bluuebunny/crossref_metadata_2025 huggingface dataset:
A First-Order Nonhomogeneous Markov Model for the Response of Spiking Neurons Stimulated by Small Phase-Continuous Signals
Authors: Tapson Jonathan , Jin Craig , van Schaik André , Etienne-Cummings Ralph
Published: February 2009

We present a first-order nonhomogeneous Markov model for the interspike-interval density of a continuously stimulated spiking neuron. The model allows the conditional interspike-interval density and the stationary interspike-interval density to be expressed as products of two separate functions, one of which describes only the neuron characteristics and the other of which describes only the signal characteristics. The approximation shows particularly clearly that signal autocorrelations and cross-correlations arise as natural features of the interspike-interval density and are particularly clear for small signals and moderate noise. We show that this model simplifies the design of spiking neuron cross-correlation systems and describe a four-neuron mutual inhibition network that generates a cross-correlation output for two input signals.
Generation of Spike Trains with Controlled Auto- and Cross-Correlation Functions
Authors: Krumin Michael , Shoham Shy
Published: February 2009

Emerging evidence indicates that information processing, as well as learning and memory processes, in both the network and single-neuron levels are highly dependent on the correlation structure of multiple spike trains. Contemporary experimental as well as theoretical studies that involve quasi-realistic neuronal stimulation thus require a method for controlling spike train correlations. This letter introduces a general new strategy for generating multiple spike trains with exactly controlled mean firing rates and correlation structure (defined in terms of auto- and cross-correlation functions). Our approach nonlinearly transforms random gaussian-distributed processes with a predistorted correlation structure into nonnegative rate processes, which are then used to generate doubly stochastic Poisson point processes with the required correlation structure. We show how this approach can be used to generate stationary or nonstationary spike trains from small or large groups of neurons with diverse auto- and cross-correlation structures. We analyze and derive analytical formulas for the high-order correlation structure of generated spike trains and discuss the limitations of this approach.
Arthroscopic versus Open Acromioplasty
Authors: Davis A. David , Kakar Sanjeev , Moros Chris , Krall Kaye Elizabeth , Schepsis Anthony A. , Voloshin Ilya
Published: February 2009

Background

To address persisting controversy in the literature concerning the efficacy of arthroscopic compared to open acromioplasty, a meta-analysis was performed to evaluate the treatment effect after both approaches.

Hypothesis

The final clinical outcomes will be the same after both open and arthroscopic acromioplasty. However, the arthroscopic technique results in faster recovery and less postoperative morbidity as reflected by faster return to work and decreased hospital stays.

Study Design

Meta-analysis; Level of evidence, 3.

Methods

We performed our search of published English language literature using PubMed. We also searched the proceedings from 4 major orthopaedic meetings convened from 2000 to 2007. Furthermore, the reference sections of all relevant articles were reviewed for pertinent studies and presentations. Nine studies met the inclusion criteria that directly compared arthroscopic versus open acromioplasty with minimum follow-up of 1 year. The analysis focused on 1-year clinical outcome and included comparison of the objective 100-point score, hospital stay, time until return to work, operative time, and complications.

Results

No significant differences were found in clinical outcomes or complications for the 2 groups. However, open acromioplasty was associated with longer hospital stays (2.3 days, P = .05) and a greater length in time until return to work (65.1 days) compared with the arthroscopic technique (48.6 days) (P < .05).

Conclusion

Arthroscopic and open acromioplasty have equivalent ultimate clinical outcomes, operative times, and low complication rates. However, arthroscopic acromioplasty results in faster return to work and fewer hospital inpatient days compared with the open technique.
A Prospective Comparison of 3 Hamstring ACL Fixation Devices—Rigidfix, BioScrew, and Intrafix—Randomized into 4 Groups with 2 Years of Follow-Up
Authors: Harilainen Arsi , Sandelin Jerker
Published: February 2009

Background

New devices for graft fixation in anterior cruciate ligament reconstruction are released to clinical use without clinical follow-up data.

Hypothesis

There is similar clinical outcome after either cross-pin or absorbable interference screw fixation in anterior cruciate ligament reconstruction with hamstring tendons.

Study Design

Randomized controlled clinical trial; Level of evidence, 1.

Methods

A total of 120 patients were randomized into 4 different groups (30 each) for anterior cruciate ligament reconstruction with hamstring tendons: femoral Rigidfix cross-pin and Intrafix tibial expansion sheath with a tapered expansion screw; Rigidfix femoral and BioScrew interference screw tibial fixation, BioScrew femoral and Intrafix tibial fixation; or BioScrew fixation into both tunnels. The evaluation methods were clinical examination, knee scores, and instrumented laxity measurements.

Results

Ten patients were completely lost to follow-up and 3 revisions were done before the 2-year follow-up, leaving 107 of 120 (89%) patients for analysis. No statistically significant differences between the groups were seen 2 years postoperatively, and all but 2 patients in the Rigidfix/Intrafix and Rigidfix/BioScrew groups, respectively, were classified into International Knee Documentation Committee A or B categories. A revision reconstruction was performed before the 2-year follow-up in 2 cases after a high-energy injury caused a rerupture (1 in Rigidfix/Intrafix and 1 in BioScrew/BioScrew groups). In addition, there were 4 nontraumatic failures revised before the 2-year follow-up (2 in Rigidfix/Intrafix and 1 each in Rigidfix/BioScrew and BioScrew/BioScrew).

Conclusion

There were no statistically or clinically relevant differences in the results 2 years postoperatively, and all 4 techniques improved patient performance.
Comparative Study of Navigated versus Freehand Osteochondral Graft Transplantation of the Knee
Authors: Koulalis Dimitrios , Di Benedetto Paolo , Citak Mustafa , O'Loughlin Padhraig , Pearle Andrew D. , Kendoff Daniel O.
Published: February 2009

Background

Osteochondral lesions are a common sports-related injury for which osteochondral grafting, including mosaicplasty, is an established treatment. Computer navigation has been gaining popularity in orthopaedic surgery to improve accuracy and precision.

Hypothesis

Navigation improves angle and depth matching during harvest and placement of osteochondral grafts compared with conventional freehand open technique.

Study Design

Controlled laboratory study.

Methods

Three cadaveric knees were used. Reference markers were attached to the femur, tibia, and donor/recipient site guides. Fifteen osteochondral grafts were harvested and inserted into recipient sites with computer navigation, and 15 similar grafts were inserted freehand. The angles of graft removal and placement as well as surface congruity (graft depth) were calculated for each surgical group.

Results

The mean harvesting angle at the donor site using navigation was 4° (standard deviation, 2.3°; range, 1°-9°) versus 12° (standard deviation, 5.5°; range, 5°-24°) using freehand technique ( P < .0001). The recipient plug removal angle using the navigated technique was 3.3° (standard deviation, 2.1°; range, 0°-9°) versus 10.7° (standard deviation, 4.9°; range, 2°-17°) in freehand ( P < .0001). The mean navigated recipient plug placement angle was 3.6° (standard deviation, 2.0°; range, 1°-9°) versus 10.6° (standard deviation, 4.4°; range, 3°-17°) with freehand technique ( P = .0001). The mean height of plug protrusion under navigation was 0.3 mm (standard deviation, 0.2 mm; range, 0-0.6 mm) versus 0.5 mm (standard deviation, 0.3 mm; range, 0.2-1.1 mm) using a freehand technique ( P = .0034).

Conclusion

Significantly greater accuracy and precision were observed in harvesting and placement of the osteochondral grafts in the navigated procedures. Clinical studies are needed to establish a benefit in vivo.

Clinical Relevance

Improvement in the osteochondral harvest and placement is desirable to optimize clinical outcomes. Navigation shows great potential to improve both harvest and placement precision and accuracy, thus optimizing ultimate surface congruity.
Parental Involvement and Children's School Achievement
Authors: Rogers Maria A. , Theule Jennifer , Ryan Bruce A. , Adams Gerald R. , Keating Leo
Published: February 2009

This study used path analytic techniques and an ecological framework to examine the association between children's perceptions of their parents' educational involvement, children's personal characteristics, and their school achievement. Fathers' academic pressure was predictive of lower achievement, whereas mothers' encouragement and support predicted higher achievement. Both parents used more academic pressure with their sons, whereas using more encouragement and support with their daughters. The effects of parental involvement were mediated through children's academic competence. This study demonstrates the interactive influences of parents' educational involvement and children's personal characteristics in predicting school achievement. Implications for practice and research in school psychology are presented.
Acute Tumefactive Demyelinating Lesions in a Pediatric Patient With Known Diagnosis of Multiple Sclerosis: Review of the Literature and Treatment Proposal
Authors: Dastgir Jahannaz , DiMario Francis J.
Published: February 2009

Tumefactive demyelinating lesions are a known but uncommon complication of multiple sclerosis, a disease rarely reported in children. This is the case of a 16-year-old African American patient with multiple sclerosis, who developed 2 tumefactive demyelinating lesions. Review of the literature and our own experience helped formulate an algorithm for therapeutic options during an acute attack.
Methyl-CpG-binding Protein 2 (MECP2) Gene Mutations in an Italian Sample of Patients with Pervasive Developmental Disorder and Mental Retardation
Authors: Parmeggiani Antonia , Tedde Maria Rita , Arbizzani Annalisa , Posar Annio , Scaduto Maria Cristina , Santucci Margherita , Sangiorgi Simonetta
Published: February 2009

Methyl-CpG-binding protein 2 (MECP2) gene mutations have been identified in girls with Rett syndrome and in boys with heterogeneous neuropsychiatric disorders. Because of the limited or inconsistent data reported in literature, the role of methyl-CpG-binding protein 2 gene in the pathogenesis of mental retardation and pervasive developmental disorders needs further study. We scanned methyl-CpG-binding protein 2 gene in 99 Italian patients with pervasive developmental disorder or with nonsyndromal mental retardation. Four methyl-CpG-binding protein 2 gene mutations were found: 2 in 4 girls with Rett disorder, the others in 2 girls with mental retardation. The wide phenotypic spectrum and the variants of methyl-CpG-binding protein 2 gene, which may play an important role in gene regulation and neurodevelopment, justify the literature's interest particularly in girls.
Kindergarten Children's Failure to Qualify for First Grade Could Result From Sleep Disturbances
Authors: Ravid Sarit , Afek Iris , Suraiya Suheir , Shahar Eli , Pillar Giora
Published: February 2009

Every year, 7% to 15% of preschool children are found to be underqualified for first grade. We examined whether sleep disturbances are factors in school readiness and their association with neurocognitive skills and behavior. The population included 148 kindergarten students. The study group consisted of 50 students who were assessed by the educational authority as unready for first grade. Children who were scheduled to attend first grade (n = 98) were in the control group. All children/parents filled in a sleep questionnaire and underwent a week of actigraphic sleep/wake study as well as cognitive and behavioral assessments. Children in the study group had significantly shorter total sleep time, reduced sleep efficiency, and increased number of nighttime awakenings. There were significant correlations between sleep variables, and cognitive and behavioral scores. In conclusion, children who fail to qualify for first grade have significantly inferior sleep patterns. Sleep disturbances were associated with cognitive and emotional immaturity.
Review of A Large Clinical Series: Intrahospital Transport of Critically Ill Patients: Outcomes, Timing, and Patterns
Authors: Voigt Louis P. , Pastores Stephen M. , Raoof Nina D. , Thaler Howard T. , Halpern Neil A.
Published: February 2009

The purpose of this study was to analyze the relationship of intrahospital transport patterns with patient throughput and outcomes in an oncological intensive care unit. We retrospectively reviewed all patients admitted to a closed medical-surgical intensive care unit at a cancer center between January 1, 2004 and December 31, 2005. We compared the clinical characteristics and outcomes of patients with and without transport and analyzed all intrahospital transports in relation to intensive care unit occupancy, length of stay, and intensive care unit and hospital outcomes. Transport patterns were also assessed by day of week, time of day, timing of the first transport to intensive care unit admission, and destination. Transported patients (n = 413, 43.5%) had significantly higher severity of illness scores on intensive care unit admission, greater use of vasopressors and mechanical ventilation, and longer intensive care unit and hospital length of stay and higher hospital mortality than nontransported patients (n = 535, 56.5%). Multiple transports (!2) occurred in 45% of the transported patients. The number of transports was directly proportional to intensive care unit length of stay. The highest transport rates and nearly half of all first transports occurred during the first 24 hours of intensive care unit admission. Transports were most common during weekdays and on afternoon and evening hours and most frequently to the computed tomography suite. Our study shows that intrahospital transport of the critically ill is a multifaceted process with important implications for intensive care unit resource analysis, workload and throughput.
Bedside Insertion of Inferior Vena Cava Filters by a Medical Intensivist: Preliminary Results
Authors: Haley Michael W. , Christmas A. Britton , Sing Ronald F.
Published: February 2009

The development of percutaneous techniques has allowed vena cava filters to be safely placed at the bedside. Such procedures appear uniquely suited for critically ill patients as they avoid the inherent risks associated with transportation. We report a ``medical intensivist's'' experience with the placement of 13 percutaneous vena cava filters. Vena cava filters were successfully placed in 12 of 13 patients as confirmed by postplacement venacavograms; 1 placement attempt was aborted because of a completely occluded inferior vena cava. These results suggest that with appropriate training and supervision, medical intensivists can safely insert vena cava filters in the intensive care unit setting. Such a practice appears safe, reduces patient risk associated with intrahospital transport, and may promote cost containment.
Recombinant Activated Factor VII Following Pediatric Cardiac Surgery
Authors: Kylasam Sharmila , Mos Krista , Fijtin Stephanie , Webster Boyd , Chard Richard , Egan Jonathan
Published: February 2009

Objective: Review the use of recombinant activated Factor VII following cardiac surgery. Specifically, we sought to define our current therapeutic practice indications and outcomes to assess the impact of recombinant activated factor VII on postoperative bleeding. Design: Retrospective case series. Setting: The study was conducted at the University affiliated pediatric intensive care unit. Patients and participants: All postcardiac surgical patients who received recombinant activated Factor VII between June 2002 and July 2006. Results: Cardiac surgery requiring cardiopulmonary bypass was performed on 1010 children during this period. In all, 25 (2.5%) children received recombinant activated factor VII for excessive bleeding. A single dose (180 μg/kg) of recombinant activated factor VII was given to 11 patients and 2 doses of 180 μg/kg to 14 patients. Intercostal drain losses were reduced from 12 (6.7-20.8) mL/kg/h to 3 (1-4.1) mL/kg/h, P = .018 following 1 dose of recombinant activated factor VII. In those receiving 2 doses; initial losses were 19.1 (7.5-31.7) mL/kg/h, after the first dose were 7.5 (3.6-13.7) mL/kg/h, P = .046, and after the second dose were 2 (1-2.9) mL/kg/h, P = .008. The plasma prothrombin time decreased in both the 1 dose, P = .003 and 2 dose, P = .009 groups. The activated partial thromboplastin time also decreased in the 1 dose group, P = .007 and 2 dose group, P = .03. There were no side effects attributable to recombinant activated factor VII. Annual rates of return to the operating theatre for excessive bleeding were coincidentally reduced in association with the routine use of recombinant activated factor VII from 4.3% to 1.5%, P = .019. Conclusions: Hemostasis occurred in 25 postoperative pediatric cardiac patients after recombinant activated Factor VII was given. In this setting, once conventional hemostatic therapy was optimized, recombinant activated Factor VII 180 μg/kg initially with intercostal losses greater than 10 mL/kg/h and a repeat dose after 2 hours if losses remained greater than 5 mL/kg/h was effective. No complications were found to have occurred and there was a coincidental reduction in annual returns to theatre for excessive bleeding.
Psychosis From Anticholinergic Medications Administered at a Smoking Cessation Clinic
Authors: Minton Jenna A. , Tofade Toyin S. , Shah Sidharth A. , Tofade Toyin S.
Published: February 2009

Anticholinergic medications are used for a variety of reasons, from their effects on the central nervous system to their effects on the gastrointestinal tract. They are used in the treatment of Parkinson’s disease, vertigo, gastroesophageal reflux disease, and peptic ulcer disease. They have also been used in the treatment of motion sickness. These medications must be used with caution due to their effects on other systems, including the central nervous system. Common central nervous system side effects due to anticholinergic medications include sedation, delirium, amnesia, and in the case of the patient presented in this report, psychosis. A 61-year-old man presented to the emergency department with visual and auditory hallucinations secondary to anticholinergic medications (scopolamine and atropine) he received in a smoking cessation clinic. Previous cases of anticholinergic medication–induced psychosis are also summarized.
Perceiving Strategic Meeting Interaction
Authors: Beck Stephenson J. , Keyton Joann
Published: February 2009

This study investigates how individuals perceive the message strategies of other team members and then explores how these perceptions are influenced by message function. Using a mixed-methods data collection, team interaction was coded using Bales's Interaction Process Analysis (IPA). Following the meetings, retrospective interviews were conducted to capture perceptions of team member contributions to weekly team meetings. To assess perceptual similarities and differences, team member perceptions were then compared to the IPA codes of meeting interactions. Findings advance knowledge of communication in team meetings, specifically, how and why team members interpret the same interaction in different ways. Study results have implications for improving member communication in task-focused team meetings.
Saving the Woodpeckers
Authors: Duit Andreas , Hall Ola , Mikusinski Grzegorz , Angelstam Per
Published: February 2009

This article investigates if higher levels of social capital, better governance structures, and a more ambitious conservation policy are positively linked to the ability of states to address biodiversity loss. Serving this purpose is a data set containing estimates of woodpecker diversity in 20 European countries. These data are argued to be a more valid indicator of biodiversity than most other available cross-national measures of environmental quality. A seemingly unrelated regression analysis reveals that none of the indicators are linked to higher levels of woodpecker diversity, which in turn leads to the conclusion that present institutions, environmental policies, and social structures have negligible effects on biodiversity compared to long-term landscape transformations.
Norway, the United States, and Commercial Whaling
Authors: Bailey Jennifer L.
Published: February 2009

Norway has long tried to portray itself as one of the most environmentally responsible states. But it has consistently refused to support the moratorium against commercial whaling. This article offers a cultural explanation for this seeming contradiction, by examining the way the global antiwhaling movement framed the issue and the Norwegian environmental organizations reframed it. It argues that two cultural differences are relevant. First, animal-rights organizations were an important part of the U.S. antiwhaling coalition, whereas such organizations are largely excluded from the Norwegian environmental activist community, where animal rights arguments have found little traction. Secondly, U.S. nongovernmental organizations (NGOs) operate in an adversarial pluralistic political culture, whereas the Norwegian environmental movement is embedded in a corporatist system where consensual decision making is the norm and has fostered a close relationship with the state. This has led to different images and strategic considerations being used by NGOs to frame the issue and ultimately to different decisions on the need for a moratorium.
Forest Management Policies and Resource Balance in China
Authors: Démurger Sylvie , Hou Yuanzhao  , Yang Weiyong
Published: February 2009

Using the latest forest inventory, this article provides a detailed analysis of China's changing forest sector by focusing on new forest trends, forest policy changes, and challenges to achieving a sustainable forest management. The authors analyze the dynamics of forest resources and provide an impact assessment of forest policies on China's forestry development during the past decades. Moreover, the analysis of the forest market highlights substantial disequilibria marked by a limited domestic supply potential and a growing demand for forest products satisfied by increasing imports. Internal and external solutions are explored, and their implications for China and supplying countries are assessed.
Writing for the Robot: How Employer Search Tools Have Influenced Résumé Rhetoric and Ethics
Authors: Amare Nicole , Manning Alan
Published: February 2009

To date, business communication scholars and textbook writers have encouraged résumé rhetoric that accommodates technology, for example, recommending keyword-enhancing techniques to attract the attention of searchbots: customized search engines that allow companies to automatically scan résumés for relevant keywords. However, few scholars have discussed the ethical implications of adjusting résumé keywords for the sole purpose of increasing searchbot hits. As the résumé genre has evolved over the past century, strategies of résumé “padding” have likewise evolved, at each stage violating one of four maxims of the Cooperative Principle. Direct factual misrepresentation violates the maxim of quality and is of course discouraged, but résumé writers have turned in succession to violations of manner (formatting tricks) and then more recently to violations of quantity and/or relevance with deceptive keywording techniques. The authors conclude by suggesting several techniques to business communication instructors that may encourage students to create more ethically sound résumés.
Preliminary Psychometric Data for the Academic Coping Strategies Scale
Authors: Sullivan Jeremy R.
Published: February 2009

The purpose of this article is to describe the psychometric characteristics of the Academic Coping Strategies Scale (ACSS), which was designed to assess college students’ coping strategies within the context of a specific academic stressor. This article will present results of analyses of factor structure, internal consistency, test-retest stability, and validity evidence based on relationships with other variables. Results suggest that items can be grouped into three easily interpretable factors (i.e., Approach, Avoidance, and Social Support) and that preliminary psychometric data are mostly favorable. The article will also describe limitations of the study, directions for future research, and potential applications of the ACSS. An important next step in the development of the ACSS will be to modify the scale for use with middle and high school students so that professionals working in the schools will have a method of assessing academic coping strategies among youth.
The Future of Restorative Neurosciences in Stroke: Driving the Translational Research Pipeline From Basic Science to Rehabilitation of People After Stroke
Authors:   Cumberland Consensus Working Group, Cheeran Binith , Cohen Leonardo , Dobkin Bruce , Ford Gary , Greenwood Richard , Howard David , Husain Masud , Macleod Malcolm , Nudo Randolph , Rothwell John , Rudd Anthony , Teo James , Ward Nicholas , Wolf Steven
Published: February 2009

Background. Major advances during the past 50 years highlight the immense potential for restoration of function after neural injury, even in the damaged adult human brain. Yet, the translation of these advances into clinically useful treatments is painstakingly slow. Objective. Here, we consider why the traditional model of a “translational research pipeline” that transforms basic science into novel clinical practice has failed to improve rehabilitation practice for people after stroke. Results. We find that (1) most treatments trialed in vitro and in animal models have not yet resulted in obviously useful functional gains in patients; (2) most clinical trials of restorative treatments after stroke have been limited to small-scale studies; (3) patient recruitment for larger clinical trials is difficult; (4) the determinants of patient outcomes and what patients want remain complex and ill-defined, so that basic scientists have no clear view of the clinical importance of the problems that they are addressing; (5) research in academic neuroscience centers is poorly integrated with practice in front-line hospitals and the community, where the majority of patients are treated; and (6) partnership with both industry stakeholders and patient pressure groups is poorly developed, at least in the United Kingdom where research in the translational restorative neurosciences in stroke depends on public sector research funds and private charities. Conclusions. We argue that interaction between patients, front-line clinicians, and clinical and basic scientists is essential so that they can explore their different priorities, skills, and concerns. These interactions can be facilitated by funding research consortia that include basic and clinical scientists, clinicians and patient/carer representatives with funds targeted at those impairments that are major determinants of patient and carer outcomes. Consortia would be instrumental in developing a lexicon of common methods, standardized outcome measures, data sharing and long-term goals. Interactions of this sort would create a research-friendly, rather than only target-led, culture in front-line stroke rehabilitation services.
Patterns and Predictors of Growth in Divorced Fathers’ Health Status and Substance Use
Authors: DeGarmo David S. , Reid John B. , Leve Leslie D. , Chamberlain Patricia , Knutson John F.
Published: February 2009

Health status and substance use trajectories are described over 18 months for a county sample of 230 divorced fathers of young children aged 4 to 11. One third of the sample was clinically depressed. Health problems, drinking, and hard drug use were stable over time for the sample, whereas depression, smoking, and marijuana use exhibited overall mean reductions. Variance components revealed significant individual differences in average levels and trajectories for health and substance use outcomes. Controlling for fathers’ antisociality, negative life events, and social support, fathering identity predicted reductions in health-related problems and marijuana use. Father involvement reduced drinking and marijuana use. Antisociality was the strongest risk factor for health and substance use outcomes. Implications for application of a generative fathering perspective in practice and preventive interventions are discussed.
Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization
Authors: Popovic Relja , Riesbeck Laurie E. , Velu Chinavenmeni S. , Chaubey Aditya , Zhang Jiwang , Achille Nicholas J. , Erfurth Frank E. , Eaton Katherine , Lu Jun , Grimes H. Leighton , Chen Jianjun , Rowley Janet D. , Zeleznik-Le Nancy J.
Published: February 2009

Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene produce chimeric proteins that cause abnormal expression of a subset of HOX genes and leukemia development. Here, we show that MLL normally regulates expression of mir-196b, a hematopoietic microRNA located within the HoxA cluster, in a pattern similar to that of the surrounding 5′ Hox genes, Hoxa9 and Hoxa10, during embryonic stem (ES) cell differentiation. Within the hematopoietic lineage, mir-196b is most abundant in short-term hematopoietic stem cells and is down-regulated in more differentiated hematopoietic cells. Leukemogenic MLL fusion proteins cause overexpression of mir-196b, while treatment of MLL-AF9 transformed bone marrow cells with mir-196–specific antagomir abrogates their replating potential in methylcellulose. This demonstrates that mir-196b function is necessary for MLL fusion-mediated immortalization. Furthermore, overexpression of mir-196b was found specifically in patients with MLL associated leukemias as determined from analysis of 55 primary leukemia samples. Overexpression of mir-196b in bone marrow progenitor cells leads to increased proliferative capacity and survival, as well as a partial block in differentiation. Our results suggest a mechanism whereby increased expression of mir-196b by MLL fusion proteins significantly contributes to leukemia development.
Forward RNAi screens in primary human hematopoietic stem/progenitor cells
Authors: Ali Nicole , Karlsson Christine , Aspling Marie , Hu Guang , Hacohen Nir , Scadden David T. , Larsson Jonas
Published: February 2009

The mechanisms regulating key fate decisions such as self-renewal and differentiation in hematopoietic stem and progenitor cells (HSPC) remain poorly understood. We report here a screening strategy developed to assess modulators of human hematopoiesis using a lentiviral short hairpin RNA (shRNA) library transduced into cord blood-derived stem/progenitor cells. To screen for modifiers of self-renewal/differentiation, we used the limited persistence of HSPCs under ex vivo culture conditions as a baseline for functional selection of shRNAs conferring enhanced maintenance or expansion of the stem/progenitor potential. This approach enables complex, pooled screens in large numbers of cells. Functional selection identified novel specific gene targets (exostoses 1) or shRNA constructs capable of altering human hematopoietic progenitor differentiation or stem cell expansion, respectively, thereby demonstrating the potential of this forward screening approach in primary human stem cell populations.
A new regularized least squares support vector regression for gene selection
Authors: Chen Pei-Chun , Huang Su-Yun , Chen Wei J , Hsiao Chuhsing K
Published: February 2009

Background

Selection of influential genes with microarray data often faces the difficulties of a large number of genes and a relatively small group of subjects. In addition to the curse of dimensionality, many gene selection methods weight the contribution from each individual subject equally. This equal-contribution assumption cannot account for the possible dependence among subjects who associate similarly to the disease, and may restrict the selection of influential genes.

Results

A novel approach to gene selection is proposed based on kernel similarities and kernel weights. We do not assume uniformity for subject contribution. Weights are calculated via regularized least squares support vector regression (RLS-SVR) of class levels on kernel similarities and are used to weight subject contribution. The cumulative sum of weighted expression levels are next ranked to select responsible genes. These procedures also work for multiclass classification. We demonstrate this algorithm on acute leukemia, colon cancer, small, round blue cell tumors of childhood, breast cancer, and lung cancer studies, using kernel Fisher discriminant analysis and support vector machines as classifiers. Other procedures are compared as well.

Conclusion

This approach is easy to implement and fast in computation for both binary and multiclass problems. The gene set provided by the RLS-SVR weight-based approach contains a less number of genes, and achieves a higher accuracy than other procedures.
Convergent and divergent patterns of morphological differentiation provide more evidence for reproductive character displacement in a wood cricket Gryllus fultoni(Orthoptera: Gryllidae)
Authors: Jang Yikweon , Won Yong-Jin , Choe Jae Chun
Published: February 2009

Background

In ecological character displacement, traits involved in reproductive isolation may not evolve in arbitrary directions when changes in these traits are by-products of adaptation to an ecological niche. In reproductive character displacement, however, selection acts directly on reproductive characters to enhance the degree of reproductive isolation between sympatric populations. Thus, the direction of change in reproductive characters may be arbitrary in relation to changes in other morphological characters. We characterized both tegminal characters and characters indicative of body size in sympatric and allopatric populations ofGryllus fultoni, a species displaying character displacement in its calling song characters in areas of sympatry withG. vernalispopulations, to infer the nature and direction of selection acting on reproductive and morphological characters in sympatry.

Results

Except for mirror area, the number of teeth in a file, and ovipositor length ofG. fultoni, all male and female morphological characters inG. fultoniandG. vernalisexhibited a uniform tendency to decrease in size with increasing latitude. There was no significant variation in female morphological characters between sympatric and allopatricG. fultonipopulations. However, males of sympatric and allopatricG. fultonipopulations significantly differed in head width, hind femur length, and mirror area even after controlling for clinal factors. Head width and hind femur length ofG. fultoniwere more similar to those ofG. vernalisin sympatric populations than in allopatric populations, resulting in morphological convergence ofG. fultoniandG. vernalisin sympatry. However, the mirror area ofG. fultonidisplayed the divergent pattern in relation to the sympatricG. vernalispopulations.

Conclusion

Divergence-enhancing selection may be acting on mirror area as well as calling song characters, whereas local adaptation or clinal effects may explain variation in other morphological characters in sympatric populations ofG. fultoni. This study also suggests that structures and behaviors that directly enhance reproductive isolation may evolve together, independently of other morphological traits.
Genetic diversity of canine olfactory receptors
Authors: Robin Stéphanie , Tacher Sandrine , Rimbault Maud , Vaysse Amaury , Dréano Stéphane , André Catherine , Hitte Christophe , Galibert Francis
Published: February 2009

Background

Evolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations.

Results

We sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47%) of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently.

Conclusion

Our demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of these genes is not? This phenomenon may be related to the nature of their ligands and their importance in everyday life.
Comparative genomic analysis of light-regulated transcripts in the Solanaceae
Authors: Rutitzky Mariana , Ghiglione Hernan O , Curá José A , Casal Jorge J , Yanovsky Marcelo J
Published: February 2009

Background

Plants use different light signals to adjust their growth and development to the prevailing environmental conditions. Studies in the model species Arabidopsis thaliana and rice indicate that these adjustments are mediated by large changes in the transcriptome. Here we compared transcriptional responses to light in different species of the Solanaceae to investigate common as well as species-specific changes in gene expression.

Results

cDNA microarrays were used to identify genes regulated by a transition from long days (LD) to short days (SD) in the leaves of potato and tobacco plants, and by phytochrome B (phyB), the photoreceptor that represses tuberization under LD in potato. We also compared transcriptional responses to photoperiod in Nicotiana tabacum Maryland Mammoth (MM), which flowers only under SD, with those of Nicotiana sylvestris, which flowers only under LD conditions. Finally, we identified genes regulated by red compared to far-red light treatments that promote germination in tomato.

Conclusion

Most of the genes up-regulated in LD were associated with photosynthesis, the synthesis of protective pigments and the maintenance of redox homeostasis, probably contributing to the acclimatization to seasonal changes in irradiance. Some of the photoperiodically regulated genes were the same in potato and tobacco. Others were different but belonged to similar functional categories, suggesting that conserved as well as convergent evolutionary processes are responsible for physiological adjustments to seasonal changes in the Solanaceae. A β-ZIP transcription factor whose expression correlated with the floral transition in Nicotiana species with contrasting photoperiodic responses was also regulated by photoperiod and phyB in potato, and is a candidate gene to act as a general regulator of photoperiodic responses. Finally, GIGANTEA, a gene that controls flowering time in Arabidopsis thaliana and rice, was regulated by photoperiod in the leaves of potato and tobacco and by red compared to far-light treatments that promote germination in tomato seeds, suggesting that a conserved light signaling cascade acts across developmental contexts and species.
A Candida albicans early stage biofilm detachment event in rich medium
Authors: Sellam Adnane , Al-Niemi Thamir , McInnerney Kathleen , Brumfield Susan , Nantel Andre , Suci Peter A
Published: February 2009

Background

Dispersal from Candida albicans biofilms that colonize catheters is implicated as a primary factor in the link between contaminated catheters and life threatening blood stream infections (BSI). Appropriate in vitro C. albicans biofilm models are needed to probe factors that induce detachment events.

Results

Using a flow through system to culture C. albicans biofilms we characterized a detachment process which culminates in dissociation of an entire early stage biofilm from a silicone elastomer surface. We analyzed the transcriptome response at time points that bracketed an abrupt transition in which a strong adhesive association with the surface is weakened in the initial stages of the process, and also compared batch and biofilm cultures at relevant time points. K means analysis of the time course array data revealed categories of genes with similar patterns of expression that were associated with adhesion, biofilm formation and glycoprotein biosynthesis. Compared to batch cultures the biofilm showed a pattern of expression of metabolic genes that was similar to the C. albicans response to hypoxia. However, the loss of strong adhesion was not obviously influenced by either the availability of oxygen in the medium or at the silicone elastomer surface. The detachment phenotype of mutant strains in which selected genes were either deleted or overexpressed was characterized. The microarray data indicated that changes associated with the detachment process were complex and, consistent with this assessment, we were unable to demonstrate that transcriptional regulation of any single gene was essential for loss of the strong adhesive association.

Conclusion

The massive dispersal of the early stage biofilm from a biomaterial surface that we observed is not orchestrated at the level of transcriptional regulation in an obvious manner, or is only regulated at this level by a small subpopulation of cells that mediate adhesion to the surface.
FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia
Authors: Loules Gedeon , Kalala Fani , Giannakoulas Nikolaos , Papadakis Emmanouil , Matsouka Panagiota , Speletas Matthaios
Published: February 2009

Background

Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 109/L).

Methods

Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of FIP1L1-PDGFRA rearrangement and the results confirmed by direct sequencing. C-KIT-D816V mutation was analysed retrospectively by PCR and restriction-fragment-length-polymorphism (PCR-RFLP), in all cases with primary eosinophilia.

Results

Two male patients with splenomegaly carried the FIP1L1-PDGFRA rearrangement, whilst 2 others were ultimately classified as suffering from idiopathic hypereosinophlic syndrome (HES) and one from systemic mastocytosis. These patients were negative for the C-KIT-D816V mutation and received imatinib (100–400 mg daily). Patients with CEL and HES responded to imatinib and remained in complete haematological, clinical and molecular (for carriers of FIP1L1-PDGFRA rearrangement) remission for a median of 28.2 months (range: 11–54), whilst the patient with systemic mastocytosis did not respond. Interestingly, in both patients with FIP1L1-PDGFRA rearrangement, the breakpoints into PDGFRA were located within exon 12 and fused with exons 8 and 8a of FIP1L1, respectively.

Conclusion

An early diagnosis of FIPIL1-PDGFRA-positive CEL and imatinib treatment offer to the affected patients an excellent clinical therapeutic result, avoiding undesirable morbidity. Moreover, although the molecular mechanisms underlying disease pathogenesis remain to be determined, imatinib can be effective in patients with idiopathic HES.
Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model
Authors: Schiller Katherine R , Zillhardt Marion R , Alley Jeremy , Borjesson Dori L , Beitz Alvin J , Mauro Laura J
Published: February 2009

Background

The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain. Although many valuable in vitro and in vivo models exist, identifying the relevant paracrine factors and deciphering their interactions is still a challenge. The aim of our study is to test an ex vivo coculture model that will allow monitoring of the expression, release and regulation of paracrine factors during interactions of an intact femur explant and tumor cells.

Methods

Intact or marrow-depleted neonatal mouse femurs and select murine and human sarcoma or carcinoma cell lines were incubated singly or in coculture in specialized well plates. Viability of the bone and cells was determined by immunohistochemical stains, microscopy and marrow cytopreps. Secretion and mRNA expression of paracrine factors was quantitated by ELISA and real-time RT-PCR.

Results

Compartments of the bone were optimally viable for up to 48 h in culture and tumor cells for up to 4 days. Bone was the major contributor of TGF-β and MMP2 whereas both bone and sarcoma cells secreted the chemokine MCP-1 in cocultures. Synergistic interaction between the femur and sarcoma resulted in enhanced MCP-1 secretion and expression in cocultures and was dependent on the presence of the hematopoietic component of the bone as well as other bone cells. In contrast, coculturing with breast carcinoma cells resulted in reduction of TGF-β and MCP-1 secretion from the bone.

Conclusion

These studies illustrate the feasibility of this model to examine paracrine interactions between intact bone and tumor cells. Further study of unique regulation of MCP-1 secretion and signaling between these cell types in different types of cancer will be possible using this simulated microenvironment.