bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from Bordetella/Alcaligenes
Authors: Meyners Christian , Baud Matthias G. J. , Fuchter Matthew J. , Meyer‐Almes Franz‐Josef
Published: January 2014

Thermodynamic studies on ligand–protein binding have become increasingly important in the process of drug design. In combination with structural data and molecular dynamics simulations, thermodynamic studies provide relevant information about the mode of interaction between compounds and their target proteins and therefore build a sound basis for further drug optimization. Using the example of histone deacetylases (HDACs), particularly the histone deacetylase like amidohydrolase (HDAH) from Bordetella/Alcaligenes, a novel sensitive competitive fluorescence resonance energy transfer‐based binding assay was developed and the thermodynamics of interaction of both fluorescent ligands and inhibitors to histone deacetylase like amidohydrolase were investigated. The assay consumes only small amounts of valuable target proteins and is suitable for fast kinetic and mechanistic studies as well as high throughput screening applications. Binding affinity increased with increasing length of aliphatic spacers (n = 4–7) between the hydroxamate moiety and the dansyl head group of ligand probes. Van't Hoff plots revealed an optimum in enthalpy contribution to the free energy of binding for the dansyl‐ligand with hexyl spacer. The selectivity in the series of dansyl‐ligands against human class I HDAC1 but not class II HDACs 4 and 6 increased with the ratio of ΔH0/ΔG0. The data clearly emphasize the importance of thermodynamic signatures as useful general guidance for the optimization of ligands or rational drug design. Copyright © 2014 John Wiley & Sons, Ltd.
Binding of azurin to cytochrome c 551 as investigated by surface plasmon resonance and fluorescence
Authors: Santini Simona , Bizzarri Anna Rita , Yamada Tohru , Beattie Craig W. , Cannistraro Salvatore
Published: January 2014

The interaction between azurin (Az) and cytochrome c 551 (CytC551) from Pseudomonas aeruginosa deserves particular interest for both its physiological aspects and their possible applications in bionano devices. Here, the kinetics of the interaction has been studied by surface plasmon resonance and fluorescence quenching. Surface plasmon resonance data have been successfully interpreted by the heterogeneous ligand model, which predicts the existence of two binding sites on the immobilized Az for CytC551 molecules in solution. On the other hand, the fluorescence study indicates the formation of a complex, with the involvement of the lone Az tryptophan (Trp) at position 48. The two different techniques point out the occurrence of an encounter complex between Az and CytC551 that evolves toward the formation of a more stable complex characterized by an equilibrium dissociation constant KD typical of transient interactions. Copyright © 2014 John Wiley & Sons, Ltd.
Chemical shift encoding‐based water–fat separation methods
Authors: Eggers Holger , Börnert Peter
Published: January 2014

The suppression of signal from fat constitutes a basic requirement in many applications of magnetic resonance imaging. To date, this is predominantly achieved during data acquisition, using fat saturation, inversion recovery, or water excitation methods. Postponing the separation of signal from water and fat until image reconstruction holds the promise of resolving some of the problems associated with these methods, such as failure in the presence of field inhomogeneities or contrast agents. In this article, methods are reviewed that rely on the difference in chemical shift between the hydrogen atoms in water and fat to perform such a retrospective separation. The basic principle underlying these so‐called Dixon methods is introduced, and some fundamental implementations of the required chemical shift encoding in the acquisition and the subsequent water–fat separation in the reconstruction are described. Practical issues, such as the selection of key parameters and the appearance of typical artifacts, are illustrated, and a broad range of applications is demonstrated, including abdominal, cardiovascular, and musculoskeletal imaging. Finally, advantages and disadvantages of these Dixon methods are summarized, and emerging opportunities arising from the availability of information on the amount and distribution of fat are discussed. J. Magn. Reson. Imaging 2014;40:251–268. © 2014 Wiley Periodicals, Inc.
Paranodal dysmyelination in peripheral nerves of Trembler mice
Authors: Rosenbluth Jack , Bobrowski‐Khoury Natasha
Published: January 2014

Subtle defects in paranodes of myelinated nerve fibers can cause significant physiological malfunction. We have investigated myelinated fibers in the peripheral nervous system (PNS) of the Trembler mouse, a model of CMT‐1A neuropathy, for evidence of such defects. Ultrastructural analysis shows that the “transverse bands,” which attach the myelin sheath to the axon at the paranodal axoglial junction, are grossly diminished in number in Trembler nerve fibers. Although paranodes often appear to be greatly elongated, it is only a short region immediately adjacent to the node of Ranvier that displays transverse bands. Where transverse bands are missing, the junctional gap widens, thus reducing resistance to short circuiting of nodal action currents during saltatory conduction and increasing the likelihood that axonal K+ channels under the myelin sheath will be activated. In addition, we find evidence that structural domains in Trembler axons are incompletely differentiated, consistent with diminution in nodal Na channel density, which could further compromise conduction. Deficiency of transverse bands may also increase susceptibility to disruption of the paranodal junction and retraction of the myelin sheath. We conclude that Trembler PNS myelinated fibers display subtle defects in paranodal and nodal regions that could contribute significantly to conduction defects and increased risk of myelin detachment. © 2014 Wiley Periodicals, Inc.
Anomalies, trends and variability in atmospheric fields related to hailstorms in north‐eastern Spain
Authors: García‐Ortega E. , Hermida L. , Hierro R. , Merino A. , Gascón E. , Fernández‐González S. , Sánchez J. L. , López L.
Published: January 2014

Hailstorms have become a serious meteorological risk in mid‐latitude countries because of their small‐scale development and short time span, and their forecasting remains problematic. Moreover, the lack of reliable hailstorm databases is an important handicap for Numerical Weather Prediction (NWP) model validation, time trend studies and establishment of hailstorm relationships with global warming and climate change. However, this can be overcome by ascertaining physical relationships between favourable synoptic patterns and mesoscale trigger factors for hailstorm development in a local study area.

North‐eastern Spain is one of the European regions with largest number of hailstorm days (HD) observed in the summer. Since 2001, from May through September, reliable databases of hailstorm occurrence in the middle Ebro Valley have been constructed, which include intensity, temporal frequency and spatial coordinate data. June and July 2006 had the largest number of HD in 2001–2010. With the objective of analysing meteorological factors responsible for this anomaly, atmospheric patterns at low and mid‐tropospheric levels were studied. We determined a set of special synoptic configurations, with an evident deviation from climatic values generating anomalies of 850 hPa temperature relative to the characteristic values of 2001–2010 and 1950–2010. An analysis of these anomalies detected a positive trend of 850 hPa temperature and geopotential height in the western Mediterranean area. As a consequence, the characteristic synoptic circulation has changed since 1950, towards low‐level patterns favouring adequate thermodynamic environments for hailstorm development in north‐eastern Spain. Finally, after a cluster analysis, we studied periodicities in the monthly 850 hPa temperature field to improve knowledge for seasonal forecasting of hailstorms.
The Usual and the Unusual: Solving Remote Associates Test Tasks Using Simple Statistical Natural Language Processing Based on Language Use
Authors: Klein Ariel , Badia Toni
Published: January 2014

In this study we show how complex creative relations can arise from fairly frequent semantic relations observed in everyday language. By doing this, we reflect on some key cognitive aspects of linguistic and general creativity. In our experimentation, we automated the process of solving a battery of Remote Associates Test tasks. By applying Statistical Natural Language Processing techniques to a large web‐based corpus, we perform a frequency and collocation analysis of the test items. Results show that 37% of the 68 tasks were automatically solved, whereas human accuracy reached 43%. Our method outperformed humans in the tasks rated as difficult: 38% and 32%, respectively. Highly relevant is that the novel and adequate relations established in order to solve theRATwere not previously present in the corpus. The frequency based approach pervades all stages of our method: during the divergent stage, highly frequent collocations are listed, while the convergent stage starts by matching each task's triads output, shrinking that list, and finalizing it by choosing the least frequent, therefore more informative and often correct, result. Finally, we discuss the implications of our model in overcoming functional fixedness and understanding cognitive salience in the creative process.
Improving ryegrass‐clover pasture dry matter yield and urea efficiency with gibberellic acid
Authors: Zaman Mohammad , Ghani Anwar , Kurepin Leonid V , Pharis Richard P , Khan Shabana , Smith Terry J
Published: January 2014

BACKGROUND

The effects of spraying gibberellic acid (GA3) at 20 or 30 g ha−1, with or without application of urea, on pasture dry matter (DM) yield, herbage nitrogen (N) concentration and feed quality were investigated in 2011 and 2012 for managed pastoral systems in New Zealand across a range of sites, in both autumn and spring.

RESULTS

On the Waikato site (autumn and spring, 2012), and at all five sites in 2011, liquid urea applied with GA3 at 20 or 30 g ha−1 consistently produced significantly higher pasture shoot DM yield, relative to liquid urea alone. Application of GA3 alone reduced feed quality by lowering metabolizable energy, crude protein and organic matter digestibility values. However, a reduced feed quality was not observed when GA3 was applied together with liquid urea. Liquid urea applied with GA3 also reduced total N and nitrate‐N concentration in herbage, relative to liquid urea applied alone.

CONCLUSION

Application of GA3 together with liquid urea provides an opportunity for the strategic use of urea to meet both production and environmental goals. © 2014 Society of Chemical Industry
Multiresidue method for the fast determination of pesticides in nutraceutical products (Camellia sinensis) by GC coupled to triple quadrupole MS
Authors: Martínez‐Domínguez Gerardo , Plaza‐Bolaños Patricia , Romero‐González Roberto , Frenich Antonia Garrido
Published: January 2014

A method based on QuEChERS (quick, easy, cheap, effective, rugged, and safe) has been developed and validated for the determination and quantification of more than 140 pesticides in nutraceutical products obtained from green tea (Camellia sinensis). Extraction was performed with acidified acetonitrile (acetic acid 1%, v/v) and a clean‐up step using primary secondary amine (50 mg), graphitized black carbon (100 mg) and magnesium sulfate (200 mg) was needed. Pesticide determination was achieved utilizing GC coupled to triple quadrupole MS/MS using the selective‐reaction monitoring mode. The total run time was 23 min. Pesticides were quantified using matrix‐matched calibration. Recoveries ranged from 70 to 120% and relative SD was lower than 25% at 10, 50, and 100 μg/kg. LOQs were lower than 10 μg/kg. 148 pesticides were validated. The validated method was applied to commercial nutraceutical products, detecting 4,4‐dichlorobenzophenone (28 μg/kg), o,p′‐dicofol (38 μg/kg) and p,p‐dicofol (44 μg/kg) in a few samples.
Microstructure characterization of a decellularized vocal fold scaffold for laryngeal tissue engineering
Authors: Tse Justin R. , Long Jennifer L.
Published: January 2014

Objectives/Hypothesis

One potential treatment for vocal fold injury or neoplasia is to replace the entire vocal fold with a tissue‐engineered scaffold. This scaffold should ideally have similar mechanical properties and extracellular matrix composition as the native vocal fold. As one approach toward this goal, we decellularized human vocal folds and characterized their mechanical properties and extracellular matrix microstructure.

Study Design

Basic science investigation.

Methods

Human vocal folds were dissected from the laryngeal framework and treated with sodium dodecyl sulfate (SDS) to remove all cells. Mechanical properties were measured by indentation before and after SDS treatment. The extracellular matrix components of collagen, laminin, elastin, and hyaluronic acid were also characterized before and after decellularization using histology and immunofluorescence.

Results

After 4 days of SDS treatment, we obtained a scaffold that retained the original geometry of the vocal fold but was devoid of cells. The elastic modulus of the vocal folds did not change significantly before and after decellularization. Upon qualitative inspection, the decellularized vocal folds retained the original collagen, elastin, and laminin content and orientation but lost the original hyaluronic acid.

Conclusions

Vocal folds can be decellularized using SDS without adversely affecting its mechanical stiffness and fibrous extracellular matrix. This preliminary study demonstrates the potential of a decellularized scaffold to serve as a tissue‐engineered construct for vocal fold replacement.

Level of Evidence

NA Laryngoscope, 124:E326–E331, 2014
In vivo optical imaging of folate receptor‐β in head and neck squamous cell carcinoma
Authors: Sun Joel Y. , Shen Jiayin , Thibodeaux Joel , Huang Gang , Wang Yiguang , Gao Jinming , Low Philip S. , Dimitrov Dimiter S. , Sumer Baran D.
Published: January 2014

Objectives/Hypothesis

Folate receptor (FR) expression, although known to be elevated in many types of cancer and inflammatory cells, has not been well characterized in head and neck squamous cell carcinoma (HNSCC). We hypothesized that tumor infiltrating inflammatory cells expressing FR‐β could allow fluorescent visualization of HNSCC tumors using folate conjugated dyes even when FR expression in cancer cells is low.

Study Design

Retrospective review of clinical pathologic specimens and in vivo animal study.

Methods

A tissue microarray with tumor and tumor‐free tissue from 22 patients with HNSCC was stained with antibodies to FR‐α and FR‐β. We characterized FR‐β+ cells by examining CD45, CD68, CD206, and transforming growth factor (TGF)‐β expression. To investigate fluorescent imaging, mice with orthotopic tumor xenografts were imaged in vivo after intravenous injections of folate conjugated fluorescein isothiocyanate (folate‐FITC) and were histologically evaluated ex vivo.

Results

All tumor samples demonstrated significant FR‐β staining and negligible FR‐α staining. FR‐β+ cells found in tumors coexpressed CD68 and had increased expression of CD206 and TGF‐β characteristic of tumor‐associated macrophages. In the xenograft models, tumors showed strong in vivo fluorescence after folate‐FITC injection in contrast to surrounding normal tissues. Histologic examination of the xenograft tissue similarly showed folate‐FITC uptake in areas of inflammatory cellular infiltrate.

Conclusions

Although HNSCC tumor cells do not express FR, HNSCC tumors contain a significant population of FR‐β–expressing macrophages. Folate conjugated fluorescent dye is able to specifically target and label tumor xenografts to permit macroscopic fluorescence imaging due to FR‐β expression on the infiltrating inflammatory cells.

Level of Evidence

NA Laryngoscope, 124:E312–E319, 2014
Low‐frequency subthalamic nucleus stimulation in Parkinson's disease: A randomized clinical trial
Authors: Khoo Hui Ming , Kishima Haruhiko , Hosomi Koichi , Maruo Tomoyuki , Tani Naoki , Oshino Satoru , Shimokawa Toshio , Yokoe Masaru , Mochizuki Hideki , Saitoh Youichi , Yoshimine Toshiki
Published: January 2014

Background

Low‐frequency, bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson's disease (PD), but it is not particularly effective for segmental symptoms.

Methods

The optimal contacts for low‐frequency (60 Hz) and high‐frequency (130 Hz) single monopolar stimulation were determined. Then, in a randomized, double‐blind, prospective crossover manner, 60‐Hz and 130‐Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD.

Results

The optimal contacts for 60‐Hz stimulation were situated more ventrally than those for 130‐Hz stimulation (P = 0.038). Under the respective optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson's Disease Rating Scale motor score (P < 0.001) and the akinesia (P = 0.011) and axial motor signs (P = 0.012) subscores without compromising the therapeutic effect on tremor and rigidity.

Conclusions

Low‐frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD. © 2014 International Parkinson and Movement Disorder Society
A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes
Authors: Hansen Maren F. , Neckmann Ulrike , Lavik Liss A. S. , Vold Trine , Gilde Bodil , Toft Ragnhild K. , Sjursen Wenche
Published: January 2014

The purpose of this study was to develop a massive parallel sequencing (MPS) workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1, PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly predispose to colorectal cancer. We used an amplicon‐based sequencing method allowing specific and preferential amplification of the MMR genes including PMS2, of which several pseudogenes exist. The amplicons were pooled at different ratios to obtain coverage uniformity and maximize the throughput of a single‐GS Junior run. In total, 60 previously identified and distinct variants (substitutions and indels), were sequenced by MPS and successfully detected. The heterozygote detection range was from 19% to 63% and dependent on sequence context and coverage. We were able to distinguish between false‐positive and true‐positive calls in homopolymeric regions by cross‐sample comparison and evaluation of flow signal distributions. In addition, we filtered variants according to a predefined status, which facilitated variant annotation. Our study shows that implementation of MPS in routine diagnostics of LS can accelerate sample throughput and reduce costs without compromising sensitivity, compared to Sanger sequencing.
Nutritional aspects of metabolic inflammation in relation to health—insights from transcriptomic biomarkers in PBMC of fatty acids and polyphenols
Authors: Afman Lydia , Milenkovic Dragan , Roche Helen M.
Published: January 2014

Recent research has highlighted potential important interaction between metabolism and inflammation, within the context of metabolic health and nutrition, with a view to preventing diet‐related disease. In addition to this, there is a paucity of evidence in relation to accurate biomarkers that are capable of reflecting this important biological interplay or relationship between metabolism and inflammation, particularly in relation to diet and health. Therefore the objective of this review is to highlight the potential role of transcriptomic approaches as a tool to capture the mechanistic basis of metabolic inflammation. Within this context, this review has focused on the potential of peripheral blood mononuclear cells transcriptomic biomarkers, because they are an accessible tissue that may reflect metabolism and subacute chronic inflammation. Also these pathways are often dysregulated in the common diet‐related diseases obesity, type 2 diabetes, and cardiovascular disease, thus may be used as markers of systemic health. The review focuses on fatty acids and polyphenols, two classes of nutrients/nonnutrient food components that modulate metabolism/inflammation, which we have used as an example of a proof‐of‐concept with a view to understanding the extent to which transcriptomic biomarkers are related to nutritional status and/or sensitive to dietary interventions. We show that both nutritional components modulate inflammatory markers at the transcriptomic level with the capability of profiling pro‐ and anti‐inflammatory mechanisms in a bidirectional fashion; to this end transcriptomic biomarkers may have potential within the context of metabolic inflammation. This transcriptomic biomarker approach may be a sensitive indicator of nutritional status and metabolic health.
99Tc NMR as a promising technique for structural investigation of biomolecules: theoretical studies on the solvent and thermal effects of phenylbenzothiazole complex
Authors: Mancini Daiana T. , Souza Eugenio F. , Caetano Melissa S. , Ramalho Teodorico C.
Published: January 2014

The phenylbenzothiazole compounds show antitumor properties and are highly selective. In this paper, the 99Tc chemical shifts based on the (99mTc)(CO)3(NNO) complex conjugated to the antitumor agent 2‐(4′‐aminophenyl)benzothiazole are reported. Thermal and solvent effects were studied computationally by quantum‐chemical methods, using the density functional theory (DFT) (DFT level BPW91/aug‐cc‐pVTZ for the Tc and BPW91/IGLO‐II for the other atoms) to compute the NMR parameters for the complex. We have calculated the 99Tc NMR chemical shifts of the complex in gas phase and solution using different solvation models (polarizable continuum model and explicit solvation). To evaluate the thermal effect, molecular dynamics simulations were carried, using the atom‐centered density matrix propagation method at the DFT level (BP86/LanL2dz). The results highlight that the 99Tc NMR spectroscopy can be a promising technique for structural investigation of biomolecules, at the molecular level, in different environments. Copyright © 2014 John Wiley & Sons, Ltd.
A mathematical formulation and efficient heuristics for the dynamic container relocation problem
Authors: Hakan Akyüz M. , Lee Chung‐Yee
Published: January 2014

The container relocation problem (CRP) is concerned with emptying a single yard‐bay which contains J containers each following a given pickup order so as to minimize the total number of relocations made during their retrieval process. The CRP can be modeled as a binary integer programming (IP) problem and is known to be NP‐hard. In this work, we focus on an extension of the CRP to the case where containers are both received and retrieved from a single yard‐bay, and call it the dynamic container relocation problem. The arrival (departure) sequences of containers to (from) the yard‐bay is assumed to be known a priori. A binary IP formulation is presented for the problem. Then, we propose three types of heuristic methods: index based heuristics, heuristics using the binary IP formulation, and a beam search heuristic. Computational experiments are performed on an extensive set of randomly generated test instances. Our results show that beam search heuristic is very efficient and performs better than the other heuristic methods.Copyright © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 101–118, 2014
Three orders of magnitude improved efficiency with high‐performance spectral crystal plasticity on GPU platforms
Authors: Mihaila Bogdan , Knezevic Marko , Cardenas Andres
Published: January 2014

We study efficient numerical implementations of crystal plasticity in the spectral representation, with emphasis on high‐performance computational aspects of the simulation. For illustrative purposes, we apply this approach to a Taylor homogenization model of fcc poly‐crystalline materials and show that the spectral representation of crystal plasticity is ideal for parallel implementations aimed at next‐generation large‐scale microstructure‐sensitive simulations of material deformation. We find that multi‐thread parallelizations of the algorithm provide two orders of magnitude acceleration of the calculation, whereas graphics processing unit‐based computing solutions allow for three orders of magnitude speedup factors over the conventional model. Copyright © 2014 John Wiley & Sons, Ltd.
Synthesis and processability into textile structures of radiopaque, biodegradable polyesters and poly(ester‐urethanes)
Authors: Rode Claudia , Schmidt Annika , Wyrwa Ralf , Weisser Jürgen , Schmidt Kathrin , Moszner Norbert , Gottlöber Ralf‐Peter , Heinemann Klaus , Schnabelrauch Matthias
Published: January 2014

Radiopaque biodegradable polymers have been synthesized by ring‐opening polymerization of l/dl‐lactide and caprolactone with the iodine‐containing starter molecule 2,2‐bis(hydroxymethyl)propane‐1,3‐diyl bis(2,3,5‐triiodobenzoate) followed by chain elongation with a diacid chloride or diisocyanates. The resulting polyesters and poly(ester‐urethanes) exhibited a radiopacity of 60−124% relative to an aluminium sample of the same thickness. The polymers were processed into monofilament fibres by melt‐spinning and into fibre meshes by electrospinning. All polymers were biodegradable in simulated body fluid medium under in vitro conditions and showed an excellent in vitro cytocompatibility even after several months of hydrolytic degradation. A current drawback is the relatively low tensile strength of the polymer monofilaments, which needs to be improved for applications as textile structures. Nevertheless, the new radiopaque and biodegradable polymers are promising candidates in fields of application where radiopacity of implants is an important parameter.
Interleukin 6 Mediates the Therapeutic Effects of Adipose-Derived Stromal/Stem Cells in Lipopolysaccharide-Induced Acute Lung Injury
Authors: Zhang Shijia , Danchuk Svitlana D. , Bonvillain Ryan W. , Xu Beibei , Scruggs Brittni A. , Strong Amy L. , Semon Julie A. , Gimble Jeffrey M. , Betancourt Aline M. , Sullivan Deborah E. , Bunnell Bruce A.
Published: January 2014

Adipose-derived stromal/stem cells (ASCs) have anti-inflammatory as well as immunosuppressive activities and are currently the focus of clinical trials for a number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory condition of the lung for which standard treatment is mainly supportive due to lack of effective therapies. Our recent studies have demonstrated the ability of both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and inflammation in a rodent model of lipopolysaccharide-induced ALI, suggesting that ASCs may also be beneficial in treating ALI. To better understand how ASCs may act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung inflammation, gene expression analysis was performed in ASC-treated (hASCs or mASCs) and control sham-treated lungs. The results revealed a dramatic difference between the expression of anti-inflammatory molecules by hASCs and mASCs. These data show that the beneficial effects of hASCs and mASCs in ALI may result from the production of different paracrine factors. Interleukin 6 (IL-6) expression in the mASC-treated lungs was significantly elevated as compared to sham-treated controls 20 hours after delivery of the cells by oropharyngeal aspiration. Knockdown of IL-6 expression in mASCs by RNA interference abrogated most of their therapeutic effects, suggesting that the anti-inflammatory properties of mASCs in ALI are explained, at least in part, by activation of IL-6 secretion. Stem Cells  2014;32:1616–1628
NogoR1 and PirB Signaling Stimulates Neural Stem Cell Survival and Proliferation
Authors: Ramasamy Srinivas , Yu Fenggang , Hong Yu Yuan , Srivats Hariharan , Stewart Dawe Gavin , Ahmed Sohail
Published: January 2014

Neural stem cells (NSCs) and neural progenitors (NPs) in the mammalian neocortex give rise to the main cell types of the nervous system. The biological behavior of these NSCs and NPs is regulated by extracellular niche derived autocrine-paracrine signaling factors on a developmental timeline. Our previous reports [Plos One 2010;5:e15341; J Neurochem 2011;117:565–578] have shown that chondroitin sulfate proteoglycan and ApolipoproteinE are autocrine-paracrine survival factors for NSCs. NogoA, a myelin related protein, is expressed in the cortical ventricular zones where NSCs reside. However, the functional role of Nogo signaling proteins in NSC behavior is not completely understood. In this study, we show that NogoA receptors, NogoR1 and PirB, are expressed in the ventricular zone where NSCs reside between E10.5 and 14.5 but not at E15.5. Nogo ligands stimulate NSC survival and proliferation in a dosage-dependent manner in vitro. NogoR1 and PirB are low and high affinity Nogo receptors, respectively and are responsible for the effects of Nogo ligands on NSC behavior. Inhibition of autocrine-paracrine Nogo signaling blocks NSC survival and proliferation. In NSCs, NogoR1 functions through Rho whereas PirB uses Shp1/2 signaling pathways to control NSC behavior. Taken together, this work suggests that Nogo signaling is an important pathway for survival of NSCs. Stem Cells  2014;32:1636–1648
Concise Review: Bone Marrow-Derived Mesenchymal Stem Cells Change Phenotype Following In Vitro Culture: Implications for Basic Research and the Clinic
Authors: Bara Jennifer J. , Richards R. Geoff , Alini Mauro , Stoddart Martin J.
Published: January 2014

Mesenchymal stem cells (MSCs) are increasingly being used in tissue engineering and cell-based therapies in all fields ranging from orthopedic to cardiovascular medicine. Despite years of research and numerous clinical trials, MSC therapies are still very much in development and not considered mainstream treatments. The majority of approaches rely on an in vitro cell expansion phase in monolayer to produce large cell numbers prior to implantation. It is clear from the literature that this in vitro expansion phase causes dramatic changes in MSC phenotype which has very significant implications for the development of effective therapies. Previous reviews have sought to better characterize these cells in their native and in vitro environments, described known stem cell interactions within the bone marrow, and discussed the use of innovative culture systems aiming to model the bone marrow stem cell niche. The purpose of this review is to provide an update on our knowledge of MSCs in their native environment, focusing on bone marrow-derived MSCs. We provide a detailed description of the differences between naive cells and those that have been cultured in vitro and examine the effect of isolation and culture parameters on these phenotypic changes. We explore the concept of “one step” MSC therapy and discuss the potential cellular and clinical benefits. Finally, we describe recent work attempting to model the MSC bone marrow niche, with focus on both basic research and clinical applications and consider the challenges associated with these new generation culture systems. Stem Cells  2014;32:1713–1723
Analysis of the bovine rumen microbiome reveals a diversity of Sus-like polysaccharide utilization loci from the bacterial phylum Bacteroidetes
Authors: Rosewarne Carly P , Pope Phillip B , Cheung Jane L , Morrison Mark
Published: January 2014

Several unique Sus-like polysaccharide utilization loci (PULs) were identified from bacteria resident in bovine rumen microbiomes through functional screening of a fosmid library. The loci were phylogenetically assigned to the genus Prevotella within the phylum Bacteroidetes. These findings were augmented by a bioinformatic re-evaluation of ruminal Prevotella genomes, revealing additional loci not previously reported in the literature. Analysis of Bacteroidales-affiliated genomes reconstructed from a bovine rumen metagenome in a previous study further expanded the diversity of Sus-like PULs resident in this microbiome. Our findings suggest that Sus-like systems represent an important mechanism for degradation of a range of plant-derived glycans in ruminants.
Synthesis, Quantum Chemical Calculations and Properties of Nonionic and Nonionic–Anionic Surfactants Based on Fatty Alkyl Succinate
Authors: Hussein Ahmed M. , Khowdiary Manal M.
Published: January 2014

Two surfactants based on maleic anhydride were synthesized by esterification with fatty alcohols C10, C12 and C14 to produce half esters [I–III]. Nonionic surfactant monoesters [I–III]a–c synthesized by ethoxylation of [I–III] with different moles of ethylene oxide [6, 8 and 10] in the presence of K10 clay as an untraditionally catalyst. The later products were sulfonated to produce nonionic–anionic surfactants [IV–VI]a–c. The structures of synthesized surfactant were elucidated by FTIR and 1H‐NMR data. Their surface activity and biodegradability were determined. All the synthesized surfactants showed good surface activity and biodegradability, but anionic‐nonionic type has better effect than nonionic one. Quantum chemical calculations were utilized to explore the electronic structure and stability of these compounds. Computational studies have been carried out at the PM3 semiempirical molecular orbitals level, to establish the highest occupied molecular orbital–lowest unoccupied molecular orbital, ionization potential energy and ESP mapping of these compounds. Also, the absorption, distribution, metabolism, elimination and toxic properties were studied to gain a clear view of the oral bioavailability of these compounds.
One‐Pot Synthesis of Poly(linoleic acid)‐g‐Poly(styrene)‐g‐Poly(ε‐caprolactone) Graft Copolymers
Authors: Allı Abdulkadir , Allı Sema , Becer C. Remzi , Hazer Baki
Published: January 2014

One‐pot synthesis of graft copolymers by ring‐opening polymerization and free radical polymerization using polymeric linoleic acid peroxide (PLina) is reported. Graft copolymers having structures of poly(linoleic acid)‐g‐polystyrene‐g‐poly(ε‐caprolactone) were synthesized from PLina, possessing peroxide groups on the main chain by the combination of free radical polymerization of styrene and ring‐opening polymerization of ε‐caprolactone in one‐step. Principal parameters, such as monomer concentration, initiator concentration, and polymerization time, which effect the one‐pot polymerization reactions were evaluated. The obtained graft copolymers were characterized by 1H‐NMR and DOSY‐NMR spectroscopy, gel permeation chromatography, thermal gravimetric analysis and differential scanning calorimetry techniques.
The epidemiology of transient synovitis in Liverpool, UK
Authors: Harrison William D. , Vooght A. K. , Singhal R. , Bruce C. E. , Perry D. C.
Published: January 2014

Background

The epidemiology of transient synovitis is poorly understood, and the aetiology is unknown, although a suggestion of a viral association predominates.

Purpose

This population-based study investigated the epidemiology in order to formulate aetiological theories of pathogenesis.

Patient and methods

Cases in Merseyside were identified between 2004 and 2009. Incidence rates were determined and analysed by age, sex, season and region of residence. Socioeconomic deprivation scores were generated using the Index of Multiple Deprivation, allocated by postcode. Poisson confidence intervals were calculated and Poisson regression was used to check for trends.

Results

Two hundred and fifty-nine cases were identified over 5.5 years. The annual incidence was 25.1 (95 % CI 22.1–28.5) per 100,000 0–14 year-olds. Male to female ratio was 3.2:1 ( p < 0.001). Mean age at presentation was 5.4 years (95 % CI 5.0–5.8), which demonstrated a near-normal distribution. No relationship was identified between seasonality and incidence ( p = 0.64). A correlation was identified with socioeconomic deprivation in Merseyside: incidence rate ratio 1.16 (95 % CI 1.06–1.26, p < 0.001), although further analysis within the subregion of Liverpool did not confirm this finding ( p = 0.35).

Conclusions

The normal distribution for age at disease presentation suggests a specific disease entity. The absence of seasonality casts some doubt on the popular theory of a viral aetiology. The absence of a consistent socioeconomic gradient in both Merseyside and Liverpool challenges a previous suggestion of an association with Perthes’ disease. This paper provides ecological evidence that may challenge existing aetiological theories, though transient synovitis remains an enigma.
Fractured Identity: A Framework for Understanding Young Asian American Women’s Self-harm and Suicidal Behaviors
Authors: Hahm Hyeouk Chris , Gonyea Judith G. , Chiao Christine , Koritsanszky Luca Anna
Published: January 2014

Despite the high suicide rate among young Asian American women, the reasons for this phenomenon remain unclear. This qualitative study explored the family experiences of 16 young Asian American women who are children of immigrants and report a history of self-harm and/or suicidal behaviors. Our findings suggest that the participants experienced multiple types of “disempowering parenting styles” that are characterized as: abusive, burdening, culturally disjointed, disengaged, and gender-prescriptive parenting. Tied to these family dynamics is the double bind that participants suffer. Exposed to multiple types of negative parenting, the women felt paralyzed by opposing forces, caught between a deep desire to satisfy their parents’ expectations as well as societal expectations and to simultaneously rebel against the image of “the perfect Asian woman.” Torn by the double bind, these women developed a “fractured identity,” which led to the use of “unsafe coping” strategies. Trapped in a “web of pain,” the young women suffered alone and engaged in self-harm and suicidal behaviors.
The VTLISFG motif in the BH1 domain plays a significant role in regulating the degradation of Mcl‐1
Authors: Xiao Kang , Chen Pengxuan , Chang Donald Choy
Published: January 2014

Mcl‐1 is a member of the Bcl‐2 family protein; its degradation is required for the initiation of apoptosis. The mechanism, however, is not yet clearly known. Previously, it was reported that Mcl‐1 is degraded through the ubiquitination‐mediated pathway and the PEST domain is the motif responsible for promoting this degradation. We found evidence that this may not be true. We generated several Mcl‐1 deletion mutants and examined their effects on protein stability. Deletion of the PEST domain did not prevent the degradation of Mcl‐1 during apoptosis. The BH1 domain, but not the PEST, BH3 or BH2 domain, exhibited a short half‐life. A peptide named “F3” (VTLISFG) in the C‐terminus of the BH1 domain appears to be critical for the rapid turnover of Mcl‐1. Deletion of F3 from GFP‐Mcl‐1‐ΔPEST retarded the degradation of this mutant. F3 appeared to be the minimum functional sequence of the degradation motif, since deletion of a single residue was sufficient to abrogate its short half‐life. Fusion of F3 with p32 resulted in the degradation of p32 during UV‐induced apoptosis, while wild type p32 was not affected. Taken together, these findings suggest that F3 (VTLISFG), instead of PEST, is the major motif responsible for the degradation of Mcl‐1 during apoptosis.
A novel cell‐penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno‐ and syngeneic systems
Authors: Massaoka Mariana H. , Matsuo Alisson L. , Figueiredo Carlos R. , Girola Natalia , Faria Camyla F. , Azevedo Ricardo A. , Travassos Luiz R.
Published: January 2014

The Wilms tumor protein 1 (WT1) transcription factor has been associated in malignant melanoma with cell survival and metastasis, thus emerging as a candidate for targeted therapy. A lysine–arginine rich peptide, WT1‐pTj, derived from the ZF domain of WT1 was evaluated as an antitumor agent against A2058 human melanoma cells and B16F10‐Nex2 syngeneic murine melanoma. Peptide WT1‐pTj quickly penetrated human melanoma cells and induced senescence, recognized by increased SA‐β‐galactosidase activity, enhanced transcriptional activity of p53, and induction of the cell cycle inhibitors p21 and p27. Moreover, the peptide bound to p53 and competed with WT1 protein for binding to p53. WT1‐pTj treatment led to sustained cell growth suppression, abrogation of clonogenicity and G2/M cell cycle arrest. Notably, in vivo studies showed that WT1‐pTj inhibited both the metastases and subcutaneous growth of murine melanoma in syngeneic mice, and prolonged the survival of nude mice challenged with human melanoma cells. The 27‐amino acid cell‐penetrating WT1‐derived peptide, depends on C3 and H16 for effective antimelanoma activity, inhibits proliferation of WT1‐expressing human tumor cell lines, and may have an effective role in the treatment of WT1‐expressing malignancies.
Second Evidence Aid Conference: Prioritizing Evidence in Disaster Aid
Authors: Vandekerckhove Philippe , Clarke Michael J. , De Buck Emmy , Allen Claire , Kayabu Bonnix
Published: January 2014

The Second Evidence Aid Conference took place in Brussels, Belgium, in October 2012, jointly organized by Evidence Aid and the Belgian Red Cross–Flanders. It provided an opportunity to build on the discussions from the 2011 First Evidence Aid Conference in Oxford, England, and prioritize the future work of Evidence Aid. Within the plenary presentations, discussions, and small work groups, the more than 80 international participants addressed issues regarding the need, use, and prioritization of evidence. Three parallel workshops focused on the prioritization of research, systematic reviews, and data to be collected during disasters, leading to a suggested prioritization framework and a commitment to identify key areas for evidence in disasters. Working with a wide variety of people and organizations from the disaster and humanitarian sectors, Evidence Aid will take this framework and develop a list of top priority questions in need of research and systematic reviews. Although Evidence Aid will not be able to address all of the research questions that will be identified in this process, it will collect them for sharing with relevant agencies. (Disaster Med Public Health Preparedness. 2013;7:593-596)
Assessing Functional Needs Sheltering in Pike County, Kentucky: Using a Community Assessment for Public Health Emergency Response
Authors: Kolwaite Amy R. , Hlady W. Gary , Simon Matthew C. , Cadwell Betsy L. , Daley W. Randolph , Fleischauer Aaron T. , May Zora , Thoroughman Doug
Published: January 2014

Objective

During 2009-2011, Pike County, Kentucky, experienced a series of severe weather events that resulted in property damage, insufficient potable water, and need for temporary shelters. A Community Assessment for Public Health Emergency Response (CASPER) survey was implemented for future planning. CASPER assesses household health status, preparedness level, and anticipated demand for shelters.

Methods

We used a 2-stage cluster sampling design to randomly select 210 representative households for in-person interviews. We estimated the proportion of households with children aged 2 years or younger; adults aged 65 years or older; and residents with chronic health conditions, visual impairments, physical limitations, and supplemental oxygen requirements.

Results

Of all households surveyed, 8% included children aged 2 years or younger, and 27% included adults aged 65 years or older. The most common chronic health conditions were heart disease (51%), diabetes (28%), lung disease (23%), and asthma (21%). Visual impairments were reported in 29% of households, physical limitations in 24%, and supplemental oxygen use in 12%.

Conclusions

Pike County residents should be encouraged to maintain an adequate supply of medications and copies of their prescriptions. Emergency response plans should include transportation for persons with physical limitations; and shelter plans should include sufficient medically trained staff and adequate supplies of infant formula, pharmaceuticals, and supplemental oxygen. (Disaster Med Public Health Preparedness. 2013;7:597-602)
States Held Hostage: Political Hold-Up Problems and the Effects of International Institutions
Authors: CARNEGIE ALLISON
Published: January 2014

This paper argues that the benefits of international institutions accrue disproportionately to pairs of states that find cooperation most difficult. It determines which states achieve the greatest gains from these institutions by identifying a central reason that states fail to cooperate in international relations: they fear being “held up” by other states for political concessions. Political hold-up problems occur when one state fails to undertake an otherwise productive investment due to the increased ability it would give another state to extract political concessions. Focusing on the World Trade Organization (WTO), I demonstrate that political hold-up problems are pervasive in international relations due to links between economic and political policies, but that international institutions can solve hold-up problems by helping to enforce agreements. I first formalize this argument and then empirically test the implications derived from the model, finding that the WTO increases trade most for politically dissimilar states by reducing states' abilities to hold up their trading partners for foreign policy concessions. I provide evidence of the causal mechanism by showing that WTO membership increases trade in contract-intensive goods and boosts fixed capital investment. I conclude that by solving political hold-up problems, international institutions can normalize relations between politically asymmetric states that differ in terms of capabilities, regime types, and alliances.
An Arctic char observed in a glacial Spitsbergen river
Authors: Ziaja Wieslaw
Published: January 2014

An anadromous Arctic char (male) was recorded in southwestern Spitsbergen, in a very muddy glacial river, in August 2008. This is apparently the first specimen of this species observed in such an unfavourable habitat in Svalbard.
DSM-5 disruptive mood dysregulation disorder: correlates and predictors in young children
Authors: Dougherty L. R. , Smith V. C. , Bufferd S. J. , Carlson G. A. , Stringaris A. , Leibenluft E. , Klein D. N.
Published: January 2014

Background

Despite the inclusion of disruptive mood dysregulation disorder (DMDD) in DSM-5, little empirical data exist on the disorder. We estimated rates, co-morbidity, correlates and early childhood predictors of DMDD in a community sample of 6-year-olds.

Method

DMDD was assessed in 6-year-old children (n = 462) using a parent-reported structured clinical interview. Age 6 years correlates and age 3 years predictors were drawn from six domains: demographics; child psychopathology, functioning, and temperament; parental psychopathology; and the psychosocial environment.

Results

The 3-month prevalence rate for DMDD was 8.2% (n = 38). DMDD occurred with an emotional or behavioral disorder in 60.5% of these children. At age 6 years, concurrent bivariate analyses revealed associations between DMDD and depression, oppositional defiant disorder, the Child Behavior Checklist – Dysregulation Profile, functional impairment, poorer peer functioning, child temperament (higher surgency and negative emotional intensity and lower effortful control), and lower parental support and marital satisfaction. The age 3 years predictors of DMDD at age 6 years included child attention deficit hyperactivity disorder, oppositional defiant disorder, the Child Behavior Checklist – Dysregulation Profile, poorer peer functioning, child temperament (higher child surgency and negative emotional intensity and lower effortful control), parental lifetime substance use disorder and higher parental hostility.

Conclusions

A number of children met DSM-5 criteria for DMDD, and the diagnosis was associated with numerous concurrent and predictive indicators of emotional and behavioral dysregulation and poor functioning.