bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an evidence-based patient pathway for non-surgical and surgically managed metacarpal fractures
Authors: Midgley Robyn , Toemen Angela
Published: February 2011

Introduction

A review of current literature was used to develop an evidence-based pathway, managing surgical and non-surgical metacarpal fractures according to their anatomical location and fracture stability. The aim of this paper is to evaluate functional outcome, splint compliance, range of motion (ROM), residual pain, return to work and patient satisfaction following treatment based on the pathway.

Method

Fifty patients referred for surgical or non-surgical management of metacarpal fracture(s) were selected to participate in the clinical evaluation. Patient demographics, fracture site, management approach, type of splint, number of appointments attended and complications were recorded. A telephone questionnaire was used to evaluate patient satisfaction, compliance with splinting, ROM, pain, return to work and functional outcome. Recorded complications included infection, malunion, nonunion, rotational deformity and angulation deformity.

Results

Thirty-six patients were contactable 10–24 weeks post-injury. A total of 23 metacarpal neck/head, eight shaft and four base fractures were included. Ninety-four percent (34/36) of fractures were treated non-operatively. Patients were compliant with splinting in 17/36 (47%) cases. There were no reported complications. Seventy-two percent reported no pain at follow-up. All employed patients returned to work. Full ROM was reported in all cases. Full functional use of the hand was present in 92% of cases. Patients reported high satisfaction with the service (8/10) and required an average of three therapy appointments.

Conclusion

The metacarpal fracture evidence-based pathway was successful with 92% of patients returning to full function. The absence of complications emphasizes hand therapy's ability to efficiently and cost-effectively manage these fractures following referral. The pathway has been further refined as a result of the clinical evaluation, with alteration of the metacarpal shaft fracture splint, removal of repeat X-rays and reduction of splinting durations. It is recommended that the revised pathway is further evaluated.
A Speculative Account (with Notes) of the Development and Initial Deployments of Shel Silverstein's Persona, Uncle Shelby, with Special Care to Articulate the Relationship of Said Persona to the Question of Shel's Ambiguous Audience(s)
Authors: Thomas Joseph T.
Published: February 2011

This essay articulates Shel Silverstein's "Uncle Shelby" persona, historicizing its development in his music, Playboy , and early children's books. Focusing on Uncle Shelby's ABZ Book (1961) and Lafcadio, the Lion Who Shot Back (1963), two books that first appeared in Playboy , the essay argues that the restoration of these works to their original context—and thinking about Shelby's relationship to Playboy in general—brings to the surface textual and ideological complexities that are likely overlooked in their children's book form, just as it raises provocative questions regarding Silverstein's construction of his child audience and our construction of Silverstein himself.
Between Cultured Young Men and Mischievous Children: Youth, Transgression, and Protest in Late Nineteenth-Century Mexico
Authors: Pensado Jaime
Published: February 2011

This article traces the progression of "youth" in Mexico from 1867 to c. 1900. It argues that the historical "images" of youth that developed during this period are telling as to youth culture, but also reveal much concerning greater societal and national aspirations. As this burgeoning vision of youth took shape in the late nineteenth century, its preeminent expression was the preparatoriano, or the student of the National Preparatory School. This "positivist image" of youth, hitherto overlooked in the historiography, was particularly celebratory and bespoke the transformative nature of the modern state. This group of young students, however, was not homogenous. As the restored nation tried its find its course (through local notions of liberalism and positivism), different notions of youth were imagined, experienced, further defined, and contested. This relationship between official ideology and reality was evident in the subcultural behavior of young men and the reactions these contested images generated among the old or the parent culture. This essay traces the contested relationship between official representation and subculture in the rise of student activism, the appropriation of new and public spaces, the creation of innovative style, and the celebration of an illicit bohemian lifestyle, on the one hand, and in public reaction, on the other.
Gustav Mahler's Second Century: Achievements in Scholarship and Challenges for Research
Authors: Zychowicz James L.
Published: February 2011

The popular and critical appeal of Mahler's music is evident in the performances of his music and the influence those pieces have on other composers. In the early twentieth century the efforts by his widow and colleagues to preserve his memory emerged in various collections of letters and other documents which were important later for the completion of various biographies; and in the mid-twentieth century, the Internationale Gustav Mahler Geselleschaft undertook the publication of a critical edition of the composer's collected works. In the latter part of the twentieth century, the revival of interest in Mahler's music spurred both performances of his music and intensive studies that involve analysis, reception history, and performing practice. His legacy continues into a second century, as research not only continues, but moves into areas that have not been explored to understand the structures Mahler used to express music of continuing relevance.
Enclosure Polemics and the Garden in the 1650s
Authors: Attie Katherine Bootle
Published: February 2011

Through close readings of husbandry manuals, religious pamphlets, and Paradise Lost , this essay explores how polemicists on both sides of the enclosure debate made strategic use of garden imagery in their writing. The argument shows that Puritan improvers at midcentury, by figuring enclosed commons as idealized gardens and England as a new Eden, invent a distinctly georgic—and distinctly English—vision of paradise. Turning to the appropriation of garden imagery by enclosure opponents, the essay juxtaposes Gerrard Winstanley and John Milton, both of whom privilege the paradise within over any imaginable earthly garden.
The Son as Collaborator in Paradise Regained
Authors: Taylor Patricia R.
Published: February 2011

In the beginning of Paradise Regained , Milton states that the Son will "Publish his Godlike office." I argue that the connotations of publication in this statement allow us to read the Son's construction of his kingship as an analogue for Milton's construction of his own authorship and vice versa. By exploring a few aspects of Milton's conceptions of authorship, inspiration, and vocation, I will show that Milton constructs the Son as a type of author and publisher with whom he sees himself collaborating, and that the discussion of kingship in the poem provides a model for political engagement through authorship.
Targeting BRAFV600E with PLX4720 Displays Potent Antimigratory and Anti-invasive Activity in Preclinical Models of Human Thyroid Cancer
Authors: Nucera Carmelo , Nehs Matthew A. , Nagarkatti Sushruta S. , Sadow Peter M. , Mekel Michal , Fischer Andrew H. , Lin Paul S. , Bollag Gideon E. , Lawler Jack , Hodin Richard A. , Parangi Sareh
Published: February 2011

Purpose.

B-RafV600E may play a role in the progression from papillary thyroid cancer to anaplastic thyroid cancer (ATC). We tested the effects of a highly selective B-RafV600E inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505cB-RafV600E and TPC-1RET/PTC-1 and wild-type B-Raf) and in primary human normal thyroid (NT) follicular cells engineered with or without B-RafV600E.

Experimental Design.

Large-scale genotyping analysis by mass spectrometry was performed in order to analyze >900 gene mutations. Cell proliferation and migration/invasion were performed upon PLX4720 treatment in 8505c, TPC-1, and NT cells. Orthotopic implantation of either 8505c or TPC-1 cells into the thyroid of severe combined immunodeficient mice was performed. Gene validations were performed by quantitative polymerase chain reaction and immunohistochemistry.

Results.

We found that PLX4720 reduced in vitro cell proliferation and migration and invasion of 8505c cells, causing early downregulation of genes involved in tumor progression. PLX4720-treated NT cells overexpressing B-RafV600E (heterozygous wild-type B-Raf/B-RafV600E) showed significantly lower cell proliferation, migration, and invasion. PLX4720 treatment did not block cell invasion in TPC-1 cells with wild-type B-Raf, which showed very low and delayed in vivo tumor growth. In vivo, PLX4720 treatment of 8505c orthotopic thyroid tumors inhibited tumor aggressiveness and significantly upregulated the thyroid differentiation markers thyroid transcription factor 1 and paired box gene 8.

Conclusions.

Here, we have shown that PLX4720 preferentially inhibits migration and invasion of B-RafV600E thyroid cancer cells and tumor aggressiveness. Normal thyroid cells were generated to be heterozygous for wild-type B-Raf/B-RafV600E, mimicking the condition found in most human thyroid cancers. PLX4720 was effective in reducing cell proliferation, migration, and invasion in this heterozygous model. PLX4720 therapy should be tested and considered for a phase I study for the treatment of patients with B-RafV600E ATC.
The origin of federal drinking water quality standards
Authors: Gurian Patrick L , Tarr Joel A
Published: February 2011

In the USA, the first federal drinking water standards were established by the Public Health Service (PHS) in 1914. This paper identifies the scientific and engineering foundations for the standards, namely an understanding of the etiology of waterborne disease, standard methods for assessing water quality and treatment methods capable of assuring water quality. The legal basis for the standards was the 1893 Interstate Quarantine Act, which gave the PHS the responsibility of preventing the spread of disease through interstate commerce, although the Act did not specifically call for the creation of water quality standards. This statutory authority limited the applicability of the standard to water served on interstate carriers, principally trains. However, it was immediately recognised that the standards would be perceived as a generally relevant standard. The standards were considered to be relatively stringent, which led to some adverse reaction from water suppliers. However, compliance with the standards gradually became the norm among major urban water suppliers. The standard setting effort may be seen as an attempt to use the prestige of the federal government to create a consensus in favour of higher quality water, through the promulgation of strict but achievable standards.
Paddington station: span 4 refurbishment and strengthening
Authors: Slade Graham
Published: February 2011

London's Paddington station, the terminus of the Great Western Railway, was the masterpiece of the company's first chief engineer, Isambard Kingdom Brunel. The core of the station is a magnificent three-span arch roof on slender iron columns. However, in the early part of the twentieth century, the station was much extended, most notably by the addition of a grand fourth span to the roof structure. In recent times, span 4 has been neglected and is now undergoing refurbishment to restore it to its proper place as a grade 1 listed structure, alongside the remainder of the station buildings. The project will complete the renovation of the station's entire roof and complement the improved passenger information systems and retail developments. This paper first reprises the significant details of the original construction and looks in detail at the recent assessment of the span 4 roof and the associated parcel deck. Network Rail, the asset steward, is in the throes of undertaking the first major refurbishment of span 4 for over half a century and the paper describes the main aspects of the investigations and design that have led to the current works.
Role of moulding water content in lime stabilisation of soil
Authors: Ramesh Heddur Nagappa Gowda , Sivapullaiah Puvvadi Venkata
Published: February 2011

The role of moulding water content, from the dry side of the optimum to the wet side of optimum, in the strength development in lime-treated soils was investigated in the present study. During compaction, the structure of clay particles can change from a flocculated to a dispersed structure as the water content is increased from the dry side of optimum to the wet side of optimum. For efficient formation of pozzolanic compounds, the water content of the soil–lime mixture should be kept as high as possible. The improvement in the strength of Indian black cotton soil treated with different amounts of lime content at different water contents and cured for varying curing periods was studied. The results clearly showed that the strength of black cotton soil treated with lime content increased better when compacted on the dry side of optimum, the other parameters remaining the same. Further, the optimum lime varied with moulding water content and curing period.
Teaching Statistics to Undergraduate Nursing Students: An Integrative Review to Inform our Pedagogy
Authors: Epstein Iris , Santa Mina Elaine E , Gaudet Julie , Singh Mina D. , Gula Taras
Published: February 2011

One goal of undergraduate nursing education is to develop competency in statistics interpretation. This competency requires adequate knowledge and skill to read and analyze the merits of research studies, quality assurance data, and patient data. The literature suggests that RNs may lack undergraduate, entry-to-practice competencies regarding statistical analysis. This review explores and critically appraises the international nursing literature concerning the pedagogy of teaching undergraduate statistics to nursing students. The following dominant three themes: (1) student and faculty characteristics, (2) conceptual framework and (3) the course characteristics of content and delivery guided our review. It was found that there is limited to no evidence concerning the pedagogy of statistics; further research is needed to establish best practices based on evidence.
Neuronal Receptor Activity–Modifying Protein 1 Promotes Energy Expenditure in Mice
Authors: Zhang Zhongming , Liu Xuebo , Morgan Donald A. , Kuburas Adisa , Thedens Daniel R. , Russo Andrew F. , Rahmouni Kamal
Published: February 2011

OBJECTIVE

Receptor activity–modifying proteins (RAMPs) 1, 2, and 3 are unusual accessory proteins that dictate the binding specificity of two G protein–coupled receptors involved in energy homeostasis: calcitonin gene–related peptide (CGRP) and amylin receptors. These proteins are expressed throughout the central nervous system (CNS), including in the brain regions involved in the regulation of energy homeostasis, but the significance of CNS RAMPs in the control of energy balance remains unknown.

RESEARCH DESIGN AND METHODS

To examine the functional significance of modulating neuronal RAMP1, we assessed the effect of overexpressing human RAMP1 (hRAMP1) in the CNS on body energy balance.

RESULTS

Nestin/hRAMP1 transgenic mice have a remarkably decreased body weight associated with reduced fat mass and circulating leptin levels. The transgenic mice exhibited higher energy expenditure as indicated by increased oxygen consumption, body temperature, and sympathetic tone subserving brown adipose tissue (BAT). Consistent with this, the nestin/hRAMP1 transgenic mice had elevated BAT mRNA levels of peroxisome proliferator–activated receptor γ coactivator 1α and uncoupling protein 1 and 3, and these changes can be reversed by chronic blockade of sympathetic nervous system signaling. Furthermore, metabolic response to amylin was enhanced in the nestin/hRAMP1 mice whereas the response to CGRP was blunted, possibly the result of higher expression of CGRP in the CNS.

CONCLUSIONS

These data demonstrate that CNS RAMP1 plays a pivotal role in the regulation of energy homeostasis by promoting energy expenditure.
Focal Adhesion Remodeling Is Crucial for Glucose-Stimulated Insulin Secretion and Involves Activation of Focal Adhesion Kinase and Paxillin
Authors: Rondas Dieter , Tomas Alejandra , Halban Philippe A.
Published: February 2011

OBJECTIVE

Actin cytoskeleton remodeling is known to be involved in glucose-stimulated insulin secretion (GSIS). We have observed glucose-stimulated changes at the β-cell basal membrane similar to focal adhesion remodeling in cell migration. This led us to study the role of two key focal adhesion proteins, focal adhesion kinase (FAK) and paxillin, in GSIS.

RESEARCH DESIGN AND METHODS

All studies were performed using rat primary β-cells or isolated islets. Protein phosphorylation and subcellular localization were determined by Western blotting and confocal immunofluorescence, respectively. Insulin was measured by radioimmunoassay. Both siRNA and pharmacological approaches were used to assess the role of FAK and paxillin in glucose-stimulated focal adhesion remodeling and insulin secretion.

RESULTS

Glucose stimulation of β-cells in monolayer significantly increased phosphorylation of FAK and paxillin as well as cell surface area. This coincided with the appearance at the basal membrane of numerous shorter actin filopodial extensions, containing not only phosphorylated paxillin, FAK, and extracellular signal–related kinase 1/2 but also two SNARE proteins, synaptosomal-associated protein 25 and syntaxin 1, indicating involvement in exocytosis. SR7037 completely inhibited this sequence of events, indicating the requirement of increased cytosolic Ca2+. Furthermore, knockdown of paxillin significantly decreased GSIS, as did inhibition of glucose-induced FAK phosphorylation by compound Y15. Key findings were confirmed in β-cells within the natural setting of islets.

CONCLUSIONS

Glucose-stimulated remodeling of focal adhesions and phosphorylation of FAK and paxillin are involved in full development of GSIS, indicating a previously unknown role for focal adhesion remodeling in pancreatic β-cell function.
Endoplasmic Reticulum Stress Promotes LIPIN2-Dependent Hepatic Insulin Resistance
Authors: Ryu Dongryeol , Seo Woo-Young , Yoon Young-Sil , Kim Yo-Na , Kim Su Sung , Kim Hye-Jin , Park Tae-Sik , Choi Cheol Soo , Koo Seung-Hoi
Published: February 2011

OBJECTIVE

Diet-induced obesity (DIO) is linked to peripheral insulin resistance—a major predicament in type 2 diabetes. This study aims to identify the molecular mechanism by which DIO-triggered endoplasmic reticulum (ER) stress promotes hepatic insulin resistance in mouse models.

RESEARCH DESIGN AND METHODS

C57BL/6 mice and primary hepatocytes were used to evaluate the role of LIPIN2 in ER stress-induced hepatic insulin resistance. Tunicamycin, thapsigargin, and lipopolysaccharide were used to invoke acute ER stress conditions. To promote chronic ER stress, mice were fed with a high-fat diet for 8–12 weeks. To verify the role of LIPIN2 in hepatic insulin signaling, adenoviruses expressing wild-type or mutant LIPIN2, and shRNA for LIPIN2 were used in animal studies. Plasma glucose, insulin levels as well as hepatic free fatty acids, diacylglycerol (DAG), and triacylglycerol were assessed. Additionally, glucose tolerance, insulin tolerance, and pyruvate tolerance tests were performed to evaluate the metabolic phenotype of these mice.

RESULTS

LIPIN2 expression was enhanced in mouse livers by acute ER stress–inducers or by high-fat feeding. Transcriptional activation of LIPIN2 by ER stress is mediated by activating transcription factor 4, as demonstrated by LIPIN2 promoter assays, Western blot analyses, and chromatin immunoprecipitation assays. Knockdown of hepatic LIPIN2 in DIO mice reduced fasting hyperglycemia and improved hepatic insulin signaling. Conversely, overexpression of LIPIN2 impaired hepatic insulin signaling in a phosphatidic acid phosphatase activity–dependent manner.

CONCLUSIONS

These results demonstrate that ER stress–induced LIPIN2 would contribute to the perturbation of hepatic insulin signaling via a DAG-protein kinase C ε–dependent manner in DIO mice.
Association Between Passive and Active Smoking and Incident Type 2 Diabetes in Women
Authors: Zhang Luxia , Curhan Gary C. , Hu Frank B. , Rimm Eric B. , Forman John P.
Published: February 2011

OBJECTIVE

Accumulating evidence has identified a positive association between active smoking and the risk of diabetes, but previous studies had limited information on passive smoking or changes in smoking behaviors over time. This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women.

RESEARCH DESIGN AND METHODS

This is a prospective cohort study of 100,526 women in the Nurses’ Health Study who did not have prevalent diabetes in 1982, with follow-up for diabetes for 24 years.

RESULTS

We identified 5,392 incident cases of type 2 diabetes during 24 years of follow-up. Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94–1.23]) or regularly (1.16 [1.00–1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12–50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20–29 years later (1.15 [1.00–1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17–1.64) for 1–14 cigarettes per day to 1.98 (1.57–2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke.

CONCLUSIONS

Our study suggests that exposure to passive smoke and active smoking are positively and independently associated with the risk of type 2 diabetes.
A Learning Algorithm based on Primary School Teaching Wisdom
Authors: Philip Ninan Sajeeth
Published: February 2011

A learning algorithm based on primary school teaching and learning is presented. The methodology is to continuously evaluate the performance of the network and to train it on the examples for which they repeatedly fail, until all the examples are correctly classified. Empirical analysis on UCI data show that the algorithm produces good training data and improves the generalization ability of the network on unseen data. The algorithm has interesting applications in data mining, model evaluations and rare objects discovery.
A simulated neuro-robotic environment for bi-directional closed-loop experiments
Authors: Mulas Marcello , Massobrio Paolo , Martinoia Sergio , Chiappalone Michela
Published: February 2011

We have developed a new simulation environment, called N
Motion Planning of a Snake-Like Robot Using an Optimized Harmonic Potential Field
Authors: Charifa Samer , Bikdash Marwan
Published: February 2011

Snake-like robots have gained popularity in the last three decades for their ability to utilize several gaits in order to navigate through different terrains. They are analogous in morphology to snakes, tentacles, and elephant trunks. We propose a novel method of navigating a snake-like robot based on the Harmonic Field with Optimized Boundary Conditions (HFOBC) and a boundary following algorithm. We apply the HFOBC navigation function using a number of fictitious charges equally spaced on each link. These charges actively follow the potential field towards the target. Futhermore, a generalized mathematical model for an n-link snake-like robot based on Lagrange formulation has also been proposed in this paper.
A Cautionary Historiography of John Smith's New England
Authors: Edney Matthew H.
Published: February 2011

This essay reviews 150 years of commentary on John Smith's famous map of New England. This commentary encompasses several disciplines, as well as both academic and popular writing, but has been structurally consistent: each account of the map is brief and repeats a received wisdom that largely contradicts the small body of empirical evidence. The structure of the received wisdom is analysed to reveal the powerful web of beliefs and convictions that constitute the modern cartographic ideal. These beliefs feature some 11 myths of observation, evaluation, representation, individuality, progress, ontology, publicity, currency, morality, functionality (or instrumentality), and efficacy. Concerned only to evaluate the map image, historians have selectively interpreted the evidence to present Smith's map as an icon of discovery, exploration, cartography, intellectual dominance, and European civilization. The essay therefore constitutes a cautionary tale of the pitfalls that await the unwary and uncritical map scholar.
Planning, implementing, and monitoring multiple‐species habitat conservation plans
Authors: Franklin Janet , Regan Helen M. , Hierl Lauren A. , Deutschman Douglas H. , Johnson Brenda S. , Winchell Clark S.
Published: February 2011

•Premise of the study: Despite numerous recommendations for various aspects of the design and monitoring of habitat conservation plans, there remains a need to synthesize existing guidelines into a comprehensive scheme and apply it to real‐world conservation programs.

•Methods: We review tools for systematic conservation planning and elements for designing and implementing ecological monitoring in an adaptive management context. We apply principles of monitoring design to the San Diego Multiple Species Conservation Program (MSCP) in California, USA—one of the first multispecies habitat conservation plans, located in a landscape where high biodiversity and urban development converge.

•Key results: Tools for spatial conservation planning are aimed to conserve biodiversity, often in the context of a limited budget. In practice, these methods may not accommodate legislative mandates, budgetary uncertainties, and the range of implementation mechanisms available across consortia of stakeholders. Once a reserve is implemented, the question becomes whether it is effective at conserving biodiversity, and if not, what actions are required to make it effective. In monitoring plan development, status and threats should be used to prioritize species and communities that require management action to ensure their persistence. Conceptual models documenting the state of knowledge of the system should highlight the main drivers affecting status and trends of species or communities. Monitoring strategies require scientifically justified decisions based on sampling, response, and data design.

•Conclusions: Because the framework illustrated here tackles multiple species, communities, and threats at the urban–wildland interface, it will have utility for ecosystem managers struggling to design monitoring programs.
Bryophyte diversity and evolution: Windows into the early evolution of land plants
Authors: Shaw A. Jonathan , Szövényi Péter , Shaw Blanka
Published: February 2011

The “bryophytes” comprise three phyla of plants united by a similar haploid‐dominant life cycle and unbranched sporophytes bearing one sporangium: the liverworts (Marchantiophyta), mosses (Bryophyta), and hornworts (Anthocerophyta). Combined, these groups include some 20000 species. As descendents of embryophytes that diverged before tracheophytes appeared, bryophytes offer unique windows into the early evolution of land plants. We review insights into the evolution of plant life cycles, in particular the elaboration of the sporophyte generation, the major lineages within bryophyte phyla, and reproductive processes that shape patterns of bryophyte evolution. Recent transcriptomic work suggests extensive overlap in gene expression in bryophyte sporophytes vs. gametophytes, but also novel patterns in the sporophyte, supporting Bower's antithetic hypothesis for origin of alternation of generations. Major lineages of liverworts, mosses, and hornworts have been resolved and general patterns of morphological evolution can now be inferred. The life cycles of bryophytes, arguably more similar to those of early embryophytes than are those in any other living plant group, provide unique insights into gametophyte mating patterns, sexual conflicts, and the efficacy and effects of spore dispersal during early land plant evolution.
A new approach to improve the scoring of mononucleotide microsatellite loci
Authors: Flores‐Rentería Lluvia , Whipple Amy V.
Published: February 2011

• Premise of the study: Mononucleotide microsatellites markers are useful for detecting genetic variation among individuals; however, scoring can be error‐prone. We developed a new approach to improve the accuracy of allele scoring.

• Methods and Results: A set of 14 mononucleotide microsatellite primers of the chloroplast were developed based on published Pinus spp. chloroplast genomes. Due to substantial scoring error for mononucleotide repeats ≥ 10 bp, we included part of the microsatellite in the reverse primer to reduce slippage and improve the scoring of these polymorphic markers. For markers 10–20 bp, the error rate in scoring with this method has a binomial 95% confidence interval of 0.7–2.1%.

• Conclusions: These new primers provide variable chloroplast markers in species of subsection Cembroides and other Pinus spp. with more accurate assignment of the alleles. This approach can be used to improve the allele scoring of mononucleotide or dinucleotide repeats from nuclear and chloroplast genomes.
Microsatellite marker development for the federally listed Prunus geniculata (Rosaceae)1
Authors: Germain‐Aubrey Charlotte C. , Soltis Pamela S. , Soltis Douglas E. , Gitzendanner Matthew A.
Published: February 2011

• Premise of the study: Prunus geniculata is a federally listed species endemic to the central Florida scrub. To investigate levels and geographic partitioning of genetic variation in this species, we developed microsatellite markers for P. geniculata and its sister species, P. maritima.

• Methods and Results: Following a protocol optimized in our laboratory, we designed 36 primer pairs, of which 8 amplified across both species and showed informative polymorphism. Product size varied from 163 to 370 bp, and the number of alleles ranged from 5 to 27. He across all populations ranged from 0.604 to 0.9155.

• Conclusions: Eight loci were useful at the population level and will be used for conservation genetic and phylogeographic studies of Prunus geniculata and P. maritima. Furthermore, from five to all eight of these loci can also be amplified in several other North American Prunus species.
Monsanto’s Claims au Royaume-Uni et aux États-Unis : les communiqués de presse de Monsanto, entre unité générique et hétérogénéité culturelle
Authors: Domenec Fanny
Published: February 2011

Cette étude vise à caractériser la communication de crise de l’entreprise Monsanto à travers l’analyse structurelle et rhétorique de deux corpus de communiqués de presse publiés en contexte britannique et américain entre 1999 et 2010. L’analyse structurelle met en lumière un genre à la fois codifié et dynamique : si les communiqués de presse américains respectent les sections prototypiques du genre, le corpus de communiqués de presse publiés en Grande-Bretagne présente des structures diverses qui empruntent à des positionnements discursifs particuliers, sans lien direct avec le monde de l’entreprise. Malgré cette hétérogénéité structurelle, il ressort de l’analyse rhétorique qu’une même stratégie argumentative est mise en œuvre dans les deux corpus : elle vise à minimiser l’importance de la crise en attirant l’attention du lecteur sur le caractère indispensable des biotechnologies agricoles. Cette réflexion sur le degré de plasticité du communiqué de presse publié par une entreprise permet de mettre en lumière l’articulation entre conventions génériques et variabilité des positionnements discursifs dans les communiqués de presse de crise de Monsanto.
Evaluation of a blended language learning environment in a French university and its effects on second language acquisition
Authors: Narcy-Combes Marie-Françoise , McAllister Julie
Published: February 2011

Cet article propose la description et l’analyse d’un projet de recherche en cours au niveau licence en LEA (commerce international) à l’Université de Nantes et concerne 660 étudiants. Nous nous proposons dans cet article d’analyser l’impact de ce dispositif sur la conception et l’organisation des apprentissages et sur la motivation et l’implication des étudiants. Les données recueillies pour l’évaluation par questionnaires, entretiens, pré-tests et post-tests, mesure du taux d’abandon, portent sur la satisfaction des utilisateurs, le niveau en langue, l’efficacité et la fiabilité du dispositif. Elles sont présentées et commentées. Le travail d’évaluation du dispositif montre un développement positif du niveau linguistique pour 35 % des étudiants qui se sont impliqués dans ce projet d’apprentissage hybride. À ce stade cependant il est nécessaire de poursuivre le travail de recherche pour déterminer les causes de cette progression, ce qui est prévu.
The Phosphatase Src Homology Region 2 Domain-Containing Phosphatase-1 Is an Intrinsic Central Regulator of Dendritic Cell Function
Authors: Ramachandran Indu R. , Song Weitao , Lapteva Natalia , Seethammagari Mamatha , Slawin Kevin M. , Spencer David M. , Levitt Jonathan M.
Published: February 2011

Dendritic cells (DCs) initiate proinflammatory or regulatory T cell responses, depending on their activation state. Despite extensive knowledge of DC-activating signals, the understanding of DC inhibitory signals is relatively limited. We show that Src homology region 2 domain-containing phosphatase-1 (SHP-1) is an important inhibitor of DC signaling, targeting multiple activation pathways. Downstream of TLR4, SHP-1 showed increased interaction with several proteins including IL-1R–associated kinase-4, and modulated LPS signaling by inhibiting NF-κB, AP-1, ERK, and JNK activity, while enhancing p38 activity. In addition, SHP-1 inhibited prosurvival signaling through AKT activation. Furthermore, SHP-1 inhibited CCR7 protein expression. Inhibiting SHP-1 in DCs enhanced proinflammatory cytokines, IL-6, IL-12, and IL-1β production, promoted survival, and increased DC migration to draining lymph nodes. Administration of SHP-1–inhibited DCs in vivo induced expansion of Ag-specific cytotoxic T cells and inhibited Foxp3+ regulatory T cell induction, resulting in an enhanced immune response against pre-established mouse melanoma and prostate tumors. Taken together, these data demonstrate that SHP-1 is an intrinsic global regulator of DC function, controlling many facets of T cell-mediated immune responses.
Rapid Recruitment and Activation of Macrophages by Anti-Gal/α-Gal Liposome Interaction Accelerates Wound Healing
Authors: Wigglesworth Kim M. , Racki Waldemar J. , Mishra Rabinarayan , Szomolanyi-Tsuda Eva , Greiner Dale L. , Galili Uri
Published: February 2011

Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95–100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.
The Danger Signal, Extracellular ATP, Is a Sensor for an Airborne Allergen and Triggers IL-33 Release and Innate Th2-Type Responses
Authors: Kouzaki Hideaki , Iijima Koji , Kobayashi Takao , O’Grady Scott M. , Kita Hirohito
Published: February 2011

The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca2+ concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y2 receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma.
Low-Dose Endotoxin Induces Inflammation by Selectively Removing Nuclear Receptors and Activating CCAAT/Enhancer-Binding Protein δ
Authors: Maitra Urmila , Gan Lu , Chang Samantha , Li Liwu
Published: February 2011

Subclinical levels of circulating endotoxin are associated with the pathogenesis of diverse human inflammatory diseases, by mildly inducing the expression of proinflammatory mediators. In this study, we examined the molecular mechanism responsible for the effect of low-dose LPS in macrophages. In contrast to high-dose LPS, which activates NF-κB and induces the robust expression of proinflammatory mediators, we observed that low-dose LPS failed to activate NF-κB. Instead, it selectively activated C/EBPδ and removed nuclear repressors, including peroxisome proliferator-activated receptor α and retinoic acid receptor α, enabling a mild and leaky expression of proinflammatory mediators. The effect of low-dose LPS required IRAK-1, which interacts with and acts upstream of IκB kinase ε to contribute to LPS-mediated induction of C/EBPδ and proinflammatory mediators. Additionally, mice fed a high-fat diet acquired elevated levels of endotoxin and proinflammatory mediators in an IRAK-1–dependent fashion. Taken together, these data reveal a distinct pathway preferentially used by low-dose endotoxin in initiating low-grade inflammation.
Regulation of GATA-3 Expression during CD4 Lineage Differentiation
Authors: Gimferrer Idoia , Hu Taishan , Simmons Amie , Wang Chi , Souabni Abdallah , Busslinger Meinrad , Bender Timothy P. , Hernandez-Hoyos Gabriela , Alberola-Ila José
Published: February 2011

GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.
β1 Integrin Is Critical for the Maintenance of Antigen-Specific CD4 T Cells in the Bone Marrow but Not Long-Term Immunological Memory
Authors: DeNucci Christopher C. , Shimizu Yoji
Published: February 2011

The long-term maintenance of memory CD4 T cells promotes protective immunity against future pathogen reinfection. As a site rich in survival cytokines, the bone marrow is proposed to be a critical niche for the survival of memory CD4 T cells. We demonstrate that endogenous, polyclonal Ag-specific CD4 T cells rapidly enter and are recovered long-term from the bone marrow following i.v. infection with Listeria monocytogenes. β1 integrin-deficient CD4 T cells also populate the bone marrow early following an infection, but their numbers in this site rapidly decline. This decline was not caused by increased death of T cells lacking β1 integrin but rather by reduced retention in the bone marrow after the primary immune response. The loss of memory CD4 T cells from the bone marrow does not lead to a loss of the predominant source of memory CD4 T cells in the spleen or the ability to mount a memory response. Thus, β1 integrin-dependent maintenance of memory CD4 T cells in the bone marrow is not required for long-term CD4 T cell memory.
Testing the Role of P2X7 Receptors in the Development of Type 1 Diabetes in Nonobese Diabetic Mice
Authors: Chen Yi-Guang , Scheuplein Felix , Driver John P. , Hewes Amanda A. , Reifsnyder Peter C. , Leiter Edward H. , Serreze David V.
Published: February 2011

Although P2rx7 has been proposed as a type 1 diabetes (T1D) susceptibility gene in NOD mice, its potential pathogenic role has not been directly determined. To test this possibility, we generated a new NOD stock deficient in P2X7 receptors. T1D development was not altered by P2X7 ablation. Previous studies found CD38 knockout (KO) NOD mice developed accelerated T1D partly because of a loss of CD4+ invariant NKT (iNKT) cells and Foxp3+ regulatory T cells (Tregs). These immunoregulatory T cell populations are highly sensitive to NAD-induced cell death activated by ADP ribosyltransferase-2 (ART2)-mediated ADP ribosylation of P2X7 receptors. Therefore, we asked whether T1D acceleration was suppressed in a double-KO NOD stock lacking both P2X7 and CD38 by rescuing CD4+ iNKT cells and Tregs from NAD-induced cell death. We demonstrated that P2X7 was required for T1D acceleration induced by CD38 deficiency. The CD38 KO-induced defects in homeostasis of CD4+ iNKT cells and Tregs were corrected by coablation of P2X7. T1D acceleration in CD38-deficient NOD mice also requires ART2 expression. If increased ADP ribosylation of P2X7 in CD38-deficient NOD mice underlies disease acceleration, then a comparable T1D incidence should be induced by coablation of both CD38 and ART2, or CD38 and P2X7. However, a previously established NOD stock deficient in both CD38 and ART2 expression is T1D resistant. This study demonstrated the presence of a T1D resistance gene closely linked to the ablated Cd38 allele in the previously reported NOD stock also lacking ART2, but not in the newly generated CD38/P2X7 double-KO line.
Defining the Herpes Simplex Virus-Specific CD8+ T Cell Repertoire in C57BL/6 Mice
Authors: St. Leger Anthony J. , Peters Bjoern , Sidney John , Sette Alessandro , Hendricks Robert L.
Published: February 2011

HSV type 1 (HSV-1) expresses its genes sequentially as immediate early (α), early (β), leaky late (γ1), and true late (γ2), where viral DNA synthesis is an absolute prerequisite only for γ2 gene expression. The γ1 protein glycoprotein B (gB) contains a strongly immunodominant CD8+ T cell epitope (gB498–505) that is recognized by 50% of both the CD8+ effector T cells in acutely infected trigeminal ganglia (TG) and the CD8+ memory T cells in latently infected TG. Of 376 predicted HSV-1 CD8+ T cell epitopes in C57BL/6 mice, 19 (gB498–505 and 18 subdominant epitopes) stimulated CD8+ T cells in the spleens and TG of HSV-1 acutely infected mice. These 19 epitopes identified virtually all CD8+ T cells in the infected TG that represent all or the vast majority of the HSV-specific CD8+ TCR repertoire. Only 11 of ∼84 HSV-1 proteins are recognized by CD8+ T cells, and most (∼80%) are expressed before viral DNA synthesis. Neither the immunodominance of gB498–505 nor the dominance hierarchy of the subdominant epitopes is due solely to MHC or TCR affinity. We conclude that the vast majority of CD8+ T cells in HSV-1 acutely infected TG are HSV specific, that HSV-1 β and γ1 proteins that are expressed before viral DNA synthesis are favored targets of CD8+ T cells, and that dominance within the TCR repertoire is likely due to the frequency or expansion and survival characteristics of CD8+ T cell precursors.
Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State
Authors: de Lalla Claudia , Rinaldi Anna , Montagna Daniela , Azzimonti Laura , Bernardo Maria Ester , Sangalli Laura M. , Paganoni Anna Maria , Maccario Rita , Di Cesare-Merlone Alessandra , Zecca Marco , Locatelli Franco , Dellabona Paolo , Casorati Giulia
Published: February 2011

Immune reconstitution plays a crucial role on the outcome of patients given T cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (hHSCT) for hematological malignancies. CD1d-restricted invariant NKT (iNKT) cells are innate-like, lipid-reactive T lymphocytes controlling infections, cancer, and autoimmunity. Adult mature iNKT cells are divided in two functionally distinct CD4+ and CD4− subsets that express the NK receptor CD161 and derive from thymic CD4+CD161− precursors. We investigated iNKT cell reconstitution dynamics in 33 pediatric patients given hHSCT for hematological malignancies, with a follow-up reaching 6 y posttransplantation, and correlated their emergence with disease relapse. iNKT cells fully reconstitute and rapidly convert into IFN-γ–expressing effectors in the 25 patients maintaining remission. CD4+ cells emerge earlier than the CD4− ones, both displaying CD161− immature phenotypes. CD4− cells expand more slowly than CD4+ cells, though they mature with significantly faster kinetics, reaching full maturation by 18 mo post-hHSCT. Between 4 and 6 y post-hHSCT, mature CD4− iNKT cells undergo a substantial expansion burst, resulting in a CD4+<CD4− NKT cell ratio similar to that found in healthy adults. In contrast with patients maintaining remission, iNKT cells failed to reconstitute in all eight patients experiencing disease relapse. These findings define the peripheral dynamics of human iNKT cells and suggest a contribution of these cells to maintain remission, possibly via early IFN-γ provision. Adoptive transfer of donor-derived iNKT cells into HLA-haploidentical patients failing to reconstitute these cells might represent a novel therapeutic option to prevent leukemia recurrence.