bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of Employed Parents About Early Childhood Obesity and the Need for Prevention Strategies
Authors: Morin Pascale , Roy Marie-Andrée
Published: December 2011

Responses to the increased prevalence of childhood obesity are merging, and employed parents will become targets for strategies designed to prevent childhood obesity. This study aimed at describing their perceptions of employed parents about childhood obesity and determining which prevention strategies they would need the most. In this cross-sectional study, 504 employed parents were recruited from 33 child care centers in Sherbrooke (Quebec, Canada) who completed a self-administered questionnaire on their perceptions about childhood obesity and the need for prevention strategies. Logistic regression was used to explore differences in needs for prevention strategies according to participant characteristics. Most participants were female, aged 32.9 ± 4.9 years, and perceived childhood obesity was an important problem. The prevention strategies that seemed most needed were the implementation of (a) physical and nutrition education programs in child care settings and (b) measures that give employed parents more time to cook for and be physically active with their children. Support for specific strategies differed across genders and education levels. Moreover, they depended on the perceived relationship between work and meal preparation. Policy makers should be aware of the needs of employed parents to develop policies that would have the greatest likelihood of success in this population.
Treatment and management of pseudogout: insights for the clinician
Authors: MacMullan Paul , McCarthy Geraldine
Published: December 2011

Pseudogout and the associated calcium pyrophosphate dihydrate (CPPD)- crystal-related arthropathies are common conditions that present particular management problems in clinical practice as they often affect older patients with multiple medical comorbidities. The epidemiology, metabolic and endocrine disease associations, and routine investigations used in the diagnostic workup are briefly reviewed. Current treatment approaches that are mainly directed at relieving the symptoms of joint inflammation are outlined. Unlike gout, there are no agents available that have been shown to decrease crystal load in CPPD-related joint disease. Recent novel insights into the pathogenesis of crystal-induced joint inflammation and subsequent joint degeneration are also discussed. The potential of colchicine as a prophylactic agent in managing recurrent attacks and the likely mechanisms of its effects on the NACHT, LRR and PYD domains-containing protein 3 (NALP-3) inflammasome of the innate immune system are highlighted. The use of agents that directly target the inflammasome, in particular drugs which inhibit the interleukin 1 pathway, in the treatment of severe, refractory pseudogout is also discussed. Finally, there is particular emphasis on the likely pathogenic role of CPPD crystal deposition in degenerative joint disease and the use of targeted anticrystal therapies as potential disease-modifying drugs.
Learning the structure of gene regulatory networks from time series gene expression data
Authors: Li Haoni , Wang Nan , Gong Ping , Perkins Edward J , Zhang Chaoyang
Published: December 2011

Background

Dynamic Bayesian Network (DBN) is an approach widely used for reconstruction of gene regulatory networks from time-series microarray data. Its performance in network reconstruction depends on a structure learning algorithm. REVEAL (REVerse Engineering ALgorithm) is one of the algorithms implemented for learning DBN structure and used to reconstruct gene regulatory networks (GRN). However, the two-stage temporal Bayes network (2TBN) structure of DBN that specifies correlation between time slices cannot be obtained by score metrics used in REVEAL.

Methods

In this paper, we study a more sophisticated score function for DBN first proposed by Nir Friedman for stationary DBNs structure learning of both initial and transition networks but has not yet been used for reconstruction of GRNs. We implemented Friedman's Bayesian Information Criterion (BIC) score function, modified K2 algorithm to learn Dynamic Bayesian Network structure with the score function and tested the performance of the algorithm for GRN reconstruction with synthetic time series gene expression data generated by GeneNetWeaver and real yeast benchmark experiment data.

Results

We implemented an algorithm for DBN structure learning with Friedman's score function, tested it on reconstruction of both synthetic networks and real yeast networks and compared it with REVEAL in the absence or presence of preprocessed network generated by Zou&Conzen's algorithm. By introducing a stationary correlation between two consecutive time slices, Friedman's score function showed a higher precision and recall than the naive REVEAL algorithm.

Conclusions

Friedman's score metrics for DBN can be used to reconstruct transition networks and has a great potential to improve the accuracy of gene regulatory network structure prediction with time series gene expression datasets.
Functional complementation between transcriptional methylation regulation and post-transcriptional microRNA regulation in the human genome
Authors: Su Zhixi , Xia Junfeng , Zhao Zhongming
Published: December 2011

Background

DNA methylation in the 5' promoter regions of genes and microRNA (miRNA) regulation at the 3' untranslated regions (UTRs) are two major epigenetic regulation mechanisms in most eukaryotes. Both DNA methylation and miRNA regulation can suppress gene expression and their corresponding protein product; thus, they play critical roles in cellular processes. Although there have been numerous investigations of gene regulation by methylation changes and miRNAs, there is no systematic genome-wide examination of their coordinated effects in any organism.

Results

In this study, we investigated the relationship between promoter methylation at the transcription level and miRNA regulation at the post-transcription level by taking advantage of recently released human methylome data and high quality miRNA and other gene annotation data. We found methylation level in the promoter regions and expression level was negatively correlated. Then, we showed that miRNAs tended to target the genes with a low DNA methylation level in their promoter regions. We further demonstrated that this observed pattern was not attributed to the gene expression level, expression broadness, or the number of transcription factor binding sites. Interestingly, we found miRNA target sites were significantly enriched in the genes located in differentially methylated regions or partially methylated domains. Finally, we explored the features of DNA methylation and miRNA regulation in cancer genes and found cancer genes tended to have low methylation level and more miRNA target sites.

Conclusion

This is the first genome-wide investigation of the combined regulation of gene expression. Our results supported a complementary regulation between DNA methylation (transcriptional level) and miRNA function (post-transcriptional level) in the human genome. The results were helpful for our understanding of the evolutionary forces towards organisms' complexity beyond traditional sequence level investigation.
Protease-associated cellular networks in malaria parasite Plasmodium falciparum
Authors: Lilburn Timothy G , Cai Hong , Zhou Zhan , Wang Yufeng
Published: December 2011

Background

Malaria continues to be one of the most severe global infectious diseases, responsible for 1-2 million deaths yearly. The rapid evolution and spread of drug resistance in parasites has led to an urgent need for the development of novel antimalarial targets. Proteases are a group of enzymes that play essential roles in parasite growth and invasion. The possibility of designing specific inhibitors for proteases makes them promising drug targets. Previously, combining a comparative genomics approach and a machine learning approach, we identified the complement of proteases (degradome) in the malaria parasitePlasmodium falciparumand its sibling species [1–3], providing a catalog of targets for functional characterization and rational inhibitor design. Network analysis represents another route to revealing the role of proteins in the biology of parasites and we use this approach here to expand our understanding of the systems involving the proteases ofP. falciparum.

Results

We investigated the roles of proteases in the parasite life cycle by constructing a network using protein-protein association data from the STRING database [4], and analyzing these data, in conjunction with the data from protein-protein interaction assays using the yeast 2-hybrid (Y2H) system [5], blood stage microarray experiments [6–8], proteomics [9–12], literature text mining, and sequence homology analysis. Seventy-seven (77) out of 124 predicted proteases were associated with at least one other protein, constituting 2,431 protein-protein interactions (PPIs). These proteases appear to play diverse roles in metabolism, cell cycle regulation, invasion and infection. Their degrees of connectivity (i.e., connections to other proteins), range from one to 143. The largest protease-associated sub-network is the ubiquitin-proteasome system which is crucial for protein recycling and stress response. Proteases are also implicated in heat shock response, signal peptide processing, cell cycle progression, transcriptional regulation, and signal transduction networks.

Conclusions

Our network analysis of proteases fromP. falciparumuses a so-called guilt-by-association approach to extract sets of proteins from the proteome that are candidates for further study. Novel protease targets and previously unrecognized members of the protease-associated sub-systems provide new insights into the mechanisms underlying parasitism, pathogenesis and virulence.
Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation
Authors: Chambers Anne E , Nayini Krishnaveni P , Mills Walter E , Lockwood Gillian M , Banerjee Subhasis
Published: December 2011

Background

Successful pregnancy via in vitro fertilization (IVF) depends on the recovery of an adequate number of healthy oocytes and on blastocyst implantation following uterine transfer. Two hormones, LH and hCG, utilize a common LH/hCG receptor (LHCGR), variations in which have profound implications in human reproduction. Soluble LHCGR (sLHCGR) is released from experimental cell lines and placental explants and it can be detected in the follicular fluid and serum.

Methods

To evaluate the impact of circulating soluble LHCGR (sLHCGR) in fertility treatment, we measured sLHCGR and LH-sLHCGR complex in serum from women seeking IVF using specifically developed quantitative enzyme-linked immunosorbent assays (ELISA). Following an IVF cycle of treatment, patients were grouped according to oocyte yield into low (lower than or equal to 7 oocytes), intermediate (8-14 oocytes) and high (greater than or equal to 15 oocytes) responders and pregnancy outcome noted.

Results

Pre-treatment sLHCGR identified many women at risk of ovarian hyperstimulation. Low levels of sLHCGR were associated with pregnancy in both high and low responders but sLHCGR did not significantly affect the treatment outcome of intermediate responders. Low responders who failed to become pregnant had high levels of circulating sLHCGR bound to LH (LH-sLHCGR).

Conclusions

Pre-treatment measurement of sLHCGR could be used to tailor individual fertility treatment programs and improve outcomes by avoiding ovarian hyperstimulation and poor embryo implantation.
Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice
Authors: Salem Mohammad , Mony Jyothi T , Løbner Morten , Khorooshi Reza , Owens Trevor
Published: December 2011

Background

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with unknown etiology. Interferon-β (IFN-β), a member of the type I IFN family, is used as a therapeutic for MS and the IFN signaling pathway is implicated in MS susceptibility. Interferon regulatory factor 7 (IRF7) is critical for the induction and positive feedback regulation of type I IFN. To establish whether and how endogenous type I IFN signaling contributes to disease modulation and to better understand the underlying mechanism, we examined the role of IRF7 in the development of MS-like disease in mice.

Methods

The role of IRF7 in development of EAE was studied by immunizing IRF7-KO and C57BL/6 (WT) mice with myelin oligodendrocyte glycoprotein using a standard protocol for the induction of EAE. We measured leukocyte infiltration and localization in the CNS using flow cytometric analysis and immunohistochemical procedures. We determined levels of CD3 and selected chemokine and cytokine gene expression by quantitative real-time PCR.

Results

IRF7 gene expression increased in the CNS as disease progressed. IRF7 message was localized to microglia and infiltrating leukocytes. Furthermore, IRF7-deficient mice developed more severe disease. Flow cytometric analysis showed that the extent of leukocyte infiltration into the CNS was higher in IRF7-deficient mice with significantly higher number of infiltrating macrophages and T cells, and the distribution of infiltrates within the spinal cord was altered. Analysis of cytokine and chemokine gene expression by quantitative real-time PCR showed significantly greater increases in CCL2, CXCL10, IL-1β and IL17 gene expression in IRF7-deficient mice compared with WT mice.

Conclusion

Together, our findings suggest that IRF7 signaling is critical for regulation of inflammatory responses in the CNS.
Generation of recombinant Orfvirus using an enhanced green fluorescent protein reporter gene as a selectable marker
Authors: Ning Zhangyong , Peng Yongzheng , Hao Wenbo , Duan Chaohui , Rock Daniel L , Luo Shuhong
Published: December 2011

Background

Reporter genes are often used as a selectable marker for generation of recombinant viruses in order to investigate the mechanism of pathogenesis and to obtain candidate vaccine viruses. Routine selection of the recombinant parapoxvirus is time-consuming and labor intensive. Therefore, developing a novel method for selection is critical.

Results

In this study, we developed a rapid method to generate recombinant Orf viruses (ORFV) based on the enhanced green fluorescent protein (EGFP) reporter gene as a selectable marker. The coding sequence of EGFP gene was amplified from pEGFP-N1 vector and subcloned into the pZIPPY-neo/gus plasmid under the control of the early-late vaccinia virus (VACV) VV7.5 promoter and flanked by two multiple cloning sites (MCS) to generate a novel transfer vector pSPV-EGFP. Using the pSPV-EGFP, two recombination cassettes pSPV-113LF-EGFP-113RF and pSPV-116LF-EGFP-116RF were constructed by cloning the flanking regions of the ORFV113 and ORFV116 and inserted into two MCS flanking the EGFP gene. Using this novel system, two single gene deletion mutants OV-IA82Δ113 and OV-IA82Δ116 were successfully generated.

Conclusions

This approach shortens the time needed to generate recombinant ORFVs (rORFVs). Thus, the pSPV-EGFP vector provides a direct, fast, and convenient way to manipulate the recombinant viruses, indicating that it is highly suited for its designed purpose.
Ovarian vein thrombosis mimicking acute abdomen: a case report and literature review
Authors: Arkadopoulos Nikolaos , Dellaportas Dionysios , Yiallourou Anneza , Koureas Andreas , Voros Dionysios
Published: December 2011

Background

Ovarian vein thrombosis (OVT) is a rare, but serious condition that affects mostly postpartum women. A high index of suspicion is required in order to diagnose this unusual cause of abdominal pain.

Case presentation

A 19-year-old woman at three days postpartum was admitted to our hospital because of severe right lower quandrant abdominal pain and fever 38.5'C. Physical examination revealed an acutely ill patient and right lower quadrant tenderness with positive rebound and Giordano signs. The patient underwent appendectomy which proved to be negative for acute appendicitis. Postoperatively fever and pain persisted and abdominal CT-scan with intravenous contrast agent demonstrated a thrombosed right ovarian vein. The patient was initiated on low-molecular weight heparin (LMWH) and antibiotic treatment and a month later a new abdominal CT-scan showed a patent right ovarian vein.

Discussion

Pathophysiologically, OVT is explained by Virchow's triad, because pregnancy is associated with a hypercoagulable state, venous stasis due to compression of the inferior vena cava by the uterus and endothelial trauma during delivery or from local inflammation. Common symptoms and signs of OVT include lower abdomen or flank pain, fever and leukocytosis usually within the first ten days after delivery. The reported incidence of OVT ranges 0,05-0,18% of pregnancies and in most cases the right ovarian vein is the one affected. Anticoagulation and antibiotics is the mainstay of treatment of OVT. Complications of OVT include sepsis, extension of the thrombus to the inferior vena cava and renal veins, and pulmonary embolism. The incidence of pulmonary embolism is reported to be 13.2% and represents the main source of mortality due to OVT.

Conclusions

OVT is a rare condition, usually in the postpartum period. A high index of suspicion is required for the prompt diagnosis and management especially in cases that mimic acute abdomen.
5'UTR mutations of ENG cause hereditary hemorrhagic telangiectasia
Authors: Damjanovich Kristy , Langa Carmen , Blanco Francisco J , McDonald Jamie , Botella Luisa M , Bernabeu Carmelo , Wooderchak-Donahue Whitney , Stevenson David A , Bayrak-Toydemir Pinar
Published: December 2011

Background

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by epistaxis, arteriovenous malformations, and telangiectases. The majority of the patients have a mutation in the coding region of the activin A receptor type II-like 1 (ACVRL1) or Endoglin (ENG) gene. However, in approximately 15% of cases, sequencing analysis and deletion/duplication testing fail to identify mutations in the coding regions of these genes. Knowing its vital role in transcription and translation control, we were prompted to investigate the 5'untranslated region (UTR) of ENG.

Methods and Results

We sequenced the 5'UTR of ENG for 154 HHT patients without mutations in ENG or ACVRL1 coding regions. We found a mutation (c.-127C > T), which is predicted to affect translation initiation and alter the reading frame of endoglin. This mutation was found in a family with linkage to the ENG, as well as in three other patients, one of which had an affected sibling with the same mutation. In vitro expression studies showed that a construct with the c.-127C > T mutation alters the translation and decreases the level of the endoglin protein. In addition, a c.-9G > A mutation was found in three patients, one of whom was homozygous for this mutation. Expression studies showed decreased protein levels suggesting that the c.-9G > A is a hypomorphic mutation.

Conclusions

Our results emphasize the need for the inclusion of the 5'UTR region of ENG in clinical testing for HHT.
Leveraging social networks for understanding the evolution of epidemics
Authors: Martín Gonzalo , Marinescu Maria-Cristina , Singh David E , Carretero Jesús
Published: December 2011

Background

To understand how infectious agents disseminate throughout a population it is essential to capture the social model in a realistic manner. This paper presents a novel approach to modeling the propagation of the influenza virus throughout a realistic interconnection network based on actual individual interactions which we extract from online social networks. The advantage is that these networks can be extracted from existing sources which faithfully record interactions between people in their natural environment. We additionally allow modeling the characteristics of each individual as well as customizing his daily interaction patterns by making them time-dependent. Our purpose is to understand how the infection spreads depending on the structure of the contact network and the individuals who introduce the infection in the population. This would help public health authorities to respond more efficiently to epidemics.

Results

We implement a scalable, fully distributed simulator and validate the epidemic model by comparing the simulation results against the data in the 2004-2005 New York State Department of Health Report (NYSDOH), with similar temporal distribution results for the number of infected individuals. We analyze the impact of different types of connection models on the virus propagation. Lastly, we analyze and compare the effects of adopting several different vaccination policies, some of them based on individual characteristics -such as age- while others targeting the super-connectors in the social model.

Conclusions

This paper presents an approach to modeling the propagation of the influenza virus via a realistic social model based on actual individual interactions extracted from online social networks. We implemented a scalable, fully distributed simulator and we analyzed both the dissemination of the infection and the effect of different vaccination policies on the progress of the epidemics. The epidemic values predicted by our simulator match real data from NYSDOH. Our results show that our simulator can be a useful tool in understanding the differences in the evolution of an epidemic within populations with different characteristics and can provide guidance with regard to which, and how many, individuals should be vaccinated to slow down the virus propagation and reduce the number of infections.
An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver
Authors: Xie Linglin , Weichel Brent , Ohm Joyce Ellen , Zhang Ke
Published: December 2011

Background

Many groups, including our own, have proposed the use of DNA methylation profiles as biomarkers for various disease states. While much research has been done identifying DNA methylation signatures in cancer vs. normal etc., we still lack sufficient knowledge of the role that differential methylation plays during normal cellular differentiation and tissue specification. We also need thorough, genome level studies to determine the meaning of methylation of individual CpG dinucleotides in terms of gene expression.

Results

In this study, we compiled unique DNA methylation signatures from normal human heart, lung, and kidney using the Illumina Infinium 27K methylation arrays and compared those to gene expression by RNA sequencing. We have identified unique signatures of global DNA methylation for human heart, kidney and liver, and showed that DNA methylation data can be used to correctly classify various tissues. It indicates that DNA methylation reflects tissue specificity and may play an important role in tissue differentiation. The integrative analysis of methylation and RNA-Seq data showed that gene methylation and its transcriptional levels were comprehensively correlated. The location of methylation markers in terms of distance to transcription start site and CpG island showed no effects on the regulation of gene expression by DNA methylation in normal tissues.

Conclusions

This study showed that an integrative analysis of methylation array and RNA-Seq data can be utilized to discover the global regulation of gene expression by DNA methylation and suggests that DNA methylation plays an important role in normal tissue differentiation via modulation of gene expression.
An integrated proteomics analysis of bone tissues in response to mechanical stimulation
Authors: Li Jiliang , Zhang Fan , Chen Jake Y
Published: December 2011

Bone cells can sense physical forces and convert mechanical stimulation conditions into biochemical signals that lead to expression of mechanically sensitive genes and proteins. However, it is still poorly understood how genes and proteins in bone cells are orchestrated to respond to mechanical stimulations. In this research, we applied integrated proteomics, statistical, and network biology techniques to study proteome-level changes to bone tissue cells in response to two different conditions, normal loading and fatigue loading. We harvested ulna midshafts and isolated proteins from the control, loaded, and fatigue loaded Rats. Using a label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) experimental proteomics technique, we derived a comprehensive list of 1,058 proteins that are differentially expressed among normal loading, fatigue loading, and controls. By carefully developing protein selection filters and statistical models, we were able to identify 42 proteins representing 21 Rat genes that were significantly associated with bone cells' response to quantitative changes between normal loading and fatigue loading conditions. We further applied network biology techniques by building a fatigue loading activated protein-protein interaction subnetwork involving 9 of the human-homolog counterpart of the 21 rat genes in a large connected network component. Our study shows that the combination of decreased anti-apoptotic factor, Raf1, and increased pro-apoptotic factor, PDCD8, results in significant increase in the number of apoptotic osteocytes following fatigue loading. We believe controlling osteoblast differentiation/proliferation and osteocyte apoptosis could be promising directions for developing future therapeutic solutions for related bone diseases.
Bayesian parameter estimation for nonlinear modelling of biological pathways
Authors: Ghasemi Omid , Lindsey Merry L , Yang Tianyi , Nguyen Nguyen , Huang Yufei , Jin Yu-Fang
Published: December 2011

Background

The availability of temporal measurements on biological experiments has significantly promoted research areas in systems biology. To gain insight into the interaction and regulation of biological systems, mathematical frameworks such as ordinary differential equations have been widely applied to model biological pathways and interpret the temporal data. Hill equations are the preferred formats to represent the reaction rate in differential equation frameworks, due to their simple structures and their capabilities for easy fitting to saturated experimental measurements. However, Hill equations are highly nonlinearly parameterized functions, and parameters in these functions cannot be measured easily. Additionally, because of its high nonlinearity, adaptive parameter estimation algorithms developed for linear parameterized differential equations cannot be applied. Therefore, parameter estimation in nonlinearly parameterized differential equation models for biological pathways is both challenging and rewarding. In this study, we propose a Bayesian parameter estimation algorithm to estimate parameters in nonlinear mathematical models for biological pathways using time series data.

Results

We used the Runge-Kutta method to transform differential equations to difference equations assuming a known structure of the differential equations. This transformation allowed us to generate predictions dependent on previous states and to apply a Bayesian approach, namely, the Markov chain Monte Carlo (MCMC) method. We applied this approach to the biological pathways involved in the left ventricle (LV) response to myocardial infarction (MI) and verified our algorithm by estimating two parameters in a Hill equation embedded in the nonlinear model. We further evaluated our estimation performance with different parameter settings and signal to noise ratios. Our results demonstrated the effectiveness of the algorithm for both linearly and nonlinearly parameterized dynamic systems.

Conclusions

Our proposed Bayesian algorithm successfully estimated parameters in nonlinear mathematical models for biological pathways. This method can be further extended to high order systems and thus provides a useful tool to analyze biological dynamics and extract information using temporal data.
A Distal Modular Enhancer Complex Acts to Control Pituitary- and Nervous System-Specific Expression of the LHX3 Regulatory Gene
Authors: Mullen Rachel D. , Park Soyoung , Rhodes Simon J.
Published: December 2011

Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency.
Rb deficiency during Drosophila eye development deregulates EMC, causing defects in the development of photoreceptors and cone cells
Authors: Popova Milena K. , He Wei , Korenjak Michael , Dyson Nicholas J. , Moon Nam-Sung
Published: December 2011

Retinoblastoma tumor suppressor protein (pRb) regulates various biological processes during development and tumorigenesis. Although the molecular mechanism by which pRb controls cell cycle progression is well characterized, how pRb promotes cell-type specification and differentiation is less understood. Here, we report that Extra Macrochaetae (EMC), the Drosophila homolog of inhibitor of DNA binding/differentiation (ID), is an important protein contributing to the developmental defects caused by Rb deficiency. An emc allele was identified from a genetic screen designed to identify factors that, when overexpressed, cooperate with mutations in rbf1, which encodes one of the two Rb proteins found in Drosophila. EMC overexpression in an rbf1 hypomorphic mutant background induces cone cell and photoreceptor defects but has negligible effects in the wild-type background. Interestingly, a substantial fraction of the rbf1-null ommatidia normally exhibit similar cone cell and photoreceptor defects in the absence of ectopic EMC expression. Detailed EMC expression analyses revealed that RBF1 suppresses expression of both endogenous and ectopic EMC protein in photoreceptors, thus explaining the synergistic effect between EMC overexpression and rbf1 mutations, and the developmental defect observed in rbf1-null ommatidia. Our findings demonstrate that ID family proteins are an evolutionarily conserved determinant of Rb-deficient cells, and play an important role during development.
Cellular self-organization by autocatalytic alignment feedback
Authors: Junkin Michael , Leung Siu Ling , Whitman Samantha , Gregorio Carol C. , Wong Pak Kin
Published: December 2011

Myoblasts aggregate, differentiate and fuse to form skeletal muscle during both embryogenesis and tissue regeneration. For proper muscle function, long-range self-organization of myoblasts is required to create organized muscle architecture globally aligned to neighboring tissue. However, how the cells process geometric information over distances considerably longer than individual cells to self-organize into well-ordered, aligned and multinucleated myofibers remains a central question in developmental biology and regenerative medicine. Using plasma lithography micropatterning to create spatial cues for cell guidance, we show a physical mechanism by which orientation information can propagate for a long distance from a geometric boundary to guide development of muscle tissue. This long-range alignment occurs only in differentiating myoblasts, but not in non-fusing myoblasts perturbed by microfluidic disturbances or other non-fusing cell types. Computational cellular automata analysis of the spatiotemporal evolution of the self-organization process reveals that myogenic fusion in conjunction with rotational inertia functions in a self-reinforcing manner to enhance long-range propagation of alignment information. With this autocatalytic alignment feedback, well-ordered alignment of muscle could reinforce existing orientations and help promote proper arrangement with neighboring tissue and overall organization. Such physical self-enhancement might represent a fundamental mechanism for long-range pattern formation during tissue morphogenesis.
Structure and CO Oxidation Activity of Pt/CeO2 Catalysts Prepared Using Arc-Plasma
Authors: Hinokuma Satoshi , Okamoto Madoka , Ando Eriko , Ikeue Keita , Machida Masato
Published: December 2011

By applying a pulsed arc-plasma process, Pt nanoparticles were deposited from a Pt cathode onto CeO2 powders to study their structure and catalytic activity for CO oxidation. Highly dispersed uniform metallic Pt crystallites with the size of 2.6 ± 0.7 nm were obtained. Because of the highly dispersed metallic Pt nanoparticles suitable for CO chemisorption, the catalyst prepared by arc-plasma exhibited higher CO oxidation activity than those prepared by conventional wet impregnation. However, the catalyst was deactivated to a larger extent compared to the impregnated catalyst after thermal aging at 900 °C in a stream of 10% H2O in air.
Hypertrophic Cardiomyopathy: A Real Risk Factor for Stroke
Authors: Badawi R A , Seetharaman S , Birns J
Published: December 2011

Hypertrophic cardiomyopathy is a common and complex heterogeneous cardiovascular entity. Its relationship to ischaemic stroke and atrial fibrillation is under-recognized and consequently, many patients who should be on oral anticoagulation for stroke prevention go untreated.
The Power of Preemption on Unrelated Machines and Applications to Scheduling Orders
Authors: Correa José R. , Skutella Martin , Verschae José
Published: December 2011

Scheduling jobs on unrelated parallel machines so as to minimize makespan is one of the basic problems in the area of machine scheduling. In the first part of the paper, we prove that the power of preemption, i.e., the worst-case ratio between the makespan of an optimal nonpreemptive and that of an optimal preemptive schedule, is at least 4. This matches the upper bound proposed in Lin and Vitter [Lin, J.-H., J. S. Vitter. 1992. ε-approximations with minimum packing constraint violation. Proc. 24th Annual ACM Sympos. Theory of Comput. (STOC), ACM, New York, 771–782] two decades ago. In the second part of the paper, we consider the more general setting in which orders, consisting of several jobs, have to be processed on unrelated parallel machines so as to minimize the sum of weighted completion times of the orders. We obtain the first constant factor approximation algorithms for the preemptive and nonpreemptive cases, improving and extending a recent result by Leung et al. [Leung, J., H. Li, M. Pinedo, J. Zhang. 2007. Minimizing total weighted completion time when scheduling orders in a flexible environment with uniform machines. Inform. Processing Lett. 103 119–129]. Finally, we study this problem in a parallel machine environment, obtaining a polynomial-time approximation scheme for several special cases.
When Unconnected Others Connect: Does Degree of Brokerage Persist After the Formation of a Multipartner Alliance?
Authors: Yin Xiaoli , Wu Jianfeng , Tsai Wenpin
Published: December 2011

In contrast with previous research that emphasizes brokerage benefits by keeping other actors separated, this study investigates the conditions in which the degree of brokerage persists in subsequent network development when previously disconnected actors are no longer kept separate in a multipartner alliance setting. Analyses of longitudinal alliance data collected from 95 firms in the aircraft, airline, chemical, and energy industries suggest that after forming a multipartner alliance through an industry-sponsored e-marketplace, a firm with greater prior brokerage is more likely to remain influential and persist in its degree of brokerage in the subsequent alliance network when (1) the multipartner alliance has more partners and (2) size heterogeneity among partners is either low or high. The findings add to network research by offering a refined understanding of brokerage dynamics.
Golfing Alone? Corporations, Elites, and Nonprofit Growth in 100 American Communities
Authors: Marquis Christopher , Davis Gerald F. , Glynn Mary Ann
Published: December 2011

We examine the link between corporations and community by showing how corporate density interacts with the local social and cultural infrastructure to affect the growth and decline of the number of local nonprofits between 1987 and 2002. We focus on two subpopulations of nonprofits in 100 American cities: (1) elite-oriented cultural and educational institutions and (2) social welfare-oriented organizations. We find that corporate density enhances the growth of both types of nonprofits, as does location in the northeast United States and a long-established business community, but corporate density is especially potent for the growth of elite-oriented nonprofits—but not social welfare nonprofits—when local networks and cultural norms support elite mobilization. We conclude that despite globalizing trends, the local geographic community continues to be an important unit of analysis for unpacking multisector organizational processes among corporations and nonprofits.
Status Conflict in Groups
Authors: Bendersky Corinne , Hays Nicholas A.
Published: December 2011

We introduce status conflicts—defined as disputes over people's relative status (i.e., respect) positions in their group's social hierarchy—as a key group process that affects task group performance. Using mixed research methods, we qualitatively identify the characteristics of status conflicts, validate a four-item survey scale that distinctly measures status conflict, and investigate the relationship between status conflict and group performance. We determine that status conflict exerts a significant negative main effect, moderates the effects of task conflict on group performance, and hurts performance by undermining information sharing more than other types of conflict do.
Quantification of Methylated Markers with a Multiplex Methylation-Specific Technology
Authors: Zou Hongzhi , Allawi Hatim , Cao Xiaoming , Domanico Mike , Harrington Jonathan , Taylor William R , Yab Tracy , Ahlquist David A , Lidgard Graham
Published: December 2011

BACKGROUND

Aberrantly methylated genes represent important markers for cancer diagnosis. We describe a multiplex detection approach to efficiently quantify these markers for clinical applications such as colorectal cancer screening.

METHODS

Quantitative allele-specific real-time target and signal amplification (QuARTS) combines a polymerase-based target amplification with an invasive cleavage-based signal amplification. The fluorescence signal is detected in a fashion similar to real-time PCR. We measured the dynamic range and analytical sensitivity of multiplex QuARTS reactions with titrated plasmid DNA. We used the QuARTS technology to quantify methylated BMP3, NDRG4, VIM, and TFPI2 genes on 91 DNA samples extracted from colorectal tissues, including 37 cancers, 25 adenomas, and 29 healthy epithelia. The assays were designed in triplex format that incorporated ACTB as a reference gene. Percent methylation was calculated by dividing methylated strands over ACTB strands and multiplying by 100.

RESULTS

The QuARTS method linearly detected methylated or unmethylated VIM gene down to 10 copies. No cross-reactivity was observed when methylated assays were used to amplify 105 copies of unmethylated gene and vice versa. The multiplex assay detected methylated genes spiked in unmethylated genes at a 0.01% ratio and vice versa. At a diagnostic specificity cutoff of 95%, methylated BMP3, NDRG4, VIM, and TFPI2 detected 84%, 92%, 86%, and 92% of colorectal cancers and 68%, 76%, 76%, and 88% of adenomas, respectively.

CONCLUSIONS

The QuARTS technology provides a promising approach for quantifying methylated markers. The markers assayed highly discriminated colorectal neoplasia from healthy epithelia.
Surface and Dermal Sampling
Authors: Brisson Michael J. , Ashley Kevin
Published: December 2011

Description

Get the latest research available on surface and dermal sampling to assess contamination levels and detect harmful agents. Twenty peer-reviewed papers discuss sampling techniques, analytical measurement technologies, reference materials, standardization, occupational hygiene, decontamination methods, and quality assurance.

Topics cover:

Standardization Issues—includes papers which summarize current standards for surface and dermal sampling and the need for additional standards, particularly in the area of dermal sampling

Dermal—addresses contaminants on skin, including sampling, removal, and adherence of contaminated materials to the skin

Lead—deals with sampling, sample preparation, analytical proficiency testing, and lead dust loadings on surfaces other than skin

Beryllium—covers beryllium surface contamination in various industries and measurement of beryllium on surface wipe samples

Asbestos—deals with evaluation of samples collected from surfaces contaminated with asbestos

Pharmaceuticals—focuses on occupational exposure to pharmaceutical substances, as well as spills and leakage of antibiotics on surfaces

General Topics—covers investigations of outdoor environmental surface particulate; microbiological contamination on surfaces; assessments of properties contaminated with methamphetamine; and more.
Derivation of Health-Based Screening Levels for Evaluating Indoor Surface Contamination
Authors: Murnyak George , Chang Hsieng-Ye
Published: December 2011

This paper describes the development of U.S. Army Public Health Command (Provisional) Technical Guide 312, Health Risk Assessment Methods and Screening Levels for Evaluating Office Worker Exposures to Contaminants on Indoor Surfaces Using Surface Wipe Data. Surface sampling of indoor surfaces may be performed to determine whether a building is safe for re-entry following an event (for example, fire, pesticide application) or change in building use (for example, laboratory to administrative office). Surface wipe sampling results may be used to assess either the degree of contamination before cleanup or to determine whether post-abatement (also post-remediation, post-clearance) actions were effective. The U.S. Army Public Health Command (Provisional) Environmental Health Risk Assessment Program has conducted risk assessments based on surface wipe sampling data and, over time, has evolved the methodology into a technical guide. The technical guide addresses the need to develop an approach to characterize potential health risk to exposed populations using surface wipe sampling results and to provide surface wipe screening levels to facilitate initial assessments. The methodology provides a means to estimate office worker exposures from inhalation of resuspended particles, dermal contact, and incidental ingestion exposure routes. Potential chemical health risks from aggregated intakes are evaluated using conventional U.S. Environmental Protection Agency risk assessment methods.
Handwipe Method for Removing Lead from Skin
Authors: Esswein Eric J. , Boeniger Mark F. , Ashley Kevin
Published: December 2011

Researchers at the U.S. National Institute for Occupational Safety and Health (NIOSH) developed a handwipe removal method for lead (Pb) after field studies showed that workers in lead-acid battery plants had significant risks for dermal-oral lead exposures, despite their attempts to remove the lead by washing with soap and water. Hand washing with soap and water remains the standard recommendation for workers (as well as the public) to clean skin known or believed to be contaminated with toxic metals, such as lead. Despite longstanding recommendations for workers to “wash hands with soap and water,” no efficacy studies show this to be a completely effective removal method for lead. Removal of toxic metals such as lead from skin constitutes a decontamination procedure; it is not, in fact, a hand-washing step. NIOSH scientists conceived and developed a highly effective (nearly 100 %) method for removal of lead from skin. A systems approach was devised incorporating four components deemed necessary for effective metal removal: Surfaction, pH control, chelation, and mechanical effects. The handwipe removal method evolved from a previous NIOSH invention, the handwipe disclosing method for the presence of lead, in the interests of providing complementary techniques for dermal lead detection and decontamination. The method is a patented, award-winning, commercialized technology that has significant potential to prevent occupational and public exposures to lead.
Development of Two Sample Preparation Methods for Determination of Lead in Composite Dust Wipe Samples
Authors: White Kenneth T. , Dewalt F. G. , Cox David C. , Schmehl Richard , Friedman Warren , Pinzer Eugene A.
Published: December 2011

Sample preparation methods for four-wipe composite dust wipe samples, used by nine different laboratories accredited under the U.S. Environmental Protection Agency (EPA) National Lead Laboratory Accreditation Program (NLLAP), were evaluated to select two methods most likely to provide the best overall performance among multiple laboratories, based on accuracy, precision and practicality of the methods. The best performing methods involved (1) hot nitric acid/hydrogen peroxide digestion and (2) nitric acid ultrasonication. In a second round of testing, two sets of composite dust wipe samples with known amounts of lead were submitted blind to each of the nine laboratories to be prepared for analysis using these two sample preparation methods. Results showed that both methods are capable of meeting all EPA NLLAP requirements for accuracy (recovery) and precision. The ultrason ication method had superior performance at lower cost.
Beryllium Measurement by Optical Fluorescence in Samples Contaminated by Strongly Fluorescent Impurities
Authors: Agrawal Anoop , Adams Lori , Agrawal Akshay , Cronin John P. , Tonazzi Juan Carlos Lopez , Duran Brandy
Published: December 2011

A fluorescence method for determination of beryllium and beryllium oxide particles has been approved as a standard test method by ASTM International and the National Institute for Occupational Safety and Health. The procedure involves dissolution of samples in ammonium bifluoride solution and adding a small aliquot of extract to a basic hydroxybenzoquinoline sulfonate fluorescent dye and measuring its fluorescence. This method is specific to beryllium and is not affected by the presence of other metals. However, the results from such a method may be compromised by organic fluorescent impurities which have optical characteristics similar to the beryllium-bonded hydroxybenzoquinoline sulfonate. This study demonstrates that such impurities can be effectively removed by activated charcoal without compromising the sensitivity of the method or any other test attributes.