bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Development and Energy
Authors: Carley Sanya , Brown Adrienne , Lawrence Sara
Published: March 2012

Energy-based economic development (EBED) can provide economic, social, and environmental benefits, such as job creation, industry development, and alternative energy deployment. The United States has recently devoted substantial financial support to EBED efforts. Although early assessments of these efforts are promising, the discipline is at risk of becoming compromised or discredited. It lacks a basic framework, common definitions, and clear goals, which is problematic for a field that requires cross-disciplinary coordination and collaboration. Most EBED evaluation efforts take place before a project is underway; without enough postproject analyses, practitioners are left with unreliable impact estimates. Finally, like early-stage energy technologies themselves, EBED relies heavily on potentially unpredictable or inconsistent funding. These factors render many practitioners ill-equipped to effectively plan, implement, and evaluate specific EBED initiatives. This study offers a working definition, typical goals, and categories of approach with the aim to mitigate difficulties in communication and understanding across disciplines.
Research Methodology in Gaming
Authors: Mäyrä Frans , Holopainen Jussi , Jakobsson Mikael
Published: March 2012

Digital games have evolved into diverse forms, and they touch many different areas of life in contemporary society. When approached together with the associated playful and serious behaviors, they profit from several research methodologies. This collection of articles introduces a range of research methodologies and aims to promote interdisciplinary dialogue in the study of games.
Behavioral/Emotional Problems of Preschoolers
Authors: Rescorla Leslie A. , Achenbach Thomas M. , Ivanova Masha Y. , Bilenberg Niels , Bjarnadottir Gudrun , Denner Silvia , Dias Pedro , Dobrean Anca , Döpfner Manfred , Frigerio Alessandra , Gonçalves Miguel , Guðmundsson Halldór , Jusiene Roma , Kristensen Solvejg , Lecannelier Felipe , Leung Patrick W. L. , Liu Jianghong , Löbel Sofia P. , Machado Bárbara César , Markovic Jasminka , Mas Paola A. , Esmaeili Elaheh Mohammad , Montirosso Rosario , Plück Julia , Pronaj Adelina Ahmeti , Rodriguez Jorge T. , Rojas Pamela O. , Schmeck Klaus , Shahini Mimoza , Silva Jaime R. , van der Ende Jan , Verhulst Frank C.
Published: March 2012

This study tested societal effects on caregiver/teacher ratings of behavioral/emotional problems for 10,521 preschoolers from 15 societies. Many societies had problem scale scores within a relatively narrow range, despite differences in language, culture, and other characteristics. The small age and gender effects were quite similar across societies. The rank orders of mean item ratings were similar across diverse societies. For 7,380 children from 13 societies, ratings were also obtained from a parent. In all 13 societies, mean Total Problems scores derived from parent ratings were significantly higher than mean Total Problems scores derived from caregiver/teacher ratings, although the size of the difference varied somewhat across societies. Mean cross-informant agreement for problem scale scores varied across societies. Societies were very similar with respect to which problem items, on average, received high versus low ratings from parents and caregivers/teachers. Within every society, cross-informant agreement for item ratings varied widely across children. In most respects, results were quite similar across 15 very diverse societies.
Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease
Authors: Perron Hervé , Germi Raphaëlle , Bernard Corinne , Garcia-Montojo Marta , Deluen Cécile , Farinelli Laurent , Faucard Raphaël , Veas Francisco , Stefas Ilias , Fabriek Babs O , Van-Horssen Jack , Van-der-Valk Paul , Gerdil Claire , Mancuso Roberta , Saresella Marina , Clerici Mario , Marcel Sébastien , Creange Alain , Cavaretta Rosella , Caputo Domenico , Arru Giannina , Morand Patrice , Lang Alois B , Sotgiu Stefano , Ruprecht Klemens , Rieckmann Peter , Villoslada Pablo , Chofflon Michel , Boucraut Jose , Pelletier Jean , Hartung Hans-Peter
Published: March 2012

Background:

The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation.

Objective:

The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS.

Methods:

103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals.

Results:

Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors ( p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC ( p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.

Conclusion:

The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements.
Ending tolerance as a solution to incompatibility: The Danish ‘crisis of multiculturalism’
Authors: Hervik Peter
Published: March 2012

Successful integration must include the long-term enactment of ‘the will to feel Danish’. As Jews in Denmark have done in the course of many generations, so immigrant Muslims must immerse themselves to the extent that feeling Danish is naturalized. Such is the perspective proposed in a recent focus group discussion in Denmark on the integration of Muslims into Danish society. This idea of incompatibility between native Danes and Muslim ‘newcomers’ has become a salient feature of what is termed ‘value-based journalism’ and ‘value-based politics’ in the last decade. This article traces the origin of the ‘end of tolerance’ strategy, which follows from this development and examines the emergence of neo-racism in Denmark with its ideas of xenophobia as a natural reaction to other ‘cultures’ which do not belong ’naturally’. It shows that migrants of non-European origin are talked about in an increasingly crass and uncompromising way as a consequence of the belief in incompatibility.
Civilizing migrants: Integration, culture and citizenship
Authors: de Leeuw Marc , van Wichelen Sonja
Published: March 2012

On the brink of multiculturalism’s demise in Europe, ‘culture’ configures prominently in the immigration politics of Europe and its nation-states. New discourses of integration emphasize dominant values and norms and define civic membership through cultural commitment or loyalty. How is Europe doing integration, and what is integration doing to Europe? Taking its cues from the Dutch Integration Exam, this article analyses how ‘culture’ is paradigmatically disciplined upon new aspiring citizens. It argues that the citizenship test functions as a technique of governmentality that normalizes secular liberalism in its appropriation of the migrant Other. By employing cultural tropes of sexual freedom, gender equality, freedom of speech and individuality as emblems of Dutchness, integration is identified as the successful adaptation to hegemonic liberal and secular virtues, leaving little room for cultural or religious variations. By reflecting on the popularity of the Dutch model, the article assesses the paradoxes and tensions involved in thinking the citizen-subject within Europe.
The Effect of Parental Support on Juvenile Drug Court Completion and Postprogram Recidivism
Authors: Alarid Leanne Fiftal , Montemayor Carlos D. , Dannhaus Summer
Published: March 2012

Juvenile drug courts (JDCs) have grown exponentially in the last 15 years. JDCs typically require more parental participation than do other community correctional options as a source of social support for juveniles. Using official data and offender case files, this study examined client behavior and parental support through various phases to determine factors that contribute toward successful program completion and postprogram recidivism reduction. Family support was a significant predictor of both graduation and of postsupervision rearrest. Time spent in the drug court program and client age were additional predictors of rearrest, while less prior adjudications were an additional predictor of whether a youth would complete the drug court program. Policy implications to increase parental support are discussed.
Minimal clinically important differences in the Carpal Tunnel Questionnaire after carpal tunnel release
Authors: Kim J. K. , Jeon S. H.
Published: March 2012

Minimal clinically important difference is the smallest difference in the score of an outcome instrument that patients perceive as important. A prospective observational study was conducted involving 66 consecutive patients undergoing limited open carpal tunnel release. Patients completed the Carpal Tunnel Questionnaire (CTQ) before surgery and 3 months post-surgery. A transition item for patient satisfaction after 3 months of surgery was used as an anchor. Receiver operator characteristic curves were used to determine the minimal clinically important differences for the CTQ and its two subscales that best separated satisfied and unsatisfied patients. A 0.92 point change in the CTQ, a 1.14 point change in the symptom subscale, and a 0.74 point change in the function subscale indicated a clinically relevant threshold of satisfaction, and those values were greater than what could be accounted for by measurement errors.
The deleterious effects of exsanguination with a tight bandage on tourniquet tolerance in the upper arm
Authors: Tanpowpong T. , Kitidumrongsook P. , Patradul A.
Published: March 2012

Tourniquet tolerance is affected by the method of exsanguination. Two commonly used methods, tight elastic bandaging and limb elevation, were tested to determine their effects on upper extremity tourniquet tolerance in 23 healthy adult volunteers. We found that tourniquet tolerance was significantly lower among the bandaging group compared with the limb elevation group (average 19.4 min and 24.1 min, respectively). Overall, the tourniquet tolerance was not affected by hand dominance or arm circumference.
A new wonderland of Asian migration: Does symbolic politics trump utilitarian politics?
Authors: Jo Jung In
Published: March 2012

Despite the wave of scholarly enthusiasm over the rising number of foreigners and migrants in Korean society, the public’s side of the story has not been clearly articulated. Against this background, this article – guided by ideas of the symbolic politics and the utilitarian politics approaches – taps into survey data to fully investigate the demand side of determinants contributing to the popular disapproval of the rise of immigrants. Unlike other studies, this article finds that individual immigration preferences reflect multifaceted utilitarian calculus and symbolic predispositions. While affective orientations toward multiculturalism and assimilation ideology influence public attitudes toward immigration policy, scholars have downplayed utilitarian self-interest induced immigration attitudes. Ordered Logit analysis of 2003 Korean National Identity Survey data demonstrates a link between an individual’s utilitarian interests and immigration preference. This analysis suggests that concerns over job security drive negative attitudes regarding the increase of immigrant inflows. Low-skilled respondents are more likely to prefer restricting the rise of migrants. Second, perceived cultural threats are related to negative views toward newcomers. Those supporting multiculturalism are inclined to support increasing immigration. These findings suggest that the factors driving immigration preferences are multifaceted.
Treaty networks, nesting, and interstate cooperation: Russia, the FSU, and the CIS
Authors: Willerton John P , Slobodchikoff Michael O , Goertz Gary
Published: March 2012

Networks of treaties with treaty nesting, wherein treaties build upon, expand upon, or are grounded in preexisting treaties, are an increasingly important dimension of interstate cooperation. Focusing on relations within the area of the former Soviet Union (FSU), with special attention to both multilateral and bilateral arrangements between Russia and other FSU states, we illuminate treaty activism and regional cooperation among Commonwealth of Independent States (CIS) members in the security domain. Beyond an analysis of multilateral and bilateral CIS alliance agreements, we evaluate the more focused security arrangements of two FSU–CIS bilateral relationships: Russia–Turkmenistan and Russia–Georgia. We intentionally analyze these two complex and problematic bilateral relationships, where treaty activism and networks permitted the signatory states to address common security issues. The breakdown of the Russian–Georgian relationship with the August 2008 war should not obscure the significant conflict management efforts of the preceding decade and a half; efforts that were grounded in intensive treaty activity. Joined together, these CIS multilateral and focused bilateral relationships point to a treaty complex and architecture that partially manage the contrasting security interests of FSU states.
von Willebrand factor (VWF) propeptide binding to VWF D′D3 domain attenuates platelet activation and adhesion
Authors: Madabhushi Sri R. , Shang Chengwei , Dayananda Kannayakanahalli M. , Rittenhouse-Olson Kate , Murphy Mary , Ryan Thomas E. , Montgomery Robert R. , Neelamegham Sriram
Published: March 2012

Noncovalent association between the von Willebrand factor (VWF) propeptide (VWFpp) and mature VWF aids N-terminal multimerization and protein compartmentalization in storage granules. This association is currently thought to dissipate after secretion into blood. In the present study, we examined this proposition by quantifying the affinity and kinetics of VWFpp binding to mature VWF using surface plasmon resonance and by developing novel anti-VWF D′D3 mAbs. Our results show that the only binding site for VWFpp in mature VWF is in its D′D3 domain. At pH 6.2 and 10mM Ca2+, conditions mimicking intracellular compartments, VWFpp-VWF binding occurs with high affinity (KD = 0.2nM, koff = 8 × 10−5 s−1). Significant, albeit weaker, binding (KD = 25nM, koff = 4 × 10−3 s−1) occurs under physiologic conditions of pH 7.4 and 2.5mM Ca2+. This interaction was also observed in human plasma (KD = 50nM). The addition of recombinant VWFpp in both flow-chamber–based platelet adhesion assays and viscometer-based shear-induced platelet aggregation and activation studies reduced platelet adhesion and activation partially. Anti-D′D3 mAb DD3.1, which blocks VWFpp binding to VWF-D′D3, also abrogated platelet adhesion, as shown by shear-induced platelet aggregation and activation studies. Our data demonstrate that VWFpp binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GpIbα.
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function
Authors: Santoni de Sio Francesca R. , Massacand Joanna , Barde Isabelle , Offner Sandra , Corsinotti Andrea , Kapopoulou Adamandia , Bojkowska Karolina , Dagklis Antonis , Fernandez Marylise , Ghia Paolo , Thomas James H. , Pinschewer Daniel , Harris Nicola , Trono Didier
Published: March 2012

Chromatin remodeling is fundamental for B-cell differentiation. In the present study, we explored the role of KAP1, the cofactor of KRAB-ZFP transcriptional repressors, in this process. B-lymphoid–specific Kap1-KO mice displayed reduced numbers of mature B cells, lower steady-state levels of Abs, and accelerated rates of decay of neutralizing Abs after viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an up-regulation of PTEN, the enzymatic counteractor of PIK3 signaling, and of genes encoding DNA-damage response factors, cell-cycle regulators, and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to several of these genes and controlled chromatin status at their promoters. Genome wide, KAP1 binding sites lacked active B cell–specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. Our results therefore reveal the role of KRAB/KAP1–mediated epigenetic regulation in B-cell development and homeostasis.
Detecting disease-associated genes with confounding variable adjustment and the impact on genomic meta-analysis: With application to major depressive disorder
Authors: Wang Xingbin , Lin Yan , Song Chi , Sibille Etienne , Tseng George C
Published: March 2012

Background

Detecting candidate markers in transcriptomic studies often encounters difficulties in complex diseases, particularly when overall signals are weak and sample size is small. Covariates including demographic, clinical and technical variables are often confounded with the underlying disease effects, which further hampers accurate biomarker detection. Our motivating example came from an analysis of five microarray studies in major depressive disorder (MDD), a heterogeneous psychiatric illness with mostly uncharacterized genetic mechanisms.

Results

We applied a random intercept model to account for confounding variables and case-control paired design. A variable selection scheme was developed to determine the effective confounders in each gene. Meta-analysis methods were used to integrate information from five studies and post hoc analyses enhanced biological interpretations. Simulations and application results showed that the adjustment for confounding variables and meta-analysis improved detection of biomarkers and associated pathways.

Conclusions

The proposed framework simultaneously considers correction for confounding variables, selection of effective confounders, random effects from paired design and integration by meta-analysis. The approach improved disease-related biomarker and pathway detection, which greatly enhanced understanding of MDD neurobiology. The statistical framework can be applied to similar experimental design encountered in other complex and heterogeneous diseases.
Modulation of TTX-sensitive voltage-dependent Na+ channels by β-bungarotoxin in rat cerebellar neurons
Authors: Guo Da , Xiang Wei , Seebahn Angela , Becker Cord-Michael , Strauß Olaf
Published: March 2012

Background

The modulation of voltage-dependent Na+ channels by lipid metabolites such as arachidonic acid or eicosanoids plays a role in physiological functions as well as in degenerative diseases. So far TTX-resistant channels were found mainly to be regulated by lipid metabolites.

Results

We investigated the lipid-dependent modulation of TTX-sensitive (TTX-s) Na+ channels using β-bungarotoxin (β-BuTX, 10 pM), which has an intrinsic phospholipase-A2 activity, and indomethacin (10 μM), which blocks cyclooxygenase activity in primary cerebellar neurons. To investigate TTX-s Na+ channels, whole-currents were measured under K+-free conditions and blocked by 10 nM TTX. The currents resulting from calculating the difference of currents measured in the presence and the absence of TTX were used for further analysis. Application of indomethacin mainly changed the current kinetics but has only minor effects on voltage-dependence. In contrast β-BuTX increased the maximal current amplitude and shifted the voltage-dependent activation towards more negative potentials. The effects of β-BuTX were blocked by indomethacin. Analysis of lipid metabolites which accumulate by treatment with β-BuTX using MALDI-TOF MS showed an increase of cyclooxygenase reaction products in relation to arachidonic acid.

Conclusions

In summary, we conclude that TTX-sensitive Na+ channels can be directly modulated by cyclooxygenase reaction products leading to higher activity at less depolarized potentials and subsequent higher excitability of neurons. Since activation of cyclooxygenase is also involved in pathways leading to apoptotic cells death this could play a role in degenerative diseases of the CNS and highlights a possible protective effect of cyclooxygenase inhibition.
Rates of IUCD discontinuation and its associated factors among the clients of a social franchising network in Pakistan
Authors: Azmat Syed Khurram , Shaikh Babar Tasneem , Hameed Waqas , Bilgrami Mohsina , Mustafa Ghulam , Ali Muhammad , Ishaque Muhammad , Hussain Wajahat , Ahmed Aftab
Published: March 2012

Background

Modern Intrauterine contraceptive device (IUCD) is very safe, highly effective reversible and inexpensive family planning method which offers 5-10 years of protection against pregnancy. The contraceptive use in Pakistan has been merely 30% for over a decade with IUCD being the least used method. Higher discontinuation rates are documented in developing countries; however no such data is available for Pakistan. Marie Stopes Society (MSS) established a social franchise outlets network branded as 'SURAJ' (Sun) in Pakistan to provide quality family planning services. This study attempts to determine IUCD discontinuation rates and its associated risk factors. Using a semi-structured questionnaire, a cross-sectional study was conducted with 3000 clients who availed IUCD services from Suraj provider 6, 12 and 24 month back,. Data were analyzed in SPSS 17.0; adjusted prevalence ratios were calculated to see associations between discontinuation and its risk factors.

Case presentation

We found that 22.7% of the IUCD acceptors experienced some health problem; while the overall discontinuation rate was 18.9% with average time of usage of 7.4 (SD ± 5.8) months before discontinuation. Half of them showed health concerns (49.8%); of which a majority (70.2%) returned to Suraj provider for IUCD removal. Women living in Punjab, residing at a travelling time of 30-60 minutes and no previous use of contraceptive are more likely to discontinue IUCD. However, among total women 81.7% still expressed willingness to avail IUCD services from Suraj provider in future, if needed.

Conclusion

The findings suggest a need for training the providers and field workers to prevent early discontinuation of IUCD among the Suraj clients and by addressing the health concerns through proper counseling, continued follow-up and immediate medical aid/referral in case of complications.
Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system
Authors: Bottelbergs Astrid , Verheijden Simon , Van Veldhoven Paul P , Just Wilhelm , Devos Rita , Baes Myriam
Published: March 2012

Background

Mice with peroxisome deficiency in neural cells (Nestin-Pex5−/−)develop a neurodegenerative phenotype leading to motor and cognitive disabilities and early death. Major pathologies at the end stage of disease include severe demyelination, axonal degeneration and neuroinflammation. We now investigated the onset and progression of these pathological processes, and their potential interrelationship. In addition, the putative role of oxidative stress, the impact of plasmalogen depletion on the neurodegenerative phenotype, and the consequences of peroxisome elimination in the postnatal period were studied.

Methods

Immunohistochemistry in association with gene expression analysis was performed onNestin-Pex5−/−mice to document demyelination, axonal damage and neuroinflammation. AlsoGnpat−/−mice, with selective plasmalogen deficiency andCMV-Tx-Pex5−/−mice, with tamoxifen induced generalized loss of peroxisomes were analysed.

Results

Activation of the innate immune system is a very early event in the pathological process inNestin-Pex5−/−mice which evolves in chronic neuroinflammation. The complement factor C1q, one of the earliest up regulated transcripts, was expressed on neurons and oligodendrocytes but not on microglia. Transcripts of other pro- and anti-inflammatory genes and markers of phagocytotic activity were already significantly induced before detecting pathologies with immunofluorescent staining. Demyelination, macrophage activity and axonal loss co-occurred throughout the brain. As in patients with mild peroxisome biogenesis disorders who develop regressive changes, demyelination in cerebellum and brain stem preceded major myelin loss in corpus callosum of bothNestin-Pex5−/−andCMV-Tx-Pex5−/−mice. These lesions were not accompanied by generalized oxidative stress throughout the brain. AlthoughGnpat−/−mice displayed dysmyelination and Purkinje cell axon damage in cerebellum, confirming previous observations, no signs of inflammation or demyelination aggravating with age were observed.

Conclusions

Peroxisome inactivity triggers a fast neuroinflammatory reaction, which is not solely due to the depletion of plasmalogens. In association with myelin abnormalities this causes axon damage and loss.
Tailored enrichment strategy detects low abundant small noncoding RNAs in HIV-1 infected cells
Authors: Althaus Claudia F , Vongrad Valentina , Niederöst Barbara , Joos Beda , Di Giallonardo Francesca , Rieder Philip , Pavlovic Jovan , Trkola Alexandra , Günthard Huldrych F , Metzner Karin J , Fischer Marek
Published: March 2012

Background

The various classes of small noncoding RNAs (sncRNAs) are important regulators of gene expression across divergent types of organisms. While a rapidly increasing number of sncRNAs has been identified over recent years, the isolation of sncRNAs of low abundance remains challenging. Virally encoded sncRNAs, particularly those of RNA viruses, can be expressed at very low levels. This is best illustrated by HIV-1 where virus encoded sncRNAs represent approximately 0.1-1.0% of all sncRNAs in HIV-1 infected cells or were found to be undetected. Thus, we applied a novel, sequence targeted enrichment strategy to capture HIV-1 derived sncRNAs in HIV-1 infected primary CD4+ T-lymphocytes and macrophages that allows a greater than 100-fold enrichment of low abundant sncRNAs.

Results

Eight hundred and ninety-two individual HIV-1 sncRNAs were cloned and sequenced from nine different sncRNA libraries derived from five independent experiments. These clones represent up to 90% of all sncRNA clones in the generated libraries. Two hundred and sixteen HIV-1 sncRNAs were distinguishable as unique clones. They are spread throughout the HIV-1 genome, however, forming certain clusters, and almost 10% show an antisense orientation. The length of HIV-1 sncRNAs varies between 16 and 89 nucleotides with an unexpected peak at 31 to 50 nucleotides, thus, longer than cellular microRNAs or short-interfering RNAs (siRNAs). Exemplary HIV-1 sncRNAs were also generated in cells infected with different primary HIV-1 isolates and can inhibit HIV-1 replication.

Conclusions

HIV-1 infected cells generate virally encoded sncRNAs, which might play a role in the HIV-1 life cycle. Furthermore, the enormous capacity to enrich low abundance sncRNAs in a sequence specific manner highly recommends our selection strategy for any type of investigation where origin or target sequences of the sought-after sncRNAs are known.
Variation in metabolic responses to meal challenges differing in glycemic index in healthy women: Is it meaningful?
Authors: Krishnan Sridevi , Newman John W , Hembrooke Tara A , Keim Nancy L
Published: March 2012

Background

Established clinical tests are commonly used in disease diagnosis, but tools that enhance identification of metabolic dysfunctions are needed. This study was conducted to identify typical and atypical metabolite temporal patterns in response to paired meal challenge tests.

Design

Metabolic responses to high and low glycemic index (GI) meals were tested in 24 healthy pre-menopausal women, aged 20-50 y, with BMI of 25-30 kg/m2 using a cross-over design. On test days, blood glucose, insulin, leptin and non-esterified fatty acids were measured after an overnight fasting, and for 8 h following test meal consumption. The data were range scaled, and multivariate statistics were used to assess the presence of distinct response groups to the meal challenge tests.

Results

As expected, participants showed higher circulating glucose and insulin in response to the high GI compared to the low GI meal challenge. However, using range-scaling and Principal Component Analysis, three distinct groups were identified based on differential responses to the paired challenges. Members of the most populated group (n = 18) displayed little deviation from the expected response to the two meal challenges. Two minor groups (n = 3/group) with distinct responses were observed, one suggestive of sub-clinical insulin resistance, and the other suggestive of hyperleptinemia.

Conclusions

The differential responses of glucose, insulin and leptin to low and high glycemic test meals revealed three response groups. Dietary intervention studies traditionally evaluate group responses, and aim to identify the overall effect in the population studied. In contrast, our study analyzed the variance in the meal challenge responses, using an integrated physiological approach, rather than a reductionist approach. This phenotyping approach may be useful for detecting subclinical metabolic dysfunctions, and it could contribute to improved personalized nutrition management. This study is registered in ClinicalTrials.gov, record #200210295
The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas
Authors: Xu Xiaoming , Jin Huiying , Liu Yafang , Liu Li , Wu Qiong , Guo Yaxiong , Yu Lina , Liu Zhijing , Zhang Ting , Zhang Xiaowei , Dong Xueyan , Quan Chengshi
Published: March 2012

Background

Claudin-6 is a candidate tumor suppressor gene in breast cancer, and has been shown to be regulated by DNA methylation and histone modification in breast cancer lines. However, the expression of claudin-6 in breast invasive ductal carcinomas and correlation with clinical behavior or expression of other markers is unclear. We considered that the expression pattern of claudin-6 might be related to the expression of DNA methylation associated proteins (methyl-CpG binding protein 2 (MeCP2) and DNA methyltransferase 1 (DNMT1)) and histone modification associated proteins (histone deacetylase 1 (HDAC1), acetyl-histone H3 (H3Ac) and acetyl- histone H4 (H4Ac)).

Methods

We have investigated the expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using immunohistochemistry.

Results

Claudin-6 protein expression was reduced in breast invasive ductal carcinomas (P< 0.001). In contrast, expression of MeCP2 (P< 0.001), DNMT1 (P= 0.001), HDAC1 (P< 0.001) and H3Ac (P= 0.004) expressions was increased. Claudin-6 expression was inversely correlated with lymph node metastasis (P= 0.021). Increased expression of HDAC1 was correlated with histological grade (P< 0.001), age (P= 0.004), clinical stage (P= 0.007) and lymph node metastasis (P= 0.001). H3Ac expression was associated with tumor size (P= 0.044) and clinical stage of cancers (P= 0.034). MeCP2, DNMT1 and H4Ac expression levels did not correlate with any of the tested clinicopathological parameters (P> 0.05). We identified a positive correlation between MeCP2 protein expression and H3Ac and H4Ac protein expression.

Conclusions

Our results show that claudin-6 protein is significantly down-regulated in breast invasive ductal carcinomas and is an important correlate with lymphatic metastasis, but claudin-6 down-regulation was not correlated with upregulation of the methylation associated proteins (MeCP2, DNMT1) or histone modification associated proteins (HDAC1, H3Ac, H4Ac). Interestingly, the expression of MeCP2 was positively correlated with the expression of H3Ac and H3Ac protein expression was positively correlated with the expression of H4Ac in breast invasive ductal carcinoma

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4549669866581452
Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease
Authors: Cabeza Carolina , Figueroa Alicia , Lazo Oscar M , Galleguillos Carolina , Pissani Claudia , Klein Andrés , Gonzalez-Billault Christian , Inestrosa Nibaldo C , Alvarez Alejandra R , Zanlungo Silvana , Bronfman Francisca C
Published: March 2012

Background

Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC) disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i) NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF) after axotomy and ii) PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF.

Results

NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT), whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A.

Conclusions

Our results suggest that the NPC cellular phenotype causes neuronal dysfunction through the abnormal up-regulation of survival pathways, which causes the perturbation of signaling cascades and anomalous phosphorylation of the cytoskeleton.
Microbial community analysis in biocathode microbial fuel cells packed with different materials
Authors: Sun Yanmei , Wei Jincheng , Liang Peng , Huang Xia
Published: March 2012

Biocathode MFCs using microorganisms as catalysts have important advantages in lowering cost and improving sustainability. Electrode materials and microbial synergy determines biocathode MFCs performance. In this study, four materials, granular activated carbon (GAC), granular semicoke (GS), granular graphite (GG) and carbon felt cube (CFC) were used as packed cathodic materials. The microbial composition on each material and its correlation with the electricity generation performance of MFCs were investigated. Results showed that different biocathode materials had an important effect on the type of microbial species in biocathode MFCs. The microbes belonging to Bacteroidetes and Proteobacteria were the dominant phyla in the four materials packed biocathode MFCs. Comamonas of Betaproteobacteria might play significant roles in electron transfer process of GAC, GS and CFC packed biocathode MFCs, while in GG packed MFC Acidovorax may be correlated with power generation. The biocathode materials also had influence on the microbial diversity and evenness, but the differences in them were not positively related to the power production.
Neuronal nitric oxide synthase regulates endothelial inflammation
Authors: Chakrabarti Subhadeep , Chan Carmen K , Jiang Yanyan , Davidge Sandra T
Published: March 2012

NO, produced by the endothelium, is a modulator of vascular inflammation. Traditionally, eNOS was believed to be the primary source of NO in the endothelium. However, recent data suggest an important role for nNOS in the endothelium, although little is known about factors regulating this novel eNOS. We examined the localization, regulation, and significance of endothelial nNOS in this study. Primary HUVECs were used as a model system. Inflammatory changes were induced by stimulation with TNF. We report that unlike eNOS, nNOS is predominantly localized to the nucleus of resting endothelial cells. This nNOS also contributed to basal NO production in the resting endothelium. Ablation of endothelial nNOS by pharmacological inhibition (using L-NPA) or siRNA further enhanced cytokine-mediated inflammatory responses, such as up-regulation of VCAM-1 and proinflammatory cytokines, as well as increased leukocyte recruitment. Based on these findings, we suggest a potential anti-inflammatory role of endothelial nNOS that can attenuate unopposed, proinflammatory cytokine actions. Our data indicate a novel location and an immunoregulatory role for nNOS in the endothelium.
The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
Authors: Yamamoto Mako , Matsuzaki Tomoko , Takahashi Rei , Adachi Eijiro , Maeda Yasuhiro , Yamaguchi Sachiyo , Kitayama Hitoshi , Echizenya Michiko , Morioka Yoko , Alexander David B. , Yagi Takeshi , Itohara Shigeyoshi , Nakamura Takashi , Akiyama Haruhiko , Noda Makoto
Published: March 2012

The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI
Authors: Pearce T , Philip S , Brown J , Koh D M , Burn P R
Published: March 2012

Objectives: The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies.

Methods: 44 whole-body MRI scans were reviewed retrospectively (coronal T  1 weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T  1 weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group.

Results: In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587).

Conclusion: Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection.
Transient CPEB dimerization and translational control
Authors: Lin Chien-Ling , Huang Yen-Tsung , Richter Joel D.
Published: March 2012

During oocyte development, the cytoplasmic polyadenylation element-binding protein (CPEB) nucleates a set of factors on mRNA that controls cytoplasmic polyadenylation and translation. The regulation of polyadenylation is mediated in part through serial phosphorylations of CPEB, which control both the dynamic integrity of the cytoplasmic polyadenylation apparatus and CPEB stability, events necessary for meiotic progression. Because the precise stoichiometry between CPEB and CPE-containing RNA is responsible for the temporal order of mRNA polyadenylation during meiosis, we hypothesized that, if CPEB production exceeded the amount required to bind mRNA, the excess would be sequestered in an inactive form. One attractive possibility for the sequestration is protein dimerization. We demonstrate that not only does CPEB form a dimer, but dimerization requires its RNA-binding domains. Dimer formation prevents CPEB from being UV cross-linked to RNA, which establishes a second pool of CPEB that is inert for polyadenylation and translational control. During oocyte maturation, the dimers are degraded much more rapidly than the CPEB monomers, due to their greater affinity for polo-like kinase 1 (plx1) and the ubiquitin E3 ligase β-TrCP. Because dimeric CPEB also binds cytoplasmic polyadenylation factors with greater affinity than monomeric CPEB, it may act as a hub or reservoir for the polyadenylation machinery. We propose that the balance between CPEB and its target mRNAs is maintained by CPEB dimerization, which inactivates spare proteins and prevents them from inducing polyadenylation of RNAs with low affinity binding sites. In addition, the dimers might serve as molecular hubs that release polyadenylation factors for translational activation upon CPEB dimer destruction.
Proteomics in the Classroom: An Investigative Study of Proteins in Microorganisms
Authors: Benskin Jon , Chen Sixue
Published: March 2012

As advances in biotechnology and molecular biology rapidly expand in research settings, it is vital that we continue to prepare high school students to enter and thrive in those modern laboratories. This multistep, inquiry-based lab describes highly adaptable methods to teach students not only current molecular techniques and technologies, but also about proteomics and microorganisms. Students participate in protein extraction, gel electrophoresis, mass spectrometry, and data analysis to identify proteins present in microorganisms.
Proteomics: Protein Identification Using Online Databases
Authors: Eurich Chris , Fields Peter A. , Rice Elizabeth
Published: March 2012

Proteomics is an emerging area of systems biology that allows simultaneous study of thousands of proteins expressed in cells, tissues, or whole organisms. We have developed this activity to enable high school or college students to explore proteomic databases using mass spectrometry data files generated from yeast proteins in a college laboratory course. Students upload files of “unknown” proteins from our public website, enter them into a proteomics search engine (Mascot), identify the proteins, and use additional proteomics websites to learn about their functions and three-dimensional structures. This activity is suitable for use in units exploring protein structure and function, metabolism, or bioinformatics.
Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up
Authors: Olsson D S , Buchfelder M , Wiendieck K , Kremenevskaja N , Bengtsson B-Å , Jakobsson K-E , Jarfelt M , Johannsson G , Nilsson A G
Published: March 2012

Objective

Most patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT.

Design

Case–control study.

Patients and methods

The criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT).

Results

The 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, <0.001) and residual tumour (3.2, <0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group.

Conclusions

In patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.
Luteal maintenance of pregnancy in the African elephant (Loxodonta africana)
Authors: Stansfield F J , Allen W R
Published: March 2012

The ovaries of eight African elephant foetuses and their mothers between 2 and 22 months of gestation, and those of two cycling and two lactating elephants, were examined grossly, histologically and immunocytochemically, with emphasis on the development and regression of accessory corpora lutea (CL) of pregnancy and the steroidogenic capacities of the accessory CL and the foetal ovaries. The results supported recent findings that the accessory CL form as a result of luteinisation, with and without ovulation, of medium-sized follicles during the 3-week inter-luteal period of the oestrous cycle. They enlarge significantly and become steroidogenically active around 5 weeks of gestation, probably in response to the placental lactogen which is secreted by the implanting trophoblast of the conceptus. The large luteal cells stained strongly for 3β hydroxysteroid dehydrogenase (3βHSD) activity throughout the 22-month gestation period although they showed vacuolation and other degenerative changes in the final months of gestation coincident with hypertrophy and hyperplasia of 3βHSD-positive interstitial cells in the foetal gonads. It is proposed that the progestagens secreted by the enlarged gonads of the elephant foetus may function both to assist the maternal ovaries in supporting the pregnancy state and to induce torpor and intrauterine immobility of the rapidly growing foetus.