bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition Evidence-Based Guidelines for Treating Hyperlipidemia in Children With Type 1 Diabetes
Authors: Robinson Megan Thomas
Published: April 2009

Purpose

The purpose of this case presentation is to review the current nutrition evidence-based guidelines and treatment goals for hyperlipidemia in children with type 1 diabetes. The American Heart Association (AHA) places children with type 1 diabetes in the highest tier for cardiovascular risk.

Methods

Early screening for hyperlipidemia in children with diabetes is recommended to identify those children at risk. If the fasting low-density lipoprotein cholesterol (LDL-C) level is ≥100 mg/dL (2.6 mmol/L), medical nutrition therapy is recommended as the first line of treatment to reach the desired goal (LDL-C <100 mg/dL). Medical nutrition therapy includes the following: decreasing saturated fat (<7% total calories), avoiding trans fatty acids, decreasing total cholesterol to <200 mg daily, increasing soluble fiber, and adding phytosterols daily.

Results

The patient discussed in this case presentation achieved a desired LDL-C level <100 mg/dL (2.6 mmol/L) by following the recommended heart-healthy guidelines. Statin therapy was not considered unless the LDL-C goal, <130 mg/dL (3.38 mmol/L), was not achieved by diet alone.

Conclusions

In this case study, evidence-based nutrition guidelines have been evaluated and reviewed to demonstrate heart-healthy eating for children with hyperlipidemia and type 1 diabetes. It is known that approximately 40% to 50% of children with elevated lipids will continue to have abnormal lipids into adolescence and early adulthood. Therefore, early screening is recommended by the AHA to track lipid changes during childhood and adolescence and to begin treating abnormal LDL-C levels to prevent the development of atherosclerosis.
The Evidence Base for Case Management Practice
Authors: Park Eun-Jun , Huber Diane L. , Tahan Hussein A.
Published: April 2009

Little is known about the role performance of case managers, who come from a variety of professional disciplines. The purpose of this secondary analysis is to identify and compare case management (CM) activities and knowledge elements by professions and by work settings. In an online field survey conducted by the Commission for Case Manager Certification in 2004, 4,419 case managers rated the frequency and importance of 103 activities (8 domains) and 64 knowledge statements (6 domains). Nursing and social work showed a relatively similar pattern as to their role activities and knowledge factors for CM practice. Similar patterns were seen in work settings: between hospitals and rehabilitation facilities; health insurance companies and managed care organizations; and CM companies, workers’ compensation agencies, and third-party administrators. These results indicate that there is evidence for how to develop CM programs consistent with both organizational characteristics and strengths of the nursing profession.
What is the long-term benefit of constraint-induced movement therapy? A four-year follow-up
Authors: Brogårdh Christina , Flansbjer Ulla-Britt , Lexell Jan
Published: April 2009

Objective: To evaluate the long-term benefits of constraint-induced movement therapy in chronic stroke.

Design: A four-year follow-up after constraint-induced group therapy assessing arm and hand function and self-reported daily hand use.

Subjects: Fourteen post-stroke individuals (six women and eight men; mean age 59.6 ± 12.7 years, range 23—75 years) with mild to moderate impairments of hand function.

Outcome measures: The Sollerman hand function test and the Motor Activity Log test.

Results: Four years after constraint-induced group therapy the participants had maintained their hand function, as measured by the Sollerman hand function test. The self-reported use and quality of movements of the more affected hand, as measured by the Motor Activity Log test, had decreased compared to post-treatment and three months follow-up (P<0.01), but was still significantly higher than pre-treatment (P<0.05).

Conclusion: There seems to be a long-term benefit of constraint-induced group therapy. Hand function was maintained over time and daily hand use had increased compared to pre-treatment. To provide guidelines about the clinical use of constraint-induced movement therapy further, larger and controlled studies are needed.
Challenging Gerontology’s Empirical Molehills
Authors: McDaniel Susan A.
Published: April 2009

Gerontology and theory have long been intellectually separate, with empirical studies dominant. Marrying Foucauldian theory, as Powell proposes, with gerontology is clever, timely and potentially fruitful for policy, practice and research. Although Foucault had little to say about age, his insights on power and on bodies are profoundly relevant to the process of ageing. Powell’s proposed application of a Foucauldian toolkit to caring for older people, enables the opening of insights into both the cared for and the carers, the latter of whom are differentially disadvantaged as well by gender, ethnicity, class and often immigration status. Viewed through Foucault’s concept of power, ageing population is observed as a fiction, justifying all manner of policy panics and woes that may not exist as actual challenges. Foucault’s concepts of power, identity, regulation, resistance and the bodily as socially shaped, have transformed sociology. A similar transformation of gerontology would be welcome.
Family Capital of Family Firms
Authors: Danes Sharon M. , Stafford Kathryn , Haynes George , Amarapurkar Sayali S.
Published: April 2009

The purpose was to present a family capital typology based on Sustainable Family Business Theory II and to document its relative contribution to short-term firm achievements and long-term sustainability using National Family Business Survey panel data. Family capital was defined as total owning-family resources composed of human, social, and financial capital. Family capital significantly contributed to firm achievements and sustainability. In the short term, all family capital types explained 13.5% of gross revenue variance and 4% of owner’s success perception variance. In the long term, all family capital types explained 26.7% of gross revenue variance and 11.6% of owner’s success perception variance.
Crime, Criminals, Treatment, and Punishment
Authors: Pasupuleti Sudershan , Lambert Eric G. , Shanhe Jiang  , Bhimarasetty Jagadish V. , Jaishankar K.
Published: April 2009

Views toward crime, criminals, punishment, and treatment are shaped by social forces, which differ across nations. Most of the research in this area has been conducted among citizens of Western nations, yet crime and responding to it is a worldwide occurrence. This study compared the crime views of Indian and U.S. college students. It was found that there were significant differences between Indian and U.S. respondents in their views toward crime, criminals, punishment, and treatment. There were mixed views on punishment and rehabilitation among both groups of students. In a multivariate analysis controlling for gender, age, academic level, and religious saliency, nation of the respondent was one of the best predictors for these views. The differences in views were attributed partly to the cultural differences between the two nations.
Social Work Abstracts Fails Again
Authors: Holden Gary , Barker Kathleen , Covert-Vail Lucinda , Rosenberg Gary , Cohen Stephanie A.
Published: April 2009

Objective: According to a prior study, there are substantial lapses in journal coverage in the Social Work Abstracts (SWA) database. The current study provides a replication and extension. Method: The longitudinal pattern of coverage of thirty-three journals categorized in SWA as core journals (published in the 1989-1996 period) is examined. Results: The proportion of issues missing from SWA is significantly greater than 0, increase over time, and is significantly biased in favor of NASW journals. Conclusion: The errors in SWA reported here, combined with those previously reported, will exert a long-term negative impact on scholarship unless their existence becomes known to all SWA users and they take steps to compensate for the situation.
Improving Scientific Inquiry for Social Work in South Korea
Authors: Choi Jae-Sung , Choi Soochan , Kim Yujin
Published: April 2009

This article examines current social issues and welfare needs in South Korea and discusses societal efforts to respond to these needs through social welfare systems nationwide. It also reviews how social work scholars, major contributors to the creation of a Korean welfare state, have contributed to the conditions of social work practice by detailing both the profile of social work research and the characteristics of social work publication. In response to the call for Korean social work practice to lay a culturally relevant foundation for empirically based practice, the authors particularly emphasize the various roles of a university-based research center and propose that the center's academic and policy level contributions be considered to help develop a unique model that the Korean welfare systems must apply in a global era.
Critiquing Human Resource Development's Dominant Masculine Rationality and Evaluating Its Impact
Authors: Bierema Laura L.
Published: April 2009

The purpose of this article is to critique human resource development's (HRD) dominant philosophy, practices, and research; illustrate how they negatively affect women HRD practitioners and recipients; and recommend alternative conceptualizations of the field. This article is grounded in a critical feminist theoretical framework, draws on critical theory and critical management studies, and is inspired by the author's ongoing disenchantment HRD's overreliance on “performative” ideas and practices.
Integrative Literature Reviews: Heterodox Economics, Social Capital, and HRD: Moving Beyond the Limits of the Neoclassical Paradigm
Authors: Storberg-Walker Julia
Published: April 2009

Social capital concepts and theories have brought about an evolution of thinking in the field of economics and expanded the boundaries that traditionally separated economics and other social science disciplines. Traditional (e.g., neoclassical) economics with its relatively undersocialized view of human nature—where individuals are seen as autonomous, rational decision makers—has had to develop new ways of understanding how “the social” influences affect economic behavior. Much of the theorizing around social capital has actually evolved from disciplines outside of economics, which has led to a truly multidisciplinary and evolving theoretical base. This article examines the most highly cited social capital theories, identifies their economic foundations, and analyzes how economic theories have been incorporated into the development of alternative social capital theories. It is then examine how heterodox economics might potentially influence HRD and suggest that a more nuanced understanding of the theoretical foundations of social capital will generate better and more diverse HRD theories and practices.
Are Physically Active Individuals Taking Statins at Increased Risk for Myopathy?
Authors: Lenz Thomas L.
Published: April 2009

Statin drugs are generally well tolerated in most patients. A limited number of studies have been published that look at the relationship of skeletal muscle injury in patients who take statin medications and exercise compared with taking statin medications without exercise. To date, the sample size of these studies is small, but there appears to be evidence to show that statin medications may exacerbate exercise-induced skeletal muscle injury. In addition, a study of professional athletes with familial hypercholesterolemia showed that 16 of 22 athletes could not tolerate statin medications. Patients with dyslipidemia who experience muscle pain and discomfort may be less likely to be compliant with their medication and/or physical activity regimens. Educating patients to recognize the signs and symptoms of medication-induced myopathy versus exercise-induced muscle soreness is an important counseling topic for health care providers.
Synbiotic Therapy Improves Quality of Life and Reduces Symptoms in Pediatric Ulcerative Colitis
Authors: Haskey Natasha , Dahl Wendy J.
Published: April 2009

The management of ulcerative colitis in children often requires aggressive pharmacological therapy or colonic resection. The authors hypothesized that synbiotic therapy would improve symptoms and quality of life in children diagnosed with ulcerative colitis. Pediatric study participants (8-18 years; n = 9) with ulcerative colitis in remission were provided synbiotic therapy (Bifidobacterium longum R0175 20 billion cfu/d, 15 g/d of inulin; n = 4) or placebo (maltodextrin + ascorbic acid capsule; 15 g/d of non-resistant maltodextrin; n = 5) for 10 months in a pilot study (phase I). At 10 months, the study was unblinded and synbiotic therapy was administered to 8 pediatric study participants (phase II). Quality of life was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). The SIBDQ was administered at baseline and every 2 months. Study participants kept a daily record of symptoms. Phase I quality-of-life scores were significantly better for those receiving the synbiotic therapy versus the placebo (P = .014). Severe symptoms occurred in 60% of the control study participants, whereas no study participants receiving synbiotic therapy experienced severe symptoms (P = .032). Phase II quality-of-life scores were significantly better posttreatment with synbiotic therapy (P = .034). No adverse effects were reported. Synbiotic therapy (B longum R0175 + inulin), when provided in addition to conventional treatment, appears to be a safe and effective strategy for managing pediatric ulcerative colitis in remission.
Nutritional Intervention to Prevent (NIP) Type 1 Diabetes A Pilot Trial
Authors: Chase H. Peter , Lescheck Ellen , Rafkin-Mervis Lisa , Krause-Steinrauf Heidi , Chritton Sonia , Asare Smita M. , Adams Sara , Skyler Jay S. , Clare-Salzler Michael ,   , and the Type 1 Diabetes TrialNet NIP Study Group
Published: April 2009

The objective of this study was to describe a pilot trial of using an omega-3 fatty acid (docosahexaenoic acid [DHA]) to prevent islet cell autoimmunity in infants with an increased risk for developing type 1 diabetes (T1D). Infants from pregnant mothers who either have T1D (or the father or a previous child has T1D) and who entered the study in the third trimester or infants younger than age 5 months having a first-degree family member with T1D were eligible for the study. Infants from either group also had to have an increased genetic (HLA) risk for T1D (or multiple first-degree relatives with T1D) to be eligible. The study is a multicenter, 2-arm, randomized, double-masked clinical trial that will last 4 years (1 year of recruitment and 3 years of treatment). Treatment with DHA (or control) began in the last trimester of pregnancy or in the first 5 months after birth. Inflammatory mediators, including cytokines, chemokines, eicosanoids, and C-reactive protein, are being measured along with fatty acids in maternal and infant blood. Ninety-eight infants were enrolled (41 during pregnancy and 57 in the 5 months after birth). HLA results of the 97 eligible infants (1 infant had a protective 0602 allele and was thus ineligible) showed that 90 have DR3 and/or DR4. Seven infants were enrolled without DR3/4 but who instead had multiple first-degree relatives with T1D. Compliance has been excellent, and no families have discontinued participation. Intervention trials in this high-risk group are feasible but require significant effort to identify potential participants.
Is Vitamin D Protective Against Development of Type 1 Diabetes Mellitus?
Authors: Zipitis Christos Steliou
Published: April 2009

The literature on vitamin D is expanding rapidly, and new associations with diseases are being described all the time. Many of these associations are derived from observational studies. Many question the importance of observations from such studies and call for a demonstration of effectiveness in what would be very long and expensive randomized controlled trials. This article focuses on the association between vitamin D and development of type 1 diabetes mellitus. Although randomized controlled trials are necessary for clarifying some aspects of intervention, this article demonstrates that the Hill criteria on causality are fulfilled and that randomization to no supplementation is in fact unethical.
Feeding Regimens and Catch-Up Growth in Premature and Full-Term Small for Gestational Age Infants
Authors: Funkquist Eva-Lotta , Tuvemo Torsten , Jonsson Björn , Serenius Fredrik , Nyqvist Kerstin Hedberg
Published: April 2009

The aim of this study was to evaluate the growth of infants born small for gestational age (SGA) as a result of 2 different feeding regimens during their hospital stay. A retrospective chart review was performed at 2 hospitals to assess the growth of 42 SGA infants (gestational age: median 37 weeks; range, 30-41 weeks) from birth up to 18 months corrected age. At one hospital, infants were fed according to a proactive nutrition regimen stipulating 200 mL milk/kg per day from day 2 to achieve better weight gain. At the other hospital, milk volumes were gradually increased to 170 mL/kg per day by day 9. Infants fed according to the proactive regimen had lower weight loss and regained their birth weight earlier but did not show better catch-up growth subsequently. The premature SGA infants (n = 20) showed catch-up growth before 40 weeks postmenstrual age. The lower the gestational age at birth, the less negative standard deviation score for length up to a corrected age of 18 months. Although infants fed according to a proactive regimen with liberal volumes of milk during the first days had lower weight loss and regained their birth weight earlier, no evidence was found that this would result in a different pattern of growth in later life.
Prevention and Treatment of Tube Dependency in Infancy and Early Childhood
Authors: Dunitz-Scheer Marguerite , Levine Arie , Roth Yehuda , Kratky Elisabeth , Beckenbach Hannes , Braegger Christian , Hauer Almuthe , Wilken Markus , Wittenberg Jean , Trabi Thomas , Scheer Peter Jaron
Published: April 2009

Tube dependency is recognized as an unintended result of long-term tube feeding in infants and young children. The condition involves disturbing side effects such as vomiting, gagging, and active food refusal. It prevents infants from making the transition from tube to oral feeding and from starting to learn to eat in the absence of any medical indication for continuation of enteral feeding. Tube dependency can have a destructive impact on the child's development, even in cases when the nutritional influence might be beneficial. The authors set up recommendations for the prevention of tube dependency and suggest guidelines for weaning tube-dependent children based on the results of the Graz program and satellite programs using a similar model. A sample of 221 tube-dependent patients aged 4 months to 15 years of age provided the clinical study group on which this article is based. Begun in 1987, a comprehensive tube-weaning program was developed on the basis of clinical experience and encounters with more than 430 tube-dependent children in 20 years, resulting in a success rate of 78/81 (96% for 2007) and 79/84 (94% for 2008). Placement must be preceded by clear criteria and a decision as to the indicated nutritional goal and time of use. The placement of a temporary tube must generate a plan covering maintenance issues, including time, method, and team for weaning. Aspects of tube feeding that go beyond purely medical and nutritional issues need to be considered to minimize the frequency and severity of unintended tube dependency in early childhood.
Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes
Authors: Drewniak Agata , van Raam Bram J. , Geissler Judy , Tool Anton T.J. , Mook Olaf R.F. , van den Berg Timo K. , Baas Frank , Kuijpers Taco W.
Published: April 2009

The treatment of healthy donors with granulocyte colony-stimulating factor (G-CSF) and dexamethasone results in sufficient numbers of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained in this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes compared with control granulocytes. More than 1000 genes displayed a differential expression pattern, with at least a 3-fold difference. Among these, a large number of genes was induced that encode proteins involved in inflammation and the immune response, such as C-type lectins and leukocyte immunoglobulin-like receptors. Because mobilized granulocytes have a prolonged life span, we focused on genes involved in the regulation of apoptosis. One of the most prominent among these was CAST, the gene encoding calpastatin. Calpastatins are the endogenous inhibitors of calpains, a family of calcium-dependent cysteine proteases recently shown to be involved in neutrophil apoptosis. Transcriptional activity of the CAST gene was induced by G-CSF/dexamethasone treatment both in vivo and in vitro, whereas the protein expression of CAST was stabilized during culture. These studies provide new insight in the genotypic changes as well as in the regulation of the immunologic functions and viability of mobilized granulocytes used for clinical transfusion purposes.
Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling–dependent CD8 T-cell activation
Authors: Yi Huanfa , Yu Xiaofei , Gao Ping , Wang Yanping , Baek Sun-Hee , Chen Xing , Kim Hyung L. , Subjeck John R. , Wang Xiang-Yang
Published: April 2009

Class A scavenger receptor (SRA), also known as CD204, has been shown to participate in the pathogenesis of atherosclerosis and the pattern recognition of pathogen infection. However, its role in adaptive immune responses has not been well defined. In this study, we report that the lack of SRA/CD204 promotes Toll-like receptor (TLR)4 agonist–augmented tumor-protective immunity, which is associated with enhanced activation of CD8+ effector T cell and improved inhibition of tumor growth. Dendritic cells (DCs) deficient in SRA/CD204 display more effective immunostimulatory activities upon TLR4 engagement than those from wild-type counterparts. Silencing of SRA/CD204 by RNA interference improves the ability of DCs to prime antigen-specific CD8+ T cells, suggesting that antigen-presenting cells, for example, DCs, play a major role in SRA/CD204-mediated immune modulation. Our findings reveal a previously unrecognized role for SRA/CD204, a non-TLR pattern recognition receptor, as a physiologic negative regulator of TLR4-mediated immune consequences, which has important clinical implications for development of TLR-targeted immunotherapeutic intervention.
Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study
Authors: Noens Lucien , van Lierde Marie-Anne , De Bock Robrecht , Verhoef Gregor , Zachée Pierre , Berneman Zwi , Martiat Philippe , Mineur Philippe , Van Eygen Koen , MacDonald Karen , De Geest Sabina , Albrecht Tara , Abraham Ivo
Published: April 2009

Imatinib mesylate (imatinib) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong, patient adherence is critical. The ADAGIO (Adherence Assessment with Glivec: Indicators and Outcomes) study aimed to assess prospectively over a 90-day period the prevalence of imatinib nonadherence in patients with CML; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence; and to examine whether treatment response is associated with adherence levels. A total of 202 patients were recruited from 34 centers in Belgium, of whom 169 were evaluable. One-third of patients were considered to be nonadherent. Only 14.2% of patients were perfectly adherent with 100% of prescribed imatinib taken. On average, patients with suboptimal response had significantly higher mean percentages of imatinib not taken (23.2%, standard deviation [SD] = 23.8) than did those with optimal response (7.3%, SD = 19.3, P = .005; percentages calculated as proportions × 100). Nonadherence is more prevalent than patients, physicians, and family members believe it is, and therefore should be assessed routinely. It is associated with poorer response to imatinib. Several determinants may serve as alert signals, many of which are clinically modifiable.
Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
Authors: Lee Youjin , Auh Sogyong L. , Wang Yugang , Burnette Byron , Wang Yang , Meng Yuru , Beckett Michael , Sharma Rohit , Chin Robert , Tu Tony , Weichselbaum Ralph R. , Fu Yang-Xin
Published: April 2009

Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.
Early iron-deficiency-induced transcriptional changes in Arabidopsis roots as revealed by microarray analyses
Authors: Buckhout Thomas J , Yang Thomas JW , Schmidt Wolfgang
Published: April 2009

Background

Iron (Fe) is an essential nutrient in plants and animals, and Fe deficiency results in decreased vitality and performance. Due to limited bio-availability of Fe, plants have evolved sophisticated adaptive alterations in development, biochemistry and metabolism that are mainly regulated at the transcriptional level. We have investigated the early transcriptional response to Fe deficiency in roots of the model plant Arabidopsis, using a hydroponic system that permitted removal of Fe from the nutrient solution within seconds and transferring large numbers of plants with little or no mechanical damage to the root systems. We feel that this experimental approach offers significant advantages over previous and recent DNA microarray investigations of the Fe-deficiency response by increasing the resolution of the temporal response and by decreasing non-Fe deficiency-induced transcriptional changes, which are common in microarray analyses.

Results

The expression of sixty genes were changed after 6 h of Fe deficiency and 65% of these were found to overlap with a group of seventy-nine genes that were altered after 24 h. A disproportionally high number of transcripts encoding ion transport proteins were found, which function to increase the Fe concentration and decrease the zinc (Zn) concentration in the cytosol. Analysis of global changes in gene expression revealed that changes in Fe availability were associated with the differential expression of genes that encode transporters with presumed function in uptake and distribution of transition metals other than Fe. It appeared that under conditions of Fe deficiency, the capacity for Zn uptake increased, most probably the result of low specificity of the Fe transporter IRT1 that was induced upon Fe deficiency. The transcriptional regulation of several Zn transports under Fe deficiency led presumably to the homeostatic regulation of the cytosolic concentration of Zn and of other transition metal ions such as Mn to avoid toxicity.

Conclusion

The genomic information obtained from this study gives insights into the rapid transcriptional responses to Fe shortage in plants, and is important for understanding how changes in nutrient availability are translated into responses that help to avoid imbalances in ion distribution. We further identified rapidly induced or repressed genes with potential roles in perception and signaling during Fe deficiency which may aid in the elucidation of these processes.
Identification and characterization of new miRNAs cloned from normal mouse mammary gland
Authors: Sdassi Nezha , Silveri Licia , Laubier Johann , Tilly Gaëlle , Costa José , Layani Sarah , Vilotte Jean-Luc , Le Provost Fabienne
Published: April 2009

Background

MicroRNAs (miRNAs) are small non-coding RNAs that have been found to play important roles in silencing target genes and that are involved in the regulation of various normal cellular processes. Until now their implication in the mammary gland biology was suggested by few studies mainly focusing on pathological situations allowing the characterization of miRNAs as markers of breast cancer tumour classes. If in the normal mammary gland, the expression of known miRNAs has been studied in human and mice but the full repertoire of miRNAs expressed in this tissue is not yet available.

Results

To extend the repertoire of mouse mammary gland expressed miRNAs, we have constructed several libraries of small miRNAs allowing the cloning of 455 sequences. After bioinformatics' analysis, 3 known miRNA (present in miRbase) and 33 new miRNAs were identified. Expression of 24 out of the 33 has been confirmed by RT-PCR. Expression of none of them was found to be mammary specific, despite a tissue-restricted distribution of some of them. No correlation could be established between their expression pattern and evolutionary conservation. Six of them appear to be mouse specific. In several cases, multiple potential precursors of miRNA were present in the genome and we have developed a strategy to determine which of them was able to mature the miRNA.

Conclusion

The cloning approach has allowed improving the repertoire of miRNAs in the mammary gland, an evolutionary recent organ. This tissue is a good candidate to find tissue-specific miRNAs and to detect miRNA specific to mammals. We provide evidence for 24 new miRNA. If none of them is mammary gland specific, a few of them are not ubiquitously expressed. For the first time 6 mouse specific miRNA have been identified.
Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone
Authors: Llamas Bastien , Verdugo Ricardo A , Churchill Gary A , Deschepper Christian F
Published: April 2009

Background

We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrYC57) was substituted for that of A/J mice (ChrYA), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrYA strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, cardiomyocytes from the resulting A/J-chrYC57 strain were larger than in their A/J counterparts. We further used these strains to test whether: 1) the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2) post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrYC57 and chrYA.

Results

The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J-chrYA resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrYA to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrYA hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1) p53 signaling, which comprises the interacting genes Ccnd1, Pten and Cdkn1a that are also potential co-regulators of the androgen receptors, and 2) circadian rhythm, which comprises Arntl/Bmal1, which may in turn regulate cell growth via the control of Cdkn1a.

Conclusion

Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from their C57BL/6J-chrYA counterparts, it affected gene expression in the hearts from both strains. However, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective manner, which provides possible mechanisms explaining how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice.
Anti-idiotypic antibodies: a new approach in prion research
Authors: Colja Venturini Anja , Bresjanac Maja , Vranac Tanja , Koren Simon , Narat Mojca , Popović Mara , Čurin Šerbec Vladka
Published: April 2009

Background

In certain cases, anti-idiotypic antibodies that recognize an antigen-combining site of an antibody can mimic the structure and/or function of certain nominal antigens. This feature makes them particularly useful if conventional experimental approaches fail to fulfil expectations, especially when the molecule of interest is infectious, toxic or difficult to isolate and purify. We suggest the application of an anti-idiotype concept to the field of prion biology, with the aim of evoking a humoral immune response against the pathological isoform of the prion protein (PrPSc). Different ways to induce anti-idiotypic responses were studied in mice and chickens using various forms of V5B2, a PrPSc-specific monoclonal antibody we have described previously.

Results

The preparation of anti-idiotypic monoclonal antibodies was achieved with well-defined strategies of immunization, selection and subsequent characterization. Our results demonstrate that it is possible to induce a strong anti-idiotypic immune response against the V5B2 monoclonal antibody in both xenogeneic and syngeneic experimental systems. From the competition seen between polyclonal and monoclonal anti-idiotypic antibodies and the original immunogen, the P1 peptide, and even more importantly, the ultimate target antigen, PrPSc, we conclude that selected antibodies bind to the antigen-combining site of the V5B2 monoclonal antibody and might even resemble the PrPSc-specific epitope. The involvement of both antigen-combining sites in the interaction between V5B2 and the most promising monoclonal anti-idiotypic antibody was further supported by molecular docking.

Conclusion

The results of the present study not only provide an example of the successful production of Ab2 monoclonal antibodies based on a well planned strategy for selection, but should also provide a new experimental approach that is applicable to the field of prion diseases.
Lab on a chip genotyping for Brucella spp. based on 15-loci multi locus VNTR analysis
Authors: De Santis Riccardo , Ciammaruconi Andrea , Faggioni Giovanni , D'Amelio Raffaele , Marianelli Cinzia , Lista Florigio
Published: April 2009

Background

Brucellosis is an important zoonosis caused by the genus Brucella. In addition Brucella represents potential biological warfare agents due to the high contagious rates for humans and animals. Therefore, the strain typing epidemiological tool may be crucial for tracing back source of infection in outbreaks and discriminating naturally occurring outbreaks versus bioterroristic event. A Multiple Locus Variable-number tandem repeats (VNTR) Analysis (MLVA) assay based on 15 polymorphic markers was previously described. The obtained MLVA band profiles may be resolved by techniques ranging from low cost manual agarose gels to the more expensive capillary electrophoresis sequencing. In this paper a rapid, accurate and reproducible system, based on the Lab on a chip technology was set up for Brucella spp. genotyping.

Results

Seventeen DNA samples of Brucella strains isolated in Sicily, previously genotyped, and twelve DNA samples, provided by MLVA Brucella VNTR ring trial, were analyzed by MLVA-15 on Agilent 2100. The DNA fragment sizes produced by Agilent, compared with those expected, showed discrepancies; therefore, in order to assign the correct alleles to the Agilent DNA fragment sizes, a conversion table was produced. In order to validate the system twelve unknown DNA samples were analyzed by this method obtaining a full concordance with the VNTR ring trial results.

Conclusion

In this paper we described a rapid and specific detection method for the characterization of Brucella isolates. The comparison of the MLVA typing data produced by Agilent system with the data obtained by standard sequencing or ethidium bromide slab gel electrophoresis showed a general concordance of the results. Therefore this platform represents a fair compromise among costs, speed and specificity compared to any conventional molecular typing technique.
Transcription profiles of hydrogenases related genes in the cyanobacterium Lyngbya majuscula CCAP 1446/4
Authors: Ferreira Daniela , Pinto Filipe , Moradas-Ferreira Pedro , Mendes Marta V , Tamagnini Paula
Published: April 2009

Background

Lyngbya majuscula CCAP 1446/4 is a N2-fixing filamentous nonheterocystous strain that contains two NiFe-hydrogenases: an uptake (encoded by hupSL) and a bidirectional enzyme (encoded by hoxEFUYH). The biosynthesis/maturation of NiFe-hydrogenases is a complex process requiring several accessory proteins for e.g. for the incorporation of metals and ligands in the active center (large subunit), and the insertion of the FeS clusters (small subunit). The last step in the maturation of the large subunit is the cleavage of a C-terminal peptide from its precursor by a specific endopeptidase. Subsequently, the mature large and small subunits can assemble forming a functional enzyme.

Results

In this work we demonstrated that, in L. majuscula, the structural genes encoding the bidirectional hydrogenase are cotranscribed, and that hoxW (the gene encoding its putative specific endopeptidase) is in the same chromosomal region but transcribed from a different promoter. The gene encoding the putative specific uptake hydrogenase endopeptidase, hupW, can be cotranscribed with the structural genes but it has its own promoter. hoxH, hupL, hoxW and hupW transcription was followed in L. majuscula cells grown under N2-fixing and non-N2-fixing conditions over a 12 h light/12 h dark cycle. The transcription of hoxH, hoxW and hupW did not vary remarkably in the conditions tested, while the hupL transcript levels are significantly higher under N2-fixing conditions with a peak occurring in the transition between the light and the dark phase. Furthermore, the putative endopeptidases transcript levels, in particular hoxW, are lower than those of the respective hydrogenase structural genes.

Conclusion

The data presented here indicate that in L. majuscula the genes encoding the putative hydrogenases specific endopeptidases, hoxW and hupW, are transcribed from their own promoters. Their transcript levels do not vary notably in the conditions tested, suggesting that HoxW and HupW are probably constantly present and available in the cells. These results, together with the fact that the putative endopeptidases transcript levels, in particular for hoxW, are lower than those of the structural genes, imply that the activity of the hydrogenases is mainly correlated to the transcription levels of the structural genes. The analysis of the promoter regions indicates that hupL and hupW might be under the control of different transcription factor(s), while both hoxH and xisH (hoxW) promoters could be under the control of LexA.
Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma
Authors: Voth Harald , Oberthuer André , Simon Thorsten , Kahlert Yvonne , Berthold Frank , Fischer Matthias
Published: April 2009

Background

HAND2, a key regulator for the development of the sympathetic nervous system, is located on chromosome 4q33 in a head-to-head orientation with DEIN, a recently identified novel gene with stage specific expression in primary neuroblastoma (NB). Both genes are expressed in primary NB as well as most NB cell lines and are separated by a genomic sequence of 228 bp. The similar expression profile of both genes suggests a common transcriptional regulation mediated by a bidirectional promoter.

Results

Northern Blot analysis of DEIN and HAND2 in 20 primary NBs indicated concurrent expression levels of the two genes, which was confirmed by microarray analysis of 236 primary NBs (Pearson's correlation coefficient r = 0.65). While DEIN expression in the latter cohort was associated with stage 4S (p = 0.02), HAND2 expression was not associated with tumor stage. In contrast, both HAND2 and DEIN transcript levels were highly associated with age at diagnosis <12 months (p = 0.001). The intergenic region shows substantial homology in different species (89%, 72% and 53% identity between human and mouse, chicken and zebrafish, respectively) and contains many highly conserved putative transcription factor binding sites. Using luciferase reporter gene constructs, asymmetrical bidirectional promoter activity was found in four NB cell lines: In DEIN orientation, an average 3.4 fold increase in activity was observed as compared to the promoterless vector, whereas an average 15.4 fold activation was detected in HAND2 orientation. The presence of two highly conserved putative regulatory elements, one of which was shown to enhance HAND2 expression in branchial arches previously, displayed weak repressor activity for both genes.

Conclusion

HAND2 and DEIN represent a gene pair that is tightly linked by a bidirectional promoter in an evolutionary highly conserved manner. Expression of both genes in NB is co-regulated by asymmetrical activity of this promoter and modulated by the activity of two cis-regulatory elements acting as weak repressors. The concurrent quantitative and tissue specific expression of HAND2 and DEIN suggests a functional link between both genes.
No relationship between 2',3'-cyclic nucleotide 3'-phosphodiesterase and schizophrenia in the Chinese Han population: an expression study and meta-analysis
Authors: Che Ronglin , Tang Wei , Zhang Jing , Wei Zhiyun , Zhang Zhao , Huang Ke , Zhao Xinzhi , Gao Jianjun , Zhou Guoquan , Huang Peirong , He Lin , Shi Yongyong
Published: April 2009

Background

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. The present study aims to investigate the relationship between CNP and schizophrenia in the Chinese population and the effect of different factors on the expression level of CNP in schizophrenia.

Methods

Five CNP single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. The results were included in the following meta-analysis. Quantitative real-time polymerase chain reaction (PCR) was conducted to examine CNP expression levels in peripheral blood lymphocytes.

Results

Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the CNP gene in schizophrenia. Our meta-analysis produced similar negative results.

Conclusion

The results suggest that the CNP gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population.
Prediction of breast cancer by profiling of urinary RNA metabolites using Support Vector Machine-based feature selection
Authors: Henneges Carsten , Bullinger Dino , Fux Richard , Friese Natascha , Seeger Harald , Neubauer Hans , Laufer Stefan , Gleiter Christoph H , Schwab Matthias , Zell Andreas , Kammerer Bernd
Published: April 2009

Background

Breast cancer belongs to the most frequent and severe cancer types in human. Since excretion of modified nucleosides from increased RNA metabolism has been proposed as a potential target in pathogenesis of breast cancer, the aim of the present study was to elucidate the predictability of breast cancer by means of urinary excreted nucleosides.

Methods

We analyzed urine samples from 85 breast cancer women and respective healthy controls to assess the metabolic profiles of nucleosides by a comprehensive bioinformatic approach. All included nucleosides/ribosylated metabolites were isolated by cis-diol specific affinity chromatography and measured with liquid chromatography ion trap mass spectrometry (LC-ITMS). A valid set of urinary metabolites was selected by exclusion of all candidates with poor linearity and/or reproducibility in the analytical setting. The bioinformatic tool of Oscillating Search Algorithm for Feature Selection (OSAF) was applied to iteratively improve features for training of Support Vector Machines (SVM) to better predict breast cancer.

Results

After identification of 51 nucleosides/ribosylated metabolites in the urine of breast cancer women and/or controls by LC- ITMS coupling, a valid set of 35 candidates was selected for subsequent computational analyses. OSAF resulted in 44 pairwise ratios of metabolite features by iterative optimization. Based on this approach ultimately estimates for sensitivity and specificity of 83.5% and 90.6% were obtained for best prediction of breast cancer. The classification performance was dominated by metabolite pairs with SAH which highlights its importance for RNA methylation in cancer pathogenesis.

Conclusion

Extensive RNA-pathway analysis based on mass spectrometric analysis of metabolites and subsequent bioinformatic feature selection allowed for the identification of significant metabolic features related to breast cancer pathogenesis. The combination of mass spectrometric analysis and subsequent SVM-based feature selection represents a promising tool for the development of a non-invasive prediction system.