bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Environmental Cognition
Authors: Henry Adam Douglas , Dietz Thomas
Published: October 2012

Many research questions in environmental policy lead us to questions of environmental cognition—how do individuals structure their thinking about environmental issues, how are these cognitions learned, and how do they influence behaviors? Although these processes tend to be understudied and undertheorized, at least two theoretical perspectives are useful for illuminating different aspects of environmental cognition. The Advocacy Coalition Framework (ACF) was developed in the political science literature to explain major policy change in technically complex issue areas, and the Values-Beliefs-Norms (VBN) theory was developed in the social psychology literature to explain environmental activism among the lay public. Unfortunately, these literatures rarely communicate with one another. This article shows how integrating key aspects of the ACF and VBN can moves us toward a more robust theory to guide future empirical work on cognition, learning, and behavior in the context of environmental issues.
Factor Structure of the Wechsler Intelligence Scale for Children
Authors: Thaler Nicholas S. , Barchard Kimberly A. , Parke Elyse , Jones W. Paul , Etcoff Lewis M. , Allen Daniel N.
Published: October 2012

Objective: Recent evidence suggests that the factor structure of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) is better explained by a five-factor model rather than the four-factor model in the standardization sample. The current study examined the WISC-IV’s factor structure in a sample of children with ADHD. Method: Participants included 314 children and adolescents who were diagnosed with ADHD. Confirmatory factor analysis was conducted on the 10 core subtests of the WISC-IV, and three models were examined including two based on Cattell–Horn–Carroll (CHC) theory. Results: A five-factor model consisting of Gc, Gf, Gv, Gsm, and Gs factors provided the best fit for the data. The Perceptual Reasoning factor identified in the original four-factor model split into the two CHC factors, Gf and Gv, and cross-loaded the Symbol Search subtest onto the Gv factor. Conclusion: A five-factor model based on CHC theory provided superior fit for the WISC-IV in children with ADHD, as has been found with the standardization sample.
Ills from the womb? A critical examination of clinical guidelines for obesity in pregnancy
Authors: Jette Shannon , Rail Geneviève
Published: October 2012

In this article, we critically examine the clinical guidelines for obesity in pregnancy put forth by the Society of Obstetricians and Gynaecologists of Canada (SOGC) that are underpinned by the rules of Evidence-Based Medicine (EBM), a system of ranking knowledge that promises to provide unbiased evidence about the effectiveness of treatments. While the SOGC guidelines are intended to direct health practitioners on ‘best practice’ as they address pregnancy weight gain with clients in the clinical context, we question their usefulness, arguing that despite their commitment to objectivity, they remain mired in cultural biases that stigmatize large female bodies and associates them to ‘unfit’ mothers.
Nursing interventions in cases of agitation and dementia
Authors: Oppikofer Sandra , Geschwindner Heike
Published: October 2012

This study had two objectives: firstly, to assess and compare the frequency and circumstances of agitation and, secondly, to generate decision-making aids for the treatment of agitation patients by applying a nursing intervention in cases of dementia and agitation. For that purpose, 1002 measurements of open nursing interventions in cases of agitation were obtained over a period of 11 weeks in two nursing homes in the city of Zurich and in the nursing home Sonnweid. Before, during and after two intervention periods of four weeks each, data were collected for 60 persons suffering from severe dementia. The results show that two-thirds of the residents were never agitated, one-quarter was moderately agitated and only very few suffered from medium-to-severe agitation. In almost half the cases, agitation occurred while the person was alone (46%), followed by cases of agitation as a constant state (26%). There was rarely any agitation while the residents were engaged in activities. After analysing 433 documented cases, it turned out that the most successful care interventions were avoiding noise, accompanying the person to the toilet, communication/validation, walking about/movement and administering beverages. Being based on newly translated observational methods and a unique longitudinal study design with combined intervention, this study provides important insights into how agitation in dementia can be influenced within the care context, as well as a practical evaluation of interventions specific to different institutions.
Is the Greening of Firms Helping Consumers to Go Green?
Authors: Raska David , Shaw Doris
Published: October 2012

Although research supports the notion that consumers look favorably upon firms that implement popular social behaviors like “going green,” little is known about how such practices impact the consumer’s own social attitudes and behaviors. In two experiments, the authors explore this underresearched area in social marketing by examining how a firm’s stated motive for its environmentally friendly behaviors as well as brand loyalty influence consumer attitudes toward, and intentions for, similar behaviors. Implications for social marketers are provided regarding the development of effective social marketing programs. These results suggest that society may best be served when marketers integrate more honesty and transparency into socially responsible claims since consumers are more likely to model their behavior under these circumstances.
The Potential for Social Marketing a Knowledge-Based Family Planning Method
Authors: Kavle Justine , Eber Maxine , Lundgren Rebecka
Published: October 2012

Social marketing is a proven private sector strategy to provide health-related products, including contraceptives. Pharmacies offer affordable, convenient, and rapid delivery of over-the-counter contraceptives directly to the consumer, providing wider availability and accessibility to family planning (FP) in sub-Saharan Africa. Pilot projects tested the feasibility of including CycleBeads®, the visual tool that supports the use of the Standard Days Method®, into Population Services International (PSI) social marketing programs. The purpose of this article is to review evidence to provide guidance for social marketing CycleBeads in pharmacies in sub-Saharan Africa. Literature on contraceptive provision through pharmacies in comparison to clinics was summarized from developing and developed country contexts, highlighting salient and relevant lessons for the African context in regard to pharmacists’ knowledge and perceptions of FP, clients’ perceptions of pharmacists’ FP knowledge and FP service delivery in pharmacies, and the impact of pharmacy access on contraceptive use. Descriptive data from PSI social marketing initiatives in several African countries, and commercial marketing information were reviewed. Evidence from CycleBeads sales suggests that there is demand for the product and it is affordable in comparison to oral contraceptives. In addition, there were high levels of correct use by women who purchased CycleBeads in pharmacies, suggesting that CycleBeads are an appropriate product for social marketing. Until awareness of and demand for the method increases, social marketing of CycleBeads requires continued subsidy to maintain viability. Training to update pharmacists’ knowledge and increase capacity to provide basic information, positioning of the method, and low profit margins for pharmacies present challenges.
Organization-Based Social Marketing
Authors: Papakosmas Mary Franks , Noble Gary , Glynn John
Published: October 2012

This article conceptualizes a new area for social marketing practitioners by focusing on individual behavior change that might occur within organizations. Organization-Based Social Marketing (OBSM) draws from organization change theory and internal marketing theory, while maintaining social marketing’s focus on beneficial behavior modification. The article argues that as such, OBSM represents a viable approach for organizations seeking to address the increasing demand for change strategies that promote proenvironmental behavior among their employees.
Integrating Public Relations and Social Marketing
Authors: Sundstrom Beth
Published: October 2012

This study examined the relationship between public relations and social marketing in a nonprofit health organization. A case study was conducted, in which internal and external organizational documents, archival records, and artifacts were analyzed and four in-depth interviews were completed. Evidence showed that public relations and social marketing were integrated into the organization’s communication function. Findings provided evidence for a tactical paradigm of public relations, which emphasizes publicity and promotion, as well as a situational approach to messaging and communication functions. The organization engaged the new two-way model of symmetry through cultivating relationships and two-way dialogue. These findings suggest the importance of social marketing approaches to behavior change and relationship cultivation strategies. This case study highlights the success of social marketing initiatives, and the opportunity for social marketing and public relations to evolve together in a new media context.
Combining multiple hypothesis testing and affinity propagation clustering leads to accurate, robust and sample size independent classification on gene expression data
Authors: Sakellariou Argiris , Sanoudou Despina , Spyrou George
Published: October 2012

Background

A feature selection method in microarray gene expression data should be independent of platform, disease and dataset size. Our hypothesis is that among the statistically significant ranked genes in a gene list, there should be clusters of genes that share similar biological functions related to the investigated disease. Thus, instead of keeping N top ranked genes, it would be more appropriate to define and keep a number of gene cluster exemplars.

Results

We propose a hybrid FS method (mAP-KL), which combines multiple hypothesis testing and affinity propagation (AP)-clustering algorithm along with the Krzanowski & Lai cluster quality index, to select a small yet informative subset of genes. We applied mAP-KL on real microarray data, as well as on simulated data, and compared its performance against 13 other feature selection approaches. Across a variety of diseases and number of samples, mAP-KL presents competitive classification results, particularly in neuromuscular diseases, where its overall AUC score was 0.91. Furthermore, mAP-KL generates concise yet biologically relevant and informative N-gene expression signatures, which can serve as a valuable tool for diagnostic and prognostic purposes, as well as a source of potential disease biomarkers in a broad range of diseases.

Conclusions

mAP-KL is a data-driven and classifier-independent hybrid feature selection method, which applies to any disease classification problem based on microarray data, regardless of the available samples. Combining multiple hypothesis testing and AP leads to subsets of genes, which classify unknown samples from both, small and large patient cohorts with high accuracy.
Bag of Naïve Bayes: biomarker selection and classification from genome-wide SNP data
Authors: Sambo Francesco , Trifoglio Emanuele , Di Camillo Barbara , Toffolo Gianna M , Cobelli Claudio
Published: October 2012

Background

Multifactorial diseases arise from complex patterns of interaction between a set of genetic traits and the environment. To fully capture the genetic biomarkers that jointly explain the heritability component of a disease, thus, all SNPs from a genome-wide association study should be analyzed simultaneously.

Results

In this paper, we present Bag of Naïve Bayes (BoNB), an algorithm for genetic biomarker selection and subjects classification from the simultaneous analysis of genome-wide SNP data. BoNB is based on the Naïve Bayes classification framework, enriched by three main features: bootstrap aggregating of an ensemble of Naïve Bayes classifiers, a novel strategy for ranking and selecting the attributes used by each classifier in the ensemble and a permutation-based procedure for selecting significant biomarkers, based on their marginal utility in the classification process. BoNB is tested on the Wellcome Trust Case-Control study on Type 1 Diabetes and its performance is compared with the ones of both a standard Naïve Bayes algorithm and HyperLASSO, a penalized logistic regression algorithm from the state-of-the-art in simultaneous genome-wide data analysis.

Conclusions

The significantly higher classification accuracy obtained by BoNB, together with the significance of the biomarkers identified from the Type 1 Diabetes dataset, prove the effectiveness of BoNB as an algorithm for both classification and biomarker selection from genome-wide SNP data.

Availability

Source code of the BoNB algorithm is released under the GNU General Public Licence and is available at http://www.dei.unipd.it/~sambofra/bonb.html.
Fine mapping of complex traits in non-model species: using next generation sequencing and advanced intercross lines in Japanese quail
Authors: Frésard Laure , Leroux Sophie , Dehais Patrice , Servin Bertrand , Gilbert Hélène , Bouchez Olivier , Klopp Christophe , Cabau Cédric , Vignoles Florence , Feve Katia , Ricros Amélie , Gourichon David , Diot Christian , Richard Sabine , Leterrier Christine , Beaumont Catherine , Vignal Alain , Minvielle Francis , Pitel Frédérique
Published: October 2012

Background

As for other non-model species, genetic analyses in quail will benefit greatly from a higher marker density, now attainable thanks to the evolution of sequencing and genotyping technologies. Our objective was to obtain the first genome wide panel of Japanese quail SNP (Single Nucleotide Polymorphism) and to use it for the fine mapping of a QTL for a fear-related behaviour, namely tonic immobility, previously localized on Coturnix japonica chromosome 1. To this aim, two reduced representations of the genome were analysed through high-throughput 454 sequencing: AFLP (Amplified Fragment Length Polymorphism) fragments as representatives of genomic DNA, and EST (Expressed Sequence Tag) as representatives of the transcriptome.

Results

The sequencing runs produced 399,189 and 1,106,762 sequence reads from cDNA and genomic fragments, respectively. They covered over 434 Mb of sequence in total and allowed us to detect 17,433 putative SNP. Among them, 384 were used to genotype two Advanced Intercross Lines (AIL) obtained from three quail lines differing for duration of tonic immobility. Despite the absence of genotyping for founder individuals in the analysis, the previously identified candidate region on chromosome 1 was refined and led to the identification of a candidate gene.

Conclusions

These data confirm the efficiency of transcript and AFLP-sequencing for SNP discovery in a non-model species, and its application to the fine mapping of a complex trait. Our results reveal a significant association of duration of tonic immobility with a genomic region comprising the DMD (dystrophin) gene. Further characterization of this candidate gene is needed to decipher its putative role in tonic immobility in Coturnix.
Electrophysiological correlates of object-repetition effects: sLORETA imaging with 64-channel EEG and individual MRI
Authors: Kim Myung-Sun , Jang Kyoung-Mi , Che Huije , Kim Do-Won , Im Chang-Hwan
Published: October 2012

Background

We investigated the electrophysiological correlates of object-repetition effects using an object categorization task, standardized low-resolution electromagnetic tomography (sLORETA), and individual magnetic resonance imaging. Sixteen healthy adults participated, and a total of 396 line drawings of living and non-living objects were used as stimuli. Of these stimuli, 274 were presented only once, and 122 were repeated after one to five intervening pictures. Participants were asked to categorize the objects as living or non-living things by pressing one of two buttons.

Results

The old/new effect (i.e., a faster response time and more positive potentials in response to repeated stimuli than to stimuli initially presented) was observed at 350-550 ms post-stimulus. The distributions of cortical sources for the old and new stimuli were very similar at 250-650 ms after stimulus-onset. Activation in the right middle occipital gyrus/cuneus, right fusiform gyrus, left superior temporal gyrus, and right inferior frontal gyrus was significantly reduced in response to old compared with new stimuli at 250-350, 350-450, 450-550, and 550-650 ms after stimulus-onset, respectively. Priming in response time was correlated with the electrophysiological priming at left parietal area and repetition suppression at left superior temporal gyrus in 450-550 ms.

Conclusions

These results suggest processing of repeated objects is facilitated by sharpening perceptual representation and by efficient detection or attentional control of repeated objects.
“The balancing act”— Licensed practical nurse experiences of falls and fall prevention: a qualitative study
Authors: Häggqvist Beatrice , Stenvall Michael , Fjellman-Wiklund Anncristine , Westerberg Kristina , Lundin-Olsson Lillemor
Published: October 2012

Background

Falls are common in old age and may have serious consequences. There are many strategies to predict and prevent falls from occurring in long-term care and hospitals. The aim of this study was to describe licensed practical nurse experiences of predicting and preventing further falls when working with patients who had experienced a fall-related fracture. Licensed practical nurses are the main caretakers that work most closely with the patients.

Methods

A qualitative study of focus groups interviews and field observations was done. 15 licensed practical nurses from a rehabilitation ward and an acute ward in a hospital in northern Sweden were interviewed. Content was analyzed using qualitative content analysis.

Results

The result of the licensed practical nurse thoughts and experiences about risk of falling and fall prevention work is represented in one theme, “the balancing act”. The theme includes three categories: “the right to decide”, “the constant watch”, and “the ongoing negotiation” as well as nine subcategories. The analysis showed similarities and differences between rehabilitation and acute wards. At both wards it was a core strategy in the licensed practical nurse work to always be ready and to pay attention to patients’ appearance and behavior. At the rehabilitation ward, it was an explicit working task to judge the patients’ risk of falling and to be active to prevent falls. At the acute ward, the words “risk of falling” were not used and fall prevention were not discussed; instead the licensed practical nurses used for example “dizzy and pale”. The results also indicated differences in components that facilitate workplace learning and knowledge transfer.

Conclusions

Differences between the wards are most probably rooted in organizational differences. When it is expected by the leadership, licensed practical nurses can express patient risk of falling, share their observations with others, and take actions to prevent falls. The climate and the structure of the ward are essential if licensed practical nurses are to be encouraged to routinely consider risk of falling and implement risk reduction strategies.
Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study
Authors: Goto Atsushi , Morita Akemi , Goto Maki , Sasaki Satoshi , Miyachi Motohiko , Aiba Naomi , Terauchi Yasuo , Noda Mitsuhiko , Watanabe Shaw ,   the Saku Cohort Study Group
Published: October 2012

Background

Sex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver.

Methods

We conducted a case–control study that included 300 diabetes cases (215 men and 85 women) and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels ≥126 mg/dL, 2-h post-load glucose levels ≥200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI), a validated measure derived from serum triglyceride levels, body mass index (BMI), waist circumference, and γ-glutamyltransferase levels.

Results

After adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02–0.96]), but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01–1.17]). In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23–0.89]), but not among women.

Conclusions

Our findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.
NF kappaB expression increases and CFTR and MUC1 expression decreases in the endometrium of infertile patients with hydrosalpinx: a comparative study
Authors: Song Yong , Wang Qiushi , Huang Wei , Xiao Li , Shen Licong , Xu Wenming
Published: October 2012

Background

Hydrosalpinx are associated with infertility, due to reduced rates of implantation and increased abortion rates. The aims of this study were to investigate the expression of cystic fibrosis transmembrane conductance regulator (CFTR), nuclear factor kappa B (NF KappaB) and mucin-1 (MUC-1), and analyze the correlation between the expression of CFTR and NF KappaB or MUC1, in the endometrium of infertile women with and without hydrosalpinx.

Methods

Thirty-one infertile women with laparoscopy-confirmed unilateral or bilateral hydrosalpinx and 20 infertile women without hydrosalpinx or pelvic inflammatory disease (control group) were recruited. Endometrial biopsy samples were collected and the expression of CFTR, NF KappaB and MUC1 were analyzed using immunohistochemistry and quantitative real-time PCR.

Results

CFTR, NF KappaB and MUC1 mRNA and protein expression tended to increase in the secretory phase compared to the proliferative phase in both groups; however, these differences were not significantly different. The endometrium of infertile patients with hydrosalpinx had significantly higher NF KappaB mRNA and protein expression, and significantly lower CFTR and MUC1 mRNA and protein expression, compared to control infertile patients. A positive correlation was observed between CFTR and MUC1 mRNA expression (r = 0.65, P < 0.05); a negative correlation was observed between CFTR mRNA and NF KappaB mRNA expression (r = −0.59, P < 0.05).

Conclusions

Increased NF KappaB expression and decreased CFTR and MUC1 expression in the endometrium of infertile patients with hydrosalpinx reinforce the involvement of a molecular mechanism in the regulation of endometrial receptivity.
Impact of antenna correlation on the performance of partial relay selection
Authors: Ferdinand Nuwan S , Jayasinghe Upul , Rajatheva Nandana , Latva-aho Matti
Published: October 2012

Antenna correlation is generally viewed as an obstacle to realize the desired performance of a wireless system. In this article, we investigate the performance of partial relay selection in the presence of antenna correlation. We consider both channel state information (csi)-assisted and fixed gain amplify-and-forward (AF) relay schemes. The source and the destination are equipped with multiple antennas communicating via the best first hop signal-to-noise ratio (SNR) relay. We derived the closed form expression for outage probability, average symbol error rate (SER) for both schemes. Further, an exact expression is derived for the ergodic capacity in the csi-assisted relay case and an approximated expression is considered for the fixed gain case. Moreover, we provide simple asymptotic results and show that the diversity order of the system remains unchanged with the effect of antenna correlation for both types of relay schemes.
Iterative common solutions for monotone inclusion problems, fixed point problems and equilibrium problems
Authors: Takahashi Wataru , Wong Ngai-Ching , Yao Jen-Chih
Published: October 2012

Let H be a real Hilbert space, and let C be a nonempty closed convex subset of H. Let

α
>
0

, and let A be an α-inverse strongly-monotone mapping of C into H. Let T be a generalized hybrid mapping of C into H. Let B and W be maximal monotone operators on H such that the domains of B and W are included in C. Let

0
<
k
<
1

, and let g be a k-contraction of H into itself. Let V be a

γ
¯

-strongly monotone and L-Lipschitzian continuous operator with

γ
¯

>
0

and

L
>
0

. Take

μ
,
γ
∈
R

as follows:

0
<
μ
<

2

γ
¯

L
2

,

0
<
γ
<

γ
¯

−

L
2

μ

2

k

.

Suppose that

F
(
T
)
∩

(
A
+
B
)

−
1

0
∩

W

−
1

0
≠
∅

, where

F
(
T
)

and

(
A
+
B
)

−
1

0

,

W

−
1

0

are the set of fixed points of T and the sets of zero points of

A
+
B

and W, respectively. In this paper, we prove a strong convergence theorem for finding a point

z
0

of

F
(
T
)
∩

(
A
+
B
)

−
1

0
∩

W

−
1

0

, where

z
0

is a unique fixed point of

P

F
(
T
)
∩

(
A
+
B
)

−
1

0
∩

W

−
1

0

(
I
−
V
+
γ
g
)

. This point

z
0

∈
F
(
T
)
∩

(
A
+
B
)

−
1

0
∩

W

−
1

0

is also a unique solution of the variational inequality

〈
(
V
−
γ
g
)

z
0

,
q
−

z
0

〉

≥
0
,

∀
q
∈
F
(
T
)
∩

(
A
+
B
)

−
1

0
∩

W

−
1

0
.

Using this result, we obtain new and well-known strong convergence theorems in a Hilbert space. In particular, we solve a problem posed by Kurokawa and Takahashi (Nonlinear Anal. 73:1562-1568, 2010).

MSC:47H05, 47H10, 58E35.
FACS-based purification of Arabidopsis microspores, sperm cells and vegetative nuclei
Authors: Borges Filipe , Gardner Rui , Lopes Telma , Calarco Joseph P , Boavida Leonor C , Slotkin R Keith , Martienssen Robert A , Becker Jörg D
Published: October 2012

Background

The male germline in flowering plants differentiates by asymmetric division of haploid uninucleated microspores, giving rise to a vegetative cell enclosing a smaller generative cell, which eventually undergoes a second mitosis to originate two sperm cells. The vegetative cell and the sperm cells activate distinct genetic and epigenetic mechanisms to control pollen tube growth and germ cell specification, respectively. Therefore, a comprehensive characterization of these processes relies on efficient methods to isolate each of the different cell types throughout male gametogenesis.

Results

We developed stable transgenicArabidopsislines and reliable purification tools based on Fluorescence-Activated Cell Sorting (FACS) in order to isolate highly pure and viable fractions of each cell/nuclei type before and after pollen mitosis. In the case of mature pollen, this was accomplished by expressing GFP and RFP in the sperm and vegetative nuclei, respectively, resulting in 99% pure sorted populations. Microspores were also purified by FACS taking advantage of their characteristic small size and autofluorescent properties, and were confirmed to be 98% pure.

Conclusions

We provide simple and efficient FACS-based purification protocols forArabidopsismicrospores, vegetative nuclei and sperm cells. This paves the way for subsequent molecular analysis such as transcriptomics, DNA methylation analysis and chromatin immunoprecipitation, in the developmental context of microgametogenesis inArabidopsis.
Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease
Authors: Crespo Isaac , Roomp Kirsten , Jurkowski Wiktor , Kitano Hiroaki , del Sol Antonio
Published: October 2012

Background

The activation of immune cells in the brain is believed to be one of the earliest events in prion disease development, where misfolded PrionSc protein deposits are thought to act as irritants leading to a series of events that culminate in neuronal cell dysfunction and death. The role of these events in prion disease though is still a matter of debate. To elucidate the mechanisms leading from abnormal protein deposition to neuronal injury, we have performed a detailed network analysis of genes differentially expressed in several mouse prion models.

Results

We found a master regulatory core of genes related to immune response controlling other genes involved in prion protein replication and accumulation, and neuronal cell death. This regulatory core determines the existence of two stable states that are consistent with the transcriptome analysis comparing prion infected versus uninfected mouse brain. An in silico perturbation analysis demonstrates that core genes are individually capable of triggering the transition and that the network remains locked once the diseased state is reached.

Conclusions

We hypothesize that this locking may be the cause of the sustained immune response observed in prion disease. Our analysis supports the hypothesis that sustained brain inflammation is the main pathogenic process leading to neuronal dysfunction and loss, which, in turn, leads to clinical symptoms in prion disease.
Functional phosphoproteomic mass spectrometry‐based approaches
Authors: López Elena , Wang Xiangdong , Madero Luis , López‐Pascual Juan , Latterich Martin
Published: October 2012

Mass Spectrometry (MS)‐based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease.

The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un‐phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future.

Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies.
Common genetic variants, acting additively, are a major source of risk for autism
Authors: Klei Lambertus , Sanders Stephan J , Murtha Michael T , Hus Vanessa , Lowe Jennifer K , Willsey A Jeremy , Moreno-De-Luca Daniel , Yu Timothy W , Fombonne Eric , Geschwind Daniel , Grice Dorothy E , Ledbetter David H , Lord Catherine , Mane Shrikant M , Martin Christa Lese , Martin Donna M , Morrow Eric M , Walsh Christopher A , Melhem Nadine M , Chaste Pauline , Sutcliffe James S , State Matthew W , Cook Edwin H , Roeder Kathryn , Devlin Bernie
Published: October 2012

Background

Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals.

Methods

By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status.

Results

By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating.

Conclusions

Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.
An activity theory analysis of boundary objects in cross-border information systems development for disaster management
Authors: Bharosa Nitesh , Lee JinKyu , Janssen Marijn , Rao H Raghav
Published: October 2012

One of the main challenges in cross-border disaster management is the development and use of information systems that cater the needs of heterogeneous relief agencies, policies, activities and cultures. Drawing upon activity theory, this paper examines cross-border information systems development for disaster management. We infuse the concept of boundary objects into activity theory by the characterization of the artifacts. This allows articulating how the socio-technical objects are meshed with the process of cross-border collaboration for systems development. Our longitudinal ethnographic field study on a cross-border flood management project, VIKING, revealed how the project was empowered and developed by four key boundary objects, i.e. the governance structure of the program, two information systems (a disaster management information system and an online collaboration portal), and recurring cross-border exercises as an evaluation and feedback mechanism. The selective institutionalizations of these key boundary objects helped the participants overcome various contradictions existed in the systems development. The study results also show that both goal-oriented actions and boundary objects can affect the outcomes of long-term large-scale disaster management systems development.
Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation
Authors: Rühl Thomas , Deuther-Conrad Winnie , Fischer Steffen , Günther Robert , Hennig Lothar , Krautscheid Harald , Brust Peter
Published: October 2012

Background

The endocannabinoid system is involved in many physiological and pathological processes. Two receptors (cannabinoid receptor type 1 (CB1) and type 2 (CB2)) are known so far. Many unwanted psychotic side effects of inhibitors of this system can be addressed to the interaction with CB1. While CB1 is one of the most abundant neuroreceptors, CB2 is expressed in the brain only at very low levels. Thus, highly potent and selective compounds for CB2 are desired. N-aryl-((hetero)aromatic)-oxadiazolyl-propionamides represent a promising class of such selective ligands for the human CB2. Here, a library of various derivatives is studied for suitable routes for labelling with 18F. Such 18F-labelled compounds can then be employed as CB2-selective radiotracers for molecular imaging studies employing positron emission tomography (PET).

Results

By varying the N-arylamide substructure, we explored the binding pocket of the human CB2 receptor and identified 9-ethyl-9H-carbazole amide as the group with optimal size. Radioligand replacement experiments revealed that the modification of the (hetero)aromatic moiety in 3-position of the 1,2,4-oxadiazoles shows only moderate impact on affinity to CB2 but high impact on selectivity towards CB2 with respect to CB1. Further, we could show by autoradiography studies that the most promising compounds bind selectively on CB2 receptors in mouse spleen tissue. Molecular docking studies based on a novel three-dimensional structural model of the human CB2 receptor in its activated form indicate that the compounds bind with the N-arylamide substructure in the binding pocket. 18F labelling at the (hetero)aromatic moiety at the opposite site of the compounds via radiochemistry was carried out.

Conclusions

The synthesized CB2-selective compounds have high affinity towards CB2 and good selectivity against CB1. The introduction of labelling groups at the (hetero)aromatic moiety shows only moderate impact on CB2 affinity, indicating the introduction of potential labelling groups at this position as a promising approach to develop CB2-selective ligands suitable for molecular imaging with PET. The high affinity for human CB2 and selectivity against human CB1 of the herein presented compounds renders them as suitable candidates for molecular imaging studies.
Mannose binding lectin: a biomarker of systemic lupus erythematosus disease activity
Authors: Panda Aditya K , Parida Jyoti R , Tripathy Rina , Pattanaik Sarit S , Ravindran Balachandran , Das Bidyut K
Published: October 2012

Introduction

A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE.

Methods

In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures.

Results

Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29).

Conclusions

Plasma MBL is a promising marker in the assessment of SLE disease activity.
Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study
Authors: Smit Menke de , Westra Johanna , Vissink Arjan , Doornbos-van der Meer Berber , Brouwer Elisabeth , van Winkelhoff Arie Jan
Published: October 2012

Introduction

The association between rheumatoid arthritis (RA) and periodontitis is suggested to be linked to the periodontal pathogen Porphyromonas gingivalis. Colonization of P. gingivalis in the oral cavity of RA patients has been scarcely considered. To further explore whether the association between periodontitis and RA is dependent on P. gingivalis, we compared host immune responses in RA patients with and without periodontitis in relation to presence of cultivable P. gingivalis in subgingival plaque.

Methods

In 95 RA patients, the periodontal condition was examined using the Dutch Periodontal Screening Index for treatment needs. Subgingival plaque samples were tested for presence of P. gingivalis by anaerobic culture technique. IgA, IgG and IgM antibody titers to P. gingivalis were measured by ELISA. Serum and subgingival plaque measures were compared to a matched control group of non-RA subjects.

Results

A higher prevalence of severe periodontitis was observed in RA patients in comparison to matched non-RA controls (27% versus 12%, p < 0.001). RA patients with severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis (p < 0.001), while no differences were seen in IgM-RF or ACPA reactivity. Furthermore, RA patients with severe periodontitis had higher IgG- and IgM-anti P. gingivalis titers than non-RA controls with severe periodontitis (p < 0.01 resp. p < 0.05), although subgingival occurrence of P. gingivalis was not different.

Conclusions

Severity of periodontitis is related to severity of RA. RA patients with severe periodontitis have a more robust antibody response against P. gingivalis than non-RA controls, but not all RA patients have cultivable P. gingivalis.
Investigating risk factors for psychological morbidity three months after intensive care: a prospective cohort study
Authors: Wade Dorothy M , Howell David C , Weinman John A , Hardy Rebecca J , Mythen Michael G , Brewin Chris R , Borja-Boluda Susana , Matejowsky Claire F , Raine Rosalind A
Published: October 2012

Introduction

There is growing evidence of poor mental health and quality of life among survivors of intensive care. However, it is not yet clear to what extent the trauma of life-threatening illness, associated drugs and treatments, or patients' psychological reactions during intensive care contribute to poor psychosocial outcomes. Our aim was to investigate the relative contributions of a broader set of risk factors and outcomes than had previously been considered in a single study.

Methods

A prospective cohort study of 157 mixed-diagnosis highest acuity patients was conducted in a large general intensive care unit (ICU). Data on four groups of risk factors (clinical, acute psychological, socio-demographic and chronic health) were collected during ICU admissions. Post-traumatic stress disorder (PTSD), depression, anxiety and quality of life were assessed using validated questionnaires at three months (n =100). Multivariable analysis was used.

Results

At follow-up, 55% of patients had psychological morbidity: 27.1% (95% CI: 18.3%, 35.9%) had probable PTSD; 46.3% (95% CI: 36.5%, 56.1%) probable depression, and 44.4% (95% CI: 34.6%, 54.2%) anxiety. The strongest clinical risk factor for PTSD was longer duration of sedation (regression coefficient = 0.69 points (95% CI: 0.12, 1.27) per day, scale = 0 to 51). There was a strong association between depression at three months and receiving benzodiazepines in the ICU (mean difference between groups = 6.73 points (95% CI: 1.42, 12.06), scale = 0 to 60). Use of inotropes or vasopressors was correlated with anxiety, and corticosteroids with better physical quality of life.

The effects of these clinical risk factors on outcomes were mediated (partially explained) by acute psychological reactions in the ICU. In fully adjusted models, the strongest independent risk factors for PTSD were mood in ICU, intrusive memories in ICU and psychological history. ICU mood, psychological history and socio-economic position were the strongest risk factors for depression.

Conclusions

Strikingly high rates of psychological morbidity were found in this cohort of intensive care survivors. The study's key finding was that acute psychological reactions in the ICU were the strongest modifiable risk factors for developing mental illness in the future. The observation that use of different ICU drugs correlated with different psychological outcomes merits further investigation. These findings suggest that psychological interventions, along with pharmacological modifications, could help reduce poor outcomes, including PTSD, after intensive care.
CHANCE: comprehensive software for quality control and validation of ChIP-seq data
Authors: Diaz Aaron , Nellore Abhinav , Song Jun S
Published: October 2012

ChIP-seq is a powerful method for obtaining genome-wide maps of protein-DNA interactions and epigenetic modifications. CHANCE (CHip-seq ANalytics and Confidence Estimation) is a standalone package for ChIP-seq quality control and protocol optimization. Our user-friendly graphical software quickly estimates the strength and quality of immunoprecipitations, identifies biases, compares the user's data with ENCODE's large collection of published datasets, performs multi-sample normalization, checks against quantitative PCR-validated control regions, and produces informative graphical reports. CHANCE is available at https://github.com/songlab/chance.
“Dinner Party of Discourse Owners”: China’s Intellectual Scene Today
Authors: Kang Liu
Published: October 2012

This article assesses the Chinese intellectual scene through sketching four groups of Chinese intellectuals: state strategists, the (politically) scandalous, professionals, and the weibo (microblogging) opinion leaders. The Chinese intellectual scene today is filled with excitement and sensationalism, a carnivalesque dinner party of festivity enjoyed by academics, media practitioners, and other cultural workers — the “discourse owners” of China’s global “cultural soft power” or “discourse power,” to use the new buzzwords. Missing, however, are well-grounded and seriously thought-out responses to the fundamental questions and dilemmas that China faces today: the absence of social consensus and coherent social values that provide not only cohesiveness to an increasingly diverse and fragmented society in rapid transformation but also clues to the world community as to the future orientations of a rising China. The GDP fetish and economic developmentalism have been the backbone of the pragmatic policies of the Chinese Communist Party since reform, but three decades of economic achievement have not bolstered the leadership’s political self-confidence, let alone their vision and courage for the inevitable reforms in political and ideological realms. The continued and omnipresent censorship and self-censorship in China’s intellectual arena, as well as the corrosive effects of corruption, fraud, and the temptations of material benefits in the academic and media sectors, contribute to further divisions among Chinese intellectuals, whose identity as such has already transformed beyond recognition. China’s global soft power and discourse power campaign may ultimately turn out to be a self-celebratory extravaganza bereft of real substance.