bluuebunny/crossref_metadata_2025 huggingface dataset:
Repression of IFN Regulatory Factor 8 by DNA Methylation Is a Molecular Determinant of Apoptotic Resistance and Metastatic Phenotype in Metastatic Tumor Cells
Authors: Yang Dafeng , Thangaraju Muthusamy , Greeneltch Kristy , Browning Darren D. , Schoenlein Patricia V. , Tamura Tomohiko , Ozato Keiko , Ganapathy Vadivel , Abrams Scott I. , Liu Kebin
Published: April 2007

Apoptotic resistance is often associated with metastatic phenotype in tumor cells and is considered a hallmark of tumor progression. In this study, IFN regulatory factor 8 (IRF8) expression was found to be inversely correlated with an apoptotic-resistant and metastatic phenotype in human colon carcinoma cell lines in vitro. This inverse correlation was further extended to spontaneously arising primary mammary carcinoma and lung metastases in a mouse tumor model in vivo. Exogenous expression of IRF8 in the metastatic tumor cell line restored, at least partially, the sensitivity of the tumor cells to Fas-mediated apoptosis, and disruption of IRF8 function conferred the poorly metastatic tumors with enhanced apoptotic resistance and metastatic capability. DNA demethylation restored IRF8 expression and sensitized the metastatic tumor cells to Fas-mediated apoptosis. Analysis of genomic DNA isolated from both primary and metastatic tumor cells with methylation-sensitive PCR revealed hypermethylation of the IRF8 promoter in metastatic tumor cells but not in primary tumor cells. Taken together, our data suggest that IRF8 is both an essential regulator in Fas-mediated apoptosis pathway and a metastasis suppressor in solid tumors and that metastatic tumor cells use DNA hypermethylation to repress IRF8 expression to evade apoptotic cell death and to acquire a metastatic phenotype. [Cancer Res 2007;67(7):3301–9]
Autoantibody Profiles Reveal Ubiquilin 1 as a Humoral Immune Response Target in Lung Adenocarcinoma
Authors: Chen Guoan , Wang Xiaoju , Yu Jianjun , Varambally Sooryanarayana , Yu Jindan , Thomas Dafydd G. , Lin Mu-Yen , Vishnu Prakash , Wang Zhuwen , Wang Rui , Fielhauer Jeff , Ghosh Debashis , Giordano Thomas J. , Giacherio Donald , Chang Andrew C. , Orringer Mark B. , El-Hefnawy Talal , Bigbee William L. , Beer David G. , Chinnaiyan Arul M.
Published: April 2007

There is considerable evidence that the presence of cancer can elicit a humoral immune response to specific proteins in the host, and these resulting autoantibodies may have potential as noninvasive biomarkers. To characterize the autoantibody repertoire present in the sera of patients with lung adenocarcinoma, we developed a high-density peptide microarray derived from biopanning a lung cancer phage display library. Using a 2,304-element microarray, we interrogated a total of 250 sera from Michigan lung cancer patients and noncancer controls to develop an “autoantibody profile” of lung adenocarcinoma. A set of 22 discriminating peptides derived from a training set of 125 serum samples from lung adenocarcinoma patients and control subjects was found to predict cancer status with 85% sensitivity and 86% specificity in an independent test set of 125 sera. Sequencing of the immunoreactive phage-peptide clones identified candidate humoral immune response targets in lung adenocarcinoma, including ubiquilin 1, a protein that regulates the degradation of several ubiquitin-dependent proteasome substrates. An independent validation set of 122 serum samples from Pittsburgh was examined using two overlapping clones of ubiquilin 1 that showed 0.79 and 0.74 of the area under the receiver operating characteristics curve, respectively. Significantly increased levels of both ubiquilin 1 mRNA and protein, as well as reduced levels of the phosphorylated form of this protein, were detected in lung tumors. Immunofluorescence using anti–ubiquilin 1 antibodies confirmed intracellular expression within tumors cells. These studies indicate that autoantibody profiles, as well as individual candidates, may be useful for the noninvasive detection of lung adenocarcinoma. [Cancer Res 2007;67(7):3461–7]
p18Ink4c Collaborates with Men1 to Constrain Lung Stem Cell Expansion and Suppress Non–Small-Cell Lung Cancers
Authors: Pei Xin-Hai , Bai Feng , Smith Matthew D. , Xiong Yue
Published: April 2007

Mutant mice lacking both cyclin-dependent kinase (CDK) inhibitors p18Ink4c and p27Kip1 develop a tumor spectrum reminiscent of human multiple endocrine neoplasia (MEN) syndromes. To determine how p18 and p27 genetically interact with Men1, the tumor suppressor gene mutated in familial MEN1, we characterized p18-Men1 and p27-Men1 double mutant mice and showed that p18, but not p27, functionally collaborates with Men1 in suppressing lung tumorigenesis. Lung tumors developed in both Men1+/− and p18−/−;Men1+/− mice at a high penetrance and contain both neuroendocrine and nonneuroendocrine cells. The remaining wild-type Men1 allele was lost in most lung tumors from Men1+/− mice but was retained in most tumors from p18−/−;Men1+/− mice, showing a functional collaboration between p18 and Men1 in lung tumor suppression. Phosphorylation of Rb protein at both CDK2 and CDK4/CDK6 sites were significantly increased in normal bronchial epithelia and tumor cells derived from p18−/−;Men1+/− mice compared to those from single p18−/− or Men1+/− mice. Lung tumors developed in p18−/−;Men1+/− mice were multifocal, more heterogeneous, and highly invasive compared to those developed in either p18−/− or Men1+/− mice. Bronchioalveolar stem cells are expanded in normal and tumorigenic lungs of p18−/− mice and are further expanded in p18−/−;Men1+/− lung tumors. These results reveal a previously unrecognized function of p18 in lung tumor suppression through collaboration with Men1 to control lung stem cell proliferation. [Cancer Res 2007;67(7):3162–70]
Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System
Authors: Pirollo Kathleen F. , Rait Antonina , Zhou Qi , Hwang Sung Hee , Dagata John A. , Zon Gerald , Hogrefe Richard I. , Palchik Guillermo , Chang Esther H.
Published: April 2007

The field of small interfering RNA (siRNA) as potent sequence-selective inhibitors of transcription is rapidly developing. However, until now, low transfection efficiency, poor tissue penetration, and nonspecific immune stimulation by in vivo administered siRNAs have delayed their therapeutic application. Their potential as anticancer therapeutics hinges on the availability of a vehicle that can be systemically administered, safely and repeatedly, and will deliver the siRNA specifically and efficiently to the tumor, both primary tumors and metastases. We have developed a nanosized immunoliposome-based delivery complex (scL) that, when systemically administered, will preferentially target and deliver molecules useful in gene medicine, including plasmid DNA and antisense oligonucleotides, to tumor cells wherever they occur in the body. This tumor-targeting nanoparticle delivery vehicle can also deliver siRNA to both primary and metastatic disease. We have also enhanced the efficiency of this complex by the inclusion of a pH-sensitive histidine-lysine peptide in the complex (scL-HoKC) and by delivery of a modified hybrid (DNA-RNA) anti-HER-2 siRNA molecule. Scanning probe microscopy confirms that this modified complex maintains its nanoscale size. More importantly, we show that this nanoimmunoliposome anti-HER-2 siRNA complex can sensitize human tumor cells to chemotherapeutics, silence the target gene and affect its downstream pathway components in vivo, and significantly inhibit tumor growth in a pancreatic cancer model. Thus, this complex has the potential to help translate the potent effects of siRNA into a clinically viable anticancer therapeutic. [Cancer Res 2007;67(7):2938–43]
Nuclear Factor-κB Accounts for the Repressor Effects of High Stromal Cell–Derived Factor-1α Levels on Tac1 Expression in Nontumorigenic Breast Cells
Authors: Corcoran Kelly E. , Rameshwar Pranela
Published: April 2007

Stromal cell–derived factor-1α (SDF-1α) is a CXC chemokine that interacts with CXCR4 receptor. Tac1 encodes peptides belonging to the tachykinins, including substance P. SDF-1α production is decreased in Tac1 knockdown breast cancer cells and is also reduced in these cancer cells following contact with bone marrow stroma when Tac1 expression is increased. Here, we report on the effects of relatively high and low SDF-1α levels on Tac1 expression in nontumorigenic breast cells MCF12A. Reporter gene assays, Northern analyses, and ELISA for substance P showed increased Tac1 expression at 20 and 50 ng/mL SDF-1α and reduced expression at 100 ng/mL. Omission of the untranslated region showed a dose-dependent effect of SDF-1α on reporter gene activity, suggesting that receptor desensitization cannot account for the suppressive effects at 100 ng/mL SDF-1α. Tac1 expression at high SDF-1α involves an intracellular signaling pathway that incorporates the activation of phosphatidylinositol 3-kinase-phosphoinositide-dependent kinase-1-AKT-nuclear factor-κB (NF-κB). The major repressive effect occurs via NF-κB located within exon 1. In summary, NF-κB is involved in the repression of Tac1 at higher levels of SDF-1α in MCF12A. These results are relevant to dysfunction of Tac1 in breast cancer cells and also provide insights on the behavior of breast cancer cells as they traverse across gradient changes of SDF-1α. (Mol Cancer Res 2007;5(4):373–81)
Parent Success Indicator
Authors: Beckert Troy E. , Strom Robert D. , Strom Paris S. , Yang Cheng-Ta , Singh Archana
Published: April 2007

This study examined whether the original factor structure of the Parent Success Indicator (PSI) could be replicated with scores from generational views on both the English- and Mandarin-language versions of the instrument. The 60-item PSI was evaluated using responses from 840 Taiwanese parents ( n = 429) and their 10- to 14-year-old adolescents ( n = 411), along with 1,618 parents ( n = 794) and their 10- to 14-year-old adolescents ( n = 824) from the United States. The six-factor solution set resulting from varimax and oblimin rotation accounted for between 46% and 54% of the total variance in the four analyses, confirming the original conceptual intent of the instrument. The pattern of item-to-factor correlation suggests a goodness of fit ranging from 51 to 56 of the 60 items for the four respondent groups.
Cultural Continuity as an Ethical Imperative
Authors: Christians Clifford G.
Published: April 2007

Mainstream Western ethics defines humans as rational beings. Ethics is a system of rules external to society and culture. Qualitative inquiry defines humans in holistic terms—as cultural beings, and cultures are value centered. The master norm for qualitative research, therefore, ought to be cultural continuity. Decisions for change are controlled by cultural groups themselves. Research ought to empower them toward the locally sustainable. Research is not neutral but a catalyst for critical consciousness.
The Maze of Care for Low Vision: Practitioner and Patient
Authors: Zekert Susan , Gingerich Barbara Stover
Published: April 2007

As an independent practitioner working with individuals with vision loss, one of the authors has had many collegial opportunities and many collegial disappointments. The road to independent practice in the field of vision loss was not a direct route but a maze of wrong turns, dead ends, and ultimately success in finding a path. This can also often be the case for the patients. They too often find a maze of wrong turns and detours en route to low-vision solution specialists and maximization of their remaining vision. Home care and community-based providers need to be aware of this important specialty that patients will be provided with the best quality care outcomes possible. This article provides an overview of the process for identification of low-vision rehabilitation candidates and treatment and service delivery in the field of low-vision solutions.
Using Public Relations and Marketing to Generate Referrals and Sales
Authors: Orsini Merrily
Published: April 2007

This article addresses how home health care managers and owners can use marketing and public relations to generate sales leads. It lays out a process: Develop your brand and key messages and then use marketing and public relations tactics, including a cohesive Web site, to reach your target audiences. The key is generating leads through relationship building by identifying referral sources and making certain they know how your company stands out from the crowd. After marketing the firm to the people who are actually making referrals, track the results. The article provides many examples of tips and ideas for generating leads and turning them into sales. A case study presents information relative to how these tips were applied at Kansas City Home Care.
Making New Memories
Authors: SUZUKI WENDY A.
Published: April 2007

Abstract:  Both aging and Alzheimer's disease target the hippocampal formation and can result in mild to devastating memory impairment depending on the severity of the condition. Understanding the normal mnemonic functions of the hippocampus and related structures of the medial temporal lobe is the first step toward the development of diagnostics and treatments designed to ameliorate these potentially devastating age‐related memory deficits. Here I describe findings from behavioral neurophysiological studies in which we have investigated the patterns of dynamic neural activity seen in the macaque monkey hippocampus during the acquisition of new associative memories. We report that hippocampal neurons signal the formation of new associations with dramatic changes in their firing rate. Because these learning‐related signals can occur just before behavioral learning is expressed, this suggests that these signals play a role in driving the learning process. Implications of these findings for understanding the memory deficits associated with aging and Alzheimer's disease are discussed.
Functional MRI Studies of Associative Encoding in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease
Authors: SPERLING REISA
Published: April 2007

Abstract:  Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that can be used to study the neural correlates of complex cognitive processes, and the alterations in these processes that occur in the course of normal aging or superimposed neurodegenerative disease. Our studies have focused on the neural substrates of successful associative encoding, particularly of face–name associations. We have found that the specific regions of the hippocampus and prefrontal cortices are critical for successful memory in both young and healthy older subjects. Our fMRI studies, as well as those of several other groups, have consistently demonstrated that, compared to cognitively intact older subjects, patients with clinical Alzheimer's disease (AD) have decreased fMRI activation in the hippocampus and related structures within the medial temporal lobe during the encoding of new memories. More recently, fMRI studies of subjects at risk for AD, by virtue of their genetics or evidence of mild cognitive impairment (MCI), have yielded variable results. Some of these studies, including our own, suggest that there may be a phase of paradoxically increased activation early in the course of prodromal AD. Further studies to validate fMRI in these populations are needed, particularly longitudinal studies to investigate the pattern of alterations in functional activity over the course of prodromal AD and the relationship to AD pathology.
Age‐Related Changes in Nociceptive Processing in the Human Brain
Authors: QUITON RAIMI L. , ROYS STEVEN R. , ZHUO JIACHEN , KEASER MICHAEL L. , GULLAPALLI RAO P. , GREENSPAN JOEL D.
Published: April 2007

Abstract:  Functional magnetic resonance imaging (fMRI) was used to compare cortical nociceptive responses to painful contact heat in healthy young (ages 22–30, n= 7) and older (ages 56–75, n= 7) subjects. Compared to young subjects, older subjects had significantly smaller pain‐related fMRI responses in anterior insula (aINS) (P < 0.04), primary somatosensory cortex (S1) (P= 0.03), and supplementary motor area (P= 0.02). Gray matter volumes in S1 and aINS were significantly smaller for the older group (P= 0.02 and 0.0001, respectively), suggesting reduced processing capacity in these regions that might account for smaller pain‐related fMRI responses.
Age‐Related Changes in Neuronal Susceptibility to Damage
Authors: WANG AI LING , YUAN MING , NEUFELD ARTHUR H.
Published: April 2007

Abstract:  To investigate whether or not the aging phenotype has increased vulnerability to axonal injury in vivo, we quantitated the loss of retinal ganglion cells (RGCs) after optic nerve crush. After crush, young animals lost 20% in 3 days and 50% of their RGCs in 7 days; however, old animals lost 40% in 3 days and 70% of their RGCs in 7 days. Our results showed that the time course in the loss of RGCs after crush in old mice is faster than that in young mice. Thus, old age increases susceptibility for the loss of RGCs following axonal damage.
An iterative algorithm for optimal mould design in high-precision compression moulding
Authors: Sellier M , Breitbach C , Loch H , Siedow N
Published: April 2007

The mould design for the manufacturing of high-precision glass parts remains a challenging task. This motivates the present study which proposes an optimization technique to identify the mould design that yields the desired glass piece profile at the end of the compression moulding process with an accuracy of the order of 1 μm. The intuitive, yet very efficient method consists in computing at each optimization loop the mismatch between the deformed and desired glass piece geometries and using this information to update the mould design. The deformed glass piece geometry is computed using the commercial finite element package ABAQUS. This package is well suited to model the multistage forming process, the complex rheology of the glass, and the varying mechanical contact between the parts involved. The feasibility of the method is demonstrated in theory by designing the required mould for a convex-concave lens, where an accuracy of the order of 1 μm is achieved.
Investigating fluid penetration of rolling contact fatigue cracks in rails using a newly developed full-scale test facility
Authors: Fletcher D I , Hyde P , Kapoor A
Published: April 2007

Fluid penetration of surface breaking rolling contact fatigue cracks in rails is believed to be a key factor in their growth to dangerous lengths. Fluid entry has been proved for surface breaking cracks in laboratory twin disc contact simulations, but the authors are not aware of direct evidence for fluid penetration of cracks in full-scale rail-wheel contacts. There is, however, a widely held view that the behaviour observed in the laboratory will translate to full-scale cases.

To investigate fluid penetration of cracks in full-scale rail-wheel contacts, cracked rails with a range of rolling contact fatigue severity were removed from mainline railway track and re-installed at a newly developed test facility. Investigation was undertaken using two different water-based marker fluids, and the rails subjected to over 1000 wheel passes with a locomotive. The rails were subsequently removed and selected crack faces broken open for observation by placing the rail in four-point bending.

Ultra-violet and visible light were used to assess the degree to which the marker fluids had entered the surface breaking cracks. Good evidence of fluid penetration was found for one of the marker fluids, but the second fluid was not observed inside the cracks. The possible reasons behind this difference in behaviour are discussed.
Development of the diesel fuel additive lubricity model
Authors: Fox M. F.
Published: April 2007

The high frequency reciprocating rig (HFRR) wear scar response of a range of different diesel fuel additives with different molecular structures and functionality is shown to be uniform between 2 and 6 × 10−3 molal concentration in contrast to a response curve based upon a mass/volume axis. The similarity of the wear scar response for the different types of additives on a molar concentration basis is analysed to show that whatever their various molecular structures, the additives have one polar group which is adsorbed onto the metal surface. The additivity of different diesel fuel additives for the HFRR wear scar diameter reduction test in a formulated mixture is explained on the basis of the summation of their molal concentrations.
Influence of operating parameters on dry sliding wear of copper-based SiC composites
Authors: Dhokey N. B. , Thool A. D. , Spapate S. G. , Paretkar R. K.
Published: April 2007

The main aim of using the factorial analysis method in the present work was to investigate the influence of parameters viz.: load, sliding speed, and concentration of SiC, so also the combined interaction of these parameters on wear rates, coefficient of friction, and rise in bulk temperature. Pure copper and 10%SiC reinforced copper composites were produced by powder metallurgy route by compaction and then sintered these compact at 860 °C for 2 h in hydrogen sintering furnace. The wear test was carried out on the Cu-SiC composites. Experimental plan of wear test consisted of two load (25 and 65 N) and two sliding speeds (0.6 and 2.4 m/s) for two compositions (Pure Cu and 10 vol% of SiC in copper matrix). The wear tests were implemented on Pin-on-Disc wear test machine as per ASTM G99. Analysis of wear test data was done by 23 factorial method. The relationship of individual and combined interactive parameters was attempted with worn surfaces and XRD in order to explore possible wear mechanisms.
Transient vehicle handling analysis with aerodynamic interactions
Authors: Hussain K , Rahnejat H , Hegazy S
Published: April 2007

This article presents transient handling analysis with a full-vehicle non-linear multi-body dynamic model, having 102 degrees of freedom. A transient cornering manoeuvre, with a constant steer angle and velocity has been undertaken. The effects of aerodynamic lift and drag forces have been included in the simulation tests. The vehicle handling characteristics with and without aerodynamic forces have been compared and various observations made. The aerodynamic forces have been predicted by a k-ε model solution of the Navier-Stokes equations for turbulent flow. The numerical predictions for the evaluation of aerodynamic lift coefficient agrees well with the scaled-down air tunnel experimental work, using hot-wire anemometry.
System fault diagnostics using fault tree analysis
Authors: Hurdle E. E. , Bartlett L. M. , Andrews J. D.
Published: April 2007

Over the last 50 years, advances in technology have led to an increase in the complexity and sophistication of systems. More complex systems can be harder to maintain and the root cause of a fault more difficult to isolate.

Downtime resultin from a system failure can be dangerous or expensive, depending on the type of system. In aircraft systems the ability to diagnose quickly the causes of a fault can have a significant impact on the time taken to rectify the problem and to return the aircraft to service. In chemical prcess plants the need to diagnose causes of a safety-critical failure in a system can be vital and a diagnosis may be required within minutes. Speed of fault isolation can save time, reduce costs, and increase company productivity and therefore profits. System fault diagnosis is the process of identifying the cause of a malfunction by observing its effect at various test points.

Fault tree analysis (FTA) is a method that describes all possible causes of a specified system state in terms of the state of the components within the system. A system model is used to identify the states that the system should be in at any point in time. This paper presents a method for diagnosing faults in systems using FTA to explain the deviations from normal operation observed in sensor outputs. The causes of a system's failure modes will be described in terms of the component states. This will be achieved with the use of coherent and non-coherent fault trees. A coherent fault tree is constructed from AND and OR logic and therefore considers only component-failed states. The non-coherent method expands this, allowing the use of NOT logic, which implies that the existence of component-failed states and component-working states are both taken into account. This paper illustrates the concepts of this method by applying the technique to a simplified water tank level control system.
Characterization and Electrochemical Property of α-Fe2O3 Nanoparticles Prepared by Microwave Heating
Authors: Kijima Norihito , Takahashi Yasuhiko , Hayakawa Hiroshi , Awaka Junji , Akimoto Junji
Published: April 2007

Ultrafine α-Fe2O3 nanoparticles with an extremely narrow distribution were prepared by microwave heating. The average diameter of the particles was approximately 7 nm. These nanoparticles were extremely stable in the colloidal state, even in the absence of stabilizers. The obtained α-Fe2O3 nanoparticles worked as a rechargeable electrode material. An initial discharge capacity exceeded 400 mA h g−1 (cut-off voltage: 1.0 V).
Synthesis of α-Tocopheryl Disaccharides as Potential Antiallergic Agents
Authors: Shimoda Kei , Kondo Yoko , Akagi Masaaki , Abe Koichi , Hamada Hatsuyuki , Hamada Hiroki
Published: April 2007

α-Tocopheryl disaccharides such as β-gentiobioside, β-maltoside, β-cellobioside, β-lactoside, β-melibioside, and β-isomaltoside were synthesized by biological and chemical glycosylation, and their inhibitory effects on superoxide generation from rat neutrophils were examined.
Expression and Subcellular Localization of a 35-kDa Carbonic Anhydrase IV in a Human Pancreatic Ductal Cell Line (Capan-1)
Authors: Fanjul Marjorie , Alvarez Laetitia , Hollande Etienne
Published: April 2007

The high intraluminal concentrations of HCO3− in the human pancreatic ducts have suggested the existence of a membrane protein supplying the Cl−/HCO3− exchanger. Membrane-bound carbonic anhydrase IV (CA IV) is one of the potential candidates for this protein. The difficulties in isolating human pancreatic ducts have led the authors to study the molecular mechanisms of HCO3− secretion in cancerous cell lines. In this work, we have characterized the CA IV expressed in Capan-1 cells. A 35-kDa CA IV was detected in cell homogenates and purified plasma membranes. Treatment of purified plasma membranes with phosphatidylinositol-phospholipase-C indicated that this CA IV was not anchored by a glycosylphosphatidylinositol (GPI). In contrast, its detection on purified plasma membranes by an antibody specifically directed against the carboxyl terminus of human immature GPI-anchored CA IV indicated that it was anchored by a C-terminal hydrophobic segment. Immunoelectron microscopy and double-labeling immunofluorescence revealed that this CA IV was present on apical plasma membranes, and in the rough endoplasmic reticulum, the endoplasmic reticulum-Golgi intermediate compartment, the Golgi complex, and secretory granules, suggesting its transport via the classical biosynthesis/secretory pathway. The expression in Capan-1 cells of a 35-kDa CA IV anchored in the apical plasma membrane through a hydrophobic segment, as is the case in the healthy human pancreas, should make the study of its role in pancreatic HCO3− secretion easier. (J Histochem Cytochem 55: 783–794, 2007)
Control of Sigma Virus Multiplication by the ref(2)P Gene of Drosophila melanogaster: An in Vivo Study of the PB1 Domain of Ref(2)P
Authors: Carré-Mlouka A , Gaumer S , Gay P , Petitjean A M , Coulondre C , Dru P , Bras F , Dezélée S , Contamine D
Published: April 2007

Ref(2)P has been described as one of the Drosophila proteins that interacts with the sigma virus cycle. We generated alleles to identify critical residues involved in the restrictive (inhibiting viral multiplication) or permissive (allowing viral multiplication) character of Ref(2)P. We demonstrate that permissive alleles increase the ability of the sigma virus to infect Drosophila when compared to null alleles and we confirm that restrictive alleles decrease this capacity. Moreover, we have created alleles unfunctional in viral cycling while functional for Ref(2)P fly functions. This type of allele had never been observed before and shows that fly- and virus-related activities of Ref(2)P are separable. The viral status of Ref(2)P variants is determined by the amino-terminal PB1 domain polymorphism. In addition, an isolated PB1 domain mimics virus-related functions even if it is similar to a loss of function toward fly-related activities. The evolutionary tree of the Ref(2)P PB1 domain that we could build on the basis of the natural allele sequences is in agreement with an evolution of PB1 domain due to successive transient selection waves.
Involving Undergraduates in the Annotation and Analysis of Global Gene Expression Studies: Creation of a Maize Shoot Apical Meristem Expression Database
Authors: Buckner Brent , Beck Jon , Browning Kate , Fritz Ashleigh , Grantham Lisa , Hoxha Eneda , Kamvar Zhian , Lough Ashley , Nikolova Olga , Schnable Patrick S , Scanlon Michael J , Janick-Buckner Diane
Published: April 2007

Through a multi-university and interdisciplinary project we have involved undergraduate biology and computer science research students in the functional annotation of maize genes and the analysis of their microarray expression patterns. We have created a database to house the results of our functional annotation of >4400 genes identified as being differentially regulated in the maize shoot apical meristem (SAM). This database is located at http://sam.truman.edu and is now available for public use. The undergraduate students involved in constructing this unique SAM database received hands-on training in an intellectually challenging environment, which has prepared them for graduate and professional careers in biological sciences. We describe our experiences with this project as a model for effective research-based teaching of undergraduate biology and computer science students, as well as for a rich professional development experience for faculty at predominantly undergraduate institutions.
Thirty-One Flavors of Drosophila Rab Proteins
Authors: Zhang Jun , Schulze Karen L , Hiesinger P Robin , Suyama Kaye , Wang Stream , Fish Matthew , Acar Melih , Hoskins Roger A , Bellen Hugo J , Scott Matthew P
Published: April 2007

Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, >75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent protein-tagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo.
Survival Quantitative Trait Locus Fine Mapping by Measuring and Testing for Hardy–Weinberg and Linkage Disequilibrium
Authors: Casellas J
Published: April 2007

I show that fine-scale localization of a survival-related locus can be accomplished on the basis of deviations from Hardy–Weinberg equilibrium and linkage disequilibrium at closely linked marker loci. The method is based on χ2-tests and they can be performed for age-specific samples of alive (or dead) individuals, as for combined samples of alive and dead individuals.
A Unified Model for Functional and Statistical Epistasis and Its Application in Quantitative Trait Loci Analysis
Authors: Álvarez-Castro José M , Carlborg Örjan
Published: April 2007

Interaction between genes, or epistasis, is found to be common and it is a key concept for understanding adaptation and evolution of natural populations, response to selection in breeding programs, and determination of complex disease. Currently, two independent classes of models are used to study epistasis. Statistical models focus on maintaining desired statistical properties for detection and estimation of genetic effects and for the decomposition of genetic variance using average effects of allele substitutions in populations as parameters. Functional models focus on the evolutionary consequences of the attributes of the genotype–phenotype map using natural effects of allele substitutions as parameters. Here we provide a new, general and unified model framework: the natural and orthogonal interactions (NOIA) model. NOIA implements tools for transforming genetic effects measured in one population to the ones of other populations (e.g., between two experimental designs for QTL) and parameters of statistical and functional epistasis into each other (thus enabling us to obtain functional estimates of QTL), as demonstrated numerically. We develop graphical interpretations of functional and statistical models as regressions of the genotypic values on the gene content, which illustrates the difference between the models—the constraint on the slope of the functional regression—and when the models are equivalent. Furthermore, we use our theoretical foundations to conceptually clarify functional and statistical epistasis, discuss the advantages of NOIA over previous theory, and stress the importance of linking functional and statistical models.
basA Regulates Cell Wall Organization and Asexual/Sexual Sporulation Ratio in Aspergillus nidulans
Authors: Li Shaojie , Bao Dapeng , Yuen Gary , Harris Steve D , Calvo Ana M
Published: April 2007

Sphingolipid C4 hydroxylase catalyzes the conversion of dihydrosphingosine to phytosphingosine. In Saccharomyces cerevisiae, Sur2 is essential for sphingolipid C4 hydroxylation activity but not essential for normal growth. Here we demonstrate that the Aspergillus nidulans Sur2 homolog BasA is also required for phytosphingosine biosynthesis but is also essential for viability. We previously reported that a point missense mutation in basA resulted in aberrant cell wall thickening. Here our data suggest that accumulation of dihydrosphingosine is responsible for this phenotype. In addition, two different mutations in basA consistently accelerated the transition from asexual development to sexual development compared to the wild-type strain. The phenotype could be suppressed by exogenous addition of phytosphingosine. Northern analysis suggests that faster sexual development in the basA mutant might be due to a higher transcription level of ppoA and steA, genes demonstrated to coordinate a balance between asexual and sexual development in A. nidulans. Consistent with these findings, mutations in the ceramide-synthase-encoding genes barA and lagA also caused faster transition from asexual to sexual development, supporting the involvement of sphingolipid metabolism in fungal morphogenesis.
The Balance Between the Novel Protein Target of Wingless and the Drosophila Rho-Associated Kinase Pathway Regulates Planar Cell Polarity in the Drosophila Wing
Authors: Chung SeYeon , Kim Sangjoon , Yoon Jeongsook , Adler Paul N , Yim Jeongbin
Published: April 2007

Planar cell polarity (PCP) signaling is mediated by the serpentine receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling utilizes Drosophila Frizzled 2 (DFz2) as a receptor and also requires Dsh for transducing signals to regulate cell proliferation and differentiation in many developmental contexts. Distinct pathways are activated downstream of Dsh in Wg- and Fz-signaling pathways. Recently, a number of genes, which have essential roles as downstream components of PCP signaling, have been identified in Drosophila. They include the small GTPase RhoA/Rho1, its downstream effector Drosophila rho-associated kinase (Drok), and a number of genes such as inturned (in) and fuzzy (fy), whose biochemical functions are unclear. RhoA and Drok provide a link from Fz/Dsh signaling to the modulation of actin cytoskeleton. Here we report the identification of the novel gene target of wingless (tow) by enhancer trap screening. tow expression is negatively regulated by Wg signaling in wing imaginal discs, and the balance between tow and the Drok pathway regulates wing-hair morphogenesis. A loss-of-function mutation in tow does not result in a distinct phenotype. Genetic interaction and gain-of-function studies provide evidence that Tow acts downstream of Fz/Dsh and plays a role in restricting the number of hairs that wing cells form.
LIN-61, One of TwoCaenorhabditis elegansMalignant-Brain-Tumor-Repeat-Containing Proteins, Acts With the DRM and NuRD-Like Protein Complexes in Vulval Development but Not in Certain Other Biological Processes
Authors: Harrison Melissa M , Lu Xiaowei , Horvitz H Robert
Published: April 2007

Vulval development in Caenorhabiditis elegans is inhibited by the redundant functions of the synthetic multivulva (synMuv) genes. At least 26 synMuv genes have been identified, many of which appear to act via transcriptional repression. Here we report the molecular identification of the class B synMuv gene lin-61, which encodes a protein composed of four malignant brain tumor (MBT) repeats. MBT repeats, domains of ∼100 amino acids, have been found in multiple copies in a number of transcriptional repressors, including Polycomb-group proteins. MBT repeats are important for the transcriptional repression mediated by these proteins and in some cases have been shown to bind modified histones. C. elegans contains one other MBT-repeat-containing protein, MBTR-1. We demonstrate that a deletion allele of mbtr-1 does not cause a synMuv phenotype nor does mbtr-1 appear to act redundantly with or in opposition to lin-61. We further show that lin-61 is phenotypically and biochemically distinct from other class B synMuv genes. Our data indicate that while the class B synMuv genes act together to regulate vulval development, lin-61 functions separately from some class B synMuv proteins in other biological processes.
Transcription of the 1.688 Satellite DNA Family Is Under the Control of RNA Interference Machinery inDrosophila melanogasterOvaries
Authors: Usakin Lev , Abad José , Vagin Vasily V , de Pablos Beatriz , Villasante Alfredo , Gvozdev Vladimir A
Published: April 2007

Here we show that RNA interference (RNAi) machinery operates in Drosophila melanogaster 1.688 satellite transcription. Mutation in the spn-E gene, known to be involved in RNAi in the oocytes, causes an increase of satellite transcript abundance. Transcripts of both strands of 1.688 satellite repeats in germinal tissues were detected. The strength of the effects of the spn-E mutation differs for 1.688 satellite DNA subfamilies and is more pronounced for autosomal pericentromeric satellites compared to the X-linked centromeric ones. The spn-E1 mutation causes an increase of the H3-AcK9 mark and TAF1 (a component of the polymerase II transcriptional complex) occupancy in the chromatin of autosomal pericentromeric repeats. Thus, we revealed that RNAi operates in ovaries to maintain the silenced state of centromeric and pericentromeric 1.688 repeats.
Nup96-Dependent Hybrid Lethality Occurs in a Subset of Species From the simulans Clade of Drosophila
Authors: Barbash Daniel A
Published: April 2007

The cross of Drosophila melanogaster females to D. simulans males typically produces lethal F1 hybrid males. F1 male lethality is suppressed when the D. simulans Lhr1 hybrid rescue strain is used. Viability of these F1 males carrying Lhr1 is in turn substantially reduced when the hybrids are heterozygous for some mutant alleles of the D. melanogaster Nup96 gene. I show here that similar patterns of Nup96-dependent lethality occur when other hybrid rescue mutations are used to create F1 males, demonstrating that Nup96 does not reduce hybrid viability by suppressing the Lhr1 rescue effect. The penetrance of this Nup96-dependent lethality does not correlate with the penetrance of the F1 hybrid rescue, arguing that these two phenomena reflect genetically independent processes. D. simulans, together with two additional sister species, forms a clade that speciated after the divergence of their common ancestor from D. melanogaster. I report here that Nup96− reduces F1 viability in D. melanogaster hybrids with one of these sister species, D. sechellia, but not with the other, D. mauritiana. These results suggest that Nup96-dependent lethality evolved after the speciation of D. melanogaster from the common ancestor of the simulans clade and is caused by an interaction among Nup96, unknown gene(s) on the D. melanogaster X chromosome, and unknown autosomal gene(s), at least some of which have diverged in D. simulans and D. sechellia but not in D. mauritiana. The genetic properties of Nup96 are also discussed relative to other hybrid lethal genes.
NEC X12 at the heart of Worcestershire Highways
Authors: Rankin J. , Jameson P. , Yarwood N.
Published: April 2007

Worcestershire County Council (WCC) is using long-term NEC contracts linked by the X12 partnering option to provide the contractual framework for the provision of a high quality highways service to the people of Worcestershire and those who travel through the county. Establishing this contractual framework has been the first step in the development of ‘Worcestershire Highways’ as the innovative vehicle for highways service delivery in Worcestershire. The present paper will show how WCC is using the NEC suite of contracts, specifically the X12 partnering option, to provide an integrated, partnership highways service for the people of Worcestershire and to examine the benefits that can be achieved through this approach.
Coventry Framework Partnership
Authors: Aggus S. R. , Hiscocks E. J. S.
Published: April 2007

The paper describes the establishment of a framework partnership involving Coventry City Council as highway authority, an engineering consultant and four contractors. The overall objective was to deliver improved performance for the implementation of an increased programme of transportation and civil engineering projects. The main feature of the partnership was the Coventry model, which included: a partnering board made up of representatives of all the parties and led by key councillors; joint financial incentives based on a pain/gain mechanism; joint value management/value engineering and open-book accounting to maximise cost savings; and performance-based contract extensions. Other supporting features were: a cost database continually updated by completed contracts; a strong emphasis on communications both between the members of the partnership and with all parties involved in specific projects; a computerised project status database to enable access to current financial and programme data on each project; quantitative and qualitative performance assessment; and an action plan of continuous comprehensive improvement. After three years the results of the framework partnership were encouraging, with rising levels of satisfaction, significant savings in design and construction costs, and a proven ability to react to changing and challenging circumstances.
Nodulating and Non‐Nodulating Soybean Rotation Influence on Soil Nitrate‐Nitrogen and Water, and Sorghum Yield
Authors: Kaye Nanga Mady , Mason Stephen C. , Galusha Tomie D. , Mamo Martha
Published: April 2007

Soybean [Glycine max (L.) Merr.] rotation has been shown to enhance grain sorghum [Sorghum bicolor (L.) Moench] growth and yield due in part to N contribution. Sorghum grain and stover yield, yield components, soil water and soil NO3–N were measured in a long‐term rotation study in 2003 and 2004 on a Sharpsburg silty clay loam (fine, smectitic, mesic Typic Argiudoll). The objectives were to separate biologically fixed N from other rotation effects on sorghum grain and stover yields, and to relate yield to yield components, soil NO3–N and water contents. The cropping sequences were continuous grain sorghum, and sorghum rotated with non‐nodulating or nodulating soybean. Soil amendment treatments consisted of control (zero), manure (17–25 Mg dry matter ha−1 yr−1), and N (41 kg ha−1 for soybean and 84 kg ha−1 yr−1 for sorghum). Cropping sequence × soil amendment interaction effects were found for most parameters measured. High soil NO3–N following soybean rotation and from amendment application promoted plant growth leading to low soil water content at anthesis, and increased kernel weight, grain and stover yield. Rotation with non‐nodulating soybean without soil amendment increased grain yield by 2.6 to 3.0 Mg ha−1 and stover yield by 1.5 to 1.8 Mg ha−1 over continuous sorghum without soil amendment. Rotation with nodulating soybean further increased grain yield by 1.7 to 1.8 Mg ha−1 and stover yield by 0.6 to 0.9 Mg ha−1. Biologically fixed N effects accounted for only 35 to 41% of enhanced sorghum yield due to crop rotation with soybean. Soil NO3–N during vegetative growth, plant height, soil water content at anthesis and kernel weight were the most important parameters related to sorghum grain yield across cropping sequences and soil amendments.
Tillage System by Planting Date Interaction Effects on Corn and Soybean Yield
Authors: Perez‐Bidegain Mario , Cruse Richard M. , Ciha Allan
Published: April 2007

Spring soil temperature and soil water content can be influenced by tillage system. If a tillage system and planting date interaction exists, planting on a single date, as is done in most tillage trials, could bias yield results. We tested for this interaction by comparing corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] yields using strip tillage, no tillage, and disk‐chisel tillage systems with planting dates determined by soil temperature and water content conditions within each tillage system. A 3‐yr study (2002–2004) was conducted on a site near Newton, IA that had three soil types: Cumulic Hapludolls, Aquic Hapludolls, and Cumulic Haplaquolls. A split‐plot design was used with tillage as whole plots arranged in four randomized complete blocks. Crops in all tillage system treatments were planted on three dates that comprised the split‐plots. The criteria to determine the planting dates were soil temperature (>10°C for corn and >13°C for soybean for 12 consecutive hours) and soil water content (less than or equal to the lower plastic limit for any of the tillage treatments) at the 0.05‐m depth. A planting date occurred for each of the tillage systems as these criteria were met. For both crops, the earliest date having these soil conditions occurred simultaneously for disk‐chisel and strip tillage. The no‐tillage plots exhibited these conditions between 4 and 28 d and between 6 and 15 d later for corn and soybean, respectively, than for the other tillage treatments. Corn planted with disk‐chisel tillage yielded 0.8 Mg ha−1 more than the mean of the other two tillage treatments across years. Planting date affected corn yield only in 2003. For soybean, planting date affected yield. Soybean planted at the early planting date yielded 0.16 Mg ha−1 more than the mean of the other planting dates across years. There was no interaction of tillage × planting date for yield of either crop. This research indicates that recommendations derived from existing tillage research using a common planting date are valid.