bluuebunny/crossref_metadata_2025 huggingface dataset:
Management Work—Family Research and Work—Family Fit
Authors: Rothausen Teresa J.
Published: June 2009

In this article, 25 years of organization science research on work—family is summarized, and its implications for building the human, social, and economic elements of family capital in family business are developed. The impact of work—family conflict; sex and gender roles; role enrichment; work—family benefits, programs, and policies; and work, job, and organization redesign are emphasized. A social systems model of environment—environment fit—work—family fit—is developed. Implications for future research and for investing in family capital are discussed.
Building Programmatic Capacity at the Grassroots Level: The Reactions of Local Nonprofit Organizations to Public Participation Geographic Information Systems
Authors: Bishop Sheilah Watson
Published: June 2009

Diffusion and acceptance of geographic information systems (GIS) technology is not fully understood in public or private organizations, and even less is known about the role of GIS in the nonprofit sector. Using spatial analysis, this study examines the extent to which nine nonprofit organizations in Columbia, Missouri, meet the needs of their target populations. Findings revealed that nonprofit entities met from less than 1% to about 20% of client demand for services. Reactions to GIS analysis of program outputs was largely positive, with most of the nonprofits expressing an interest in using GIS technology to further communication and networking with other organizations. GIS is viewed by nonprofit administrators as a potentially useful tool in grant applications, strategic planning, program reporting, and advocacy activities, among others. Nonprofit administrators embrace GIS if they can use it to help with more immediate and practical concerns, such as improving client care and services.
The Unlikely Securitizer: Humanitarian Organizations and the Securitization of Indistinctiveness
Authors: Vaughn Jocelyn
Published: June 2009

The securitization framework has greatly improved empirical analysis of security threats. Yet, it could benefit from heightened analysis of two often neglected aspects. First, this article argues that securitizers may invoke multiple referent objects to strengthen their argument that the referent object possesses the `right to survive'. Second, by drawing attention to the presentation of securitizing moves, as well as their content, it highlights how securitizers attempt to persuade multiple audiences that their securitizing moves should be accepted and countermeasures enacted. These claims are illustrated through the analysis of an atypical case of securitization performed by an unlikely set of securitizers, humanitarian aid organizations, as they argue that indistinctiveness poses an existential threat both to their material security and to their identity.
The First Weeklong Technical Writers’ Institute and Its Impact
Authors: Whitburn Merrill D.
Published: June 2009

Rensselaer’s Technical Writers’ Institute, the first program of its kind, had a profound impact on technical communication. It enabled technical communicators without formal education in the field to gain important knowledge, provided a forum for communicators from different industries to meet in order to solve mutual problems, played a key role in defining the field and its needs, encouraged recruitment (including the hiring of more women), promoted professional societies and formal degree programs, and seriously affected industry training programs by enabling them to use institute teaching materials. Knowledge gained through the Technical Writers’ Institute enabled Rensselaer to develop many other innovations.
‘‘Sort of Set My Goal to Come to Class’’
Authors: Sligo Frank , Tilley Elspeth
Published: June 2009

This article documents a novel yet theory-informed process of preparing research reports designed for government officials who are concerned with creating adult-literacy policy. The authors use cartoons that include verbatim dialogue from the transcripts of interviews with research participants with low functional literacy. This dialogue, which depicts positive messages about the participants’ moral character, strengths, and resilience, is set against photographic backdrops of the participants’ lived environment to give a sense of real people in a real place. Inclusion of such images is an attempt to change policy-report readers’ thinking about adult literacy because creative visual communication offers ways to approach this challenge that text alone cannot.
A Steering Taxis Model and the Qualitative Analysis of its Trajectories
Authors: Rañó I.
Published: June 2009

Taxis is a well-known steering technique used by simple animals to approach a stimulus in the real world. However, no mathematical motion model of taxis can be found in the literature. This article derives the differential ordinary equations describing the motion of a Braitenberg vehicle, a widely used taxis model. A qualitative technique for non-linear dynamical systems analysis is applied to investigate the motion generated by the model. Validation of the analysis is performed through several simulations, and conditions for the stimulus source to be reached are obtained. This work fills the theoretical hole in formal models of Braitenberg vehicles and thereby provides theoretical support for the many previous experimental uses of those vehicles for steering tasks.
Re-embodiment of Honeybee Aggregation Behavior in an Artificial Micro-Robotic System
Authors: Kernbach Serge , Thenius Ronald , Kernbach Olga , Schmickl Thomas
Published: June 2009

In this article we describe the re-embodiment of biological aggregation behavior of honeybees in Jasmine micro-robots. The observed insect behavior, in the context of the insect's sensor—actor system, is formalized as behavioral and motion-sensing meta-models. These meta-models are transformed into a sensor—actor system of micro-robots by means of a sensors virtualization technique. This allows us to keep the efficiency and scalability of the bio-inspired approach. We also demonstrate the systematic character of this re-embodiment procedure on collective aggregation in a real robotic swarm.
Oppression Through Acceptance?
Authors: Hockett Jericho M. , Saucier Donald A. , Hoffman Bethany H. , Smith Sara J. , Craig Adam W.
Published: June 2009

Feminist theories of rape motivation are based on research suggesting a relationship between dominance and sexual aggression. However, the relationship between dominance and rape myth acceptance (RMA), a predictor of rape proclivity and sexual aggression and a key component in feminist theory, is understudied. The current study tests the hypotheses that individuals' scores on sex-based oppression and intergroup dominance measures will improve the predictive models for RMA and attitudes toward rape and rape victims. The hypotheses are supported. Individuals' general intergroup dominance and sex-based oppression attitudes provide significant unique prediction beyond previously studied predictors of attitudes about rape and rape victims.
Clinicians' Knowledge of 2007 Food and Drug Administration Recommendation to Discontinue Nelfinavir Use During Pregnancy
Authors: Fogler Jessica , Weber Shannon , Mahoney Megan R. , Goldschmidt Ronald H.
Published: June 2009

In 2007, the US Food and Drug Administration (FDA) and Pfizer Inc recommended immediate discontinuation of nelfinavir (NFV) during pregnancy due to contamination with a potential teratogen. A few weeks after the announcement, we surveyed antenatal HIV care providers to determine how widely the warning was disseminated. Overall, 69 of 121 (57.0%) providers knew to discontinue NFV. Callers with more than 50 HIV-infected patients were 2.54 times as likely to be aware as callers with 1-3 HIV-infected patients (P < .01). Only 12 (33.3%) obstetricians were aware, compared to 21 (80.8%) infectious diseases specialists (P < .001). The FDA/Pfizer Inc recommendation to avoid nelfinavir mesylate (NFV) in pregnancy appears to have successfully reached HIV experts. However, not all pregnant women have access to experts and may receive most of their care from providers without extensive HIV experience. More effective dissemination of critical HIV-related information to all antenatal care providers, including general obstetricians, family physicians, and midwives, may be needed.
The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5′-diphosphate-ribose) polymerase-1
Authors: Zhu Pengcheng , Martinvalet Denis , Chowdhury Dipanjan , Zhang Dong , Schlesinger Ann , Lieberman Judy
Published: June 2009

Granzyme A (GzmA) in killer cells induces caspase-independent programmed cell death. In this study, we show that GzmA cleaves the DNA damage sensor poly(adenosine 5′-diphosphate-ribose) polymerase-1 (PARP-1) after Lys498 in its automodification domain, separating the DNA binding domain from the catalytic domain, which interferes with repair of GzmA-induced DNA damage and enhances susceptibility to GzmA-mediated death. Overexpressing K498A PARP-1 reduces GzmA-mediated death and drives dying cells to necrosis rather than apoptosis. Conversely, inhibiting or genetically disrupting PARP-1 enhances cell vulnerability. The N-terminal GzmA cleavage fragment of PARP-1 acts as a PARP-1 dominant negative, binding to DNA and blocking DNA repair. Disrupting PARP-1, which is also a caspase target, is therefore required for efficient apoptosis by both caspase-independent and caspase-dependent pathways.
Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells
Authors: Shao Esther S. , Lin Laura , Yao Yucheng , Boström Kristina I.
Published: June 2009

Expression of vascular endothelial growth factor (VEGF) is tightly regulated to achieve normal angiogenesis. The objective was to examine regulation of VEGF by the activin-like kinase receptors (ALKs) ALK1 and ALK5. Transforming growth factor β1 (TGFβ1) and bone morphogenetic protein-9 (BMP-9) enhanced and suppressed VEGF expression, respectively, in aortic endothelial cells, as determined by real-time polymerase chain reaction, immunoblotting, cell proliferation, and tube formation. The use of small interfering RNA revealed that TGFβ1 stimulated VEGF expression by activating ALK5, TGFβ type II receptor, and SMAD2, whereas BMP-9 suppressed it by activating ALK1, BMP type II receptor, and SMAD1. ALK1 signaling occurred independently of ALK5 activity. Partial ALK1 deficiency in vitro and in vivo resulted in elevated VEGF expression. In vitro, increased BMP-9 levels normalized VEGF expression in cells with partial, but not severe, ALK1 deficiency. Time course experiments revealed that an increase in ALK1 expression induced by BMP-4, an angiogenic stimulus, preceded induction of ALK5 and VEGF in control cells. In ALK1-deficient cells, however, VEGF expression occurred earlier and was abnormally high, even though ALK5 was not induced. Our results suggest that ALK1 and ALK5 are both essential for correct regulation of VEGF, and that disruption of either pathway leads to disease.
Primate phylogenomics: developing numerous nuclear non-coding, non-repetitive markers for ecological and phylogenetic applications and analysis of evolutionary rate variation
Authors: Peng Zuogang , Elango Navin , Wildman Derek E , Yi Soojin V
Published: June 2009

Background

Genetic analyses are often limited by the availability of appropriate molecular markers. Markers from neutrally evolving genomic regions may be particularly useful for inferring evolutionary histories because they escape the constraints of natural selection. For the majority of taxa however, obtaining such markers is challenging. Advances in genomics have the potential to alleviate the shortage of neutral markers. Here we present a method to develop numerous markers from putatively neutral regions of primate genomes.

Results

We began with the available whole genome sequences of human, chimpanzee and macaque. Using computational methods, we identified a total of 280 potential amplicons from putatively neutral, non-coding, non-repetitive regions of these genomes. Subsequently we amplified, using experimental methods, many of these amplicons from diverse primate taxa, including a ring-tailed lemur, which is distantly related to the genomic resources. Using a subset of 10 markers, we demonstrate the utility of the developed markers in phylogenetic and evolutionary rate analyses. Particularly, we uncovered substantial evolutionary rate variation among lineages, some of which are previously not reported.

Conclusion

We successfully developed numerous markers from putatively neutral regions of primate genomes using a strategy combining computational and experimental methods. Applying these markers to phylogenetic and evolutionary rate variation analyses exemplifies the utility of these markers. Diverse ecological and evolutionary analyses will benefit from these markers. Importantly, methods similar to those presented here can be applied to other taxa in the near future.
Gene expression profiling within the spleen of Clostridium perfringens- challenged Broilers fed antibiotic-medicated and non-medicated diets
Authors: Sarson Aimie J , Wang Ying , Kang Zhumei , Dowd Scot E , Lu Yang , Yu Hai , Han Yanming , Zhou Huaijun , Gong Joshua
Published: June 2009

Background

Clostridium perfringens(Cp) is a Gram-positive anaerobic bacterium that causes necrotic enteritis (NE) in poultry when it overgrows in the small intestine. NE disease has previously been controlled through the use of growth-promoting antibiotics. This practice was recently banned in European countries, leading to significantly increased incidence of NE threatening the poultry industry. Control strategies and technology as substitutes to dietary antibiotics are therefore urgently required. To develop the substitutes, it is important to understand host immune responses to Cp infection. However, the knowledge is still lacking. We therefore investigated gene expression profiles within immunologically-relevant tissue, the spleen, in order to identify factors that are involved in immunity to NE and have potential as therapeutic targets.

Results

Use of a 44 K Agilent chicken genome microarray revealed significant up-regulation of many immune-associated genes in Cp-challenged chickens, includinggalectin 3,IFNAR1,IgY-receptor,TCRγ,granzyme A, andmannose-6-P-R, which were subsequently validated by quantitative PCR assays. Functional annotation of differentially expressed genes was conducted using the High Throughput Gene Ontology Functional Annotation database. Medicated and Non-medicated chickens had similar annotation profiles with cell activities and regulation being the most dominant biological processes following Cp infection.

Conclusion

Broiler chickens demonstrated an intricate and holistic magnitude of host response to Cp challenge and the development of NE. Although the influence of dietary antibiotics appeared to be less significant than the disease process, both had a considerable impact on the host response. Markers previously identified in intestinal inflammatory diseases of other species, including humans, and indicators of enhanced antibody responses, appeared to be involved in the chicken response to Cp challenge. The significance in host immune responses of immune mediators identified from the present study warrants further studies to verify their functions during NE development and to determine their potential application to control NE disease.
Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells
Authors: Law Helen KW , Cheung Chung Yan , Sia Sin Fun , Chan Yuk On , Peiris JS Malik , Lau Yu Lung
Published: June 2009

Background

The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS.

Results

Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs.

Conclusion

The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.
Promoter analysis of macrophage- and tick cell-specific differentially expressed Ehrlichia chaffeensis p28-Omp genes
Authors: Peddireddi Lalitha , Cheng Chuanmin , Ganta Roman R
Published: June 2009

Background

Ehrlichia chaffeensis is a rickettsial agent responsible for an emerging tick-borne illness, human monocytic ehrlichiosis. Recently, we reported that E. chaffeensis protein expression is influenced by macrophage and tick cell environments. We also demonstrated that host response differs considerably for macrophage and tick cell-derived bacteria with delayed clearance of the pathogen originating from tick cells.

Results

In this study, we mapped differences in the promoter regions of two genes of p28-Omp locus, genes 14 and 19, whose expression is influenced by macrophage and tick cell environments. Primer extension and quantitative RT-PCR analysis were performed to map transcription start sites and to demonstrate that E. chaffeensis regulates transcription in a host cell-specific manner. Promoter regions of genes 14 and 19 were evaluated to map differences in gene expression and to locate RNA polymerase binding sites.

Conclusion

RNA analysis and promoter deletion analysis aided in identifying differences in transcription, DNA sequences that influenced promoter activity and RNA polymerase binding regions. This is the first description of a transcriptional machinery of E. chaffeensis. In the absence of available genetic manipulation systems, the promoter analysis described in this study can serve as a novel molecular tool for mapping the molecular basis for gene expression differences in E. chaffeensis and other related pathogens belonging to the Anaplasmataceae family.
Fragments of the key flowering gene GIGANTEA are associated with helitron-type sequences in the Pooideae grass Lolium perenne
Authors: Langdon Tim , Thomas Ann , Huang Lin , Farrar Kerrie , King Julie , Armstead Ian
Published: June 2009

Background

Helitrons are a class of transposable elements which have been identified in a number of species of plants, animals and fungi. They are unique in their proposed rolling-circle mode of replication, have a highly variable copy-number and have been implicated in the restructuring of coding sequences both by their insertion into existing genes and by their incorporation of transcriptionally competent gene fragments. Helitron discovery depends on identifying associated DNA signature sequences and comprehensive evaluation of helitron contribution to a particular genome requires detailed computational analysis of whole genome sequence. Therefore, the role which helitrons have played in modelling non-model plant genomes is largely unknown.

Results

Cloning of the flowering geneGIGANTEA(GI) from a BAC library of the Pooideae grassLolium perenne(perennial ryegrass) identified the target gene and severalGIpseudogene fragments spanning the first five exons. Analysis of genomic sequence 5' and 3' of one theseGIfragments revealed motifs consistent with helitron-type transposon insertion, specifically a putative 5'-A↓T-3' insertion site containing 5'-TC and CTAG-3' borders with a sub-terminal 16 bp hairpin. Screening of a BAC library of the closely related grass speciesFestuca pratensis(meadow fescue) indicated similar helitron-associatedGIfragments present in this genome, as well as non-helitron associatedGIfragments derived from the same region ofGI. In order to investigate the possible extent of ancestral helitron-activity inL. perenne, a methylation-filtered GeneThresher®genomic library developed from this species was screened for potential helitron 3' hairpin sequences associated with a 3'-CTRR motif. This identified 7 potential helitron hairpin-types present between at least 9 and 51 times within theL. perennemethylation-filtered library.

Conclusion

This represents evidence for a possible ancestral role for helitrons in modelling the genomes ofLoliumand related species.
Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer
Authors: Dai Shun-Dong , Wang Yan , Miao Yuan , Zhao Yue , Zhang Yong , Jiang Gui-Yang , Zhang Peng-Xin , Yang Zhi-Qiang , Wang En-Hua
Published: June 2009

Background

Kaiso has been identified as a new member of the POZ-zinc finger family of transcription factors that are implicated in development and cancer. Although controversy still exists, Kaiso is supposed to be involved in human cancer. However, there is limited information regarding the clinical significance of cytoplasmic/nuclear Kaiso in human lung cancer.

Methods

In this study, immunohistochemical studies were performed on 20 cases of normal lung tissues and 294 cases of non-small cell lung cancer (NSCLC), including 50 cases of paired lymph node metastases and 88 cases with complete follow-up records. Three lung cancer cell lines showing primarily nuclear localization of Kaiso were selected to examine whether roles of Kaiso in cytoplasm and in nucleus are identical. Nuclear Kaiso was down-regulated by shRNA technology or addition a specific Kaiso antibody in these cell lines. The proliferative and invasive abilities were evaluated by MTT and Matrigel invasive assay, transcription of Kaiso's target gene matrilysin was detected by RT-PCR.

Results

Kaiso was primarily expressed in the cytoplasm of lung cancer tissues. Overall positive cytoplasmic expression rate was 63.61% (187/294). The positive cytoplasmic expression of Kaiso was higher in advanced TNM stages (III+IV) of NSCLC, compared to lower stages (I+II) (p = 0.019). A correlation between cytoplasmic Kaiso expression and lymph node metastasis was found (p = 0.003). In 50 paired cases, cytoplasmic expression of Kaiso was 78.0% (41/50) in primary sites and 90.0% (45/50) in lymph node metastases (p = 0.001). The lung cancer-related 5-year survival rate was significantly lower in patients who were cytoplasmic Kaiso-positive (22.22%), compared to those with cytoplasmic Kaiso-negative tumors (64.00%) (p = 0.005). Nuclear Kaiso staining was seen in occasional cases with only a 5.10% (15/294) positive rate and was not associated with any clinicopathological features of NSCLC. Furthermore, after the down-regulation of the nuclear expresses Kaiso in vitro, both proliferative and invasive abilities of three cancer cell lines were significantly enhanced, along with the up-regulation of Kaiso target gene, matrilysin.

Conclusion

Our data suggest cytoplasmic Kaiso expression is associated with poor prognosis of NSCLC and various subcellular localizations of Kaiso may play differential biological roles in NSCLC.
Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods
Authors: Rexach José A Serra , Ruiz Jonatan R , Bustamante-Ara Natalia , Villarán Margarita Hierro , Gil Pedro González , Sanz Ibáñez Maria J , Sanz Nekane Blanco , Santamaría Victor Ortega , Sanz Natalia Gutiérrez , Prada Ana B Marín , Gallardo Cristian , Romo Gabriel Rodríguez , Lucia Alejandro
Published: June 2009

Background

The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians.

Methods

Sixty (51 women) nonagenarians (age range: 90–102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enrol in three weekly non-consecutive individualized training sessions (~45–50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3–5 to 15 minutes at 12–14 points in the rate of perceived exertion scale).

Results

Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups.

Conclusion

The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.

Trail Registration

ClinicalTrials.gov ID: NCT00848978
PimT, an amino acid exporter controls polyene production via secretion of the quorum sensing pimaricin-inducer PI-factor in Streptomyces natalensis
Authors: Vicente Cláudia M , Santos-Aberturas Javier , Guerra Susana M , Payero Tamara D , Martín Juan F , Aparicio Jesús F
Published: June 2009

Background

Polyenes represent a major class of antifungal agents characterised by the presence of a series of conjugated double bonds in their planar hydroxylated macrolide ring structure. Despite their general interest, very little is known about the factors that modulate their biosynthesis. Among these factors, we have recently discovered a new inducing compound (PI-factor) in the pimaricin producer Streptomyces natalensis, which elicits polyene production in a manner characteristic of quorum sensing. Here, we describe the involvement of an amino-acid exporter from S. natalensis in modulating the expression of pimaricin biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor.

Results

Adjacent to the pimaricin gene cluster lies a member of the RhtB family of amino-acid exporters. Gene deletion and complementation experiments provided evidence for a role for PimT in the export of L-homoserine, L-serine, and L-homoserine lactone. Expression of the gene was shown to be induced by homoserine and by the quorum-sensing pimaricin-inducer PI-factor. Interestingly, the mutant displayed 65% loss of pimaricin production, and also 50% decrease in the production of PI, indicating that PimT is used as PI-factor exporter, and suggesting that the effect in antifungal production might be due to limited secretion of the inducer.

Conclusion

This report describes the involvement of an amino acid exporter (encoded by pimT in the vicinity of the pimaricin cluster) in modulating the expression of antibiotic biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor. The discovery of the participation of amino acid exporters in a signal transduction cascade for the production of polyene macrolides is unexpected, and represents an important step forward towards understanding the regulatory network for polyene regulation. Additionally, this finding constitutes the first detailed characterization of an amino-acid exporter in an Actinomycete, and to our knowledge, the first evidence for the implication of this type of exporters in quorum sensing.
Spatial and temporal distribution of the malaria mosquito Anopheles arabiensis in northern Sudan: influence of environmental factors and implications for vector control
Authors: Ageep Tellal B , Cox Jonathan , Hassan M'oawia M , Knols Bart GJ , Benedict Mark Q , Malcolm Colin A , Babiker Ahmed , El Sayed Badria B
Published: June 2009

Background

Malaria is an important public health problem in northern Sudan, but little is known about the dynamics of its transmission. Given the characteristic low densities of Anopheles arabiensis and the difficult terrain in this area, future vector control strategies are likely to be based on area-wide integrated pest management (AW-IPM) that may include the sterile insect technique (SIT). To support the planning and implementation of future AW-IPM activities, larval surveys were carried out to provide key data on spatial and seasonal dynamics of local vector populations.

Methods

Monthly cross-sectional larval surveys were carried out between March 2005 and May 2007 in two localities (Dongola and Merowe) adjacent to the river Nile. A stratified random sampling strategy based on the use of Remote Sensing (RS), Geographical Information Systems (GIS) and the Global Positioning System (GPS) was used to select survey locations. Breeding sites were mapped using GPS and data on larval density and breeding site characteristics were recorded using handheld computers. Bivariate and multivariate logistic regression models were used to identify breeding site characteristics associated with increased risk of presence of larvae. Seasonal patterns in the proportion of breeding sites positive for larvae were compared visually to contemporaneous data on climate and river height.

Results

Of a total of 3,349 aquatic habitats sampled, 321 (9.6%) contained An. arabiensis larvae. The frequency with which larvae were found varied markedly by habitat type. Although most positive sites were associated with temporary standing water around the margins of the main Nile channel, larvae were also found at brickworks and in areas of leaking pipes and canals – often far from the river. Close to the Nile channel, a distinct seasonal pattern in larval populations was evident and appeared to be linked to the rise and fall of the river level. These patterns were not evident in vector populations breeding in artificial water sources away from the river.

Conclusion

The GIS-based survey strategy developed in this study provides key data on the population dynamics of An. arabiensis in Northern State. Quantitative estimates of the contributions of various habitat types and their proximity to settlements provide a basis for planning a strategy for reducing malaria risk by elimination of the vector population.
An early burst of IFN-γ induced by the pre-erythrocytic stage favours Plasmodium yoelii parasitaemia in B6 mice
Authors: Soulard Valérie , Roland Jacques , Gorgette Olivier , Barbier Eliane , Cazenave Pierre-André , Pied Sylviane
Published: June 2009

Background

In murine models of malaria, an early proinflammatory response has been associated with the resolution of blood-stage infection. To dissect the protective immune mechanims that allow the control of parasitaemia, the early immune response of C57BL/6 mice induced during a non-lethal plasmodial infection was analysed.

Methods

Mice were infected withPlasmodium yoelii265BY sporozoites, the natural invasive form of the parasite, in order to complete its full life cycle. The concentrations of three proinflammatory cytokines in the sera of mice were determined by ELISA at different time points of infection. The contribution of the liver and the spleen to this cytokinic response was evaluated and the cytokine-producing lymphocytes were identified by flow cytometry. The physiological relevance of these results was tested by monitoring parasitaemia in genetically deficient C57BL/6 mice or wild-type mice treated with anti-cytokine neutralizing antibody. Finally, the cytokinic response in sera of mice infected with parasitized-RBCs was analysed.

Results

The early immune response of C57BL/6 mice to sporozoite-induced malaria is characterized by a peak of IFN-γ in the serum at day 5 of infection and splenic CD4 T lymphocytes are the major producer of this cytokine at this time point. Somewhat unexpected, the parasitaemia is significantly lower inP. yoelii-infected mice in the absence of IFN-γ. More precisely, at early time points of infection, IFN-γ favours parasitaemia, whereas helping to clear efficiently the blood-stage parasites at later time points. Interestingly, the early IFN-γ burst is induced by the pre-erythrocytic stage.

Conclusion

These results challenge the current view regarding the role of IFN-γ on the control of parasite growth since they show that IFN-γ is not an essential mediator of protection inP. yoelii-infected C57BL/6 mice. Moreover, the mice parasitaemia is more efficiently controlled in the absence of an early IFN-γ production, suggesting that this cytokine promotes parasite's growth. Finally, this early burst of IFN-γ is induced by the pre-erythrocytic stage, showing the impact of this stage on the immune response taking place during the subsequent erythrocytic stage.
Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo
Authors: Nuhn Philipp , Künzli Beat M , Hennig René , Mitkus Tomas , Ramanauskas Tadas , Nobiling Rainer , Meuer Stefan C , Friess Helmut , Berberat Pascal O
Published: June 2009

Background

Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy in vitro.

Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells.

PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested in vivo and in vitro.

Results

High HO-1 expression in PaCa cell lines was associated with increased chemoresistance in vitro. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects in vivo significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.

Conclusion

In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy in vivo. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.
Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial
Authors: Elwanis Mostafa Abd , Maximous Doaa W. , Elsayed Mohamed Ibrahim , Mikhail Nabiel N. H.
Published: June 2009

Introduction

Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery.

Aim

To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine.

Patients and methods

This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique.

Results

Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively.

Conclusion

In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.
In vivo properties of the proangiogenic peptide QK
Authors: Santulli Gaetano , Ciccarelli Michele , Palumbo Gianluigi , Campanile Alfonso , Galasso Gennaro , Ziaco Barbara , Altobelli Giovanna Giuseppina , Cimini Vincenzo , Piscione Federico , D'Andrea Luca Domenico , Pedone Carlo , Trimarco Bruno , Iaccarino Guido
Published: June 2009

The main regulator of neovascularization is Vascular Endothelial Growth Factor (VEGF). We recently demonstrated that QK, a de novo engineered VEGF mimicking peptide, shares in vitro the same biological properties of VEGF, inducing capillary formation and organization. On these grounds, the aim of this study is to evaluate in vivo the effects of this small peptide. Therefore, on Wistar Kyoto rats, we evaluated vasomotor responses to VEGF and QK in common carotid rings. Also, we assessed the effects of QK in three different models of angiogenesis: ischemic hindlimb, wound healing and Matrigel plugs. QK and VEGF present similar endothelium-dependent vasodilatation. Moreover, the ability of QK to induce neovascularization was confirmed us by digital angiographies, dyed beads dilution and histological analysis in the ischemic hindlimb as well as by histology in wounds and Matrigel plugs. Our findings show the proangiogenic properties of QK, suggesting that also in vivo this peptide resembles the full VEGF protein. These data open to new fields of investigation on the mechanisms of activation of VEGF receptors, offering clinical implications for treatment of pathophysiological conditions such as chronic ischemia.
The mathematics of tanning
Authors: Thingnes Josef , Øyehaug Leiv , Hovig Eivind , Omholt Stig W
Published: June 2009

Background

The pigment melanin is produced by specialized cells, called melanocytes. In healthy skin, melanocytes are sparsely spread among the other cell types in the basal layer of the epidermis. Sun tanning results from an UV-induced increase in the release of melanin to neighbouring keratinocytes, the major cell type component of the epidermis as well as redistribution of melanin among these cells. Here we provide a mathematical conceptualization of our current knowledge of the tanning response, in terms of a dynamic model. The resolution level of the model is tuned to available data, and its primary focus is to describe the tanning response following UV exposure.

Results

The model appears capable of accounting for available experimental data on the tanning response in different skin and photo types. It predicts that the thickness of the epidermal layer and how far the melanocyte dendrites grow out in the epidermal layers after UV exposure influence the tanning response substantially.

Conclusion

Despite the paucity of experimental validation data the model is constrained enough to serve as a foundation for the establishment of a theoretical-experimental research programme aimed at elucidating the more fine-grained regulatory anatomy underlying the tanning response.
Yield-determining factors in high-solids enzymatic hydrolysis of lignocellulose
Authors: Kristensen Jan B , Felby Claus , Jørgensen Henning
Published: June 2009

Background

Working at high solids (substrate) concentrations is advantageous in enzymatic conversion of lignocellulosic biomass as it increases product concentrations and plant productivity while lowering energy and water input. However, for a number of lignocellulosic substrates it has been shown that at increasing substrate concentration, the corresponding yield decreases in a fashion which can not be explained by current models and knowledge of enzyme-substrate interactions. This decrease in yield is undesirable as it offsets the advantages of working at high solids levels. The cause of the 'solids effect' has so far remained unknown.

Results

The decreasing conversion at increasing solids concentrations was found to be a generic or intrinsic effect, describing a linear correlation from 5 to 30% initial total solids content (w/w). Insufficient mixing has previously been shown not to be involved in the effect. Hydrolysis experiments with filter paper showed that neither lignin content nor hemicellulose-derived inhibitors appear to be responsible for the decrease in yields. Product inhibition by glucose and in particular cellobiose (and ethanol in simultaneous saccharification and fermentation) at the increased concentrations at high solids loading plays a role but could not completely account for the decreasing conversion. Adsorption of cellulases was found to decrease at increasing solids concentrations. There was a strong correlation between the decreasing adsorption and conversion, indicating that the inhibition of cellulase adsorption to cellulose is causing the decrease in yield.

Conclusion

Inhibition of enzyme adsorption by hydrolysis products appear to be the main cause of the decreasing yields at increasing substrate concentrations in the enzymatic decomposition of cellulosic biomass. In order to facilitate high conversions at high solids concentrations, understanding of the mechanisms involved in high-solids product inhibition and adsorption inhibition must be improved.
Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer
Authors: Li Meng , Balch Curt , Montgomery John S , Jeong Mikyoung , Chung Jae Hoon , Yan Pearlly , Huang Tim HM , Kim Sun , Nephew Kenneth P
Published: June 2009

Background

Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s) underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI) methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition.

Methods

To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis.

Results

Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99) between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance) following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells.

Conclusion

Selective epigenetic disruption of distinct biological pathways was observed during development of platinum resistance in ovarian cancer. Integrated analysis of DNA methylation and gene expression may allow for the identification of new therapeutic targets and/or biomarkers prognostic of disease response. Finally, our results suggest that epigenetic therapies may facilitate the prevention or reversal of transcriptional repression responsible for chemoresistance and the restoration of sensitivity to platinum-based chemotherapeutics.
Fractionated irradiation induced radio-resistant esophageal cancer EC109 cells seem to be more sensitive to chemotherapeutic drugs
Authors: Xie Li , Song Xianrang , Yu Jinming , Wei Ling , Song Bao , Wang Xingwu , Lv Liyan
Published: June 2009

Background

Chemo-radiotherapy, a combination of chemotherapy and radiotherapy, is the most frequent treatment for patients with esophageal cancer. In the process of radiotherapy, the radiosensitive cancer will become a radio-resistant one.

Methods

In order to detect the chemotherapeutic drug sensitivity in radio-resistant cancer cells and improve the therapy efficiency, we firstly established a radio-resistant esophageal cancer cell model (referred to as EC109/R) from the human esophageal squamous cell carcinoma cell line EC109 through fractionated irradiation using X-rays. The radio-sensitivity of EC109/R cells was measured by clonogenic assay. To detect the drug sensitivity for EC109/R compared to its parent cells, we employed MTT method to screen the effectiveness of five different drugs commonly used in clinical therapy. The ratio of apoptosis was examined by flow cytometry.

Results

EC109/R cells were more sensitive to 5-fluorouracil, doxorubicin, paclitaxel and etoposide, but tolerant to cisplatin compared to its original cells.

Conclusion

Our study implies that fractionated irradiation induced radio-resistant esophageal cancer cell is more sensitive to certain kind of chemotherapeutic drugs. It provides evidence for choosing the sequence of radiotherapy and chemotherapy in esophageal cancer.