bluuebunny/crossref_metadata_2025 huggingface dataset:
ABrowse - a customizable next-generation genome browser framework
Authors: Kong Lei , Wang Jun , Zhao Shuqi , Gu Xiaocheng , Luo Jingchu , Gao Ge
Published: January 2012

Background

With the rapid growth of genome sequencing projects, genome browser is becoming indispensable, not only as a visualization system but also as an interactive platform to support open data access and collaborative work. Thus a customizable genome browser framework with rich functions and flexible configuration is needed to facilitate various genome research projects.

Results

Based on next-generation web technologies, we have developed a general-purpose genome browser framework ABrowse which provides interactive browsing experience, open data access and collaborative work support. By supporting Google-map-like smooth navigation, ABrowse offers end users highly interactive browsing experience. To facilitate further data analysis, multiple data access approaches are supported for external platforms to retrieve data from ABrowse. To promote collaborative work, an online user-space is provided for end users to create, store and share comments, annotations and landmarks. For data providers, ABrowse is highly customizable and configurable. The framework provides a set of utilities to import annotation data conveniently. To build ABrowse on existing annotation databases, data providers could specify SQL statements according to database schema. And customized pages for detailed information display of annotation entries could be easily plugged in. For developers, new drawing strategies could be integrated into ABrowse for new types of annotation data. In addition, standard web service is provided for data retrieval remotely, providing underlying machine-oriented programming interface for open data access.

Conclusions

ABrowse framework is valuable for end users, data providers and developers by providing rich user functions and flexible customization approaches. The source code is published under GNU Lesser General Public License v3.0 and is accessible at http://www.abrowse.org/. To demonstrate all the features of ABrowse, a live demo for Arabidopsis thaliana genome has been built at http://arabidopsis.cbi.edu.cn/.
Actinobaculum schaalii- invasive pathogen or innocent bystander? A retrospective observational study
Authors: Tschudin-Sutter Sarah , Frei Reno , Weisser Maja , Goldenberger Daniel , Widmer Andreas F
Published: January 2012

Background

Actinobaculum schaalii is a Gram-positive, facultative anaerobic coccoid rod, classified as a new genus in 1997. It grows slowly and therefore is easily overgrown by other pathogens, which are often found concomitantly. Since 1999, Actinobaculum schaalii is routinely investigated at our hospital, whenever its presence is suspected due to the detection of minute grey colonies on blood agar plates and negative reactions for catalase. The objective of this study was to determine the clinical significance of Actinobaculum schaalii, identified in our microbiology laboratory over the last 11 years.

Methods

All consecutive isolates with Actinobaculum schaalii were obtained from the computerized database of the clinical microbiology laboratory and patients whose cultures from any body site yielded this pathogen were analyzed. Observation of tiny colonies of Gram-positive, catalase-negative coccoid rods triggered molecular identification based on 16S rRNA gene sequencing.

Results

40 isolates were obtained from 27 patients during the last 11 years. The patient's median age was 81 (19-101) years, 25 (92.6%) had underlying diseases and 12 (44.4%) had a genitourinary tract pathology. Actinobaculum schaalii was isolated in 12 urine cultures, 21 blood cultures, and 7 deep tissue biopsies. Twenty-five (62.5%) specimens were monobacterial, the remaining 15 (37.5%) were polybacterial 7/7 deep tissue samples (three bloodcultures and five urine cultures). Recovery from urine was interpreted as colonization in 5 (18.6%) cases (41.6% of all urine samples). Six (22.2%) suffered from urinary tract infections, six (22.2%) from abscesses (skin, intraabdominal, genitourinary tract, and surgical site infections) and 10 (37.0%) from bacteremia.

Conclusions

In this largest case series so far, detection of Actinobaculum schaalii was associated with an infection - primarily sepsis and abscesses - in 81.5% of our patients. Since this pathogen is frequently part of polymicrobial cultures (42.5%) it is often overlooked or considered a contaminant. Detection of Actinobaculum schaalii in clinical isolates mainly reflects infection indicating that this Gram-positive rod is not an innocent bystander.
Construction of permanently inducible miRNA-based expression vectors using site-specific recombinases
Authors: Garwick-Coppens Sara E , Herman Adam , Harper Scott Q
Published: January 2012

Background

RNA interference (RNAi) is a conserved gene silencing mechanism mediated by small inhibitory microRNAs (miRNAs).

Promoter-driven miRNA expression vectors have emerged as important tools for delivering natural or artificially designed miRNAs to eukaryotic cells and organisms. Such systems can be used to query the normal or pathogenic functions of natural miRNAs or messenger RNAs, or to therapeutically silence disease genes.

Results

As with any molecular cloning procedure, building miRNA-based expression constructs requires a time investment and some molecular biology skills. To improve efficiency and accelerate the construction process, we developed a method to rapidly generate miRNA expression vectors using recombinases instead of more traditional cut-and-paste molecular cloning techniques. In addition to streamlining the construction process, our cloning strategy provides vectors with added versatility. In our system, miRNAs can be constitutively expressed from the U6 promoter, or inducibly expressed by Cre recombinase. We also engineered a built-in mechanism to destroy the vector with Flp recombinase, if desired. Finally, to further simplify the construction process, we developed a software package that automates the prediction and design of optimal miRNA sequences using our system.

Conclusions

We designed and tested a modular system to rapidly clone miRNA expression cassettes. Our strategy reduces the hands-on time required to successfully generate effective constructs, and can be implemented in labs with minimal molecular cloning expertise. This versatile system provides options that permit constitutive or inducible miRNA expression, depending upon the needs of the end user. As such, it has utility for basic or translational applications.
Palmitic and linoleic acids induce ER stress and apoptosis in hepatoma cells
Authors: Zhang Yong , Xue Rongliang , Zhang Zhenni , Yang Xia , Shi Hongyang
Published: January 2012

Objectives

Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease. In this study, we tried to investigate the effects of saturated and unsaturated fatty acids on hepatoma cell apoptosis.

Methods

H4IIE liver cells were treated with palmitic acid, linoleic acid, or both with or without the calcium-specific chelator BAPTA-AM after which the expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels, and calcium flux were measured.

Results

Palmitic or linoleic acid (250 μM) induced H4IIE cell apoptosis, which required calcium flux but not caspase-3. Apoptosis was not observed when cells were co-treated with linoleic acid (125 μM) and palmitic acid (250 μM). Importantly, the release of cytochrome C from mitochondria into cytoplasm during cell apoptosis was specifically detected only when linoleic acid (125 μM), but not palmitic acid (250 μM), was added to the cells. Depletion of intracellular calcium flux by the calcium-specific chelator, BAPTA-AM, abolished linoleic acid-induced apoptosis. Moreover, in the presence of BAPTA-AM, expression of the unfolded protein response (UPR)-associated genes, CHOP, GRP78, and GRP94, was induced by linoleic acid, but not palmitic acid.

Conclusions

The results suggest that linoleic acid promotes cell apoptosis through the release of cytochrome C, only if the intracellular calcium flux is unperturbed and intact. These results confirm that ER stress contributes to fatty acid-induced liver cell apoptosis.
5-Azacytidine Is Insufficient For Cardiogenesis In Human Adipose-Derived Stem Cells
Authors: Wan Safwani Wan Kamarul Zaman , Makpol Suzana , Sathapan Somasundaram , Chua Kien Hui
Published: January 2012

Background

Adipose tissue is a source of multipotent adult stem cells and it has the ability to differentiate into several types of cell lineages such as neuron cells, osteogenic cells and adipogenic cells. Several reports have shown adipose-derived stem cells (ASCs) have the ability to undergo cardiomyogenesis. Studies have shown 5-azacytidine can successfully drive stem cells such as bone marrow derived stem cells to differentiate into cardiomyogenic cells. Therefore, in this study, we investigated the effect 5-azacytidine on the cardiogenic ability of ASCs.

Methods

The cardiogenic potential of ASCs was analysed by studying the morphological changes after induction, the changes in the cardiogenic genes expression i.e. GATA4, MLC-2v, MLC-2a, NKX2.5, β-MHC, α-MHC, Atrial natriuretic peptide (ANP), Connexin 43, Cardiac Troponin C, Cardiac Troponin I and myocyte enhancer factor (MEF2C) and the changes of embryonic stem cells genes expression at P5 and P10 using quantitative PCR.

Results

Our results showed that the induced ASCs did not show significant morphological difference compared to the non-induced ASCs. While quantitative PCR data indicated that most cardiogenic genes and stemness genes expression level decreased after induction at P5 and P10.

Conclusion

5-azacytidine is insufficient for the cardiogenic induction of the ASCs.
Effects of adjuvants on IgG subclasses elicited by virus-like Particles
Authors: Visciano Maria Luisa , Tagliamonte Maria , Tornesello Maria Lina , Buonaguro Franco M , Buonaguro Luigi
Published: January 2012

Background

Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model.

Results

Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826.

Conclusions

The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.
Polystyrene-Al2O3 composite solid polymer electrolyte for lithium secondary battery
Authors: Lim Yu-Jeong , An Yu-Ha , Jo Nam-Ju
Published: January 2012

In a common salt-in-polymer electrolyte, a polymer which has polar groups in the molecular chain is necessary because the polar groups dissolve lithium salt and coordinate cations. Based on the above point of view, polystyrene [PS] that has nonpolar groups is not suitable for the polymer matrix. However, in this PS-based composite polymer-in-salt system, the transport of cations is not by segmental motion but by ion-hopping through a lithium percolation path made of high content lithium salt. Moreover, Al2O3 can dissolve salt, instead of polar groups of polymer matrix, by the Lewis acid-base interactions between the surface group of Al2O3 and salt. Notably, the maximum enhancement of ionic conductivity is found in acidic Al2O3 compared with neutral and basic Al2O3 arising from the increase of free ion fraction by dissociation of salt. It was revealed that PS-Al2O3 composite solid polymer electrolyte containing 70 wt.% salt and 10 wt.% acidic Al2O3 showed the highest ionic conductivity of 9.78 × 10-5 Scm-1 at room temperature.
Structural and optical properties of ZnS thin films deposited by RF magnetron sputtering
Authors: Hwang Dong Hyun , Ahn Jung Hoon , Hui Kwun Nam , Hui Kwan San , Son Young Guk
Published: January 2012

Zinc sulfide [ZnS] thin films were deposited on glass substrates using radio frequency magnetron sputtering. The substrate temperature was varied in the range of 100°C to 400°C. The structural and optical properties of ZnS thin films were characterized with X-ray diffraction [XRD], field emission scanning electron microscopy [FESEM], energy dispersive analysis of X-rays and UV-visible transmission spectra. The XRD analyses indicate that ZnS films have zinc blende structures with (111) preferential orientation, whereas the diffraction patterns sharpen with the increase in substrate temperatures. The FESEM data also reveal that the films have nano-size grains with a grain size of approximately 69 nm. The films grown at 350°C exhibit a relatively high transmittance of 80% in the visible region, with an energy band gap of 3.79 eV. These results show that ZnS films are suitable for use as the buffer layer of the Cu(In, Ga)Se2 solar cells.
Carbon-coated iron oxide nanoparticles as contrast agents in magnetic resonance imaging
Authors: Bae Hongsub , Ahmad Tanveer , Rhee Ilsu , Chang Yongmin , Jin Seong-Uk , Hong Sungwook
Published: January 2012

Coprecipitated ferrite nanoparticles were coated with carbon using a hydrothermal method. From transmission electron microscope pictures, we could see that the coated iron oxide nanoparticles were spherical in shape with an average diameter of 90 nm. The strong bonding of carbon on the nanoparticle surfaces was checked by noting the C = O and C = C vibrations in Fourier transform infrared spectra. The spin-lattice relaxation process [T
1] and spin-spin relaxation process [T
2] relaxivities of hydrogen protons in the aqueous solution of coated nanoparticles were determined to be 1.139 (mM·s)-1 and 1.115 (mM·s)-1, respectively. These results showed that the carbon-coated iron oxide nanoparticles are applicable as both T
1 and T
2 contrast agents in magnetic resonance imaging.

PACS: 81.05.y; 76.60.Es; 61.46; 75.50.k; 87.61.
Influences of phase transition and microstructure on dielectric properties of Bi0.5Na0.5Zr1-xTixO3 ceramics
Authors: Jaiban Panupong , Rachakom Ampika , Jiansirisomboon Sukanda , Watcharapasorn Anucha
Published: January 2012

Bismuth sodium zirconate titanate ceramics with the formula Bi0.5Na0.5Zr1-xTixO3 [BNZT], where x = 0.3, 0.4, 0.5, and 0.6, were prepared by a conventional solid-state sintering method. Phase identification was investigated using an X-ray diffraction technique. All compositions exhibited complete solubility of Ti4+ at the Zr4+ site. Both a decrease of unit cell size and phase transition from an orthorhombic Zr-rich composition to a rhombohedral crystal structure in a Ti-rich composition were observed as a result of Ti4+ substitution. These changes caused dielectric properties of BNZT ceramics to enhance. Microstructural observation carried out employing SEM showed that average grain size decreased when addition of Ti increased. Grain size difference of BNZT above 0.4 mole fraction of Ti4+ displayed a significant increase of dielectric constant at room temperature.
Effects of ZnO nanoparticulate addition on the properties of PMNT ceramics
Authors: Promsawat Methee , Watcharapasorn Anucha , Jiansirisomboon Sukanda
Published: January 2012

This research was conducted in order to study the effect of ZnO nanoparticulate addition on the properties of 0.9 Pb(Mg1/3Nb2/3)O3-0.1PbTiO3 [PMNT] ceramics. The PMNT ceramics were prepared by a solid-state reaction. The ZnO nanoparticles were added into PMNT ceramics to form PMNT/x ZnO (x = 0, 0.05, 0.1, 0.5, and 1.0 wt.%). The PMNT/x ZnO ceramics were investigated in terms of phase, microstructure, and mechanical and electrical properties. It was found that the density and grain size of PMNT ceramics tended to increase with an increasing amount of ZnO content. Moreover, a transgranular fracture was observed for the samples containing ZnO, while pure PMNT ceramics showed only a intergranular fracture. An addition of only 0.05 wt.% of ZnO was also found to enhance the hardness and dielectric and ferroelectric properties of the PMNT ceramics.
Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons
Authors: Chen Ting , Zhang Die , Dragomir Andrei , Kobayashi Kunikazu , Akay Yasemin , Akay Metin
Published: January 2012

Background

All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA). The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC). Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine.

Methods

We used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler) divergence analysis method for the present study.

Results

Our results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence) may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level.

Conclusions

Our results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.
Evolution before genes
Authors: Vasas Vera , Fernando Chrisantha , Santos Mauro , Kauffman Stuart , Szathmáry Eörs
Published: January 2012

Background

Our current understanding of evolution is so tightly linked to template-dependent replication of DNA and RNA molecules that the old idea from Oparin of a self-reproducing 'garbage bag' ('coacervate') of chemicals that predated fully-fledged cell-like entities seems to be farfetched to most scientists today. However, this is exactly the kind of scheme we propose for how Darwinian evolution could have occurred prior to template replication.

Results

We cannot confirm previous claims that autocatalytic sets of organic polymer molecules could undergo evolution in any interesting sense by themselves. While we and others have previously imagined inhibition would result in selectability, we found that it produced multiple attractors in an autocatalytic set that cannot be selected for. Instead, we discovered that if general conditions are satisfied, the accumulation of adaptations in chemical reaction networks can occur. These conditions are the existence of rare reactions producing viable cores (analogous to a genotype), that sustains a molecular periphery (analogous to a phenotype).

Conclusions

We conclude that only when a chemical reaction network consists of many such viable cores, can it be evolvable. When many cores are enclosed in a compartment there is competition between cores within the same compartment, and when there are many compartments, there is between-compartment competition due to the phenotypic effects of cores and their periphery at the compartment level. Acquisition of cores by rare chemical events, and loss of cores at division, allows macromutation, limited heredity and selectability, thus explaining how a poor man's natural selection could have operated prior to genetic templates. This is the only demonstration to date of a mechanism by which pre-template accumulation of adaptation could occur.

Reviewers

This article was reviewed by William Martin and Eugene Koonin.
Effects of Gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: study protocol for a randomized controlled trial
Authors: Park Jeong-Su , Park Sunju , Cheon Chun-Hoo , Go Ho-Yeon , Sun Seung-Ho , Shin Yong-Cheol , Jang Bo-Hyoung , Ko Seong-Gyu
Published: January 2012

Background

Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation.

Methods

This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3rd, 4th and 5th menstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks.

Discussion

This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis.

Trial registration

Current Controlled Trials: ISRCTN30426947
Evidence that GTP-binding domain but not catalytic domain of transglutaminase 2 is essential for epithelial-to-mesenchymal transition in mammary epithelial cells
Authors: Kumar Anupam , Xu Jia , Sung Bokyung , Kumar Santosh , Yu Dihua , Aggarwal Bharat B , Mehta Kapil
Published: January 2012

Introduction

The expression of proinflammatory protein tissue transglutaminase 2 (TG2) is frequently upregulated in multiple cancer cell types. However, the exact role of TG2 in cancer cells is not well-understood. We recently initiated studies to determine the significance of TG2 in cancer cells and observed that sustained expression of TG2 resulted in epithelial-to-mesenchymal transition (EMT) and promoted cancer stem cell (CSC) traits in mammary epithelial cells. These results suggested that TG2 could serve as a promising therapeutic target for overcoming chemoresistance and inhibiting metastatic spread of cancer cells.

Methods

Using various mutant constructs, we analyzed the activity of TG2 that is essential for promoting the EMT-CSC phenotype.

Results

Our results suggest that catalytically inactive TG2 (TG2-C277S) is as effective as wild-type TG2 (TG2-WT) in inducing the EMT-CSC in mammary epithelial cells. In contrast, overexpression of a GTP-binding-deficient mutant (TG2-R580A) was completely incompetent in this regard. Moreover, TG2-dependent activation of the proinflammatory transcription factor NF-κB is deemed essential for promoting the EMT-CSC phenotype in mammary epithelial cells.

Conclusions

Our results suggest that the transamidation activity of TG2 is not essential for promoting its oncogenic functions and provide a strong rationale for developing small-molecule inhibitors to block GTP-binding pockets of TG2. Such inhibitors may have great potential for inhibiting the TG2-regulated pathways, reversing drug resistance and inhibiting the metastasis of cancer cells.
Magnetic, electrical, and GPR waterborne surveys of moraine deposits beneath a lake: A case history from Turin, Italy
Authors: Sambuelli Luigi , Comina Cesare , Bava Silvia , Piatti Claudio
Published: January 2012

Bathymetry and bottom sediment types of inland water basins provide meaningful information to estimate water reserves and possible connections between surface and groundwater. Waterborne geophysical surveys can be used to obtain several independent physical parameters to study the sediments. We explored the possibilities of retrieving information on both shallow and deep geological structures beneath a morainic lake by means of waterborne nonseismic methods. In this respect, we discuss simultaneous magnetic, electrical, and ground-penetrating radar (GPR) waterborne surveys on the Candia morainic lake in northerly Turin (Italy). We used waterborne GPR to obtain information on the bottom sediment and the bathymetry needed to constrain the magnetic and electrical inversions. We obtained a map of the total magnetic field (TMF) over the lake from which we computed a 2D constrained compact magnetic inversion for selected profiles, along with a laterally constrained inversion for one electrical profile. The magnetic survey detected some deep anomalous bodies within the subbottom moraine. The electrical profiles gave information on the more superficial layer of bottom sediments. We identify where the coarse morainic material outcrops from the bottom finer sediments from a correspondence between high GPR reflectivity, resistivity, and magnetic anomalies.
Earthquakes and errors: Methods for industrial applications
Authors: Foulger Gillian R. , Julian Bruce R.
Published: January 2012

The high accuracies and realistic confidence assessments demanded for seismic monitoring of hydraulic fracturing work require specialist experimental approaches. These include seismic network design based on quantitative modeling, high-quality instrument deployments, and accurate and detailed crustal models. Confidence estimates must take into account uncertainties about crustal structure, which may dominate error budgets. Earthquake size should be expressed in terms of scalar seismic moment or the associated moment magnitude [Formula: see text], which is related to fundamental physical source processes, and not as traditional earthquake magnitudes. Representing earthquake mechanisms in terms of seismic moment tensors allows for processes such as volume changes and complex types of shearing that are important in hydrocarbon and geothermal reservoirs. Traditional fault-plane solutions are based on simplifying assumptions such as shear slip on a planar faults, and isotropic crustal structures, which may introduce large uncertainties. Quantitative assessment of confidence regions for moment-tensor source mechanisms, a newly emerging field, is important for distinguishing computational artifacts from real physical phenomena. We review methods currently available for realistic error estimation for earthquake locations and moment tensors, with particular emphasis on surface sensor arrays in geothermal areas.
Cilia in vertebrate development and disease
Authors: Oh Edwin C. , Katsanis Nicholas
Published: January 2012

Through the combined study of model organisms, cell biology, cell signaling and medical genetics we have significantly increased our understanding of the structure and functions of the vertebrate cilium. This ancient organelle has now emerged as a crucial component of certain signaling and sensory perception pathways in both developmental and homeostatic contexts. Here, we provide a snapshot of the structure, function and distribution of the vertebrate cilium and of the pathologies that are associated with its dysfunction.
The extracellular loops of Smoothened play a regulatory role in control of Hedgehog pathway activation
Authors: Carroll Candace E. , Marada Suresh , Stewart Daniel P. , Ouyang J. Xiaoxi , Ogden Stacey K.
Published: January 2012

The Hedgehog (Hh) signaling pathway plays an instructional role during development, and is frequently activated in cancer. Ligand-induced pathway activation requires signaling by the transmembrane protein Smoothened (Smo), a member of the G-protein-coupled receptor (GPCR) superfamily. The extracellular (EC) loops of canonical GPCRs harbor cysteine residues that engage in disulfide bonds, affecting active and inactive signaling states through regulating receptor conformation, dimerization and/or ligand binding. Although a functional importance for cysteines localized to the N-terminal extracellular cysteine-rich domain has been described, a functional role for a set of conserved cysteines in the EC loops of Smo has not yet been established. In this study, we mutated each of the conserved EC cysteines, and tested for effects on Hh signal transduction. Cysteine mutagenesis reveals that previously uncharacterized functional roles exist for Smo EC1 and EC2. We provide in vitro and in vivo evidence that EC1 cysteine mutation induces significant Hh-independent Smo signaling, triggering a level of pathway activation similar to that of a maximal Hh response in Drosophila and mammalian systems. Furthermore, we show that a single amino acid change in EC2 attenuates Hh-induced Smo signaling, whereas deletion of the central region of EC2 renders Smo fully active, suggesting that the conformation of EC2 is crucial for regulated Smo activity. Taken together, these findings are consistent with loop cysteines engaging in disulfide bonds that facilitate a Smo conformation that is silent in the absence of Hh, but can transition to a fully active state in response to ligand.
DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress
Authors: Kim Byunghyuk , Cooke Howard J. , Rhee Kunsoo
Published: January 2012

Mammalian male germ cells should be maintained below body temperature for proper development. Here, we investigated how male germ cells respond to heat stress. A short exposure of mouse testes to core body temperature induced phosphorylation of eIF2α and the formation of stress granules (SGs) in male germ cells. We observed that DAZL, a germ cell-specific translational regulator, was translocated to SGs upon heat stress. Furthermore, SG assembly activity was significantly diminished in the early male germ cells of Dazl-knockout mice. The DAZL-containing SGs played a protective role against heat stress-induced apoptosis by the sequestration of specific signaling molecules, such as RACK1, and the subsequent blockage of the apoptotic MAPK pathway. Based on these results, we propose that DAZL is an essential component of the SGs, which prevent male germ cells from undergoing apoptosis upon heat stress.
The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α
Authors: Goulbourne Chris N. , Malhas Ashraf N. , Vaux David J.
Published: January 2012

Farnesylated prelamin A accumulates when the final endoproteolytic maturation of the protein fails to occur and causes a dysmorphic nuclear phenotype; however, the morphology and mechanisms of biogenesis of these changes remain unclear. We show here that acute prelamin A accumulation after reduction in the activity of the ZMPSTE24 endoprotease by short interfering RNA knockdown, results in the generation of a complex nucleoplasmic reticulum that depends for its formation on the enzyme CTP:phosphocholine-cytidylyltransferase-α (CCT-α, also known as choline-phosphate cytidylyltransferase A). This structure can form during interphase, confirming that it is independent of mitosis and therefore not a consequence of disordered nuclear envelope assembly. Serial-section dual-axis electron tomography reveals that these invaginations can take two forms: one in which the inner nuclear membrane infolds alone with an inter membrane space interior, and the other in which an invagination of both nuclear membranes occurs, enclosing a cytoplasmic core. Both types of invagination can co-exist in one nucleus and both are frequently studded with nuclear pore complexes (NPC), which reduces NPC abundance on the nuclear surface.
The Short- and Long-Term Career Effects of Graduating in a Recession
Authors: Oreopoulos Philip , von Wachter Till , Heisz Andrew
Published: January 2012

This paper analyzes the magnitude and sources of long-term earnings declines associated with graduating from college during a recession. Using a large longitudinal university-employer-employee dataset, we find that the cost of recessions for new graduates is substantial and unequal. Unlucky graduates suffer persistent earnings declines lasting ten years. They start to work for lower paying employers, and then partly recover through a gradual process of mobility toward better firms. We document that more advantaged graduates suffer less from graduating in recessions because they switch to better firms quickly, while earnings of less advantaged graduates can be permanently affected by cyclical downgrading. (JEL E32, I23, J22, J23, J31)
Investing Cash Transfers to Raise Long-Term Living Standards
Authors: Gertler Paul J , Martinez Sebastian W , Rubio-Codina Marta
Published: January 2012

Using data from a randomized experiment, we find that poor rural Mexican households invested part of their cash transfers from the Oportunidades program in productive assets, increasing agricultural income by almost 10 percent after 18 months of benefits. We estimate that for each peso transferred, households consume 74 cents and invest the rest, permanently increasing long-term consumption by about 1.6 cents. Results suggest that cash transfers can achieve long-term increases in consumption through investment in productive activities, thereby permitting beneficiary households to attain higher living standards that are sustained even after transitioning off the program. (JEL D14, H23, I38, O12)
Determination of iodine in selected foods and diets by inductively coupled plasma-mass spectrometry
Authors: Tinggi Ujang , Schoendorfer Niikee , Davies Peter S. W. , Scheelings Pieter , Olszowy Henry
Published: January 2012

Iodine is an essential trace element, and its deficiency has caused concern in many countries. Foods are the principal source of iodine, and its levels are generally low. In this study, selected food items were obtained from food market outlets in Brisbane, Australia. Food samples of dietary intakes of selected healthy children in Brisbane, Australia, were also collected for analysis and assessment of iodine nutritional status. In Australia, there has been little study on iodine dietary intakes, particularly in young children. The aims of this study were to provide further information on iodine levels in foods for Australian food composition data, and to estimate the iodine daily intakes of selected healthy children. Food samples were analyzed for iodine concentrations using inductively coupled plasma-mass spectrometry (ICP-MS) after alkaline digestion with tetramethylammonium hydroxide (TMAH), and the method was validated using a certified reference material of nonfat milk (NIST, SRM 1549). The results of this study indicated a wide variation of iodine in foodstuffs, which ranged from <0.02 to 0.101 mg/kg for cereals, 87 to 299 μg/kg for milk, and 86 to 271 μg/kg for cheese products. The study also showed that the daily intakes of iodine in these children (n= 15) varied widely and ranged from 36.9 to 288.1 μg/day (mean ± s.d, 93.1 ± 76.7 μg/day).
Displacement and denial: IDPs in today's Iraq
Authors: MARFLEET PHILIP
Published: January 2012

There has been little sustained research on Iraq's internally displaced people. It is nonetheless clear that millions now live far from their original homes, many with little prospect of return. Increasing numbers are marginalized – marooned in communities of urban poor and largely
ignored by government authorities. This article examines their circumstances in the context of the wider displacement crisis.
Tracing Twitter: The rise of a microblogging platform
Authors: DIJCK JOSÉ VAN
Published: January 2012

This article uses ‘interpretative flexibility’ as a concept to analyse the early development of one specific microblogging site: Twitter. By tracing microblogging’s instable meaning in its early years (2006–10), we try to understand how the platform’s meaning
was shaped by a variety of human and non-human actors: technological design, usage, content and business models. By tracking microblogging’s instable meaning in its infant years, we may get a fuller understanding of how this new technology plays out in a complex Internet milieu of push-and-pull
forces. Reconstructing interpretative flexibility while the technology is still in flux – and thus open to manoeuvring – may give rise to new perspectives on how power relationships transpire in a networked environment.
Perception as Transcendence: Interview with Paweł Wojtasik
Authors: MacDonald Scott
Published: January 2012

An interview with an avant-garde filmmaker who combines a Buddhist sensibility (emphasizing detached contemplation of the world) with sometimes shocking or disgusting subject matter (a sewage plant, autopsy). Paweł Wojtasik is a cine-alchemist whose quest is to turn the disgusting, the horrifying, the taboo into gold, using perception as a means to transcendence.
Parent Perspectives on Pediatric Genetic Research and Implications for Genotype-Driven Research Recruitment
Authors: Tabor Holly K. , Brazg Tracy , Crouch Julia , Namey Emily E. , Fullerton Stephanie M. , Beskow Laura M. , Wilfond Benjamin S.
Published: January 2012

As genetic research is increasingly conducted in children, it is important to understand how parents make decisions about enrolling their children and what they think about receiving their children's genetic research results. We conducted semi-structured phone interviews with 23 parents of children enrolled in genetic studies of autism or diabetes. Qualitative thematic analysis focused on two important components of genetic research and genotype-driven recruitment: Participation in genetic research and return of results. Our findings suggest that parents' preferences and perspectives may be specific to their child's disease and the needs of the family as a whole. Assessing the expectations of target research populations will be beneficial for developing best practices for pediatric genetic research, return of results, and genotype-driven recruitment.
Informed Consent and Genomic Incidental Findings: IRB Chair Perspectives
Authors: Simon Christian M. , Williams Janet K. , Shinkunas Laura , Brandt Debra , Daack-Hirsch Sandra , Driessnack Martha
Published: January 2012

It is unclear how genomic incidental finding (GIF) prospects should be addressed in informed consent processes. An exploratory study on this topic was conducted with 34 purposively sampled Chairs of institutional review boards (IRBs) at centers conducting genome-wide association studies. Most Chairs (96%) reported no knowledge of local IRB requirements regarding GIFs and informed consent. Chairs suggested consent processes should address the prospect of, and study disclosure policy on, GIFs; GIF management and follow-up; potential clinical significance of GIFs; potential risks of GIF disclosure; an opportunity for participants to opt out of GIF disclosure; and duration of the researcher's duty to disclose GIFs. Chairs were concerned about participant disclosure preferences changing over time; inherent limitations in determining the scope and accuracy of claims about GIFs; and making consent processes longer and more complex. IRB Chair and other stakeholder perspectives can help advance informed consent efforts to accommodate GIF prospects.
What Women Who Use Drugs Have to Say about Ethical Research: Findings of an Exploratory Qualitative Study
Authors: Bell Kirsten , Salmon Amy
Published: January 2012

Drug users are generally seen as a vulnerable population requiring special protection in research; however, to date there has been little empirical research into the ethics of research with illicit drug users. Moreover, the available research has tended to treat “drug users” as a homogeneous category, and has failed to consider potential gender differences in users' experiences. Drawing on focus groups with twenty-seven female drug users in Vancouver, Canada, this study examines women's experiences of research and what they see as ethical and respectful engagement. Many study participants talked about feeling dehumanized as a result of prior research participation. Women were critical of the assumption that drug users lack the capacity to take part in research, and affirmed the appropriateness of financial incentives. A variety of motivations for research participation were identified, including a desire for financial gain and altruistic concerns such as a desire to help others. These findings suggest that women drug users' views on ethical research differ from prevailing assumptions among institutional review boards about how research with such populations should proceed.
Testing a Typology of Adaptations to Same-Sex Sexual Orientation among Men
Authors: Barrett Donald C. , Pollack Lance M.
Published: January 2012

Previous research has yielded important understandings of how sexual minorities adjust to living in a heteronormative culture, but scholarly critiques of assimilation and Merton's research on adaptations to deviance suggest value in examining whether there are distinct types of adaptation. Applying Merton's definition of adaptations in anomic environments suggests that different patterns can be defined depending on the importance placed on assimilation and on sexual expression. Using the 1997 Urban Men's Health Study data (n=2,585), four different adaptation patterns are defined: MSM conformist, MSM innovator, MSM nonconformist, and MSM uninvolved. To establish criterion validity, expected correlates of membership in each group are then examined. The distinct groups, each representing from 20 percent to 30 percent of the sample, largely conformed to expectations on measures of sexual self-identification, involvement in gay culture, intimacy and sexual exploration, health, and income. Scholarly and policy implications of the adaptation typology are considered.
Emotions Matter after All: How Reproductive Rights Advocates Orchestrate Emotions to Influence Policies in Peru
Authors: Coe Anna-Britt , Schnabel Annette
Published: January 2012

Emotions clearly matter in social movements, but it is less apparent how social movement participants actively handle emotions in their line of activities. In this article, the authors address this question by examining how two reproductive rights coalitions in Peru employ and manage emotions in relation to different actors who they must deal with to influence policies. Empirical materials consist of participant observation, focus groups, and individual interviews conducted with the coalitions and their members. Grounded theory was used to analyze the data. The authors distinguish relationships with five relevant actors: The internal members of the coalitions, allies, the general public, the Catholic Church as the major opponent, and government officials as the main target. As each relationship requires distinct emotion work, coalition members simultaneously adjust to contradictory emotional expectations while actively evoking and coordinating emotions. The authors refer to this as the orcherstration of emotion work.
Befriending the “Other”: Patterns of Social Ties between the Religious and Non-Religious
Authors: Vargas Nicholas , Loveland Matthew T.
Published: January 2012

Aside from the literature on inter-racial and cross-sex relationships, few studies have examined the determinants of relationships that cross social boundaries. The authors contribute to this literature by considering the social boundary between the religious and the non-religious. Surveys of U.S. adults provide evidence of popular aversion toward the non-religious, but this analysis of the Baylor Religion Survey (2005) shows that the majority of religious Americans report a friendship with someone who is not religious at all. The authors find that such boundary-crossing relationships are largely structured by homophily, opportunities for intergroup contact, and religious barriers to intergroup contact. These findings reveal that some religiously themed conflicts that are common among cultural elites may not be particularly salient in the realm of daily social life.
Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome
Authors: Donà Gabriella , Sabbadin Chiara , Fiore Cristina , Bragadin Marcantonio , Giorgino Francesco L , Ragazzi Eugenio , Clari Giulio , Bordin Luciana , Armanini Decio
Published: January 2012

Objective

Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations in erythrocytes and anti-inflammatory effects of inositol in women with PCOS before and after treatment with myo-inositol (MYO).

Methods

Twenty-six normal-weight PCOS patients were investigated before and after MYO administration (1200 mg/day for 12 weeks;n=18) or placebo (n=8) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, insulin area under the curve (AUC), and glucose AUC after oral glucose tolerance test and homeostasis model of assessment–IR. In erythrocytes, band 3 tyrosine phosphorylation (Tyr-P) level, glutathione (GSH) content, and glutathionylated proteins (GSSP) were also assessed.

Results

Data show that PCOS patients' erythrocytes underwent oxidative stress as indicated by band 3 Tyr-P values, reduced cytosolic GSH content, and increased membrane protein glutathionylation. MYO treatment significantly improved metabolic and biochemical parameters. Significant reductions were found in IR and serum values of androstenedione and testosterone. A significant association between band 3 Tyr-P levels and insulin AUC was found at baseline but disappeared after MYO treatment, while a correlation between band 3 Tyr-P and testosterone levels was detected both before and after MYO treatment.

Conclusions

PCOS patients suffer from a systemic inflammatory status that induces erythrocyte membrane alterations. Treatment with MYO is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.