bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing Program Fidelity Using Onsite Observations and Program Provider Descriptions of Program Delivery
Authors: Melde Chris , Esbensen Finn-Aage , Tusinski Karin
Published: November 2006

Over the past quarter-century, evaluation researchers have recognized the importance of documenting implementation practices of programs as they are transferred from controlled to realworld settings. As programs become widely disseminated in the general population, there is a tendency for practitioners to alter programs in a manner more conducive to their immediate needs, which may adversely affect program outcomes. The current paper uses findings from an ongoing evaluation of a school-based victimization prevention program to highlight some of the difficulties in maintaining a high degree of fidelity when providing prevention programming in a school-based setting. The results, based on observations of program delivery and program provider descriptions of implementation, allow for the examination of fidelity based on different data collection techniques.
Statistical Models for Causation
Authors: Freedman David A.
Published: November 2006

Experiments offer more reliable evidence on causation than observational studies, which is not to gainsay the contribution to knowledge from observation. Experiments should be analyzed as experiments, not as observational studies. A simple comparison of rates might be just the right tool, with little value added by “sophisticated” models. This article discusses current models for causation, as applied to experimental and observational data. The intention-totreat principle and the effect of treatment on the treated will also be discussed. Flaws in perprotocol and treatment-received estimates will be demonstrated.
‘I’m Not One of Those Women’s Libber Type People but...’: Gender, Class and Professional Power within the Third Branch of the English Legal Profession
Authors: Francis Andrew
Published: November 2006

Legal executives are the third branch of the legal profession in England and Wales. While their professional body (ILEX) has made progress in recent years, they remain in a subordinate position to solicitors. Drawing on detailed interviews with legal executives in a range of settings, this article will argue that women legal executives experience a distinctive disadvantage in legal practice. Intersections of class, gender and professional power contribute to a highly unstable professional identity for legal executives, and one which is particularly acute for women. The dissonance between their ‘expected’ and ‘experienced’ professional identity reinforces their lack of engagement with ILEX. This article argues that the negative and gendered connotations of the professional identity of legal executives reinforce the hierarchies of legal practice.
Genetics, Fathers and Families: Exploring the Implications of Changing the Law in Favour of Identifying Sperm Donors
Authors: Donovan Catherine
Published: November 2006

In April 2005 amendments to the Human Fertilisation and Embryology Act 1990 allowed adult children of gamete donors access to identifying information about their donor. Focusing on sperm donation as the most often used donated gamete in Britain, this article concentrates on the original decision in the legislation to secure donor anonymity in order to highlight the ways in which societal trends have shifted in favour of the importance of genetic fathers. This will involve discussing how anomalous this decision was in comparison to changes elsewhere in family law where genetic fathers-and genetic kin relationships-were being given increasing priority in regulating families living outside the heteronormative, married, nuclear family. The author discusses the impact of the new genetics in providing a rationale for the increasing emphasis placed on knowledge of genetic fatherhood for the ontological security of individuals, their well-being and identity. The article ends with a discussion of some of the implications for families living outside the heteronormative ideal of the increasing prioritization given to genetic fathers.
Increasing Population Diversity Through Cultural Learning
Authors: Curran Dara , O'Riordan Colm
Published: November 2006

A number of learning models are commonly employed in the simulation of social behavior. These include population learning, lifetime learning and cultural learning. Population learning allows popula tions as a whole to evolve over time, typically through a Darwinian model of natural selection. Lifetime learning allows individuals to acquire knowledge during their lifetimes and cultural learning allows indi viduals to pass this knowledge to their peers or subsequent generations. This work examines the effects of cultural learning on both the fitness and the diversity of a population of neural network agents. A population employing population learning alone and one employing both population and cultural learning are assigned three benchmark tasks: the 5-bit parity problem, the game of tic-tac-toe and the game of connect-four. Each agent contains a genome which encodes a neural network controller used by the agent to perceive and react to environmental stimuli. Results show that the addition of cultural learning promotes improved fitness and significantly increases both genotypic (the genetic make up of individuals) and phenotypic (the behavior of individuals) diversity in the population.
EPICURE: Spatial and Knowledge Limitations in Group Foraging
Authors: Roberts Michael E. , Goldstone Robert L.
Published: November 2006

We propose an agent-based model of group foraging, EPICURE, for patchily distributed resources. Each agent makes probabilistic movement decisions in a gridworld through a linear combination of cur rent perceptual information and a reinforcement history. EPICURE captures the empirical results from several foraging conditions in previous works, and it leads to a reevaluation of findings from those papers. In particular, human foragers show contingent usage of information, initially using social infor mation to discover resource pools before private sampling information has been established. We describe a series of simulations that test the sources of resource undermatching often found in group foraging experiments. After testing the effects of foragers' starting locations, travel costs, the number of foragers, and the size of uniform food distributions, we discuss a novel hypothesis for undermatch ing. Spatial constraints lead to inadequate individual and group information sampling and cause group undermatching. The foraging group size, food rate, spatial distribution of food, and resulting forager reinforcement histories interact to produce undermatching, and occasionally overmatching, to resources.
Emotional Behavior: A Resource Management Approach
Authors: Zadeh Saman Harati , Shouraki Saeed Bagheri , Halavati Ramin
Published: November 2006

Emotions are the subject of study in many research areas, including psychology, physiology and arti ficial intelligence. However, there is not yet a general computational definition for emotions and many of the related works in artificial intelligence are based on uncertain assumptions about the origin, fea tures, and applications of emotions. Therefore, we direct our studies toward achieving a better understanding of emotions and generating a computational model that could be a base for further research in the field. As a first step, we present the results of our study into the possible role of emotions in men tal resource management. To do so, we will introduce a model of emotions based on managing mental resources. We have applied it to a general model of mind and the whole model has been implemented in an artificial life simulation environment called Zamin to evaluate its ability to produce emotional behavior and to make better decisions. The results, as discussed in this article, show that a resource management mechanism could be the source of emotion generation in the mind.
Adaptation of Controllers for Image-Based Homing
Authors: Zampoglou Markos , Szenher Matthew , Webb Barbara
Published: November 2006

Visual homing is a short-range robot navigation method which can lead an agent to a position with accuracy, provided that the majority of the scene visible from the home position is also visible from the current robot position. Recently Zeil, Hoffmann and Chahl (2003) showed that a simple calculation— the root mean square (RMS) difference between the current image and the home image—produces a monotonic function leading to the home position for natural images. In this article we propose a gradi ent descent algorithm based on Caenorhabditis elegans chemotaxis (Ferree & Lockery, 1999) for hom ing with the RMS signal. The parameters for this algorithm are evolved for a simulated agent, and the resulting homing behavior compared with alternative algorithms in simulation and using a real robot. A simulated agent using this algorithm in an environment constructed from real world images homes effi ciently and shows generalization to variations in lighting and changes in the scene. In the real robot this algorithm is affected by noise resulting from imperfect sensors, and alternative algorithms appear more robust. However, the best performing algorithm for unchanging environments, image warping (Franz, Schölkopf, Mallot, & Bülthoff, 1998), is completely disabled by scene changes that do not affect algo rithms utilizing the RMS difference.
Political Deadlock and Devolved Wildlife Management in Zimbabwe
Authors: Mapedza Everisto , Bond Ivan
Published: November 2006

Since February 2000, Zimbabwe has been experiencing an unparalleled period of political, economic, and social uncertainty. The most prominent features are the political deadlock generated by (a) confrontation between the ruling Zimbabwe African National Union–Patriotic Front (ZANU-PF) and the Movement for Democratic Change (MDC) party; (b) the illegal invasion of private land; (c) hyperinflation; and (d) the withdrawal of bilateral donor funds. Generally, a culture of impunity exists that compromises the rule of law. Within this crisis, very little attention has been given to the impact that this political deadlock and uncertainty have on natural resource management in the communal lands of Zimbabwe. Between 1990 and 2000, Zimbabwe's Communal Areas Management Programme for Indigenous Resources (CAMPFIRE) was considered one of the leading community conservation initiatives attracting considerable international interest and analysis. This article analyzes the changes that are taking place within Nenyunga Ward, Gokwe North Rural District Council (RDC), since 2000. By comparing selected natural resource management activities before and after 2000, the article demonstrates how the larger macroeconomic and political processes are undermining natural resource management at the ward level.
Balancing Access and Benefit Sharing and Legal Protection of Innovations From Bioprospecting
Authors: Rosendal G. Kristin
Published: November 2006

Biodiversity conservation, access and benefit sharing (ABS), and protection of intellectual property rights (IPR) linked to biotechnologies are all internationally agreed—but not necessarily compatible—objectives. The Convention on Biological Diversity aims for a balance between the needs and interests of owners of genetic resources and technology owners. Can current proposals for handling existing IPR legislation, such as disclosure of origin and certificates of legal provenance, contribute to finding a balance between the interests? Will the growing concern for legitimacy in international transactions with genetic resources be helpful to countries providing genetic resources for technological innovation or are the benefits too few? The article concludes that the success of establishing a multilateral system for access and benefit sharing still depends on compatible legislation in user and provider countries to counterbalance strengthened patent protection systems worldwide. Moreover, it is necessary to overcome the old schism between wildlife conservation and access issues in agricultural biodiversity to boost overall implementation efforts.
Biodiversity Policy Making in Costa Rica
Authors: Miller Michael J.
Published: November 2006

Costa Rica's Biodiversity Law of 1998 is perhaps the most comprehensive legislation implementing the Convention on Biological Diversity. It includes provisions to better protect the intellectual property rights of rural communities regarding uses they have developed for natural resources and plants and animals they have bred. This article addresses how groups representing these peoples—the National Indigenous Board and National Peasant Board—obtained these provisions despite opposition from traditionally more powerful scientific and business communities. Data were collected on the formulation of the Biodiversity Law through qualitative techniques, including intensive interviews and archival research. It was found that fortuitous political conditions, or political opportunity structures, were crucial to the success of organizations representing rural communities. These supports included better-resourced allies, favorable international legal obligations and public opinion, and existing law that could be built on. Indicating broader patterns, it also was found that such political conditions have been salient during indigenous and peasant political activism elsewhere in Latin America and during formulation of similar biodiversity policy in developing countries.
Neglected user perspectives in the design of an online hospital bed-state system: implications for the National Programme for IT in the NHS
Authors: Harrop Nick , Wood-Harper Trevor , Gillies Alan
Published: November 2006

Technical aspects of the National Programme for IT in the National Health Service have run ahead of genuine engagement with front-line users. We have explored with front-line NHS staff the factors which limit their contribution to management information from operational systems. Staff place psychological distance between ‘the real job’ and the reporting of information. Even where accurate reporting is heavily incentivized, and operational control is shared between staff and shift leader, the reporting of information to the computer represents a division between caregiving and computer input, and between information openly declared and that waiting to be disclosed. The Programme needs to reconsider how clinicians are to be engaged. Equally, information systems designers, if they expect to obtain management information and want to understand the limitations of that process, need to be socialized into the fields where systems are to be deployed.
Computer-based decision support for pediatric asthma management: description and feasibility of the Stop Asthma Clinical System
Authors: Shegog Ross , Bartholomew Leona K. , Sockrider Marianna M. , Czyzewski Danita I. , Pilney Susan , Mullen Patricia Dolan , Abramson Stuart L.
Published: November 2006

Clinical guidelines can assist in the management of asthma. Decision support systems (DSSs) can enhance adherence to clinical guidelines but tend not to provide clinicians with cues for behavioral change strategies to promote patient self-management. The Stop Asthma Clinical System (SACS) is a DSS designed for this purpose. To assess feasibility, seven clinicians used SACS to guide well visits with 26 predominantly persistent pediatric asthma patients. Data were collected via survey and in-depth semi-structured interviews. SACS improved assessment of asthma severity and control, classification of and intervention in medicine and environmental trigger management problems, and development of an action plan (all p< 0.05). Clinician-patient communication was enhanced. The primary challenge was that SACS increased clinic visit time. SACS can enhance clinician behavior to improve patient asthma self-management, but more studies are indicated to mitigate temporal constraints and evaluate impact on clinician and patient communication and behavior as well as clinical outcomes.
CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins
Authors: Sloand Elaine M. , Pfannes Loretta , Chen Gubin , Shah Simant , Solomou Elena E. , Barrett John , Young Neal S.
Published: November 2006

CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) are distinguished from other MDS cells and from normal hematopoietic cells by their pronounced expression of apoptotic markers. Paradoxically, trisomy 8 clones can persist in patients with bone marrow failure and expand following immunosuppression. We previously demonstrated up-regulation of c-myc and CD1 by microarray analysis. Here, we confirmed these findings by real-time polymerase chain reaction (PCR), demonstrated up-regulation of survivin, c-myc, and CD1 protein expression, and documented comparable colony formation by annexin+ trisomy 8− CD34+ and annexin− CD34 cells. There were low levels of DNA degradation in annexin+ trisomy 8 CD34 cells, which were comparable with annexin− CD34 cells. Trisomy 8 cells were resistant to apoptosis induced by gamma irradiation. Knock-down of survivin by siRNA resulted in preferential loss of trisomy 8 cells. These results suggest that trisomy 8 cells undergo incomplete apoptosis and are nonetheless capable of colony formation and growth.
The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish
Authors: Patterson Lucy J. , Gering Martin , Eckfeldt Craig E. , Green Anthony R. , Verfaillie Catherine M. , Ekker Stephen C. , Patient Roger
Published: November 2006

The transcription factors Scl and Lmo2 are crucial for development of all blood. An important early requirement for Scl in endothelial development has also been revealed recently in zebrafish embryos, supporting previous findings in scl−/− embryoid bodies. Scl depletion culminates most notably in failure of dorsal aorta formation, potentially revealing a role in the formation of hemogenic endothelium. We now present evidence that the requirements for Lmo2 in zebrafish embryos are essentially the same as for Scl. The expression of important hematopoietic regulators is lost, reduced, or delayed, panendothelial gene expression is down-regulated, and aorta-specific marker expression is lost. The close similarity of the phenotypes for Scl and Lmo2 suggest that they perform these early functions in hemangioblast development within a multiprotein complex, as shown for erythropoiesis. Consistent with this, we find that scl morphants cannot be rescued by a non-Lmo2–binding form of Scl but can be rescued by non-DNA–binding forms, suggesting tethering to target genes through DNA-binding partners linked via Lmo2. Interestingly, unlike other hematopoietic regulators, the Scl/Lmo2 complex does not appear to autoregulate, as neither gene's expression is affected by depletion of the other. Thus, expression of these critical regulators is dependent on continued expression of upstream regulators, which may include cell-extrinsic signals.
K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis
Authors: Wang Suizhao , Wang Shu , Maeng Hoyoung , Young Daniel P. , Prakash Om , Fayad Luis E. , Younes Anas , Samaniego Felipe
Published: November 2006

Expression of the K1 gene of human herpesvirus 8 activates nuclear factor-κB and induces lymph node hyperplasia and lymphomas in transgenic mice. To further delineate its role in cell survival, we determined whether K1 altered apoptosis of lymphoma cells. K1 protein is expressed in Kaposi sarcoma and primary effusion lymphoma. We retrovirally transfected BJAB lymphoma, THP-1, U937, and Kaposi sarcoma SLK cells to express K1 and a K1 mutant with the deleted immunoreceptor tyrosine-based activation motif (K1m). We challenged cells with an agonistic anti-Fas antibody, Fas ligand, irradiation, and tumor necrosis factor–related apoptosis-inducing ligand. K1 transfectants but not K1m transfectants exhibited reduced levels of apoptosis induced by the anti-Fas antibody but not apoptosis induced by the tumor necrosis factor–related apoptosis-inducing ligand or irradiation. K1 expression resulted in reduced apoptosis rates as shown in several assays. K1 induced a modest reduction in levels of Fas-associated death domain protein, and procaspase 8 recruited to the death-inducing signaling complex. Finally, K1 transfectants cleaved procaspase 8 at significantly lower rates than did K1m transfectants. K1-transfected mice, compared with vector-transfected mice, showed lower death rates after challenge with anti-Fas antibody. K1 may contribute to lymphoma development by stimulating cell survival by selectively blocking Fas-mediated apoptosis.
Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates
Authors: Nathwani Amit C. , Gray John T. , McIntosh Jenny , Ng Catherine Y. C. , Zhou Junfang , Spence Yunyu , Cochrane Melanie , Gray Elaine , Tuddenham Edward G. D. , Davidoff Andrew M.
Published: November 2006

The safety and efficacy of peripheral venous administration of a self-complementary adeno-associated viral vector encoding the human FIX gene (scAAV-LP1-hFIXco) was evaluated in nonhuman primates for gene therapy of hemophilia B. Peripheral vein infusion of 1 × 1012 vg/kg scAAV-LP1-hFIXco pseudotyped with serotype 8 capsid, in 3 macaques, resulted in stable therapeutic expression (more than 9 months) of human FIX (hFIX) at levels (1.1 ± 0.5 μg/mL, or 22% of normal) that were comparable to those achieved after direct delivery of the same vector dose into the portal circulation (1.3 ± 0.3 μg/mL, or 26% of normal). Importantly, the pattern of vector biodistribution after systemic and portal vein administration of scAAV-LP1-hFIXco was almost identical. Additionally, comparable levels of gene transfer were achieved in macaques with preexisting immunity to AAV8 following peripheral vein administration of 1 × 1012 vg/kg AAV5-pseudotyped scAAV-LP1-hFIXco. This confirms that alternative serotypes can circumvent preexisting naturally acquired immunity to AAV. Thus, peripheral venous administration of AAV5 and AAV8 vectors is safe and as effective at transducing the liver in nonhuman primates as direct vector administration into the portal circulation. These results should make vector administration to patients, especially those with a severe bleeding diathesis, significantly easier and safer.
In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells
Authors: Aranguren Xabier L. , Luttun Aernout , Clavel Carlos , Moreno Cristina , Abizanda Gloria , Barajas Miguel A. , Pelacho Beatriz , Uriz Maialen , Araña Miriam , Echavarri Ana , Soriano Mario , Andreu Enrique J. , Merino Juana , Garcia-Verdugo Jose Manuel , Verfaillie Catherine M. , Prósper Felipe
Published: November 2006

Many stem cell types have been shown to differentiate into endothelial cells (ECs); however, their specification to arterial or venous endothelium remains unexplored. We tested whether a specific arterial or venous EC fate could be induced in human multipotent adult progenitor cells (hMAPCs) and AC133+ cells (hAC133+). In vitro, in the presence of VEGF165, hAC133+ cells only adopted a venous and microvascular EC phenotype, while hMAPCs differentiated into both arterial and venous ECs, possibly because hMAPCs expressed significantly more sonic hedgehog (Shh) and its receptors as well as Notch 1 and 3 receptors and some of their ligands. Accordingly, blocking either of those pathways attenuated in vitro arterial EC differentiation from hMAPCs. Complementarily, stimulating these pathways by addition of Delta-like 4 (Dll-4), a Notch ligand, and Shh to VEGF165 further boosted arterial differentiation in hMAPCs both in vitro and in an in vivo Matrigel model. These results represent the first demonstration of adult stem cells with the potential to be differentiated into different types of ECs in vitro and in vivo and provide a useful human model to study arteriovenous specification.
Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels
Authors: van Schooten Carina J. M. , Denis Cécile V. , Lisman Ton , Eikenboom Jeroen C. J. , Leebeek Frank W. , Goudemand Jenny , Fressinaud Edith , van den Berg H. Marijke , de Groot Philip G. , Lenting Peter J.
Published: November 2006

The glycosylation profile of von Willebrand factor (VWF) is known to strongly influence its plasma levels. VWF contains several carbohydrate structures, including O-linked glycans that primarily consist of sialylated T antigen (NeuAc(α2-3)Gal-(β1-3)-[NeuAc(α2-6)]GalNAc). It is not yet known whether O-linked carbohydrates affect VWF levels. We developed an immunosorbent assay based on neuraminidase incubation allowing subsequent binding of peanut agglutinin (PNA) to desialylated O-linked T antigen on VWF. An inverse relation was found between PNA binding and VWF antigen levels in healthy individuals (n = 111; Pearson rank = −0.43; P < .001). A similar inverse association was observed in randomly selected plasma samples from our diagnostic laboratory: 252% ± 125% for VWF levels less than 0.5 U/mL (n = 15); 131% ± 36% for VWF levels between 0.5 and 1.5 U/mL (n = 32); and 92% ± 40% for VWF levels more than 1.5 U/mL (n = 19). Reduced or increased PNA binding was also observed in patients with increased (liver cirrhosis) or reduced (von Willebrand disease [VWD] type 1) VWF antigen levels, respectively. VWD type 1 patients further displayed increased ratios of propeptide over mature VWF antigen levels (0.38 ± 0.18 versus 0.17 ± 0.03 for patients and controls, respectively; P < .001), which is indicative of reduced VWF survival in these patients. Of interest, a linear relation between PNA binding and propeptide/VWF ratio was observed (Spearman rank = 0.47), suggesting a potential association between O-linked glycosylation and VWF survival. Finally, we detected a marked decrease in PNA binding in post-DDAVP (1-deamino-8-D-arginine vasopressin) samples from various patients, indicating that the O-linked glycosylation profile of VWF stored in endothelial storage organelles may differ from circulating VWF.
Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation
Authors: Wang Ying , Cai Dali , Brendel Cornelia , Barett Christine , Erben Philipp , Manley Paul W. , Hochhaus Andreas , Neubauer Andreas , Burchert Andreas
Published: November 2006

Overcoming imatinib mesylate (IM) resistance and disease persistence in patients with chronic myeloid leukemia (CML) is of considerable importance to the issue of potential cure. Here we asked whether autocrine signaling contributes to survival of BCR/ABL+ cells in the presence of IM and nilotinib (NI; AMN107), a novel, more selective Abl inhibitor. Conditioned media (CM) of IM-resistant LAMA84 cell clones (R-CM) was found to substantially protect IM-naive LAMA cells and primary CML progenitors from IM- or NI-induced cell death. This was due to an increased secretion of the granulocyte-macrophage colony-stimulating factor (GM-CSF), which was identified as the causative factor mediating IM resistance in R-CM. GM-CSF elicited IM and NI drug resistance via a BCR/ABL-independent activation of the janus kinases 2 (JAK-2)/signal transducer and activator of transcription 5 (STAT-5) signaling pathway in GM-CSF receptor α receptor (CD116)–expressing cells, including primary CD34+/CD116+ GM progenitors (GMPs). Elevated mRNA and protein levels of GM-CSF were detected in IM-resistant patient samples, suggesting a contribution of GM-CSF secretion for IM and NI resistance in vivo. Importantly, inhibition of JAK-2 with AG490 abrogated GM-CSF–mediated STAT-5 phosphorylation and NI resistance in vitro. Together, adaptive autocrine secretion of GM-CSF mediates BCR/ABL-independent IM and NI resistance via activation of the antiapoptotic JAK-2/STAT-5 pathway. Inhibition of JAK-2 overcomes GM-CSF–induced IM and NI progenitor cell resistance, providing a rationale for the application of JAK-2 inhibitors to eradicate residual disease in CML.
Huntingtin gene evolution in Chordata and its peculiar features in the ascidian Ciona genus
Authors: Gissi Carmela , Pesole Graziano , Cattaneo Elena , Tartari Marzia
Published: November 2006

Background

To gain insight into the evolutionary features of the huntingtin (htt) gene in Chordata, we have sequenced and characterized the full-length htt mRNA in the ascidian Ciona intestinalis, a basal chordate emerging as new invertebrate model organism. Moreover, taking advantage of the availability of genomic and EST sequences, the htt gene structure of a number of chordate species, including the cogeneric ascidian Ciona savignyi, and the vertebrates Xenopus and Gallus was reconstructed.

Results

The C. intestinalis htt transcript exhibits some peculiar features, such as spliced leader trans-splicing in the 98 nt-long 5' untranslated region (UTR), an alternative splicing in the coding region, eight alternative polyadenylation sites, and no similarities of both 5' and 3'UTRs compared to homologs of the cogeneric C. savignyi. The predicted protein is 2946 amino acids long, shorter than its vertebrate homologs, and lacks the polyQ and the polyP stretches found in the the N-terminal regions of mammalian homologs. The exon-intron organization of the htt gene is almost identical among vertebrates, and significantly conserved between Ciona and vertebrates, allowing us to hypothesize an ancestral chordate gene consisting of at least 40 coding exons.

Conclusion

During chordate diversification, events of gain/loss, sliding, phase changes, and expansion of introns occurred in both vertebrate and ascidian lineages predominantly in the 5'-half of the htt gene, where there is also evidence of lineage-specific evolutionary dynamics in vertebrates. On the contrary, the 3'-half of the gene is highly conserved in all chordates at the level of both gene structure and protein sequence. Between the two Ciona species, a fast evolutionary rate and/or an early divergence time is suggested by the absence of significant similarity between UTRs, protein divergence comparable to that observed between mammals and fishes, and different distribution of repetitive elements.
Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial
Authors: Weydert Joy A , Shapiro Daniel E , Acra Sari A , Monheim Cynthia J , Chambers Andrea S , Ball Thomas M
Published: November 2006

Background

Because of the paucity of effective evidence-based therapies for children with recurrent abdominal pain, we evaluated the therapeutic effect of guided imagery, a well-studied self-regulation technique.

Methods

22 children, aged 5 – 18 years, were randomized to learn either breathing exercises alone or guided imagery with progressive muscle relaxation. Both groups had 4-weekly sessions with a therapist. Children reported the numbers of days with pain, the pain intensity, and missed activities due to abdominal pain using a daily pain diary collected at baseline and during the intervention. Monthly phone calls to the children reported the number of days with pain and the number of days of missed activities experienced during the month of and month following the intervention. Children with ≤ 4 days of pain/month and no missed activities due to pain were defined as being healed. Depression, anxiety, and somatization were measured in both children and parents at baseline.

Results

At baseline the children who received guided imagery had more days of pain during the preceding month (23 vs. 14 days, P = 0.04). There were no differences in the intensity of painful episodes or any baseline psychological factors between the two groups. Children who learned guided imagery with progressive muscle relaxation had significantly greater decrease in the number of days with pain than those learning breathing exercises alone after one (67% vs. 21%, P = 0.05), and two (82% vs. 45%, P < 0.01) months and significantly greater decrease in days with missed activities at one (85% vs. 15%, P = 0.02) and two (95% vs. 77%. P = 0.05) months. During the two months of follow-up, more children who had learned guided imagery met the threshold of ≤ 4 day of pain each month and no missed activities (RR = 7.3, 95%CI [1.1,48.6]) than children who learned only the breathing exercises.

Conclusion

The therapeutic efficacy of guided imagery with progressive muscle relaxation found in this study is consistent with our present understanding of the pathophysiology of recurrent abdominal pain in children. Although unfamiliar to many pediatricians, guided imagery is a simple, noninvasive therapy with potential benefit for treating children with RAP.
PCR detection of Plasmodium falciparum in human urine and saliva samples
Authors: Mharakurwa Sungano , Simoloka Christopher , Thuma Philip E , Shiff Clive J , Sullivan David J
Published: November 2006

Background

Current detection or screening for malaria infection necessitates drawing blood by fingerprick or venipuncture, which poses risks and limitations for repeated measurement. This study presents PCR detection of Plasmodium falciparum in human urine and saliva samples, and illustrates this potential application in genotyping malaria infections.

Methods

Urine and saliva were obtained from 47 thick film positive and 4 negative individuals one day after collection of blood slides and filter paper blood spots. P. falciparum DNA was extracted from blood, urine and saliva, in separate groups, using the Chelex method or Qiagen DNEasy® kit (urine and saliva only). Blood, urine and saliva extracts were subjected to PCR in separate batches. Amplicons from the various sample types were examined for MSP2 polymorphisms and restriction fragment patterns on DHFR amino acid codon 59.

Results and discussion

Malaria infections exhibited primarily low-grade parasite densities, with a geometric mean of 775 asexual parasites/μl. Regularly matching polymorphic MSP2 genotypes were found between the corresponding urine, saliva and peripheral blood amplicons of each individual, with different inter-individual polymorphic genotypes. Amplicon yields were significantly dependent on DNA extraction method, parasite density and primer set (p < 0.001). A Qiagen® kit extraction had more than 2× higher amplicon yield than the Chelex method, for both urine and saliva. Amplicon yields were 1.6 fold higher from saliva than urine. For each unit increase in log parasite density, the probability of amplicon enhanced 1.8 fold. Highest amplicon yields were obtained from the primer set with the shortest PCR product.

Conclusion

P. falciparum infection is detectable by PCR on human urine and saliva samples. Subject to further refinement of extraction technique and amplicon yields, large-scale malaria parasite screening and epidemiological surveys could be possible without the need to collect blood and use of needles or sharps.
The hepatic transcriptome in human liver disease
Authors: Shackel Nicholas A , Seth Devanshi , Haber Paul S , Gorrell Mark D , McCaughan Geoffrey W
Published: November 2006

The transcriptome is the mRNA transcript pool in a cell, organ or tissue with the liver transcriptome being amongst the most complex of any organ. Functional genomics methodologies are now being widely utilized to study transcriptomes including the hepatic transcriptome. This review outlines commonly used methods of transcriptome analysis, especially gene array analysis, focusing on publications utilizing these methods to understand human liver disease. Additionally, we have outlined the relationship between transcript and protein expressions as well as summarizing what is known about the variability of the transcriptome in non-diseased liver tissue. The approaches covered include gene array analysis, serial analysis of gene expression, subtractive hybridization and differential display. The discussion focuses on primate whole organ studies and in-vitro cell culture systems utilized. It is now clear that there are a vast number research opportunities for transcriptome analysis of human liver disease as we attempt to better understand both non-diseased and disease hepatic mRNA expression. We conclude that hepatic transcriptome analysis has already made significant contributions to the understanding of human liver pathobiology.
Regulation of CDK4
Authors: Bockstaele Laurence , Coulonval Katia , Kooken Hugues , Paternot Sabine , Roger Pierre P
Published: November 2006

Cyclin-dependent kinase (CDK)4 is a master integrator that couples mitogenic and antimitogenic extracellular signals with the cell cycle. It is also crucial for many oncogenic transformation processes. In this overview, we address various molecular features of CDK4 activation that are critical but remain poorly known or debated, including the regulation of its association with D-type cyclins, its subcellular location, its activating Thr172-phosphorylation and the roles of Cip/Kip CDK "inhibitors" in these processes. We have recently identified the T-loop phosphorylation of CDK4, but not of CDK6, as a determining target for cell cycle control by extracellular factors, indicating that CDK4-activating kinase(s) might have to be reconsidered.
Serum antibody response to Human papillomavirus (HPV) infections detected by a novel ELISA technique based on denatured recombinant HPV16 L1, L2, E4, E6 and E7 proteins
Authors: Di Bonito Paola , Grasso Felicia , Mochi Stefania , Accardi Luisa , Donà Maria Gabriella , Branca Margherita , Costa Silvano , Mariani Luciano , Agarossi Alberto , Ciotti Marco , Syrjänen Kari , Giorgi Colomba
Published: November 2006

Background

Human papillomaviruses (HPVs) are the primary etiological agents of cervical cancer and are also involved in the development of other tumours (skin, head and neck). Serological survey of the HPV infections is important to better elucidate their natural history and to disclose antigen determinants useful for vaccine development. At present, the analysis of the HPV-specific antibodies has not diagnostic value for the viral infections, and new approaches are needed to correlate the antibody response to the disease outcome. The aim of this study is to develop a novel ELISA, based on five denatured recombinant HPV16 proteins, to be used for detection HPV-specific antibodies.

Methods

The HPV16 L1, L2, E4, E6 and E7 genes were cloned in a prokaryotic expression vector and expressed as histidine-tagged proteins. These proteins, in a denatured form, were used in ELISA as coating antigens. Human sera were collected from women with abnormal PAP smear enrolled during an ongoing multicenter HPV-PathogenISS study in Italy, assessing the HPV-related pathogenetic mechanisms of progression of cervical cancer precursor lesions. Negative human sera were collected from patients affected by other infectious agents. All the HPV-positive sera were also subjected to an avidity test to assess the binding strength in the antigen-antibody complexes.

Results

Most of the sera showed a positive reactivity to the denatured HPV16 proteins: 82% of the sera from HPV16 infected women and 89% of the sera from women infected by other HPV genotypes recognised at least one of the HPV16 proteins. The percentages of samples showing reactivity to L1, L2 and E7 were similar, but only a few serum samples reacted to E6 and E4. Most sera bound the antigens with medium and high avidity index, suggesting specific antigen-antibody reactions.

Conclusion

This novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype-specific, as it detects antibodies also in women infected by other genital HPVs. The assay is easy to perform and has low cost, making it suitable for monitoring the natural history of HPV infections as well as for detecting pre-existing HPV antibodies in women who receive VLP-based HPV vaccination.
Rac1-mediated Bcl-2 induction is critical in antigen-induced CD4 single-positive differentiation of a CD4+CD8+ immature thymocyte line
Authors: Oda Hiroyo , Suzuki Harumi , Sakai Kouhei , Kitahara Seiji , Patrick Michael S , Azuma Yoshinao , Sugi Kazuro , Kitamura Toshio , Kaye Jonathan , Shirai Mutsunori
Published: November 2006

Rac1, one of the Rho family small guanosine triphosphatases, has been shown to work as a “molecular switch” in various signal transduction pathways. To assess the function of Rac1 in the differentiation process of CD4 single-positive (CD4-SP) T cells from CD4CD8 double-positive (DP) cells, we used a DP cell line DPK, which can differentiate into CD4-SP cells upon TCR stimulation in vitro. DPK expressing dominant-negative (dn)Rac1 underwent massive apoptosis upon TCR stimulation and resulted in defective differentiation of CD4-SP cells. Conversely, overexpression of dnRac2 did not affect differentiation. TCR-dependent actin polymerization was inhibited, whereas early ERK activation was unaltered in dnRac1-expressing DPK. We found that TCR-dependent induction of Bcl-2 was suppressed greatly in dnRac1-expressing DPK, and this suppression was independent of actin rearrangement. Furthermore, introduction of exogenous Bcl-2 inhibited TCR-dependent induction of apoptosis and restored CD4-SP generation in dnRac1-expressing DPK without restoring TCR-induced actin polymerization. Collectively, these data indicate that Rac1 is critical in differentiation of CD4-SP from the DP cell line by preventing TCR-induced apoptosis via Bcl-2 up-regulation.
Eating habits and attitudes among 10-year-old children of mothers with eating disorders
Authors: Stein Alan , Woolley Helen , Cooper Sandra , Winterbottom Jonathan , Fairburn Christopher G. , Cortina-Borja Mario
Published: November 2006

Background

Children of mothers with eating disorders are at increased risk of developmental disturbance, but there has been little research in middle childhood, when disturbed eating habits tend to emerge.

Aims

To examine whether maternal eating disorders identified in the postnatal year are associated with the development of disturbed eating habits and attitudes in children at 10 years of age.

Method

Follow-up comparative study of 56 families (33 mothers with eating disorders and 23 controls). Psychopathology of children, mothers and fathers was assessed by interview, and mother-child interaction observed.

Results

The index group of children scored higher than controls on three of four domains of eating disorder psychopathology and on a global score. Children's eating disturbance was associated with length of exposure to mothers' eating disorder and mother-child mealtime conflict at 5 years. There was some evidence of increased emotional problems in index children.

Conclusions

The children of mothers with eating disorders manifested disturbed eating habits and attitudes compared with controls, and may be at heightened risk of developing frank eating disorder psychopathology.
Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia
Authors: Glatt Stephen J. , Stone William S. , Faraone Stephen V. , Seidman Larry J. , Tsuang Ming T.
Published: November 2006

Background

Evaluation of individuals at high genetic risk of schizophrenia is a powerful method for identifying precursors of the illness.

Aims

To identify aspects of personality, psychopathology and social development that differentiate high-risk and control individuals.

Method

Adolescent and young-adult first-degree relatives (n=35) of people with schizophrenia or schizoaffective disorder and a control group (n=55) were compared on 36 measures at baseline of a longitudinal study Measures differentiating high-risk and control participants were related to four genetic loading indices.

Results

High-risk participants older than 17 years showed more physical anhedonia, less positive involvement with peers and more problems with peers, siblings and the opposite gender. Older high-risk individuals also were less cooperative, less self-directed and less reward-dependent. Problems with peers and the opposite gender, as well as reward dependence, were related linearly to genetic loading.

Conclusions

Alterations in personality traits and social development are present in high-risk individuals, and may be markers for genetic liability toward the illness.
Distribution of symptom dimensions across Kraepelinian divisions
Authors: Dikeos Dimitris G. , Wickham Harvey , McDonald Colm , Walshe Muriel , Sigmundsson Thordur , Bramon Elvira , Grech Anton , Toulopoulou Timothea , Murray Robin , Sham Pak C.
Published: November 2006

Background

Dimensional structures are established for many psychiatric diagnoses, but dimensions have not been compared between diagnostic groups.

Aims

To examine the structure of dimensions in psychosis, to analyse their correlations with disease characteristics and to assess the relative contribution of dimensions v. diagnosis in explaining these characteristics.

Method

Factor analysis of the OPCRIT items of 191 Maudsley Family Study patients with schizophrenia, mood disorders with psychosis, schizoaffective disorder, and other psychotic illnesses, followed by regression of disease characteristics from factor scores and diagnosis.

Results

Five factors were identified (mania, reality distortion, depression, disorganisation, negative); all were more variable in schizophrenia than in affective psychosis. Mania was the best discriminator between schizophrenia and affective psychosis; the negative factor was strongly correlated with poor premorbid functioning, insidious onset and worse course. Dimensions explained more of the disease characteristics than did diagnosis, but the explanatory power of the latter was also high.

Conclusions

Kraepelinian diagnostic categories suffice for understanding illness characteristics, but the use of dimensions adds substantial information.
Influence of social perception and social knowledge on cognitive and social functioning in early psychosis
Authors: Addington Jean , Saeedi Huma , Addington Donald
Published: November 2006

Background

Social cognition has been implicated in the relationship between cognition and social functioning.

Aims

To test the hypothesis that social cognition mediates the relationship between cognitive and social functioning.

Method

This was a 1-year longitudinal cohort study comparing three groups: 50 people with first-episode psychosis, 53 people with multi-episode schizophrenia and 55 people without psychiatric disorder as controls. Participants were assessed on social perception, social knowledge, interpersonal problem-solving, cognition and social functioning.

Results

There were significant associations between social cognition, cognition and social functioning in all three groups. Deficits in social cognition were stable over time. In the first two groups, controlling for social cognition reduced the relationship between cognitive and social functioning.

Conclusions

This study provides some evidence that social cognition mediates the relationship between cognitive and social functioning.