potential diagnostic use of RNA in human extracellular fluids has ignited interest in understanding mechanisms that enable the movement of RNA between animal cells. Genetic model systems will be essential to gain more confidence in proposed mechanisms of RNA transport and to connect an extracellular RNA with a specific biological function. Studies in the worm C. elegans and in other animals have begun to reveal parts of this novel mechanism of cell‐to‐cell communication. Here, I summarize the current state of this nascent field, highlight the many unknowns, and suggest future directions. genesis 53:395–416, 2015. © 2015 Wiley Periodicals, Inc.
High genetic diversity and geographic subdivision of three lance nematode species (Hoplolaimus spp.) in the United States
Authors: Holguin Claudia M. , Baeza Juan A. , Mueller John D. , Agudelo Paula
Published: July 2015

Lance nematodes (Hoplolaimus spp.) feed on the roots of a wide range of plants, some of which are agronomic crops. Morphometric values of amphimictic lance nematode species overlap considerably, and useful morphological characters for their discrimination require high magnification and significant diagnostic time. Given their morphological similarity, these Hoplolaimus species provide an interesting model to investigate hidden diversity in crop agroecosystems. In this scenario, H. galeatus may have been over‐reported and the related species that are morphologically similar could be more widespread in the United States that has been recognized thus far. The main objectives of this study were to delimit Hoplolaimus galeatus and morphologically similar species using morphology, phylogeny, and a barcoding approach, and to estimate the genetic diversity and population structure of the species found. Molecular analyses were performed using sequences of the cytochrome c oxidase subunit 1 (Cox1) and the internal transcribed spacer (ITS1) on 23 populations. Four morphospecies were identified: H. galeatus, H. magnistylus, H. concaudajuvencus, and H. stephanus, along with a currently undescribed species. Pronounced genetic structure correlated with geographic origin was found for all species, except for H. galeatus. Hoplolaimus galeatus also exhibited low genetic diversity and the shortest genetic distances among populations. In contrast, H. stephanus, the species with the fewest reports from agricultural soils, was the most common and diverse species found. Results of this project may lead to better delimitation of lance nematode species in the United States by contributing to the understanding the diversity within this group.
Maternal effects on offspring size and number in mosquitofish, Gambusia holbrooki
Authors: O'Dea Rose E. , Vega‐Trejo Regina , Head Megan L. , Jennions Michael D.
Published: July 2015

Given a trade‐off between offspring size and number, all mothers are predicted to produce the same optimal‐sized offspring in a given environment. In many species, however, larger and/or older mothers produce bigger offspring. There are several hypotheses to explain this but they lack strong empirical support. In organisms with indeterminate growth, there is the additional problem that maternal size and age are positively correlated, so what are their relative roles in determining offspring size? To investigate this, we measured the natural relationship between maternal and offspring size in a wild population of Gambusia holbrooki (eastern mosquitofish), and experimentally disentangled the effects of maternal age and size on offspring size in the laboratory. In combination, our data indicate that the relationship between maternal and offspring size is nonlinear. Small mothers seem to produce larger than average offspring due to integer effects associated with very small broods. For extremely large mothers, which were only sampled in our wild data, these larger than average offspring may result from greater maternal resources or age effects. However, maternal age had no effect on offspring size or number in the laboratory experiment. Our results highlight the importance of sampling the full size–range of mothers when investigating maternal effects on offspring size. They also point to the difficulty of experimentally manipulating maternal size, because any change in size is invariably associated with a change in at least one factor affecting growth (be it temperature, food availability, or density) that might also have an indirect effect on offspring size.
The two‐pore domain K2P channel TASK2 drives human NK‐cell proliferation and cytolytic function
Authors: Schulte‐Mecklenbeck Andreas , Bittner Stefan , Ehling Petra , Döring Frank , Wischmeyer Erhard , Breuer Johanna , Herrmann Alexander M. , Wiendl Heinz , Meuth Sven G. , Gross Catharina C.
Published: July 2015

Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor‐ and virus‐infected cells without prior stimulation. Killing of target cells is a multistep process including adhesion to target cells, formation of an immunological synapse, and polarization and release of cytolytic granules. The role of distinct potassium channels in this orchestrated process is still poorly understood. The current study reveals that in addition to the voltage‐gated KV1.3 and the calcium‐activated KCa3.1 channels, human NK cells also express the two‐pore domain K2P channel TASK2 (TWIK‐related acid‐sensitive potassium channel). Expression of Task2 varies among NK‐cell subsets and depends on their differentiation and activation state. Despite its different expression in TASK2highCD56brightCD16− and TASK2lowCD56dimCD16+ NK cells, TASK2 is involved in cytokine‐induced proliferation and cytolytic function of both subsets. TASK2 is crucial for leukocyte functional antigen (LFA‐1) mediated adhesion of both resting and cytokine‐activated NK cells to target cells, an early step in killing of target cells. With regard to the following mechanism, TASK2 plays a role in release of cytotoxic granules by resting, but not IL‐15‐induced NK cells. Taken together, our data exhibit two‐pore potassium channels as important players in NK‐cell activation and effector function.
Innate immune system favors emergency monopoiesis at the expense of DC‐differentiation to control systemic bacterial infection in mice
Authors: Pasquevich Karina A. , Bieber Kristin , Günter Manina , Grauer Matthias , Pötz Oliver , Schleicher Ulrike , Biedermann Tilo , Beer‐Hammer Sandra , Bühring Hans‐Jörg , Rammensee Hans‐Georg , Zender Lars , Autenrieth Ingo B. , Lengerke Claudia , Autenrieth Stella E.
Published: July 2015

DCs are professional APCs playing a crucial role in the initiation of T‐cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC‐depletion in humans and mice. The mechanisms of pathogen‐induced DC‐depletion remain poorly understood. Previously, we showed that mice infected with Yersinia enterocolitica (Ye) had impaired de novo DC‐development, one reason for DC‐depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC‐depletion and the impact of different bacteria on DC‐development. We show that the number of bone marrow (BM) hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram‐positive and Gram‐negative bacteria. This is associated with a TLR4‐ and IFN‐γ−signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye‐infection. Adoptive transfer experiments revealed that infection‐induced monopoiesis occurs at the expense of DC‐development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC‐development leads to DC‐depletion, possibly driving transient immunosuppression in bacterial sepsis.
An automated shotgun lipidomics platform for high throughput, comprehensive, and quantitative analysis of blood plasma intact lipids
Authors: Surma Michal A. , Herzog Ronny , Vasilj Andrej , Klose Christian , Christinat Nicolas , Morin‐Rivron Delphine , Simons Kai , Masoodi Mojgan , Sampaio Julio L.
Published: July 2015

Blood plasma has gained protagonism in lipidomics studies due to its availability, uncomplicated collection and preparation, and informative readout of physiological status. At the same time, it is also technically challenging to analyze due to its complex lipid composition affected by many factors, which can hamper the throughput and/or lipidomics coverage. To tackle these issues, we developed a comprehensive, high throughput, and quantitative mass spectrometry‐based shotgun lipidomics platform for blood plasma lipid analyses. The main hallmarks of this technology are (i) it is comprehensive, covering 22 quantifiable different lipid classes encompassing more than 200 lipid species; (ii) it is amenable to high‐throughput, with less than 5 min acquisition time allowing the complete analysis of 200 plasma samples per day; (iii) it achieves absolute quantification, by inclusion of internal standards for every lipid class measured; (iv) it is highly reproducible, achieving an average coefficient of variation of <10% (intra‐day), approx. 10% (inter‐day), and approx. 15% (inter‐site) for most lipid species; (v) it is easily transferable allowing the direct comparison of data acquired in different sites. Moreover, we thoroughly assessed the influence of blood stabilization with different anticoagulants and freeze‐thaw cycles to exclude artifacts generated by sample preparation.

Practical applications: This shotgun lipidomics platform can be implemented in different laboratories without compromising reproducibility, allowing multi‐site studies and inter‐laboratory comparisons. This possibility combined with the high‐throughput, broad lipidomic coverage and absolute quantification are important aspects for clinical applications and biomarker research.

This MS‐based automated shotgun lipidomics platform for comprehensive analysis of the blood plasma lipidome (covering 22 lipid classes) achieves high inter‐day and inter‐site reproducibility and accuracy and enables unprecedented large scale lipidomics studies.
Acyclic Pseudopeptidic Hosts as Molecular Receptors and Transporters for Anions
Authors: Martí Inés , Burguete M. Isabel , Gale Philip A. , Luis Santiago V.
Published: July 2015

The synthesis and characterization of different pseudopeptidic hosts derived from open chain systems with C2 and C3 symmetry has been achieved. These receptors are based on structures containing phenylalanine amino acid residues and amine, amide, urea and thiourea groups as the structural elements providing their capability to interact with anions. The transport of chloride and organic anions of biological relevance (L‐lactate, L‐maleate and L‐aspartate) through lipid bilayer membranes has been studied for these receptors. The chloride‐binding properties of the selected hosts have been studied in solution by NMR titrations. In addition, in order to rationalize the results, lipophilicity studies have been carried out. It has been observed that transport activity is affected by the nature of the aliphatic central spacer and the side chains, the most active receptors being 9b, derived from a tripodal precursor with the shortest aliphatic side chain and 3c, derived from a bis(amino amide) but having the longest spacer. These hosts are more selective for the anion chloride than for the studied organic anions.
Electrophoretic mobility of oil droplets in electrolyte and surfactant solutions
Authors: Wuzhang Jiachen , Song Yongxin , Sun Runzhe , Pan Xinxiang , Li Dongqing
Published: July 2015

Electrophoretic mobility of oil droplets of micron sizes in PBS and ionic surfactant solutions was measured in this paper. The experimental results show that, in addition to the applied electric field, the speed and the direction of electrophoretic motion of oil droplets depend on the surfactant concentration and on if the droplet is in negatively charged SDS solutions or in positively charged hexadecyltrimethylammonium bromide (CTAB) solutions. The absolute value of the electrophoretic mobility increases with increased surfactant concentration before the surfactant concentration reaches to the CMC. It was also found that there are two vortices around the oil droplet under the applied electric field. The size of the vortices changes with the surfactant and with the electric field. The vortices around the droplet directly affect the drag of the flow field to the droplet motion and should be considered in the studies of electrophoretic mobility of oil droplets. The existence of the vortices will also influence the determination and the interpretation of the zeta potential of the oil droplets based on the measured mobility data.
Simultaneous removal of CO2 and salts from saline water by a combined process
Authors: Chaalal Omar , Hossain Md M.
Published: July 2015

The emission of CO2 has been increasing steadily and with the increasing demand of desalinated water (especially in Gulf Cooperation Council countries) this is expected to increase at a faster rate. CO2 removal from sour natural gas, from the water desalination power plants and similar sources is important not only to these industries but also to reduce the effect on global warming. In this study, a simple process is investigated experimentally to remove CO2 from a synthetic mixture of natural gas containing it. The method is based on the modified Solvay process and involves the chemical reaction between CO2 and ammonia in saline solution. The process can reduce CO2 by about 99% and at the same time reduce water salinity by 40%. The process is potentially much more effective than the amine scrubbing process, without the operational problems for environmental damage posed by monoethanolamine organic compounds. The innovative process shows the technical feasibility of sweetening natural gas in the laboratory‐scale operation. It can also be applied to the removal of CO2 from polluting sources like car exhaust. Simultaneous reduction of salinity is additional benefit of this process. © 2015 American Institute of Chemical Engineers Environ Prog, 35: 250–256, 2016
Characterisation of erosional features associated with tsunami terrains on rocky coasts of the Maltese islands
Authors: Mottershead Derek N. , Bray Malcolm J. , Soar Philip J. , Farres Paul J.
Published: July 2015

In recent years there has been a growing body of literature on depositional signatures associated with historic extreme waves on rocky coasts. Here, in the context of the Maltese islands, we place an innovative focus on evidence of erosional forms. The field evidence is concentrated along the NE flank of the islands at a topographically varied range of sites and up to an altitude of 13 m asl. A range of forms is broadly classified in terms of their morphologies and the forces responsible for their formation. Sockets, eroded scarps, scoured terrains, clifftop erosion scars, swept terrains and spillways are interpreted as consequences of overwashing of the landscape by an extreme wave or waves. These forms are shown to be controlled by flow intensity, topography and lithology, and especially rock bedding and jointing. They comprise the source areas for associated depositional evidence allowing transport paths to be estimated, and may significantly enhance the reconstruction of extreme wave events. It is likely that similar (and additional) erosional forms are present elsewhere in the Mediterranean domain, where comparable lithological and topographic situations are exposed to extreme waves. Copyright © 2015 John Wiley & Sons, Ltd.
Sublethal health effects in laboratory rodents from environmentally relevant exposures to oil sands contaminants
Authors: Rodríguez-Estival Jaime , North Michelle A. , Smits Judit E.G.
Published: July 2015

Increasing activity of oil sands extraction and processing in northern Alberta is marked by ongoing controversy about the nature and extent of associated environmental impacts. Bitumen contains a mixture of toxic chemicals, including metals and residual polycyclic aromatic hydrocarbons (PAHs), whose release into the environment poses a distinct risk to the surrounding environment, plus wildlife and human health. In the present study, the authors evaluated several subclinical biomarkers of exposure and effect to mixtures of metals (Pb, Cd, and Hg) and/or PAHs (3 alkylated forms) at environmentally relevant concentrations (100-fold and 10-fold higher than the maximum dissolved concentrations found in snow, to simulate a worst-case scenario), using laboratory mice as a model for future studies of small mammals in the wild. Both metals and alkyl-PAHs exposure were associated with 1) increased relative liver, kidney, and spleen size; 2) alterations in the homeostasis of the antioxidant vitamins A and E in liver; and 3) compromised glutathione redox status in testes, with results also indicating synergistic interactions from co-exposure. The combination of morphometric and oxidative stress biomarkers provide reliable and sensitive measures of the response to contaminant exposure in a mammalian model, suggesting associated physiological costs. Based on the present experimental study, the authors propose that wild small mammals will prove to be valuable sentinel species reflecting sublethal health effects from oil sands–related contaminants. The present study's results also present a basis for the interpretation of future field data. Environ Toxicol Chem 2015;34:2884–2897. © 2015 SETAC
Development of a recombinant human ovarian (BG1) cell line containing estrogen receptor α and β for improved detection of estrogenic/antiestrogenic chemicals
Authors: Brennan Jennifer C. , Bassal Arzoo , He Guochun , Denison Michael S.
Published: July 2015

Estrogenic endocrine-disrupting chemicals are found in environmental and biological samples, commercial and consumer products, food, and numerous other sources. Given their ubiquitous nature and potential for adverse effects, a critical need exists for rapidly detecting these chemicals. The authors developed an estrogen-responsive recombinant human ovarian (BG1Luc4E2) cell line recently accepted by the US Environmental Protection Agency (USEPA) and Organisation for Economic Co-operation and Development (OECD) as a bioanalytical method to detect estrogen receptor (ER) agonists/antagonists. Unfortunately, these cells appear to contain only 1 of the 2 known ER isoforms, ERα but not ERβ, and the differential ligand selectivity of these ERs indicates that the currently accepted screening method only detects a subset of total estrogenic chemicals. To improve the estrogen screening bioassay, BG1Luc4E2 cells were stably transfected with an ERβ expression plasmid and positive clones identified using ERβ-selective ligands (genistein and Br-ERβ-041). A highly responsive clone (BG1LucERβc9) was identified that exhibited greater sensitivity and responsiveness to ERβ-selective ligands than BG1Luc4E2 cells, and quantitative reverse-transcription polymerase chain reaction confirmed the presence of ERβ expression in these cells. Screening of pesticides and industrial chemicals identified chemicals that preferentially stimulated ERβ-dependent reporter gene expression. Together, these results not only demonstrate the utility of this dual-ER recombinant cell line for detecting a broader range of estrogenic chemicals than the current BG1Luc4E2 cell line, but screening with both cell lines allows identification of ERα- and ERβ-selective chemicals. Environ Toxicol Chem 2016;35:91–100. © 2015 SETAC
Efficient multigrid preconditioners for atmospheric flow simulations at high aspect ratio
Authors: Dedner Andreas , Müller Eike , Scheichl Robert
Published: July 2015

Many problems in fluid modelling require the efficient solution of highly anisotropic elliptic partial differential equations (PDEs) in ‘flat’ domains. For example, in numerical weather and climate prediction, an elliptic PDE for the pressure correction has to be solved at every time step in a thin spherical shell representing the global atmosphere. This elliptic solve can be one of the computationally most demanding components in semi‐implicit semi‐Lagrangian time stepping methods, which are very popular as they allow for larger model time steps and better overall performance. With increasing model resolution, algorithmically efficient and scalable algorithms are essential to run the code under tight operational time constraints. We discuss the theory and practical application of bespoke geometric multigrid preconditioners for equations of this type. The algorithms deal with the strong anisotropy in the vertical direction by using the tensor‐product approach originally analysed by Börm and Hiptmair [Numer. Algorithms, 26/3 (2001), pp. 219–234]. We extend the analysis to three dimensions under slightly weakened assumptions and numerically demonstrate its efficiency for the solution of the elliptic PDE for the global pressure correction in atmospheric forecast models. For this, we compare the performance of different multigrid preconditioners on a tensor‐product grid with a semi‐structured and quasi‐uniform horizontal mesh and a one‐dimensional vertical grid. The code is implemented in the Distributed and Unified Numerics Environment, which provides an easy‐to‐use and scalable environment for algorithms operating on tensor‐product grids. Parallel scalability of our solvers on up to 20 480 cores is demonstrated on the HECToR supercomputer. Copyright © 2015 John Wiley & Sons, Ltd.
GABAA receptor deficits predict recovery in patients with disorders of consciousness: A preliminary multimodal [11C]Flumazenil PET and fMRI study
Authors: Qin Pengmin , Wu Xuehai , Duncan Niall W. , Bao Weiqi , Tang Weijun , Zhang Zhengwei , Hu Jin , Jin Yi , Wu Xing , Gao Liang , Lu Lu , Guan Yihui , Lane Timothy , Huang Zirui , Bodien Yelena G. , Giacino Joseph T. , Mao Ying , Northoff Georg
Published: July 2015

Objectives

Disorders of consciousness (DoC)—that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state—are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker.

Experimental design

In our preliminary study, we used [11C]Flumazenil positron emission tomography to establish global GABAA receptor binding potential values and the local‐to‐global (LTG) ratio of these for specific regions. These values were then compared between DoC patients and healthy controls. In addition, they were correlated with behavioral improvements for the patients between the time of scanning and 3 months later. Functional magnetic resonance imaging resting‐state functional connectivity was also calculated and the same comparisons made.

Principal observations

lobal GABAA receptor binding was reduced in DoC, as was the LTG ratio in specifically the supragenual anterior cingulate. Both of these measures correlated with behavioral improvement after 3 months. In contrast to these measures of GABAA receptor binding, functional connectivity did not correlate with behavioral improvement.

Conclusions

Our preliminary findings point toward GABAA receptor binding being a marker of consciousness recovery in DoC. Hum Brain Mapp 36:3867–3877, 2015. © 2015 Wiley Periodicals, Inc.
Effects of sex and proficiency in second language processing as revealed by a large‐scale fNIRS study of school‐aged children
Authors: Sugiura Lisa , Ojima Shiro , Matsuba‐Kurita Hiroko , Dan Ippeita , Tsuzuki Daisuke , Katura Takusige , Hagiwara Hiroko
Published: July 2015

Previous neuroimaging studies in adults have revealed that first and second languages (L1/L2) share similar neural substrates, and that proficiency is a major determinant of the neural organization of L2 in the lexical‐semantic and syntactic domains. However, little is known about neural substrates of children in the phonological domain, or about sex differences. Here, we conducted a large‐scale study (n = 484) of school‐aged children using functional near‐infrared spectroscopy and a word repetition task, which requires a great extent of phonological processing. We investigated cortical activation during word processing, emphasizing sex differences, to clarify similarities and differences between L1 and L2, and proficiency‐related differences during early L2 learning. L1 and L2 shared similar neural substrates with decreased activation in L2 compared to L1 in the posterior superior/middle temporal and angular/supramarginal gyri for both sexes. Significant sex differences were found in cortical activation within language areas during high‐frequency word but not during low‐frequency word processing. During high‐frequency word processing, widely distributed areas including the angular/supramarginal gyri were activated in boys, while more restricted areas, excluding the angular/supramarginal gyri were activated in girls. Significant sex differences were also found in L2 proficiency‐related activation: activation significantly increased with proficiency in boys, whereas no proficiency‐related differences were found in girls. Importantly, cortical sex differences emerged with proficiency. Based on previous research, the present results indicate that sex differences are acquired or enlarged during language development through different cognitive strategies between sexes, possibly reflecting their different memory functions. Hum Brain Mapp 36:3890–3911, 2015. © 2015 Wiley Periodicals, Inc.
Intracranial recordings reveal transient response dynamics during information maintenance in human cerebral cortex
Authors: Noy Niv , Bickel Stephan , Zion‐Golumbic Elana , Harel Michal , Golan Tal , Davidesco Ido , Schevon Catherine A. , McKhann Guy M. , Goodman Robert R. , Schroeder Charles E. , Mehta Ashesh D. , Malach Rafael
Published: July 2015

Despite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on “working memory”—typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory. However, multi‐item working memory constitutes only a subset of storage phenomena that may occur during daily life. A common task in naturalistic situations is short term memory of a single item—for example, blindly reaching to a previously placed cup of coffee. Little is known about such single‐item, effortless, storage in the human brain. Here, we examined the dynamics of brain responses during a single‐item maintenance task, using intracranial recordings implanted for clinical purpose in patients (ECoG). Our results reveal that active electrodes were dominated by transient short latency visual and motor responses, reflected in broadband high frequency power increases in occipito‐temporal, frontal, and parietal cortex. Only a very small set of electrodes showed activity during the early part of the delay period. Interestingly, no cortical site displayed a significant activation lasting to the response time. These results suggest that single item encoding is characterized by transient high frequency ECoG responses, while the maintenance of information during the delay period may be mediated by mechanisms necessitating only low‐levels of neuronal activations. Hum Brain Mapp 36:3988–4003, 2015. © 2015 Wiley Periodicals, Inc.
Does Overweight and Obesity Impact on Self‐Rated Health? Evidence Using Instrumental Variables Ordered Probit Models
Authors: Cullinan John , Gillespie Paddy
Published: July 2015

This paper, for the first time, presents estimates of the causal impact of overweight and obesity on self‐rated health (SRH) using instrumental variables (IV) econometric methods. While a number of previous studies have sought to better understand the determinants of SRH, there is no consensus in relation to the impact of overweight and obesity. Using data from a large nationally representative sample of Irish parents and their children, we estimate a range of ordered probit models to isolate the causal effect of overweight and obesity on SRH. Our data includes independently and objectively recorded weight and height measures for parents and their children and we instrument for parental body mass index (BMI) status using the BMI of a biological child. After controlling for a range of individual, socioeconomic, health and lifestyle related variables, we find that being overweight has a negligible impact on SRH, while being obese has a practically and statistically significant negative impact on SRH, with these effects most pronounced for those who are most obese. We find only minor differences in these effects across gender. Copyright © 2015 John Wiley & Sons, Ltd.
Temporal dynamics of inflammatory cytokines/chemokines during sofosbuvir and ribavirin therapy for genotype 2 and 3 hepatitis C infection
Authors: Carlin Aaron F. , Aristizabal Paula , Song Qinghua , Wang Huan , Paulson Matthew S. , Stamm Luisa M. , Schooley Robert T. , Wyles David L.
Published: July 2015

The analysis of inflammatory cytokines and chemokines produced during hepatitis C virus (HCV) infection has advanced our understanding of viral‐host interactions and identified predictors of treatment response. Administration of interferons (IFNs) made it difficult to interpret biomarkers of immune activation during treatment. Direct‐acting antiviral (DAA) regimens without IFN are now being used to treat HCV with excellent efficacy. To gain insight into HCV‐host interactions occurring before, during, and after HCV treatment, we performed a case‐control study that measured serial plasma levels of IFN‐γ‐inducible protein 10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), macrophage inflammatory protein 1 beta (MIP‐1β), and interleukin‐18 (IL‐18) in 131 patients with chronic HCV treated with sofosbuvir (SOF) plus ribavirin (RBV). A linear regression analysis using baseline factors identified strong positive associations between elevated alanine aminotransferase and pretreatment IP‐10 and between the presence of cirrhosis and elevated pretreatment IL‐18. Mean IP‐10, MCP‐1, MIP‐1β, and IL‐18 levels all decline on therapy, but display different dynamics late in treatment and after cessation of therapy. On treatment, IP‐10 and MIP‐1β levels were significantly higher in individuals who achieved sustained virological response (SVR). Logistic regression analyses examining treatment response in all patients demonstrated significant associations between higher baseline MIP‐1β levels and smaller decreases in MIP‐1β early in treatment and SVR. Higher early MIP‐1β levels were also significantly associated with SVR in subsets of patients with cirrhosis and individuals with genotype 3 (GT3) infection, two factors associated with decreased responsiveness to treatment. Conclusion: Changes in IP‐10 levels mirror HCV RNA, suggesting that IP‐10 is an indicator of innate immune viral recognition. MIP‐1β levels remain elevated in GT2/3 patients who achieved SVR, suggesting differential immune activation in those who respond to SOF/RBV therapy and a potential role in predicting treatment responses. (Hepatology 2015;62:1047‐1058)
Incidence of cancer in Nairobi, Kenya (2004–2008)
Authors: Korir Anne , Okerosi Nathan , Ronoh Victor , Mutuma Geoffrey , Parkin Max
Published: July 2015

Cancer incidence rates are presented for the Nairobi Cancer Registry, a population‐based cancer registry (PBCR) covering the population of the capital city of Kenya (3.2 million inhabitants in 2009). Case finding was by active methods, with standard and checks for accuracy and validity. During the period 2004–2008 a total of 8,982 cases were registered comprising 3,889 men (an age standardized incidence rate (ASR) of 161 per 100,000) and 5,093 women (ASR 231 per 1,00,000). Prostate cancer was the most common cancer in men (ASR 40.6 per 100,000) while breast cancer was the most common among women (ASR 51.7 per 100,000). Cervical cancer ranked the second most common cancer among women in Nairobi with an ASR of 46.1 per 100,000, somewhat lower than those of other registries in East Africa region. Breast and cervical cancers accounted for 44% of all cancers in women. Cancer of the oesophagus was common in both sexes, with a slight excess of cases in men (sex ratio 1.3). Unlike other regions in East Africa, the rate of Kaposi sarcoma was relatively low during the period (men 3.6/100,000; women 2.0/100,000). Although incidence rates cannot be calculated for the early years of the registry, the increase in relative frequency of prostate cancer and declines in frequency of Kaposi sarcoma may indicate underlying trends in the risk of these cancers.
4‐Aryl‐4H‐Chromene‐3‐Carbonitrile Derivates: Synthesis and Preliminary Anti‐Breast Cancer Studies
Authors: Thomas Nancy , Zachariah Subin Mary , Ramani Prasanna
Published: July 2015

A series of new 4‐aryl‐4H‐chromene‐3‐carbonitrile derivatives were obtained by one‐pot synthesis using substituted benzaldehydes, malononitrile, and substituted phenols. All the synthesized compounds (1a, 1b, 1c, 1d, 1e) were screened in vitro for antioxidant and anticancer activities. Compounds 1c, 1d, 1e showed significant antioxidant activity in nitric oxide free radical scavenging method while compounds 1c and 1e showed significant activity in hydrogen peroxide free radical scavenging method. The other compounds showed significant to moderate activities in both the methods in comparison with ascorbic acid and butylated hydroxytoluene as standards. Compounds 1c, 1d, 1e exhibited good anticancer activity, using Michigan Cancer Foundation‐7 (MCF‐7) cell line, compared with those of other synthesized compounds.
Glycoprotein nonmetastatic melanoma protein B ameliorates skeletal muscle lesions in a SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Nagahara Yuki , Shimazawa Masamitsu , Tanaka Hirotaka , Ono Yoko , Noda Yasuhiro , Ohuchi Kazuki , Tsuruma Kazuhiro , Katsuno Masahisa , Sobue Gen , Hara Hideaki
Published: July 2015

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and subsequent muscular atrophy. The quality of life of patients with ALS is significantly improved by ameliorating muscular symptoms. We previously reported that glycoprotein nonmetastatic melanoma protein B (GPNMB; osteoactivin) might serve as a target for ALS therapy. In the present study, superoxide dismutase 1/glycine residue 93 changed to alanine (SOD1G93A) transgenic mice were used as a model of ALS. Expression of the C‐terminal fragment of GPNMB was increased in the skeletal muscles of SOD1G93A mice and patients with sporadic ALS. SOD1G93A/GPNMB transgenic mice were generated to determine whether GPNMB expression ameliorates muscular symptoms. The weight and cross‐sectional area of the gastrocnemius muscle, number and cross‐sectional area of myofibers, and denervation of neuromuscular junctions were ameliorated in SOD1G93A/GPNMB vs. SOD1G93A mice. Furthermore, direct injection of a GPNMB expression plasmid into the gastrocnemius muscle of SOD1G93A mice increased the numbers of myofibers and prevented myofiber atrophy. These findings suggest that GPNMB directly affects skeletal muscle and prevents muscular pathology in SOD1G93A mice and may therefore serve as a target for therapy of ALS. © 2015 Wiley Periodicals, Inc.
Reconstructed centennial variability of Late Holocene storminess from Cors Fochno, Wales, UK
Authors: ORME L. C. , DAVIES S. J. , DULLER G. A. T.
Published: July 2015

Future anthropogenic climate forcing is forecast to increase storm intensity and frequency over Northern Europe, due to a northward shift of the storm tracks, and a positive North Atlantic Oscillation. However understanding the significance of such a change is difficult because the natural variability of storminess beyond the range of instrumental data is poorly known. Here we present a decadal‐resolution record of storminess covering the Late Holocene, based on a 4‐m‐long core taken from the peat bog of Cors Fochno in mid‐Wales, UK. Storminess is indicated by variations in the minerogenic content as well as bromine deposited from sea spray. Twelve episodes of enhanced storm activity are identified during the last 4.5 cal ka BP. Although the age model gives some uncertainty in the timings, it appears that storminess increased at the onset and close of North Atlantic cold events associated with oceanic changes, with reduced storm activity at their peak. Cors Fochno is strongly influenced by westerly moving storms, so it is suggested that the patterns were due to variations in the intensity of westerly airflow and atmospheric circulation during times when the latitudinal temperature gradient was steepened.
The ability of in vitro antioxidant assays to predict the efficiency of a cod protein hydrolysate and brown seaweed extract to prevent oxidation in marine food model systems
Authors: Jónsdóttir Rósa , Geirsdóttir Margrét , Hamaguchi Patricia Y , Jamnik Polona , Kristinsson Hordur G , Undeland Ingrid
Published: July 2015

BACKGROUND

The ability of different in vitro antioxidant assays to predict the efficiency of cod protein hydrolysate (CPH) and Fucus vesiculosus ethyl acetate extract (EA) towards lipid oxidation in haemoglobin‐fortified washed cod mince and iron‐containing cod liver oil emulsion was evaluated. The progression of oxidation was followed by sensory analysis, lipid hydroperoxides and thiobarbituric acid‐reactive substances (TBARS) in both systems, as well as loss of redness and protein carbonyls in the cod system.

RESULTS

The in vitro tests revealed high reducing capacity, high DPPH radical scavenging properties and a high oxygen radical absorbance capacity (ORAC) value of the EA which also inhibited lipid and protein oxidation in the cod model system. The CPH had a high metal chelating capacity and was efficient against oxidation in the cod liver oil emulsion.

CONCLUSION

The results indicate that the F. vesiculosus extract has a potential as an excellent natural antioxidant against lipid oxidation in fish muscle foods while protein hydrolysates are more promising for fish oil emulsions. The usefulness of in vitro assays to predict the antioxidative properties of new natural ingredients in foods thus depends on the knowledge about the food systems, particularly the main pro‐oxidants present. © 2015 Society of Chemical Industry
Relationship between age differences and display parameters on visual comfort for autostereoscopic display
Authors: Wang Qin , Wang Qiong‐Hua , Liao Yong‐Chuan
Published: July 2015

In order to investigate the age differences for viewing autostereoscopic display, we conduct a 3 × 3 × 3 × 4 mixed design with repeated measurement experiment by using three‐dimensional (3D) video clips. Visual comfort is compared between four age groups with a questionnaire. Results of subjective evaluation are compared through the chi‐square test to check if there is a statistical significance between groups with respect to the distribution of number and proportion according to five levels of visual comfort. Then we examine age differences of visual comfort under three key display parameters including crosstalk, ambient illumination, and disparity. The results indicate that the degree of comfort varies considerably among age groups as the parameters of the display system change. Although the seniors feel most discomfort and the children get best experience in general, there is no statistical difference among the subjects when the ambient illumination is medium or disparity is large. So, it is necessary to take account of the age differences in designing 3D display parameters for enhancing visual comfort.
Impact of gas chromatography and mass spectrometry combined with gas chromatography and olfactometry for the sex differentiation of Baccharis articulata by the analysis of volatile compounds
Authors: Minteguiaga Manuel , Umpiérrez Noelia , Fariña Laura , Falcão Manuel A. , Xavier Vanessa. B. , Cassel Eduardo , Dellacassa Eduardo
Published: July 2015

The Baccharis genus has more than 400 species of aromatic plants. However, only approximately 50 species have been studied in oil composition to date. From these studies, very few take into consideration differences between male and female plants, which is a significant and distinctive factor in Baccharis in the Asteraceae family. Baccharis articulata is a common shrub that grows wild in south Brazil, northern and central Argentina, Bolivia, Paraguay and Uruguay. It is considered to be a medicinal plant and is employed in traditional medicine. We report B. articulata male and female volatile composition obtained by simultaneous distillation–extraction technique and analyzed by gas chromatography with mass spectrometry. Also, an assessment of aromatic differences between volatile extracts was evaluated by gas chromatography with olfactometry. The results show a very similar chemical composition between male and female extracts, with a high proportion of terpene compounds of which β‐pinene, limonene and germacrene D are the main components. Despite the chemical similarity, great differences in aromatic profile were found: male plant samples exhibited the strongest odorants in number and intensity of aromatic attributes. These differences explain field observations which indicate differences between male and female flower aroma, and might be of ecological significance in the attraction of pollinating insects.
Conjugated Polythiophene/Porphyrin Complex for Rapid and Simple Detection of Bacteria in Drinking Water
Authors: Yan Wenmin , Yuan Hongbo , Li Ruihua , Fan Yibing , Zhan Yong , Qi Junjie , An Hailong , Niu Ruimin , Li Gang , Xing Chengfen
Published: July 2015

An electrostatic complex combining anionic water‐soluble conjugated polythiophene (PTP) with commercial cationic porphyrin ([5,10,15,20‐tetrakis(4‐(trimethylammonio)‐phenyl)‐21H,23H‐porphine tetratosylate] (TMP)) has been designed for rapid and simple detection of bacteria infection in drinking water by applying fluorescence resonance energy transfer (FRET) strategy. There is efficient FRET from PTP to TMP for the electrostatic complex of PTP/TMP. Upon the addition of bacteria, the cationic TMP is adsorbed tightly to the negatively charged membrane surface of bacteria through electrostatic interactions, making the PTP reside in much farther proximity to TMP than that in the absence of bacteria. Therefore, much weaker FRET is observed. Interesting, the detection for bacteria based on FRET changes of PTP/TMP complex is visual in view of the color changes under ultraviolet (UV) irradiation. This assay takes advantage of the light‐harvesting property of conjugated polymer and the ratiometric measurements for minimizing the nonspecific binding effect. The strategy is promising in pathogen detection in drinking water and other sources.

image