bluuebunny/crossref_metadata_2025 huggingface dataset:
Netrins: versatile extracellular cues with diverse functions
Authors: Sun Karen Lai Wing , Correia James P. , Kennedy Timothy E.
Published: May 2011

Netrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues.
Engrailed homeoprotein acts as a signaling molecule in the developing fly
Authors: Layalle Sophie , Volovitch Michel , Mugat Bruno , Bonneaud Nathalie , Parmentier Marie-Laure , Prochiantz Alain , Joliot Alain , Maschat Florence
Published: May 2011

Homeodomain transcription factors classically exert their morphogenetic activities through the cell-autonomous regulation of developmental programs. In vertebrates, several homeoproteins have also been shown to have direct non-cell-autonomous activities in the developing nervous system. We present the first in vivo evidence for homeoprotein signaling in Drosophila. Focusing on wing development as a model, we first demonstrate that the homeoprotein Engrailed (En) is secreted. Using single-chain anti-En antibodies expressed under the control of a variety of promoters, we delineate the wing territories in which secreted En acts. We show that En is a short-range signaling molecule that participates in anterior crossvein development, interacting with the Dpp signaling pathway. This report thus suggests that direct signaling with homeoproteins is an evolutionarily conserved phenomenon that is not restricted to neural tissues and involves interactions with bona fide signal transduction pathways.
Dronc caspase exerts a non-apoptotic function to restrain phospho-Numb-induced ectopic neuroblast formation in Drosophila
Authors: Ouyang Yingshi , Petritsch Claudia , Wen Hong , Jan Lily , Jan Yuh Nung , Lu Bingwei
Published: May 2011

Drosophila neuroblasts have served as a model to understand how the balance of stem cell self-renewal versus differentiation is achieved. Drosophila Numb protein regulates this process through its preferential segregation into the differentiating daughter cell. How Numb restricts the proliferation and self-renewal potentials of the recipient cell remains enigmatic. Here, we show that phosphorylation at conserved sites regulates the tumor suppressor activity of Numb. Enforced expression of a phospho-mimetic form of Numb (Numb-TS4D) or genetic manipulation that boosts phospho-Numb levels, attenuates endogenous Numb activity and causes ectopic neuroblast formation (ENF). This effect on neuroblast homeostasis occurs only in the type II neuroblast lineage. We identify Dronc caspase as a novel binding partner of Numb, and demonstrate that overexpression of Dronc suppresses the effects of Numb-TS4D in a non-apoptotic and possibly non-catalytic manner. Reduction of Dronc activity facilitates ENF induced by phospho-Numb. Our findings uncover a molecular mechanism that regulates Numb activity and suggest a novel role for Dronc caspase in regulating neural stem cell homeostasis.
Peter Pan functions independently of its role in ribosome biogenesis during early eye and craniofacial cartilage development in Xenopus laevis
Authors: Bugner Verena , Tecza Aleksandra , Gessert Susanne , Kühl Michael
Published: May 2011

The Xenopus oocyte possesses a large maternal store of ribosomes, thereby uncoupling early development from the de novo ribosome biosynthesis required for cell growth. Brix domain-containing proteins, such as Peter Pan (PPan), are essential for eukaryotic ribosome biogenesis. In this study, we demonstrate that PPan is expressed maternally as well as in the eye and cranial neural crest cells (NCCs) during early Xenopus laevis development. Depletion of PPan and interference with rRNA processing using antisense morpholino oligonucleotides resulted in eye and cranial cartilage malformations. Loss of PPan, but not interference with rRNA processing, led to an early downregulation of specific marker genes of the eye, including Rx1 and Pax6, and of NCCs, such as Twist, Slug and FoxD3. We found that PPan protein is localized in the nucleoli and mitochondria and that loss of PPan results in increased apoptosis. These findings indicate a novel function of PPan that is independent of its role in ribosome biogenesis.
RSL genes are sufficient for rhizoid system development in early diverging land plants
Authors: Jang Geupil , Yi Keke , Pires Nuno D. , Menand Benoît , Dolan Liam
Published: May 2011

Land plants are anchored to their substratum from which essential inorganic nutrients are taken up. These functions are carried out by a system of rhizoids in early diverging groups of land plants, such as mosses, liverworts and hornworts. Physcomitrella patens RHD SIX-LIKE1 (PpRSL1) and PpRSL2 transcription factors are necessary for rhizoid development in mosses. Similar proteins, AtRHD6 and AtRSL1, control the development of root hairs in Arabidopsis thaliana. Auxin positively regulates root hair development independently of AtRHD6 and AtRSL1 in A. thaliana but the regulatory interactions between auxin and PpRSL1 and PpRSL2 are unknown. We show here that co-expression of PpRSL1 and PpRSL2 is sufficient for the development of the rhizoid system in the moss P. patens; constitutive expression of PpRSL1 and PpRSL2 converts developing leafy shoot axes (gametophores) into rhizoids. During wild-type development, PpRSL1 and PpRSL2 are expressed in the specialized cells that develop rhizoids, indicating that cell-specific expression of PpRSL1 and PpRSL2 is sufficient to promote rhizoid differentiation during wild-type P. patens development. In contrast to A. thaliana, auxin promotes rhizoid development by positively regulating PpRSL1 and PpRSL2 activity in P. patens. This indicates that even though the same genes control the development of root hairs and rhizoids, the regulation of this transcriptional network by auxin is different in these two species. This suggests that auxin might have controlled the development of the first land plant soil anchoring systems that evolved 465 million years ago by regulating the expression of RSL genes and that this regulatory network has changed since mosses and angiosperms last shared a common ancestor.
Size and specificity of radiopharmaceuticals for sentinel lymph node detection
Authors: Núñez Eutimio Gustavo Fernández , Teodoro Rodrigo , Wiecek Danielle Pereira , da Silva Natanael Gomes , Martinelli Jose Roberto , de Oliveira Filho Renato Santos
Published: May 2011

Background

Biological performance of radiotracers for sentinel node detection analyzed in the light of molecular design and dimension is not widely available.

Purpose

To evaluate the effect of dextran molecular size and the presence of tissue-binding units (mannose) within the model of 99mTc-carbonyl conjugate for sentinel lymph node detection.

Material and Methods

Four dextran conjugates with and without mannose in the chemical backbone were included. All polymers were radiolabeled using the precursor [99mTc(OH2)3(CO)3]+. Radiolabeling conditions targeted the best radiochemical purity and specific activity for each radiopharmaceutical, and partition coefficients were also defined. Lymphoscintigraphy and ex-vivo biodistribution in popliteal lymph node, liver and kidneys were performed in Wistar rats. The effects of molecular weight and mannose presence were assessed by a two-level factorial design.

Results

Radiochemical purity was indirectly related to molecular weight and presence of mannose in the polymer structure. All products were able to detect popliteal lymph node, however, uptake was strongly influenced by use of mannose (4-fold higher). Excretion was similarly modulated by differences in molecular weight. Mannose-enhanced lymph node uptake and higher molecule size in the range under study benefitted lymphoscintigraphic performance.

Conclusion

Screening of radiopharmaceuticals for lymphoscintigraphy might improve with attention to the mentioned physico-chemical features of the molecule.
A family of doctors over 250 years: innovation and controversy
Authors: Watkins Peter J
Published: May 2011

A family of Watkins doctors originating in the Northamptonshire town of Towcester included 13 doctors in seven generations during 250 years. In each generation there were between one and four doctors. Three doctors involved themselves actively in innovative yet controversial practises, described in their own writings and publications. Timothy Watkins' (1755–1834) own handwritten lecture notes describe the problems affecting an 18th-century man-midwife, while his accounts book provides insights into his lifestyle. The concept of the waterborne spread of cholera during the 1854 epidemic in Towcester is described by Robert Webb Watkins (1822–1901) during the same year as the observations made by John Snow (1813–58). John Webb Watkins (1833–1903) in his MD thesis (1856) describes his use of chloroform in labour in Towcester during the early 1850s, followed by self-experimentation with chloroform administered to him between 40 and 50 times by Sir James Young Simpson (1811–70) in Edinburgh. Descriptions of the two 19th-century general practitioners offer insights into the exemplary extent of their civic involvement in all walks of local community life, and of their family ties.
Guidance on the severity classification of scientific procedures involving fish: Report of a Working Group appointed by the Norwegian Consensus-Platform for the Replacement, Reduction and Refinement of animal experiments (Norecopa)
Authors: Hawkins P , Dennison N , Goodman G , Hetherington S , Llywelyn-Jones S , Ryder K , Smith A J
Published: May 2011

The severity classification of procedures using animals is an important tool to help focus the implementation of refinement and to assist in reporting the application of the 3Rs (replacement, reduction and refinement). The recently revised Directive that regulates animal research and testing within the European Union requires Member States to ensure that all procedures are classified as ‘non-recovery’, ‘mild’, ‘moderate’ or ‘severe’, using assignment criteria set out by the European Commission (EC). However, these are focused upon terrestrial species, so are of limited relevance to fish users. A Working Group set up by the Norwegian Consensus-Platform for the 3Rs (Norecopa) has produced guidance on the classification of severity in scientific procedures involving fish, including examples of ‘subthreshold’, ‘mild’, ‘moderate’, ‘severe’ and ‘upper threshold’ procedures. The aims are to complement the EC guidelines and help to ensure that suffering in fish is effectively predicted and minimized. Norecopa has established a website ( www.norecopa.no/categories ) where more information on severity classification for procedures using fish, including field research, will be made available.
Low typing endurance in keyboard workers with work-related upper limb disorder
Authors: Povlsen Bo
Published: May 2011

Objective

To compare results of typing endurance and pain before and after a standardized functional test.

Design

A standardized previously published typing test on a standard QWERTY keyboard.

Setting

An outpatient hospital environment.

Participants

Sixty-one keyboard and mouse operating patients with WRULD and six normal controls.

Main outcome measure

Pain severity before and after the test, typing endurance and speed were recorded.

Results

Thirty-two patients could not complete the test before pain reached VAS 5 and this group only typed a mean of 11 minutes. The control group and the remaining group of 29 patients completed the test. Two-tailed student T test was used for evaluation. The endurance was significantly shorter in the patient group that could not complete the test ( P < 0.00001) and the pain levels were also higher in this group both before ( P = 0.01) and after the test ( P = 0.0003). Both patient groups had more pain in the right than the left hand, both before and after typing.

Conclusions

Low typing endurance correlates statistically with more resting pain in keyboard and mouse operators with work-related upper limb disorder and statistically more pain after a standardized typing test. As the right hands had higher pain levels, typing alone may not be the cause of the pain as the left hand on a QWERTY keyboard does relative more keystrokes than the right hand.
The Effect of Environmental Regulations and other Government Controls on Oil and Gasoline Production
Authors: Simpson Brian P.
Published: May 2011

This paper demonstrates that oil and gasoline prices are much higher than they need to be. However, the higher than necessary prices are not due to the depletion of fossil fuels. They are due to manmade factors. Furthermore, the problem is not being caused by greedy oil and gasoline producers. Prices are higher because of environmental regulations and other government controls. Government controls restrict our ability to produce and purchase oil and gasoline. The paper indicates that the solution to high priced oil and gasoline is the abolition of government controls restricting our ability to gain access to these goods.
Expert Perceptions of the Role of Biochar as a Carbon Abatement Option with Ancillary Agronomic and Soil-Related Benefits
Authors: Shackley Simon , Carter Sarah , Sims Kirsten , Sohi Saran
Published: May 2011

Biochar is the solid remains of organic material that has been heated to > 350°C in an oxygen-limited environment, frequently intended to be mixed with soils. Biochar usually contains 80 – 90% stable aromatic carbon that is resistant to decomposition and mineralization (possibly for hundreds to thousands of years): it is, therefore, a potential way of removing carbon from the atmosphere for storage and has received considerable attention in the specialist media. Because the field is new there is no authoritative scientific assessment of the state-of-knowledge and its certainty. We therefore undertook an internet-based survey (n=145) to elicit expert opinion on the state-of-knowledge on biochar science and engineering. While expert opinion broadly supports the proposed benefits of biochar, the survey also identified a high degree of uncertainty attached to most of the knowledge-claims: more basic underpinning R&D will be necessary before policymakers will have confidence in implementing biochar projects.
Communication and responsibility: Open universities in China and community music education
Authors: Luyi Sun , Zhifang Gong
Published: May 2011

In the process of building a learning society in China, the government has paid more and more attention to education in communities. Community education is oriented towards all social members of society and offers a vast space for the popularization of music education. China's open
universities are able to provide a learning platform and systematic support and service for music education in communities. Open universities can play an active role in promoting the construction of a harmonious society. This article discusses the necessity of music education in communities,
advantages enjoyed by open and distance education, and the channels and methods for conducting community music education. This is illustrated by several recent initiatives made by the open universities in China, particularly the organization of the 2009 National Community Music Activity Broadcasting
and Exhibition and the Community Singing Rating Activity. These efforts have generated new community music experiences and serve as examples to further study the concept and the social impact of community music.
The charm of community music
Authors: Ruisen Xu
Published: May 2011

Music education in communities is a newly sprouted thing and is gradually catching people's attention. Music education seeks to promote community members' aesthetic senses. Music and the arts, the best tools for moving people's souls, link different hearts across various boundaries,
affecting all aspects of social life. Music education can serve as a major force to intensify cohesion within communities that are purely formed by economic relationships. Starting with an explanation of community and community music in modern China, this article expounds the content, influence
and functions of community music, with illustrations from a case study, to unveil the charm of community music.
Do they know they're composing': Music making and understanding among newly arrived immigrant and refugee children
Authors: Howell Gillian
Published: May 2011

This article discusses issues of creative music making and understanding as they arose in the context of a music programme for newly arrived refugee and immigrant children. How do young people make sense of a music environment when they do not understand the language of the facilitator
or other participants Visual information and imitation offer reliable entry points into participation, but are not always sufficient for more complex creative processes such as group composition and invention. The author draws upon her experiences working in an English Language School for
recent immigrants and refugees, and explores some key points of cross-cultural adaptation as they intersect with musical understanding and engagement in a composition process.
Community, communication, social change: Music in dispossessed Indian communities
Authors: Quadros Andr de , Dorstewitz Philipp
Published: May 2011

The interface of music and health has principally been through music therapy and the use of music to build individual wellness. Community music as a tool for communicating health messages in combination with other arts and as a part of an epidemiological study has not been widely used.
This article considers the relationship between public health, community music in particular, and the arts more generally. It discusses various ideas that give shape to an interdisciplinary enquiry centering on health policy. It introduces several aspects of Dewey's philosophy to support the
idea of a community musichealth nexus as a source of projects that are both beneficial and have genuine aesthetic value. The study examines issues relating both to artistic value and health impact effectiveness in an Indian dispossessed community context, and provides a narrative of community
music interventions in India with an analysis of the inherent aesthetic value.
Network Effects and Personal Influences: The Diffusion of an Online Social Network
Authors: Katona Zsolt , Zubcsek Peter Pal , Sarvary Miklos
Published: May 2011

This article discusses the diffusion process in an online social network given the individual connections between members. The authors model the adoption decision of individuals as a binary choice affected by three factors: (1) the local network structure formed by already adopted neighbors, (2) the average characteristics of adopted neighbors (influencers), and (3) the characteristics of the potential adopters. Focusing on the first factor, the authors find two marked effects. First, an individual who is connected to many adopters has a greater adoption probability (degree effect). Second, the density of connections in a group of already adopted consumers has a strong positive effect on the adoption of individuals connected to this group (clustering effect). The article also records significant effects for influencer and adopter characteristics. For adopters, specifically, the authors find that position in the entire network and some demographic variables are good predictors of adoption. Similarly, in the case of already adopted individuals, average demographics and global network position can predict their influential power on their neighbors. An interesting counterintuitive finding is that the average influential power of individuals decreases with the total number of their contacts. These results have practical implications for viral marketing, a context in which a variety of technology platforms are increasingly considering leveraging their consumers' revealed connection patterns. The model performs particularly well in predicting the next set of adopters.
Price Competition and Endogenous Valuation in Search Advertising
Authors: Xu Lizhen , Chen Jianqing , Whinston Andrew
Published: May 2011

This article studies how to endogenously assess the value of a “superior” advertising position in the price competition and examines the resulting location competition outcomes and price dispersion patterns. The authors consider a game-theoretic model in which firms compete for advertising positions and then compete in price for customers in a product market. Firms differ in their competence, and positions are differentiated in their prominence, which reflects consumers' online search behavior. They find that when endogenously evaluated within the product market competition, a prominent advertising position might not always be desirable for a firm with competitive advantage, even if it is cost-free. The profitability of a prominent advertising position depends on the trade-off between the extra demand from winning the position and the higher equilibrium prices when the weaker competitor wins it. Furthermore, the authors show that the bidding outcome might not align with the relative competitive strength, and an advantaged firm might not be able to win the prominent position even when it values that position. They derive two-dimensional equilibrium price dispersion with the realized prices at the same position varying and the expected prices differing across different positions. They find that the expected price in the prominent position might not always be higher, implying that an expensive location does not necessarily lead to expensive products.
Sildenafil protects human mammary epithelial cells against ROS production induced by estradiol
Authors: Taibi Gennaro , Cocciadiferro Letizia , Miceli Vitale , Carruba Giuseppe , Nicotra Concetta M.A.
Published: May 2011

Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form (XO) play an important role in various types of ischemic and vascular injuries. Recently, we have demonstrated that estradiol (E2) induces a significant decrease of the expression and activity of XDH and of its conversion to XO in human mammary epithelial cells. E2 is known to induce upregulation of eNOS gene expression in aortic endothelial cells. Because the XO-derived O2·– combines with ·NO to yield ONOO–, and considering that ONOO– converts XDH to XO, the resulting increase of XO activity and reactive oxygen species production would eventually lead to a further increase of ONOO– production, thus creating a vicious cycle of oxidative stress. Our previous study has indicated that sildenafil has a protective effect on human mammary epithelial cells as a consequence of XO inhibition and of the resulting decrease of free oxygen radicals that can impair the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the present study, we report that the dual inhibitory effect exerted by sildenafil on both XO and PDE-5 is a consequence of a structural modification induced by O2·–, also consisting of the release of a piperazine group that could in turn inhibit the XO enzyme.
ZR Die Eigentumsverhältnisse in der Ehe
Authors: Coester-Waltjen Dagmar
Published: May 2011

Was gehört wem? Diese Frage spielt auch in der Ehe eine wichtige Rolle. Während des Bestehens der Ehe ist dies vor allem für Dritte (Gläubiger, Erwerber) eine wichtige Frage, im Trennungs- und Auflösungsstadium der Ehe aber auch für die Ehegatten selbst. In der Praxis – und dementsprechend auch in den Examensaufgaben – ist dies daher eine wichtige Thematik.
Die aktuelle Entscheidung Unionsbürgerstatus und nationale Staatsangehörigkeit – Souveränität unter unionsrechtlichem Vorbehalt?
Authors: Kahl Wolfgang
Published: May 2011

Mit Urteil vom 2.3.2010 hat der EuGH die Pflicht der Mitgliedstaaten bekräftigt, von ihrer Zuständigkeit im Staatsangehörigkeitsrecht unter Beachtung des Unionsrechts Gebrauch zu machen. In der Entscheidung des Gerichtshofs spiegelt sich insbesondere die wachsende Bedeutung sowohl des Unionsbürgerstatus (Art. 20 AEUV) als auch des Prinzips loyaler Zusammenarbeit (Art. 4 III EUV) als »Europäisierungshebel « auch in klassischen »Reservaten« nationaler Souveränität wie dem Staatsangehörigkeitsrecht wider. Das Urteil gibt zugleich Anlass für eine Wiederholung von Grundproblemen des Staatsangehörigkeitsrechts und der Rücknahme von Verwaltungsakten (§ 48 VwVfG).
ÖR Rechtsschutz gegen die Umbenennung von Straßen
Authors: Schoch Friedrich
Published: May 2011

Die Probleme um den Rechtsschutz gegen die Umbenennung von Straßen (Wegen, Plätzen) verbinden in hervorragender Weise Fragen des Allgemeinen Verwaltungsrechts mit Anforderungen des Verwaltungsprozessrechts. Es geht insbesondere um das behördliche Handeln durch Allgemeinverfügung und die Anfechtungsklage, das subjektive öffentliche Recht und die Klagebefugnis sowie das Verwaltungsermessen und die gerichtliche Kontrolldichte. Anhand anschaulicher Praxisbeispiele aus der Rechtsprechung werden nachfolgend die Rechtsprobleme analysiert und die Lösungen aufgezeigt.
ÖR Zu den Grenzen der Meinungsfreiheit innerhalb politischer Parteien
Authors: Sonder Nicolas
Published: May 2011

Der Beitrag setzt sich mit der Frage auseinander, inwieweit sich Mitglieder politischer Parteien im Rahmen der von ihnen vorgenommen öffentlichen Äußerungen auf ihr Grundrecht der freien Meinungsäußerung berufen können. Dabei soll unter anderem erörtert werden, ob auf Grund ihrer Eigenschaft als Parteipolitiker eine Einschränkung des Schutzbereichs vorzunehmen ist, welche Rolle die Drittwirkung der Grundrechte hierbei einnimmt, in welcher Form Eingriffe durch die Partei selbst erfolgen können und schließlich, wie diese durch die verfassungsrechtliche Stellung der Parteien nach Art. 21 GG und den Regelungen des Parteiengesetzes gerechtfertigt werden können.
Survivin upregulation, dependent on leptin–EGFR–Notch1 axis, is essential for leptin-induced migration of breast carcinoma cells
Authors: Knight Brandi B , Oprea-Ilies Gabriela M , Nagalingam Arumugam , Yang Lily , Cohen Cynthia , Saxena Neeraj K , Sharma Dipali
Published: May 2011

Obese breast cancer patients exhibit a higher risk for larger tumor burden and an increased likelyhood of metastasis. The molecular effects of obesity on carcinogenesis are mediated by the autocrine and paracrine effects of the adipocytokine leptin. Leptin participates in the tumor progression and metastasis of human breast. We show that leptin induces clonogenicity and increases the migration potential of breast cancer cells. We found that survivin expression is induced in response to leptin. In this study, we examine the role and leptin-mediated regulation of survivin. Leptin treatment leads to survivin upregulation, due in part to the activation of Notch1 and the release of a transcriptionally active Notch1 intracellular domain (NICD). Chromatin immunoprecipitation analysis shows that NICD gets recruited to the survivin promoter at the CSL (CBF1/RBP-Jk, Su(H), Lag-1) binding site in response to leptin treatment. Inhibition of Notch1 activity inhibits leptin-induced survivin upregulation. Leptin-induced transactivation of epidermal growth factor receptor (EGFR) is involved in leptin-mediated Notch1 and survivin upregulation, demonstrating a novel upstream role of leptin–EGFR–Notch1 axis. We further show that leptin-induced migration of breast cancer cells requires survivin, as overexpression of survivin further increases, whereas silencing survivin abrogates leptin-induced migration. Using a pharmacological approach to inhibit survivin, we show that 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase inhibitors, such as lovastatin, can effectively inhibit leptin-induced survivin expression and migration. Importantly, leptin increased breast tumor growth in nude mice. These data show a novel role for survivin in leptin-induced migration and put forth pharmacological survivin inhibition as a potential novel therapeutic strategy. This conclusion is supported byin vivodata showing the overexpression of leptin and survivin in epithelial cells of high-grade ductal carcinomasin situand in high-grade invasive carcinomas.
eNOS activation and NO function: Pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium–new insights into eNOS regulation through adaptive cell signaling
Authors: Boeldt D S , Yi F X , Bird I M
Published: May 2011

In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca2+]iconcentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca2+]isignaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca2+]isignaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase ‘capacitative entry’ [Ca2+]iresponse, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca2+]isignaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension.
Matrix metalloproteinases: keys to healthier blood vessels in diabetes?
Authors: Mulder Hindrik
Published: May 2011

In this issue of Journal of Endocrinology, Schuyler et al. show that intimal lesions in atherosclerosis-prone diabetic apoE−/− mice are reduced by insulin treatment. An increase of metalloproteinase-9 expression was observed in untreated diabetic apoE−/− mice; this was absent in insulin-treated mice. The study suggests that hindering of tissue-remodeling metalloproteinases may account for the beneficial effects of proper metabolic control in patients with diabetes. This clinically relevant finding prompts further exploration.
A role for lipoxin A4 as an anti-inflammatory mediator in the human endometrium
Authors: Macdonald Linsay J , Boddy Sheila C , Denison Fiona C , Sales Kurt J , Jabbour Henry N
Published: May 2011

Lipoxin A4is a lipid mediator that elicits anti-inflammatory and pro-resolution actions via its receptor, formyl peptide receptor 2 (FPR2/ALX). In this study, we aimed to investigate the expression and potential role of lipoxin A4and FPR2/ALX in the regulation of inflammation associated with cyclical remodeling of the human endometrium across the menstrual cycle and during early pregnancy. Using quantitative RT-PCR analysis, we found that FPR2/ALX expression is upregulated during the menstrual phase of the cycle and in decidua tissue from the first trimester of pregnancy. We localized the site of expression of FPR2/ALX in menstrual phase endometrium and first-trimester decidua tissue to glandular epithelial cells and cells within the stromal compartment, including cells lining the blood vessels and immune cells. Measurement of serum lipoxin A4by ELISA revealed no difference in its levels across the menstrual cycle but an elevation in early pregnancy (P<0.001). We found that lipoxin A4was regulated by human chorionic gonadotrophin (hCG) during early pregnancy, because treatment of human decidua tissue with hCG increased lipoxin A4release (P<0.01). Finally, we have shown that lipoxin A4can suppress phorbol myristate acetate-induced expression of the inflammatory cytokines interleukin 6 and 8 in human endometrium and decidua tissue. These results demonstrate for the first time that lipoxin A4and its receptor FPR2/ALX can regulate inflammatory events in the human endometrium and decidua of early pregnancy.
Serotonin-enhanced hyperactivation of hamster sperm
Authors: Fujinoki Masakatsu
Published: May 2011

The effects of serotonin on reproductive function were examined using hamster spermatozoa. When serotonin at concentrations from 1 fmol/l to 1 μmol/l was added to modified Tyrode's albumin lactate pyruvate (mTALP) medium, hyperactivation was significantly enhanced. Agonists and antagonists of 5-hydroxytryptamine hydrochloride (5-HT) receptors (5-HT2and 5-HT4receptors) were added to the medium. Both 5-HT2and 5-HT4receptor agonists significantly enhanced hyperactivation, although the effect was greater than the former. However, both 5-HT2and 5-HT4receptor antagonists significantly suppressed serotonin-enhanced hyperactivation, with the former suppressing stimulation by a lower concentration of serotonin than the latter. These results indicate that serotonin enhances hyperactivation via 5-HT2and/or 5-HT4receptors in a dose-dependent manner.
Functions of Yeast Hsp40 Chaperone Sis1p Dispensable for Prion Propagation but Important for Prion Curing and Protection From Prion Toxicity
Authors: Kirkland P Aaron , Reidy Michael , Masison Daniel C
Published: May 2011

Replication of amyloid-based yeast prions [PSI+], [URE3], and [PIN+] depends on the protein disaggregation machinery that includes Hsp104, Hsp70, and Hsp40 molecular chaperones. Yet, overexpressing Hsp104 cures cells of [PSI+] prions. An Hsp70 mutant (Ssa1-21p) antagonizes propagation of [PSI+] in a manner resembling elevated Hsp104. The major cytosolic Hsp40 Sis1p is the only Hsp40 required for replication of these prions, but its role in [PSI+] curing is unknown. Here we find that all nonessential functional regions of Sis1p are dispensable for [PSI+] propagation, suggesting that other Hsp40’s might provide Hsp40 functions required for [PSI+] replication. Conversely, several Sis1p functions were important for promoting antiprion effects of both Ssa1-21p and Hsp104, which implies a link between the antiprion effects of these chaperones and suggests that Sis1p is a specific Hsp40 important for [PSI+] curing. These contrasting findings suggest that the functions of Hsp104 that are important for propagation and elimination of [PSI+] are either distinct or specified by different Hsp40's. This work also uncovered a growth inhibition caused by [PSI+] when certain functions of Sis1p were absent, suggesting that Sis1p protects cells from cytotoxicity caused by [PSI+] prions.
National Ambulatory Antibiotic Prescribing Patterns for Pediatric Urinary Tract Infection, 1998–2007
Authors: Copp Hillary L. , Shapiro Daniel J. , Hersh Adam L.
Published: May 2011

OBJECTIVE:

The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs).

METHODS:

We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use.

RESULTS:

Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2–18.7, compared with children 13–17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6–8.5]), and temperature ≥100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0–8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection.

CONCLUSIONS:

Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower alternatives.
Asymmetry of the latent heat signature in b-axis oriented single crystal Gd5Si2Ge2
Authors: Morrison K. , Pecharsky V.K. , Gschneidner K.A. , Cohen L.F.
Published: May 2011

A 100 micron fragment of a b-axis oriented single crystal Gd5Si2Ge2 has been studied using microcalorimetry, enabling the separate measurement of the heat capacity and the latent heat. The sample was taken from the same crystal previously studied with Hall probe imaging, which showed that the phase transition is seeded by a second phase of Gd5Si1.5Ge1.5 nanoplatelets on the increasing field sweep direction only. The multiple transition features observed in the latent heat signature suggests a nucleation size of approximately 20 μm, consistent with the lengthscale suggested by Hall imaging. The difference in nucleation and growth process with field sweep direction is clearly identified in the latent heat. We show that the latent heat contribution to the entropy change is of the order of 50% of the total entropy change and unlike other systems studied, the transition does not broaden (and the latent heat contribution does not diminish significantly) as magnetic field and temperature are increased within the parameter range explored in these experiments.
Preparation and Assessment of Superhydrophobic Organic-Inorganic Hybrid Coatings for Conservation of Yungang Grottoes
Authors: Tian Shipeng , Liu Shaojun , Gao Feng , Fan Min , Ren Jianguang
Published: May 2011

Yungang Grottoes in Shanxi, China, which represent outstanding example of Chinese outdoor immovable stone artifacts, are precious world cultural heritage. In the present study, the preparation and assessment of superhydrophobic hybrid coatings with photocatalytic activity on the sandstone substrate collected from Yungang were explored preliminarily. The protection efficiency of coating is investigated by measuring the water-stone contact angles, water vapor permeability, water absorption, and resistance to acid and salt corrosion. Results show that the superhydrophobic organic-inorganic hybrid coatings with photocatalytic and self-cleaning properties are highly suitable for the conservation of stone monuments.
The Early Iron Age Metal Workshop at Tell Tayinat, Turkey
Authors: Roames Jim
Published: May 2011

Scholars have tried to link the dramatic rise of iron production in the Near East during the Early Iron Age with changes to the political landscape that occurred at the end of the Late Bronze Age. These attempts have been hindered by a lack of excavated iron production contexts dating to the Early Iron Age. The recent discovery of an Early Iron Age metal workshop at the site of Tell Tayinat, Turkey, provides an opportunity to reexamine some previous assumptions. Preliminary chemical analysis of metal and slag samples indicates that during the 12th century BC iron- and bronze-working were not separate, specialized industries. Instead, production of both materials took place within the same workshop context. Furthermore, this work highlights the importance of prestige goods in the Early Iron Age repertoire.
Sheehan's syndrome with central diabetes insipidus
Authors: Laway Bashir Ahmad , Mir Shahnaz Ahmad , Dar Mohd Iqbal , Zargar Abdul Hamid
Published: May 2011

Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.
O inquérito eletrocardiográfico
Authors: Gonçalves José Geraldo Ferreira , Prata Aluízio , Dias João Carlos Pinto , Macêdo Vanize
Published: May 2011

Entre 1977 e 1981, foi realizado um inquérito eletrocardiográfico nacional tendo por objetivo avaliar a prevalência da cardiomiopatia chagásica no Brasil. Foram feitos 5.347 eletrocardiogramas. Após o pareamento dos indivíduos, segundo a idade e gênero, a distribuição dos eletrocardiogramas dos autóctones, em cada estado, ficou assim constituída: Rio Grande do Sul (1.078), Minas Gerais (760), Bahia (612), Paraná (400), Paraíba (340), Piauí (218), Sergipe (216), Goiás (176), Pernambuco (170), Ceará (136) e Alagoas (134). Os maiores percentuais de alterações eletrocardiográficas entre os indivíduos com soros reagentes foram encontrados nos Estados de Goiás (63,6%), Minas Gerais (57,6%), Ceará (57,3%), Paraná (54,5%), Piauí (53,2%) e Paraíba (52,3%). Entre os controles, nestes estados, a prevalência das alterações eletrocardiográficas foi de 25%, 25,7%, 25%, 12,5%, 22,9% e 26,5% respectivamente. Observou-se diferença estatisticamente significativa em relação à prevalência das alterações eletrocardiográficas, entre os indivíduos soro reagentes e os não reagentes, em todos os estados, exceção feita para o de Alagoas. O cálculo do gradiente mostrou-se maior no Estado do Paraná (42%), seguido por Goiás (38,6%), Ceará (32,3%) Minas Gerais (31,9%), Piauí (30,3%), Paraíba (25,8%), Pernambuco (22,3%), Bahia (18,9%), Sergipe (16,7%), Rio Grande do Sul (9,9%) e Alagoas (7,5%). Em relação à distribuição das alterações eletrocardiográficas encontradas, nos onze estados analisados, verificou-se que as extrassístoles ventriculares, o bloqueio de grau avançado do ramo direito, o bloqueio da divisão ântero-superior do ramo esquerdo, a associação do bloqueio de grau avançado do ramo direito com o bloqueio da divisão ântero-superior do ramo esquerdo e alterações primárias do segmento ST e da onda T, mostraram diferença estatisticamente significativa, entre os indivíduos com sororreagentes e os não reagentes Além disto, estas alterações eletrocardiográficas foram as de maior prevalência no grupo dos indivíduos chagásicos.
Variabilidade genética de Colletotrichum guaranicola usando marcadores AFLP
Authors: Bentes Jânia Lilia da Silva , Costa Neto Pedro Queiroz
Published: May 2011

Foi detectada a variabilidade genética de vinte isolados de Colletotrichum guaranicola (Albuq.) provenientes de diferentes localidades produtoras de guaraná no Amazonas, utilizando-se marcadores moleculares AFLP. Foi possível separar os isolados em dois grupos. O coeficiente de variação genética entre os isolados foi de 0,0216 e a similaridade genética foi de 94,95%, confirmando que os isolados pertencem à mesma espécie, no entanto, foi observada variabilidade intra-específica.
Ensino médico, SUS e início da profissão: como se sente quem está se formando?
Authors: Oliveira Neilton Araujo de , Alves Luiz Anastácio
Published: May 2011

A construção do SUS e o crescimento do nosso país têm suscitado uma discussão maior sobre mudanças no ensino médico. Iniciativas para implementar as Diretrizes Curriculares Nacionais aumentam o cardápio de estratégias de mudanças na preparação do fu turo médico. Para compreender melhor essas modificações, aplicamos questionários in locu a 1.004 alunos do internato de Medicina em 13 cursos médicos de seis Estados brasileiros entre 2004 e 2007, e realizamos entrevistas com alunos, docentes e gestores de Saúde. Neste artigo, destacamos o que pensam os formandos a respeito de sua formação no começo de sua atuação profissional. Aproximadamente 19% dos alunos se sentem aptos ao exercício imediato da medicina; 81% querem buscar formação complementar; 63% desejam ser "especialistas"; só 20% querem trabalhar em medicina geral, como o PSF, e apenas 5% querem trabalhar em pequenos municípios. Há discrepâncias entre o que os alunos querem fazer, como se sentem preparados e o que acabarão por fazer. Este estudo fornece dados que podem ajudar na melhoria da educação médica de acordo com as demandas do SUS e na integração ensino-serviços-comunidade.
O uso da Aprendizagem Baseada em Problemas (ABP) como reforço ao ensino presencial utilizando o ambiente de aprendizagem Moodle
Authors: Mezzari Adelina
Published: May 2011

Este estudo teve por objetivo implementar mudanças na disciplina de Parasitologia e Micologia Médica do curso de Medicina da Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), que sempre foi oferecida na modalidade presencial. O estudo foi realizado de março a julho de 2009 com os alunos do primeiro semestre do primeiro ano do curso de Medicina. A mudança consistiu em utilizar parte do ensino a distância (EAD) com aplicação do método de ensino ABP, no ambiente virtual Moodle, disponível na instituição. Os resultados deste estudo apontam que a utilização do EAD e os recursos de ABP como complemento do ensino presencial de graduação nos cursos da área da saúde podem se tornar efetivos para a formação profissional.
Comparação florística e estrutural de duas florestas de várzea no estuário amazônico, Pará, Brasil
Authors: Batista Fábio de Jesus , Jardim Mário Augusto Gonçalves , Medeiros Tonny David Santiago , Lopes Isaac Luiz Magalhães
Published: May 2011

O objetivo deste trabalho foi conhecer e comparar a composição florística e a estrutura de duas áreas de florestas de várzea localizadas na reserva extrativista Chocoaré-Mato Grosso, Santarém Novo-PA. O inventário florístico abrangeu 1,5 ha em parcelas de 10 x 100 m, distribuídas na área 1 (1,0 ha) e área 2 (0,5 ha). Foram identificados os indivíduos arbóreos com circunferência a 1,3 m altura do solo (CAP > 30 cm e demonstrada a riqueza, área basal e o IVI (Índice de Valor de Importância) para cada área. A relação entre as áreas foi realizada por meio da similaridade de espécies, densidade, área basal, análise de agrupamento e espécies indicadoras. Na área 1, ocorreram 613 ind.ha-1 (26,67 m².ha-1) distribuídos em 17 famílias, 33 gêneros e 34 espécies com Euterpe oleracea, Enterolobium maximum, Symphonia globulifera, Pterocarpus amazonicus e Virola surinamensis apresentando os maiores IVI's e a área 2 com 744 ind.ha-1 (35,34 m².ha-1) em 13 famílias, 24 gêneros e 26 espécies com Mauritia flexuosa, Euterpe oleracea, Virola surinamensis, Tapirira guianensis e Inga thibaudiana com os maiores IVI's. As áreas registraram baixas similaridades entre si (0,18) e tanto a densidade quanto a área basal foram superiores na área 2. O agrupamento separou as áreas entre si e das 51 espécies, apenas 15 foram indicadoras. Conclui-se que, as florestas apresentaram baixa riqueza com pouca semelhança entre as populações arbóreas e as espécies indicadoras ocorreram nas áreas 1 e 2.