bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails
Authors: Huang Hongda , Zhang Jiahai , Shen Weiqun , Wang Xingsheng , Wu Jiawen , Wu Jihui , Shi Yunyu 
Published: September 2007

AbstractBackgroundBrd2 is a transcriptional regulator and belongs to BET family, a less characterized novel class of bromodomain-containing proteins. Brd2 contains two tandem bromodomains (BD1 and BD2, 46% sequence identity) in the N-terminus and a conserved motif named ET (extra C-terminal) domain at the C-terminus that is also present in some other bromodomain proteins. The two bromodomains have been shown to bind the acetylated histone H4 and to be responsible for mitotic retention on chromosomes, which is probably a distinctive feature of BET family proteins. Although the crystal structure of Brd2 BD1 is reported, no structure features have been characterized for Brd2 BD2 and its interaction with acetylated histones.ResultsHere we report the solution structure of human Brd2 BD2 determined by NMR. Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommonπ-helix, termedπD. The helixπD forms a portion of the acetyl-lysine binding site, which could be a structural characteristic of Brd2 BD2 and other BET bromodomains. Unlike Brd2 BD1, BD2 is monomeric in solution. With NMR perturbation studies, we have mapped the H4-AcK12 peptide binding interface on Brd2 BD2 and shown that the binding was with low affinity (2.9 mM) and in fast exchange. Using NMR and mutational analysis, we identified several residues important for the Brd2 BD2-H4-AcK12 peptide interaction and probed the potential mechanism for the specific recognition of acetylated histone codes by Brd2 BD2.ConclusionBrd2 BD2 is monomeric in solution and dynamically interacts with H4-AcK12. The additional secondary elements in the long ZA loop may be a common characteristic of BET bromodomains. Surrounding the ligand-binding cavity, five aspartate residues form a negatively charged collar that serves as a secondary binding site for H4-AcK12. We suggest that Brd2 BD1 and BD2 may possess distinctive roles and cooperate to regulate Brd2 functions. The structure basis of Brd2 BD2 will help to further characterize the functions of Brd2 and its BET members.
Factors considered by medical students when formulating their specialty preferences in Japan: findings from a qualitative study
Authors: Saigal Priya , Takemura Yousuke , Nishiue Takashi , Fetters Michael D 
Published: September 2007

Abstract

Background
Little research addresses how medical students develop their choice of specialty training in Japan. The purpose of this research was to elucidate factors considered by Japanese medical students when formulating their specialty choice.

Methods
We conducted qualitative interviews with 25 Japanese medical students regarding factors influencing specialty preference and their views on roles of primary versus specialty care. We qualitatively analyzed the data to identify factors students consider when developing specialty preferences, to understand their views about primary and subspecialty care, and to construct models depicting the pathways to specialization.

Results
Students mention factors such as illness in self or close others, respect for family member in the profession, preclinical experiences in the curriculum such as labs and dissection, and aspects of patient care such as the clinical atmosphere, charismatic role models, and doctor-patient communication as influential on their specialty preferences. Participating students could generally distinguish between subspecialty care and primary care, but not primary care and family medicine. Our analysis yields a "Two Career" model depicting how medical graduates can first train for hospital-based specialty practice, and then switch to mixed primary/specialty care outpatient practice years later without any requirement for systematic training in principles of primary care practice.

Conclusion
Preclinical and clinical experiences as well as role models are reported by Japanese students as influential factors when formulating their specialty preferences. Student understanding of family medicine as a discipline is low in Japan. Students with ultimate aspirations to practice outpatient primary care medicine do not need to commit to systematic primary care training after graduation. The Two Career model of specialization leaves the door open for medical graduates to enter primary care practice at anytime regardless of post-graduate residency training choice.
Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report
Authors: Zagouri Flora , Sergentanis Theodoros N , Koulocheri Dimitra , Nonni Afroditi , Bousiotou Aggeliki , Domeyer Philip , Michalopoulos Nikolaos V , Dardamanis Dimitrios , Konstadoulakis Manousos M , Zografos George C 
Published: September 2007

AbstractBackgroundBreast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.Case presentationA 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.ConclusionThis extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.
Centrosomal pre-integration latency of HIV-1 in quiescent cells
Authors: Zamborlini Alessia , Lehmann-Che Jacqueline , Clave Emmanuel , Giron Marie-Lou , Tobaly-Tapiero Joëlle , Roingeard Philippe , Emiliani Stéphane , Toubert Antoine , de Thé Hugues , Saïb Ali 
Published: September 2007

Abstract
Human immunodeficiency virus type 1 (HIV-1) efficiently replicates in dividing and non-dividing cells. However, HIV-1 infection is blocked at an early post-entry step in quiescent CD4+ T cells in vitro. The molecular basis of this restriction is still poorly understood. Here, we show that in quiescent cells, incoming HIV-1 sub-viral complexes concentrate and stably reside at the centrosome for several weeks. Upon cell activation, viral replication resumes leading to viral gene expression. Thus, HIV-1 can persist in quiescent cells as a stable, centrosome-associated, pre-integration intermediate.
Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network
Authors: Li Wen-Chang , Cooke Tom , Sautois Bart , Soffe Stephen R , Borisyuk Roman , Roberts Alan 
Published: September 2007

Abstract
Background
How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron.

Results
The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity.

Conclusion
Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming.
Insights into spatial configuration of a galactosylated epitope required to trigger arthritogenic T-cell receptors specific for the sugar moiety
Authors: Glatigny Simon , Blaton Marie-Agnès , Marin Julien , Mistou Sylvie , Briand Jean-Paul , Guichard Gilles , Fournier Catherine , Chiocchia Gilles 
Published: September 2007

AbstractThe immunodominant epitope of bovine type II collagen (CII256–270) in Aq mice carries a hydroxylysine-264 linked galactose (Gal-Hyl264), the recognition of which is central to the development of collagen-induced arthritis. This study explores the molecular interactions involved in the engagement of T-cell receptors (TCRs) with such epitopes. Responses of three anti-CII T-cell hybridomas and clone A9.2 (all sharing close TCR sequences) to a panel of CII256–270 analogues incorporating Gal-Hyl264 with a modified side chain were determined. Recognition of naturally occurring CII256–270 peptides by either group of T cells depended strictly upon the presence of the carbohydrate and, more precisely, its intact HO-4 group. Modifications of primary amino group on the hydroxylysine side chain eliminated T-cell reactivity, notwithstanding the presence of the galactosyl moiety. Moderate stereochemical changes, such as altered sugar orientation and methylation at the galactose anchor position, were still permissive. Conversely, robust transformations affecting the relative positions of the key elements were detrimental to TCR recognition. To conclude, these data provide strong new experimental evidence that integrity of both galactose HO-4 and hydroxylysine side chain primary amino groups are mandatory for activation of anti-Gal-Hyl264 TCRs. They also indicate that there is a certain degree of TCR plasticity in peptide-TCR interactions.
How to evaluate the microcirculation: report of a round table conference
Authors: De Backer Daniel , Hollenberg Steven , Boerma Christiaan , Goedhart Peter , Büchele Gustavo , Ospina-Tascon Gustavo , Dobbe Iwan , Ince Can 
Published: September 2007

Abstract
Introduction
Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis.

Methods
The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology.

Results
The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future.

Conclusion
We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index.
Emergency Department Management of Pediatric Asthma at a University Teaching Hospital
Authors: Ly Cynthia D , Dennehy Cathi E 
Published: September 2007

Background: Asthma is a major health problem and the most frequent cause of chronic illness and emergency department (ED) visits in children. Limited data examining the ED management of pediatric asthma within university teaching hospitals across the US exist. Objective: To compare the ED management of children (aged 1–17 y) with asthma at a university teaching hospital using National Asthma Education and Prevention Program (NAEPP) guidelines. Methods: All cases of pediatric asthma that presented to the University ot California, San Francisco, Medical Center ED between October 1, 2003, and October 31, 2004, were included. Patients who required hospital admission were excluded. Data pertaining to patient demographics, primary diagnosis, pharmacologic management, diagnostic tests performed, and follow-up plans were abstracted and compared with NAEPP guidelines issued in 1997 and updated topics released in 2002. Results: A total of 141 cases were Identified. Mean patient age was 5.8 years. Most (61.7%) patients were male and of African American ethnicity (31.9%). Asthma severity was typically mild (66.7%) or moderate (29.1%). In persons at least 6 years of age (n = 58), peak expiratory flow rate (PEFR) was performed in 25.9% of cases. Pulse oximetry, however, was always performed. Based on NAEPP guidelines, β-agonists and corticosteroids should have been used, but were not, in 2.8% and 31.9% ot cases, respectively. At discharge, no corticosteroid prescription was given in 40.4% of the cases, no written action plan was prepared in 80.1% of the cases, no formal device training was administered in 67.3% of cases, and no peak flow meter was provided for persons at least 6 years of age in 50.0% of cases. Conclusions: NAEPP guidelines were met in all patients regarding pulse oximetry and in most patients with respect to the use of β-agonists. Improvements could be made, however, in the use of corticosteroids in the ED: in performing PEFR measurements for persons al least 6 years of age upon arrival; and in providing formal device training, a written action plan, prescriptions for steroids, and peak flow meters at discharge.
The roles of perceived task interdependence and group members' interdependence in the development of collective efficacy in university student group contexts
Authors: Alavi Seyyed Babak , McCormick John 
Published: September 2007

Background. Although the relationship between collective efficacy and group performance has been frequently investigated, a few studies have investigated the development of collective efficacy.Aim. This paper proposes some determinants of collective efficacy in small university groups. Group level hypotheses and research questions relating collective efficacy to collective cognition activities, task interdependence, self‐efficacy for group work, and collective orientation were posited.Sample. The sample comprised 145 university students in 40 work‐groups.Method. A two‐phase longitudinal design was employed in the context of university student groups. All groups were required to perform interdependent academic tasks. Aggregated variables were used after testing for within‐group agreement.Results. The results of multiple regression analysis provided some evidence that the more group members perceived themselves to be interdependent in the early stages of group work and assigned their tasks interdependently during group processes, the more likely they were to develop high collective efficacy in the final stages of group work. Collective efficacy was also related to the group average of self‐efficacy for group work especially when task interdependence was perceived to be high.Conclusions. The results suggest that forming groups with capable university students in group work, strengthening university students' perceptions of themselves as interdependent in the early stages of academic group work and assigning interdependent group tasks during group work may contribute to the development of high collective efficacy.
Organization of co‐occurring Axis II features in borderline personality disorder
Authors: Critchfield Kenneth L. , Clarkin John F. , Levy Kenneth N. , Kernberg Otto F. 
Published: September 2007

ObjectivesConsiderable heterogeneity exists in the comorbid Axis II features that frequently accompany borderline personality disorder (BPD). These features have potential to be meaningfully organized, relate to specific BPD presentation, and have implications for treatment process and outcome. The present study explored patterns of Axis II comorbidity in order to identify subtypes of BPD.DesignA well‐defined sample of 90 patients diagnosed with BPD was recruited as part of an RCT study. Participants were administered the International Personality Disorder Examination (Loranger, 1999) to diagnose BPD and assess comorbid Axis II features. Other measures were also administered to assess aspects of current work and relationship functioning, symptomatology, and self‐concept.Methods and resultsQ‐factoring was used to develop subtypes based on commonly occurring Axis II profiles, identifying three: Cluster A (elevated paranoid and schizotypal features), Cluster B (elevated narcissistic and histrionic features), and Cluster C (elevated avoidant and obsessive–compulsive features). An additional factor analysis revealed two dimensions underlying the comorbid features identifiable as: extraversion versus introversion and antagonism versus constraint. Validity of these two maps of comorbidity was explored in terms of the BPD criteria themselves, as well as on work and relationship functioning, identity diffusion, views of self and others, positive and negative affect, behavioural dyscontrol, and symptomatic distress.ConclusionsClinically meaningful subtypes can be identified for BPD based on co‐occurring Axis II features. Further research is needed to replicate and further establish base‐rates of these subtypes as well as their differential implications for treatment.
The role of confirmation bias in suspect interviews: A systematic evaluation
Authors: Hill Carole , Memon Amina , McGeorge Peter 
Published: September 2007

Purpose. The three studies presented in this paper systematically examined the effect of expectations of guilt on interviewer questioning style, confession, denial rates, and suspects' verbal behaviour during interview.Method. Undergraduate students were recruited to participate in the three studies. In Study 1, 61 participants formulated questions that they wanted to ask a suspect to determine whether or not they cheated on a task. Prior to formulating their questions, participants were led to believe that the suspect was likely to be guilty or innocent. In Study 2, 45 ‘innocent’ and ‘guilty’ participants were accused of cheating on a task and were interviewed with either guilt‐presumptive questions or neutral questions. In the final study, 58 participants listened to a selection of audiotaped interviews from Study 2. They then rated various aspects of the suspects' verbal behaviour.Results. As hypothesized expectations of guilt resulted in the formulation of more guilt‐presumptive questions even when participants were free to generate their own questions (Study 1). A significant association was found between suspect guilt/innocence and whether they confessed or denied, although there was no association between questioning style and confession or denial rates (Study 2). However, as expected, ratings of independent observers who listened to tape recordings of the suspect interviews indicated an influence of questioning style on the suspects' verbal behaviour whereby a self‐fulfilling prophecy effect occurred (Study 3).Conclusions. These results indicate that expectations of guilt can indeed have an effect on questioning style and that this in‐turn can lead to a self‐fulfilling prophecy effect.
A randomized group intervention trial to enhance mood and self‐efficacy in people with multiple sclerosis
Authors: Rigby S. A. , Thornton E. W. , Young C. A. 
Published: September 2007

ObjectivesTo document mood, self‐efficacy, and resiliency in people with multiple sclerosis (MS) following a brief group psychological intervention, and to examine whether benefits were greater than those derived from provision of education or group social interaction.DesignA randomized controlled intervention trial assessing outcomes at five time points over a 1‐year follow‐up.MethodsParticipants with MS were assigned to one of three groups: one receiving brief group psychological intervention (PG) comprising three 90 minute cognitive behavioural sessions supported by an Information Booklet dealing with mental and emotional issues relating to MS; a group provided only with educational material – the information booklet group (IBG); and a group who not only received the booklet but also participated in non‐structured social discussion (SDG) sessions similar in length and number to PG participants. Outcomes were documented using questionnaires.ResultsOutcomes were assessed using area under the curve (AUC) analysis: a summary measure that considers individual changes serially over time to provide a more meaningful picture than the one based on single time points. Ninety participants were followed up over the 12‐month post‐intervention, and their data are included in the analysis. Analyses indicated benefits in all outcome dimensions for the psychotherapeutic (PG) and social discussion groups (SDG) relative to theIBGgroup, but no differences betweenPGandSDG.ConclusionThe study indicates benefits from psychosocial intervention compared with bibliotherapy, with some additional benefit from psychological intervention compared with a social discussion group. Results suggest that much of the benefit may derive from non‐specific therapeutic components. Without psychosocial intervention, the psychological status of people with MS worsened over time.