bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase, Hck
Authors: Pene-Dumitrescu Teodora , Shu Sherry T , Wales Thomas E , Alvarado John J , Shi Haibin , Narute Purushottam , Moroco Jamie A , Yeh Joanne I , Engen John R , Smithgall Thomas E 
Published: March 2012

Abstract

Background
Nef is an HIV-1 accessory protein essential for viral replication and AIDS progression. Nef interacts with a multitude of host cell signaling partners, including members of the Src kinase family. Nef preferentially activates Hck, a Src-family kinase (SFK) strongly expressed in macrophages and other HIV target cells, by binding to its regulatory SH3 domain. Recently, we identified a series of kinase inhibitors that preferentially inhibit Hck in the presence of Nef. These compounds also block Nef-dependent HIV replication, validating the Nef-SFK signaling pathway as an antiretroviral drug target. Our findings also suggested that by binding to the Hck SH3 domain, Nef indirectly affects the conformation of the kinase active site to favor inhibitor association.

Results
To test this hypothesis, we engineered a "gatekeeper" mutant of Hck with enhanced sensitivity to the pyrazolopyrimidine tyrosine kinase inhibitor, NaPP1. We also modified the RT loop of the Hck SH3 domain to enhance interaction of the kinase with Nef. This modification stabilized Nef:Hck interaction in solution-based kinase assays, as a way to mimic the more stable association that likely occurs at cellular membranes. Introduction of the modified RT loop rendered Hck remarkably more sensitive to activation by Nef, and led to a significant decrease in the Km for ATP as well as enhanced inhibitor potency.

Conclusions
These observations suggest that stable interaction with Nef may induce Src-family kinase active site conformations amenable to selective inhibitor targeting.
Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites
Authors: Cruz Laura Nogueira , Juliano Maria Aparecida , Budu Alexandre , Juliano Luiz , Holder Anthony A , Blackman Michael J , Garcia Célia RS 
Published: March 2012

AbstractBackgroundPlasmodiumhas a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host.MethodsUsing the fluorescence resonance energy transfer (FRET) peptide substrate Abz-AIKFFARQ-EDDnp and Fluo4/AM, the effects of extracellular ATP on triggering proteolysis and Ca2+signalling inPlasmodium bergheiandPlasmodium yoeliimalaria parasites were investigated.ResultsThe protease activity was blocked in the presence of the purinergic receptor blockers suramin (50 μM) and PPADS (50 μM) or the extracellular and intracellular calcium chelators EGTA (5 mM) and BAPTA/AM (25, 100, 200 and 500 μM), respectively forP. yoeliiandP. berghei. Addition of ATP (50, 70, 200 and 250 μM) to isolated parasites previously loaded with Fluo4/AM in a Ca2+-containing medium led to an increase in cytosolic calcium. This rise was blocked by pre-incubating the parasites with either purinergic antagonists PPADS (50 μM), TNP-ATP (50 μM) or the purinergic blockers KN-62 (10 μM) and Ip5I (10 μM). IncubatingP. bergheiinfected cells with KN-62 (200 μM) resulted in a changed profile of merozoite surface protein 1 (MSP1) processing as revealed by western blot assays. Moreover incubatingP. bergheifor 17 h with KN-62 (10 μM) led to an increase in rings forms (82% ± 4, n = 11) and a decrease in trophozoite forms (18% ± 4, n = 11).ConclusionsThe data clearly show that purinergic signalling modulatesP. bergheiprotease(s) activity and that MSP1 is one target in this pathway.
Involvement of metabotropic glutamate receptor 5, AKT/PI3K Signaling and NF-κB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes
Authors: Shah Ankit , Silverstein Peter S , Singh Dhirendra P , Kumar Anil 
Published: March 2012

Abstract
Methamphetamine (MA) is one of the commonly used illicit drugs and the central nervous system toxicity of MA is well documented. The mechanisms contributing to this toxicity have not been fully elucidated. In this study, we investigated the effect of MA on the expression levels of the proinflammatory cytokines/chemokines, IL-6 and IL-8 in an astrocytic cell line. The IL-6 and IL-8 RNA levels were found to increase by 4.6 ± 0.2 fold and 3.5 ± 0.2 fold, respectively, after exposure to MA for three days. Exposure of astrocytes to MA for 24 hours also caused increased expression of IL-6 and IL-8 at the level of both RNA and protein. The potential involvement of the nuclear factor-Kappa B (NF-κB) pathway was explored as one of the possible mechanism(s) responsible for the increased induction of IL-6 and IL-8 by MA. The MA-mediated increases in IL-6 and IL-8 were significantly abrogated by SC514. We also found that exposure of astrocytes to MA results in activation of NF-κB through the phosphorylation of IκB-α, followed by translocation of active NF-κB from the cytoplasm to the nucleus. In addition, treatment of cells with a specific inhibitor of metabotropic glutamate receptor-5 (mGluR5) revealed that MA-mediated expression levels of IL-6 and IL-8 were abrogated by this treatment by 42.6 ± 5.8% and 65.5 ± 3.5%, respectively. Also, LY294002, an inhibitor of the Akt/PI3K pathway, abrogated the MA-mediated induction of IL-6 and IL-8 by 77.9 ± 6.6% and 81.4 ± 2.6%, respectively. Thus, our study demonstrates the involvement of an NF-κB-mediated signaling mechanism in the induction of IL-6 and IL-8 by MA. Furthermore, we showed that blockade of mGluR5 can protect astrocytes from MA-mediated increases of proinflammatory cytokines/chemokines suggesting mGluR5 as a potential therapeutic target in treating MA-mediated neurotoxicity.
Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a case report
Authors: Scheel Andreas Hans , Krause Daniel , Haars Helmut , Schmitz Inge , Junker Klaus 
Published: March 2012

Abstract

Background
Talcosis, a granulomatous inflammation of the lungs caused by inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative occupational exposure, intravenous abuse of adulterated drugs is a major cause for this condition. Minerals such as talcum (magnesium silicate) and sand (predominant silicon dioxide) are used to increase both volume and weight of illicit substances. In intravenous heroin-abuse, talcosis is a well-known complication. Here we describe a case of talcosis caused by inhalative abuse of adulterated marijuana.

Clinical history
A 29-year old man presented with persistent fever, dyspnea and cervical emphysema. He admitted consumption of 'cut' marijuana for several years, preferentially by water pipe smoking.

Morphologic findings
Lung-biopsies showed chronic interstitial lung disease, anthracotic pigments and birefringent material. Energy dispersive x-ray spectroscopy revealed silicon-containing particles (1-2 μm) and fine aluminum particles (< 1 μm), magnesium and several other elements forming a spectrum compatible with the stated water pipe smoking of talcum-adulterated marijuana.

Conclusions
The exacerbated chronic interstitial lung disease in a 29-year old patient could be attributed to his prolonged abuse of talcum-adulterated marjuana by histopathology and x-ray spectroscopy. Since cannabis consumption is widely spread among young adults, it seems to be justified to raise attention to this form of interstitial pulmonary disease.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnomx.eu/vs/krause/html/start.html.
Unknotting night‐time muscle cramp: a survey of patient experience, help‐seeking behaviour and perceived treatment effectiveness
Authors: Blyton Fiona , Chuter Vivienne , Burns Joshua 
Published: March 2012

AbstractBackgroundNight‐time calf cramping affects approximately 1 in 3 adults. The aim of this study was to explore the experience of night‐time calf cramp; if and where people seek treatment advice; and perceived treatment effectiveness.Methods80 adults who experienced night‐time calf cramp at least once per week were recruited from the Hunter region, NSW, Australia through newspaper, radio and television advertisements. All participants completed a pilot‐tested survey about muscle cramp. Quantitative data were analysed with independent‐sample t‐tests, Chi square tests and Fisher's tests. Qualitative data were transcribed and sorted into categories to identify themes.ResultsMedian recalled age of first night‐time calf cramp was 50 years. Most participants recalled being awoken from sleep by cramping, and experiencing cramping of either calf muscle, calf‐muscle soreness in the days following cramp and cramping during day‐time. Despite current therapies, mean usual pain intensity was 66 mm on a 100 mm visual analogue scale. Participants described their cramps as being ‘unbearable’, ‘unmanageable’ and ‘cruel’. One participant stated that ‘sometimes I just wish I could cut my legs open’ and another reported ‘getting about 2 h sleep a night due to cramps’. Most participants had sought advice about their night‐time calf cramps from a health professional. Participants identified 49 different interventions used to prevent night‐time calf cramp. Of all treatment ratings, 68% described the intervention used to prevent cramp as being ‘useless’ or of ‘a little help’. Of 14 participants who provided additional information regarding their use of quinine, eight had a current prescription of quinine for muscle cramp at the time of the survey. None had been asked by their prescribing doctor to stop using quinine.ConclusionNight time calf cramps typically woke sufferers from sleep, affected either leg and caused ongoing pain. Most participants experienced little or no relief with current therapies used to prevent muscle cramp. Most people who were taking quinine for muscle cramp were unaware that the Australian Therapeutic Goods Administration withdrew support of quinine for muscle cramp in 2004 due to the risk of thrombocytopaenia. Case‐control studies are required to identify therapeutic targets so that clinical trials can evaluate safe interventions to prevent recurrent cramp.
Civic Universalism and Its Internal Exclusions: The Issue of Anthropological Difference
Authors: Balibar Etienne 
Published: March 2012

Modern universalism, arising from the generalization of the “right to have rights” (or the access to citizenship for all), produces a paradoxical effect on the recognition and definition of anthropological differences, such as gender and sexuality, race and culture, normality and abnormality.
Its “civic-bourgeois” foundation, which is purely political (neither theological nor cosmological), accounts for a neutralization of differences in the abstract realm of liberty and equality, which justifies claims of emancipation. On the other hand, discriminations barring individuals and groups from (full) access to citizenship need to be rooted in human nature, which is supposed to consist therefore of hierarchized “characters.” As a consequence, differences become also principles of exclusion: this is more violent symbolically (or even practically) but much less stable and “legitimate” than was the case in previous forms of historical hegemony.
Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis
Authors: Harrelson Zachary , Kaestner Klaus H. , Evans Sylvia M. 
Published: March 2012

Summary
Axial mesendoderm is comprised of prechordal plate and notochord. Lack of a suitable Cre driver has hampered the ability to genetically dissect the requirement for each of these components, or genes expressed within them, to anterior patterning. Here, we have utilized Isl1-Cre to investigate roles of the winged helix transcription factor Foxa2 specifically in prechordal plate and ventral endoderm. Foxa2loxP/loxP; Isl1-Cre mutants died at 13.5 dpc, exhibiting aberrations in anterior neural tube and forebrain patterning, and in ventral foregut morphogenesis and cardiac fusion. Molecular analysis of Foxa2loxP/loxP; Isl1-Cre mutants indicated that Foxa2 is required in Isl1 lineages for expression of notochord and dorsal foregut endoderm markers, Shh. Brachyury, and Hlxb9. Our results support a requirement for Foxa2 in prechordal plate for notochord morphogenesis, axial patterning, and patterning of dorsal foregut endoderm. Loss of Foxa2 in ventral endoderm resulted in reduced expression of Sox17, Gata4, and ZO proteins, accounting at least in part for observed lack of foregut fusion, cardia bifida, and increased apoptosis of ventral endoderm.
Evaluation of two minimal-preparation regimes for CT colonography: optimising image quality and patient acceptability
Authors: Pollentine A , Mortimer A , Mccoubrie P , Archer L 
Published: March 2012

Objective: To compare a 2 day bowel preparation regime of barium, iodine and a mild stimulant laxative with a 1 day iodine-only regime for CT colonography (CTC).
Methods: 100 consecutive patients underwent CTC. The first 50 patients (Regime 1) ingested 1 bisacodyl tablet twice a day 3 days before CTC and 1 dose each of 50 ml of barium and 20 ml of iodinated contrast per day starting 2 days before CTC. The second 50 patients (Regime 2) ingested 3 doses of iodinated contrast over 24 h prior to CTC. Volumes of residual stool and fluid, and the effectiveness of stool and fluid tagging, were graded according to methods established by Taylor et al (Taylor S, Slaker A, Burling D, Tam E, Greenhalgh R, Gartner L, et al. CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging. Eur Radiol 2008; 18: 32–42). A 3 day low-residue diet was taken by both cohorts. Questionnaires rating the side-effects and burden of the bowel preparation were compared to a control cohort of patients undergoing barium enema.
Results: The proportion of colons producing none/scattered stool (score 1) was 90.3% with Regime 1 and 65.0% with Regime 2 (p&lt;0.005). Any residual stool was significantly better tagged with Regime 1 (score 5), with 91.7% of Regime 1 exhibiting optimum tagging vs 71.3% of Regime 2 (p&lt;0.05). No significant differences in side-effects between the bowel preparation regimes for CTC were elicited. Bowel preparation for barium enema was tolerated significantly worse than both of the CTC bowel preparation regimes.
Conclusion: Regime 1, containing a 3 day preparation of a mild laxative, barium and iodine, produced a significantly better prepared colon, with no difference in patient acceptability.
Unser Katalog soll besser werden! Kataloge und Portale im Web-2.0-Zeitalter. Ergebnisse einer Online-Umfrage im HeBIS-Verbund
Authors: Nienerza Heike , Sunckel Bettina , Meier Berthold 
Published: March 2012

Zusammenfassung
Vom 13. Dezember 2010 bis zum 21. Januar 2011 führte der HeBIS-Verbund eine Online-Umfrage zu den Oberflächen der Kataloge und Katalogportale seiner Mitgliedsbibliotheken durch. Insgesamt erklärten sich 16 HeBIS-Bibliotheken unterschiedlichen Typs zu einer Teilnahme bereit. Die HeBIS-Verbundzentrale wurde bei der Konzeption und Durchführung von einer studentischen Projektgruppe im Rahmen eines bibliothekarischen Studienprojektes im Bachelor-Studiengang Information Science and Engineering / Informationswissenschaft der Hochschule Darmstadt unterstützt. Mit fast 22 000 vollständig ausgefüllten Fragebögen übertraf der Rücklauf der Umfrage alle Erwartungen. Unabhängig von den Auswertungen für die einzelnen Bibliotheken wird hier in einer Gesamtauswertung ein bibliotheksübergreifender Überblick über die Ergebnisse gegeben. Zusammenfassend lässt sich sagen, dass die klassische Aufgabe von Online-Katalogen, nämlich ein effektives Retrieval des gesamten Bibliotheksbestands zu ermöglichen und Auskunft über den Standort und die aktuelle Verfügbarkeit von Medien zu geben, für die Katalognutzer auch in Zeiten des Internet und Social Web weiterhin im Vordergrund steht.
New records of red algae from mangroves in El Salvador and Pacific Mexico, combining culture and molecular observations
Authors: Zuccarello Giuseppe C. , Kamiya Mitsunobu , Ootsuki Ryo , de Goër Susan Loiseaux , Pedroche Francisco F. , West John A. 
Published: March 2012

Abstract
The algae of El Salvador have received limited attention. We combined collections from the mangroves of El Salvador and neighboring southern Mexico, and used culture studies and molecular analysis to gain insights into the diversity in this poorly explored region. Bostrychia montagnei, Caloglossa apomeiotica, and Caloglossa ogasawaraensis were newly recorded in El Salvador. Bostrychia montagnei has not been reported from the Pacific Americas before. B. montagnei normally produced axial cells with two-tier cells, typical of the species, but sometimes a series of axial cells had three-tier cells. This was a significant tier cell number variation not previously seen in Bostrychia species. Bostrychia montagnei had a Polysiphonia-type sexual life history with both unisexual and bisexual gametophytes. Caloglossa apomeiotica isolates in culture from El Salvador and Chiapas, Mexico, either had a normal sexual life history or asexual recycling of tetrasporophytes. Those found in El Salvador were the first record of C. apomeiotica south of Jalisco, Mexico, a distance of 1200 km. Four strains isolated from El Salvador and Chiapas, Mexico, which were morphologically part of the Caloglossa leprieurii sensu lato lineage, were analyzed; however, they were not closely related to any named species, indicating that this is a new species that will require further study.
Seasonal dynamic of macroalgae in intertidal pools formed by beds of Crassostrea gigas (Mollusca, Bivalvia) on the north Patagonian Atlantic coast
Authors: Croce M. Emilia , Parodi Elisa R. 
Published: March 2012

Abstract
Intertidal pools represent restricted habitats for macroalgal assemblages, and their structure is determined by physical and biotic factors. The establishment of the exotic oyster Crassostrea gigas on the north Patagonian Atlantic coast led to the formation of intertidal pools; these provide habitats for macroalgal settlement. We aimed to determine the composition, distribution and abundance of the macroalgal assemblage inhabiting these pools, and to establish the structuring variables. Several biotic and abiotic variables were evaluated in 36 pools in winter and summer. Correlations were calculated and permutation analysis of variance and constrained redundancy analysis were conducted to determine the structuring variables. Unlike other Patagonian coasts, richness was low and pools were characterized by a dominance of red algae. Richness was higher in winter, while diversity was lower because of the dominance of Polysiphonia abscissa, which had the highest percentage of occurrence. Temperature was a putative factor determining seasonal richness and diversity. Elevation and surface area of the pools were structuring factors for assemblage biomass. We demonstrated distinct assemblage dynamics. Polysiphonia abscissa developed large populations in winter, which declined towards the summer, while Gelidium maggsiae and Gelidiella calcicola formed dense turfs during summer stress.
Three Dinophyceae from Clipperton Island lagoon (eastern Pacific Ocean), including a description of Peridiniopsis
cristata var. tubulifera var. nov.
Authors: Couté Alain , Perrette Catherine , Chomérat Nicolas 
Published: March 2012

Abstract
Clipperton Island is a small French coral atoll in the eastern Pacific Ocean, which has been rarely investigated because of its remote location and difficult access. There is little scientific information on this ecosystem and only a few microalgae have been reported from the lagoon. To date, only one dinoflagellate taxon, Peridiniopsis cristata, is known to inhabit the lagoon. During an expedition in 2005 to study the lagoon and the surrounding oceanic waters of Clipperton Island, a further investigation of the lagoon phytoplankton was undertaken. In addition to P. cristata, which was still abundant in the upper water layer, two other thecate dinoflagellates were recorded. One dinoflagellate was identified as Durinskia baltica, while the other had the same thecal plate arrangement as P. cristata but was slightly smaller, (27) 30–40 μm long, 26–32 μm wide, and its plates were unornamented and devoid of prominent lists. Hence, the latter taxon is described as P. cristata var. tubulifera since it represents an extreme variation in the ornamentation of the nominate variety. This study provides a description and detailed illustrations of the three taxa found in this peculiar tropical marine ecosystem.
Capecitabine Monotherapy: Review of Studies in First-Line HER-2-Negative Metastatic Breast Cancer
Authors: O'Shaughnessy Joyce A. , Kaufmann Manfred , Siedentopf Friederike , Dalivoust Philippe , Debled Marc , Robert Nicholas J. , Harbeck Nadia 
Published: March 2012

AbstractThe goals of treatment for metastatic breast cancer (MBC) are to prolong overall survival (OS) while maximizing quality of life, palliating symptoms, and delaying tumor progression. For many years, anthracyclines and taxanes have been the mainstay of treatment for MBC, but these agents are now commonly administered earlier in the course of the disease. A recent meta-analysis revealed adverse effects on OS and overall response rates in patients with MBC receiving first-line anthracycline-based chemotherapy following relapse on adjuvant chemotherapy. Noncrossresistant cytotoxic agents and combinations that combine high clinical activity and acceptable tolerability while being convenient for patients are therefore needed for the first-line treatment of MBC patients. Capecitabine has substantial antitumor activity in the first-line treatment of patients with MBC in prospective, randomized, phase II/III clinical trials as monotherapy and in combination with biologic and novel agents. First-line capecitabine monotherapy has a favorable safety profile, lacking myelosuppression and alopecia, and does not compromise the administration of further lines of chemotherapy. Capecitabine is suitable for long-term administration without the cumulative toxicity that can limit the prolonged use of other chemotherapy agents. Here, we review the available data on capecitabine as a single agent for first-line treatment of patients with human epidermal growth factor receptor 2–negative MBC.
Implementing Childhood Obesity Policy in a New Educational Environment: The Cases of Mississippi and Tennessee
Authors: Amis John M. , Wright Paul M. , Dyson Ben , Vardaman James M. , Ferry Hugh 
Published: March 2012

Objectives. Our purpose was to investigate the processes involved in, and outcomes of, implementing 3 new state-level, school-oriented childhood obesity policies enacted between 2004 and 2007. Methods. We followed policy implementation in 8 high schools in Mississippi and Tennessee. We collected data between 2006 and 2009 from interviews with policymakers, administrators, teachers, and students; observations of school-based activities; and documents. Results. Significant barriers to the effective implementation of obesity-related policies emerged. These most notably include a value system that prioritizes performances in standardized tests over physical education (PE) and a varsity sport system that negatively influences opportunities for PE. These and other factors, such as resource constraints and the overloading of school administrators with new policies, mitigate against the implementation of policies designed to promote improvements in student health through PE. Conclusions. Policies designed to address health and social problems in high-school settings face significant barriers to effective implementation. To have a broad impact, obesity-related policies must be tied to mainstream educational initiatives that both incentivize, and hold accountable, the school-level actors responsible for their implementation.