bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic use among 8-month-old children in Malmö, Sweden – in relation to child characteristics and parental sociodemographic, psychosocial and lifestyle factors
Authors: Mangrio Elisabeth , Wremp Anna , Moghaddassi Mahnaz , Merlo Juan , Bramhagen Ann-Cathrine , Rosvall Maria
Published: May 2009

Background

In the county of Scania, Sweden, antibiotic use among small children is among the highest in the country. The aim of this study was to investigate the associations between antibiotic use among 8-month-old children in Malmö and characteristics of the child as well as parental sociodemographic characteristics, lifestyle factors, and psychosocial support.

Methods

The study was a population-based cross-sectional survey. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmö for their 8-month health checkup during 2003–2006 and whose parents answered a self-administered questionnaire (n = 7266 children). The questionnaire was distributed to parents of children registered with the CHC and invited for an 8-month checkup during the study period.

Results

The odds of using antibiotics increased as parental educational level decreased. Using high educational level as a reference group, low maternal educational level was associated with an increased antibiotic use for the child, odds ratio (OR) = 1.61 (95% CI: 1.34–1.93). Furthermore, children whose parents were born outside Sweden showed higher antibiotic use, OR = 1.43 (95% CI: 1.24–1.65), in comparison with children whose parents were born in Sweden. Exposure to environmental smoking, parental experience of economic stress, and a low level of emotional support increased the odds for antibiotic use. Boys had higher odds of use of antibiotics than girls, OR = 1.40 (95% CI: 1.25–1.57). Having a low birth weight, having an allergy and having siblings also increased the odds for early antibiotic use, while breastfeeding seemed to have a protective role.

Conclusion

There were clear associations between parental factors such as sociodemographic, psychosocial and lifestyle factors and antibiotic use at this early stage of life. Several characteristics of the child also affected the use of antibiotics.
Insufficient quality of sputum submitted for tuberculosis diagnosis and associated factors, in Klaten district, Indonesia
Authors: Sakundarno Mateus , Nurjazuli Nurjazuli , Jati Sutopo Patria , Sariningdyah Retna , Purwadi Sumarsono , Alisjahbana Bachti , van der Werf Marieke J
Published: May 2009

Background

Sputum smear microscopy is the standard diagnostic method for detection of smear positive pulmonary tuberculosis (TB). Insufficient quality of sputum might result in missing cases. In this study we aimed at assessing the quality of sputum in a district in Central Java and determining patient and health worker factors associated with submission of three good quality sputum samples.

Methods

In 16 health centers information was collected on the quality of sputum submitted by TB suspects, i.e. volume, color, and viscosity. TB suspects were interviewed to assess their knowledge of TB, motivation to provide sputum and whether they were informed why and how to produce a sputum sample. Health workers were interviewed to assess what information they provided to TB suspects about the reason for sputum examination, methods to produce sputum and characteristics of a good quality sputum sample. All health worker and patient factors were evaluated for association with sputum quality.

Results

Of 387 TB suspects, 294 (76.0%) could be traced and interviewed, and of 272 (70.3%) information about sputum quality was available. Of those 203 (74.6%) submitted three samples, 90 (33.1%) provided at least one good sample, and 37 (13.6%) provided three good quality sputum samples. Of the 272 TB suspects, 168 (61.8%) mentioned that information on the reason for sputum examination was provided, 66 (24.3%) remembered that they were informed about how to produce sputum and 40 (14.7%) recalled being informed about the characteristics of good quality sputum. Paramedics reported to provide often/always information on the importance of sputum examination, and when to produce sputum. Information on how to produce sputum and characteristics of a good sputum sample was less often provided. None of the studied patient characteristics or health worker factors was associated with providing good quality sputum.

Conclusion

A considerable number of TB suspects did not provide three sputum samples and a large number of sputum samples were of insufficient quality. Training of health workers in providing health education to the TB suspect about the reason for sputum examination and how to produce a good quality sputum sample should be a priority of the TB program.
Maternal and perinatal guideline development in hospitals in South East Asia: results from the SEA-ORCHID project
Authors: Thinkhamrop Jadsada , Turner Tari , Subramaniam Sivasangari ,   The SEA-ORCHID Study Group
Published: May 2009

Background

Recognising the potential of clinical practice guidelines (CPGs) to improve practice, one of the strategies of the SEA-ORCHID project was to facilitate the development of evidence-based CPGs, and to support clinical staff in each of the four countries to build their skills in development of CPGs in the nine participating hospitals in Thailand, Malaysia, Philippines and Indonesia. This study was undertaken to investigate the impact of the SEA-ORCHID project on development of evidence-based CPGs.

Methods

Data on the CPGs available to support maternal and perinatal healthcare were collected by SEA-ORCHID team members at each hospital before and after the intervention period of the project.

Results

There were only a few evidence-based CPGs available in the SEA-ORCHID hospitals before the intervention period. After the intervention period, in the SEA-ORCHID hospitals in Malaysia and Indonesia there was no change in evidence-based CPG development activity in maternal and perinatal care. In Thailand and The Philippines there was a small increase in evidence-based CPG development activity in maternal and perinatal care.

Conclusion

Despite the wide range of interventions to support evidence-based CPG development implemented in the hospitals participating in the SEA-ORCHID, very little change was seen in the development of evidence-based CPGs.
The receptor RAGE: Bridging inflammation and cancer
Authors: Riehl Astrid , Németh Julia , Angel Peter , Hess Jochen
Published: May 2009

The receptor for advanced glycation end products (RAGE) is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability ofRageknockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.
Phylogenetic analysis of three genes of Penguinpox virus corresponding to Vaccinia virus G8R (VLTF-1), A3L (P4b) and H3L reveals that it is most closely related to Turkeypox virus, Ostrichpox virus and Pigeonpox virus
Authors: Carulei Olivia , Douglass Nicola , Williamson Anna-Lise
Published: May 2009

Phylogenetic analysis of three genes of Penguinpox virus, a novel Avipoxvirus isolated from African penguins, reveals its relationship to other poxviruses. The genes corresponding to Vaccinia virus G8R (VLTF-1), A3L (P4b) and H3L were sequenced and phylogenetic trees (Neighbour-Joining and UPGMA) constructed from MUSCLE nucleotide and amino acid alignments of the equivalent sequences from several different poxviruses. Based on this analysis, PEPV was confirmed to belong to the genus Avipoxvirus, specifically, clade A, subclade A2 and to be most closely related to Turkeypox virus (TKPV), Ostrichpox virus (OSPV)and Pigeonpox virus (PGPV).
Dietary fatty acid intake affects the risk of developing bone marrow lesions in healthy middle-aged adults without clinical knee osteoarthritis: a prospective cohort study
Authors: Wang Yuanyuan , Davies-Tuck Miranda L , Wluka Anita E , Forbes Andrew , English Dallas R , Giles Graham G , O'Sullivan Richard , Cicuttini Flavia M
Published: May 2009

Introduction

Fatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.

Methods

Two hundred ninety-seven middle-aged adults without clinical knee OA underwent magnetic resonance imaging (MRI) of their dominant knee at baseline. BMLs were assessed. Of the 251 participants with no BMLs in their knee at baseline, 230 underwent MRI of the same knee approximately 2 years later. Intakes of fatty acids were estimated from a food frequency questionnaire.

Results

Increased consumption of saturated fatty acids was associated with an increased incidence of BMLs over 2 years after adjusting for energy intake, age, gender, and body mass index (odds ratio of 2.56 for each standard deviation increase in dietary intake, 95% confidence interval 1.03 to 6.37, P = 0.04). Intake of monounsaturated or polyunsaturated fatty acids was not significantly associated with the incidence of BMLs.

Conclusions

Increased fatty acid consumption may increase the risk of developing BMLs. As subchondral bone is important in maintaining joint integrity and the development of OA, this study suggests that dietary modification of fatty acid intake may be one strategy in the prevention of knee OA which warrants further investigation.
Gene expression in murine mammary epithelial stem cell-like cells shows similarities to human breast cancer gene expression
Authors: Williams Cecilia , Helguero Luisa , Edvardsson Karin , Haldosén Lars-Arne , Gustafsson Jan-Åke
Published: May 2009

Introduction

Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a detailed characterization of the transcriptome in mammary stem cells is essential.

Methods

We have used a murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique. Subsequently, we have performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures, and correlated gene expression to in vivo mammary gland development.

Results

Our analysis of mammary stem-like and stepwise cell differentiation, and an in-depth description of our findings in a breast cancer perspective provide a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. We correlate the alterations to in vivo mammary gland differentiation, and describe novel changes in nuclear receptor gene expression. Interestingly, our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression.

Conclusions

The transcriptional characterization of these mammary stem-like cells and their differentiation-induced gene expression patterns is here made widely accessible and provides a basis for research on mammary stem-like cells. Our comparisons suggest that some tumors are more stem-like than others, with a corresponding worse prognosis. This information would, if established, be important for treatment decisions. We also suggest several marker candidates valuable to investigate further.
Follicle-Stimulating Hormone (FSH) Transiently Blocks FSH Receptor Transcription by Increasing Inhibitor of Deoxyribonucleic Acid Binding/Differentiation-2 and Decreasing Upstream Stimulatory Factor Expression in Rat Sertoli Cells
Authors: Viswanathan Pushpa , Wood Michelle A. , Walker William H.
Published: May 2009

FSH acts through the FSH receptor (FSHR) to modulate cell processes that are required to support developing spermatozoa. Within the testis, only Sertoli cells possess receptors for FSH and are the major targets for this regulator of spermatogenesis. FSH stimulation of Sertoli cells for 24–48 h is known to induce Fshr mRNA expression through an E-box motif (CACGTG) located 25 bp upstream of the transcription start site. In contrast, FSH stimulation for 8 h inhibits Fshr transcription. DNA-protein binding studies performed using nuclear extracts from Sertoli cells show that protein binding to the Fshr promoter E-box was reduced 68% after 6 h of FSH stimulation but increased 191% over basal levels after 48 h of stimulation. The proteins binding to the Fshr E-box were identified as upstream stimulatory factor (USF)-1 and -2. FSH stimulation transiently decreased USF1 levels and increased the expression of the inhibitor of DNA binding/differentiation (ID)-2 repressor protein with the same kinetics as the decreased USF/E-box interactions. Overexpression of ID2 resulted in a dose-dependent decrease in USF-driven Fshr promoter activity in the MSC-1 Sertoli cell line, and ID2 inhibited USF binding to the Fshr E-box. Together, these studies suggest that stimulation of Sertoli cells with FSH transiently decreases expression of the USF1 activator and induces accumulation of the ID2 repressor, to block USF binding to the Fshr promoter and delay activation of Fshr transcription. This FSH-regulated mechanism may explain the cyclical changes in Fshr expression that occurs in Sertoli cells in vivo.
Testosterone Programs Adult Social Behavior before and during, But Not after, Adolescence
Authors: Schulz Kalynn M. , Zehr Julia L. , Salas-Ramirez Kaliris Y. , Sisk Cheryl L.
Published: May 2009

Whereas the adolescent brain is a major target for gonadal hormones, our understanding of hormonal influences on adolescent neural and behavioral development remains limited. These experiments investigated how variations in the timing of testosterone (T) exposure, relative to adolescence, alters the strength of steroid-sensitive neural circuits underlying social behavior in male Syrian hamsters. Experiment 1 simulated early, on-time, and late pubertal development by gonadectomizing males on postnatal d 10 and treating with SILASTIC brand T implants for 19 d before, during, or after adolescence. T treatment before or during, but not after, adolescence facilitated mating behavior in adulthood. In addition, preadolescent T treatments most effectively increased mating behavior overall, indicating that the timing of exposure to pubertal hormones contributes to individual differences in adult behavior. Experiment 2 examined the effects of preadolescent T treatment on behavior and brain regional volumes within the mating neural circuit of juvenile males (i.e. still preadolescent). Although preadolescent T treatment did not induce reproductive behavior in juvenile males, it did increase volumes of the bed nucleus of the stria terminalis, sexually dimorphic nucleus, posterodorsal medial amygdala, and posteroventral medial amygdala to adult-typical size. In contrast, juvenile anterodorsal medial amygdala and ventromedial hypothalamus volumes were not changed by preadolescent T treatment yet differed significantly in volume from adult controls, suggesting that further maturation of these brain regions during adolescence is required for the expression of male reproductive behavior. Thus, adolescent maturation of social behavior may involve both steroid-independent and -dependent processes, and adolescence marks the end of a postnatal period of sensitivity to steroid-dependent organization of the brain.
Adipose Tissue Inflammation: Developmental Ontogeny and Consequences of Gestational Nutrient Restriction in Offspring
Authors: Sharkey Don , Symonds Michael E. , Budge Helen
Published: May 2009

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient-restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28–80 d, term ∼147 d) or late (110–147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.
The Enhanced Hypercalcemic Response to 20-Epi-1,25-Dihydroxyvitamin D3 Results from a Selective and Prolonged Induction of Intestinal Calcium-Regulating Genes
Authors: Zella Lee A. , Meyer Mark B. , Nerenz Robert D. , Pike J. Wesley
Published: May 2009

20-Epi-1,25-dihydroxyvitamin D3 (20-epi-1,25(OH)2D3) is a vitamin D analog that exhibits unique biologic properties. The mechanism(s) responsible for these activities remains unclear. Here we explore the ability of 20-epi-1,25(OH)2D3 to induce calcemic responses in mice in vivo and identify a potential mechanism. Surprisingly, the levels of calcemia induced at 24 h after single injections of equivalent doses of 1,25(OH)2D3 or 20-epi-1,25(OH)2D3 were similar, suggesting that both compounds were equal in both potency and efficacy. This similarity was also observed at genes involved in calcium homeostasis including, S100g (calbindin D9K), Trpv6, Cldn2 (claudin 2), Trpv5, and Tnfsf11 (Rankl) as well as Cyp24a1. Despite this, the activities of the two compounds at 48 h were strikingly different. Thus, whereas the activity of 1,25-dihydroxyvitamin D3 declined at this time point, the response to 20-epi-1,25(OH)2D3 was increased. This unique profile was not due to an exaggerated induction of calcium regulating genes in the intestine, kidney, or bone but to a sustained action on these genes in the intestine. This conclusion was supported by studies using in vivo chromatin immunoprecipitation analysis, which revealed a prolonged presence of vitamin D receptor and RNA polymerase II at the Trpv6 and Cyp24a1 promoters and a sustained increase in histone 4 acetylation in these gene regions as well. We conclude that 20-epi-1,25(OH)2D3 displays superagonist properties largely as a result of its duration of action in the intestine. This action is likely due to a decrease in the rate of intestinal-specific degradation of the ligand rather than to an increase in the functional stability of the vitamin D receptor.
Insulin and Insulin-Like Growth Factor-I Receptors Differentially Mediate Insulin-Stimulated Adhesion Molecule Production by Endothelial Cells
Authors: Li Guolian , Barrett Eugene J. , Ko Seung-Hyun , Cao Wenhong , Liu Zhenqi
Published: May 2009

Patients with type 2 diabetes are hyperinsulinemic and insulin resistant and develop premature atherosclerosis. High concentrations of insulin stimulate the production of adhesion molecules by endothelial cells (ECs). ECs express abundant IGF-I receptors as well as insulin receptors. Whether IGF-I receptors contribute to insulin-induced endothelial production of adhesion molecules is unknown. Bovine aortic ECs (BAECs) were incubated with insulin (100 nm) for 24 h. The cellular content of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was measured, and monocyte adhesion to ECs was quantified. Insulin increased both VCAM-1 (P < 0.001) and ICAM-1 (P < 0.0002) content, which was accompanied by an increased number of monocytes adherent to BAECs (P = 0.0001). Inhibition of either MAPK kinase-1 or p38 MAPK but not phosphatidylinositol 3-kinase abolished insulin-mediated production of adhesion molecules. Insulin receptor small interfering RNA knockdown abolished insulin-stimulated increases of ICAM-1 but not VCAM-1. Conversely, IGF-I receptor blockade with either a neutralizing antibody or specific small interfering RNA eliminated insulin-induced VCAM-1 but not ICAM-1 production. Blockade of signaling via either the insulin or IGF-I receptors decreased monocyte adherence to BAECs (P < 0.01 for each). We conclude that insulin and IGF-I receptors differentially mediate the production of adhesion molecules by ECs and monocyte adhesion onto the vascular endothelium in response to the hyperinsulinemic state. Dual-receptor activation may most effectively contribute to the pathogenesis of atherosclerotic disease in diabetes.
Extralarge XLαs (XXLαs), a Variant of Stimulatory G Protein α-Subunit (Gsα), Is a Distinct, Membrane-Anchored GNAS Product that Can Mimic Gsα
Authors: Aydin Cumhur , Aytan Nurgul , Mahon Mathew J. , Tawfeek Hesham A. W. , Kowall Neil W. , Dedeoglu Alpaslan , Bastepe Murat
Published: May 2009

GNAS gives rise to multiple imprinted gene products, including the α-subunit of the stimulatory G protein (Gsα) and its variant XLαs. Based on genomic sequence, the translation of XLαs begins from the middle of a long open reading frame, suggesting the existence of an N-terminally extended variant termed extralarge XLαs (XXLαs). Although XXLαs, like Gsα and XLαs, would be affected by most disease-causing GNAS mutations, its authenticity and biological significance remained unknown. Here we identified a mouse cDNA clone that comprises the entire open reading frame encoding XXLαs. Whereas XXLαs mRNA was readily detected in mouse heart by RT-PCR, it appeared virtually absent in insulinoma-derived INS-1 cells. By Northern blots and RT-PCR, XXLαs mRNA was detected primarily in the mouse brain, cerebellum, and spleen. Immunohistochemistry using a specific anti-XXLαs antibody demonstrated XXLαs protein in multiple brain areas, including dorsal hippocampus and cortex. In transfected cells, full-length human XXLαs was localized to the plasma membrane and mediated isoproterenol- and cholera toxin-stimulated cAMP accumulation. XXLαs-R844H, which bears a mutation analogous to that in the constitutively active Gsα mutant Gsα-R201H (gsp oncogene), displayed elevated basal signaling. However, unlike Gsα-R201H, which mostly remains in the cytoplasm, both XXLαs-R844H and a constitutively active XLαs mutant localized to the plasma membrane. Hence, XXLαs is a distinct GNAS product and can mimic Gsα, but the constitutively active XXLαs and Gsα mutants differ from each other regarding subcellular targeting. Our findings suggest that XXLαs deficiency or hyperactivity may contribute to the pathogenesis of diseases caused by GNAS mutations.
p54nrb Is a Transcriptional Corepressor of the Progesterone Receptor that Modulates Transcription of the Labor-Associated Gene, Connexin 43 (Gja1)
Authors: Dong Xuesen , Yu Celeste , Shynlova Oksana , Challis John R. G. , Rennie Paul S. , Lye Stephen J.
Published: May 2009

The progesterone receptor (PR) plays important roles in the establishment and maintenance of pregnancy. By dynamic interactions with coregulators, PR represses the expression of genes that increase the contractile activity of myometrium and contribute to the initiation of labor. We have previously shown that PTB-associated RNA splicing factor (PSF) can function as a PR corepressor. In this report, we demonstrated that the PSF heterodimer partner, p54nrb (non-POU-domain-containing, octamer binding protein), can also function as a transcription corepressor, independent of PSF. p54nrb Interacts directly with PR independent of progesterone. In contrast to PSF, p54nrb neither enhances PR protein degradation nor blocks PR binding to DNA. Rather, p54nrb recruits mSin3A through its N terminus to the PR-DNA complex, resulting in an inhibition of PR-mediated transactivation of the progesterone-response element-luciferase reporter gene. PR also repressed transcription of the connexin 43 gene (Gja1), an effect dependent on the presence of an activator protein 1 site within the proximal Gja1 promoter. Mutation of this site abolished PR-mediated repression and decreased the recruitment of PR and p54nrb onto the Gja1 promoter. Furthermore, knockdown p54nrb expression by small interfering RNA alleviated PR-mediated repression on Gja1 transcription, whereas overexpression of p54nrb enhanced it. In the physiological context of pregnancy, p54nrb protein levels decrease with the approach of labor in the rat myometrium. We conclude that p54nrb is a transcriptional corepressor of PR. Decreased expression of p54nrb at the time of labor may act to derepress PR-mediated inhibition on connexin 43 expression and contribute to the initiation of labor.
Drosophila ptipis essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways
Authors: Fang Ming , Ren Hongyan , Liu Jiabin , Cadigan Ken M. , Patel Sanjeevkumar R. , Dressler Gregory R.
Published: May 2009

Development of the fruit fly Drosophila depends in part on epigenetic regulation carried out by the concerted actions of the Polycomb and Trithorax group of proteins, many of which are associated with histone methyltransferase activity. Mouse PTIP is part of a histone H3K4 methyltransferase complex and contains six BRCT domains and a glutamine-rich region. In this article, we describe an essential role for the Drosophila ortholog of the mammalian Ptip (Paxip1)gene in early development and imaginal disc patterning. Both maternal and zygotic ptip are required for segmentation and axis patterning during larval development. Loss of ptip results in a decrease in global levels of H3K4 methylation and an increase in the levels of H3K27 methylation. In cell culture, Drosophila ptip is required to activate homeotic gene expression in response to the derepression of Polycomb group genes. Activation of developmental genes is coincident with PTIP protein binding to promoter sequences and increased H3K4 trimethylation. These data suggest a highly conserved function for ptip in epigenetic control of development and differentiation.
SDF1/CXCR4 signalling regulates two distinct processes of precerebellar neuronal migration and its depletion leads to abnormal pontine nuclei formation
Authors: Zhu Yan , Matsumoto Tomoko , Mikami Sakae , Nagasawa Takashi , Murakami Fujio
Published: May 2009

The development of mossy-fibre projecting precerebellar neurons (PCN)presents a classical example of tangential neuronal migration. PCN migrate tangentially along marginal streams beneath the pial surface from the lower rhombic lip to specific locations in the hindbrain, where they form precerebellar nuclei. Among them, the pontine neurons follow a stereotypic anteroventral-directed pathway to form the pontine nuclei in the pons. The guidance mechanisms that determine the marginal migration of PCN and the anterior migration of pontine neurons are poorly understood. Here, we report that a chemokine SDF1 (also known as CXCL12) derived from the meningeal tissue regulates the migratory pathways of PCN. PCN are chemoattracted by the meningeal tissue, an effect that is mimicked by an SDF1 source. Analysis of knockout mice for the Sdf1 receptor Cxcr4 shows that both the marginal migration of PCN and the anterior migration of pontine neurons are disrupted. We provide further evidence that SDF1/CXCR4 signalling regulates these two processes cell-autonomously. As a result of disrupted neuronal migration, pontine nuclei formation was highly abnormal, with the presence of multiple ectopic pontine clusters posteriorly. The ectopic pontine clusters led to ectopic collateral branch formation from the corticospinal tract. Our results together demonstrate crucial roles for SDF1/CXCR4 in multiple aspects of PCN migration and highlight the deleterious consequence of derailed migration on proper nuclei formation. Furthermore, we provide the first in vivo evidence that pontine neurons themselves induce collateral branching from the corticospinal axons.
Regulation of membrane trafficking and organ separation by the NEVERSHED ARF-GAP protein
Authors: Liljegren Sarah J. , Leslie Michelle E. , Darnielle Lalitree , Lewis Michael W. , Taylor Sarah M. , Luo Ruibai , Geldner Niko , Chory Joanne , Randazzo Paul A. , Yanofsky Martin F. , Ecker Joseph R.
Published: May 2009

Cell separation, or abscission, is a highly specialized process in plants that facilitates remodeling of their architecture and reproductive success. Because few genes are known to be essential for organ abscission, we conducted a screen for mutations that alter floral organ shedding in Arabidopsis. Nine recessive mutations that block shedding were found to disrupt the function of an ADP-ribosylation factor-GTPase-activating protein (ARF-GAP) we have named NEVERSHED (NEV). As predicted by its homology to the yeast Age2 ARF-GAP and transcriptional profile, NEV influences other aspects of plant development, including fruit growth. Co-localization experiments carried out with NEV-specific antiserum and a set of plant endomembrane markers revealed that NEV localizes to the trans-Golgi network and endosomes in Arabidopsis root epidermal cells. Interestingly, transmission electron micrographs of abscission zone regions from wild-type and nev flowers reveal defects in the structure of the Golgi apparatus and extensive accumulation of vesicles adjacent to the cell walls. Our results suggest that NEV ARF-GAP activity at the trans-Golgi network and distinct endosomal compartments is required for the proper trafficking of cargo molecules required for cell separation.
The neural crest epithelial-mesenchymal transition in 4D: a `tail' of multiple non-obligatory cellular mechanisms
Authors: Ahlstrom Jon D. , Erickson Carol A.
Published: May 2009

An epithelial-mesenchymal transition (EMT) is the process whereby epithelial cells become mesenchymal cells, and is typified by the generation of neural crest cells from the neuroepithelium of the dorsal neural tube. To investigate the neural crest EMT, we performed live cell confocal time-lapse imaging to determine the sequence of cellular events and the role of cell division in the EMT. It was observed that in most EMTs, the apical cell tail is retracted cleanly from the lumen of the neuroepithelium, followed by movement of the cell body out of the neural tube. However, exceptions to this sequence include the rupture of the neural crest cell tail during retraction(junctional complexes not completely downregulated), or translocation of the cell body away from the apical surface while morphologically rounded up in M phase (no cell tail retraction event). We also noted that cell tail retraction can occur either before or after the redistribution of apical-basolateral epithelial polarity markers. Surprisingly, we discovered that when an EMT was preceded by a mitotic event, the plane of cytokinesis does not predict neural crest cell fate. Moreover, when daughter cells are separated from the adherens junctions by a parallel mitotic cleavage furrow, most re-establish contact with the apical surface. The diversity of cellular mechanisms by which neural crest cells can separate from the neural tube suggests that the EMT program is a complex network of non-linear mechanisms that can occur in multiple orders and combinations to allow neural crest cells to escape from the neuroepithelium.
Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte
Authors: Norris Rachael P. , Ratzan William J. , Freudzon Marina , Mehlmann Lisa M. , Krall Judith , Movsesian Matthew A. , Wang Huanchen , Ke Hengming , Nikolaev Viacheslav O. , Jaffe Laurinda A.
Published: May 2009

Mammalian oocytes are arrested in meiotic prophase by an inhibitory signal from the surrounding somatic cells in the ovarian follicle. In response to luteinizing hormone (LH), which binds to receptors on the somatic cells, the oocyte proceeds to second metaphase, where it can be fertilized. Here we investigate how the somatic cells regulate the prophase-to-metaphase transition in the oocyte, and show that the inhibitory signal from the somatic cells is cGMP. Using FRET-based cyclic nucleotide sensors in follicle-enclosed mouse oocytes, we find that cGMP passes through gap junctions into the oocyte,where it inhibits the hydrolysis of cAMP by the phosphodiesterase PDE3A. This inhibition maintains a high concentration of cAMP and thus blocks meiotic progression. LH reverses the inhibitory signal by lowering cGMP levels in the somatic cells (from ∼2 μM to ∼80 nM at 1 hour after LH stimulation)and by closing gap junctions between the somatic cells. The resulting decrease in oocyte cGMP (from ∼1 μM to ∼40 nM) relieves the inhibition of PDE3A, increasing its activity by ∼5-fold. This causes a decrease in oocyte cAMP (from ∼700 nM to ∼140 nM), leading to the resumption of meiosis.
Selection Neglect in Mutual Fund Advertisements
Authors: Koehler Jonathan J. , Mercer Molly
Published: May 2009

Mutual fund companies selectively advertise their better-performing funds. However, investors respond to advertised performance data as if those data were unselected (i.e., representative of the population). We identify the failure to discount selected or potentially selected data as selection neglect. We examine these phenomena in an archival study (Study 1) and two controlled experiments (Studies 2 and 3). Study 1 identifies selection bias in mutual fund advertising by showing that the median performance rank for advertised funds is between the 79th and 100th percentile. Study 2 finds that both novice investors and financial professionals fall victim to selection neglect in a financial advertising task unless the advertisement makes the selective nature of available performance data transparent. Study 3 shows that selection neglect associated with a large well-known company can be debiased with a simple extrinsic sample space cue, although individual differences in statistical reasoning also matter. We argue that selection neglect results from a general tendency to ignore underlying sample spaces rather than a fundamental misunderstanding about the data selection process or the value of selected data.
Technological Innovation and Acquisitions
Authors: Zhao Xinlei
Published: May 2009

I examine whether technological innovation is a motivating factor in firms' acquisition decisions and how an acquisition (or an acquisition withdrawal) affects technological innovation in subsequent years. I find that firms engaging in acquisition activities are less innovative and have often experienced declines in technological innovation during the years prior to the bid. Among the bidders, the relatively more innovative ones are less likely to complete a deal. During the three years after the bid, successful bidders do not underperform matching firms, whereas failed bidders significantly underperform their nonbidding peers. I further find that formerly less innovative bidders benefit more from acquisitions. These findings suggest that technological innovation affects firms' acquisition decisions, and in turn, acquisitions help firms' innovation efforts.
New Insights into Pedestrian Flow Through Bottlenecks
Authors: Seyfried Armin , Passon Oliver , Steffen Bernhard , Boltes Maik , Rupprecht Tobias , Klingsch Wolfram
Published: May 2009

Capacity estimation is an important tool for the design and dimensioning of pedestrian facilities. The literature contains different procedures and specifications that show considerable differences with respect to the estimated flow values. Moreover, new experimental data indicate a stepwise growth of capacity with width and thus challenge the validity of the specific flow concept. To resolve these differences, we experimentally studied the unidirectional pedestrian flow through bottlenecks under laboratory conditions. The time development of quantities such as individual velocities, density, and individual time gaps in bottlenecks of different widths is presented. The data show a linear growth of flow with width. The comparison of the results with experimental data from other authors indicates that the basic assumption of the capacity estimation for bottlenecks has to be revised. In contrast to most planning guidelines, our main result is that a jam occurs even if the incoming flow does not overstep the capacity defined by the maximum flow according to the fundamental diagram.
A Study of Demand Stochasticity in Service Network Design
Authors: Lium Arnt-Gunnar , Crainic Teodor Gabriel , Wallace Stein W.
Published: May 2009

The objective of this paper is to investigate the importance of introducing stochastic elements into service network design formulations. To offer insights into this issue, we take a basic version of the problem in which periodic schedules are built for a number of vehicles and where only the demand may vary stochastically. We study how solutions based on uncertain demand differ from solutions based on deterministic demand and provide qualitative descriptions of the structural differences. Some of these structural differences provide a hedge against uncertainty by using consolidation. This way we get consolidation as output from the model rather than as an a priori required property. Service networks with such properties are robust, as seen by the customers, by providing operational flexibility.
Managing the impact of psychosis: A grounded theory exploration of recovery processes in psychosis
Authors: Dilks Sarah , Tasker Fiona , Wren Bernadette
Published: May 2009

Objectives. There has been little conceptual bridge building between what individuals report as helpful in recovery and how psychological therapy might impact on recovery in psychosis. This study explores the links between therapy and recovery in psychosis.

Design. Grounded theory was chosen as an appropriate methodology to distil an explanatory account across the qualitative data collected.

Methods. An initial sample of 19 therapy session tapes and 23 interviews with psychologists and clients engaged in psychological therapy in psychosis was collected and analysed using grounded theory. This data set was extended through the additional sampling and analysis of 31 published personal accounts of the experience of psychosis.

Results. The study reports on specific elements of a larger grounded theory study that particularly relate to recovery processes in psychosis. Specific categories of activity were conceptualised to theorise the key activities involved in managing the impact of psychosis.

Conclusions. Therapy in psychosis appeared to be aimed at enhancing clients' functioning in the social world. In an effort to achieve this, it seemed that clients engaged in an ongoing effort to manage the impact of psychosis on both their subjective experience and on day to day life. The conceptualisation of this effort as an active, ongoing, and individually‐directed process was consistent with other examinations of service user accounts.
Self‐engagement as a predictor of performance and emotional reactions to performance outcomes
Authors: Britt Thomas W. , McKibben Eric S. , Greene‐Shortridge Tiffany M. , Beeco Adam , Bodine Ashley , Calcaterra Jennifer , Evers Terri , McNab Jessica , West Amanda
Published: May 2009

Three studies examined the relationship between engagement in different types of tasks, performance on those tasks, and reactions to performance outcomes. The three studies included voting in the 2004 presidential election, test performance in an undergraduate course, and completion of personal projects during the course of the semester. Engagement in voting predicted voting in the presidential election and magnified positive feelings of voting for the winning candidate. Test engagement predicted performance on the test, and magnified positive feelings of not showing a discrepancy between expected and actual test performance. Engagement in personal projects interacted with task complexity to predict project completion, with engagement being related to goal completion for tasks high in complexity. Project engagement also magnified the positive effects of a high probability of completing the project. The results provide support for task engagement as a predictor of performance and as a facilitator of positive feelings following success.
Pro‐self, prosocial, and pro‐organizational foci of proactive behaviour: Differential antecedents and consequences
Authors: Belschak Frank D. , Den Hartog Deanne N.
Published: May 2009

The paper aims to further knowledge of proactive employee behaviour by exploring whether pro‐organizational, prosocial, and pro‐self focused proactive behaviour can be measured in an empirically distinct manner, and whether these types of proactive behaviour show differential relationships with other variables. Results of two multi‐source studies using self‐rated and peer‐rated measures empirically support the distinctiveness of the different foci of proactive behaviour. Study 1 (N = 117 dyads) shows that the different foci of proactive behaviour are differentially related to different foci of affective commitment. Study 2 (N = 126 dyads) builds on these findings and shows that different foci of proactive behaviour have differential relationships with transformational leadership, goal orientations, and individual task performance.
Cognitive behavioural therapy and psycho‐education for chronic fatigue syndrome in young people: Reflections from the families' perspective
Authors: Dennison Laura , Stanbrook Rachel , Moss‐Morris Rona , Yardley Lucy , Chalder Trudie
Published: May 2009

Objectives

Recent trials have produced optimistic results for family‐focussed cognitive behavioural therapy (CBT) for chronic fatigue syndrome (CFS) in young people. This study sought to examine the under‐researched question of the views and experiences of patients and families who take part.

Design

Semi‐structured interviews and qualitative analysis were chosen in order to address clients' perspectives in depth.

Methods

Sixteen young people and sixteen parents who participated in a trial of CBT versus psycho‐education (PE) for CFS were interviewed. Key themes were discerned using inductive thematic analysis.

Results

Most families had low expectations of a cure but hope for improvement. Generally speaking, participants found both CBT and PE acceptable and helpful. Behavioural aspects of CBT (e.g. goal‐setting, graded activity) were found helpful. The opportunity to gain support, recognition and validation was important. Cognitive elements of therapy were sometimes deemed inappropriate and some felt emotional aspects of CFS were not adequately addressed. Participants were ambivalent towards the extent of family involvement. Negative experiences related to the therapy setting and feeling inappropriately labeled. Most participants felt therapy was a stepping‐stone towards normal life, although many felt recovery was incomplete. Very few differences were found between themes from CBT and PE participants. A notable exception was that every young person who experienced CBT described therapy as helpful, whereas the participants who strongly opposed the therapy approach had all experienced PE.

Conclusions

The detailed insights regarding families' therapy experiences suggest areas of improvement for service delivery and topics for further investigation.
Molecular Species of the Alcohol Biomarker Phosphatidylethanol in Human Blood Measured by LC-MS
Authors: Helander Anders , Zheng Yufang
Published: May 2009

Background: The alcohol biomarker phosphatidylethanol (PEth) comprises a group of ethanol-derived phospholipids formed from phosphatidylcholine by phospholipase D. The PEth molecular species have a common phosphoethanol head group onto which 2 fatty acid moieties are attached. We developed an electrospray ionization (ESI) LC-MS method for qualitative and quantitative measurement of different PEth species in human blood.

Methods: We subjected a total lipid extract of whole blood to HPLC gradient separation on a C4 column and performed LC-ESI-MS analysis using selected ion monitoring of deprotonated molecules for the PEth species and phosphatidylpropanol (internal standard). Identification of individual PEth species was based on ESI–tandem mass spectrometry (MS/MS) analysis of product ions.

Results: The fatty acid moieties were the major product ions of PEth, based on comparison with PEth-16:0/16:0, 18:1/18:1, and 16:0/18:1 reference material. For LC-MS analysis of different PEth species in blood, we used a calibration curve covering 0.2–7.0 μmol/L PEth-16:0/18:1. The lower limit of quantitation of the method was <0.1 μmol/L, and intra- and interassay CVs were <9% and <11%. In blood samples collected from 38 alcohol patients, the total PEth concentration ranged between 0.1 and 21.7 μmol/L (mean 8.9). PEth-16:0/18:1 and 16:0/18:2 were the predominant molecular species, accounting for approximately 37% and 25%, respectively, of total PEth. PEth-16:0/20:4 and mixtures of 18:1/18:1 plus 18:0/18:2 (not separated using selected ion monitoring because of identical molecular masses) and 16:0/20:3 plus 18:1/18.2 made up approximately 13%, 12%, and 8%.

Conclusions: This LC-MS method allows simultaneous qualitative and quantitative measurement of several PEth molecular species in whole blood samples.