bluuebunny/crossref_metadata_2025 huggingface dataset:
Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease
Authors: Zheng Hong , Matte-Martone Catherine , Li Hongmei , Anderson Britt E. , Venketesan Srividhya , Sheng Tan Hung , Jain Dhanpat , McNiff Jennifer , Shlomchik Warren D.
Published: November 2007

Much of the efficacy of allogeneic hematopoietic stem cell transplantation (alloSCT) in curing hematologic malignancies is due to a graft-versus-leukemia (GVL) effect mediated by donor T cells that recognize recipient alloantigens on leukemic cells. Donor T cells are also important for reconstituting immunity in the recipient. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-versus-host disease (GVHD). We previously reported that donor CD4+ effector memory T cells (TEMs) do not cause GVHD but transfer functional T-cell memory. In the present work, we demonstrate in an MHC-mismatched model that CD4+ TEMs (unprimed to recipient antigens) mediate GVL against clinically relevant mouse models of chronic phase and blast crisis chronic myelogenous leukemia, without causing GVHD. By creating gene-deficient leukemias and using perforin-deficient T cells, we demonstrate that direct cytolytic function is essential for TEM-mediated GVL, but that GVL is retained when killing via FasL, TNF-α, TRAIL, and perforin is individually impaired. However, TEM-mediated GVL was diminished when both FasL and perforin pathways were blocked. Taken together, our studies identify TEMs as a clinically applicable cell therapy for promoting GVL and immune reconstitution, particularly in MHC-mismatched haploidentical alloSCTs in which T cell–depleted allografts are commonly used to minimize GVHD.
Cadherin-mediated adhesion regulates posterior body formation
Authors: Harrington Michael J , Hong Elim , Fasanmi Oluwafoyinsa , Brewster Rachel
Published: November 2007

Background

The anterior-posterior axis of the vertebrate embryo undergoes a dramatic elongation during early development. Convergence and extension of the mesoderm, occurring during gastrulation, initiates the narrowing and lengthening of the embryo. However the lengthening of the axis continues during post-gastrula stages in the tailbud region, and is thought to involve convergent extension movements as well as other cell behaviors specific to posterior regions.

Results

We demonstrate here, using a semi-dominant N-cadherin allele, that members of the classical cadherin subfamily of cell-cell adhesion molecules are required for tailbud elongation in the zebrafish. In vivo imaging of cell behaviors suggests that the extension of posterior axial mesodermal cells is impaired in embryos that carry the semi-dominant N-cadherin allele. This defect most likely results from a general loss of cell-cell adhesion in the tailbud region. Consistent with these observations, N-cadherin is expressed throughout the tailbud during post-gastrulation stages. In addition, we show that N-cadherin interacts synergistically with vang-like 2, a member of the non-canonical Wnt signaling/planar cell polarity pathway, to mediate tail morphogenesis.

Conclusion

We provide the first evidence here that N-cadherin and other members of the classical cadherin subfamily function in parallel with the planar cell polarity pathway to shape the posterior axis during post-gastrulation stages. These findings further highlight the central role that adhesion molecules play in the cellular rearrangements that drive morphogenesis in vertebrates and identify classical cadherins as major contributors to tail development.
Assessing the evolutionary rate of positional orthologous genes in prokaryotes using synteny data
Authors: Lemoine Frédéric , Lespinet Olivier , Labedan Bernard
Published: November 2007

Background

Comparison of completely sequenced microbial genomes has revealed how fluid these genomes are. Detecting synteny blocks requires reliable methods to determining the orthologs among the whole set of homologs detected by exhaustive comparisons between each pair of completely sequenced genomes. This is a complex and difficult problem in the field of comparative genomics but will help to better understand the way prokaryotic genomes are evolving.

Results

We have developed a suite of programs that automate three essential steps to study conservation of gene order, and validated them with a set of 107 bacteria and archaea that cover the majority of the prokaryotic taxonomic space. We identified the whole set of shared homologs between two or more species and computed the evolutionary distance separating each pair of homologs. We applied two strategies to extract from the set of homologs a collection of valid orthologs shared by at least two genomes. The first computes the Reciprocal Smallest Distance (RSD) using the PAM distances separating pairs of homologs. The second method groups homologs in families and reconstructs each family's evolutionary tree, distinguishingbona fideorthologs as well as paralogs created after the last speciation event. Although the phylogenetic tree method often succeeds where RSD fails, the reverse could occasionally be true. Accordingly, we used the data obtained with either methods or their intersection to number the orthologs that are adjacent in for each pair of genomes, the Positional Orthologous Genes (POGs), and to further study their properties. Once all these synteny blocks have been detected, we showed that POGs are subject to more evolutionary constraints than orthologs outside synteny groups, whichever the taxonomic distance separating the compared organisms.

Conclusion

The suite of programs described in this paper allows a reliable detection of orthologs and is useful for evaluating gene order conservation in prokaryotes whichever their taxonomic distance. Thus, our approach will make easy the rapid identification of POGS in the next few years as we are expecting to be inundated with thousands of completely sequenced microbial genomes.
Treatment outcome of new pulmonary tuberculosis in Guangzhou, China 1993–2002: a register-based cohort study
Authors: Bao Qing-Song , Du Yu-Hua , Lu Ci-Yong
Published: November 2007

Background

Completion of treatment for tuberculosis (TB) is of utmost priority for TB control programs. The aims of this study were to evaluate the treatment outcome of TB cases registered in Guangzhou during the period 1993–2002, and to identify factors associated with treatment success.

Methods

Two (of eight) districts in Guangzhou were selected randomly as objects of study and their surveillance database was analyzed to assess the treatment outcome and identify factors associated with treatment success for TB cases registered in Guangzhou. Six treatment outcome criteria were assessed based on guidelines set by the World Health Organization (WHO). Logistic regression was used to estimate risk factors for treatment outcome.

Results

A total of 6743 pulmonary tuberculosis cases (4903 males, 1840 females) were included in this study. The treatment success rate (including cured and complete treatment) was 88% (95%CI 87%–89%). One hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted treatment. In multivariate analysis, treatment success was found to be associated with young age, lack of cavitation and compliance with treatment.

Conclusion

The total treatment success rate in the current study was similar to the WHO target for all smear positive cases, while the failure rate and the default rate in 2002 were slightly higher. Good care of elderly patients, early diagnosis of cavitation and compliance with treatment could improve the success rate of TB treatment.
Selecting process quality indicators for the integrated care of vulnerable older adults affected by cognitive impairment or dementia
Authors: Kröger Edeltraut , Tourigny André , Morin Diane , Côté Lise , Kergoat Marie-Jeanne , Lebel Paule , Robichaud Line , Imbeault Shirley , Proulx Solange , Benounissa Zohra
Published: November 2007

Background

This study aimed at evaluating face and content validity, feasibility and reliability of process quality indicators developed previously in the United States or other countries. The indicators can be used to evaluate care and services for vulnerable older adults affected by cognitive impairment or dementia within an integrated service system in Quebec, Canada.

Methods

A total of 33 clinical experts from three major urban centres in Quebec formed a panel representing two medical specialties (family medicine, geriatrics) and seven health or social services specialties (nursing, occupational therapy, psychology, neuropsychology, pharmacy, nutrition, social work), from primary or secondary levels of care, including long-term care. A modified version of the RAND®/University of California at Los Angeles (UCLA) appropriateness method, a two-round Delphi panel, was used to assess face and content validity of process quality indicators. The appropriateness of indicators was evaluated according to a) agreement of the panel with three criteria, defined as a median rating of 7–9 on a nine-point rating scale, and b) agreement among panellists, judged by the statistical measure of the interpercentile range adjusted for symmetry. Feasibility of quality assessment and reliability of appropriate indicators were then evaluated within a pilot study on 29 patients affected by cognitive impairment or dementia. For measurable indicators the inter-observer reliability was calculated with the Kappa statistic.

Results

Initially, 82 indicators for care of vulnerable older adults with cognitive impairment or dementia were submitted to the panellists. Of those, 72 (88%) were accepted after two rounds. Among 29 patients for whom medical files of the preceding two years were evaluated, 63 (88%) of these indicators were considered applicable at least once, for at least one patient. Only 22 indicators were considered applicable at least once for ten or more out of 29 patients. Four indicators could be measured with the help of a validated questionnaire on patient satisfaction. Inter-observer reliability was moderate (Kappa = 0.57).

Conclusion

A multidisciplinary panel of experts judged a large majority of the initial indicators valid for use in integrated care systems for vulnerable older adults in Quebec, Canada. Most of these indicators can be measured using patient files or patient or caregiver interviews and reliability of assessment from patient-files is moderate.
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage
Authors: Pelizon Ana Cláudia , Martins Douglas R , Zorzella Sofia FG , Trombone Ana Paula F , Lorenzi Júlio CC , Carvalho Robson F , Brandão Izaíra T , Coelho-Castelo Arlete AM , Silva Célio L , Sartori Alexandrina
Published: November 2007

Background

Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) fromMycobacterium leprae(pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated.

Methods

Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA.

Results

This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life.

Conclusion

These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.
Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses
Authors: Yassine Hadi M , Al-Natour Mohammad Q , Lee Chang-Won , Saif Yehia M
Published: November 2007

1. Abstract

The triple reassortant H3N2 viruses were isolated for the first time from pigs in 1998 and are known to be endemic in swine and turkey populations in the United States. In 2004, we isolated two H3N2 triple reassortant viruses from two turkey breeder flocks in Ohio and Illinois. Infected hens showed no clinical signs, but experienced a complete cessation of egg production. In this study, we evaluated three triple reassortant H3N2 isolates of turkey origin and one isolate of swine origin for their transmission between swine and turkeys. Although all 4 viruses tested share high genetic similarity in all 8 genes, only the Ohio strain (A/turkey/Ohio/313053/04) was shown to transmit efficiently both ways between swine and turkeys. One isolate, A/turkey/North Carolina/03, was able to transmit from pigs to turkeys but not vice versa. Neither of the other two viruses transmitted either way. Sequence analysis of the HA1 gene of the Ohio strain showed one amino acid change (D to A) at residue 190 of the receptor binding domain upon transmission from turkeys to pigs. The Ohio virus was then tested for intraspecies transmission in three different avian species. The virus was shown to replicate and transmit among turkeys, replicate but does not transmit among chickens, and did not replicate in ducks. Identifying viruses with varying inter- and intra-species transmission potential should be useful for further studies on the molecular basis of interspecies transmission.
Characteristics of Urologists Predict the Use of Androgen Deprivation Therapy for Prostate Cancer
Authors: Shahinian Vahakn B. , Kuo Yong-fang , Freeman Jean L. , Orihuela Eduardo , Goodwin James S.
Published: November 2007

Purpose

We previously have reported wide variations among urologists in the use of androgen deprivation for prostate cancer. Using the Surveillance, Epidemiology, and End Results–Medicare linked database, we examined how individual urologist characteristics influenced the use of androgen deprivation therapy.

Methods

Participants included 82,375 men with prostate cancer who were diagnosed from January 1, 1992, through December 31, 2002, and the 2,080 urologists who provided care to them. Multilevel analyses were used to estimate the likelihood of androgen deprivation use within 6 months of diagnosis in the overall cohort, in a subgroup in which use would be of uncertain benefit (primary therapy for localized prostate cancer), and in a subgroup in which use would be evidence-based (adjuvant therapy with radiation for locally advanced disease).

Results

In the overall cohort of patients, a multilevel model adjusted for patient characteristics, tumor characteristics, and urologist characteristics (eg, board certification, academic affiliation, patient panel size, years since medical school graduation) showed that the likelihood of androgen deprivation use was significantly greater for patients who saw urologists without an academic affiliation. This pattern also was noted when the analysis was limited to settings in which androgen deprivation would have been of uncertain benefit. Odds ratios for use in that context were 1.66 (95% CI, 1.27 to 2.16) for urologists with no academic affiliation and 1.45 (95% CI, 1.13 to 1.85) for urologists with minor versus major academic affiliations.

Conclusion

Use of androgen deprivation for prostate cancer varies by the characteristics of the urologist. Patients of non–academically affiliated urologists were significantly more likely to receive primary androgen deprivation therapy for localized prostate cancer, a setting in which the benefits are uncertain.
Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299
Authors: Hochster Howard S. , Luo Weixiu , Popa Elizabeta C. , Lyman Bruce T. , Mulcahy Mary , Beatty Peter A. , Benson Al Bowen
Published: November 2007

Purpose

To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer.

Patients and Methods

Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression.

Results

Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk.

Conclusion

The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.
Long-Term Toxicity Monitoring via Electronic Patient-Reported Outcomes in Patients Receiving Chemotherapy
Authors: Basch Ethan , Iasonos Alexia , Barz Allison , Culkin Ann , Kris Mark G. , Artz David , Fearn Paul , Speakman John , Farquhar Rena , Scher Howard I. , McCabe Mary , Schrag Deborah
Published: November 2007

Purpose

In cancer treatment trials, clinicians traditionally report patient toxicity symptoms. Alternatively, patients could provide this information directly.

Patients and Methods

The Common Terminology Criteria for Adverse Events (CTCAE) is the mandated instrument for tracking patient toxicity symptoms in National Cancer Institute (NCI)-sponsored cancer treatment trials. We adapted CTCAE symptom items into patient language and uploaded these to an online platform. Lung cancer outpatients receiving chemotherapy were invited to self-report selected symptoms at visits via waiting area computers or optional home access. Symptom reports were printed for nurses at visits, but no instructions were given with regard to use of this information.

Results

From June 2005 through March 2006, 125 patients were invited to participate, and 107 chose to enroll. Mean length of participation was 42 weeks (range, 1 to 71 weeks), by which time 35% died. The average number of clinic visits was 12 (range, 1 to 40 visits). At each consecutive visit, most patients (mean, 78%) logged in without significant attrition. Reasons for failure to log in included having no reminder and having inadequate time. Although 76% of enrollees had home computers, only 15% self-reported from home. Satisfaction with the system was high (90%), but only 51% felt communication was improved. All participating nurses understood the reports and felt this information was useful for clinical decisions, documentation, and discussions. However, only one of seven nurses discussed reports with patients frequently, with insufficient time being the most common barrier to discussions.

Conclusion

Online patient self-reporting is a feasible long-term strategy for toxicity symptom monitoring during chemotherapy, even among patients with advanced cancer and high symptom burdens. However, without explicit reminders and clinician feedback, patients demonstrated limited voluntary interest in self-reporting between visits.
Prospective Study of Long-Term Impact of Adjuvant High-Dose and Conventional-Dose Chemotherapy on Health-Related Quality of Life
Authors: Buijs Ciska , Rodenhuis Sjoerd , Seynaeve Caroline M. , van Hoesel Quirinus G.C.M. , van der Wall Elsken , Smit Wim J.M. , Nooij Marianne A. , Voest Emile , Hupperets Pierre , TenVergert Els M. , van Tinteren Harm , Willemse Pax H.B. , Mourits Marian J.E. , Aaronson Neil K. , Post Wendy J. , de Vries Elisabeth G.E.
Published: November 2007

Purpose

To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer.

Patients and Methods

Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were followed by radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist and assessed every 6 months for 5 years after random assignment. For the SF-36, data from healthy Dutch women with the same age distribution served as reference values.

Results

Eight hundred four patients (conventional-dose chemotherapy, n = 405; high-dose chemotherapy, n = 399) were included. Median follow-up time was 57 months. Directly after high-dose chemotherapy, HRQOL decreased more compared with conventional chemotherapy for all SF-36 subscales. After 1 year, the reference value of healthy women was reached in both groups. Small differences were observed between the two groups in the role-physical and role-emotional subscales, but 1 year after treatment, these differences were minor and not clinically relevant. During follow-up, patients with a lower educational level and many complaints before chemotherapy experienced a worse HRQOL.

Conclusion

Shortly after high-dose chemotherapy, HRQOL was more affected than after conventional-dose chemotherapy. One year after random assignment, differences were negligible. Identifying patients who have a higher chance of persistent impaired quality of life after treatment (which, in the present study, included patients with a lower educational level and many complaints before chemotherapy) is important and may open the way for better patient-tailored prevention strategies.
Quantitative Justification of the Change From 10% to 30% for Human Epidermal Growth Factor Receptor 2 Scoring in the American Society of Clinical Oncology/College of American Pathologists Guidelines: Tumor Heterogeneity in Breast Cancer and Its Implications for Tissue Microarray–Based Assessment of Outcome
Authors: Moeder Christopher B. , Giltnane Jennifer M. , Harigopal Malini , Molinaro Annette , Robinson Andrew , Gelmon Karen , Huntsman David , Camp Robert L. , Rimm David L.
Published: November 2007

Purpose

The variability in scoring of immunohistochemistry, whether a result of true heterogeneity or artifacts in preparation, has led to decreased reliability in companion diagnostics and the recommendation for new standards (eg, the American Society of Clinical Oncology/College of American Pathologists [ASCO-CAP] guidelines). The basis of this problem is the amount of tissue required to be representative of an entire tumor. Because protein expression on tissue microarrays (TMAs) can be rigorously measured and one 0.6-mm spot is equivalent to two to three high-power fields, we used TMAs to assess levels of heterogeneity and to determine optimal representation as a function of outcome.

Patients and Methods

We analyzed estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) expression in two cohorts (n = 676 and n = 152) on a series of four to five separate TMA cores and assessed heterogeneity by linear regression analysis. Minimum, average, and maximum scores were generated for each set, which were then assessed for prognostic and predictive value.

Results

Each marker shows some heterogeneity, but average r values between 0.7 and 0.8 are seen between TMA spots. Analysis for prognostic value shows that the highest maximum score (of five spots) is the most prognostic for ER, whereas a high HER-2 minimum score is most prognostic for poor outcome and most predictive of response to trastuzumab.

Conclusion

These results suggest that the representivity required for each biomarker may be a function of its role in tumorigenesis. Furthermore, these results provide scientific basis for the ASCO-CAP guidelines for assessment of HER-2 expression but perhaps suggest that the 30% figure is still too conservative.
Calcium fluxes in dorsal forerunner cells antagonize β-catenin and alter left-right patterning
Authors: Schneider Igor , Houston Douglas W. , Rebagliati Michael R. , Slusarski Diane C.
Published: November 2007

Establishment of the left-right axis is essential for normal organ morphogenesis and function. Ca2+ signaling and cilia function in the zebrafish Kuppfer's Vesicle (KV) have been implicated in laterality. Here we describe an endogenous Ca2+ release event in the region of the KV precursors (dorsal forerunner cells, DFCs), prior to KV and cilia formation. Manipulation of Ca2+ release to disrupt this early flux does not impact early DFC specification, but results in altered DFC migration or cohesion in the tailbud at somite stages. This leads to disruption of KV formation followed by bilateral expression of asymmetrical genes, and randomized organ laterality. We identify β-catenin inhibition as a Ca2+-signaling target and demonstrate that localized loss of Ca2+ within the DFC region or DFC-specific activation ofβ-catenin is sufficient to alter laterality in zebrafish. We identify a previously unknown DFC-like cell population in Xenopus and demonstrate a similar Ca2+-sensitive stage. As in zebrafish,manipulation of Ca2+ release results in ectopic nuclearβ-catenin and altered laterality. Overall, our data support a conserved early Ca2+ requirement in DFC-like cell function in zebrafish and Xenopus.
Chromatin assembly factor 1 regulates the cell cycle but not cell fate during male gametogenesis inArabidopsis thaliana
Authors: Chen Zhong , Tan Jeanie Li Hui , Ingouff Mathieu , Sundaresan Venkatesan , Berger Frederic
Published: November 2007

The interdependence of cell cycle control, chromatin remodeling and cell fate determination remains unclear in flowering plants. Pollen development provides an interesting model, as it comprises only two cell types produced by two sequential cell divisions. The first division separates the vegetative cell from the generative cell. The generative cell divides and produces the two sperm cells, transported to the female gametes by the pollen tube produced by the vegetative cell. We show in Arabidopsis thaliana that loss of activity of the Chromatin assembly factor 1 (CAF1) pathway causes delay and arrest of the cell cycle during pollen development. Prevention of the second pollen mitosis generates a fraction of CAF1-deficient pollen grains comprising a vegetative cell and a single sperm cell, which both express correctly cell fate markers. The single sperm is functional and fertilizes indiscriminately either female gamete. Our results thus suggest that pollen cell fate is independent from cell cycle regulation.
The E1 ubiquitin-activating enzyme Uba1 inDrosophilacontrols apoptosis autonomously and tissue growth non-autonomously
Authors: Lee Tom V. , Ding Tian , Chen Zhihong , Rajendran Vani , Scherr Heather , Lackey Melinda , Bolduc Clare , Bergmann Andreas
Published: November 2007

Ubiquitination is an essential process regulating turnover of proteins for basic cellular processes such as the cell cycle and cell death (apoptosis). Ubiquitination is initiated by ubiquitin-activating enzymes (E1), which activate and transfer ubiquitin to ubiquitin-conjugating enzymes (E2). Conjugation of target proteins with ubiquitin is then mediated by ubiquitin ligases (E3). Ubiquitination has been well characterized using mammalian cell lines and yeast genetics. However, the consequences of partial or complete loss of ubiquitin conjugation in a multi-cellular organism are not well understood. Here, we report the characterization of Uba1, the only E1 in Drosophila. We found that weak and strong Uba1 alleles behave genetically differently with sometimes opposing phenotypes. Whereas weak Uba1 alleles protect cells from cell death, clones of strong Uba1 alleles are highly apoptotic. Strong Uba1 alleles cause cell cycle arrest which correlates with failure to reduce cyclin levels. Surprisingly, clones of strong Uba1 mutants stimulate neighboring wild-type tissue to undergo cell division in a non-autonomous manner giving rise to overgrowth phenotypes of the mosaic fly. We demonstrate that the non-autonomous overgrowth is caused by failure to downregulate Notch signaling in Uba1 mutant clones. In summary, the phenotypic analysis of Uba1 demonstrates that impaired ubiquitin conjugation has significant consequences for the organism, and may implicate Uba1 as a tumor suppressor gene.
Sisyphus, theDrosophilamyosin XV homolog, traffics within filopodia transporting key sensory and adhesion cargos
Authors: Liu Raymond , Woolner Sarah , Johndrow James E. , Metzger David , Flores Adriana , Parkhurst Susan M.
Published: November 2007

Unconventional myosin proteins of the MyTH-FERM superclass are involved in intrafilopodial trafficking, are thought to be mediators of membrane-cytoskeleton interactions, and are linked to several forms of deafness in mammals. Here we show that the Drosophila myosin XV homolog, Sisyphus, is expressed at high levels in leading edge cells and their cellular protrusions during the morphogenetic process of dorsal closure. Sisyphus is required for the correct alignment of cells on opposing sides of the fusing epithelial sheets, as well as for adhesion of the cells during the final zippering/fusion phase. We have identified several putative Sisyphus cargos, including DE-cadherin (also known as Shotgun) and the microtubule-linked proteins Katanin-60, EB1, Milton and aPKC. These cargos bind to the Sisyphus FERM domain, and their binding is in some cases mutually exclusive. Our data suggest a mechanism for Sisyphus in which it maintains a balance between actin and microtubule cytoskeleton components, thereby contributing to cytoskeletal cross-talk necessary for regulating filopodial dynamics during dorsal closure.
A stem-loop structure in thewinglesstranscript defines a consensus motif for apical RNA transport
Authors: dos Santos Gilberto , Simmonds Andrew J. , Krause Henry M.
Published: November 2007

Although the subcellular localization of mRNA transcripts is a well-established mechanism for controlling protein localization, the basis for the recognition of mRNA localization elements is only now emerging. For example, although localization elements have been defined for many mRNAs that localize to apical cytoplasm in Drosophila embryos, no unifying properties have been identified within these elements. In this study, we identify and characterize an apical localization element in the 3′UTR of the Drosophila wingless mRNA. We show that this element, referred to as WLE3, is both necessary and sufficient for apical RNA transport. Full,unrestricted activity, however, requires the presence of one of several downstream potentiating elements. Comparison of WLE3 sequences within the Drosophila genus, and their predicted secondary structures, defines a highly conserved stem-loop structure. Despite these high levels of sequence and predicted structure conservation, however, mutagenesis shows significant leeway for both sequence and structure variation in the predicted stem-loop. Importantly, the features that emerge as crucial include an accessible distal helix sequence motif, which is also found in the predicted structures of other apical localization elements.
Catalonia, the right and the military
Authors: Casanova Julin
Published: November 2007

Commenting on the political controversy that has sprung up around the Catalan parliament's decision to seek approval from the Cortes on an amended and strengthened version of its autonomy Statute, in which Catalonia declares itself a nation, Julin Casanova reflects on historic reactions
to Catalan aspirations for autonomy and deplores the resurgence of anti-catalanism.
Foresight, Hindsight, and the Rhetoric of Self-Fashioning in Demosthenes' Philippic Cycle
Authors: Mader Gottfried
Published: November 2007

Abstract This paper analyses Demosthene' self-fashioning in the Philippic cycle as rhetorical process, focussing crucially on the role of foresight as constituent of symbouleutic authority and justification for his uncompromising political line. To legitimate his role as adviser, Demosthenes needed continually to proclaim his own competence. In the early days and before Philip was a major issue, Demosthenes constructs his foresight through “entechnic” arguments based on probability. Over time, self-referential passages that invoke his own prior interventions become notable sites of quasi-“atechnic” self-justification. These are further enhanced by a group of mutually reinforcing images that articulate the need for prudent foresight.
Engagement in Reading: Lessons Learned From Three PISA Countries
Authors: Brozo William G. , Shiel Gerry , Topping Keith
Published: November 2007

The Program for International Student Assessment (PISA) is a global effort to assess reading literacy. The authors of this article focus on the variable of engagement—the student characteristic on PISA that had the largest correlation with achievement in reading. Next, salient findings related to engagement from three English‐speaking PISA countries (the United States, the United Kingdom, and Ireland) are presented. The authors conclude with a discussion of lessons about reading engagement derived from findings common to the authors' three nations with implications for policy and practice.
Trust, Betrayal, and Authorship: Plagiarism and How We Perceive Students
Authors: Williams Bronwyn T.
Published: November 2007

Emotional responses to plagiarism are rarely addressed in professional literature that focuses on ethics and good teaching practices. Yet, the emotions that are unleashed by cases of plagiarism, or suspicions of plagiarism, influence how we perceive our students and how we approach teaching them. Such responses have been complicated by online plagiarism‐detection services that emphasize surveillance and detection. My opposition to such plagiarism software services grows from the conviction that if we use them we are not only poisoning classroom relationships, but also we are missing important opportunities for teaching.
Story Innovation: An Instructional Strategy for Developing Vocabulary and Fluency
Authors: Griffith Priscilla L. , Ruan Jiening
Published: November 2007

Story innovation is a form of scaffold writing in which the sentence and text patterns remain intact but the content is altered through the substitution of vocabulary to change the setting, characters, or action in a story. Story innovation is presented as a way to develop vocabulary knowledge through deep processing and to provide fluency practice. Teachers will also find story innovation useful for working with struggling readers or students learning English as a second language. It is a way to foster a nonthreatening, low‐anxiety, and highly supportive learning environment. The authors describe the scenario in one classroom in which the students wrote a story innovation, and they provide a step‐by‐step process teachers can follow when implementing story innovation in the classroom.
Putting Youth Violent Victimization Into Context: Sex, Race/Ethnicity, and Community Differences Among a Multisite Sample of Youths
Authors: Taylor Terrance J. , Esbensen Finn-Aage , Peterson Dana , Freng Adrienne
Published: November 2007

The increased risk of violent victimization for adolescents relative to other age groups has recently become a major public health concern. The current study uses data from a multisite study of eighth grade youths attending public schools in 11 cities to determine the extent and nature of youth general and serious violent victimization among both sexes and five racial/ethnic groups in 11 diverse communities. This study explores differences in sex, race/ethnicity, and community independently and explores interactions between sex and community and race/ethnicity and community. Our findings suggest important differences in victimization prevalence and individual victimization rates by sex and community of residence. Racial differences were found to be closely tied to community. Policy implications resulting from our findings are discussed.
Perpetrators and Targets of Bullying at Work: Role Stress and Individual Differences
Authors: Matthiesen Stig Berge , Einarsen Ståle
Published: November 2007

A workplace survey study (N = 2215, response rate 47%) revealed that about 16% of the sample may be categorized as either perpetrators (5.4%), provocative victims (2.1%), or as targets of bullying (8.3%). Targets of bullying, provocative victims, and bullies were compared with those 84% who do not report any involvement with respect to bullying at work, self-esteem, aggressive tendencies, prior experiences of bullying, or experiences of role stress. Perpetrators were found to have a higher level of aggression than did the comparison group and the targets. Provocative victims manifested a low level of self-esteem and social competency combined with a high level of aggressiveness. Targets of bullying revealed low levels of self-esteem and social competency. Targets, provocative victims, and perpetrators reported elevated levels of role stress in the form of unclear or conflicting demands and expectations around work tasks and daily work.
Quality Assurance Validation of Computerized Toxicology Data
Authors: Goeke Jane E. , Hoberman Alan M. , Christian Mildred S.
Published: November 2007

The validity of computer-entered and computer-generated toxicology data is currently of concern to the quality assurance professional. In order to insure this validity, a suitable quality assurance program must be devised. This program should include (1) maintenance of standard operational procedures for both system maintenance and operation, (2) documentation of program changes, (3) inspection of automated data collection, (4) audit of acquired data, (5) establishment of the data trail, including the use of intermediate printouts and inspection of edit procedures, (6) validation of security procedures, and (7) documentation of system failure.
Meeting the Quality Assurance Challenges of the 1980s: Team Auditing by Toxicologists and QA Professionals
Authors: Hoover B. Kristin , Baldwin Judith K.
Published: November 2007

The major challenge of the 1980s is to continue to provide a productive contribution to the conduct of scientific research. Major factors that may be expected to affect the ability of quality assurance to meet this challenge are economics, ever changing and expanding regulatory requirements, increasing test complexity, computerization, and continuing product liability needs.

Team auditing is an effective way to utilize resources to meet the requirements imposed by these factors. This approach results in a highly cost-efficient use of personnel in order to accomplish large and difficult tasks in a short period of time. In addition, it can decrease the need for large-scale training programs and be used as a method for upgrading present staff expertise. Individual perspectives are broadened as team members learn from each other. Morale is improved as the professional isolation of working alone or in small units is overcome.

If team auditing is to be successful, it must be properly planned and executed. The team must be selected, objectives established, methods defined, and time constraints determined. These factors and ways to build a cohesive audit team capable of accomplishing specific goals will be discussed in detail. In addition, useful applications of this approach will be suggested.
What's driving you? A template which underpins the assessment of preschool children by speech and language therapists
Authors: ROULSTONE SUE
Published: November 2007

Abstracts

This paper presents a diagrammatic representation of features which underpin the initial assessment of preschool children newly referred, to speech and language therapy. This model forms part of the results of a project whose overall aim was to make explicit the way in which expert speech and language therapists consider preschool children for intervention. Within a mainly qualitative methodology, data were collected by use of semistructured interviews, case analyses and a focus group workshop. The notational tool used for analysis, systemic grammar networks, is described and used to represent an assessment paradigm. The model is presented as a potential support for less experienced therapists or as a stimulus to reflection in more experienced therapists.

L'article présente sous forme de diagrammes les modalités qui étayent l'évaluation primordiale d'enfants d'age préscolaire que l'on venait d'adresser à une thérapie orthophonique. Ce modèle fait partie des résultats d'un projet dont le but général est d'expliciter la méthode utilisée par les orthophonistes pour déterminer ceux des enfants qui auront besoin de soins correctifs. Dans le cadre d'une méthodologie surtout qualitative, la récolte des données a utilisé des entretiens semi‐structures, des analyses de cas et des séminaires de groupes cibles. L'on décrit l'outil utilisé pour noter les enfants: il s'agit de réseaux de grammaire systémique, dont on se sert pour représenter un paradigme d'évaluation. L'on montre que le modèle peut servir d'aide pour les orthophonistes débutants ou encore d'incitation à la réflexion chez les orthophonistes plus expérimentés.

In diesem Aufsatz wird eine diagrammatische Repräsentation der Merkmale vorgestellt, die der Anfangsbewertung von zur sprachtherapeutischen Behandlung überwiesenen Vorschulkindern zugrundeliegen. Das dahinterliegende Modell stellt einen Teil der Ergebnisse eines Projektes dar, dessen Ziel die Explizierung der Kriterien war, die von Experten (d.h. von erfahrenen LogopädInnen) bei der Entscheidung zur Sprachtherapie fur Vorschulkinder angewandt werden. Die Daten dafür wurden in einem hauptsächlich qualitativen methodologischen Rahmen erhoben, d.h., bei teilstrukturierten Interviews, Einzelfallanalysen und bei einem Fokusgruppenworkshop. Der analytische Notationsansatz, Netzwerke der systemischen Grammatik, wird beschrieben und zur Darstellung des Bewertungsparadigmas verwendet. Dos Modell ist als potentiell Unterstützung für weniger erfahrenen Therapeuten bzw. als Anregung zum Nachdenken für erfahrene intendiert.
Syntactic bootstrapping in children with specific language impairment
Authors: O'Hara Margaret , Johnston Judith
Published: November 2007

Syntactic bootstrapping was assessed in six children with normally developing language (NL) and six children with specific language impairment (SLI), ages 6 and 8, respectively. Children earned normal range non‐verbal IQs and were matched by raw scores on a test of sentence comprehension. They were asked to listen to sentences containing novel verbs and to act out the meanings with toys. The SLI children earned reliably lower scores, but their errors suggested processing limitations rather than deficits in syntactic representation.

L'on a évalué la programmation syntactique chez six enfants agis de 6 ans dont le langage se développait normalement, et chez six enfants souffrant de déficience linguistique spécifique. Les enfants présentaient un éventail normal de Q.I. non verbaux; ils avaient été soumis à un test de compreháension de phrases, pour lequel Us avaient obtenu une note en première approximation, et chacun des enfants d'un groupe a He assorti a un enfant de l'autre groupe selon la note obtenue. On leur a demands d'icouter dix phrases contenant des verbes nouveaux pour eux et d'en jouer la signification au moyen de jouets. Les enfants souffrant de déficience linguistique spécifique ont eu des notes nettement inférieures, mais leurs erreurs suggèrent des limitations dans leurs capacités d'analyse plutot que des déficits dans les représentations syntactiques.

Syntaktische ‘Bootstrapping’ wurde bei 6 sechsjährigen Kindern mit normaler Sprachentwicklung (Engl: NL) und bei 6 achtjährigen Kindern mit spezifischen Sprachstörungen (Engl.: SLI) under‐sucht. Die Kinder zeigten eine normale IQ‐Spanne und warden nach dem Maβ ihres Satzverstehens gepaart. Sie hatten die Aufgabe, Sätzen mit neuen Verben zuzuhören und die Bedeutung mit Spielzeugen vorzuspielen. Die Kinder der SLI‐Gruppe zeigten niedrigere Leistungen, aber ihre Fehler deuteten eher auf Verarbeitungsgrenzen als auf Mängel in der syntaktischen Representätion.
Bilingualism and specific language impairment in children attending language units
Authors: Crutchley Alison , Botting Nicola , Conti‐Ramsden Gina
Published: November 2007

Abstracts

Bilingual children were found to form a distinct subgroup within a large cohort of children with specific language‐impairment (SLI) attending language units across England. They differed from the cohort as a whole, and from a language‐matched monolingual ‘controL’ group, on measures including language profile on entry to the unit, performance on standardised tests, emotional‐behavioural state and probable future educational placement. This paper sets out the nature of these differences in more detail, and suggests some possible explanations for them.

II s'est révélé que des enfants bilingues formaient un sous groupe distinct au sein d'un vaste ensemble d'enfants souffrant de déficience linguistique spécifique qui fréquentaient des établissements spécialisés de langage un peu partout en Angleterre. lis différaient de l'ensemble pris dans sa totalité, et d'un groupe témoin monolingue et assorti du point de vue du langage, d'après des mesures comprenant leur profil linguistique au moment de l'admission dans l'établissement, leur fonctionnement lors de tests de connaissances communs à tous les établissements, leur état émotionnel et de comportement, et leur orientation probable à venir dans Tenseignement. Cet article donne des détails supplémentaires sur la nature de ces differences et leur suggère des explications possibles.

Es wurde festgestellt, daβ zweisprachige Kinder eine erkennbare Untergruppe innerhalb eines groβen Kohorts von Kindern mil speziflschen Sprachstörungen in den sprachtherapeutischen Einrichtungen in England bilden. Sie unterscheiden sich vom Gesamtkohort und von einer sprachlich gepaarten einsprachigen Kontrollgruppe in mehreren Meβkirterien, u.a. im Sprachprofil bei der Aufnahme in die Einrichtung, in der Leistung in standardisierten Tests, im emotionalen Verhal‐tenszustand und in der Prognose für ihre zukünftige Schulbildung. In diesem Aufsatz werden die Unterschiede detaillierter dargelet und einige mögliche Erklärungen dafür vorgeschlagen.