bluuebunny/crossref_metadata_2025 huggingface dataset:
The Wealth Tax and Entrepreneurial Activity
Authors: Hansson Asa
Published: December 2008

Entrepreneurship is often credited with generating important positive economic externalities, such as promoting innovation, discovering new markets and serving as a mechanism for knowledge spill-over. Governments increasingly view encouragement of entrepreneurship as an important policy objective. Economists have found taxation as an important determinant of entrepreneurship, particularly income tax and capital gains tax. One form of taxation that has not been considered so far is the wealth tax. The wealth tax is likely to influence entrepreneurship negatively by affecting the pool of capital available for start-up businesses as well as reducing the net return to successful entrepreneurs. This article illustrates the impact of wealth tax on entrepreneurship using a simple model of the choice between becoming an entrepreneur or an employee. Actual data are then used to investigate whether the wealth tax indeed has a measurable effect on self-employment in Organisation for Economic Cooperation and Development (OECD) countries. A differences-in-differences type estimator using the abolition of the wealth tax as a ‘natural experi-ment’ points to a consistent pattern of perceptible, but small impact.
Socio-economic Background of the Entrepreneurs and the Industrial Climate of the Small Scale Sector Industries in Orissa
Authors: Meher Rajkishor , Sahoo Renubala
Published: December 2008

The article seeks to analyse the causes of low growth/failure of small-scale industries (SSI) in a poor and industrially backward state like Orissa, notwithstanding its rich mineral resource endowments and a good number of professionally qualified and well experienced people heading the SSI units of the state as entrepreneurs. Based on a survey of the SSI units and interview of Oriya entrepreneurs by using a structured questionnaire in three of the largest and important cities of Orissa, the researchers have analysed the social, cultural and political factors that have stifled the growth of a conducive industrial climate for the success of SSI units in the State. Also, the factors that are responsible for the deficiency of good entrepreneurial quality among the Oriya entrepreneurs of the SSI sector have been looked into from the political economy and socio-political angles.
The Emergence of Family Nursing in Brazil
Authors: Angelo Margareth
Published: December 2008

A family perspective has been influencing Brazilian nursing practice and research, in particular in the past decade. Despite this development, there is evidence from research and from nurses' narratives that nurses still experience serious challenges in providing nursing care to families in Brazil. These challenges are analyzed and strategies are offered to support nurses in Brazil to “think family” and stimulate advanced practice in family nursing.
Cross Cultural Management Research
Authors: Gerhart Barry
Published: December 2008

National culture is widely viewed as a constraint on management practice. However, that view is increasingly inconsistent with available empirical evidence. Building on earlier work, this article maps out the key assumptions that must be met for cross cultural management research that uses national culture (mean) scores, such as those available from Hofstede and the GLOBE project, to yield relevant and interpretable findings. It is found that these assumptions are either inconsistent with available empirical evidence or have not been adequately addressed empirically. For example, for national culture to act as a constraint on management, cultural differences within countries should be small relative to differences between countries. Evidence shows, however, that this is not the case. As a consequence of the lack of support for this and other assumptions, the article suggests that cross cultural management research needs to proceed differently in the future and provides specific recommendations in this regard.
On measurement of retained austenite in multiphase TRIP steels — results of blind round robin test involving six different techniques
Authors: Jacques P. J. , Allain S. , Bouaziz O. , De A. , Gourgues A.-F. , Hance B. M. , Houbaert Y. , Huang J. , Iza-Mendia A. , Kruger S. E. , Radu M. , Samek L. , Speer J. , Zhao L. , van der Zwaag S.
Published: December 2008

The present paper reports the results of a blind round robin test dedicated to the measurement of the retained austenite content of different TRIP assisted multiphase steels. Various surface and volume techniques, i.e. light microscopy, X-ray diffraction, electron backscattered diffraction (EBSD), magnetic saturation, thermal diffusivity and laser ultrasonics, were used by different partners. The compiled results show a quite large variability of the estimated retained austenite content, particularly for well established techniques, such as X-ray diffraction (XRD) and magnetisation. On the other hand, emerging techniques like EBSD, thermal diffusivity and laser ultrasonics warrant further investigations.
Diffusion reaction between Zircaloy-2 and Inconel 750X
Authors: Laik A. , Gawde P. S. , Kale G. B. , Bhanumurthy K.
Published: December 2008

The interdiffusion reactions between Zircaloy-2 and a Ni based alloy (Inconel 750X) have been studied in the temperature range 1083–1173 K by employing annealing of diffusion couples. The reaction zone developed at the interface was characterised using an optical microscope and electron probe microanalyser (EPMA). The diffusion reaction between Zircaloy-2 and Inconel shows that the reaction products form both as a layered structure and as two phase mixture in the diffusion zone. Three layers were found to form in the diffusion zone, namely, Zr2Ni ( ξ phase) and ψ1 phase close to Zircaloy-2 and a mixture of ψ1 and ψ2 phases close to Inconel. The kinetics for the growth of the three layers as well as the total diffusion zone was established. The growth of all the layers shows Arrhenius type of relation with respect to temperature. The temperature dependence for the reaction constants, K, for the various phases was also established.
Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemia
Authors: French Deborah , Yang Wenjian , Cheng Cheng , Raimondi Susana C. , Mullighan Charles G. , Downing James R. , Evans William E. , Pui Ching-Hon , Relling Mary V.
Published: December 2008

Methotrexate polyglutamates (MTXPGs) determine in vivo efficacy in acute lymphoblastic leukemia (ALL). MTXPG accumulation differs by leukemic subtypes, but genomic determinants of MTXPG variation in ALL remain unclear. We analyzed 3 types of whole genome variation: leukemia cell gene expression and somatic copy number variation, and inherited single nucleotide polymorphism (SNP) genotypes and determined their association with MTXPGs in leukemia cells. Seven genes (FHOD3, IMPA2, ME2, RASSF4, SLC39A6, SMAD2, and SMAD4) displayed all 3 types of genomic variation associated with MTXPGs (P < .05 for gene expression, P < .01 for copy number variation and SNPs): 6 on chromosome 18 and 1 on chromosome 10. Increased chromosome 18 (P = .002) or 10 (P = .036) copy number was associated with MTXPGs even after adjusting for ALL subtype. The expression of the top 7 genes in leukemia cells accounted for more variation in MTXPGs (46%) than did the expression of the top 7 genes in normal HapMap cell lines (20%). The top 7 inherited SNPs in patients accounted for approximately the same degree of variation (17%) in MTXPGs as did the top 7 SNP genotypes in HapMap cell lines (20%). We conclude that acquired genetic variation in leukemia cells has a stronger influence on MTXPG accumulation than inherited genetic variation.
Arp2/3 complex activity in filopodia of spreading cells
Authors: Johnston Simon A , Bramble Jonathan P , Yeung Chun L , Mendes Paula M , Machesky Laura M
Published: December 2008

Background

Cells use filopodia to explore their environment and to form new adhesion contacts for motility and spreading. The Arp2/3 complex has been implicated in lamellipodial actin assembly as a major nucleator of new actin filaments in branched networks. The interplay between filopodial and lamellipodial protrusions is an area of much interest as it is thought to be a key determinant of how cells make motility choices.

Results

We find that Arp2/3 complex localises to dynamic puncta in filopodia as well as lamellipodia of spreading cells. Arp2/3 complex spots do not appear to depend on local adhesion or on microtubules for their localisation but their inclusion in filopodia or lamellipodia depends on the activity of the small GTPase Rac1. Arp2/3 complex spots in filopodia are capable of incorporating monomeric actin, suggesting the presence of available filament barbed ends for polymerisation. Arp2/3 complex in filopodia co-localises with lamellipodial proteins such as capping protein and cortactin. The dynamics of Arp2/3 complex puncta suggests that they are moving bi-directionally along the length of filopodia and that they may be regions of lamellipodial activity within the filopodia.

Conclusion

We suggest that filopodia of spreading cells have regions of lamellipodial activity and that this activity affects the morphology and movement of filopodia. Our work has implications for how we understand the interplay between lamellipodia and filopodia and for how actin networks are generated spatially in cells.
Genome wide survey, discovery and evolution of repetitive elements in three Entamoeba species
Authors: Lorenzi Hernan , Thiagarajan Mathangi , Haas Brian , Wortman Jennifer , Hall Neil , Caler Elisabet
Published: December 2008

Background

Identification and mapping of repetitive elements is a key step for accurate gene prediction and overall structural annotation of genomes. During the assembly and annotation of three highly repetitive amoeba genomes, Entamoeba histolytica, Entamoeba dispar, and Entamoeba invadens, we performed comparative sequence analysis to identify and map all class I and class II transposable elements in their sequences.

Results

Here, we report the identification of two novel Entamoeba-specific repeats: ERE1 and ERE2; ERE1 is spread across the three genomes and associated with different repeats in a species-specific manner, while ERE2 is unique to E. histolytica. We also report the identification of two novel subfamilies of LINE and SINE retrotransposons in E. dispar and provide evidence for how the different LINE and SINE subfamilies evolved in these species. Additionally, we found a putative transposase-coding gene in E. histolytica and E. dispar related to the mariner transposon Hydargos from E. invadens. The distribution of transposable elements in these genomes is markedly skewed with a tendency of forming clusters. More than 70% of the three genomes have a repeat density below their corresponding average value indicating that transposable elements are not evenly distributed. We show that repeats and repeat-clusters are found at syntenic break points between E. histolytica and E. dispar and hence, could work as recombination hot spots promoting genome rearrangements.

Conclusion

The mapping of all transposable elements found in these parasites shows that repeat coverage is up to three times higher than previously reported. LINE, ERE1 and mariner elements were present in the common ancestor to the three Entamoeba species while ERE2 was likely acquired by E. histolytica after its separation from E. dispar. We demonstrate that E. histolytica and E. dispar share their entire repertoire of LINE and SINE retrotransposons and that Eh_SINE3/Ed_SINE1 originated as a chimeric SINE from Eh/Ed_SINE2 and Eh_SINE1/Ed_SINE3. Our work shows that transposable elements are organized in clusters, frequently found at syntenic break points providing insights into their contribution to chromosome instability and therefore, to genomic variation and speciation in these parasites.
Rapid dissemination of Francisella tularensisand the effect of route of infection
Authors: Ojeda Sandra S , Wang Zheng J , Mares Chris A , Chang Tingtung A , Li Qun , Morris Elizabeth G , Jerabek Paul A , Teale Judy M
Published: December 2008

Background

Francisella tularensis subsp. tularensis is classified as a Category A bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. However, the virulence mechanisms of this organism are not well characterized. Francisella tularensis subsp. novicida, which is an equally virulent subspecies in mice, was used in concert with a microPET scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such dissemination compares with other routes of infection. Adult mice were inoculated intranasally with F. tularensis subsp. novicida radiolabeled with 64Cu and imaged by microPET at 0.25, 2 and 20 hours post-infection.

Results

64Cu labeled F. tularensis subsp. novicida administered intranasally or intratracheally were visualized in the respiratory tract and stomach at 0.25 hours post infection. By 20 hours, there was significant tropism to the lung compared with other tissues. In contrast, the images of radiolabeled F. tularensis subsp. novicida when administered intragastrically, intradermally, intraperitoneally and intravenouslly were more generally limited to the gastrointestinal system, site of inoculation, liver and spleen respectively. MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.

Conclusion

Our findings suggest that Francisella has a differential tissue tropism depending on the route of entry and that the virulence of Francisella by the pulmonary route is associated with a rapid bacteremia and an early preferential tropism to the lung. In addition, the use of the microPET device allowed us to identify the cecum as a novel site of colonization of Francisella tularensis subsp. novicida in mice.
Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells
Authors: Choi Chul Hee , Lee Jun Sik , Lee Yoo Chul , Park Tae In , Lee Je Chul
Published: December 2008

Background

Acinetobacter baumannii is a nosocomial pathogen of increasing importance, but the pathogenic mechanism of this microorganism has not been fully explored. This study investigated the potential of A. baumannii to invade epithelial cells and determined the role of A. baumannii outer membrane protein A (AbOmpA) in interactions with epithelial cells.

Results

A. baumannii invaded epithelial cells by a zipper-like mechanism, which is associated with microfilament- and microtubule-dependent uptake mechanisms. Internalized bacteria were located in the membrane-bound vacuoles. Pretreatment of recombinant AbOmpA significantly inhibited the adherence to and invasion of A. baumannii in epithelial cells. Cell invasion of isogenic AbOmpA- mutant significantly decreased as compared with wild-type bacteria. In a murine pneumonia model, wild-type bacteria exhibited a severe lung pathology and induced a high bacterial burden in blood, whereas AbOmpA- mutant was rarely detected in blood.

Conclusion

A. baumannii adheres to and invades epithelial cells. AbOmpA plays a major role in the interactions with epithelial cells. These findings contribute to the understanding of A. baumannii pathogenesis in the early stage of bacterial infection.
Intragenic tandem repeat variation between Legionella pneumophila strains
Authors: Coil David A , Vandersmissen Liesbeth , Ginevra Christophe , Jarraud Sophie , Lammertyn Elke , Anné Jozef
Published: December 2008

Background

Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system.

Results

In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs).

Conclusion

These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin.
Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone
Authors: Ma Minmin , Ma Yuping , Yi Xueming , Guo Ruibing , Zhu Wusheng , Fan Xinying , Xu Gelin , Frey William H , Liu Xinfeng
Published: December 2008

Background

The effect of neurotrophic factors in enhancing stroke-induced neurogenesis in the adult subventricular zone (SVZ) is limited by their poor blood-brain barrier (BBB) permeability.

Intranasal administration is a noninvasive and valid method for delivery of neuropeptides into the brain, to bypass the BBB. We investigated the effect of treatment with intranasal transforming growth factor-β1 (TGF-β1) on neurogenesis in the adult mouse SVZ following focal ischemia. The modified Neurological Severity Scores (NSS) test was used to evaluate neurological function, and infarct volumes were determined from hematoxylin-stained sections. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling was performed at 7 days after middle cerebral artery occlusion (MCAO). Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) and neuron- or glia-specific markers for identifying neurogenesis in the SVZ at 7, 14, 21, 28 days after MCAO.

Results

Intranasal treatment of TGF-β1 shows significant improvement in neurological function and reduction of infarct volume compared with control animals. TGF-β1 treated mice had significantly less TUNEL-positive cells in the ipsilateral striatum than that in control groups. The number of BrdU-incorporated cells in the SVZ and striatum was significantly increased in the TGF-β1 treated group compared with control animals at each time point. In addition, numbers of BrdU- labeled cells coexpressed with the migrating neuroblast marker doublecortin (DCX) and the mature neuronal marker neuronal nuclei (NeuN) were significantly increased after intranasal delivery of TGF-β1, while only a few BrdU labeled cells co-stained with glial fibrillary acidic protein (GFAP).

Conclusion

Intranasal administration of TGF-β1 reduces infarct volume, improves functional recovery and enhances neurogenesis in mice after stroke. Intranasal TGF-β1 may have therapeutic potential for cerebrovascular disorders.
Risk factors for developing a cutaneous injection-related infection among injection drug users: a cohort study
Authors: Lloyd-Smith Elisa , Wood Evan , Zhang Ruth , Tyndall Mark W , Montaner Julio SG , Kerr Thomas
Published: December 2008

Background

Cutaneous injection-related infections (CIRI), such as abscesses and cellulitis, are common and preventable among injection drug users (IDU). However, risk factors for CIRI have not been well described in the literature. We sought to characterize the risk factors for current CIRI among individuals who use North America's first supervised injection facility (SIF).

Methods

A longitudinal analysis of factors associated with developing a CIRI among participants enrolled in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort between January 1, 2004 and December 31, 2005 was conducted using generalized linear mixed-effects modelling.

Results

In total, 1065 participants were eligible for this study. The proportion of participants with a CIRI remained under 10% during the study period. In a multivariate generalized linear mixed-effects model, female sex (Adjusted Odds Ratio (AOR) = 1.68 [95% Confidence Interval (CI): 1.16–2.43]), unstable housing (AOR = 1.49 [95% CI: 1.10–2.03]), borrowing a used syringe (AOR = 1.60 [95% CI: 1.03–2.48]), requiring help injecting (AOR = 1.42 [95% CI: 1.03–1.94]), and injecting cocaine daily (AOR = 1.41 [95% CI: 1.02–1.95]) were associated with an increased risk of having a CIRI.

Conclusion

CIRI were common among a subset of IDU in this study, including females, those injecting cocaine daily, living in unstable housing, requiring help injecting or borrowing syringes. In order to reduce the burden of morbidity associated with CIRI, targeted interventions that address a range of factors, including social and environmental conditions, are needed.
Interpreting results of cluster surveys in emergency settings: is the LQAS test the best option?
Authors: Bilukha Oleg O , Blanton Curtis
Published: December 2008

Cluster surveys are commonly used in humanitarian emergencies to measure health and nutrition indicators. Deitchler et al. have proposed to use Lot Quality Assurance Sampling (LQAS) hypothesis testing in cluster surveys to classify the prevalence of global acute malnutrition as exceeding or not exceeding the pre-established thresholds. Field practitioners and decision-makers must clearly understand the meaning and implications of using this test in interpreting survey results to make programmatic decisions. We demonstrate that the LQAS test–as proposed by Deitchler et al. – is prone to producing false-positive results and thus is likely to suggest interventions in situations where interventions may not be needed. As an alternative, to provide more useful information for decision-making, we suggest reporting the probability of an indicator's exceeding the threshold as a direct measure of "risk". Such probability can be easily determined in field settings by using a simple spreadsheet calculator. The "risk" of exceeding the threshold can then be considered in the context of other aggravating and protective factors to make informed programmatic decisions.
An unusual presentation of atrial myxoma in an elderly patient: a case report
Authors: Biswas Anneka , Thakur Ashish K
Published: December 2008

Left atrial myxoma is the most common intracardiac tumour. It could be seen in patients between 3–83 years of age, with the majority presenting in fifth decade of life as sporadic cases (90%) and second decade as familial cases (10%) [1]. It is an important source of central nervous system embolism [2]. Elderly patients often present with non specific symptoms that are often overlooked in the absence of a supporting cardiac history which makes an early diagnosis challenging. This case report discusses an unusual presentation of left atrial myxoma in an elderly patient.
Wire-loop surface conductor for airborne EM system testing
Authors: Yin Changchun , Hodges Greg
Published: December 2008

The known mineral deposits used to test and compare airborne electromagnetic systems are often difficult to model because of nonideal geology, and may also be inconvenient or costly to survey. A simple wire-loop conductor has the advantage of being easily transported to the survey location and can be tuned to deliver a range of responses that will closely match the theoretical response, particularly on resistive ground. We calculated the response for such a tuned loop laid out at the surface of conductive ground and compared that response to field data. For an AEM system flown over a surface loop, when neglecting the second order of mutual induction, the receiver signal can be divided into three parts: (1) transmitter-earth-receiver (TER) signal; (2) transmitter-loop-receiver (TLR) signal; and (3) loop-earth-receiver (LER) signal. While the TER response has been extensively addressed in the literature, we modeled the more complex case of TLR and LER system responses. We first calculated the mutual inductance between the transmitter and the surface loop, tak-ing the loop impedance (resistance and inductance) into account, and then we calculated the signal in the receiver by calculating the mutual inductance between the loop and the receiver. To calculate the LER response, we divided the surface loop into a series of transmitting dipoles, with the “transmitting” current in the dipoles obtained by analyzing the mutual induction between the transmitter and loop. The numerical experiments show that the free-space wire-loop response (TLR system) displays the standard exponential decay for a conductor. The loop resistance and inductance define the decay constant and initial signal value. While the TER system largely influences the receiver signal at early time channels for conductive earth, the LER system influences very late time channels. The more resistive the test ground is, the longer the time window is for the free-space wire-loop signal to dominate. For the survey over a test loop on conductive ground in the Dominican Republic, using the Fugro HeliGEOTEM system, the predicted response compares well to the collected data.
Spatial organization of nucleotide excision repair proteins after UV-induced DNA damage in the human cell nucleus
Authors: Solimando Liliana , Luijsterburg Martijn S. , Vecchio Lorella , Vermeulen Wim , van Driel Roel , Fakan Stanislav
Published: December 2008

Nucleotide excision repair (NER) is an evolutionary conserved DNA repair system that is essential for the removal of UV-induced DNA damage. In this study we investigated how NER is compartmentalized in the interphase nucleus of human cells at the ultrastructural level by using electron microscopy in combination with immunogold labeling. We analyzed the role of two nuclear compartments: condensed chromatin domains and the perichromatin region. The latter contains transcriptionally active and partly decondensed chromatin at the surface of condensed chromatin domains. We studied the distribution of the damage-recognition protein XPC and of XPA, which is a central component of the chromatin-associated NER complex. Both XPC and XPA rapidly accumulate in the perichromatin region after UV irradiation, whereas only XPC is also moderately enriched in condensed chromatin domains. These observations suggest that DNA damage is detected by XPC throughout condensed chromatin domains, whereas DNA-repair complexes seem preferentially assembled in the perichromatin region. We propose that UV-damaged DNA inside condensed chromatin domains is relocated to the perichromatin region, similar to what has been shown for DNA replication. In support of this, we provide evidence that UV-damaged chromatin domains undergo expansion, which might facilitate the translocation process. Our results offer novel insight into the dynamic spatial organization of DNA repair in the human cell nucleus.
MT1-MMP promotes vascular smooth muscle dedifferentiation through LRP1 processing
Authors: Lehti Kaisa , Rose Nina F. , Valavaara Sara , Weiss Stephen J. , Keski-Oja Jorma
Published: December 2008

At sites of vessel-wall injury, vascular smooth muscle cells (VSMCs) can dedifferentiate to express an invasive and proliferative phenotype, which contributes to the development of neointimal lesions and vascular disorders. Herein, we demonstrate that the loss of the VSMC differentiated phenotype, as the repression of contractile-protein expression, is correlated with a dramatic upregulation of the membrane-anchored matrix metalloproteinase MT1-MMP (also known as MMP14 and membrane-type 1 matrix metalloproteinase). Matrix metalloproteinase (MMP) inhibitors or MT1-MMP deficiency led to attenuated VSMC dedifferentiation, whereas the phenotypic switch was re-engaged following the restoration of MT1-MMP activity in MT1-MMP–/– cells. MT1-MMP-dependent dedifferentiation was mediated by the PDGF-BB–PDGFRβ pathway in parallel with the proteolytic processing of the multifunctional LDL receptor-related protein LRP1 and the dynamic internalization of a PDGFRβ–β3-integrin–MT1-MMP–LRP1 multi-component complex. Importantly, LRP1 silencing allowed the PDGF-BB-induced dedifferentiation program to proceed in the absence of MT1-MMP activity, supporting the role of unprocessed LRP1 as a gatekeeper of VSMC differentiation. Hence, MT1-MMP and LRP1 serve as a new effector–target-molecule axis that controls the PDGF-BB–PDGFRβ-dependent VSMC phenotype and function.
DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling
Authors: Scholz Rolf-Peter , Regner Jennifer , Theil Anke , Erlmann Patrik , Holeiter Gerlinde , Jähne Ruth , Schmid Simone , Hausser Angelika , Olayioye Monilola A.
Published: December 2008

Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.
Severe Pseudomembranous Colitis After Moxifloxacin Use: A Case Series
Authors: Gallagher Jason C , Du Jennifer K , Rose Christina
Published: December 2008

OBJECTIVE

To describe the illnesses of 4 patients who developed severe pseudomembranous colitis after receiving moxifloxacin.

CASE SUMMARY

Four patients received moxifloxacin for pulmonary infections prior to developing positive Clostridium difficile toxin assays; all 4 later died from complications associated with C. difficile–associated disease (CDAD). Three patients developed CDAD while outpatients, although all of them had recent hospitalizations and their disease was presumed to be hospital related. All patients presented with diffuse abdominal pain, fever, and diarrhea. The patients were all treated surgically with total abdominal colectomies and medically with metronidazole.

DISCUSSION

Recent reports have highlighted the connection between fluoroquinolones and CDAD, in contrast to historical studies and assumptions. Evidence in the literature about differences in the propensity of various fluoroquinolones to cause CDAD is conflicting. The Naranjo probability scale revealed a probable relationship between moxifloxacin and CDAD for 3 patients, and a possible relationship for 1 patient.

CONCLUSIONS

Our cases highlight the need for vigilance in monitoring patients for signs of CDAD when using any antibiotic, including moxifloxacin. Patients with suspected severe CDAD need to be managed aggressively to avoid poor outcomes.
Japan and the Iraq War: cultural and theoretical perspectives
Authors: Adem Seifudein
Published: December 2008

With critical input from Japan's culture and guidance from theories of international relations, this article addresses in a limited way some of the issues in the current debate about Japan's foreign policy by examining how its major assumptions fared under Prime Minister Junichiro Koizumi (200106) who, in the post-September 11 setting, presided over the government during the US invasion and occupation of Iraq. The widely known assumptions about the foreign policy model of Japan, examined in this essay, pertain to decision-making by consensus; pacifism and anti-militarism; centrality of the United Nations; and the role of public opinion. I argue that the foreign policy of Japan has undergone major changes during this period, and that the significance of the changes, inspired by domestic and external variables, lies in the far-reaching implication they carry for the Japanese state.
Inertial Disruption: The Impact of a New Competitive Entrant on Online Consumer Search
Authors: Moe Wendy W. , Yang Sha
Published: December 2008

The objective of this article is to examine the impact of a new competitive entry on online consumer search behavior. The authors use store visitation as a measure of online search and decompose a shopper's tendency to search a given Web site into a baseline search preference for that site and an inertial effect of visiting that site. They find that inertia is an important driver in search behavior and is easily disrupted by a new competitive entry. This is a new and significant finding that contributes to the competitive entry literature. The authors develop a Bayesian model of search that separates the role of baseline search preference and inertia on store visitation and captures the effect of a new competitive entry. They apply this model to Internet clickstream data for the online bookstore market, in which they focus on the entry of Borders.com in 1998.
Tireóide e gravidez
Authors: Maciel Léa Maria Zanini , Magalhães Patrícia K. R.
Published: December 2008

A gravidez está associada com a necessidade aumentada de secreção hormonal pela tireóide desde as primeiras semanas após a concepção. Para que esta maior demanda ocorra, a gestação induz uma série de alterações fisiológicas que afetam a função tireoidiana e, portanto, os testes de avaliação da função glandular. Para as mulheres grávidas normais que vivem em áreas suficientes em iodo, este desafio em ajustar a liberação de hormônios tireoidianos para o novo estado de equilíbrio e manter até o término da gestação, geralmente, ocorre sem dificuldades. Entretanto, em mulheres com a capacidade funcional da tireóide prejudicada por alguma doença tireoidiana ou naquelas que residem em áreas de insuficiência iódica, isso não ocorre. O manejo de disfunções tireoidianas durante a gestação requer considerações especiais, pois tanto o hipotireoidismo quanto o hipertireoidismo podem levar a complicações maternas e fetais. Além disso, nódulos tireoidianos são detectados, com certa freqüência, em gestantes, o que pode gerar a necessidade do diagnóstico diferencial entre benignos e malignos ainda durante a gestação.
Estresse oxidativo: revisão da sinalização metabólica no diabetes tipo 1
Authors: Reis Janice Sepúlveda , Veloso Clara Araújo , Mattos Rafael Teixeira , Purish Saulo , Nogueira-Machado José Augusto
Published: December 2008

O diabetes melito e suas complicações apresentam origem multifatorial. Mecanismos bioquímicos e patológicos estão associados com hiperglicemia crônica no diabetes e o aumento do estresse oxidativo tem sido postulado com papel central nestas desordens. Evidências sugerem que a lesão celular oxidativa causada pelos radicais livres contribuem para o desenvolvimento das complicações no diabetes tipo 1 (DM1) e a diminuição das defesas antioxidantes (enzimáticas e não-enzimáticas) parecem correlacionar-se com a gravidade das alterações patológicas no DM1. Nesta revisão, relata-se como o estresse oxidativo pode exercer efeitos deletérios no diabetes e são apresentadas as opções terapêuticas em estudo para modulação da injúria vascular.
Qualidade de vida e aspectos socioeconômicos em diabéticos tipo 1
Authors: Araújo Angelo Fontes , Souza Maria Eliane Alves , Menezes Carlos Alberto
Published: December 2008

OBJETIVOS: Avaliar a qualidade de vida (QV) em diabéticos tipo 1 assistidos na Associação dos Diabéticos de Itabuna, BA (ASDITA), e verificar suas relações com as variáveis clínicas e sociodemográficas (escolaridade, renda familiar e ocupação). MÉTODOS: Foram estudados 34 pacientes (γ = 88%, ε = 5%; 53% mulheres, média de idade 20,4 ± 8,4 anos e média de tempo de diagnóstico 5,7 ± 4,9 anos), por meio de entrevista e antropometria (medidas de peso e altura). RESULTADOS: O perfil sociodemográfico da amostra revelou renda familiar per capita de 0,70 ± 0,56 salários mínimos, 53% possuíam o ensino fundamental, 64,7% eram estudantes. Em média, a qualidade de vida (QV) foi regular (58,8%). Não interferiram na QV: escolaridade, ocupação, etnia, índice de massa corpórea, número de aplicações diárias de insulina e perfil de monitoração da glicemia capilar. Associaram-se a pior QV: sexo feminino, ser adulto, tempo de diagnóstico maior ou igual a dez anos e baixa renda familiar. CONCLUSÕES: A QV destes pacientes foi inferior ao descrito na literatura, entretanto, estudos adicionais são necessários para comparações com diabéticos em condições socioeconômicas e culturais semelhantes às observadas nesta pesquisa.
Efeito hepatoprotetor do consumo crônico de dieptanoína e trieptanoína contra a esteatose em ratos
Authors: Silva Maria A. Firmino da , Ataide Terezinha da R. , Oliveira Suzana L. de , Sant'Ana Antonio E. G. , Cabral Júnior Cyro R. , Balwani Maria do C. L. V. , Oliveira Fernanda G. S. de , Santos Mércia C.
Published: December 2008

OBJETIVO: Avaliar o efeito do consumo crônico de di e trieptanoínas sobre a esteatose hepática (EH) em ratos. METODOLOGIA: Ratos Wistar submetidos à dieta AIN-93 com 0%, 30% ou 50% de substituição do óleo por óleo rico em di e trieptanoína, grupos TAGC(7)0, TAGC(7)30 e TAGC(7)50, respectivamente, por nove meses. O grupo-controle recebeu ração Labina®. Analisaram-se histologia e provas de função e lesão hepática, glicemia e perfil lipídico sérico. Realizaram-se análise de variância, teste F, teste de Dunnet e análises de regressão uni e multivariadas (p < 0,05). RESULTADOS: TAGC(7)0, TAGC(7)30 e TAGC(7)50 desenvolveram EH; 80% de casos graves no TAGC(7)0 contra 40% no TAGC(7)50. Os pesos absoluto (PAF) e relativo do fígado (PRF) foram maiores em TAGC(7)0 e TAGC(7)30 e a glicemia foi maior em TAGC(7)30 e TAGC(7)50, que no grupo-controle. Colesterol total, LDL-c, LDL-c/HDL-c e proteínas totais foram maiores no grupo-controle. O óleo experimental reduziu o PRF e determinou tendência de redução do peso corporal, PAF, percentual de lipídios hepáticos e graus de EH (GHE). As variáveis explicativas para GHE foram peso final, glicemia, albumina, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c e fosfatase alcalina. CONCLUSÕES: Sugere-se que di e trieptanoínas exerçam efeito hepatoprotetor contra a EH, em ratos, em uma feição dose-dependente.
Aplicação da cromatografia a líquido em substituição à técnica de radioimunoensaio como auxílio diagnóstico visando ao gerenciamento de resíduos de serviço da saúde em laboratório de pesquisa
Authors: Ribeiro Neto Luciane M. , Sugawara Eduardo K. , Verreschi Ieda T. N.
Published: December 2008

A elaboração do Plano de Gerenciamento dos Resíduos dos Serviços de Saúde, normatizado na RDC nº 306/2004, é de responsabilidade de todos os geradores. Sendo o radioimunoensaio (RIE) uma das técnicas mais empregadas, estudou-se o impacto da substituição dessa técnica por cromatografia líquida (HPLC), no aspecto da redução na geração de resíduos radioativos na rotina do Laboratório de Esteróides da Universidade Federal de São Paulo (Unifesp). Os resíduos gerados nas determinações de cortisol e 17α-hidroxiprogesterona séricos foram classificados, e aqueles pertencentes aos grupos B e C foram avaliados. Observou-se que no emprego de RIE há geração de resíduos químicos (grupo B) e rejeitos radioativos (grupo C), enquanto no HPLC gerou-se apenas resíduos químicos. A adequação dessas técnicas teve vantagem de redução significativa no tempo de análise e, sobretudo, a eliminação e/ou a diminuição na geração de rejeitos radioativos, estimulando a sua aplicação para outras metodologias, bem como a implantação em outras unidades de pesquisas.
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism
Authors: Cross Graciela A. de , Suarez Horacio , Pitoia Fabián , Moncet Daniel , Vanegas María , Bruno Oscar D. , Niepomniszcze Hugo
Published: December 2008

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.
Acesso transmaxilar à base do crânio: avaliação de 11 casos
Authors: Caubi Antonio Figueiredo , Lago Carlos Augusto Pereira , Vasconcelos Belmiro Cavalcanti do Egito , Silva Emanuel Dias e Oliveira , Rocha Nelson Studart , Morais Hécio Henrique Araújo de
Published: December 2008

O acesso cirúrgico à região de base do crânio é sempre difícil principalmente pelas estruturas anatômicas nobres associadas. A osteotomia maxilar proporciona visão direta à região de clivus e coluna cervical, além de apresentar uma menor morbidade em relação aos diversos acessos descritos na literatura. OBJETIVO: Avaliar 11 casos submetidos à osteotomia transmaxilar, descrevendo técnica cirúrgica, resultados e complicações pós-operatórias. PACIENTES E MÉTODOS: O estudo retrospectivo de onze pacientes foi submetido à cirurgia transmaxilar para acesso à região do tronco encefálico. Registros quanto à oclusão dentária, hemorragia trans e pós-operatória, necrose óssea e alterações de tecido mole foram estudados. Todos seguiram o mesmo protocolo cirúrgico e acompanhamento médio de dois anos. RESULTADOS: Após o tratamento todos os pacientes apresentaram melhora do quadro clínico e nenhum dano neurológico, hemorragia trans e pós-operatória ou intercorrências maiores foram identificadas. Dentre as complicações, em dois pacientes ocorreu fratura incompleta da maxila, dois apresentaram laceração da mucosa nasal e um apresentou como complicação tardia uma fístula bucossinusal. CONCLUSÃO: A osteotomia transmaxilar possibilitou adequado acesso a região de clivus para descompressão do tronco encefálico com baixo índice de complicações nesta série de casos.
Influência do AMP cíclico na regeneração do nervo facial em ratos
Authors: Borin Andrei , Toledo Ronaldo Nunes , Ho Paulo Lee , Testa José Ricardo Gurgel , Cruz Oswaldo Laércio Mendonça , Fukuda Yotaka
Published: December 2008

Estimular a regeneração do nervo facial é ainda hoje um desafio. OBJETIVO: Estudar a possível influência neurotrófica do nucleotídeo cíclico adenosina monofosfato (AMPc) na regeneração do nervo facial de ratos Wistar. MÉTODO: Trinta e dois animais foram submetidos à transecção completa com sutura imediata do nervo facial direito, sendo divididos em expostos ou não expostos à aplicação tópica de AMPc, com análises comportamentais (movimentação de vibrissas e fechamento da rima palpebral) e histométrica (contagem de fibras mielinizadas) em dois períodos, 14 e 28 dias após a lesão. RESULTADO: Encontramos diferenças estatísticas (p<0,05) nas análises comportamental e histométrica no 14º dia, sugerindo uma precocidade na regeneração do nervo facial exposto ao AMPc. CONCLUSÃO: Nosso estudo constatou uma possível ação neurotrófica do AMPc na regeneração do nervo facial em ratos.
Interação entre audiologia e genética no estudo de uma família: a complexidade do diagnóstico molecular e do aconselhamento genético
Authors: Hoffmann Flavia Maria Rodrigues , Rodrigues Patrícia Fernandes , Santos Teresa Maria Momensohn dos , Sartorato Edi Lucia , Maciel-Guerra Andréa Trevas , Matas Carla Gentile , de Moraes Vanessa Cristine Sousa
Published: December 2008

A deficiência auditiva como déficit sensorial mais comum tem dentre suas diferentes etiologias as alterações genéticas. Assim, é importante que a investigação audiológica se associe à busca do diagnóstico etiológico. OBJETIVO: Relatar o perfil audiológico e genético de três irmãos portadores de deficiência auditiva neurossensorial não-sindrômica. MATERIAL E MÉTODO: Estudo de caso de três irmãos, do sexo masculino, com 3, 5 e 16 anos, respectivamente, submetidos à avaliação audiológica comportamental e eletrofisiológica, e estudo molecular. RESULTADOS: Os achados audiológicos mostraram: audiometria do tipo neurossensorial, bilateral, simétrica, de grau moderado a moderadamente severo e configuração descendente acentuada. EOAT e EOAPD ausentes nos dois irmãos mais novos. PEATE compatível com perda auditiva moderadamente severa a severa. Presença do P300 com latências dentro da normalidade bilateralmente no irmão mais velho. Os achados do exame molecular mostraram que as duas crianças mais novas eram heterozigotos para a mutação 35delG no gene GJB2 e o mais velho não apresentava essa mutação. CONCLUSÃO: A associação das avaliações fonoaudiológicas e genéticas permite o diagnóstico etiológico de perdas auditivas que à primeira vista são semelhantes, mas que não obedecem à mesma estrutura genética. Os estudos moleculares devem ser abrangentes, evitando diagnósticos precipitados que prejudiquem o aconselhamento genético.
O Mismatch Negativity em pacientes com distúrbios do processamento auditivo (central)
Authors: Roggia Simone Mariotto , Colares Nádia Tenório
Published: December 2008

O Mismatch Negativity (MMN) é um potencial evocado auditivo de longa latência que fornece uma medida objetiva das habilidades de discriminação e memória sensorial auditiva. Assim, pode ser utilizado como uma avaliação eletrofisiológica do processamento auditivo (central). OBJETIVO: Estudar o MMN em pacientes com Distúrbios do Processamento Auditivo (Central) - DPA(C). FORMA DO ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Foram avaliados oito sujeitos com DPA(C), na faixa etária de nove a 14 anos, bem como um grupo controle. O MMN foi eliciado para estímulos tonais (tone bursts) diferindo quanto à freqüência (MMNf - estímulo padrão: 750Hz e estímulo diferente: 1000Hz ), bem como quanto à duração (MMNd - estímulo padrão: 100 ms e estímulo diferente: 50 ms; na freqüência de 1000Hz). RESULTADOS: A presença do MMNf e do MMNd foi comprovada estatisticamente em ambos os grupos estudados. Não foram constatadas diferenças significantes estatisticamente entre os valores de latência e de amplitude do MMNf e do MMNd obtidos nos dois grupos. Também não foram verificadas diferenças significantes estatisticamente entre o MMNf e o MMNd em nenhum dos grupos estudados. CONCLUSÃO: Os sujeitos com DPA(C) avaliados não apresentaram alterações no MMNf, nem no MMNd.