Optoelectronic Devices: Ultrahigh Mobility in an Organic Semiconductor by Vertical Chain Alignment (Adv. Mater. 12/2016)

Vertical chain backbone alignment in a semiconducting polythiophene film is illustrated by D. R. Barbero and co-workers on page 2359. The chain alignment enables fast charge transport and ultrahigh mobility, reaching a record high average mobility of 3.1 cm² V⁻¹ s⁻¹ in the vertical direction, showing that mobilities comparable to those of inorganic materials can be obtained over relatively large distances in polymers through control of the polymer chain orientation.

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Contents: (Adv. Mater. 12/2016)

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Evaluation of the anti-inflammatory action of curcumin analog (DM1): effect on iNOS and COX-2 gene expression and autophagy pathways

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Niraldo Paulino, Amarilis Scremin Paulino, Susana N. Diniz, Sergio de Mendonça, Ivair D. Gonçalves, Fernanda Faião Flores, Reginaldo Pereira Santos, Carina Rodrigues, Paulo Celso Pardi, José Agustin Quincoces Suarez
This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Graphical abstract

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Exploration of the P3 region of PEXEL peptidomimetics leads to a potent inhibitor of the Plasmodium protease, plasmepsin V

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Michelle Gazdik, Kate E. Jarman, Matthew T. O'Neill, Anthony N. Hodder, Kym N. Lowes, Helene Jousset Sabroux, Alan F. Cowman, Justin A. Boddey, Brad E. Sleebs
The use of arginine isosteres is a known strategy to overcome poor membrane permeability commonly associated with peptides or peptidomimetics that possess this highly polar amino acid. Here, we apply this strategy to peptidomimetics that are potent inhibitors of the malarial protease, plasmepsin V, with the aim of enhancing their activity against Plasmodium parasites, and exploring the structure-activity relationship of the P³ arginine within the S3 pocket of plasmepsin V. Of the arginine isosteres trialled in the P³ position, we discovered that canavanine was the ideal and that this peptidomimetic potently inhibits plasmepsin V, efficiently blocks protein export and inhibits parasite growth. Structure studies of the peptidomimetics bound to plasmepsin V provided insight into the structural basis for the enzyme activity observed in vitro and provides further evidence why plasmepsin V is highly sensitive to substrate modification.

Graphical abstract

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Identification of Small-Molecule Compounds Targeting the Dishevelled PDZ Domain by Virtual Screening and Binding Studies

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Jiwon Choi, SongLing Ma, Hyun-Yi Kim, Ji-Hye Yun, Jung-Nyoung Heo, Weontae Lee, Kang-Yell Choi, Kyoung Tai No
The Dishevelled (Dvl) protein, which conveys signals from receptors to the downstream effectors, is a critical constituent of the Wnt/β-catenin signaling pathway. Because the PDZ domain of Dvl protein functions through associations with a wide range of protein partners, Dvl protein involved in the Wnt signaling pathway has been considered to be therapeutic targets in cancers. In this study, we performed structure-based pharmacophore model of the Dvl PDZ domain to discover novel small-molecule binders and identified eight compounds with micromolar affinity. The most potent compound identified, BMD4702, efficiently bound to the Dvl PDZ domain with 11.2 μM affinity and had a 0.186 μM KD value according to surface plasmon resonance and fluorescence spectroscopy, respectively. Combining both structural-kinetic relationship analyses and docking studies, we fourmulated that the ligand-binding site is composed of three H-bonds and three hydrophobic features. Thus, our approach led to the identification of potent binders of the Dvl PDZ domain and the findings provide novel insights into structure-based approaches to design high-affinity binders for the Dvl PDZ domain.

Graphical abstract

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Synthesis and Hydrolysis of Alkoxy(aminoalkyl)diorganylsilanes of the Formula Type R2(RO)Si(CH2)nNH2 (R = Alkyl, n = 1–3): A Systematic Experimental and Computational Study

Abstract

Alkoxy(aminoalkyl)silanes are important precursors for the formation of amino-functionalized polysiloxanes, which are used in many technical applications. To better understand the mechanism of the hydrolytic cleavage of the Si–alkoxy moiety of alkoxy(aminoalkyl)silanes (an important key step in the formation of amino-functionalized polysiloxanes), a systematic experimental and computational study on the hydrolysis of alkoxy(aminoalkyl)diorganylsilanes of the formula type R₂(RO)Si(CH₂)_nNH₂ (R = alkyl, n = 1–3) was conducted. For reasons of comparison, silanes of the formula types R₂(RO)SiC(H)MeCH₂NH₂ and R₂(RO)Si(CH₂)_nX [R = alkyl; n = 1–3; X = N(H)Me, NMe₂, piperidino, NMe₃⁺I^–, N(H)COOMe, N(Me)COOMe] and compounds Me₂(MeO)Si(CH₂)₆Me and Me₂(MeO)Si(CH₂)₆NH₂ were included in this study. For this purpose, the various silanes were synthesized and studied for their hydrolysis kinetics in CD₃CN/D₂O under acidic and basic conditions by using ¹H NMR spectroscopy as the analytic tool. These experimental investigations were complemented by computational studies (calculation of proton affinities, reaction barriers, and energies relative to reactants of intermediate transition complexes). The different hydrolysis reactivities observed are the result of a number of parameters, such as electronic and steric effects, the strong impact of the pD value, and intramolecular N–H···O hydrogen bonds between the protonated amino group and the alkoxy leaving group. This comprehensive study provided deep insight into the mechanism of hydrolysis of analogous α-, β-, and γ-amino-functionalized alkoxy(aminoalkyl)diorganylsilanes of the formula type R₂(RO)Si(CH₂)_nNH₂ (R = organyl, n = 1–3) and a series of related α/β/γ analogues with other nitrogen-based functional groups.

Kinetic studies provided a deep insight into the mechanism of hydrolysis of analogous α-, β-, and γ-amino-functionalized alkoxy(aminoalkyl)diorganylsilanes of the formula type R₂(RO)Si(CH₂)_nNH₂ (R = organyl, n = 1–3) and a series of related α/β/γ analogues with other nitrogen-based functional groups.

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Single-cell Mass Spectrometry with Multi-solvent Extraction Identifies Metabolic Differences between Left and Right Blastomeres in the 8-cell Frog (Xenopus) Embryo

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00200E, Paper

Rosemary M. Onjiko, Sydney E. Morris, Sally A. Moody, Peter Nemes
Single-cell metabolic mass spectrometry enables the discovery (untargeted) analysis of small molecules in individual cells. Using single-cell capillary electrophoresis high-resolution mass spectrometry (CE-HRMS), we recently uncovered small-molecule differences between embryonic...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Quantification of Tunicamycin-Induced Protein Expression and N-Glycosylation Changes in Yeast

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00144K, Paper

Haopeng Xiao, Johanna M Smeekens, Ronghu Wu
Tunicamycin is a potent protein N-glycosylation inhibitor that has frequently been used to manipulate protein glycosylation in cells. However, protein expression and glycosylation changes as a result of tunicamycin treatment...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice

Recent data indicate a role for airway epithelial necroptosis, a regulated form of necrosis, and the associated release of damage-associated molecular patterns (DAMPs) in the development of chronic obstructive pulmonary disease (COPD). DAMPs can activate pattern recognition receptors (PRRs), triggering innate immune responses. We hypothesized that cigarette smoke (CS)-induced epithelial necroptosis and DAMP release initiate airway inflammation in COPD. Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE), and necrotic cell death (membrane integrity by propidium iodide staining) and DAMP release (i.e., double-stranded DNA, high-mobility group box 1, heat shock protein 70, mitochondrial DNA, ATP) were analyzed. Subsequently, BEAS-2B cells were exposed to DAMP-containing supernatant of CS-induced necrotic cells, and the release of proinflammatory mediators [C-X-C motif ligand 8 (CXCL-8), IL-6] was evaluated. Furthermore, mice were exposed to CS in the presence and absence of the necroptosis inhibitor necrostatin-1, and levels of DAMPs and inflammatory cell numbers were determined in bronchoalveolar lavage fluid. CSE induced a significant increase in the percentage of necrotic cells and DAMP release in BEAS-2B cells. Stimulation of BEAS-2B cells with supernatant of CS-induced necrotic cells induced a significant increase in the release of CXCL-8 and IL-6, in a myeloid differentiation primary response gene 88-dependent fashion. In mice, exposure of CS increased the levels of DAMPs and numbers of neutrophils in bronchoalveolar lavage fluid, which was statistically reduced upon treatment with necrostatin-1. Together, we showed that CS exposure induces necrosis of bronchial epithelial cells and subsequent DAMP release in vitro, inducing the production of proinflammatory cytokines. In vivo, CS exposure induces neutrophilic airway inflammation that is sensitive to necroptosis inhibition.

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Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs

Abstract

Introduction

Several types of stem cells have been successfully demonstrated to exist in the human degenerated intervertebral disc (IVD), which is composed of annulus fibrosus (AF), nucleus pulposus (NP) and cartilage endplate (CEP). However, the differences in the biological characteristics among these and bone marrow derived mesenchymal stem cells (BM-MSCs) remain unclear.

Materials and methods

To investigate this issue, cells were harvested from human AF, NP, CEP, and bone marrow, respectively; passage 2 cells were selected using the agarose suspension culture system to obtain stem cell clones. Following expansion in vitro, stem cells from different anatomical regions were compared regarding the morphology, proliferation ability, immunophenotypic expression, and multi-lineage differentiation capacity. In addition, stem cell-alginate bead compositions were constructed for the comparison of DNA and sGAG content.

Results

There were subtle differences regarding cell morphology, but no significant differences in proliferation ability among the four types of stem cells. For the immunophenotypic analysis, all stem cells basically fulfilled the criteria for mesenchymal stem cells (MSCs), which have been published by the International Society for Cellular Therapy (ISCT), with a significant difference in CD105 expression. A comparison of the osteogenic capacities indicated: cartilage endplate-derived stem cells (CESCs) > annulus fibrosus-derived stem cells (AFSCs) > BM-MSCs > nucleus pulposus-derived stem cells (NPSCs). The chondrogenesis difference was similar to osteogenesis. For adipogenesis: BM-MSCs >NPSCs >CESCs >AFSCs. In the stem cell/alginate composition, the CESCs consistently showed the superior chondrogenic potential among all those cell types.

Conclusions

Our data indicated that all the four types of stem cells shared some similar biological properties (regarding shape, proliferation ability and immunophenotypic expression). CESCs, which had the strongest osteogenic and chondrogenic potentials, may serve as excellent seed cells for NP/cartilage or bone tissue engineering.

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Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina

A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in...

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Colorectal Adenomas

Since the last review of colorectal adenomas in the Journal, a wealth of new data has emerged that is improving our understanding of their clinical significance. In the past 10 years, several large studies, performed predominantly in the United States, have evaluated persons at average risk for…

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Colorectal Adenomas

Since the last review of colorectal adenomas in the Journal, a wealth of new data has emerged that is improving our understanding of their clinical significance. In the past 10 years, several large studies, performed predominantly in the United States, have evaluated persons at average risk for…

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Pyridylborates as a New Type of Robust Scorpionate Ligand: From Metal Complexes to Polymeric Materials

Abstract

The importance of scorpionate ligands in modern coordination chemistry continues to increase, because of their outstanding versatility, tunability and user-friendliness. Herein, we provide a short overview of recent developments in the classes of scorpionate ligands, derived from pyrazoles, triazoles, imidazoles, oxazolines, thioimidazoles and other similar systems, followed by an in-depth discussion of a new type of robust and tunable scorpionate ligand, tris(2-pyridyl)borates. The structure and synthesis of tris(2-pyridyl)borate (Tpyb) ligands are discussed, and key features of coordination of Tpyb ligands with metal ions, as well as supramolecular crystal packing, transmetallation and applications in metallo-supramolecular polymer chemistry are addressed.

An overview of the different classes of scorpionate ligands is provided, and an in-depth discussion of a new type of robust and tunable ligand, the tris(2-pyridyl)borates. The structure and synthesis of the ligands, key features of coordination with metal ions, the supramolecular crystal packing, transmetallation and applications in metallo-supramolecular polymer chemistry are addressed.

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Ionic Immobilization of Silicotungstic Acid on Amine-Functionalized Zirconia: A Mesoporous Catalyst for Esterification of Maleic Acid

Abstract

Silicotungstic acid (H₄SiW₁₂O₄₀) has been immobilized onto the mesopores of amine-functionalized zirconia by exploitation of electrostatic interactions. The ionic grafting of silicotungstic acid was confirmed by XPS, FTIR, UV/Vis-DRS and TGA analysis. The mesoporosity of the material was confirmed through N₂ adsorption/desorption analysis. The morphology of the material was established by TEM analysis. The immobilized silicotungstate material was found to be an efficient heterogeneous catalyst for selective esterification of maleic acid with butan-1-ol. A 98 % level of conversion of maleic acid and 82 % selectivity for dibutyl maleate within 5 h at 95 °C was achieved. The catalyst could be reused thrice without loss of activity.

Silicotungstic acid was supported on amine-functionalized mesoporous zirconia with the aid of electrostatic interactions. Its catalytic activity in the selective esterification of maleic acid has been established.

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A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV coreceptor, CCR5. Here we describe the development and optimization of a scalable low-cost production process for 5P12-RANTES based on expression in Pichia pastoris. At pilot (150 L) scale, this cGMP compliant process yielded 30 g of clinical grade 5P12-RANTES. As well as providing sufficient material for the first stage of clinical development, this process represents an important step towards achieving production of 5P12-RANTES at a cost and scale appropriate to meet needs for topical HIV prevention worldwide.

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Thiamine-induced priming against root-knot nematode infection in rice involves lignification and hydrogen peroxide generation

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Meloidogyne graminicola a major threat to rice agriculture

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Targeting MALT1 proteolytic activity in immunity, inflammation and disease: good or bad?

MALT1 is a signaling protein that plays a key role in immunity, inflammation, and lymphoid malignancies. For a long time MALT1 was believed to function as a scaffold protein, providing an assembly platform for other signaling proteins. This view changed dramatically when MALT1 was also found to have proteolytic activity and a capacity to fine-tune immune responses. Preclinical studies have fostered the belief that MALT1 is a promising therapeutic target in autoimmunity and B cell lymphomas. However, recent studies have shown that mice expressing catalytically-inactive MALT1 develop multi-organ inflammation and autoimmunity, and thus have tempered this initial enthusiasm. We discuss recent findings, highlighting the urgent need for a better mechanistic and functional understanding of MALT1 in host defense and disease.

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The impact of stress on the prevalence of prednisolone in bovine urine: a metabolic fingerprinting approach

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Poor nutritional status is associated with other geriatric domain impairments and adverse postoperative outcomes in onco-geriatric surgical patients – A multicentre cohort study

Publication date: Available online 17 March 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Monique G. Huisman, Giacomo Veronese, Riccardo A. Audisio, Giampaolo Ugolini, Isacco Montroni, Geertruida H. de Bock, Barbara L. van Leeuwen
BackgroundNutritional status (NS), though frequently affected in onco-geriatric patients, is no standard part of a geriatric assessment. The aim of this study was to analyse the association between a preoperatively impaired NS and geriatric domain impairments and adverse postoperative outcomes in onco-geriatric surgical patients.Methods309 patients ≥70 years undergoing surgery for solid tumours were prospectively recruited. Nine screening tools were preoperatively administered as part of a geriatric assessment. NS was based on BMI, weight loss and food intake. Odds ratio's (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression analysis. The occurrence of 30-day adverse postoperative outcomes was recorded.ResultsAt a median age of 76 years, 107 patients (34.6%) had an impaired NS. Decreased performance status and depression were associated with an impaired NS, when adjusted for tumour characteristics and comorbidities (ORPS>1 3.46; 95%CI 1.56-7.67. ORGDS>5 2.11; 95%CI 1.05-4.26). An impaired NS was an independent predictor for major complications (OR 3.3; 95%CI 1.6-6.8). Ten out of 11 patients who deceased had an impaired NS.ConclusionAn impaired NS is prevalent in onco-geriatric patients considered to be fit for surgery. It is associated with decreased performance status and depression. An impaired NS is a predictor for adverse postoperative outcomes. NS should be incorporated in a geriatric assessment.



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Cloning and Expression of the γ-Polyglutamic Acid Synthetase Gene pgsBCA in Bacillus subtilis WB600

To clone and express the γ-polyglutamic acid (γ-PGA) synthetase gene pgsBCA in Bacillus subtilis, a pWB980 plasmid was used to construct and transfect the recombinant expression vector pWB980-pgsBCA into Bacillus subtilis WB600. PgsBCA was expressed under the action of a P43 promoter in the pWB980 plasmid. Our results showed that the recombinant bacteria had the capacity to synthesize γ-PGA. The expression product was secreted extracellularly into the fermentation broth, with a product yield of 1.74 g/L or higher. γ-PGA samples from the fermentation broth were purified and characterized. Hydrolysates of γ-PGA presented in single form, constituting simple glutamic acid only, which matched the characteristics of the infrared spectra of the γ-PGA standard, and presented as multimolecular aggregates with a molecular weight within the range of 500–600 kDa. Expressing the γ-PGA synthetase gene pgsBCA in B. subtilis system has potential industrial applications.

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Changes in pigment, spectral transmission and element content of pink chicken eggshells with different pigment intensity during incubation

Objective. The objective of this study was to investigate changes in pigment, spectral transmission and element content of chicken eggshells with different intensities of pink pigment during the incubation period. We also investigated the effects of the region (small pole, equator and large pole) and pink pigment intensity of the chicken eggshell on the percent transmission of light passing through the chicken eggshells. Method. Eggs of comparable weight from a meat-type breeder (Meihuang) were used, and divided based on three levels of pink pigment (light, medium and dark) in the eggshells. During the incubation (0–21 d), the values of the eggshell pigment (ΔE, L∗, a∗, b∗) were measured. The percent transmission of light for different regions and intensities of eggshell pigmentation was measured by using the visible wavelength range of 380–780 nm. Result. Three measured indicators of eggshell color, ΔE, L∗ and a∗, did not change significantly during incubation. Compared with other regions and pigment intensities, eggshell at the small pole and with light pigmentation intensity showed the highest percent transmission of light. The transmission value varied significantly (P

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Sponge distribution and the presence of photosymbionts in Moorea, French Polynesia

Photosymbionts play an important role in the ecology and evolution of diverse host species within the marine environment. Although sponge-photosymbiont interactions have been well described from geographically disparate sites worldwide, our understanding of these interactions from shallow water systems within French Polynesia is limited. We surveyed diverse habitats around the north coast of Moorea, French Polynesia and screened sponges for the presence of photosymbionts. Overall sponge abundance and diversity were low, with

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Omega-3 fatty acids shown to exert a positive effect on the aging brain

Changes in cognitive function and memory decline form a normal part of aging. However, in neurodegenerative diseases such as Alzheimer's disease or mild cognitive impairment (the pre-dementia phase of Alzheimer's disease), these changes occur more quickly. There are currently no effective treatments for these diseases. Physicians and researchers are constantly looking for new treatment methods that will maintain their patients' cognitive performance and independence for as long as possible. Targeted prevention is another essential component when trying to preserve cognitive function for as long as possible.

"Ideally, any measures used should be aimed at long-term prevention. This means that measures must be suitable for use in healthy older adults, and should be easy to integrate into day-to-day life," says Dr. Nadine Külzow, a researcher at Charité's Department of Neurology. Nutritional supplements represent one such option. "A number of different dietary components, including omega-3 fatty acids, are currently thought to have a direct effect on nerve cell function. This is why we decided to study the effects on memory function of a daily dose of 2,200 milligrams taken for a duration of six months," says Dr. Külzow.

Study participants who received omega-3 fatty acids showed greater improvements on an object location memory task than participants who received a placebo containing sunflower oil. However, there was no evidence of improved performance on a verbal learning test. "Results from this study suggest that a long-term approach to prevention is particularly effective in preserving cognitive function in older individuals. A targeted approach involving dietary supplements can play a central role in this regard," concluded the researchers. Whether or not the improvements recorded can make a noticeable difference in day-to-day life will need to be investigated as part of a larger clinical study. As a next step, however, the researchers are planning to test the effect of supplementation with a combination of omega-3 fatty acids and vitamin B. According to research conducted at Oxford, this combination may be associated with synergistic effects.

Külzow N, Witte AV, Kerti L, Grittner U, Schuchardt JP, Hahn A, Flöeel A (2016). Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults. J Alzheimers Dis 2016 Feb 10. DOI: 10.3233/JAD-150886

The article will be published in the The Journal of Alzheimer's Disease 51(3), which is scheduled for publication on March 29, 2016.

Boilerplate:

ABOUT THE JOURNAL OF ALZHEIMER'S DISEASE (JAD)

The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 4.151 according to Thomson Reuters' 2014 Journal Citation Reports. The Journal is published by IOS Press.

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New insights into the structure of multi-component virus populations in a host

Read the full article on ScienceDirect.

Intra-host structure of multi-genotype populations of a plant RNA virus assessed by a novel RNA in situ hybridization approach

Text by Svetlana Folimonova and María Bergua 

 

Citrus tristeza virus (CTV) represents a peculiar, somewhat unique, virus model. It has been known since long time that field populations of CTV are often composed of different genotypes or strains of the virus. As we demonstrated in our recent study, this results from the fact that superinfection exclusion between variants of CTV follows a specific rule: only virus variants of the same strain exclude each other, while no exclusion occurs between variants belonging to different CTV strains permitting their co-existence in the same plant (Folimonova et al., 2010). On the other hand, little was known about the intra-host structure of such complex virus populations and, for instance, whether individual genotypes spatially segregate within the infected tissues or they are well mixed and are able to co-infect the same cells. A novel RNA in situ hybridization (ISH) approach employed in this work allowed us to address these questions.

 

Some time ago we engineered a green fluorescent protein-tagged virus using a cDNA clone of a CTV variant of the T36 strain and used it to study virus distribution and movement within citrus hosts (Folimonova et al., 2008). The lack of the infectious clones of other CTV strains limited, however, further studies of the interaction and distribution of CTV variants representing heterologous strains upon their co-infection. While searching for a technique that enables differential labeling of individual variants of CTV simultaneously present in a plant, we came across the RNAscope ISH assay (Advanced Cell Diagnostics, Inc.). The manufacturer claimed that this novel method allows specific detection and separation of two RNA targets sharing up to 90% of sequence identity. This seemed exciting!

 

Using the assistance from Advanced Cell Diagnostics, we designed probes that target the RNA genomes of two distinct CTV genotypes, T36 and T68. The probes were tested in the ISH assay using tissue samples from singly or doubly infected citrus plants. One of the challenging parts was to optimize the RNAscope protocol for virus-infected plant tissue. The final results, however, were remarkable. Highly specific labeling showing no cross-reaction between a probe targeting one virus variant and RNA molecules produced by another variant allowed us to demonstrate that in doubly infected plants the two virus variants appeared to be well mixed and often co-infected the same cells. According to our knowledge, this is the first report of simultaneous in situ visualization of two distinct strains of a plant virus.

 

Figure legend

Simultaneous visualization of Citrus tristeza virus (CTV) T36 (blue stain) and T68-1 (red stain) RNA in cross sections from petioles of a Citrus macrophylla plant coinfected with T36 and T68-1 isolates using a multiplex RNAscope in situ hybridization assay. Both CTV variants were found occupying the same cells (black stain).

Introducing the authors

 

At the left: María Bergua, she is a former postdoctoral researcher in Svetlana Folimonova's laboratory at the University of Florida. Currently María is a postdoctoral researcher at the University of California, Department of Plant Pathology, Davis, CA, USA.

At the right: Svetlana Folimonova, Assistant Professor at the University of Florida, Department of Plant Pathology, Gainesville, FL, USA.

 

About the research

Simultaneous visualization of two Citrus tristeza virus genotypes provides new insights into the structure of multi-component virus populations in a host

María Bergua, Dane M. Phelan, Aurélie Bak, David C. Bloom, Svetlana Y. Folimonova

Virology, Volume 491, April 2016, Pages 10–19

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Fundic gland differentiation of oncocytic/pancreatobiliary subtypes of pancreatic intraductal papillary mucinous neoplasms

Abstract

Aims

Intraductal papillary mucinous neoplasms (IPMNs) differentiate in several histological directions, which are related to IPMNs' clinical behaviour. IPMNs' differentiation to the gastric foveolar epithelium/pyloric gland (PG) is well-known. However, no study has been conducted regarding the fundic gland (FG) differentiation. To determine the frequency of FG-differentiation and its relationship with IPMNs' clinicopathological features, 48 surgically resected IPMN cases consisting of 17 gastric (G), 15 intestinal (I), 10 pancreatobiliary (PB), and 6 oncocytic (O) subtypes were studied.

Methods and Results

Clinicopathological data, including histological tumour grade, immunohistochemical data for MUCs, pepsinogen I/II, and H.K-ATPase, as well as GNAS/KRAS status were analysed. FG-differentiation was assessed by pepsinogen I and H.K-ATPase, while pepsinogen II and MUC6 were utilised to identify the equivalent cell type of the normal FG. RT-PCR for PGA5/PGC (pepsinogen I/ II mRNA, respectively) and qRT-PCR for PGA5 were performed to confirm the immunohistochemistry results. Pepsinogen I expression was detected in 12.5% (6/48 cases) of total IPMN cases, of which 66.7% (4/6 cases) of O- and 20.0% (2/10 cases) of PB-IPMN were pepsinogen I-positive. No H.K-ATPase-positive cases were detected. Three O-cases with pepsinogen I expression showed similar histology to normal FG. RT-PCR and qRT-PCR confirmed the immunohistochemical results. All IPMNs with FG differentiation were O- or PB-subtype, histologically high grade, and without GNAS mutation.

Conclusions

IPMNs' differentiation to gastric FG relates to O-/PB-subtypes and with high grade. This is the first report describing IPMNs' differentiation to the FG and revealing its relationship with IPMNs' clinicopathological features.

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Syntheses and magnetic properties of a pyrimidyl-substituted nitronyl nitroxide radical and its cobalt(II) complexes

Chem. Commun., 2016, Advance Article
DOI: 10.1039/C6CC00915H, Communication

Jian Wang, Jia-Nan Li, Shao-Liang Zhang, Xin-Hua Zhao, Dong Shao, Xin-Yi Wang
A new bis-bidentate pyrimidyl-substituted nitronyl nitroxide radical and two cobalt(II) complexes of this ligand were synthesized and characterized.
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1,7-Naphthodiyne: a new platform for the synthesis of novel, sterically congested PAHs

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01214K, Communication

Dolores Perez, Iago Pozo, Agustin Cobas, Diego Pena, Enrique Guitian
The synthesis of an efficient precursor of the novel 1,7-naphthodiyne synthon is reported. Preliminary experiments demonstrate the usefulness of this platform for the synthesis of sterically congested polyarenes, such as...
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Localized Castleman’s Disease in the Breast in a Young Woman

Castleman's disease (CD) is a rare lymphoproliferative disorder of unknown etiology. It typically occurs in adulthood but it may also develop in childhood. Clinically, this disease may be classified as localized (unicentric) or systemic (multicentric). Six cases of breast CD have been described in the literature, and all have been reported in adults. Herein we describe the case of a 15-year-old female who presented with a slow-growing tumor in the right breast. The tumor was excised and histopathological examination demonstrated hyaline vascular variant CD. After two years of follow-up, the patient was asymptomatic without evidence of cervical or axillary lymphadenopathy.

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A Tough Nut to Crack: detection of peanuts in nuts with HRMS

As Monaci et al (2015) explain, when peanuts are packaged or stored adjacent to other nuts there is a risk of cross contamination. Since peanuts can cause serious allergic reactions even in small amounts, it is vital to accurately identify and isolate these sources of contamination. To this end, researchers have developed specialized testing such Read the rest of this article

The post A Tough Nut to Crack: detection of peanuts in nuts with HRMS appeared first on Accelerating Science.

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Clinical and echocardiographic outcomes after bariatric surgery in obese patients with left ventricular systolic dysfunction

Circulation: Heart Failure

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Effectiveness of anti-TNF? drugs in patients with Crohn's disease who do not achieve remission with their first anti-TNF? agent

Digestive and Liver Diseases

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Bundled payments for surgical colectomy among medicare enrollees

JAMA Surgery

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Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: A multicenter phase 2 study

Cancer

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Burden of rotavirus disease in Norway: using national registries for public health research

The Pediatric Infectious Disease Journal

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Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from astral-1 placebo-controlled trial

Journal of Hepatology

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Effect of Kuijie granule on the expression of TGF-β/Smads signaling pathway in patients with ulcerative colitis

Evidence-based Complementary and Alternative Medicine

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Presence of hepatitis C (HCV) infection in baby boomers with medicare is independently associated with mortality and resource utilisation

Alimentary Pharmacology and Therapeutics

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Impaired outcome colitis associated rectal cancer versus sporadic

Journal of Surgical Research

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Combining routine markers improves the accuracy of transient elastography for hepatitis B cirrhosis detection

Digestive and Liver Diseases

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Decrease in seroma rate after adopting progressive tension sutures without drains: a single surgery center experience of 451 abdominoplasties over 7 years

Aesthetic Surgery Journal

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Responder interferon lambda genotypes are associated with higher risk of liver fibrosis in HIV-hepatitis C virus co-infection

The Journal of Infectious Diseases

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Expression of chemokine receptor CCR7 is a negative prognostic factor for patients with gastric cancer: A meta-analysis

Gastric Cancer

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The ability of hepascore to predict liver fibrosis in chronic liver disease: a meta-analysis

Liver International

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Contribution of alcoholic and non-alcoholic fatty liver disease to the burden of liver-related morbidity and mortality

Gastroenterology

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Hepatocellular carcinoma detected by regular surveillance: Does timely confirmation of diagnosis matter?

Digestive and Liver Diseases

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Laparoscopic revision of Roux-en-Y gastric bypass to sleeve gastrectomy: A ray of hope for failed Roux-en-Y gastric bypass

Asian Journal of Endoscopic Surgery

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Cost effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial

Gastrointestinal Endoscopy

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HIV/HCV coinfection in Spain: Prevalence and patient characteristics

Open Forum Infectious Diseases

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